MCQ OF Davidson’s Principles and Practice of th 20 Edition This book is downloaded from the Website www.studentconsult.com CONTENTS Serial 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 1 Subject Good prescribing Molecular mechanisms of disease Immunological factors in disease Environmental & nutritional factors in disease Principles of infectious disease Ageing and disease Critical care and emergency medicine Poisoning Medical psychiatry Oncology Palliative care and pain management Infectious diseases HIV infection and the human AIDS Sexually transmitted infections Clinical biochemistry and metabolism Kidney and urinary tract disease Cardiovascular disease Respiratory disease Endocrine disease Diabetes mellitus Alimentary tract and pancreatic disease Liver and biliary tract disease Blood disorders Musculoskeletal disorders Neurological disease Skin disease Part 1 Question 3 5 7 9 12 15 16 19 23 25 27 28 35 37 39 42 48 59 68 73 77 85 91 98 104 113 Part 2 Answer 118 120 123 125 128 131 133 136 139 142 144 146 153 156 158 163 170 181 188 195 200 208 213 221 227 238 No of Question 11 14 16 21 17 8 16 19 15 11 6 44 15 9 25 44 80 48 36 24 54 40 43 42 68 25 PART 1 QUESTIONS 2 Chapter 1 GOOD PRESCRIBING Answers page 118 Question 1. Warfarin has a low therapeutic index. What exactly does this term mean? A) It causes adverse effects at doses close to the usual therapeutic range B) It is effective at low plasma concentrations C) It causes toxicity at low plasma concentrations D) It has a low incidence of adverse effects and toxicity E) It is only effective at high plasma concentrations life-threatening haemorrhage, compared with 40 of the treatment group. Based only on these data, what would be the number of patients treated to cause one lifethreatening haemorrhage (i.e. the number needed to treat to cause one episode of harm, NNTH, sometimes called 'the number needed to harm')? A) 2 B) 16 C) 25 D) 31 E) 50 Question 2. In a randomised, double-blind placebo-controlled trial of a new inhaler for asthma there were half as many acute severe exacerbations in patients who took the inhaler every day for 1 year compared with placebo. The study authors quote a number needed to treat (NNTB) of 25 for the benefit of preventing one severe exacerbation in 1 year. Based on these data, which one of the following statements is valid? A) Only 1 in 25 patients will experience any benefit from taking the new inhaler B) On average, two severe exacerbations will be prevented for every 50 patients treated for 1 year with the new inhaler C) On average, two severe exacerbations will be prevented for every 25 patients treated with the new inhaler for 2 years D) Patients treated with the new inhaler for 1 year are 25% less likely to have a severe exacerbation during that time than those not treated E) The number needed to harm is greater than 25 Question 4. Before you prescribe a new drug for heart disease, your patient asks you how likely it is to help him. After a quick search you find the following information from clinical trials relating to the risk of myocardial infarction over 5 years while taking the drug: • Risk of a myocardial infarction without the new drug: 20% • Risk of a myocardial infarction with the new drug: 17% • Absolute risk reduction: 3% • Relative risk reduction: 15% • Number needed to treat (to prevent one myocardial infarction): 33 (95% confidence interval: 30.4 to 35.6) How would you express this information to the patient? A) Taking this drug for 5 years will reduce your chance of a heart attack by 15% B) If you take the drug for 5 years, there is a 15% chance that it will prevent you from having a heart attack C) Taking this drug for 5 years will reduce the chances of your having a heart attack by 3% D) If 100 people like you were to take this drug for 5 years it would prevent 15 heart attacks E) There is a 1 in 33 chance that taking this drug for 5 years will reduce your chance of a heart attack by 95% Question 3. A new drug is shown to reduce mortality from sepsis from 310 out of 1000 in the placebo group to 250 out of 1000 in the treatment group. A total of 20 of the placebo group develop 3 Question 5. A drug company representative tells you that a new drug, 'Potentol', is 10 times more potent than the currently popular drug of the same class, 'Weakol'. Which of the following statements concerning the two drugs can be made with greatest confidence? A) The maximum effect of Potentol will be greater than the maximum effect of Weakol B) Potentol will be a more effective drug C) Potentol and Weakol must act on different receptors D) Potentol will have a more favourable adverse effects profile E) The dose-response curve for Potentol lies to the left of the curve for Weakol Question 6. The dose of which one of the following drugs should be reduced in patients with mild renal insufficiency? A) Co-amoxiclav (amoxicillin plus clavulanic acid) B) Paracetamol C) Digoxin D) Simvastatin E) Furosemide Question 7. Which one of the following drug combinations is most likely to be harmful? A) Digoxin and warfarin B) Paracetamol and dihydrocodeine C) Trimethoprim and sulfamethoxazole D) Allopurinol and azathioprine E) Atenolol and ciclosporin Question 8. Which one of the following pieces of information must be included in a drug prescription outside hospital in the UK? 4 A) The prescribing doctor's General Medical Council (GMC) registration number B) The route of administration of the drug C) The condition that is being treated D) The proprietary name of the prescribed drug E) The duration of treatment Question 9. Which one of the following is not required on a prescription for a controlled drug? A) Patient's date of birth B) Doctor's address C) Patient's address D) Exact size of each dose specified in words and figures E) Total quantity to be dispensed Question 10. Treatment with which one of the following drugs is often initiated with a loading dose? A) Codeine B) Amiodarone C) Atenolol D) Allopurinol E) Furosemide Question 11. In a trial of a new treatment for fulminant sepsis the mortality in the treatment group is 20%, whereas the mortality in the placebo group is 40%. What is the relative risk of death with the new treatment? A) 0.1 B) 0.2 C) 0.4 D) 0.5 E) 2.0 Chapter 2 MOLECULAR MECHANISMS OF DISEASE Answers page 120 Question 1. Which of the following human cells contain 46 chromosomes? A) Erythrocytes B) Spermatozoa C) Platelets D) Neutrophils E) Ova Question 2. The term 'transcription' refers to which of the following cellular processes? A) Activation of second messengers such as adenyl cyclase B) Formation of messenger RNA from DNA by RNA polymerase C) Splicing out of introns from RNA D) Protein synthesis from RNA on ribosomes E) Protein modification in the Golgi apparatus Question 3. Mutation of the CFTR gene in patients with cystic fibrosis mediates its effect by interfering with which of the following cellular processes? A) Protein modification in the Golgi apparatus B) Active transport of sodium and potassium via the Na/K ATPase pump on the cell membrane C) Chloride transport through channels on the cell membrane D) Endocytosis of extracellular debris E) Binding of transcription factors in lung tissue to upstream gene promoters Question 4. All of the following molecules except one bind to intracellular receptors. Which is the exception? A) Vitamin A B) Glucocorticoids C) Noradrenaline (norepinephrine) D) Triiodothyronine E) Oestrogen 5 Question 5. Which of the following statements about cell death by apoptosis is true? A) The process only occurs in elderly individuals B) Cell destruction occurs by an antibodymediated process C) The cell membrane remains intact D) There is an associated acute inflammatory response E) It is the major mechanism underlying myocyte death in acute myocardial infarction Question 6. A 45-year-old man is diagnosed with Huntington's disease. He and his wife have non-identical twins, now aged 19. After genetic counselling, one of the twins undergoes testing for the Huntingtin gene which is found to be positive. What is the risk of the other twin inheriting the Huntingtin gene? A) Zero B) 25% C) 50% D) 75% E) 100% Question 7. Which of the following conditions is not correctly paired with its usual mode of inheritance? A) Wilson's disease - autosomal recessive B) Friedreich's ataxia - autosomal recessive C) Familial adenomatous polyposis coli autosomal dominant D) Haemochromatosis - autosomal dominant E) Myotonic dystrophy - autosomal dominant Question 8. What is the underlying chromosomal abnormality in Down's syndrome? A) 45,XO B) 47,XXY C) Trisomy 13 D) Trisomy 18 E) Trisomy 21 Question 9. Which one of the following familial cancer syndromes is associated with mutations in BRCA genes? A) Von Hippel-Lindau disease B) Peutz-Jeghers syndrome C) Li-Fraumeni syndrome D) Hereditary non-polyposis colorectal cancer (HNPCC) E) Familial breast/ovarian cancer Question 10. Which one of the following conditions does not show autosomal dominant inheritance? A) Gilbert's disease B) Congenital adrenal hyperplasia C) Familial hypercholesterolaemia D) Marfan's syndrome E) Adult polycystic kidney disease Question 11. Which one of the following features is not characteristic of Turner's syndrome? A) Only females are affected B) Short stature C) Webbed neck D) Secondary amenorrhoea E) Coarctation of the aorta 6 Question 12. A man with haemophilia A is married to a woman who is not a carrier for haemophilia. They are planning to start a family and so attend the genetic counselling clinic. What advice would you give them? A) A son would have haemophilia and a daughter would have a 50% chance of being a carrier B) A son would have haemophilia and a daughter would have a 100% chance of being a carrier C) A son would be unaffected and a daughter would have a 50% chance of being a carrier D) A son would be unaffected and a daughter would have a 100% chance of being a carrier E) A son would have a 50% chance of being a carrier and a daughter would have haemophilia Question 13. Which one of the following terms refers to the proportion of individuals inheriting an abnormal gene who go on to exhibit clinical disease? A) Anticipation B) Imprinting C) Penetrance D) Lyonisation E) Translocation Question 14. The cluster of cerebellar haemangioblastoma, renal cell carcinoma and phaeochromocytoma occurs in which one of the following conditions? A) Peutz-Jeghers syndrome B) Von Hippel-Lindau disease C) Li-Fraumeni syndrome D) Wermer's syndrome E) Gardner's syndrome Chapter 3 IMMUNOLOGICAL FACTORS IN DISEASE Answers page 123 Question 1. Which of the following is a component of the acquired immune response in humans? A) Low pH of skin B) Secretion of lysozyme C) Colonisation with commensal bacteria D) Phagocytes E) T lymphocytes Question 2. A gardener cuts his finger while using a rusty knife. Over the following 24 hours, his finger becomes red, warm and painful. Which cell type is most important in immune defence during these initial stages of infection? A) Eosinophils B) Neutrophils C) T cells D) B cells E) Basophils Question 3. The infection described in the previous question (Q2) spreads and the gardener is given a course of antibiotics by his general practitioner. Which of the following blood tests would be most useful in monitoring his response to treatment? A) C-reactive protein (CRP) B) T-cell count C) Complement (C3 and C4) D) Immunoglobulin IgM levels E) Immunoglobulin IgG levels Question 4. A 48-year-old man presents with progressive visual loss and is found to have fulminant cytomegalovirus (CMV) infection of the retina. He also has recurrent oral candidiasis. A deficiency of which of the following immune components is most likely to cause these problems? 7 A) Phagocyte deficiency B) Complement deficiency C) T-lymphocyte deficiency D) Antibody deficiency E) Neutrophil deficiency Question 5. A 35-year-old man presents with his third episode of meningococca meningitis. What is the most likely primary immune deficiency that could account for This ? A) Complement deficiency B) T-cell deficiency C) Neutrophil deficiency D) Antibody deficiency E) Primary cytokine deficiency Question 6. A 30-year-old woman, who is known to be hepatitis C-positive, develops joint pain, microscopic haematuria and a purpuric rash. Which diagnosis would best explain her symptoms? A) Anti-phospholipid syndrome B) Autoimmune thrombocytopenia C) Liver cirrhosis D) Cryoglobulinaemia E) Autoimmune hepatitis Question 7. A 30-year-old woman is being investigated for recurrent miscarriages. She has recently developed a deep venous thrombosis and is on warfarin. Which of the following tests would be most useful in investigating her underlying disease? A) Erythrocyte sedimentation rate B) Rheumatoid factor C) T-cell count D) Anticardiolipin antibodies E) Lupus anticoagulant Question 8. An 8-year-old boy presents with recurrent bacterial chest infections and bronchiectasis. What is the most likely primary immune deficiency that could account for this? A) Complement deficiency B) T-cell deficiency C) Neutrophil function disorder D) Antibody deficiency E) Cytokine defect Question 9. Which of the following measures is least likely to form part of the management of a patient with an antibody deficiency syndrome? A) Long-term prophylactic antibiotics B) Vaccination with live attenuated vaccines C) Intravenous immunoglobulin infusion D) Aggressive treatment of even mild infections E) Monitoring of immunoglobulin levels Question 10. In DiGeorge syndrome, abnormal development of which of the following structures leads to immune deficiency? A) Thymus B) Pituitary C) Thyroid D) Parathyroid E) Spleen Question 11. Which one of the following human leucocyte antigen (HLA) genotypes is strongly associated with ankylosing spondylitis? A) HLA-DR3 B) HLA-B27 C) HLA-DR4 D) HLA-B12 E) HLA-DR2 Question 12. According to the Gell and Coombs classification of hypersensitivity, which of the following is an example of a type II (antibody-mediated) reaction? A) Acute anaphylaxis 8 B) Acute cell-mediated transplant rejection C) ABO blood transfusion reaction D) Farmer's lung E) Nickel hypersensitivity Question 13. Which of the following conditions is associated with anticentromere antibodies? A) CREST syndrome B) Rheumatoid arthritis C) Systemic lupus erythematosus D) Sjögren's syndrome E) Mixed connective tissue disease Question 14. Which of the following conditions is particularly associated with anti-Ro and anti-La antibodies? A) Dermatomyositis B) Drug-induced lupus C) Mixed connective tissue disease D) Diffuse scleroderma E) Sjögren's syndrome Question 15. c-ANCA (anti-neutrophil cytoplasmic antibody with cytoplasmic fluorescence) is commonly associated with which one of the following conditions? A) Churg-Strauss syndrome B) Wegener's granulomatosis C) Henoch-Schönlein purpura D) Temporal arteritis E) Rheumatoid vasculitis Question 16. Which of the following best describes the characteristic features of the amyloid diseases? A) Extracellular deposition of insoluble proteins B) Intracellular deposition of insoluble proteins C) Extracellular deposition of soluble proteins D) Intracellular deposition of soluble proteins E) Intracellular deposition of insoluble carbohydrates Chapter 4 ENVIRONMENTAL AND NUTRITIONAL FACTORS IN DISEASE Answers page 125 Question 1. Which one of the following terms describes the number of new cases of a disease occurring in a population at risk during a defined period of time? A) Rate of the disease B) Prevalence of the disease C) Relative risk of the disease D) Attributable risk of the disease E) Incidence of the disease Question 2. A nuclear power station is built in close proximity to a village with a population of 3000 (village X). The residents are concerned about the rising incidence of disease Z. The incidence of disease Z in village X in 1 year was 150 cases. In a matched population of 3000 people not living in proximity to a nuclear power station, the incidence of disease Z is 30 cases per year. What is the relative risk of disease Z in village X? A) 5 B) 10 C) 3 D) 30 E) 50 Question 3. Regular cigarette smoking has been associated with an increased risk of developing all of the following diseases except one. Which is the exception? A) Peripheral vascular disease B) Peptic ulcer disease C) Bronchogenic carcinoma D) Ulcerative colitis E) Stroke 9 Question 4. After which one of the following interventions is a patient most likely to be abstinent from cigarettes 6 months later? A) Bupropion B) Nicotine replacement therapy (NRT) C) NRT plus behavioural support D) Behavioural support E) Opportunistic advice from the doctor Question 5. Which one of the following statements about the physiological adaptations that occur at high altitude is true? A) The oxyhaemoglobin dissociation curve moves to the right B) In those acclimatised to high altitude, 2,3-DPG production is decreased C) In those acclimatised to high altitude, erythropoietin (Epo) production is decreased D) Full physiological adaptation to altitude is complete in 3-4 hours in most individuals E) Hypoventilation is one of the adaptive mechanisms used by the body when ascending to high altitude Question 6. A traveller on an expedition to the Andes (altitude 3850 m) becomes unwell on the third day of the trip. He initially complains of breathlessness, dry cough and fatigue. The cough subsequently becomes productive of bloody sputum and on examination he is found to be hypoxic with crepitations in both lung fields. What is the likeliest diagnosis? A) Acute mountain sickness B) Pulmonary embolism C) High-altitude pulmonary oedema D) Acute respiratory distress syndrome E) Pneumothorax Question 7. In a patient diagnosed with acute mountain sickness, the appearance of which of the following clinical features should lead to a review of the diagnosis? A) Headache B) Visual loss C) Difficulty sleeping D) Fatigue E) Nausea and vomiting Question 8. Which one of the following is not a complication of near-drowning? A) Haemoptysis B) Hypotension C) Metabolic alkalosis D) Dehydration E) Cardiac arrhythmias Question 9. Non-starch polysaccharides (NSP) are the most important source of fibre in the human diet. Which one of the following is not classed as an NSP? A) Hemicellulose B) Cellulose C) Pectin D) Linoleic acid E) Gums Question 10. The calorific value of one gram of protein is 5 kcal. How many calories are in one gram of fat? A) 5 kcal B) 7 kcal C) 9 kcal D) 12 kcal E) 17 kcal Question 11. Which one of the following statements regarding dietary proteins is false? A) The term 'biological value' of a protein refers to the relative proportions of essential amino acids which it contains B) Proteins typically contribute < 20% to overall energy intake C) Some essential amino acids cannot be obtained from vegetarian diets, necessitating the use of supplements D) Essential amino acids are so called because they cannot be synthesised in humans, but are essential for the synthesis of important proteins E) The 'energy density' of protein (in kcal/g) is lower than that of fat 10 Question 12. Which one of the following statements regarding artificial nutritional support in hospital is true? A) Aspiration pneumonia is a recognised complication of parenteral feeding B) High-energy supplement drinks are an adequate replacement for normal diet in the hospital inpatient C) Parenteral nutrition is preferable to enteral feeding in most cases D) Hyperosmolar feeding solutions can be administered through a wide-bore venous cannula inserted into a large peripheral vein E) Feeding via a central (subclavian or internal jugular) line carries a higher risk of sepsis than feeding via a percutaneous endoscopic gastrostomy (PEG) tube Question 13. Which one of the following drug treatments is most likely to lead to weight gain? A) Thyroxine B) Combined oral contraceptive pill C) Metformin D) Sibutramine E) Omeprazole Question 14. Which one of the following statements regarding obesity is true? A) Obesity is defined by World Health Organization criteria as a body mass index (BMI) of 25 kg/m2 and above B) Obesity is more common in smokers C) Hypothyroidism is an irreversible cause of obesity D) Known genetic mutations account for 60% of the susceptibility to obesity E) Obese people have a higher basal metabolic rate than lean people Question 15. Obesity is associated with an increased risk of all of the following conditions except one. Which is the exception? A) Coronary heart disease B) Non-alcoholic steatohepatitis C) Osteoporosis D) Endometrial cancer E) Obstructive sleep apnoea Question 16. Which of the following interventions is likely to produce the greatest magnitude of weight loss in patients with morbid obesity? A) Bariatric gastric surgery B) Modified diet C) Orlistat D) Graded exercise programme E) Sibutramine Question 17. Which of the following is not a fat-soluble vitamin? A) Vitamin K B) Vitamin A C) Vitamin D D) Vitamin C E) Vitamin E Question 18. Which one of the following vitamins is incorrectly matched with its deficiency state? A) Vitamin C Scurvy B) Vitamin B2 (riboflavin) Beri-beri C) Niacin (nicotinic acid) Pellagra D) Folate (folic acid) Neural tube defects in the fetus E) Vitamin A Night blindness Question 19. The district nurse asks you to review an 84-year-old man at his home. She has been administering regular dressings for a chronic venous stasis ulcer that has been slow to heal, but is now concerned that he has developed several 11 large bruises and has been bleeding from his gums. Routine blood tests have also revealed a mild iron-deficiency anaemia. You suspect that there is a nutritional element to his complaints. Which of the following vitamins is the patient most likely to be deficient in? A) Vitamin C B) Vitamin A C) Vitamin B1 D) Vitamin B12 E) Vitamin K Question 20. Which one of the following inorganic nutrients is incorrectly paired with its deficiency state? A) Iodine Congenital hypothyroidism B) Calcium Impaired bone mineralisation C) Fluoride Discoloration of teeth D) Zinc Dermatitis and chronic diarrhoea E) Selenium Cardiomyopathy in children Question 21. All of the following except one are clinical features suggestive of severe adult malnutrition. Which is the exception? A) Thinning of hair B) Increased skinfold thickness over the triceps C) Dependent oedema D) Amenorrhoea or impotence E) Dryness of skin with occasional pigmented patches Chapter 5 PRINCIPLES OF INFECTIOUS DISEASE Answers page 128 Question 1. Which one of the following statements regarding infectious agents is incorrect? A) Bacteria possess a cell wall B) Viruses contain either DNA or RNA C) Prions are highly complex structures consisting of > 100 different proteins D) Fungal cells contain a defined nucleus E) Viruses cannot reproduce autonomousl Question 2. Which one of the following organisms is incorrectly matched with its mode of transmission? A) Legionella Water aerosol B) Salmonella Faecal-oral C) Listeria Ingestion D) Hepatitis A Needlestick injury E) Tetanus Direct skin penetration Question 3. Which one of the following vaccines is inactivated (as opposed to live)? A) Pertussis B) Measles C) Mumps D) BCG (tuberculosis) E) Rubella Question 4. Which one of the following vaccines is not given to children until the second year of life? A) HiB (Haemophilus influenzae type B) vaccine B) Oral polio vaccine C) Meningitis group C vaccine D) MMR (measles, mumps, rubella) vaccine E) DPT (diphtheria, pertussis, tetanus) vaccine 12 Question 5. Which of the following measures is of least importance in the management of asplenic patients? A) Yearly receipt of the polyvalent flu vaccine B) Yearly receipt of the pneumococcal vaccine C) Receipt of the meningococcal C vaccine D) Prophylactic antibiotics prior to dental procedures E) Long-term daily dose of penicillin Question 6. Which one of the following conditions is a notifiable disease in the UK under the Public Health (Infectious Diseases) Regulations 1988? A) Chicken pox B) HIV C) Scabies D) Syphilis E) Meningococcal meningitis Question 7. Which one of the following human pathogens is correctly matched with its most common method of identification? A) Streptococcus pyogenes Polymerase chain reaction (PCR) B) Hepatitis B virus Blood culture C) Neisseria gonorrhoeae Direct microscopy D) Mycobacterium tuberculosis Enzymelinked immunosorbent assay (ELISA) E) Candida albicans Complement fixation test Question 8. Which one of the antibiotics below is correctly paired with its predominant mode of action? A) Penicillin Disrupts bacterial protein synthesis by binding to the 50S subunit of bacterial ribosomes B) Gentamicin Inhibits cell wall synthesis C) Ciprofloxacin Inhibits DNA gyrase, thereby blocking DNA replication D) Minocycline Inhibits dihydrofolate and tetradihydrofolate reductase to block bacterial folate synthesis E) Erythromycin Forms superoxides that damage proteins, nuclear acid and lipids Question 9. One of the following definitions of terms relating to the pharmacokinetics of antibiotics is incorrect.Which is it? A) Minimum inhibitory concentration (MIC) is the lowest concentration of an antibiotic required to inhibit 50% of the colonies of a particular organism B) t{1/2} (plasma half-life) of an antibiotic is the time taken for the concentration of the drug in the body to be reduced by half C) Post-antibiotic effect (PAE) is the clinically useful property of some classes of antibiotic whereby inhibition of microbial replication continues beyond the time when the MIC is reached in plasma D) Inoculum effect is the reduction in activity of an antibiotic by the presence of large numbers of organisms despite apparent MIC-based sensitivity E) Synergism is the enhanced efficacy achieved by co-administration of two different antibiotics that exceeds the effect predicted by their combined MICs 13 Question 10. In which one of the following clinical scenarios is the suggested prophylactic agent inappropriate for the purpose described? A) Prevention of spontaneous bacterial peritonitis in a patient with cirrhosis Norfloxacin B) Prevention of bacteraemia in a postsplenectomy patient Phenoxymethylpenicillin C) Prevention of endocarditis in a patient with a prosthetic mitral valve undergoing tooth extraction Amoxicillin D) Prevention of gas gangrene in a patient with a contaminated wound Flucloxacillin E) Prevention of varicella infection in a healthy newborn exposed to varicella zoster during delivery Varicella immune globulin Question 11. Which one of the following statements regarding ß-lactam antibiotics is incorrect? A) Benzylpenicillin, flucloxacillin and meropenem are all subtypes of this class B) They are bactericidal antibiotics C) Most patients with established allergy to benzylpenicillin are also allergic to cephalosporins D) Synergism occurs in combination with the aminoglycosides (e.g. gentamicin) E) Potential side-effects include gastrointestinal upset and interstitial nephritis Question 12. A previously healthy 14year-old girl is admitted to the paediatric intensive care unit with a severe lower respiratory tract infection (LRTI). Serological investigations subsequently reveal very high titres of Mycoplasma pneumoniae. Which of the following antibiotics is most effective against this organism? A) Flucloxacillin B) Metronidazole C) Clarithromycin D) Co-amoxiclav E) Ceftriaxone Question 13. An 83-year-old lady is admitted to the stroke unit with a right partial anterior circulation stroke after being found at home on the floor, surrounded by vomit. On day 2 of her admission, she develops a productive cough, and oxygen saturations fall from 96% to 89% on air. Her temperature is 38.5°C. She has coarse crepitations at the right base and opacification of the right lower zone on chest X-ray. While awaiting the results of microbiological investigations, which one of the following antibiotic regimens would you prescribe? A) IV ceftriaxone and metronidazole B) IV vancomycin alone C) IV benzylpenicillin and flucloxacillin D) Oral co-amoxiclav and clarithromycin E) IV amoxicillin alone Question 14. Which of the following adverse effects is least likely to occur as a result of aminoglycoside (e.g. gentamicin) administration? A) Renal toxicity B) Cochlear toxicity C) Neuromuscular blockade following rapid IV infusion D) Hepatotoxicity E) Nausea and vomiting Question 15. Which one of the following statements regarding ciprofloxacin is true? A) It has poor oral bioavailability 14 B) It has potent anti-Gram-negative properties, but little or no anti-Grampositive activity C) Side-effects involving the gastrointestinal tract and skin are frequent and troublesome D) It has a small volume of distribution and poor tissue penetration E) Oral absorption is enhanced by administration with food Question 16. Which one of the following statements about glycopeptide antibiotics (such as vancomycin) is incorrect? A) Rapid infusion may produce an anaphylactoid reaction from histamine release B) They exhibit good activity against meticillin-resistant Staphylococcus aureus (MRSA) C) Therapeutic monitoring of drug levels is required D) Cover against Gram-negative organisms is poor E) They have good oral bioavailability Question 17. Which one of the following antimicrobials is incorrectly matched with its adverse side-effect? A) Chloramphenicol 'Grey baby syndrome' B) Minocycline Tooth discoloration in children C) Doxycycline Photosensitivity D) Ketoconazole Nephrotoxicity E) Erythromicin Cholestatic jaundice Chapter 6 AGEING AND DISEASE Answers page 131 Question 1. Features of ageing include all of the following except one. Which is the exception? A) Reduced glomerular filtration rate B) Lens opacification C) Neuronal loss D) Increased insulin secretion E) Reduced maximum heart rate Question 2. Which of the following drugs is least likely to contribute to recurrent falls in an elderly patient? A) Codeine phosphate B) Temazepam C) Amitriptyline D) Omeprazole E) Furosemide Question 3. Which one of the following is not an established risk factor for recurrent falls in the elderly? A) Cognitive impairment B) Depression C) Osteoarthritis D) Visual impairment E) Bisphosphonate therapy Question 4. A 79-year-old man is referred to the day hospital with recurrent falls. He has a history of hypertension and type II diabetes. He normally takes aspirin, amlodipine, metformin and simvastatin. Blood pressure is 121/86 mmHg when supine, falling to 96/61 mmHg when standing. What would the most appropriate initial treatment be? A) Continue current treatment B) Continue current treatment and start fludrocortisone C) Stop amlodipine D) Stop amlodipine and start bendrofluazide E) Stop all medication except aspirin Question 5. Causes of acute confusion in the elderly include all of the following except one. Which is the exception? A) Pulmonary embolism B) Urinary tract infection C) Recent prescription for tramadol 15 D) Alzheimer's disease E) Hyponatraemia Question 6. Which one of the following statements regarding urinary incontinence is true? A) It is a feature of normal ageing B) It can be caused by hypocalcaemia C) It affects 50% of women over the age of 65 D) Bladder catheterisation is usually the firstline treatment E) Laxatives may be helpful Question 7. An 82-year-old man is referred to the medical outpatient clinic with recurrent dizzy spells. He describes periodic lightheadedness occurring several times a week, typically lasting for less than 1 minute. Symptoms are unrelated to posture. He has never lost consciousness and denies chest pain or palpitations. He has a past history of hypertension and osteoarthritis and normally takes atenolol and paracetamol. Examination is unremarkable and the resting ECG normal. What would the most useful initial investigation be? A) Cervical spine X-ray B) 24-hour ambulatory ECG C) Echocardiogram D) CT head scan E) MRI head scan Question 8. An 86-year-old lady on the care of the elderly ward is found to have a coin-shaped lesion suggestive of a malignancy on a routine chest X-ray. She has a profound expressive dysphasia resulting from a previous stroke and suffers from severe chronic obstructive pulmonary disease. Which of the following factors should least influence further investigation and management? A) The patient's comorbidity B) The patient's ability to tolerate the available treatments C) Chronological age D) Biological age E) An advance directive prepared by the patient Chapter 7 CRITICAL CARE AND EMERGENCY MEDICINE Answers page 133 Question 1. You are asked to prescribe fluids for a 66-year-old, previously well man on the high-dependency unit, who returned from a radical prostatectomy 8 hours ago. Preoperatively, his blood pressure was 145/78 mmHg. He lost 2 litres of blood in theatre and has since received intravenous fluids and 4 units of red cells. In the past 4 hours his intravenous intake has consisted of a 500 ml bag of 0.9% saline. He is alert and complains of feeling thirsty. He does not have an epidural. The observation chart shows: Which of the following is the most appropriate fluid regimen to prescribe? A) 6-hourly Hartman's solution B) 8-hourly alternating 0.9% saline and 5% dextrose, with potassium supplementation C) 4-hourly 0.9% saline D) Immediate transfusion with O-negative blood E) 250 ml of gelofusine over 15 minutes Question 4. A 65-year-old patient in the ICU appears to be making an excellent recovery from pneumonia but then deteriorates acutely. He has the following observations: Which of the following diagnoses is the most likely cause of his deterioration? A) Major haemorrhage B) Pulmonary embolism C) Septic shock (pre-volume load) D) Neurogenic shock E) Acute left ventricular failure secondary to myocardial infarction Question 2. Which of the following haemodynamic parameters is represented by pulmonary artery wedge pressure (PAWP)? A) Central venous pressure B) Pulmonary arterial pressure C) Left atrial pressure D) Systemic capillary pressure E) Intrathoracic pressure Question 6. Which of the following drugs causes an increase in systemic vascular resistance? A) Sodium nitroprusside B) Noradrenaline (norepinephrine) C) Dobutamine D) Dopexamine E) Glyceryl trinitrate (GTN) Question 3. Which of the following factors has the least direct bearing on central venous pressure? A) Pulmonary artery pressure B) Systemic arterial pressure C) Venous tone D) Intravascular volume E) Intrathoracic pressure 16 Question 5. Which one of the following would be the best intramuscular dose of adrenaline (epinephrine) in a patient with acute anaphylactic shock and airway compromise? A) 1 ml of 1 in 1000 adrenaline B) 1 ml of 1 in 10 000 adrenaline C) 1 ml of 1 in 100 000 adrenaline D) 10 ml of 0.1% adrenaline E) 10 ml of 1% adrenaline Question 7. Which one of the following forms part of the diagnostic criteria for acute respiratory distress syndrome (ARDS)? A) Normal chest X-ray B) PaCO2 > 6.5 C) Blood pressure < 90/50 mmHg D) Pulmonary artery wedge pressure (PAWP) < 15 mmHg E) Increased lung compliance Question 8. A patient presents critically ill in type 1 respiratory failure with the following arterial blood gas measurements: E) There is a metabolic alkalosis in the second ABG Which of the following conditions is least likely to explain these findings? A) Diamorphine overdose B) Pulmonary embolus C) Acute asthma D) Pneumothorax E) Pulmonary oedema Question 12. A 35-year-old man is admitted to the ICU with abdominal sepsis following a laparotomy for a ruptured appendix. He is systemically unwell and requires ventilation. One day postoperatively, bleeding is noticed from his abdominal wound and sites of line insertion. The following results are obtained from tests of coagulation: Question 9. In which of the following conditions is continuous positive airways pressure (CPAP) usually most effective? A) Acute severe asthma B) Pulmonary oedema secondary to left ventricular failure (LVF) C) Exacerbation of chronic obstructive pulmonary disease (COPD) D) Narcotic drug overdose E) Neuromuscular disorder leading to respiratory failure Question 10. This series of arterial blood gas (ABG) measurements was taken from the same patient 24 hours apart: Which one of the following statements is true? A) There is a respiratory alkalosis in the first ABG B) There is a respiratory acidosis in the second ABG C) Arterial bicarbonate (HCO3-) must be lower in the second ABG D) Pulmonary gas exchange has improved in the second ABG 17 Question 11. Which of the following metabolic derangements is most likely to cause coma? A) Hyperkalaemia B) Hypercalcaemia C) Hypokalaemia D) Hyponatraemia E) Hyperuricaemia Which of the following is the most likely underlying problem? A) Warfarin effect B) Heparin effect C) Disseminated intravascular coagulation (DIC) D) Haemolytic uraemic syndrome (HUS) E) Idiopathic thrombocytopaenic purpura Question 13. Which one of the following is an appropriate strategy for controlling intracranial pressure in a patient with a head injury? A) 30° head-down tilt B) Use intravenous dextrose to reduce plasma sodium C) Use of positive end-expiratory pressure (PEEP) ventilation D) Mild hyperventilation to reduce PaCO2 to 4-4.5 kPa E) Aggressive fluid resuscitation to keep CVP above 20 cmH2O Question 14. Which of the following complications is associated with treatment of ventilated patients with ranitidine? A) Stress ulceration B) Ischaemic bowel C) Hyperbilirubinaemia D) Pneumonia E) Acute tubular necrosis Question 15. A 72-year-old patient with a history of ischaemic heart disease is being monitored in the surgical high-dependency unit following drainage of an intraabdominal abscess. At 2000 hours he complains of feeling nauseated and feverish. He is referred to the critical care team. Below is his observation chart for the previous 6 hours (breathing air): 18 He is transferred to the ICU. Which of the following measures would be most appropriate as part of his further management? A) Intubation and ventilation B) Administration of a diuretic C) Central venous catheterisation D) Commencement of inotrope infusion E) Haemofiltration Question 16. The patient from the previous question is resuscitated over the next 6 hours in the ICU. Despite him receiving 4 litres of intravenous fluid, his blood pressure and urine output fail to improve significantly. An oesophageal cardiac output monitor is placed and demonstrates a cardiac output of 8 litres/min. (A normal cardiac output would be 5 litres/min for a man of this size.) Which of the following is the likeliest diagnosis? A) Hypovolaemic shock B) Septic shock C) Anaphylactic shock D) Cardiogenic shock E) Obstructive shock Chapter 8 POISONING Answers page 136 Question 1. A rural hospital Accident and Emergency department is overwhelmed when 21 people present with poisoning due to contamination of the local water supply. They all have small pupils, muscle fasciculation, excessive salivation and lacrimation, vomiting, diarrhoea and hyper-reflexia. What is the likeliest contaminant? A) Amphetamine-related compounds B) Methadone C) Organophosphate insecticides D) Arsenic E) Fluoride Question 2. A 19-year-old girl is brought to hospital by her partner, having been found unconscious at home after a night out. Her partner has brought an empty bottle of the tricyclic antidepressant, amitriptyline, which he believes she has taken in overdose. You meet her on her arrival at the hospital Accident and Emergency department. What is the priority on her arrival at the hospital? A) A history from the partner of the estimated dose and any possible coingestants, such as alcohol B) Cardiac monitoring and/or a portable defibrillator in case of cardiac arrhythmias C) Assess the patient's pulse rate to identify any tachyarrhythmia D) Ensure a patent airway E) Administer 100% oxygen 19 Question 3. Which of the following drugs is most effectively removed by haemodialysis? A) Paracetamol B) Venlafaxine C) Amitriptyline D) Metformin E) Aspirin Question 4. Activated charcoal may be useful in the treatment of overdose with all of the following drugs except one. Which is the exception? A) Theophylline B) Ethanol C) Paracetamol D) Quinine E) Carbamazepine Question 5. Which of the following drugs is the most appropriate treatment for paracetamol overdose? A) Glucagon B) Gamma-hydroxybutyrate C) Desferrioxamines D) N-acetylcysteine E) Pralidoxime Question 6. A 16-year-old female with anorexia is brought to hospital by her mother 2 hours after attempting suicide by taking 22 g of paracetamol. She was drowsy when her mother found her, and on arrival at hospital she is unresponsive to pain. Observations on admission are as follows: After assessment and appropriate management of airway, breathing and circulation, which of the following is the most appropriate next step in her management? A) Give activated charcoal via a nasogastric tube B) Give N-acetylcysteine intravenously C) Administer vitamin K intravenously to prevent hepatic coagulopathy D) Urgently measure blood paracetamol levels E) Communicate with the mother to be certain of the timing of the overdose and to identify possible co-ingestants Question 7. A 21-year-old patient is brought to the hospital Accident and Emergency department by the police on a Sunday morning. He had been arrested at an all-night party but on the way to the police station, became very agitated and appeared unwell. On arrival he complains of thirst and nausea, and on examination exhibits large pupils, hypertension and global hyper-reflexia. He admits to illicit drug use the night before. Which of the following substances is the most likely cause of his symptoms? A) Methanol B) Gammahydroxybutyrate (GHB) C) Ecstasy (MDMA) D) Heroin E) D-lysergic acid diethylamide (LSD) 20 Question 8. A known drug addict is brought to hospital, having been found in a collapse. He has a respiratory rate of 3 breaths per minute and pinpoint pupils, and is completely unresponsive to painful stimuli. Which of the following drug treatments should he receive? A) Flumazenil B) Naloxone C) Desferrioxamine D) Adrenaline (epinephrine) E) Glucagon Question 9. A 62-year-old lady is brought to hospital by her son-in-law after being found at home behaving strangely. She is on several medications for cardiac disease, including warfarin, and has recently started a drug for depression. Observations on admission are as follows When you see her she is confused and disorientated but appears to be able to hear normally. She complains of seeing a yellow hue over everything and vomits three times. The cardiac monitor shows sinus bradycardia with brief selfterminating runs of ventricular tachycardia. Her ECG shows downwardsloping ST segment depression. Toxicity from which one of the following agents best explains her presentation? A) Warfarin B) Verapamil C) Quinine D) Fluoxetine E) Digoxin Question 10. An unkempt 43-year-old man staggers into the hospital Accident and Emergency department smelling strongly of alcohol and complaining that he cannot see. He vomits twice on arrival and is incontinent of urine. His blood results are as follows: Question 12. A patient with an overdose has been successfully treated with desferrioxamine. What agent was ingested? A) Iron B) Paracetamol C) Aspirin D) Lead E) Cyanide Question 13. A 23-year-old man is brought to the hospital Accident and Emergency department by the ambulance service. He is drowsy, speaking incoherently and has small pupils. Observations on admission are as follows: Toxicity from which of the following drugs best explains his presentation? A) Amitriptyline B) Diamorphine C) Temazepam D) Cocaine E) Venlafaxine What is the diagnosis? A) Diabetic ketoacidosis (DKA) B) Ethanol poisoning C) Salicylate poisoning D) Methanol poisoning E) Carbon monoxide (CO) poisoning Question 11. Which one of the following agents is used in the treatment of overdose with ß-blockers? A) N-acetylcysteine B) Calcium gluconate C) Naloxone D) Methionine E) Glucagon 21 Question 14. Treatment of paracetamol overdoses is usually decided by referring to this nomogram: A patient with which of the following conditions should be treated according to the normal risk line? A) Anorexia nervosa B) Epilepsy treated with phenytoin C) Chronic alcoholism D) Chronic malnourishment E) Co-ingestion of ecstasy (MDMA) Question 15. A 45-year-old woman is brought to hospital at 2330 hours by her partner, who found her lying in bed with three empty packets of paracetamol. She tells you that she attempted suicide by taking some of the tablets that morning, but then took more tablets in the afternoon, and some more after watching the ten o'clock news. Her partner has brought the packets to hospital. She is normally healthy and is on no regular medications. How would you decide whether to administer N-acetylcysteine? A) Treat if the most recent dose was more than 75 mg/kg B) Treat if a paracetamol level taken 4 hours after the last dose is above the normal-risk treatment line on a standard nomogram C) Treat if a paracetamol level taken 4 hours after the last dose is above the highrisk treatment line on a standard nomogram D) Treat if the total 24-hour dose was more than 150 mg/kg E) Treat if the total 24-hour dose was more than 75 mg/kg Question 16. Which one of the following drugs does not usually cause bradycardia in overdose? A) Atenolol B) Digoxin C) Lithium D) Verapamil E) Diltiazem 22 Question 17. A pet snake is brought to the hospital Accident and Emergency department by the friends of a patient who was bitten by it some 12 hours previously. The patient was dead on arrival at the hospital. A medical student examining the snake to identify it is accidentally bitten on the forearm. Which of the following is the most important action to take before intravenous administration of the specific antivenin? A) Inject 0.02 ml of saline-diluted antivenin subcutaneously and observe the injection site for 10 minutes B) Apply a tourniquet to the affected limb C) Incise the bite and aspirate the poison D) Check prothrombin time and fibrinogen levels E) Check renal function and creatine kinase (CK) levels Question 18. Overdose with which one of the following agents causes large pupils? A) Morphine B) Aspirin C) Paracetamol D) Amitriptyline E) Atenolol Question 19. A blood level would be most useful in the management of poisoning with which of the following agents? A) Aspirin B) Fluoxetine C) Morphine D) Quinine E) Organophosphates Chapter 9 MEDICAL PSYCHIATRY Answers page 139 Question 1. Pressure of speech and grandiose ideas are most suggestive of which of the following psychiatric conditions? A) Mania B) Schizophrenia C) Generalised anxiety disorder D) Obsessive-compulsive disorder E) Depression Question 2. Common somatic symptoms of anxiety disorders include all of the following except one. Which is the exception? A) Sweating B) Palpitations C) Constipation D) Dizziness E) Breathlessness Question 3. Which one of the following is not a risk factor for suicide? A) Male sex B) Unemployed C) Alcohol misuse D) Living alone E) Age under 45 Question 4. As the house officer on call you are asked to review a patient who appears to be hallucinating. The patient describes seeing large spiders crawling over the floor and the bed. Which of the following features, elicited through a careful mental state examination, would point most strongly to an organic cause for these hallucinations? A) Impaired cognition and drowsiness B) Pressure of speech C) Unshakeable belief that spiders are from another planet D) Associated auditory hallucinations E) Flat, blunted affect 23 Question 5. Which one of the following statements regarding electroconvulsive therapy (ECT) is false? A) Use has declined since the advent of antidepressant drugs B) It is of proven efficacy for severe depressive illness C) It is rarely used due to the high incidence of serious side-effects D) It may cause both anterograde and retrograde amnesia E) It requires a general anaesthetic and paralysis with muscle relaxants Question 7. Which of the following psychiatric drugs may interact with foods rich in tyramine, such as cheese and red wine, to produce a potentially fatal hypertensive crisis? A) Tricyclic antidepressants B) Dopamine receptor antagonists C) Monoamine oxidase inhibitors D) Selective serotonin re-uptake inhibitors E) Benzodiazepines Question 8. Which one of the following statements regarding antidepressant drug treatments is true? A) They are more effective than psychological treatments for mild to moderate depression B) Selective serotonin re-uptake inhibitors (SSRIs) have greater anticholinergic sideeffects and are more dangerous in overdose than tricyclic antidepressants C) The majority of patients experience an improvement in symptoms within one week of starting treatment D) Newer antidepressants have greater efficacy than older agents such as tricyclic antidepressants E) Treatment should be continued for at least 6 months to reduce the high risk of relapse Question 9. Adverse effects associated with lithium therapy include all of the following except one. Which is the exception? A) Tremor B) Teratogenicity C) Hypothyroidism D) Diabetes mellitus E) Convulsions Question 10. Which one of the following is not a 'first-rank' symptom of schizophrenia? A) Thought insertion B) Poverty of speech C) Delusional perception D) Passivity experiences E) Auditory hallucinations in the third person Question 11. A 23-year-old male is brought to Accident & Emergency by the police after exhibiting bizarre behaviour. He is extremely agitated and claims that he is being followed by various agencies, all with apparently sinister intent. Which one of the following would make the diagnosis of schizophrenia least likely? A) Incomprehensible speech B) Claims by the patient that the above agencies were stealing thoughts from his head C) No previous history of mental illness D) Ingestion of amphetamines within the last 24 hours E) Lack of insight Question 12. Which one of the following is not a recognised criterion for alcohol dependence? A) Feeling of compulsion to drink B) Priority of drinking over other activities C) Relief of withdrawal symptoms by further drinking 24 D) Driving under the influence of alcohol E) Reinstatement of drinking behaviour after abstinence Question 13. A 55-year-old male with a long history of alcohol excess is admitted to a medical ward, having been found by neighbours in a state of gross self-neglect. On admission he is noted to be confused and very unsteady on his feet. On examination he is clearly malnourished, disorientated in time, person and place and exhibits horizontal jerk nystagmus on lateral gaze. He does not smell of alcohol and there are no features of chronic liver disease. Which of the following is the likeliest diagnosis? A) Korsakoff's syndrome B) Hepatic encephalopathy C) Delirium tremens D) Wernicke's encephalopathy E) Acute alcohol intoxication Question 14. With reference to the patient from the previous question (Q13) who has Wernicke's encephalopathy, which of the following steps should be undertaken first in his management? A) Rehydration with IV dextrose B) CT scan of the brain C) High-dose intravenous thiamin (Pabrinex) D) Oral benzodiazepines E) Full septic screen Question 15. All of the following except one are diagnostic criteria for anorexia nervosa. Which is the exception? A) Body mass index 17.5 or less B) Avoidance of high-calorie foods C) Self-induced vomiting or purgation D) Distortion of body image E) Amenorrhea for at least 3 month Chapter 10 ONCOLOGY Answers page 142 Question 1. All of the following statements except one are correct epidemiological associations of malignancy. Which is the exception? A) BRCA 1 gene and ovarian cancer B) Asbestos exposure and mesothelioma C) Schistosomiasis and squamous bladder cancer D) Human papillomavirus and oesophageal cancer E) Adenopolyposis coli (APC) gene and colorectal cancer Question 5. A 63-year-old woman receiving chemotherapy for breast cancer attends the hospital accident and emergency department, complaining of headache, malaise and a dry cough. Routine observations show a temperature of 38.5°C, pulse of 104 bpm, BP of 128/83 mmHg, respiratory rate of 20 and oxygen saturation of 97% on air. Examination is otherwise unremarkable. Initial investigations reveal the following Question 2. Which one of the following is a risk factor for breast carcinoma? A) Early menarche B) Fibrocystic breast disease C) Premature menopause D) First full-term pregnancy at age 16 E) Multiple endocrine neoplasia (MEN) type I Question 3. Which one of the following is not a recognised extrapulmonary manifestation of bronchial carcinoma? A) Syndrome of inappropriate antidiuretic hormone secretion (SIADH) B) Acanthosis nigricans C) Finger clubbing D) Eaton-Lambert syndrome E) Ectopic adrenocorticotrophic hormone (ACTH) production Question 4. Which one of the following tumour markers is not paired with the correct malignancy? A) Carcinoembryonic antigen (CEA) and colonic carcinoma B) Alpha-fetoprotein (AFP) and bladder carcinoma C) Prostate-specific antigen (PSA) and prostatic carcinoma D) CA-125 and ovarian carcinoma E) Human chorionic gonadotrophin (HCG) and choriocarcinoma 25 What should the next step in her treatment be? A) Perform a full septic screen and start antibiotics if cultures are positive B) Take blood cultures and start broadspectrum antibiotics immediately C) Insert a central line to allow measurement of central venous pressure D) Administer granulocyte-colony stimulating factor (G-CSF) to stimulate white blood cell production E) Discharge her home to prevent her contracting a hospital-acquired infection Question 6. A 73-year-old man with known prostate cancer is admitted to hospital with a 24-hour history of back pain and difficulty walking. Examination of the lower limbs reveals bilaterally increased tone with reduced power, brisk reflexes and extensor plantars. What would the most useful investigation be? A) Plain X-ray of the spine B) Spinal CT scan C) Spinal MRI scan D) Nerve conduction studies E) Electromyography Question 7. A 76-year-old man undergoing treatment for lung cancer attends hospital with polyuria, thirst and mild confusion. Initial blood tests reveal a corrected calcium level of 3.02 mmol/l (reference range 2.12-2.62). What is the most important initial treatment? A) Intravenous saline B) Intravenous bisphosphonate C) Intravenous furosemide D) Calcium gluconate E) Calcitonin Question 8. A 68-year-old man with small-cell lung cancer complains of worsening shortness of breath and a persistent headache. On examination, the jugular venous pressure is raised but nonpulsatile, prominent vessels are seen on the chest wall and there is facial oedema. What is the most likely diagnosis? A) Congestive heart failure B) Lymphangitis carcinomatosa C) Nephrotic syndrome D) Superior vena caval obstruction E) Side-effects of radiotherapy 26 Question 9. A 55-year-old woman with breast cancer is admitted to hospital complaining of headaches which are worst in the morning, together with nausea and vomiting. The result of a CT head scan is show: Which one of the following would be the best initial treatment? A) Furosemide B) Dexamethasone C) Radiotherapy D) Chemotherapy E) Surgical resection of the abnormal lesions Question 10. Which of the following sideeffects is least likely to result from radiotherapy? A) Pulmonary fibrosis B) Erythema and desquamation of the skin C) Ischaemic heart disease D) Peripheral neuropathy E) Diarrhoea Question 11. Which one of the following statements about the drug tamoxifen is true? A) It commonly causes neutropenia B) It should be offered to all patients with breast cancer C) It is an alkylating agent D) Evidence supports its use in metastatic breast cancer only E) It exerts its effect by acting as an oestrogen receptor antagonist Chapter 11 PALLIATIVE CARE AND PAIN MANAGEMENT Answers page 144 Question 1. All of the following features except one suggest a neuropathic origin of pain. Which is the exception? A) Occurs in an area of sensory loss B) Is burning in nature C) Occurs in response to non-painful stimuli D) Has a better response to non-steroidal antiinflammatory drugs (NSAIDs) than tricyclic antidepressants E) Is associated with abnormal unpleasant sensations Question 2. Which one of the following pain treatments is least appropriately paired with the type of pain? A) Bone pain Non-steroidal anti-inflammatory drugs (NSAIDs) B) Liver capsule pain Opioids C) Raised intracranial pressure Corticosteroids D) Neuropathic pain Anticonvulsants E) Abdominal colic Antispasmodics Question 3. A patient with widespread metastatic prostatic carcinoma complains of troublesome, constant pain at multiple sites. He takes regular paracetamol, codeine and ibuprofen at full dose but continues to experience severe pain. According to the WHO analgesic ladder, what is the most appropriate next step in his pain management? A) Replace codeine with a strong opioid such as morphine B) Replace ibuprofen with a strong opioid such as morphine C) Replace ibuprofen with an alternative nonsteroidal anti-inflammatory drug (NSAID) such as diclofenac D) Add dihydrocodeine to existing medications E) Add a neuropathic agent to existing medications Question 4. Which one of the following statements regarding side-effects of strong opioids used in cancer pain is true? A) Nausea and vomiting tend to worsen with increased duration of treatment 27 B) Excessive salivation is common C) Constipation should be managed with a reduction in dose rather than laxative agents D) Respiratory depression is more likely to be a problem in acute dosing than with patients on regular opioids E) Sedation and drowsiness are uncommon in patients under 65 years Question 5. A patient with metastatic pancreatic carcinoma was admitted to hospital from home with a 4-day history of worsening drowsiness and confusion. Her dose of 12hourly controlled-release (CR) morphine had been doubled 1 week previously, as her pain had been poorly controlled. On admission she has a Glasgow Coma score of 13 (E3 M6 V4), with small pupils and periodic myoclonic jerks. After 24 hours free of opiates she is now much more alert but starting to experience pain again. Which of the following would be the best strategy for managing her pain? A) Restart her CR morphine at the same dose and also prescribe 'as required' doses of immediate-release (IR) morphine B) Restart her CR morphine at the same dose but withhold 'as required' doses C) Reduce the CR morphine to the previous dose (prior to adjustment) and also prescribe 'as required' doses of IR morphine D) Change from CR morphine to regular IR morphine at a lower equivalent dose and also prescribe 'as required' doses of IR morphine E) Change from CR morphine to a fentanyl patch at a lower equivalent dose and also prescribe 'as required' doses of oral IR morphine Question 6. A patient with advanced bowel cancer presents with persistent large-volume vomiting and severe colicky abdominal pain. Abdominal imaging reveals multiple levels of gastrointestinal obstruction. Which one of the following antiemetics is contraindicated? A) Cyclizine B) Metoclopramide C) Levomepromazine D) Ondansetron E) Prochlorperazin Chapter 12 INFECTIOUS DISEASES Answers page 146 Question 1. A gap-year student returns from the Far East with a temperature of 39°C. You take a detailed history of exposures. Which one of the following exposures is incorrectly paired with the resulting infection? A) Fresh-water swimming Schistosomiasis B) Unprotected sexual contact Hepatitis B C) Unpasteurised milk Leptospirosis D) Tick bite Typhus E) Mosquito bite Dengue fever Question 2. All of the following except one are infective causes of splenomegaly. Which is the exception? A) Brucellosis B) Falciparum malaria C) Giardiasis D) Leishmaniasis E) Subacute bacterial endocarditis Question 3. A 24-year-old medical student returns from her elective in Mauritius and attends the tropical diseases unit with an intensely itchy rash on her foot, present since just before she came home. She admits to having walked barefoot a lot while abroad. On examination, there is a serpiginous linear lesion on the sole of her foot. It is now 7-8 cm in length, and she says that it has been elongating. What is the most likely diagnosis? A) Staphyloccus aureus cellulitis B) Cutaneous larva migrans C) Scabies D) Onchocerciasis E) Strongyloidiasis 28 Question 4. A traveller, returning from East Africa to the UK with a fever of 38.7°C, has a full blood count performed as part of his initial work-up. This reveals an eosinophilia (eosinophil count 0.6 × 109). Which one of the following diagnoses is least consistent with this finding? A) Schistosomiasis B) Strongyloidiasis C) Ascariasis D) Tuberculosis E) Filariasis Question 5. Regarding measles, which one of the following statements is correct? A) The incubation period is 5 days to onset of rash B) Koplik's spots on the retina are pathognomonic C) Antibiotics should be given to prevent the development of bacterial pneumonia D) Infants are protected for the first 6 months of life by passive immunity from maternal antibodies E) Children with the disease should be offered vaccination as soon as they recover Question 6. Which of the following pairings of childhood exanthems and their complications is incorrect? A) Rubella Myocarditis B) Measles Subacute sclerosing panencephalitis (SSPE) C) Human erythrovirus 19 (parvovirus B19) Anaemia D) Mumps Orchitis E) Chickenpox Pneumonia Question 7. A 76-year-old gentleman presents to his general practitioner with a 2-day history of burning discomfort around the left side of his chest. On examination, you find a vesicular rash in a band-like distribution around his left side: Question 10. All of the following statements about cytomegalovirus (CMV) are true except one. Which is the exception? A) In immunosuppressed patients, infection may cause sight-threatening retinitis B) In pregnant women, the infection may have neurological sequelae for the fetus C) In healthy young adults, infection is usually asymptomatic D) The peak incidence of acquisition is in the sixth decade E) The virus is shed in saliva, urine and semen Which of the following is the most likely causative organism? A) Treponema pallidum B) Herpes simplex virus C) Varicella zoster virus D) Staphylococcus aureus E) Human erythrovirus 19 (parvovirus B19) Question 11. A 19-year-old male attends his general practitioner 3 days after returning from back-packing in South-east Asia. He complains of headache, generalised aches and pains, painful eye movements and a rash. He recalls a number of mosquito bites in the week prior to returning home but appears to have taken appropriate antimalarial prophylaxis throughout the trip and since his return. On examination, he has lymphadenopathy, a temperature of 38.2°C, and a maculopapular morbilliform rash on his trunk. Which one of the following diagnoses is most likely? A) Salmonella B) Schistosomiasis C) Leishmaniasis D) Dengue E) Strongyloidiasis Question 8. Which one of the following statements about smallpox is true? A) It has been used as a bioterrorist agent B) Infection carries a mortality rate of 90% C) The vesiculo-pustular rash is most dense on the trunk, with sparing of the extremities D) No successful vaccine has ever been developed E) It is caused by a DNA poxvirus Question 9. A 14-year-old boy, living in London, is brought to the hospital accident and emergency department by his mother with a 6-day history of malaise, fever and sore throat. He gives no history of recent foreign travel. His temperature is 38°C. On examination, you note that he has an inflamed pharynx, cervical lymphadenopathy, a tender enlarged liver and a palpable spleen. What is the most likely diagnosis? A) Infectious mononucleosis B) Malaria C) Influenza D) Mumps E) Listeriosis 29 Question 12. Fifteen patients in a large care of the elderly unit in the UK develop nausea and vomiting in the space of 3 days. A number of nursing and medical staff also report vomiting. Which one of the following agents is the most likely cause of the outbreak? A) Meticillin-resistant Staphylococcus aureus (MRSA) B) Clostridium difficile C) E. coli D) Calicivirus E) Norovirus Question 13. Infection with Staphylococcus aureus is commonly responsible for all of the following conditions except one. Which is the exception? A) Endocarditis B) Pneumonia C) Hepatitis D) Osteomyelitis E) Cellulitis Question 14. A 16-year-old girl is brought to the hospital accident and emergency department by her parents, having developed a high fever, headache and sore throat over the last 12 hours. She tells you that she has just finished menstruating. On examination, she has a temperature of 38.6°C, blood pressure of 90/40 mmHg and a generalised erythematous blanching rash. There are no signs of meningism or petechiae. Which of the following is the most likely diagnosis? A) Infectious mononucleosis B) Staphylococcal toxic shock syndrome C) Scarlet fever D) Rubella E) Rheumatic fever Question 15. Which of the following conditions is least likely to occur as a consequence of streptococcal infection? A) Scarlet fever B) Endocarditis C) Rheumatic fever D) Glomerulonephritis E) Haemolytic uraemic syndrome 30 Question 16. All of the following except one are recognised clinical features of brucellosis. Which is the exception? A) Pyoderma gangrenosum B) Uveitis C) Meningitis D) Endocarditis E) Septic arthritis Question 17. A 24-year-old student presents to the dermatology clinic with an expanding red macule on her left calf; this appeared 2 weeks previously, shortly after returning from holiday in Connecticut, USA. She reports that the lesion has been progressively increasing in size since it appeared. On examination, the lesion now measures approximately 15 cm across and appears to be clearing from the centre outwards. Which of the following is the likely diagnosis of her rash? A) Necrobiosis lipoidica B) Erythema nodosum C) Pyoderma gangrenosum D) Cellulitis E) Erythema chronicum migrans Question 18. With reference to the patient from the previous question (Q17), the diagnosis of Lyme borreliosis is confirmed by polymerase chain reaction (PCR) testing of her urine. She is not pregnant and has no known allergies. Which of the following is the most appropriate treatment? A) 14-day course of doxycycline B) 1-month course of clarithromycin C) 1-month course of metronidazole D) Observation only E) 14-day course of penicillin Question 19. A 45-year-old male who is a keen water-skier is brought to the infectious diseases unit with a 24-hour history of jaundice, fever and nosebleeds. There is no history of recent foreign travel. On examination, his temperature is 39°C, he is deeply jaundiced and has an enlarged liver. His conjunctivae are hyperaemic and there is a marked purpuric rash on the trunk and limbs. Blood results are as follows: Question 21. Which of the following statements about staphylococcal food poisoning is false? A) Dairy products and cooked meat are an important source of infection B) Refrigeration of food products encourages the growth of heat-stable enterotoxins C) Symptoms arise within 1-6 hours of ingestion of contaminated foodstuffs D) Vomiting is a more common symptom than diarrhoea E) A marked neutrophilia is common Question 22. Which one of the following statements is incorrect with regard to Escherichia coli? A) It is the most common cause of travellers' diarrhoea B) The incubation period of enterotoxigenic E. coli (ETEC) is 1-2 days C) Enteropathic E. coli (EPEC) is an important cause of infant diarrhoea D) Enterohaemorrhagic E. coli (EHEC) may lead to haemolytic uraemic syndrome E) Entero-invasive E. coli (EIEC) causes symptoms through production of an enterotoxin Which of the following is the most likely diagnosis? A) Listeriosis B) Hepatitis A C) Meningococcal sepsis D) Weil's disease (leptospirosis) E) Infectious mononucleosis (Epstein-Barr virus) Question 20. Which type of transmission does typhoid fever demonstrate? A) Droplet spread B) A bite from an infected animal vector C) Faecal-oral D) Sexual E) Blood-borne, i.e. needlestick injuries 31 Question 23. Which of the following antibiotics is used as first-line therapy for symptomatic infection with Clostridium difficile? A) Co-amoxiclav B) Metronidazole C) Cefuroxime D) Clarithromycin E) Clindamycin Question 24. Which one of the following gastrointestinal infections does not cause bloody diarrhoea? A) Cholera B) Salmonella C) Shigella D) Entamoeba histolytica E) Campylobacter Question 25. Which one of the following statements is correct regarding the correction of fluid and electrolyte balance in the patient with acute diarrhoea? A) 48 hours of diarrhoea in the average adult will result in a fluid deficit of half a litre B) Intravenous fluid replacement is preferable to oral rehydration for most patients with acute diarrhoea C) Oral rehydration solution (ORS) contains carbohydrate, sodium, potassium and chloride D) Prolonged bouts of diarrhoea result in the development of a metabolic alkalosis E) Infants with gastroenteritis should not be breastfed while they have diarrhoea Question 26. A sales executive, recently returned to the UK from Ukraine, is referred to the local infectious diseases unit by his general practitioner with a sore throat of unusual appearance. On arrival, he is tachycardic with a heart rate of 110 bpm, and has a mild pyrexia of 37.7°C. There is a slight blood-stained discharge at the nasal orifices. His neck is visibly swollen. Examination of the mouth reveals a greyish-green membrane overlying the tonsils, which does not come off with gentle scraping with the tongue depressor. What is the likely diagnosis? A) Streptococcal throat infection B) Diphtheria C) Oral candidiasis D) Mumps E) Tonsillar carcinoma Question 27. A 45-year-old Indian man visiting his family in the UK is brought to the infectious diseases unit by his son who is concerned about the appearance of what he terms a 'rash' on his father's back. On examination, there are three well-defined hypopigmented macules that are completely anaesthetic. You note that both the patient's median and ulnar nerves are palpably thickened bilaterally, with variable sensory loss distal to the wrists in both upper limbs. Which of the following is the most likely underlying diagnosis? A) Toxoplasmosis B) Botulism C) Cutaneous leishmaniasis D) Leprosy E) Tuberculosis Question 28. With regard to the patient in the previous question (Q27), which one of the following investigations will confirm the diagnosis of leprosy? A) Leprosy serology B) Polymerase chain reaction (PCR) of serum for Mycobacterium leprae DNA C) Microscopy of split skin smears D) Nasal swab E) Blood culture Question 29. Which of the following antimicrobial agents is commonly used in the treatment of leprosy? A) Clindamycin B) Chloroquine C) Chloramphenicol D) Rifampicin E) Penicillin V Question 30. Which of the following organisms is responsible for cat scratch disease? A) Toxoplasma gondii B) Chlamydia psittaci C) Rickettsia rickettsii D) Bartonella henselae E) Coxiella burnetti 32 Question 31. A 19-year-old gap-year student returns to the UK after working for 6 weeks in West Africa on a charity project. Shortly after returning, he presents to his general practitioner with a 4-day history of intermittent fevers, tiredness, headache and general malaise. On examination, he is mildly jaundiced. His heart rate is 110 bpm and temperature is 38.2°C. He has a palpable spleen and a tender liver edge but no rash or lymphadenopathy. Question 34. Which of the following statements regarding the treatment and chemoprophylaxis of malaria is correct? A) Chloroquine resistance is rare B) Falciparum malaria is still largely sensitive to quinine C) Chemoprophylaxis with doxycycline should be continued for 7 days after leaving a malarious area D) Quinine is associated with troublesome neuropsychiatric side-effects E) Fansidar is suitable for chemoprophylaxis Question 35. Which one of the following statements regarding visceral leishmaniasis is incorrect? A) It is transmitted from human to human by the sandfly B) Both splenomegaly and hepatomegaly are common clinical features C) Dermatological manifestations include black discoloration of the skin D) Blood tests typically reveal thrombocytosis and neutrophilia E) The treatment of choice is pentavalent antimony Which one of the following is the most likely diagnosis? A) Leishmaniasis B) Falciparum malaria C) HIV seroconversion illness D) Q fever E) Infectious mononucleosis Question 32. All of the following except one are potential complications of falciparum malaria. Which is the exception? A) Convulsions B) Acute renal failure C) Nephrotic syndrome D) Hypoglycaemia E) Metabolic acidosis Question 33. Which one of the following investigations is diagnostic for malaria? A) Thin blood film B) Full blood count C) Blood culture D) Serology for P. falciparum E) Coagulation screen 33 Question 36. A 19-year-old woman is referred by her general practitioner to the local dermatology department, 3 months after returning from a trip to Central America. She has an ulcer on the lateral aspect of her calf, which has failed to heal with a 2-week course of flucloxacillin. It began 1 month previously as a raised red 'lump', then increased in size to about 6 cm, before ulcerating and developing a crust. Swabs of the ulcer have grown skin commensals only, but a biopsy shows numerous parasites. What is the most likely diagnosis? A) Toxoplasmosis B) Cutaneous leishmaniasis C) Babesiosis D) Plasmodium vivax malaria E) Trypanosomiasis Question 37. Infection with which one of the following organisms is most commonly associated with cardiac complications, including dilated cardiomyopathy and conduction defects? A) Toxoplasma gondii B) Trypanosoma cruzi C) Leishmania donovani D) Ancylostoma braziliense E) Cytomegalovirus Question 38. Which of the following is a vector for African trypanosomiasis (African sleeping sickness)? A) African sandfly B) Tsetse fly C) Mosquito D) Ixodes tick E) Freshwater snail Question 39. With regard to toxoplasmosis, which one of the following statements is incorrect? A) Domestic cats are important hosts in the life cycle of Toxoplasma gondii B) Infection is asymptomatic in the majority of individuals C) Congenital toxoplasmosis is characterised by retinochoroiditis, microcephaly and hydrocephalus D) Serological tests are available for the detection of past and present infection with Toxoplasma gondii E) The most common presenting features of acquired toxoplasmosis are fever, photophobia and a non-specific rash Question 40. Which one of the following statements regarding amoebiasis is correct? A) The parasite typically invades the small bowel B) The incubation period of the Entamoeba histolytica cyst is 48 hours C) Clinically, the disease manifests as diarrhoea alternating with constipation, with the presence of blood and mucus D) Diagnosis is made on stool culture 34 E) The infection is responsive to penicillin antibiotics Question 41. Which one of the following features is least characteristic of strongyloidiasis? A) Abdominal pain B) Urticaria C) Diarrhoea D) Motile larvae on stool microscopy E) Neutrophilia Question 42. A 53-year-old man, recently returned to the UK from a holiday in Indonesia, presents with a tender, erythematous right leg and thigh. On examination, his right leg is swollen, warm, painful and red along the length of its medial aspect. There is marked oedema. He also has an acutely tender right testicle and swelling of the right inguinal lymph nodes. A full blood count reveals eosinophilia. Which one of the following is the most likely diagnosis? A) Acute streptococcal cellulitis B) Filiariasis C) Cutaneous larva migrans infection D) Tinea pedis E) Histoplasmosis Question 43. Which of the five senses is most commonly affected by infection with Onchocerca volvulus (onchocerciasis)? A) Vision B) Taste C) Hearing D) Touch E) Smell Question 44. The following are all recognised sequelae of chronic infection with schistosomiasis except one. Which is the exception? A) Hydronephrosis B) Oesophageal varices C) Splenomegaly D) Urticaria E) Recurrent urinary tract infection Chapter 13 HIV INFECTION AND THE AIDS Answers page 153 Question 1. Which of the following best describes the human immunodeficiency virus (HIV)? A) Single-stranded RNA virus B) Double-stranded RNA virus C) Single-stranded DNA virus D) Double-stranded DNA virus E) Prion Question 2. What is the main mode of transmission of HIV in northern Europe and the United States? A) Blood transfusion B) Heterosexual transmission C) Homosexual transmission D) Intravenous drug use E) Vertical (mother to child) transmission Question 3. Which of the following exposures has the highest transmission risk for HIV? A) Genital mucous membrane contact B) Intravenous drug use using a contaminated needle C) Being born to a mother who is HIVpositive but not on highly active antiretroviral therapy (HAART) D) Homosexual intercourse between two men E) Receipt of infected blood products Question 4. Which one of the following options best characterises the virological and immunological progression of HIV infection in the first 4-8 weeks following exposure? A) CD4 count rises, viral load falls B) CD4 count falls, viral load rises C) Both CD4 count and viral load rise D) Both CD4 count and viral load fall E) CD4 count remains stable, viral load rises 35 Question 5. Which one of the following is not an AIDS-defining disease? A) Pulmonary tuberculosis B) Kaposi's sarcoma C) Cytomegalovirus retinitis D) Oropharyngeal candidiasis E) Cerebral toxoplasmosis Question 6. Which one of the following statements regarding Cryptosporidium infection is incorrect? A) Patients typically present with profuse, bloody diarrhea B) It tends to occur when the CD4 count is < 200 cells/mm3 C) Definitive diagnosis is made on stool microscopy D) Complications include cholecystitis, cholangitis and pneumonitis E) Cryptosporidium is a protozoal enteric pathogen Question 7. Which one of the following pathogens is least likely to be responsible for chronic diarrhoea in the HIV-positive patient? A) Isospora B) Mycobacterium avium intracellulare C) Microsporidium D) Cytomegalovirus E) Toxoplasma Question 8. Which one of the following options would not be supportive of a diagnosis of Pneumocystis carinii (jirovecii) pneumonia? A) 2-3-week history of shortness of breath B) A cough productive of green sputum C) Marked oxygen desaturation on exercise D) A lack of response to penicillin antibiotics E) Pyrexia Question 9. Which one of the following statement regarding cryptococcal meningitis is true? A) The organism is identified on cerebrospinal fluid (CSF) microscopy with Ziehl-Neelsen staining B) The majority of affected patients have a CD4 count > 200 cells/mm3 C) Deafness and blindness are the most common complications D) Neck stiffness is invariably present E) Penicillin is the treatment of choice Question 10. A 27-year-old HIV-positive patient with a CD4 count of 20 cells/mm3 presents to the hospital accident and emergency department with visual difficulties. He reports a 6-week history of flashing lights and dark 'clouds' floating in front of his eyes. In the past fortnight he has experienced problems with driving, narrowly escaping a collision with a cyclist whom he did not see on the road beside him. On examination, the conjunctivae are injected and fundoscopy reveals haemorrhagic exudates near the retinal vessels. What is the likeliest diagnosis? A) Bacterial conjunctivitis B) Herpes simplex keratitis C) Anterior uveitis D) Cytomegalovirus (CMV) retinitis E) Acute retinal necrosis Question 11. A 37-year-old homosexual male who is HIV-positive (CD4 count 300 cells/mm3) is found on a routine visit to the infectious diseases clinic to have purplish-blue papules across the bridge of his nose; these have appeared in the last 4 months. He is otherwise asymptomatic. On examination, he has cervical lymphadenopathy and hepatosplenomegaly. Which one of the following diagnoses is most likely? A) Seborrhoeic dermatitis B) Disseminated cutaneous herpes simplex C) Molluscum contagiosum D) HIV-associated lymphoma E) Kaposi's sarcoma 36 Question 12. Which one of the following is not a characteristic side-effect of treatment with nucleoside reverse transcriptase inhibitors (NRTIs)? A) Cranial nerve palsies B) Peripheral neuropathy C) Pancreatitis D) Anaemia E) Lipoatrophy Question 13. Which one of the following statements about protease inhibitors (PIs) is incorrect? A) They act by preventing posttranslational cleavage of polypeptides into functional viral proteins B) They cause glucose intolerance and frank diabetes in a proportion of patients C) Metabolism is via the P450 system of enzymes D) They improve the lipid profile of most patients by lowering total cholesterol and low-density lipoprotein (LDL), and by raising high-density lipoprotein (HDL) E) Monitoring of plasma levels helps to optimise antiviral effect and reduce toxicity Question 14. All of the following except one are advantages of non-nucleoside reverse transcriptase inhibitors (NNRTIs) over other anti-HIV agents. Which is the exception? A) Once-daily dosing B) Good oral bioavailability C) Lower tablet numbers than with NRTIs D) No association with fat redistribution E) Low incidence of drug rashes Question 15. Which one of the following opportunistic infections is incorrectly matched with its appropriate prophylactic agent? A) Tuberculosis Rifampicin and isoniazid B) Toxoplasmosis Erythromycin C) Pneumocystis carinii (jirovecii) pneumonia Co-trimoxazole D) Cryptococcus Itraconazole E) Mycobacterium avium intracellulare (MAI) Azithromycin Chapter 14 SEXUALLY TRANSMITTED INFECTIONS Answers page 156 Question 1. Worldwide, which of the following is the most common curable sexually transmitted infection (STI)? A) Syphilis B) Gonorrhoea C) Chlamydia D) Trichomonas vaginalis E) HIV Question 2. A 22-year-old heterosexual male presents to the STI clinic with a 2week history of purulent urethral discharge and dysuria. He has been sexually active in the past month with two new partners. Gram-stained smear of urethral exudate shows Gram-negative diplococci, along with prominent polymorphonuclear cells. What is the most likely cause for the gentleman's urethral discharge? A) Non-gonococcal urethritis B) Syphilis C) Genital warts D) Gonorrhoea E) Staphylococcal infection Question 3. A 23-year-old girl presents to her GP, with a 3-day history of a painful rash over her perineum. This was preceded by 2 days of 'flu-like symptoms'. She has been sexually active with a new partner for the last 6 weeks and takes the oral contraceptive pill, but does not use barrier contraception. On examination, she has a cluster of small vesicles on both labia majora. Which is the most appropriate next investigation? A) High vaginal swab B) Urethral swab C) HIV test D) Swab of the contents of a vesicle E) Urine microscopy and cultu 37 Question 4. Which of the following genotypes of human papillomavirus (HPV) is associated with dysplastic conditions and cancers of the genital tract? A) HPV 6 and 11 B) HPV 16 and 18 C) HPV 10 and 15 D) HPV 6 only E) HPV 10 and 13 Question 5. A 34-year-old Englishwoman is referred to the local gynaecology outpatient department with a 2-year history of intermittent pelvic pain. In her history, she also describes dyspareunia and occasional post-coital bleeding. She and her husband have been trying to conceive without success for the past 18 months. Examination of the external genitalia is unremarkable. On per vaginam examination, you see an inflamed cervix, which is partly covered by a mucopurulent discharge. Which of the following diagnoses is most likely? A) Syphilis B) Herpes simplex type 1 infection C) Herpes simplex type 2 infection D) Trichomoniasis E) Chlamydial infection Question 6. A 35-year-old lady is referred to Gynaecology triage with a 7-day history of a profuse, foul-smelling vaginal discharge. She is very distressed by this, as the quantities produced are necessitating the use of sanitary towels. On speculum examination, the external genitalia are entirely normal but the vagina itself is slightly inflamed. High and low vaginal swabs are taken, as well as a wet film of some of the discharge, which is sent immediately for microscopy. Motile flagellate organisms are seen in large numbers. What is the diagnosis? A) Trichomoniasis B) Bacterial vaginosis C) Herpes simplex type 2 infection D) Chlamydial infection E) Gonorrhoea Question 7. Which one of the following is not a feature of secondary syphilis? A) Condylomata lata B) Meningitis C) Generalised lymphadenopathy D) A maculo-papular rash on the trunk and limbs 38 E) Syphilitic chancre Question 8. Which one of the following is not a feature of congenital syphilis? A) Hutchinson's incisors B) Saddle nose C) Sabre tibia D) Webbed neck E) Mulberry molars Question 9. A 17-year-old female reluctantly attends her GP to discuss the problem of a 2-month history of a whitish vaginal discharge and vulval pruritus. She is not sexually active and her only past medical history is of acne, for which she takes regular minocycline. On examination, her external genitalia are inflamed and traces of a curd-like discharge can be seen at the vaginal orifice. What is the most likely diagnosis? A) Human papillomavirus infection B) Vaginal candidiasis C) Chlamydial infection D) Toxic shock syndrome (TSS) E) Gonorrhoea Chapter 15 CLINICAL BIOCHEMISTRY AND METABOLISM Answers page 158 Question 1. A typical adult male has a total body water of 40 litres. How much of this is located within the extracellular fluid compartment? A) 25 litres B) 15 litres C) 9 litres D) 6 litres E) 3 litres Question 2. The most abundant cation within the intracellular fluid compartment is: A) Sodium B) Chloride C) Potassium D) Hydrogen E) Calcium Question 3. A blood sample is analysed after significant in vitro haemolysis has occurred. Which of the following spurious results is most likely to occur in the measured electrolytes? A) High sodium B) High potassium C) Low sodium D) Low potassium E) High chloride Question 4. The total body content of which ion is a principal determinant of ECF volume? A) Sodium B) Potassium C) Calcium D) Chloride E) Bicarbonate 39 Question 5. What proportion of filtered sodium is normally reabsorbed within the proximal tubule? A) 90% B) 65% C) 40% D) 25% E) 5% Question 6. Which one of the following clinical signs would be an unexpected finding in the presence of hypovolaemia? A) Low jugular venous pulse B) Reduced skin turgor C) Bradycardia D) Postural hypotension E) Reduced urine output Question 7. The normal physiological response to loss of sodium and water comprises all of the following except one. Which is the exception? A) Enhanced conversion of angiotensinogen to angiotensin I B) Reduced glomerular filtration rate C) Activation of the sympathetic nervous system D) Increased release of atrial natriuretic peptide E) Stimulation of thirst Question 8. Which one of the following clinical conditions would be least likely to cause sodium and water excess? A) Chronic renal failure B) Nephrotic syndrome C) Conn's syndrome D) Congestive cardiac failure E) Addison's disease Question 9. The diuretic furosemide acts principally at which of the following sites within the kidney? A) Glomerulus B) Proximal tubule C) Loop of Henle D) Early distal tubule E) Collecting ducts Question 10. Which one of the following metabolic abnormalities is most likely to be caused by treatment with a thiazide diuretic? A) Hypocalcaemia B) Hyponatraemia C) Hyperkalaemia D) Hypermagnesaemia E) Hypoglycaemia Question 11. Which one of the following conditions is a cause of hypovolaemic hyponatraemia? A) Primary polydipsia B) Hyperlipidaemia C) Nephrotic syndrome D) Syndrome of inappropriate ADH secretion (SIADH) E) Diuretic therapy Question 12. During an employment medical, a 59-year-old male is found to have a plasma sodium of 126 mmol/l. He is asymptomatic and clinical examination reveals no abnormal findings other than mild obesity. Further blood tests reveal a plasma osmolality of 250 mmol/kg (normal range 280-290 mmol/kg) and a urine osmolality of 360 mmol/kg. Which of the following is the likeliest diagnosis? A) Diuretic abuse B) Primary polydipsia C) Nephrotic syndrome D) Syndrome of inappropriate ADH secretion (SIADH) E) Cranial diabetes insipidus Question 13. Aside from identifying and treating possible underlying causes, what is the most appropriate initial management for the patient in the previous question who has SIADH? A) Infusion of 0.9% saline (normal saline) B) Infusion of hypertonic saline 40 C) Increased oral salt intake D) Fluid restriction of 1-1.5 litres per day E) Demeclocycline therapy Question 14. Which of the following drugs is most likely to cause SIADH? A) Metformin B) Carbamazepine C) Digoxin D) Amiodarone E) Alendronate Question 15. Which one of the following ECG changes is most typical of hyperkalaemia? A) Peaked P wave B) Presence of U wave C) ST segment depression D) Peaked T wave E) Narrowed QRS complex Question 16. Which one of the following would be most likely to produce hypokalaemia (plasma K < 3.5 mmol/l)? A) Addison's disease B) Amiloride therapy C) Conn's syndrome D) Rhabdomyolysis E) Acute renal failure Question 17. Treatment with which one of the following drugs is most likely to lead to hyperkalaemia? A) Bendroflumethiazide B) Warfarin C) Ramipril D) Salbutamol E) Calcium resonium Question 18. Which one of the following treatments for hyperkalaemia is not used to lower the concentration of plasma potassium? A) Insulin B) Salbutamol C) Calcium resonium D) Dialysis E) Calcium gluconate Question 19. Which one of the following conditions would be most likely to cause a normal anion gap metabolic acidosis? A) Sepsis B) Salicylate poisoning C) Starvation D) Diabetic ketoacidosis E) Renal tubular acidosis Question 20. The following laboratory results are obtained from a patient on a general surgical ward: Urine pH: 5.5 What is the acid-base abnormality? A) Raised anion gap metabolic acidosis B) Normal anion gap metabolic acidosis C) Metabolic alkalosis D) Respiratory acidosis E) Respiratory alkalosis Question 21. Which one of the following disorders is most likely to be responsible for the results seen in the previous question? (shown again below) Urine pH: 5.5 A) Gastric outlet obstruction B) Acute renal failure C) Traveller's diarrhea D) Hypothyroidism E) Salicylate ingestion Question 22. Which of the following lipoproteins is primarily responsible for reverse cholesterol transport? A) Chylomicrons B) Very low-density lipoprotein 41 C) Low-density lipoprotein D) Intermediate-density lipoprotein E) High-density lipoprotein Question 23. Which one of the following clinical features is more characteristic of hypertriglyceridaemia than hypercholesterolaemia? A) Xanthelasma B) Corneal arcus C) Eruptive xanthomas D) Achilles tendon xanthomas E) Premature cardiovascular disease Question 24. Regarding therapy with HMGCoA reductase inhibitors (statins), which one of the following statements is true? A) The incidence of rhabdomyolysis is around 10% B) In patients with hypercholesterolaemia and risk factors for atherosclerosis, they reduce the risk of coronary events but not stroke C) They inhibit endogenous cholesterol synthesis D) They lead to a modest reduction in high-density lipoprotein (HDL) cholesterol E) They have a greater effect on triglyceride levels than low-density lipoprotein (LDL) cholesterol levels Question 25. Which one of the following clinical features would be an unexpected finding in an attack of acute intermittent porphyria? A) Acute abdominal pain B) Bullae on sun-exposed areas of skin C) Behavioural disturbance D) Hypertension and tachycardia E) Constipation Chapter 16 KIDNEY AND URINARY TRACT DISEASE Answers page 163 Question 1. A renal bruit is associated with which of the following disorders? A) Conn's syndrome B) Hypertensive nephropathy C) Wegener's granulomatosis D) Polyarteritis nodosa E) Renal artery stenosis Question 2. The following are all causes of a palpably enlarged kidney except one. Which is the exception? A) Polycystic kidney disease B) Renal cell carcinoma C) Diabetic nephropathy D) Hydronephrosis E) Renal amyloidosis Question 3. In a 70 kg man who has a normal diet, what is the minimum volume of urine production required each day to excrete the daily solute load? A) 15 ml B) 50 ml C) 100 ml D) 500 ml E) 1200 ml Question 4. All of the following except one would be expected to cause an increase in serum urea concentration. Which is the exception? A) Severe burns B) Reduction in glomerular filtration rate (GFR) C) Malnutrition D) Dehydration E) Upper gastrointestinal haemorrhage 42 Question 5. Serum creatinine is often used as a surrogate measure of glomerular filtration rate (GFR). Which of the following best describes the relationship between the change in serum creatinine concentration and GFR? A) Negative exponential B) Direct proportion (positive linear) C) Inverse proportion (negative linear) D) Positive exponential E) 'Build-up' exponential Question 6. Which of the following is freely filtered in the normal glomerulus? A) Albumin B) Glucose C) Red blood cells D) Platelets E) Fibrinogen Question 7. The presence of red cell casts on urine microscopy is most likely to be due to which one of the following? A) Urethral trauma B) Urinary tract infection C) Bladder carcinoma D) Ureteric stone E) Post-streptococcal glomerulonephritis Question 8. When serum creatinine is used as a guide to renal excretory function, which one of the following might lead to under-estimation of the degree of renal impairment? A) Upper gastrointestinal haemorrhage B) Reduced muscle bulk C) Excessive dietary protein D) Liver failure E) Catabolic state Question 9. Intravenous urography (IVU) is superior to renal ultrasound for which one of the following purposes? A) Detection of urothelial malignancy B) Assessing size and symmetry of kidneys C) Distinguishing between solid and cystic masses D) Identifying hydronephrosis E) Assessing renal blood flow Question 10. Which of the following investigations provides most information on the relative contribution of each kidney to overall renal function? A) Renal biopsy B) Renal ultrasound C) Magnetic resonance imaging (MRI) of kidneys D) Dimercaptosuccinic acid (DMSA) isotope renogram E) Renal arteriogram Question 11. Which one of the following is a contraindication to renal biopsy? A) Haematuria B) Kidneys < 60% normal size C) Anaemia D) Rapid deterioration in renal function E) Angiotensin-converting enzyme (ACE) inhibitor therapy Question 12. Which of the following organisms is the most common cause of community-acquired lower urinary tract infection (UTI)? A) Escherichia coli B) Staphylococcus aureus C) Pseudomonas aeruginosa D) Klebsiella spp. E) Proteus mirabilis Question 13. A 73-year-old man collapses at home following a stroke. He is found 24 hours later, still lying on the floor. On admission to hospital he appears only mildly dehydrated but is in acute renal failure. He is treated with IV fluids but remains oliguric and his renal function continues to deteriorate. Dipstick urinalysis is strongly positive for blood but 43 microscopy reveals no red cells. What is the most likely diagnosis? A) Renal calculus B) Urinary sepsis C) Rapidly progressive glomerulonephritis D) Renal infarction E) Rhabdomyolysis Question 14. A 68-year-old man reports visible blood in his urine for the past 8 weeks. He is otherwise asymptomatic and has no history of renal disease. Urine culture has been negative on two occasions and serum creatinine is within the normal range. Repeat urinalysis shows: Blood +++, Protein nil. Which of the following pairs of investigations would now be most appropriate for this patient? A) Renal biopsy and intravenous urography (IVU) B) Cytological analysis of urine and microscopy for acid-fast bacilli C) Cystoscopy and renal ultrasound D) Prostatic biopsy and prostate-specific antigen (PSA) level E) Anti-glomerular basement membrane (GBM) and c-ANCA (antineutrophil cytoplasmic antibodies) Question 15. Which of the following conditions would not account for the finding of proteinuria on routine testing with standard dipsticks? A) Urinary tract trauma B) Urinary tract infection C) Transitional cell bladder carcinoma D) Minimal change nephropathy E) Microalbuminuria Question 16. A 55-year-old man with persistent proteinuria on dipstick analysis has 3.6 g of protein in a 24-hour urine collection. Which one of the following disorders would account for this? A) Persistent urinary tract infection B) Acute tubular necrosis C) Transitional cell carcinoma D) Chronic interstitial nephritis E) Focal segmental glomerulosclerosis Question 17. Which of the following abnormalities is most commonly associated with the nephrotic syndrome? A) Impaired clotting B) Lymphatic obstruction C) Excessive urinary sodium loss D) Centripetal obesity E) Hypercholesterolaemia Question 18. Which of the following is least likely to cause polyuria? A) Polydipsia B) Cranial diabetes insipidus C) Lithium therapy D) Hypocalcaemia E) Diabetes mellitus Question 19. Anticholinergics are most useful in the treatment of which of the following patterns of incontinence? A) Urge incontinence B) Stress incontinence C) Overflow incontinence D) Continual incontinence E) Neurogenic incontinence Question 20. A patient complains of erectile dysfunction. He is taking the following regular medications. Which one is most likely to be responsible? A) Valsartan B) Ibuprofen C) Sildenafil D) Fluoxetine E) Atenolol 44 Question 21. A patient presents for the first time with renal failure and no previous blood results are available. Which of the following features would most strongly suggest chronic impairment of renal function? A) Presence of haematuria and proteinuria B) Serum potassium > 6.5 mmol/l C) Urine output < 500 ml/day D) Bilateral small kidneys on renal ultrasound E) Clinical evidence of dehydration Question 22. Which of the following drugs is most likely to increase the risk of renal failure in a patient receiving intravenous X-ray contrast for a radiological procedure? A) Heparin B) Ibuprofen C) Insulin D) Diazepam E) N-acetylcysteine Question 23. A patient is diagnosed with pre-renal acute renal failure. She is taking the drugs listed below. Which one is least likely to worsen her condition? A) Furosemide B) Lisinopril C) Diclofenac D) Amoxicillin E) Bendroflumethiazide Question 24. What is the main physiological function of the medullary concentration gradient? A) Promotes water reabsorption from urine B) Secretes water into urine C) Increases glomerular filtration rate (GFR) D) Promotes sodium reabsorption from urine E) Controls renal vasomotor tone Question 25. A previously well patient is admitted to the renal ward with severe acute renal failure and the following blood results: She is treated with 20 units of intravenous Actrapid insulin and 50 ml of 50% dextrose, as well as salbutamol nebulisers. Her blood tests are repeated 2 hours later and show: ????NOT FOUND IN THE WEB SITE??????? Which of the following is the most appropriate treatment at this stage to reduce her serum potassium concentration? A) A further 20 units of soluble shortacting insulin (Actrapid) with 50 ml of 50% dextrose B) IV calcium gluconate C) IV sodium bicarbonate 1.26% D) Calcium resonium E) Haemodialysis Question 26. A 62-year-old lady presents in acute renal failure with severe bilateral loin pain. A renal tract ultrasound shows dilatation of both ureters and dilatation of the collecting system within both kidneys, probably due to retroperitoneal fibrosis. Blood results are shown below: Which of the following is the most appropriate treatment? A) Haemodialysis B) Continuous veno-venous haemofiltration (CVVH) C) Bilateral nephrostomies D) 1.5 litre/day fluid restriction E) Suprapubic bladder catheterisation 45 Question 27. Which of the following biochemical abnormalities in venous blood is least likely to be present in a patient with untreated chronic renal failure? A) Reduced bicarbonate B) Elevated parathyroid hormone (PTH) C) Reduced phosphate D) Elevated cholesterol E) Reduced calcium Question 28. Which of the following statements about the management of anaemia in patients with chronic renal failure is most accurate? A) Treatment with human recombinant erythropoietin is only beneficial in patients with a subnormal plasma erythropoietin level B) Target haemoglobin should be 130-140 g/l to achieve maximal benefit C) Transferrin saturation should be maintained below 20% to avoid iron overload D) Patients not receiving dialysis should receive oral rather than parenteral erythropoietin E) Complications of erythropoietin include hypertension and hypercoagulability Question 29. In patients with hypertension and proteinuria, which of the following classes of drug has been shown to be most effective in retarding the progression of chronic renal failure? A) Beta-blockers B) Angiotensin-converting enzyme (ACE) inhibitors C) Calcium channel blockers D) Nitrates E) Thiazide diuretics Question 30. Which of the following factors does not contribute to the increased risk of cardiovascular mortality in patients with chronic renal failure? A) Hypercholesterolaemia B) Vascular calcification C) Hypertension D) Enhanced platelet function E) Anaemia Question 31. Deficiency of which one of the following contributes to renal osteodystrophy? A) 1V-hydroxylase B) Phosphate C) Aluminium D) 25-hydroxycholecalciferol E) Parathyroid hormone Question 32. Which of the following adverse features of chronic renal failure is least effectively treated by haemodialysis? A) Accumulation of uraemic toxins B) Abnormal electrolyte balance C) Fluid overload D) Anaemia E) Acidosis Question 33. Which of the following statements about the differences between peritoneal dialysis (PD) and haemodialysis (HD) is true? A) PD requires a more restrictive diet than HD B) PD enables a more efficient transfer of solutes than HD C) PD may be performed less frequently than HD D) Symptomatic fluid shift is less common with PD than HD E) Previous abdominal surgery is more likely to impede HD than PD Question 34. Which one of the following is an absolute contraindication to renal transplantation? A) Age > 55 years B) Active anti-glomerular basement membrane (GBM) disease C) Diabetes mellitus D) Past history of malignant melanoma excised 4 years ago E) Previous failed renal transplant Question 35. Deterioration of renal function on commencement of angiotensin-converting enzyme (ACE) inhibitor therapy is most characteristic of: A) Diabetic nephropathy B) Hypertensive nephropathy C) Adult polycystic kidney disease D) Renal artery stenosis E) Goodpasture's syndrome 46 Question 36. A 26-year-old man presents with the nephrotic syndrome. Which of the following conditions is most likely to be the underlying cause? A) Acute tubular necrosis B) Membranous nephropathy C) Post-streptococcal glomerulonephritis D) Anti-glomerular basement membrane (GBM) disease E) Small-vessel vasculitis Question 37. Which of the following causes of glomerular disease is most likely to present as rapidly progressive glomerulonephritis? A) Membranous nephropathy B) Focal segmental glomerulosclerosis C) Goodpasture's disease (anti-glomerular basement membrane (anti-GBM) disease) D) Diabetic nephropathy E) Mesangiocapillary glomerulonephritis Question 38. Which of the following glomerular diseases is most likely to respond to treatment with corticosteroids? A) Minimal change nephropathy B) IgA nephropathy C) Primary focal segmental glomerulosclerosis D) Diabetic nephropathy E) Post-streptococcal glomerulonephritis Question 39. In addition to renal failure in early adulthood, which of the following is associated with Alport's syndrome? A) Pulmonary haemorrhage B) Gastrointestinal telangiectasia C) Osteopenia D) Intellectual impairment E) Sensorineural deafness Question 40. Which of the following is not associated with adult polycystic kidney disease (APKD)? A) Hepatomegaly B) Hypertension C) Subarachnoid haemorrhage D) Urinary tract infection E) Renal cell carcinoma Question 41. Which of the following is least likely to precipitate acute urinary retention in a patient with benign prostatic hyperplasia (BPH)? A) Alcohol excess B) Alpha-adrenoceptor blockers C) Constipation D) Prostatic infection E) Anticholinergic agents Question 42. All of the following except one are characteristic findings in a patient presenting with metastatic prostate cancer. Which is the exception? A) Lytic bony metastases B) Elevated alkaline phosphatase C) Positive radioisotope bone scan D) Prostate specific antigen (PSA) > 100 ng/ml E) Enlarged, irregular prostate on rectal examination 47 Question 43. Which of the following hormones is least likely to be secreted by a renal adenocarcinoma? A) Erythropoietin B) Adrenaline (epinephrine) C) Parathyroid hormone-related peptide D) Human chorionic gonadotrophin E) Renin Question 44. Which one of the following drugs is associated with the development of glomerulonephritis? A) Ciclosporin B) Gentamicin C) Angiotensin-converting enzyme (ACE) inhibitors D) Penicillamine E) Lithium Chapter 17 CARDIOVASCULAR DISEASE Answers page 170 Question 1. Which one of the following statements about the jugular venous pulse (JVP) is true? A) The height reflects left atrial pressure B) The JVP falls with abdominal compression C) It is best examined with the patient supine D) Large systolic waves are associated with tricuspid regurgitation E) Prominent a waves suggest atrial fibrillation Question 2. In the majority of individuals, the atrioventricular (AV) node is supplied by the: A) Left main stem artery B) Left anterior descending artery C) Circumflex artery D) Right coronary artery E) Obtuse marginal artery Question 3. A 57-year-old man presents with an acute myocardial infarction affecting the anterior part of the septum and anterior wall of the left ventricle. Which of the following vessels is most likely to have been occluded? A) Left anterior descending artery B) Circumflex artery C) Right coronary artery D) Right posterior descending artery E) Obtuse marginal artery 48 Question 4. Which one of the following statements regarding the nerve supply of the heart is correct? A) Beta1-adrenoceptors mediate negatively chronotropic effects B) Beta2-adrenoceptors mediate positively inotropic effects C) Adrenergic fibres reach the heart via the vagus nerves D) Cholinergic nerve fibres act on the sinoatrial node to slow heart rate E) Parasympathetic nerve fibres act on muscle fibres in the atria and ventricles to reduce the strength of myocardial contraction Question 5. Which one of the following is not an appropriate indication for an exercise (stress) ECG? A) Evaluation of stable angina B) Evaluation of unstable angina C) Assessment of prognosis following a myocardial infarction D) Assessment of outcome following coronary angioplasty E) Diagnosis of exercise-induced arrhythmias Question 6. Which of the following symptoms is most suggestive of myocardial ischaemia? A) Epigastric discomfort after eating B) Exertional breathlessness and wheeze C) Exertional breathlessness and throat tightness D) Breathlessness with perioral and digital paraesthesia E) Rapid palpitation on exertion Question 7. A 58-year-old woman presents with dyspnoea and central chest and throat tightness, which occur when walking her dog and force her to stop and rest. She has smoked 20 cigarettes a day for the last 30 years. Examination is unremarkable apart from some lesions around her eye: Question 10. Which of the following disorders is most likely to present with isolated right heart failure? A) Aortic stenosis B) Mitral regurgitation C) Systemic hypertension D) Dilated cardiomyopathy E) Recurrent pulmonary emboli Question 11. Which of the following findings on clinical examination is most suggestive of left heart failure over right heart failure? A) Raised jugular venous pressure (JVP) B) Hepatomegaly C) Fine bi-basal crepitations D) Peripheral oedema E) Ascites What abnormality is likely to be found on blood tests? A) Renal impairment B) Hypercholesterolaemia C) Hyperthyroidism D) Hyperglycaemia E) Hypocalcaemia Question 8. The patient from the previous question (Q7) is found to have a normal 12-lead ECG and chest X-ray. Which of the following would be the most appropriate next investigation? A) Coronary angiogram B) Exercise ECG C) Echocardiogram D) 24-hour tape E) Pulmonary function tests Question 9. The patient from the previous two questions (Q7 and Q8) undergoes an exercise ECG, which is positive but shows no high-risk features. Blood tests confirm a raised plasma cholesterol of 7.2 and blood pressure is 158/92 mmHg. All of the following are appropriate secondary prevention measures except one. Which is the exception? A) Aspirin B) Ramipril C) Spironolactone D) Simvastatin E) Smoking cessation 49 Question 12. A 68-year-old man presents with acute pulmonary oedema. Which one of the following examination findings is most suggestive of pre-existing structural heart disease? A) Elevated jugular venous pressure B) Basal lung crepitations C) Displaced apex beat D) Gallop rhythm E) Cool, clammy peripheries Question 13. Which of the following cardiac medications most commonly causes peripheral oedema? A) Digoxin B) Amlodipine C) Atenolol D) Nicorandil E) Ramipril Question 14. A patient presents with severe bilateral lower limb pitting oedema. Which of the following features would suggest a cause other than chronic cardiac failure? A) Raised jugular venous pressure B) Hepatomegaly C) Peripheral muscle wasting D) Hyponatraemia E) Heavy proteinuria Question 15. A 63-year-old man with ischaemic heart disease attends the cardiology clinic with worsening symptoms of chronic heart failure. His treatment is modified. Three weeks later, routine blood tests by the GP reveal a serum potassium of 6.5 mmol/l (reference range 3.6-5.1). Which of the following drugs is the most likely culprit? A) Furosemide B) Ramipril C) Digoxin D) Bisoprolol E) Aspirin Question 16. Which one of the following treatments should be avoided in patients with acute left ventricular failure? A) Intravenous glyceryl trinitrate B) Non-invasive positive pressure ventilation C) Beta-blockers D) Loop diuretics E) Intravenous morphine Question 17. Angiotensin receptor blockers (ARBs) are frequently used in patients intolerant of ACE inhibitors. Which of the following adverse effects of ACE inhibitor therapy is most likely to be improved by switching to an ARB? A) Renal impairment B) Postural hypotension C) Dry cough D) Hyperkalaemia E) Hyponatraemia Question 18. All of the following agents except one have been shown to reduce mortality in patients with chronic heart failure. Which is the exception? A) Angiotensin receptor blockers B) ACE inhibitors C) Beta-blockers D) Loop diuretics E) Spironolactone 50 Question 19. Which one of the following diagnoses is least likely to account for an episode of loss of consciousness? A) Carotid sinus syndrome B) Transient ischaemic attack C) Stokes-Adams attack D) Ventricular tachycardia E) Hypertrophic obstructive cardiomyopathy Question 20. In differentiating cardiac syncope from seizures, which one of the following most strongly suggests cardiac syncope? A) No warning prior to blackout B) Cyanosis during unconscious period C) Urinary incontinence D) Brief twitching during unconscious period E) Rapid recovery (< 1 min) following the collapse Question 21. A patient admitted to the coronary care unit with an acute anterior myocardial infarction loses consciousness during the morning ward round. Below is a rhythm strip taken from his continuous cardiac telemetry: What is the most urgent priority in this patient's management? A) IV amiodarone B) External cardiac pacing C) IV adrenaline (epinephrine) D) Endotracheal intubation and ventilation E) Defibrillation Question 22. A 74-year-old man with severe pneumonia on the medical highdependency unit suffers a cardiac arrest. The cardiac monitor shows asystole. Cardiopulmonary resuscitation (CPR) is commenced and IV adrenaline (epinephrine) is administered. Which one other drug should be given at this stage? A) Amiodarone B) Atropine C) Lidocaine D) Magnesium sulphate E) Sodium bicarbonate Question 23. Which of the following disorders characteristically produces a loud first heart sound (S1)? A) Atrial septal defect B) Mitral stenosis C) Aortic regurgitation D) Left ventricular hypertrophy E) Constrictive pericarditis Question 24. Wide fixed splitting of the second heart sound occurs in which one of the following disorders? A) Patent ductus arteriosus B) Aortic stenosis C) Ventricular septal defect D) Mitral regurgitation E) Atrial septal defect Question 25. A fourth heart sound is least likely to be heard in which of the following conditions? A) Systemic hypertension B) Aortic stenosis C) Hypertrophic cardiomyopathy D) Atrial fibrillation E) Ischaemic heart disease Question 26. The combination of a third heart sound and soft first heart sound is most characteristic of which of the following disorders? A) Aortic regurgitation B) Pulmonary stenosis C) Mitral regurgitation D) Atrial septal defect E) Ventricular septal defect Question 27. Which of the following conditions is most likely to produce a murmur in early diastole? A) Ventricular septal defect (VSD) B) Mitral stenosis C) Tricuspid regurgitation D) Aortic regurgitation E) Pulmonary stenosis Question 28. Which one of the following not a cause of sinus tachycardia? A) Anaemia B) Raised intracranial pressure C) Thyrotoxicosis D) Phaeochromocytoma E) Nebulised salbutamol 51 Question 29. A 58-year-old woman presents to the hospital Accident and Emergency department with sudden onset of palpitations. Below is a rhythm strip of her ECG before and after carotid sinus massage: What is the cause of her palpitations? A) Atrial fibrillation B) Atrial tachycardia C) Atrial flutter D) Atrioventricular (AV) nodal re-entry tachycardia E) Sinus tachycardia Question 30. A 47-year-old man presents to the hospital Accident and Emergency department with palpitations and is found to be in atrial fibrillation (AF) with a rapid ventricular rate. He cardioverts spontaneously but this is his third such episode in the last 2 years. He is otherwise well and drinks no alcohol. Blood pressure is 152/88 mmHg. Routine blood tests are normal and an echocardiogram reveals no structural heart disease. Which of the following medications would be the most appropriate first-line therapy to prevent further episodes? A) Bisoprolol B) Verapamil C) Ramipril D) Digoxin E) Amiodarone Question 31. Which one of the following is a contraindication to DC cardioversion for persistent atrial fibrillation? A) Age over 75 B) Atrial fibrillation present for > 1 year C) Moderate to severe left ventricular impairment D) Subtherapeutic INR E) Relapse after two previous cardioversions Question 32. Which one of the following medications would not be suitable for rate control in persistent atrial fibrillation? A) Digoxin B) Atenolol C) Verapamil D) Diltiazem E) Amlodipine Question 33. Intravenous adenosine is most likely to restore sinus rhythm in which of the following tachyarrhythmias? A) Atrial flutter B) Atrial fibrillation C) Atrioventricular (AV) nodal re-entrant tachycardia D) Atrial tachycardia E) Ventricular tachycardia Question 34. A 24-year-old woman presents to her GP with recurrent episodes of palpitation. She describes several episodes where she has suddenly felt her heart beating very rapidly. They last anywhere from a few minutes to an hour before self-terminating. She feels very frightened during these episodes and is worried she may have a serious heart condition. Examination is normal and she appears to be in sinus rhythm. A segment of her 12-lead ECG is shown below. What is the likely diagnosis? A) Paroxysmal atrial fibrillation B) Panic attacks C) Wolff-Parkinson-White syndrome D) Ventricular ectopic beats E) Recurrent ventricular tachycardia Question 35. The patient in the previous question (Q34) finds these episodes of palpitation distressing and asks about treatment to prevent further episodes. Which of the following is the treatment of choice? A) Digoxin B) Dual chamber pacemaker C) Verapamil D) Catheter ablation of accessory pathway E) Amiodarone 52 Question 36. A 55-year-old man is brought to the emergency department by ambulance after collapsing at work. His ECG shows a broad complex tachycardia: Which of the following features most strongly favours a diagnosis of ventricular tachycardia (VT) over supraventricular tachycardia with bundle branch block? A) History of ischaemic heart disease B) Termination with IV adenosine C) Presence of capture and fusion beats on ECG D) QRS duration of 150 ms E) Right axis deviation on ECG Question 37. The patient in the previous question (Q36) is diagnosed with ventricular tachycardia (VT). He is aware of his heart racing but is otherwise asymptomatic. Heart rate is 170 bpm. Blood pressure is 110/70 mmHg. There is no evidence of pulmonary oedema. What is the most appropriate next treatment? A) IV metoprolol B) IV amiodarone C) IV flecainide D) DC cardioversion E) Overdrive pacing Question 38. Below is an ECG recording from a patient on the coronary care unit, who is on continuous telemetry. She had been admitted the previous day with an episode of syncope: What is the diagnosis? A) Idioventricular rhythm ('slow ventricular tachycardia') B) Ventricular fibrillation C) Torsades de pointes D) Supraventricular tachycardia with aberrant conduction E) Sick sinus syndrome Question 39. What abnormality is most likely to be seen on a 12-lead ECG from the patient in the previous question (Q38) when she was in sinus rhythm? A) ST elevation B) Prolonged PR interval C) Broad QRS complexes D) Prolonged QT interval E) Delta wave Question 40. Which of the following drugs is most likely to cause a prolonged QT interval? A) Omeprazole B) Digoxin C) Clarithromycin D) Diazepam E) Morphine Question 41. Which of the following drug treatments is most appropriate for a patient with torsades de pointes? A) Magnesium B) Amiodarone C) Lidocaine D) Digoxin E) Sotalol Question 42. A 77-year-old patient is referred to the cardiology outpatient clinic with recurrent dizzy spells, and a 24-hour tape is performed. The ECG strip below is recorded during a typical episode of dizziness: What rhythm abnormality is shown? A) First-degree atrioventricular (AV) block B) Mobitz type I second-degree AV block C) Mobitz type II second-degree AV block D) Third-degree (complete) heart block E) Junctional rhythm 53 Question 43. What is the most appropriate management of the patient in the previous question (Q42)? A) Review in 6 months and consider treatment if any syncopal episodes B) Start amiodarone and repeat 24-hour tape C) Atrial pacemaker D) Dual-chamber pacemaker E) Implantable cardiac defibrillator Question 44. Which one of the following is not a manifestation of digoxin toxicity? A) Nephrotoxicity B) Altered colour vision C) Bradycardia D) Vomiting E) Ventricular tachycardia Question 45. Which of the following features renders an atherosclerotic plaque most vulnerable to rupture? A) Thick fibrous cap B) Calcification C) Lipid-rich core D) Extensive collagenous cross-struts E) High concentration of smooth muscle cells Question 46. Which one of the following is not an independent risk factor for atherosclerosis? A) Systolic hypertension B) Raised high-density lipoprotein (HDL) cholesterol C) Hyperhomocysteinaemia D) Central obesity E) Diabetes mellitus Question 47. A 60-year-old man is referred to the cardiology outpatient department with a 6-month history of exertional chest pain relieved by rest and glyceryl trinitrate (GTN) spray. As part of his assessment he undergoes an exercise ECG. Which of the following features on exercise ECG would be the strongest indication for proceeding to coronary angiography? A) Rise in systolic blood pressure of 60 mmHg during test B) Widespread 1-2 mm upward-sloping ST depression during stage 2 of the Bruce protocol without symptoms C) Failure to complete stage 1 of the Bruce protocol due to hip pain D) Chest pain and 2-3 mm horizontal ST depression in lateral leads during stage 4 of the Bruce protocol E) Chest pain and 1-2 mm downwardsloping ST depression in inferior leads during stage 1 of the Bruce protocol Question 48. Which one of the following drugs is not an anti-anginal agent? A) Clopidogrel B) Atenolol C) Diltiazem D) Nicorandil E) Isosorbide mononitrate Question 49. Which one of the following features is least consistent with a diagnosis of unstable angina? A) Chest pain on minimal exertion B) Persistent ST segment elevation on ECG C) No preceding history of stable angina D) More than two episodes of chest pain at rest in the last 24 hours E) T wave inversion on ECG 54 Question 50. A 68-year-old man with a long history of angina presents with a worsening of anginal symptoms. He was previously able to walk up to 1 mile before the onset of symptoms but for the past few days has been experiencing pain after just 50 yards and, on one occasion, at rest. Which of the following factors would have the least impact on his short-term risk of death or acute myocardial infarction? A) Recurrent pain at rest B) ST segment depression on ECG C) Elevated serum cholesterol D) Persistent deep T-wave inversion on ECG E) Elevated serum troponin Question 51. The patient from the previous question (Q50) is admitted to hospital and an admission ECG reveals 1 mm ST depression in leads V5 and V6. In the absence of any contraindications, which of the following would be the optimal combination of antiplatelet agents and anticoagulants to prescribe? A) Aspirin alone B) Aspirin and low molecular weight heparin C) Aspirin and clopidogrel D) Aspirin, clopidogrel and low molecular weight heparin E) Aspirin, clopidogrel and warfarin Question 52. After 48 hours of optimal medical treatment, the patient from the previous question (Q51) is still experiencing occasional short-lived episodes of chest pain at rest. His ECGs while he is pain-free are normal, but those taken during pain show recurrence of ST segment depression in the lateral leads. Troponin T is modestly elevated. What would be the best investigation to perform next in this patient? A) 24-hour ECG B) Exercise ECG C) Echocardiogram D) Myocardial perfusion scan E) Coronary angiogram Question 53. A 48-year-old man presents with a 6-hour history of severe central chest pain. He is unable to give much history but declares that the pain is the worst he has ever felt. He was previously well with no history of cardiovascular disease. On examination he appears pale, sweaty and distressed. His ECG is shown below: What is the diagnosis? A) Aortic dissection B) Acute anterior myocardial infarction C) Acute inferior myocardial infarction D) Unstable angina E) Pericarditis Question 54. The patient from the previous question (Q53) with acute anterior ST elevation myocardial infarction (MI) is treated immediately with IV morphine, sublingual glyceryl trinitrate and aspirin. He appears less distressed but his heart rate is 118 bpm and blood pressure is 195/115 mmHg. Heart sounds 1 and 2 are present with no added sounds or murmurs and the chest is clear to auscultation. Which of the following options would be the +best next step in his management? A) Thrombolysis B) IV magnesium C) Sublingual nifedipine D) IV metoprolol E) Oral ramipril 55 Question 55. A 62-year-old woman presents with a 2-hour history of severe chest pain and has the following ECG: While awaiting thrombolysis, she complains of lightheadedness. Her pulse rate is 38 beats per minute and telemetry shows sinus bradycardia. What is the most appropriate next treatment? A) Insertion of temporary pacing wire B) IV atropine C) External cardiac pacing D) IV isoprenaline E) IV atenolol Question 56. Which one of the following long-term treatments does not confer prognostic benefit in survivors of acute myocardial infarction (MI)? A) Aspirin B) Angiotensin-converting enzyme (ACE) inhibitor C) Beta-blocker D) Statin E) Isosorbide mononitrate Question 57. In a patient with peripheral arterial disease, which one of the following features suggests the worst prognosis? A) Claudication distance of 50-100 metres B) Night pain C) Diminished pedal pulses D) Ankle:brachial pressure index (ABPI) ratio of 0.8 E) Bruit over femoral artery Question 58. In a patient presenting with acute lower limb ischaemia, which one of the following clinical features would favour a diagnosis of embolism over thrombosis in situ? A) Onset of symptoms over hours B) History of intermittent claudication C) Previously undiagnosed atrial fibrillation D) Absent contralateral lower limb pulses E) Presence of bruits Question 59. Which one of the following clinical features is least consistent with a type B aortic dissection? A) Severe tearing chest pain B) Elevated blood pressure C) Asymmetry of femoral pulses D) New early diastolic murmur E) Acute renal failure Question 63. A 53-year-old male with hypertension has been taking 10 mg of ramipril for several months. Despite this, his blood pressure control remains suboptimal. There are no compliance issues. Which one of the following agents would be the best add-on therapy? A) Angiotensin receptor blocker B) Beta-blocker C) Calcium channel antagonist D) Hydralazine E) Alpha-blocker Question 60. Which of the following is not a recognised risk factor for essential hypertension? A) Hyperlipidaemia B) Obesity C) High salt intake D) Intrauterine growth retardation E) Alcohol excess Question 64. A 19-year-old man presents with recent onset of breathlessness and sharp, central chest pain exacerbated by movement and coughing. His heart rate is 110 beats per minute. On auscultation there is a soft pansystolic murmur and a pericardial friction rub. Echocardiography demonstrates mitral regurgitation. Antistreptolysin O antibody titres (ASOT) are 500 U/ml (normal range < 200). What is the likeliest diagnosis? A) Infective endocarditis B) Viral myocarditis C) Acute rheumatic fever D) Viral pericarditis E) Dressler's syndrome Question 61. The following endocrine diseases are all recognised causes of secondary hypertension except one. Which is the exception? A) Acromegaly B) Congenital adrenal hyperplasia C) Conn's syndrome D) Phaeochromocytoma E) Addison's disease Question 65. In the patient from the previous question (Q64), which one of the following features would clinch the diagnosis of rheumatic fever? A) Temperature > 38oC B) Positive throat swab culture C) Cardiac dilatation on echocardiography D) First-degree block on ECG E) Flitting polyarthritis Question 62. A 77-year-old woman in good health is found by her general practitioner to have persistently elevated blood pressure, with a typical reading of 162/84 mmHg. Which of the following agents would be the most appropriate initial treatment? A) Angiotensin-converting enzyme (ACE) inhibitor B) Angiotensin receptor blocker C) Beta-blocker D) Thiazide diuretic E) Alpha-blocker 56 Question 66. A 53-year-old lady complains of progressively worsening exertional dyspnoea associated with deterioration in exercise tolerance over the past 2 years. On examination her pulse is irregularly irregular and of small volume. There is a low-pitched mid-diastolic murmur audible at her apex. What is the likeliest cause of her breathlessness? A) Dilated cardiomyopathy B) Ischaemic heart disease C) Ventricular septal defect D) Mitral stenosis E) Aortic regurgitation Question 67. With reference to the patient from the previous question (Q66) who has mitral stenosis, which one of the following features would suggest that her condition has been complicated by pulmonary hypertension? A) Loud first heart sound (S1) B) Opening snap C) Pansystolic murmur radiating to the axilla D) Tapping apex beat E) Loud pulmonary component of second heart sound (P2) Question 71. A 64-year-old man is found to have an ejection systolic murmur during a routine medical examination. Which of the following associated clinical signs would lend most support to a diagnosis of aortic stenosis? A) Displaced apex beat B) Loud aortic component of second heart sound (A2) C) Louder in inspiration D) Wide pulse pressure E) Slow-rising carotid pulse Question 68. Which one of the following would be a contraindication to mitral balloon valvuloplasty? A) Mitral valve orifice < 2 cm2 B) Concomitant mitral regurgitation C) Mobile valvular apparatus D) Atrial fibrillation E) Enlarged left atrium Question 73. You are asked to examine a dyspnoeic patient on the cardiology ward. She has bounding peripheral pulses, a blood pressure of 190/70 mmHg, a displaced, heaving apex beat and a loud early diastolic murmur. Which of the following underlying pathologies would be least likely to account for these physical findings? A) Rheumatic heart disease B) Acute aortic dissection C) Syphilitic aortitis D) Marfan's syndrome E) Ankylosing spondylitis Question 69. The following are all recognised causes of mitral regurgitation except one. Which is the exception? A) Papillary muscle rupture B) Dilated cardiomyopathy C) Acute rheumatic fever D) Subacute bacterial endocarditis E) Congenitally bicuspid mitral valve Question 70. Which one of the following features is likely to be found in mitral regurgitation but not in mitral stenosis? A) Irregularly irregular pulse B) Third heart sound (S3) C) Right ventricular heave D) Accentuated pulmonary component of second heart sound E) Bi-basal crepitations 57 Question 72. A patient with known aortic stenosis is followed up annually in the cardiology outpatient clinic. Which of the following would be the strongest indication for aortic valve replacement? A) Syncopal episodes B) Prolonged murmur and thrusting apex beat on examination C) Left bundle branch block on ECG D) Reduced valve area on echocardiography E) High pressure gradient between left ventricle and aorta at cardiac catheterisation Question 74. A patient with a history of long-standing rheumatic mitral stenosis presents with a 6-week history of malaise, drenching sweats and lethargy. On examination she has poor dentition, a temperature of 38.5°C and a loud pansystolic murmur at apex radiating to axilla. You suspect a diagnosis of subacute bacterial endocarditis. Which of the following microorganisms is the likeliest culprit? A) Viridans streptococci B) Staphylococcus aureus C) Coxiella burnetti D) Coagulase-negative staphylococci E) Haemophilus Question 78. An 18-year-old boy, who previously attended the paediatric cardiology clinic but defaulted from follow-up after his 14th birthday, now presents to his GP with increasingly severe breathlessness, fatigue and reduced exercise tolerance. On examination he is centrally cyanosed with clubbing of the fingers and toes. Which of the following is the most likely underlying congenital cardiac abnormality? A) Ventricular septal defect B) Coarctation of the aorta C) Pulmonary stenosis D) Bicuspid aortic valve E) Patent foramen ovale Question 75. Echocardiography confirms the presence of a vegetation on the mitral valve and mitral regurgitation. Six sets of blood cultures are sent. While awaiting results, which of the following antibiotic regimens would be the most appropriate empirical treatment? A) Flucloxacillin B) Benzyl penicillin C) Gentamicin D) Benzyl penicillin and gentamicin E) Vancomycin and flucloxacillin Question 79. Which one of the following does not constitute a component of Fallot's tetralogy? A) Pulmonary stenosis B) Ventricular septal defect C) Overriding aorta D) Patent ductus arteriosus E) Right ventricular hypertrophy Question 76. According to the modified Duke criteria, which one of the following is considered a major criterion for the diagnosis of infective endocarditis? A) Pyrexia > 38°C B) Pre-existing aortic stenosis C) Splinter haemorrhages D) Vegetations on echocardiography E) Osler's nodes Question 77. A continuous machinery murmur, loudest over the left second intercostal space, is associated with which of the following congenital cardiac abnormalities? A) Atrial septal defect B) Ventricular septal defect C) Patent ductus arteriosus D) Tricuspid atresia E) Pulmonary stenosis 58 Question 80. A patient who immigrated to the UK from West Africa 18 months ago presents with progressive ankle swelling and abdominal distension. On examination he has marked bilateral lower limb oedema, a palpably enlarged liver and ascites. His jugular venous pulse is elevated and rises during inspiration. Lung fields are clear to auscultation. His chest X-ray is shown below: Which of the following is the likeliest underlying aetiology? A) Tuberculosis B) TrypanosomiasisC) Syphilis D) Malaria E) Haemochromatosis Chapter 18 RESPIRATORY DISEASE Answers page 181 Question 1. A 21-year-old woman presents to the hospital accident and emergency department with an acute exacerbation of asthma. Which of the following features in her presentation would give greatest cause for concern? A) Peak expiratory flow (PEF) 40% of predicted B) Inability to complete sentences in one breath C) PaCO2 of 5.8 kPa D) Respiratory rate of 30 breaths per minute E) Sinus tachycardia of 120 beats per minute Question 2. A 67-year-old lifelong smoker with a history of one previous myocardial infarction attends the respiratory clinic with shortness of breath. On examination she is clinically hyperinflated, and has a respiratory rate of 19 breaths per minute at rest and quiet vesicular breath sounds bilaterally. Bilateral ankle oedema is present to the mid-calves. Pulmonary function tests show a forced vital capacity (FVC) of 70% predicted, a forced expiratory volume in 1 second (FEV1) of 25% predicted and an FEV1:FVC ratio of 55%. These abnormalities are only partially reversed by inhaled salbutamol. Which of the following conditions is the most likely diagnosis? A) Asthma B) Chronic obstructive pulmonary disease (COPD) C) Congestive cardiac failure D) Sarcoidosis E) Bronchial carcinoma 59 Question 3. The patient with COPD from the previous question (Q2) has the following arterial blood gas (ABG) results: How should these results be interpreted? A) Compensated metabolic acidosis B) Compensated respiratory acidosis C) Mixed respiratory and metabolic alkalosis D) Compensated metabolic alkalosis E) Mixed respiratory and metabolic acidosis Question 4. In the treatment of stable COPD, which one of the following interventions will provide the greatest survival benefit? A) Home nebuliser with salbutamol B) Long-acting ß2-agonist C) Oral steroid therapy D) Smoking cessation E) Daily inhaled tiotropium Question 5. A previously well, nonsmoking, 24-year-old Turkish woman presents to the hospital accident and emergency department with a 1-day history of non-productive cough, chills and sore throat. Her voice is not hoarse but there is a harsh rasping sound from her throat with each breath and she is unable to swallow her own saliva. Her routine observations are: Which of the following is the most appropriate initial action? A) Carefully examine the throat under direct vision B) Check arterial blood gases C) Perform a CT scan of the chest and neck D) Transfer to a critical care environment and consider endotracheal intubation by an experienced anaesthetist E) Administer nebulised bronchodilator Question 7. With reference to the patient in the previous question (Q6), which of the following investigations would be of greatest use in establishing a diagnosis? A) CT scan of thorax B) Lateral chest X-ray C) Serum rheumatoid factor, anti-nuclear factor and anti-DNA antibodies D) Pleural aspiration E) Arterial blood gas Question 8. The patient from the previous two questions (Q6 and Q7) has 30 ml of serous fluid aspirated from his left pleural space and sent for analysis. Initial biochemistry results are shown below, along with the results of some routine blood tests: Which of the following conditions is the most likely cause of his pleural effusion? A) Nephrotic syndrome B) Parapneumonic effusion C) Thoracic duct occlusion D) Acute pancreatitis E) Congestive cardiac failure Question 6. This chest X-ray was taken from a 69-year-old man who presented with confusion and a vague history of increasing shortness of breath: Which of the following clinical signs is most likely to be present on examination of the chest? A) Bronchial breathing at left base B) Reduced chest expansion on right side C) Stony dull percussion note at left base D) Inspiratory crepitations at left base E) Reduced cricosternal distance 60 Question 9. A 34-year-old woman presents to the hospital accident and emergency department with sudden onset of acute severe breathlessness. She is able to talk in broken sentences. She reports that she cannot get enough air and also feels tingling in both fingertips. She has had several similar episodes in the past. On examination, she appears very distressed. Respiratory rate is 30 breaths per minute but examination of her chest reveals no abnormal findings. Oxygen saturations on air are 99%. What is the most likely diagnosis? A) Psychogenic hyperventilation B) Acute asthma C) Pneumothorax D) Pulmonary oedema E) Pneumonia Question 10. A previously healthy 35year-old man presents with fever, tachypnoea and hypoxia on air. Which one of the following features would not lend support to a diagnosis of Pneumocystis carinii (jirovecii) pneumonia? A) Oropharyngeal candidiasis B) Rusty, golden yellow-coloured sputum C) Poor response to standard antibiotics D) Marked worsening of hypoxia on exertion E) Normal chest X-ray but nodular ground-glass attenuation on highresolution CT Question 11. An 18-year-old asthmatic patient presents to the hospital accident and emergency department 1 hour after developing breathlessness and wheeze. On admission she is struggling to complete sentences in one breath, and has a peak flow of 150 l/min (her best peak expiratory flow rate (PEFR) is 310 l/min) and widespread wheeze throughout her chest. Observations are shown below: All of the following are appropriate steps in her immediate management except one. Which is the exception? A) High-concentration oxygen B) Nebulised salbutamol C) Systemic corticosteroids D) Nebulised ipratropium E) Intravenous aminophylline Question 12. After 1 hour of treatment with salbutamol, oxygen, systemic corticosteroids and intravenous magnesium, the patient in the previous question (Q11) has made no improvement and appears to be tiring. Her PEFR is now 100 l/min and auscultation of the chest reveals quiet wheeze bilaterally. Below are the results of arterial blood gas measurements taken on admission (first ABG) then repeated after treatment (second ABG), both on 60% O2: 61 Which of the following would be the most appropriate next step? A) Discharge with advice to return if the wheeze worsens B) Admit to the medical ward for overnight observation C) Refer to the intensive treatment unit for consideration of mechanical ventilation D) Refer to the high-dependency unit for a trial of non-invasive ventilation E) Reduce oxygen concentration to 28% and repeat the ABG in 1 hour Question 13. Which of the following best describes the mode of action of ipratropium? A) ß2-adrenoceptor agonist B) Leukotriene receptor antagonist C) Corticosteroid D) Anticholinergic E) Cholinergic agonist Question 14. A patient presents to the respiratory clinic complaining of 6 months' history of cough. Respiratory examination and chest X-ray are normal. Which of the following is least likely to explain her symptom? A) Treatment with ramipril B) Post-nasal drip C) Gastro-oesophageal reflux disease D) Viral pneumonia E) Asthma Question 15. A previously fit and healthy 54-year-old woman returns to the UK from a family holiday in Spain. She reports fever, rigors, right-sided pleuritic chest pain and general fatigue over the last 24 hours. On examination her temperature is 37.8°C, she appears confused, respiratory rate is 32/min, heart rate 110/min, BP 88/50 mmHg and SaO2 92% on high-concentration oxygen. Examination findings relating to the right side of the chest are as follows: reduced expansion, dull percussion note, bronchial breathing, increased vocal resonance and whispering pectoriloquy. Initial blood tests show a D-dimer of 1000 U, white cell count of 15 × 109/l and serum urea of 10 mmol/l. Which one of the following statements is true concerning the management of this patient? A) Therapeutic dose low-molecular weight heparin should be commenced to treat pulmonary embolism B) Aggressive fluid resuscitation is necessary immediately C) Antibiotic therapy should begin following the results of sputum culture D) The most appropriate antibiotics are an oral aminopenicillin in combination with an oral macrolide E) She should be admitted to a general medical or general respiratory unit Question 16. A 62-year-old lady with mild chronic obstructive pulmonary disease is admitted following sudden onset of shortness of breath at rest and left-sided pleuritic chest pain. Her chronic cough is unchanged and she denies any haemoptysis or change in sputum production. Her only medications are an as-required ß2-agonist inhaler and oestrogen replacement therapy. Clinical examination reveals tachypnoea at rest and signs of hyperinflation. There is no audible wheeze on auscultation. Observations are as follows: • respiratory rate 22/min, heart rate 102 beats per minute, BP 140/72 mmHg, SpO2 88% on air • ECG shows sinus tachycardia but no other abnormality • chest X-ray shows hyperexpanded lung fields with no evidence of pneumothorax, collapse or consolidation. 62 What is the likeliest cause of her presentation? A) Infective exacerbation of COPD B) Pulmonary embolism C) Acute left ventricular failure D) Psychogenic hyperventilation E) Pneumonia Question 17. With reference to the patient in the previous question (Q16), which of the following investigations would be most likely to confirm the diagnosis? A) Computed tomography pulmonary angiogram (CTPA) B) Echocardiogram C) Plasma D-dimer level D) Ventilation/perfusion (V/Q) scan E) High-resolution CT (HRCT) scan of thorax Question 18. A 23-year-old man is rushed to hospital after complaining of severe left-sided chest pain whilst drinking in a bar. On arrival at the hospital accident and emergency department he is in considerable distress and too short of breath to give a meaningful history. His blood pressure in the ambulance was 83/40 mmHg. He is maintaining his airway but his trachea is shifted to the right and he has distended neck veins. Which of the following is the most appropriate way to get enough diagnostic information to begin treatment? A) Chest X-ray B) Percussion and auscultation of the lung fields C) ECG D) Arterial blood gas analysis E) Check for flapping tremor (asterixis) Question 19. A 50-year-old patient is referred to the respiratory clinic with shortness of breath. On examination he has finger clubbing, central cyanosis and fine end-inspiratory crepitations at both lung bases. Which of the following types of pathology would be most consistent with all these examination findings? A) Chronic obstructive pulmonary disease (COPD) B) Extrathoracic restrictive lung disease C) Fibrotic lung disease D) Left ventricular failure E) Cystic fibrosis Question 20. What is the primary anatomical source of normal healthy breath sounds? A) Larynx and central airways B) Small bronchi C) Terminal bronchioles D) Respiratory bronchioles E) Opening of alveoli Question 21. Which of the following is the correct description of the normal lobes of the lungs? A) Two lobes on the right, three on the left B) Two lobes on the right, one on the left C) Three lobes on the right and left D) Three lobes on the right, two on the left E) One lobe on the right, two on the left Question 22. A 29-year-old lady presents to the dermatology clinic with tender, red, raised lesions on her shins. She also complains of joint pains and pyrexial symptoms. A chest X-ray shows bilateral hilar lymphadenopathy (BHL) but no other abnormality. Which of the following is the most likely explanation for these findings? A) Tuberculosis B) Lymphoma C) Sarcoidosis D) Wegener's granulomatosis E) Rheumatoid arthritis 63 Question 23. This flow-volume loop (labelled 'patient A') was taken during pulmonary function testing at a respiratory clinic: Which of the following statements is true? A) The pattern of flow limitation suggests large airway obstruction B) Obstruction is equally severe during inspiration and expiration C) The limitation of vital capacity indicates a restrictive defect D) Reduced mid-expiratory flow indicates collapse of small intrathoracic airways E) Patient A could produce a normal reading on a peak flow meter Question 24. This is a graph of lung volume plotted against time: What is the parameter labelled 'A' (red arrow)? A) Residual volume B) Inspiratory capacity C) Tidal volume D) Vital capacity E) Functional residual capacity Question 25. A 23-year-old known asthmatic is admitted with acute severe breathlessness and tightness in his chest. On examination, polyphonic wheeze is heard throughout both lung fields, but is quieter on the right. There is some response to initial medical therapy, but after 15 minutes of standard treatment he remains tachypnoeic and distressed. Which of the following investigations is most urgent? A) Chest X-ray B) Urea and electrolytes C) ECG D) Doppler ultrasound of leg veins E) Direct laryngoscopy Question 29. At 0200 hrs, the on-call respiratory physician is called to see a patient who was admitted at 1600 hrs with an acute exacerbation of chronic obstructive pulmonary disease (COPD). This is her first admission with chest problems. She is centrally cyanosed and drowsy and has bounding peripheral pulses. What is the most urgent investigation? A) Chest X-ray B) Arterial blood gas (ABG) analysis C) Blood samples for salicylates and paracetamol levels D) ECG E) CT of the head Question 26. Which of the following treatments has been shown to prolong life in chronic obstructive pulmonary disease (COPD)? A) Long-term oxygen therapy B) Inhaled tiotropium C) PRN salbutamol D) Furosemide E) Sildenafil (Viagra) Question 30. Below are the arterial blood gases of the patient in the previous question (Q29): Question 27. In the investigation of a solitary lung nodule, which of the following tends to suggest benign, rather than malignant, pathology? A) Spiculated appearance B) Size > 3 cm C) Long smoking history D) Calcification on chest X-ray E) Hilar lymphadenopathy Question 28. Which of the following is not a risk factor for obstructive sleep apnoea/hypopnoea syndrome (OSAHS)? A) Male sex B) Obesity C) Protuberant mandible D) Acromegaly E) Hypothyroidism 64 Which one of the following treatments is most appropriate? A) Increase to 40% Venturi oxygen B) Decrease to 28% Venturi oxygen C) Administer 15 l/min oxygen via trauma (reservoir bag) mask D) Remove oxygen E) Mechanical ventilatory support Question 31. Which one of the following conditions is more likely to cause type II respiratory failure rather than type I? A) Pulmonary fibrosis B) Pneumothorax C) Acute respiratory distress syndrome D) Pulmonary embolus E) Severe kyphoscoliosis Question 32. A 56-year-old man is referred for investigation of recurrent pneumonia. He suffers from asthma, which seems poorly controlled despite regular use of high doses of fluticasone and salmeterol. He reports on-going cough, wheeze and sticky, difficult-toclear sputum and requires frequent courses of oral corticosteroids. He has never smoked, keeps no pets, complies with therapy and has worked in the same office for 12 years. Chest X-rays show evidence of a left lower lobe collapse 1 year ago and more recently a right middle lobe collapse. The peripheral blood count shows an eosinophil count of 0.6 × 109/l. Which one of the following statements is true? A) He should be investigated for carcinoma of the bronchus B) Cystic fibrosis is the most likely diagnosis C) A trial of itraconazole should be considered D) Induced sputum is likely to be rich in neutrophils E) Prolonged therapy with high-dose oral corticosteroids should be considered Question 33. Which of the following classes of drug may precipitate an acute attack of asthma? A) Beta-adrenoceptor agonists B) Non-steroidal anti-inflammatory drugs C) Calcium channel blocking drugs D) Histamine H1 receptor antagonists E) Leukotriene receptor antagonists Question 34. In a patient with a clinical history compatible with asthma, which one of the following clinches the diagnosis? A) Clinical improvement during a course of oral steroids B) A 20% improvement in forced expiratory volume in 1 second (FEV1) following administration of a bronchodilator C) An 8% spontaneous change in peak expiratory flow (PEF) during 1 week of home monitoring D) A normal chest X-ray E) Elevated peripheral blood eosinophil count 65 Question 35. A 34-year-old man with asthma sees his general practitioner and explains that his asthma is still troublesome despite the recent addition of a low-dose inhaled corticosteroid to his prescription. He is currently on regular low-dose inhaled steroid therapy and an as-needed short-acting ß2-adrenoceptor agonist. Which of the following is the most appropriate next step in drug treatment? A) Short-term oral corticosteroid therapy B) Addition of long-acting ß2adrenoceptor agonist C) Addition of short-acting anticholinergic bronchodilator D) One-week course of empirical antibiotic therapy E) Addition of leukotriene receptor antagonist Question 36. All of the options below describe clinically stable patients with chronic obstructive pulmonary disease and forced expiratory volume in 1 second (FEV1) < 1.5 litres on optimal medical therapy. Patients breathed air for at least 20 minutes before arterial blood gases (ABGs) were taken. Which one patient meets the criteria for long-term oxygen therapy (LTOT)? A) 65-year-old smoker with maximum PaO2 of 5.9 kPa on two ABGs 3 weeks apart B) 71-year-old ex-smoker with maximum PaO2 of 7.5 kPa on two ABGs 3 weeks apart C) 76-year-old ex-smoker with bilateral pitting oedema to knees and maximum PaO2 of 7.7 kPa on two ABGs 3 weeks apart D) 79-year-old ex-smoker with congestive cardiac failure and maximum PaO2 of 7.6 kPa on two ABGs 3 weeks apart E) 85-year-old ex-smoker with pulmonary hypertension and PaO2 of 8.7 kPa on two ABGs 3 weeks apart Question 37. What is the usual pattern of inheritance in cystic fibrosis? A) Autosomal recessive B) Autosomal dominant C) X-linked recessive D) X-linked dominant E) New mutations are most common Question 40. A previously healthy 58year-old smoker presents with a 2-month history of cough productive of bloodstreaked sputum. His chest X-ray is shown below: Question 38. Which of the following drugs is most likely to cause alveolitis in chronic use? A) Digoxin B) Amiodarone C) Nifedipine D) Furosemide E) Atenolol Question 39. A 64-year-old lady who recently travelled to the UK from Baghdad presents with a 3-month history of loss of appetite, weight loss, pyrexial symptoms and productive cough. On examination she is pyrexial at 38.4°C and has hepatosplenomegaly. After 2 weeks in hospital all cultures have been negative so a liver biopsy is taken. This shows caseating liver granulomas. What is the underlying diagnosis? A) Sarcoidosis B) Tuberculosis C) Lymphoma D) Bronchogenic carcinoma E) Amyloidosis Question 39. A 64-year-old lady who recently travelled to the UK from Baghdad presents with a 3-month history of loss of appetite, weight loss, pyrexial symptoms and productive cough. On examination she is pyrexial at 38.4°C and has hepatosplenomegaly. After 2 weeks in hospital all cultures have been negative so a liver biopsy is taken. This shows caseating liver granulomas. What is the underlying diagnosis? A) Sarcoidosis B) Tuberculosis C) Lymphoma D) Bronchogenic carcinoma E) Amyloidosis 66 Which one of the following abnormalities is apparent on the chest X-ray? A) Left upper lobe collapse B) Left lower lobe collapse C) Right upper lobe collapse D) Right middle lobe collapse E) Right lower lobe collapse Question 41. The same patient from the previous question (Q40) then has some routine blood tests: Which of the following is the most likely unifying diagnosis? A) Tuberculosis B) Small-cell bronchogenic carcinoma C) Bronchial adenocarcinoma D) Sarcoidosis E) Aspergilloma Question 42. Which of the following histological subtypes of lung cancer is most commonly associated with hypercalcaemia in the absence of bony metastases? A) Small-cell carcinoma B) Bronchoalveolar carcinoma C) Squamous carcinoma D) Adenocarcinoma E) Adenosquamous carcinoma Question 43. All of the following except one are contraindications to surgical resection in bronchial carcinoma. Which is the exception? A) Continued cigarette smoking B) Malignant pleural effusion C) Involvement of contralateral mediastinal lymph nodes D) Forced expiratory volume in 1 second (FEV1) of 0.8 litres E) Presence of bony metastases Question 44. Which of the following is not normally associated with persistent pulmonary arterial hypertension? A) Chronic venous thromboembolism B) Progressive systemic sclerosis C) Chronic obstructive pulmonary disease D) Chronic exposure to high altitude E) Asthma Question 45. Which of the following disorders is not associated with the development of pulmonary fibrosis? A) Systemic lupus erythematosus B) Rheumatoid arthritis C) Systemic sclerosis D) Rheumatic fever E) Sarcoidosis Question 46. All of the following treatments except one are used in the management of primary pulmonary hypertension. Which is the exception? A) Sildenafil (Viagra) B) Warfarin C) Intravenous prostacyclin infusion D) Heart-lung transplantation E) Intravenous endothelin 67 Question 47. A 28-year-old gentleman with no prior history of chest trouble is referred following the receipt of a chest Xray report performed as part of routine occupational health screening. For the last 10 years he has been employed by a fireplace firm as a stone cutter. The factory is extremely dusty and although he has been supplied with a face mask, he finds it uncomfortable to wear. His chest X-ray shows multiple well-circumscribed 3-5 mm nodular opacities predominantly in the mid- and upper zones Which one of the following statements is correct? A) The most likely diagnosis is miliary tuberculosis B) The most likely diagnosis is silicosis C) The disease is unlikely to progress following cessation of exposure D) Lung function is likely to show an obstructive defect E) Screening of the other employees is unnecessary Question 48. A 60-year-old man has been undergoing treatment for stage IIIA Hodgkins disease. He received chemotherapy with adriamycin, bleomycin, vinblastine and dacarbazine. Several months later he developed a dry cough, exertional breathlessness and intermittent pyrexia. Examination revealed fine late inspiratory crackles. The full blood count was normal (including white cell count), and sputum samples were negative for acid-fast bacilli and bacterial pathogens. Serology showed no evidence of infection with atypical pathogens. The chest X-ray showed diffuse reticulonodular shadowing. Which one of the following statements is correct? A) Bronchoalveolar lavage would be the investigation of choice to diagnose Pneumocystis carinii (jirovecii) pneumonia (PCP) B) The clinical scenario could be explained by bleomycin toxicity C) Lung function tests would be expected to show an obstructive defect D) Lung toxicity could be decreased by the administration of G-CSF therapy E) The appearances on high-resolution CT (HRCT) scan are likely to be diagnostic Chapter 19 ENDOCRINE DISEASE Answers page 188 Question 1. Which of the following molecules does not contain iodine? A) Thyroxine (T4) B) Thyroid-stimulating hormone (TSH) C) Triiodothyronine (T3) D) Reverse triiodothyronine (rT3) E) Amiodarone Question 2. A 38-year-old woman is referred to the medical outpatient clinic with a 6-month history of heat intolerance, palpitations and weight loss despite a normal appetite. Examination reveals a fine tremor and sinus tachycardia but is otherwise unremarkable. Blood tests show the following results: TSH receptor antibodies are detected in her serum. What is the most likely diagnosis? A) Toxic multinodular goiter B) Toxic thyroid adenoma C) Graves' thyrotoxicosis D) Secondary thyrotoxicosis due to a pituitary tumour E) Factitious thyrotoxicosis Question 3. A 59-year-old man with clinical and biochemical evidence of thyrotoxicosis undergoes 99mtechnetium scanning (scintigraphy) of the thyroid. This reveals a well-defined area of increased isotope uptake with no uptake through the rest of the gland. What is the most likely diagnosis? A) Thyroiditis B) Papillary thyroid carcinoma C) Toxic multinodular goiter D) Medullary carcinoma of the thyroid E) Toxic thyroid adenoma 68 Question 4. Which of the following ocular signs of thyrotoxicosis is not specific to Graves' disease? A) Exophthalmos B) Lid lag C) Periorbital oedema D) Chemosis E) Ophthalmoplegia Question 5. Which of the following autoantibodies are most strongly associated with Graves' disease? A) Anti-thyroid peroxidase antibodies B) Anti-thyroglobulin antibodies C) Anti-nuclear antibodies (ANA) D) Thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) E) Anti-neutrophil cytoplasmic antibodies (ANCA) Question 6. A 75-year-old woman attends the hospital accident and emergency department with palpitations. Her past medical history is unremarkable, although she has recently developed a troublesome tremor. ECG reveals atrial fibrillation with a ventricular rate of 145 bpm. Blood pressure is 129/68 mmHg. Blood tests show biochemical evidence of thyrotoxicosis. What would be the most appropriate initial treatment? A) Digoxin B) Propranolol C) Verapamil D) Amiodarone E) DC cardioversion Question 7. All of following except one are recognised causes of hypothyroidism. Which is the exception? A) Hashimoto's thyroiditis B) Post-partum thyroiditis C) Graves' disease D) Hyperprolactinaemia E) Radioactive iodine treatment for hyperthyroidism Question 8. A 52-year-old woman attends her general practitioner with a 1-year history of fatigue, cold intolerance, weight gain and pain in her left hand at night. Blood tests reveal the following: The most appropriate initial management would be: A) Arrange an ultrasound scan of the thyroid B) Arrange a 99mtechnetium scan of the thyroid C) Start treatment with thyroxine D) Start carbimazole E) Do not start treatment now but recheck thyroid function tests in 3 months Question 9. Which of the following might necessitate a decrease in the maintenance dose of thyroxine in patients with primary hypothyroidism? A) Pregnancy B) Normal ageing C) Treatment for epilepsy with phenytoin D) Treatment for tuberculosis with rifampicin E) Development of coeliac disease 69 Question 10. A 74-year-old woman is brought to the hospital accident and emergency department with severe drowsiness. According to her daughter, she has become increasingly fatigued and lethargic over the past year and has gained considerable weight. Her memory has also deteriorated but over the last few days she has become significantly more confused and drowsy. On examination, her Glasgow Coma Score is 12/15, temperature is 32.4°C, blood pressure 96/53 mmHg and pulse 48 bpm. She is pale and her face and hands appear puffy. A provisional diagnosis of myxoedema coma is made and urgent thyroid function tests are requested. The most appropriate initial management would be to: A) Wait for the thyroid function test results B) Give oral thyroxine via a nasogastric tube C) Give IV triiodothyronine D) Give IV triiodothyronine and IM hydrocortisone E) Insert a temporary transvenous pacing wire Question 11. All of the following except one are recognised complications of subtotal thyroidectomy for Graves' thyrotoxicosis. Which is the exception? A) Facial nerve injury B) Transient hypocalcaemia C) Keloid scar formation D) Hoarse voice E) Primary hypothyroidism Question 12. Which of the following statements is true of the drug carbimazole in the treatment of Graves' disease? A) It reduces peripheral conversion of thyroxine (T4) to triiodothyronine (T3) B) There is a 30% risk of agranulocytosis C) The risk of relapse is greater than 30% within 2 years of stopping the drug D) It is preferable to propylthiouracil in treating hyperthyroidism in breastfeeding mothers E) It is associated with an increased risk of thyroid malignancy Question 13. Serum calcitonin levels are useful in monitoring response to treatment of which thyroid condition? A) Medullary carcinoma B) Thyroid lymphoma C) Riedel's thyroiditis D) Follicular carcinoma E) Hashimoto's thyroiditis Question 14. Which one of the following is not employed in the investigation and treatment of papillary carcinoma of the thyroid? A) Fine needle aspiration of the thyroid B) Carbimazole C) Total thyroidectomy D) Radioactive iodine E) Measurement of serum thyroglobulin Question 15. All of the following except one are causes of hypogonadotrophic hypogonadism. Which is the exception? A) Pituitary adenoma B) Anorexia nervosa C) Cystic fibrosis D) Autoimmune gonadal failure E) Excessive physical exercise Question 16. Which of the following statements is true regarding postmenopausal oestrogen-containing hormone replacement therapy (HRT)? A) Treatment is usually continued until the age of 65 B) Women with an intact uterus should receive both oestrogen and progesterone C) It has been demonstrated to reduce the risk of ischaemic heart disease D) It is a useful adjuvant treatment for thrombophilia E) It reduces the risk of breast cancer Question 17. Which of the following is least likely to cause hyperprolactinaemia? A) Bromocriptine B) Metoclopramide C) Pituitary adenoma D) Pregnancy E) Hypothyroidism 70 Question 18. All of the following measures except one have a role in the treatment of polycystic ovarian syndrome (PCOS). Which is the exception? A) Metformin B) Combined oral contraceptive pill C) Gliclazide D) Weight loss E) Cyproterone acetate Question 19. All of the following are recognised features of Turner's syndrome except one. Which is the exception? A) Short stature B) Coarctation of the aorta C) Widely spaced nipples D) Webbing of the neck E) Low follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels Question 20. Which one of the following statements is true of Klinefelter's syndrome? A) It is associated with a 47XYY karyotype B) Affected individuals suffer from hypogonadotrophic hypogonadism C) There is an increased incidence of gynaecomastia D) Treatment with growth hormone is usually required E) Testes are usually absent Question 21. Which of the following tumour markers is most useful in the diagnosis and prognosis of testicular tumours? A) Carcinoembryonic antigen (CEA) B) Prostate-specific antigen (PSA) C) Lactate dehydrogenase (LDH) D) Alpha-fetoprotein (AFP) E) CA125 Question 22. Which one of the following statements regarding parathyroid hormone PTH) is false? A) It is a polypeptide hormone B) It inhibits 1V-hydroxylation of vitamin D in the kidney C) It stimulates calcium resorption from bone D) It promotes calcium resorption from renal tubules E) Its release is inhibited by hypercalcaemia Question 23. All of the following except one are recognised causes of hypercalcaemia. Which is the exception? A) Primary hyperparathyroidism B) Secondary hyperparathyroidism C) Tertiary hyperparathyroidism D) Multiple myeloma E) Squamous cell bronchial carcinoma Question 24. Which cluster of features is classically seen in multiple endocrine neoplasia (MEN) type 2 (Sipple's syndrome)? A) Hyperparathyroidism, pituitary adenoma, pancreatic neuro-endocrine tumour B) Hyperparathyroidism, follicular thyroid carcinoma, phaeochromocytoma C) Hyperparathyroidism, medullary thyroid carcinoma, phaeochromocytoma D) Hyperparathyroidism, small cell lung carcinoma, colon carcinoma E) Phaeochromocytoma, renal cell carcinoma, cerebellar haemangioblastoma Question 25. A 41-year-old woman with Graves' disease undergoes subtotal thyroidectomy. Twenty-four hours postoperatively she complains that she is unable to straighten her fingers. She also describes tingling around her mouth. What pattern of abnormalities is most likely to be seen on blood testing? A) High calcium, high phosphate, low parathyroid hormone B) High calcium, low phosphate, high parathyroid hormone C) Low calcium, high phosphate, low parathyroid hormone 71 D) Low calcium, high phosphate, high parathyroid hormone E) Low calcium, high phosphate, normal parathyroid hormone Question 26. Which one of the following skeletal changes is not a feature of primary hyperparathyroidism? A) Osteophyte formation B) Reduced bone mineral density C) Osteitis fibrosa cystica D) Chondrocalcinosis E) Terminal resorption in the phalanges Question 27. A 43-year-old woman attends her GP with a 1-year history of progressive weight gain and malaise. She bruises easily and has trouble climbing stairs. She also has increased facial hair. On examination she has a body mass index of 32 kg/m2. Her abdomen is obese with visible striae, although her arms and thighs appear wasted. What is the most likely diagnosis? A) Conn's syndrome B) Cushing's syndrome C) Addison's disease D) Phaeochromocytoma E) Congenital adrenal hyperplasia Question 28. What is the most common cause of Cushing's syndrome? A) Pituitary adenoma B) Adrenal adenoma C) Adrenal carcinoma D) Chronic glucocorticoid therapy E) Ectopic adrenocorticotrophic (ACTH) syndromes Question 29. What is the most useful initial diagnostic investigation in a patient with suspected Cushing's syndrome? A) Random plasma cortisol measurement B) Short Synacthen test C) Overnight dexamethasone suppression test D) Oral glucose tolerance test E) Twenty-four-hour urine metanephrines Question 30. Which of the following clinical and serum biochemical parameters is most consistent with Addison's disease? A) High blood pressure, low sodium, high potassium B) Low blood pressure, low sodium, high potassium C) Low blood pressure, high sodium, high potassium D) Low blood pressure, high sodium, low potassium E) High blood pressure, high sodium, high potassium Question 31. Which of the following drugs is the most appropriate medical treatment for hypertension associated with Conn's syndrome? A) Bendroflumethiazide B) Atenolol C) Perindopril D) Amlodipine E) Spironolactone Question 32. A 32-year-old man describes a 4-month history of recurrent headaches associated with sweating and palpitations. During one of these episodes he is found to have a blood pressure of 210/105 mmHg and pulse of 112 bpm. A 24-hour urine collection shows elevated metanephrine and normetanephrine excretion. An abdominal CT scan shows a large left adrenal mass. What is the most appropriate first-line antihypertensive agent? A) Atenolol B) Phenoxybenzamine C) Ramipril D) Nifedipine E) Bendroflumethiazide Question 33. A 17-year-old woman with a strong family history of diabetes mellitus is brought to the hospital accident and emergency department after collapsing at home. On arrival she has a Glasgow Coma Score of 9/15. Laboratory blood glucose is 1.2 mmol/l. Plasma insulin levels are elevated and C-peptide levels are low. Her condition improves following treatment 72 with IV dextrose. She has had three similar episodes over the preceding 6 months. What is the most likely diagnosis? A) Insulinoma B) Alcohol excess C) Diabetes mellitus D) Administration of exogenous insulin E) Sulphonylurea ingestion Question 34. Excessive secretion of which hormone is responsible for carcinoid syndrome? A) Gastrin B) Vasoactive intestinal peptide (VIP) C) Glucagon D) 5-hydroxytryptamine (5-HT) E) Somatostatin Question 35. A 29-year-old man is referred to the medical outpatient clinic with a 3-month history of polyuria. He describes increasing thirst and drinks large volumes of fluid. On examination he appears euvolaemic. A water deprivation test reveals the following results: The most likely diagnosis is: A) Diabetes mellitus B) Nephrogenic diabetes insipidus C) Cranial diabetes insipidus D) Addison's disease E) Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Question 36. A 43-year-old man is referred to the endocrinology clinic with a 1-year history of headaches and sweating. His shoe size has increased and his wedding ring no longer fits. Which of the following is the investigation of choice in establishing the cause of his symptoms? A) Oral glucose tolerance test B) CT head scan C) MRI head scan D) Insulin tolerance test E) 24-hour urinary cortisol measurement Chapter 20 DIABETES MELLITUS Answers page 195 Question 1. Which one of the following is a physiological action of insulin? A) Increased lipolysis B) Increased gluconeogenesis C) Increased ketogenesis D) Decreased glycogenolysis E) Decreased protein synthesis Question 2. All of the following are causes of secondary diabetes mellitus except one. Which is the exception? A) Acromegaly B) Corticosteroid treatment C) Haemochromatosis D) Phaeochromocytoma E) Addison's disease Question 3. All of the following statements about type 1 diabetes are true except one. Which is the exception? A) Viral infection has been implicated in the aetiology B) There is an association with pernicious anaemia C) There is destruction of the pancreatic islet ß-cells D) Treatment with insulin is essential E) Concordance rates between monozygotic twins are greater than 90% Question 4. All of the following statements except one are true of type 2 diabetes. Which is the exception? A) It is frequently detected incidentally on blood testing B) It is associated with the metabolic syndrome C) Ketoacidosis is a common complication D) There is an increased risk of ischaemic heart disease E) The prevalence is higher than that of type 1 diabetes 73 Question 5. A 58-year-old lady presents to her GP with a 6-month history of general malaise and fatigue. The GP does routine blood tests and finds her to have a fasting glucose of 7.5 mmol/l. A repeat fasting glucose 1 month later is 7.4 mmol/l. The most appropriate next step would be to: A) Repeat a fasting glucose measurement in 1 month's time B) Perform an oral glucose tolerance test C) Measure C-peptide levels D) Explain to the patient that she has diabetes mellitus E) Reassure the patient that she has normal glucose tolerance Question 6. What is the most common cause of glycosuria? A) Type 1 diabetes B) Type 2 diabetes C) A low renal threshold for glucose in an otherwise healthy individual D) Urine testing immediately after a meal in an otherwise healthy individual E) Pyelonephritis Question 7. What is the most informative method of assessing a patient's glycaemic control in the diabetic outpatient clinic? A) Performing urine dipstick analysis for glucose B) Performing urine dipstick analysis for protein C) Measuring plasma glucose D) Measuring glycated haemoglobin (HbA1C) E) Careful analysis of the patient's dietary intake according to carbohydrate exchanges Question 8. A 23-year-old man with type 1 diabetes presents to the hospital Accident and Emergency department with a 24-hour history of nausea, poor appetite and feeling unwell. Initial investigations show the following results: What is the most immediate management priority? A) Administration of intravenous insulin and intravenous saline B) Administration of intravenous insulin and intravenous potassium C) Administration of intravenous insulin and broad-spectrum antibiotics D) Administration of intravenous insulin and intravenous sodium bicarbonate E) Central line insertion to enable accurate monitoring of fluid balance Question 9. A 63-year-old man with diabetes presents to the hospital Accident and Emergency department with a 4-day history of feeling tired and unwell. He complains of severe thirst. On examination he appears dehydrated with a pulse of 116 bpm and blood pressure of 114/68 mmHg. After routine investigations, he is found to be in a hyperosmolar non-ketotic hyperglycaemic state. Which one of the following statements regarding this condition is true? A) Higher doses of insulin are usually required compared to diabetic ketoacidosis B) Subcutaneous heparin should be administered within the first 24 hours C) There is usually a profound metabolic acidosis D) People with types 1 and 2 diabetes are affected equally E) Large volumes of intravenous sodium bicarbonate are often needed 74 Question 10. Features of hypoglycaemia include all the following except one. Which is the exception? A) Sweating B) Kussmaul breathing C) Confusion D) Coma E) Tachycardia Question 11. You are asked to review a 67-year-old lady on the ward with insulintreated type 2 diabetes, who is complaining of nausea, sweating and palpitations. Blood glucose strip testing gives a reading of 2.6 mmol/l. What would be the most appropriate initial management? A) Intravenous dextrose B) Intramuscular glucagon C) Intravenous glucagon D) Oral carbohydrate E) Taking a blood sample for a formal laboratory measurement of blood glucose Question 12. A 73-year-old lady with type 2 diabetes presents to hospital with an acute myocardial infarction (MI). She normally takes metformin. What is the most appropriate way to maintain glycaemic control in the peri-infarct period? A) Continue metformin at the current dose B) Continue metformin at a higher dose C) Stop metformin and monitor blood glucose readings over the first 24 hours D) Stop metformin and commence a sulphonylurea E) Stop metformin and commence intravenous insulin Question 13. A 29-year-old pregnant woman is referred to clinic with a diagnosis of gestational diabetes. What would the best treatment be? A) Gliclazide alone B) Metformin alone C) Insulin alone D) Insulin plus gliclazide E) Insulin plus metformin Question 14. What is the correct perioperative management of an insulintreated type 2 diabetic patient undergoing a laparotomy? A) Position the patient at the head of the operation list and omit insulin until after the operation B) Administer his or her usual subcutaneous insulin pre-operatively and monitor blood glucose C) Administer half his or her usual subcutaneous dose pre-operatively and monitor blood glucose D) Start an intravenous infusion of dextrose and insulin in place of the patient's usual therapy E) Give him or her one dose of an oral anti-diabetic agent to prevent high blood glucose levels peri-operatively Question 15. A patient with type 2 diabetes and a body mass index of 34 kg/m2 has suboptimal glycaemic control with dietary therapy alone. Which of the following would be the most appropriate first-line pharmacological treatment? A) Gliclazide B) Metformin C) Rosiglitazone D) Insulin E) Metformin plus insulin Question 16. Which of the following statements about the thiazolidinediones (glitazones) is false? A) They act by binding to peroxisome proliferator-activated receptor-W (PPAR-W) B) They do not increase insulin secretion C) They are particularly useful in diabetic patients with left ventricular dysfunction D) They are useful agents in obese type 2 diabetic patients E) They rarely cause hypoglycaemia Question 17. Which one of the following drugs is correctly paired with its predominant side-effect? A) Metformin X hypoglycaemia B) Metformin X weight gain C) Gliclazide X lipohypertrophy D) Glipizide X hypoglycaemia E) Rosiglitazone X lactic acidosis 75 Question 18. What is the biggest cause of mortality in diabetic patients? A) Ischaemic heart disease B) Hypoglycaemia C) Renal failure D) Diabetic ketoacidosis E) Infection Question 19. Which of the following fundal abnormalities is not typical of diabetic retinopathy? A) Hard exudates B) Microaneurysms C) Flame haemorrhages D) Cotton wool spots E) Venous loops and beading Question 20. Which one of the following retinal appearances is a key feature of preproliferative diabetic retinopathy? A) Microaneurysms with hard exudates B) Papilloedema C) Neovascularisation D) Venous beading with cotton wool spots E) Pre-retinal haemorrhage Question 21. A 61-year-old man with type 2 diabetes has evidence of background diabetic retinopathy when examined at the diabetic clinic. He normally takes gliclazide, metformin and lisinopril. What is the most appropriate management? A) Urgent referral to an ophthalmologist for laser photocoagulation B) Routine referral to an ophthalmologist C) Regular follow-up in the diabetic clinic but no referral to ophthalmology D) Stop metformin and follow up in the diabetic clinic E) Stop lisinopril and follow up in the diabetic clinic Question 22. In the absence of contraindications, which of the drugs in the following list is the optimal antihypertensive agent in a diabetic patient with microalbuminuria? A) Bendroflumethiazide (bendrofluazide) B) Atenolol C) Ramipril D) Doxazosin E) Amlodipine Question 23. All of the following statements except one are true of diabetic neuropathy. Which is the exception? A) The incidence can be reduced by strict glycaemic control B) Motor, sensory and autonomic nerves can all be involved C) The majority of patients are asymptomatic D) Charcot joints are a recognised complication 76 E) It is typically associated with painful foot ulcers Question 24. Which one of the following is a feature of diabetic autonomic neuropathy? A) VI nerve palsy B) Carpal tunnel syndrome C) Diabetic amyotrophy D) Gastroparesis E) Stocking distribution of sensory loss in the legs Chapter 21 ALIMENTARY TRACT AND PANCREATIC DISEASE Answers page 200 Question 1. Which one of the following features on clinical examination would suggest a kidney rather than a spleen as the cause of a palpable left upper quadrant mass? A) Cannot palpate above it B) Presence of a notch C) Dullness to percussion D) Extends towards the right iliac fossa E) Rounded mass Question 2. The major enzyme responsible for protein digestion in the small bowel is: A) Trypsin B) Amylase C) Lipase D) Cholecystokinin E) Pepsin Question 3. The enzyme amylase is principally responsible for the breakdown of which one of the following? A) Protein B) Cholesterol C) Glycogen D) Bile salts E) Triglycerides Question 4. The gut hormone cholecystokin (CCK) produces all of the following effects except one. Which is the exception? A) Gallbladder contraction B) Increased secretion of pancreatic enzymes C) Satiety D) Increased gastric acid secretion E) Relaxation of the sphincter of Oddi 77 Question 5. A 55-year-old lady with a 3month history of progressive dysphagia and weight loss is investigated with a barium swallow: What is the most likely diagnosis? A) Achalasia B) Oesophageal candidiasis C) External oesophageal compression by bronchial carcinoma D) Oesophageal carcinoma E) Myasthenia gravis Question 6. Which of the following tests is most useful in the assessment of pancreatic exocrine function? A) Faecal elastase B) CT scan of abdomen C) 3-day faecal fat D) Fasting blood glucose E) Lactose hydrogen breath test Question 7. The urea breath test is useful in the diagnosis of which one of the following conditions? A) Bacterial overgrowth B) Helicobacter pylori infection C) Lactose intolerance D) Fat malabsorption E) Coeliac disease Question 8. In which of the following causes of dysphagia would oesophageal manometry be most likely to provide the diagnosis? A) Myasthenia gravis B) Bulbar palsy C) Pseudobulbar palsy D) Carcinoma of oesophagus E) Achalasia Question 9. An otherwise fit and well 40year-old man presents with a history of troublesome dyspepsia. Which of the following features in his presentation would be the strongest indication for proceeding to upper gastrointestinal endoscopy? A) Poor response to antacids B) Symptoms worse at night C) Family history of peptic ulcer disease D) Symptoms persistent for > 3 months prior to treatment E) Associated difficulty in swallowing Question 10. Which of the following drugs is least likely to be implicated in a patient presenting with vomiting? A) Erythromycin B) Codeine phosphate C) Atenolol D) Cisplatin E) Digoxin Question 11. In patients presenting with acute upper gastrointestinal haemorrhage, all of the following factors except one are associated with an increased risk of death. Which is the exception? A) Pulse > 100 bpm B) Mallory-Weiss tear as the cause of bleeding C) Visible but non-bleeding vessel present at endoscopy D) Age over 60 years E) Associated renal failure 78 Question 12. A patient presents with acute lower gastrointestinal bleeding and features of shock. Which of the following conditions would be least likely to account for this presentation? A) Diverticular disease B) Angiodysplasia C) Meckel's diverticulum D) Bowel ischaemia E) Anal fissure Question 13. In the assessment of diarrhoea, which one of the following clinical features most strongly suggests a colonic aetiology? A) Right iliac fossa pain B) Undigested food in stool C) Blood and mucus in stool D) Large-volume stool E) Abdominal bloating Question 14. Which one of the following physical consequences of malabsorption is incorrectly matched with the corresponding vitamin or mineral deficiency? A) Acrodermatitis enteropathica Zinc B) Purpura and bruising Vitamin K C) Koilonychia Iron D) Peripheral neuropathy Vitamin C E) Night blindness Vitamin A Question 15. A patient recently commenced on a new medication complains of constipation. Which of the following drugs is most likely to be implicated? A) Erythromycin B) Digoxin C) Orlistat D) Metformin E) Verapamil Question 16. Which of the following conditions is least likely to cause oral ulceration? A) Coeliac disease B) Kaposi's sarcoma C) Behçet's disease D) Herpes simplex virus E) Psoriasis Question 17. Which one of the following factors does not predispose to gastrooesophageal reflux disease (GORD)? A) Pregnancy B) High intake of coffee C) Weight loss D) Delayed gastric emptying E) Hiatus hernia Question 18. Which one of the following statements is true of Barrett's oesophagus? A) It refers to neoplastic change in the normal squamous cells of the lower oesophagus B) The majority of patients with the condition ultimately develop carcinoma of the oesophagus C) It is associated with increased alcohol intake D) Patients with the condition should undergo regular endoscopic surveillance with biopsies E) Antireflux surgery has been shown to induce regression of the condition Question 19. A 34-year-old man presents with severe retrosternal burning discomfort, worse at night and after large meals and eased by various 'over-thecounter' antacid remedies. There are no other symptoms and his general health is good. Which of the following statements concerning his condition is true? A) Upper gastrointestinal endoscopy is mandatory to exclude Barrett's oesophagus B) A history of weight gain prior to the onset of symptoms would raise doubt as to the diagnosis C) Proton pump inhibitors (PPIs) and H2receptor antagonists are equally effective in relieving symptoms and inducing healing of oesophagitis D) Recurrence of symptoms following cessation of medical treatment is common E) Antireflux surgery is rarely successful in relieving symptoms Question 20. A 57-year-old woman presents with a 12-month history of slowly progressive dysphagia for solids, eased by drinking liquids. She also experiences intermittent episodes of severe chest pain. 79 A barium swallow is performed: What is the most likely diagnosis? A) Diffuse oesophageal spasm B) Achalasia C) Systemic sclerosis D) Carcinoma of oesophagus E) Myasthenia gravis Question 21. Which one of the following statements is true concerning carcinoma of the oesophagus? A) The overall 5-year survival is approximately 40% B) CT is superior to endoscopic ultrasound in local staging C) A history of painful, intermittent dysphagia for solids and liquids is the usual presenting complaint D) The presence of hoarseness suggests mediastinal invasion E) Symptomatic relief of swallowing difficulties is best achieved by palliative radiotherapy Question 22. A 45-year-old male presents with a 10-month history of recurrent, 'gnawing' epigastric pain. The pain does not radiate and can be absent for up to a month at a time but, when present, seems to be relieved by eating. He has also experienced occasional vomiting. With which of the following diagnoses would his symptoms fit best? A) Chronic peptic ulcer B) Biliary colic C) Chronic pancreatitis D) Mesenteric ischaemia E) Crohn's disease Question 23. The patient from the previous question (Q22) who has suspected peptic ulcer disease has an endoscopy performed. This reveals a chronic duodenal ulcer. The CLO test is positive. Which one of the following statements regarding further management is false? A) Treatment with acid-suppressant therapy and H. pylori eradication is likely to cure the ulcer B) Advice should be given that cigarette smoking increases the risk of ulcer complications and reduces the chance of healing C) It is unlikely the patient will require surgery for the ulcer D) The patient should be given specific advice on dietary restriction E) Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided Question 24. Which one of the following statements concerning the bacterium Helicobacter pylori is true? A) It is a Gram-positive rod B) It produces an enzyme called 'urease' that lowers the surrounding pH C) It exclusively colonises gastric-type epithelium D) Strains expressing the enzyme cagA are less often associated with disease E) On colonising the stomach it induces increased secretion of somatostatin from D cells Question 25. All of the following statements concerning the consequences of H. pylori infection are true except one. Which is the exception? A) The majority of colonised individuals remain healthy and asymptomatic B) It is the most common cause of chronic gastritis C) Around 40% of patients with duodenal ulcer are infected with H. pylori D) It is a recognised risk factor for the development of gastric cancer E) Some gastric lymphomas may be cured solely by H. pylori eradication 80 Question 26. Which of the following is least likely to occur as a complication of partial gastrectomy? A) Weight gain B) Flushing, sweating and lightheadedness after meals with large carbohydrate content C) Postprandial diarrhoea and abdominal discomfort D) Anaemia E) Early satiety Question 27. A 32-year-old woman presents with severe recurrent epigastric pain. Endoscopy reveals multiple ulcers in the duodenum, stomach and oesophagus. There is no history of ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) and tests for H. pylori are negative. Serum gastrin levels are grossly elevated. What is the likely diagnosis? A) Covert NSAID abuse B) Carcinoid syndrome C) Zollinger-Ellison syndrome D) Crohn's disease E) Biliary reflux Question 28. All of the following except one are recognised risk factors for gastric carcinoma. Which is the exception? A) Autoimmune chronic gastritis B) Zollinger-Ellison syndrome C) Cigarette smoking D) H. pylori infection E) Familial adenomatous polyposis (FAP) Question 29. Which one of the following conditions is not associated with coeliac disease? A) Type 1 diabetes mellitus B) Pernicious anaemia C) Conn's syndrome D) Primary biliary cirrhosis E) Dermatitis herpetiformis Question 30. The differential diagnosis of subtotal villous atrophy includes all of the following conditions except one. Which is the exception? A) Tropical sprue B) AIDS enteropathy C) Giardiasis D) Dermatitis herpetiformis E) Mesenteric ischaemia Question 31. Which of the following statements is true concerning coeliac disease in adults? A) Patients are intolerant of maize and rice B) Peak onset is in the third decade C) Almost all patients who do not follow a gluten-free diet are symptomatic D) Adhering to a strict gluten-free diet increases the risk of metabolic bone disease E) There is an increased risk of T-cell lymphoma Question 32. A 55-year-old male presents with a 6-hour history of severe, constant upper abdominal pain radiating to the back. He drinks approximately 80 units of alcohol per week. On examination there is marked epigastric tenderness but no guarding or rebound tenderness. Which of the following tests is likely to be most useful in reaching a positive diagnosis? A) Plain abdominal X-ray B) C-reactive protein C) Erect chest X-ray D) ECG E) Serum amylase Question 33. All of the following except one are uncommon but recognised causes of acute pancreatitis. Which is the exception? A) Azathioprine therapy B) Mumps C) Hypocalcaemia D) Hypothermia E) Seat belt injury 81 Question 34. Which one of the following is not an adverse prognostic factor in acute pancreatitis? A) White blood cell count 16 × 109/l (normal range 4-11 × 109/l) B) Urea 20 mmol/l (normal range 2.5-6.6 mmol/l) C) Albumin 28 g/l (normal range 35-50 g/l) D) Amylase 1000 U/l (normal range < 100 U/l) E) Glucose 14 mmol/l (normal range 3.65.8 mmol/l) Question 35. Concerning the management of acute pancreatitis, which one of the following statements is true? A) Hypocalcaemia should be corrected urgently if the corrected calcium falls below 2.0 mmol/l B) Enteral feeding should be started at an early stage in patients with severe pancreatitis C) Prophylaxis of thromboembolism is inadvisable in the first 48 hours D) In gallstone pancreatitis, emergency endoscopic retrograde cholangiopancreatography (ERCP) and stone extraction should be avoided if there is evidence of ascending cholangitis E) Opiate analgesia is usually not require Question 36. Which one of the following would be considered an unexpected clinical feature in chronic pancreatitis? A) Steatorrhoea B) Weight loss C) Pain relieved by drinking alcohol D) Recurrent hypoglycaemia E) Skin pigmentation over the back Question 37. A 56-year-old lady presents with a 4-week history of weight loss and progressively worsening jaundice with pruritus. On examination she is deeply icteric and has a palpable gallbladder. What is the likeliest diagnosis? A) Chronic cholecystitis B) Hepatocellular carcinoma C) Ascending cholangitis D) Carcinoma of pancreas E) Amoebic abscess Question 38. Which one of the following statements regarding carcinoma of the pancreas is true? A) The majority of tumours are amenable to potentially curative resection B) The body of the pancreas is the most common site of origin C) Coeliac plexus neurolysis is useful in relieving pruritus D) The liver is a common site for metastatic deposits E) The prognosis is better than for carcinoma of the ampulla of Vater Question 39. Which one of the following pathological features would favour a diagnosis of ulcerative colitis over Crohn's disease? A) Presence of fistulae B) Proximal colitis with rectal sparing C) Lymphoid aggregates and microgranulomas D) Ulceration within the small intestine E) Inflammation limited to the mucosa Question 40. Which of the following would be least expected to provoke a relapse ('flare') of ulcerative colitis? A) Loss of job B) Cigarette smoking C) Ankle sprain treated with oral diclofenac D) Viral laryngitis E) Course of antibiotics for falsely suspected urinary tract infection Question 41. A 19-year-old male presents with a 10-day history of bloody diarrhoea and lower abdominal pain associated with fever, malaise and anorexia. Which of the following investigations would be least helpful in establishing a diagnosis? A) Stool culture and microscopy B) Sigmoidoscopy and rectal biopsy C) Blood cultures and serological tests of infection D) Serum albumin E) Examination of stool for Clostridium difficile toxin 82 Question 42. With reference to the patient in the previous question (Q41) who has bloody diarrhoea and lower abdominal pain, stool is negative for culture, Clostridium difficile toxin, ova and cysts. Sigmoidoscopy and rectal biopsy reveal typical features of ulcerative colitis. In the assessment of the severity of this attack, all of the following except one suggest severe disease. Which is the exception? A) 10 bowel motions per day B) Stool volume 200 g/24 hrs C) Temperature of 38°C on 2 consecutive days D) Pulse 110 bpm E) Erythrocyte sedimentation rate 80 mm/hr Question 43. The patient from the previous question (Q42) has several clinical and laboratory parameters indicating severe ulcerative colitis. Which one of the following is true regarding the management of this attack? A) Nutritional support, if required, should be provided intravenously rather than enterally B) The patient should be treated with intravenous corticosteroids C) Surgery should not be considered until he has had at least 10 days of maximal medical therapy D) Prophylaxis of venous thromboembolism with heparin should be avoided E) Sulfasalazine overcomes the need for surgery in around 80% of patients who fail to respond to corticosteroids Question 44. On the fourth day of medical treatment the patient from the previous question (Q43) does not show any signs of improvement. A plain abdominal X-ray is performed: Which one of the following statements is true? A) It is unusual for this complication to occur in the first attack of colitis B) The original diagnosis of ulcerative colitis was probably incorrect C) The patient should be referred for urgent colectomy D) No further action should be taken but the X-ray should be repeated in 24 hours E) Azathioprine treatment may avoid the need for surgery in patients with this complication Question 45. Which one of the following statements concerning intestinal complications of inflammatory bowel disease (IBD) is incorrect? A) In ulcerative colitis, colonic perforation may occur without the development of toxic megacolon B) In Crohn's disease, enterovesical fistulation may present with pneumaturia C) The risk of developing colon cancer in ulcerative colitis is related to both the extent and the duration of colitis D) Both conditions may present with acute life-threatening haemorrhage E) Diarrhoea in ulcerative colitis may be due to enteroenteric fistulae 83 Question 46. Which one of the following systemic complications of inflammatory bowel disease is not related to the activity of bowel disease? A) Conjunctivitis B) Primary sclerosing cholangitis C) Erythema nodosum D) Arthralgia E) Pyoderma gangrenosum Question 47. Concerning the management of Crohn's disease, which one of the following statements is false? A) Due to high rates of relapse, infliximab therapy should be combined with diseasemodifying agents B) Maintenance of remission is improved by cessation of cigarette smoking C) Corticosteroids are preferred to methotrexate for maintaining remission D) Surgical intervention should be conservative to minimise loss of viable intestine E) Azathioprine is an effective maintenance treatment Question 48. Which one of the following clinical features is least suggestive of irritable bowel syndrome (IBS)? A) Colicky abdominal pain relieved by defaecation B) Sensation of incomplete defaecation C) Symptoms disturbing sleep D) Alternating diarrhoea and constipation E) Passage of mucus Question 49. Regarding the management of irritable bowel syndrome (IBS), which one of the following statements is true? A) Patients with constipation as the predominant symptom benefit most from tricyclic antidepressant therapy B) Elimination diets are the mainstay of treatment C) Probiotics are of proven benefit D) Reassurance alone may lead to resolution of symptoms E) All patients should be advised to increase dietary fibre Question 50. A 75-year-old lady presents with a 2-hour history of sudden-onset severe abdominal pain and per rectum bleeding. Other than a stroke 2 years ago she keeps well. She has been on aspirin and ramipril since her stroke and takes digoxin for an irregular heart rhythm. On examination she is very distressed; her abdomen is soft with no evidence of peritonism. Bowel sounds are audible. An arterial blood gas shows a metabolic acidosis. What is the likeliest diagnosis? A) Ruptured aortic aneurysm B) Acute small bowel ischaemia C) Perforated peptic ulcer D) Diverticulitis E) Irritable bowel syndrome Question 51. A 73-year-old lady is admitted to hospital with a severe community-acquired pneumonia. She is treated with intravenous antibiotics and on the sixth day of her admission develops profuse diarrhoea associated with cramping lower abdominal pain. What test is most likely to reveal the cause of her diarrhoea? A) Stool microscopy for ova and parasites B) Barium enema C) Stool culture for Escherichia coli D) Legionella serology E) Stool analysis for Clostridium difficile toxin 84 Question 52. With regard to colonic polyps, which one of the following statements is true? A) They usually present with lower gastrointestinal bleeding or anaemia B) The size of the polyp has no bearing on the risk of malignant change C) Asymptomatic polyps found at colonoscopy should be biopsied but not removed D) Polyps with a villous architecture carry a higher risk of malignant change than those with tubular architecture E) The polyps in Peutz-Jeghers syndrome are predominantly colonic adenomas Question 53. All of the following except one are recognised risk factors for colorectal cancer. Which is the exception? A) Presence of colorectal adenomas B) Smoking C) High dietary calcium D) Acromegaly E) Long-standing extensive ulcerative colitis Question 54. A 68-year-old lady presents to her GP with tiredness and weight loss and is found to have iron deficiency anaemia. On examination there is a palpable mass in the right iliac fossa. Which of the following is the most appropriate next investigation to establish the diagnosis? A) Flexible sigmoidoscopy B) Abdominal CT scan C) Abdominal ultrasound D) Colonoscopy E) Serum carcinoembryonic antigen (CEA) Chapter 22 LIVER AND BILIARY TRACT DISEASE Answers page 208 Question 1. Which of the following is not a function of the liver? A) Synthesis of clotting factors B) Production of vitamin K C) Production of glucose during fasting D) Storage of copper E) Excretion of potentially toxic compounds Question 2. In a hepatic acinus, zone 3 is closest to the central hepatic vein. Which of the following statements concerning zone 3 is true? A) It is exposed to the highest concentrations of toxins B) It is closer to the bile duct than zones 1 and 2 C) It is the primary site of bile salt formation D) It has a good oxygen supply relative to zones 1 and 2 E) It is the primary site of lipolysis in the liver Question 3. A hospital inpatient is noted to have an elevated gamma-glutamyl transferase (GGT) with otherwise normal liver function tests. She is taking the following regular medications. Which one is most likely to have caused this abnormality? A) Omeprazole B) Paracetamol C) Phenytoin D) Ibuprofen E) Sodium valproate 85 Question 4. Of the following conditions, which is the most likely cause of jaundice accompanied by a seven-fold elevation of alanine aminotransferase and two-fold elevation of alkaline phosphatase? A) Viral hepatitis B) Acute cholecystitis C) Gilbert's syndrome D) Haemolysis E) Pancreatic carcinoma Question 5. Which one of the following is most suggestive of haemolysis as the cause of jaundice? A) Pale stools B) Raised alanine aminotransferase (ALT) C) Presence of spider naevi D) Bilirubinuria E) Raised reticulocyte count Question 6. Which one of the following coagulation factors depends on vitamin K for complete synthesis in the liver? A) Factor IV B) Factor V C) Factor VIII D) Factor IX E) Factor XI Question 7. Which of the following tests provides the most information about hepatic synthetic function within the last 12 hours? A) Activated partial thromboplastin time (APTT) B) Albumin C) Fibrinogen D) Urea E) Prothrombin time (PT) Question 8. Which one of the following is a contraindication to percutaneous liver biopsy? A) Chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of 37% B) Failure to comply with fasting requirements C) Platelet count of 190 D) Prothrombin time prolonged by 2 seconds E) Family history of haemochromatosis Question 9. A jaundiced patient has the following liver function test (LFT) results: Which one of the following is the most appropriate initial investigation to identify the underlying problem? A) Endoscopic retrograde cholangiopancreatography (ERCP) B) Hepatic portal venography C) Abdominal X-ray D) Abdominal ultrasound E) Liver biopsy Question 10. Only one of the following options associates the disease with the correct initial diagnostic test. Which is it? A) Wilson's disease Transferrin saturation B) Primary biliary cirrhosis (PBC) Antimitochondrial antibody (AMA) C) Alpha1-antitrypsin deficiency Caeruloplasmin D) Primary sclerosing cholangitis Antiendomysial antibody E) Coeliac disease 24-hour urinary copper Question 11. A patient presents to her GP after noticing that the whites of her eyes have become yellow. Direct questioning also reveals that her urine has been very dark for several days. Which of the following diagnoses is the most likely explanation for these symptoms? A) Carotenaemia B) Cholestatic jaundice C) Hyperbilirubinaemia secondary to Gilbert's syndrome 86 D) Rhabdomyolysis E) Dehydration Question 12. A 47-year-old man with a history of alcoholic cirrhosis is well known on the general medical ward after recurrent admissions for drainage of ascites. He presents with confusion, fever (38.5°C), ascites and abdominal pain. Which of the following investigations is most important to establish the diagnosis? A) Stool culture and microscopy for ova, cysts and parasites B) Diagnostic laparoscopy C) Abdominal ultrasound scan D) CT scan of abdomen E) Ascitic fluid white cell count Question 13. Which of the following is the first-line drug of choice to treat chronic ascites secondary to hepatic cirrhosis? A) Furosemide B) Spironolactone C) Digoxin D) Bendroflumethiazide E) Vasopressin Question 14. Which of the following blood results confers the worst prognosis on a patient with acute liver failure secondary to paracetamol overdose? A) Prothrombin time (PT) > 100 secs B) Aspartate aminotransferase (AST) > 6 times normal C) Alanine aminotransferase (ALT) > 2.5 times normal D) Platelets < 100 × 109/l E) Albumin < 35 g/dl Question 15. Which of the following examination findings is not characteristic of a palpable spleen? A) A palpable mass that the examiner cannot get above B) Dull to percussion C) May be balloted D) Moves with respiration E) Felt superficially Question 16. Which of the following statements about primary biliary cirrhosis is true? A) It is more common in men B) Transplant is contraindicated because of the high risk of disease recurrence C) Pruritus is a more common presenting feature than jaundice D) A positive antinuclear antibody is diagnostic E) Immunosuppression prevents disease progression Question 17. Which of the following drugs is most useful in a patient with a suspected variceal haemorrhage, where urgent upper gastrointestinal endoscopy is not available? A) Noradrenaline (norepinephrine) B) Activated protein C C) Dopamine D) Terlipressin E) Ciprofloxacin Question 18. Which of the following viruses is not capable of causing infection without concurrent infection with another hepatitis virus? A) Hepatitis A B) Hepatitis B C) Hepatitis C D) Hepatitis D E) Hepatitis E Question 19. Which one of the following statements about hepatitis A virus (HAV) infection is true? A) It is commonly spread by sexual transmission B) It may be spread by the faecal-oral route C) A chronic carrier state occurs in a minority of infected patients D) No vaccine is available E) Anti-HAV of IgG type is useful diagnostically Question 20. Which one of the following statements about hepatitis B infection is true? A) It may be spread in faeces B) The route of infection does not affect clinical course C) It is caused by an RNA virus 87 D) No vaccine is available E) It may cause cirrhosis Question 21. In a patient with suspected hepatitis B infection, which of the following serological tests is most suggestive of previous exposure to hepatitis B virus? A) HBsAg alone B) HBsAg and HBeAg C) HBsAb alone D) Anti-HBc IgM alone E) Anti-HBc IgG and HBsAb Question 22. A 23-year-old nurse is found to have abnormal liver function tests, and serological tests for hepatitis B are performed. He has a positive titre for antiHBs but no other positive serological tests. What is the significance of this finding? A) It indicates a hepatitis B chronic carrier state B) It suggests acute hepatitis B C) It effectively rules out hepatitis B as the cause of his illness D) It is consistent with convalescence following acute hepatitis B E) It indicates concurrent infection with hepatitis D Question 23. Which one of the following statements about infection with hepatitis B virus (HBV) is false? A) The majority of patients make a full recovery from acute infection B) Chronic infection may lead to hepatocellular carcinoma C) HBeAg-negative patients respond less well to treatment D) Antiviral therapy usually results in resistant mutants of HBV E) Treatment with interferon is ineffective in chronic infection Question 24. Which one of the following statements is true of hepatitis C infection? A) It is usually sexually transmitted B) A minority of patients exposed to the virus will become chronically infected C) Once infected, cure is impossible D) Liver transplantation is contraindicated due to the risk of reinfection of the transplanted liver E) Acute infection is usually asymptomatic Question 25. Which of the following statements about alcoholic liver disease (ALD) is true? A) Once cirrhosis develops, abstinence does not affect prognosis B) There is a genetic predisposition C) Binge drinkers are more likely to develop ALD than those with a consistent intake D) The presence of fatty liver (steatosis) on biopsy suggests an alternative diagnosis E) Transplantation is contraindicated Question 26. A 34-year-old woman is referred to the gastrointestinal clinic after her GP discovers abnormal liver function tests (LFTs). She denies alcohol abuse or sexual risk factors. She received a blood transfusion in the UK in 2002 following a road traffic accident. Her past medical history includes obesity (body mass index = 42), type 2 diabetes mellitus and anxiety/depression. What is the most likely cause of her deranged LFTs? A) Occult drug overdose B) Alcoholic liver disease C) Non-alcoholic fatty liver disease D) Hepatitis B infection E) Hepatitis A infection Question 27. A 42-year-old hospital inpatient, with previously normal liver function and weighing 73 kg, develops abnormal liver function tests. She has taken the following medications at therapeutic doses in the last 28 days. Which one is most likely to have caused the problem? A) Co-amoxiclav B) Paracetamol C) Temazepam D) Morphine E) Furosemide Question 28. A 37-year-old man presents to his GP complaining of tiredness, polyuria and thirst. On examination, he is found to have 4 cm hepatomegaly and a greyish pigmentation to his skin. Urinalysis reveals a large amount of glycosuria. His past medical history includes osteoarthritis, for which he takes 88 regular ibuprofen. Which of the following provides the best unifying diagnosis? A) Wilson's disease B) Diabetes insipidus C) Acute viral hepatitis D) Infectious mononucleosis E) Hereditary haemochromatosis Question 29. With reference to the patient in the previous question (Q28) who has hereditary haemochromatosis, which of the following is the most appropriate initial treatment? A) Liver transplant B) Weekly venesection of 500 ml blood C) Warfarin D) Hepatic lobe resection E) Metformin Question 30. A 25-year-old patient presents with an episode of acute hepatitis from which he recovers spontaneously and is discharged from hospital with a presumptive diagnosis of occult drug use. A year later he presents with fatigue, tremor at rest affecting both hands, and occasional wild, purposeless movements of his upper limbs. The admitting hospital doctor notes an abnormality on examination of the eyes: What is the most likely diagnosis? A) Ecstasy (MDMA) abuse B) Budd-Chiari syndrome C) Wilson's disease D) Hereditary haemochromatosis E) Amanita phalloides poisoning Question 31. Which of the following treatments is most appropriate for Wilson's disease (hepatolenticular degeneration)? A) Penicillamine B) Desferrioxamine C) Exchange transfusion D) Venesection E) Smoking cessation Question 32. World-wide, which of the following is the most important risk factor for hepatocellular carcinoma? A) Alcoholic liver disease B) Haemochromatosis C) Non-alcoholic steatohepatitis (NASH) D) Alpha1-antitrypsin deficiency E) Chronic viral hepatitis Question 33. An overweight 41-year-old woman with a body mass index of 32 presents with a 5-day history of severe right upper quadrant pain. Initially the pain was intermittent, lasting for 2 hours then subsiding, but for the past 12 hours it has been constant. On examination she is pyrexial (38.5°C) and there is tenderness and rigidity in the right upper quadrant. Her white cell count is 18 × 109/l and Creactive protein 130 mg/l. Liver function tests (LFTs) and amylase are within the normal range. Which of the following diagnoses is most likely? A) Biliary colic B) Acute pancreatitis C) Acute cholecystitis D) Mirizzi's syndrome E) Choledocholithiasis Question 34. Which one of the following hormones causes contraction of the gallbladder and release of bile acids in the fed state? A) Insulin B) Somotostatin C) Cholecystokinin D) Glucagon E) Noradrenaline (norepinephrine) 89 Question 35. Which of the following patterns of symptoms is most characteristic of acute blockage of the cystic duct by a gallstone? A) Recurrent epigastric pain, radiating to the back, lasting 2 hours then subsiding spontaneously B) Constant severe interscapular pain associated with sweating and hypotension C) Constant severe epigastric pain and recurrent vomiting D) Intermittent burning epigastric pain relieved by drinking milk E) Crushing, heavy epigastric pain radiating to the jaw associated with sweating, nausea and a terror of imminent death Question 36. Which of the following investigations is most appropriate for the initial diagnosis of acute symptomatic gallstone disease? A) CT of the abdomen B) Abdominal ultrasound scan C) Chest X-ray D) Plain abdominal X-ray E) Kidney-ureter-bladder (KUB) X-ray Question 37. Which of the following is most important before performing a transjugular intrahepatic portosystemic shunt insertion (TIPSS)? A) Sclerotherapy to oesophageal varices B) Correction of any coagulopathy with fresh-frozen plasma C) Normalisation of urea and electrolytes D) Cessation of alcohol abuse E) Psychiatric evaluation Question 38. Which one of the following statements about alcoholic liver disease is true? A) The characteristic pathological lesion is microvesicular steatosis B) Once fatty change has developed, the condition is irreversible C) Cholestasis and hepatitis are both common presentations D) Cirrhosis is an inevitable consequence of chronic alcoholism E) Beverages containing less than 10% alcohol are unlikely to cause liver damage Question 39. In which one of the following conditions is hepatomegaly least likely to be found on clinical examination? A) Alcoholic hepatitis B) Hepatic venous outflow obstruction (Budd-Chiari syndrome) C) Hepatic metastases D) Haemochromatosis E) Chronic hepatitis C infection 90 Question 40. Which of the following factors is least likely to be a precipitant of hepatic encephalopathy? A) Constipation B) Upper gastrointestinal bleed C) Hypokalaemia D) Hypoglycaemia E) Urinary tract infection Chapter 23 BLOOD DISORDERS Answers page 213 Question 1. Which one of the following statements regarding red blood cells is false? A) They are derived from megakaryocytes B) Production is stimulated by erythropoietin from the kidneyss C) Increased production is associated with increased numbers of circulating reticulocytes D) Mature red blood cells have a biconcave disc shape E) Mature red blood cells do not possess a nucleus or mitochondria Question 2. Which one of the following conditions is not typically associated with an eosinophilia? A) Asthma B) Hay fever C) Eczema D) Pneumococcal infection E) Hookworm infection Question 3. Which of the following drugs is most likely to induce neutropenia? A) Omeprazole B) Prednisolone C) Carbimazole D) Ciprofloxacin E) Alendronate Question 4. Which one of the following conditions is most likely to produce a microcytosis on blood film examination? A) Autoimmune haemolytic anaemia B) Alcohol excess C) Thalassaemia D) Vitamin B12 deficiency E) Hypothyroidism 91 Question 5. The presence of target cells on the peripheral blood film is most likely to be explained by which of the following disorders? A) Myelofibrosis B) Cirrhosis C) Haemolytic uraemic syndrome D) Lead poisoning E) Vitamin B12 deficiency Question 6. All of the following except one are causes of splenomegaly. Which is the exception? A) Chronic myeloid leukaemia B) Multiple myeloma C) Alcoholic cirrhosis D) Malaria E) Myelofibrosis Question 7. Which one of the following statements regarding the coagulation cascade is true? A) Most clotting factors are synthesised in the bone marrow B) Coagulation by the extrinsic pathway is initiated by the interaction of factor VII with tissue factor C) The intrinsic pathway is the major mechanism underlying coagulation in vivo D) Heparin exerts its anticoagulant effect by binding to protein C E) The final step in the cascade is the conversion of prothrombin to thrombin Question 8. Which one of the following clotting factors does not require vitamin K for its activation? A) Factor II B) Factor V C) Factor VII D) Factor IX E) Factor X Question 9. Which one of the following statements regarding the prothrombin time is false? A) It assesses the extrinsic pathway of the coagulation cascade B) It is prolonged in patients taking warfarin C) It provides an accurate assessment of platelet function D) It is normal in haemophilia A E) It is prolonged in patients with factor X deficiency Question 10. In a patient presenting with a bleeding disorder, which of the following clinical features would be most suggestive of a coagulation defect as opposed to a platelet disorder? A) Epistaxis B) Haemarthrosis C) Menorrhagia D) Prolonged bleeding from superficial cuts E) Purpura Question 11. All of the following statements regarding haemophilia A are correct except one. Which is the exception? A) The condition shows X-linked recessive inheritance B) There is deficiency of factor VIII C) Muscle haematomas are a characteristic manifestation D) Desmopressin aggravates the tendency to bleeding E) It may be complicated by secondary osteoarthritis Question 12. A 29-year-old woman attends hospital with a painful swollen right leg. She flew back to the UK from Australia 2 days previously. According to the Wells scoring system, her clinical risk of deep vein thrombosis (DVT) is 'high'. Which of the following tests is the most appropriate first step in her investigation? A) Coagulation screen B) Plasma D-dimer C) Doppler ultrasound scan of the leg D) Venous plethysmography E) Thrombophilia screen 92 Question 13. Which one of the following statements about ABO red cell groups is true? A) The most common blood group in the UK is group B B) Individuals with blood group AB will have circulating antibodies against both A and B antigens C) Infusion of group A red cells to a group O recipient should cause no more than a mild transfusion reaction D) Patients with group B blood group can only receive group B red cells E) ABO incompatibility reactions are mediated by complement Question 14. Which one of the following statements regarding the Rhesus D (RhD) blood group is false? A) Around 85% of Caucasians express the RhD red cell antigen B) Anti-RhD antibodies of IgG type can cross the placenta C) Transfusion of RhD-negative blood to an RhD-positive woman may result in production of anti-RhD antibodies D) Rhesus antibodies may cause severe anaemia and hyperbilirubinaemia in RhDpositive fetuses E) RhD-negative women of child-bearing potential exposed to RhD-positive blood should receive anti-RhD immunoglobulin (anti-D) Question 15. A 73-year-old woman on a regular transfusion programme is admitted for a blood transfusion. Her baseline observations are satisfactory. Twenty minutes into the transfusion she is noted to have a temperature of 37.9°C. She feels well in herself and examination is otherwise unremarkable. What is the most appropriate course of action? A) Stop transfusion and give oral iron instead B) Stop transfusion and administer IV chlorphenamine and hydrocortisone C) Administer broad-spectrum antibiotics D) Give paracetamol and continue transfusion at a slower rate E) Take an urgent blood sample for a repeat 'group and screen' test Question 16. In the UK blood products are screened for all of the following infections except one. Which is the exception? A) Human immunodeficiency virus (HIV) B) Syphilis C) Hepatitis B D) Hepatitis C E) Creutzfeldt-Jakob disease (CJD) Question 17. Long-term use of which of the following drugs can lead to iron malabsorption? A) Omeprazole B) Ferrous sulphate C) Aspirin D) Mesalazine E) Sodium valproate Question 18. A 76-year-old man is admitted to hospital with a 4-month history of increasing shortness of breath, lethargy and weight loss. He has a past history of angina, and takes aspirin, atenolol and simvastatin. Examination is unremarkable. Blood tests reveal the following: Which of the following would be the most appropriate initial investigation? A) Abdominal ultrasound scan B) Abdominal CT scan C) Upper gastrointestinal endoscopy D) Cystoscopy E) Laparoscopy Question 19. All of the following except one are recognised causes of iron deficiency anaemia. Which is the exception? A) Pregnancy B) Coeliac disease C) Cold agglutinin disease D) Partial gastrectomy E) Menorrhagia Question 20. Which one of the following tests is the most specific indicator of iron deficiency in the investigation of patients with anaemia? A) Reduced mean cell volume B) Reduced transferrin saturation C) Low serum iron D) Reduced ferritin E) Raised total iron binding capacity (TIBC) Question 21. Which one of the following statements regarding vitamin B12 deficiency is false? A) Mean cell volume is usually raised B) It may be caused by terminal ileal Crohn's disease C) Neutrophil hypersegmentation on the blood film is characteristic D) It is often due to dietary deficiency E) There may be associated pancytopenia Question 22. Which of the following neurological findings is not a feature of vitamin B12 deficiency? A) Cognitive impairment B) Nystagmus C) Ataxic gait D) Extensor plantar responses E) Symmetrical peripheral neuropathy 93 Question 23. Which one of the following statements about folate is true? A) Deficiency may result from pernicious anaemia B) Dairy products offer a rich source of folate C) Total body stores are small D) The Schilling test is useful in establishing the reason for folate deficiency E) Serum folate is the most accurate indicator of overall body stores Question 24. A 29-year-old woman attends her GP with increasing lethargy and malaise. Blood tests reveal the following: Question 25. In a patient with haemolytic anaemia, which of the following findings would be most suggestive of intravascular haemolysis? A) Raised reticulocyte count B) Haemosiderinuria C) Raised lactate dehydrogenase (LDH) D) Splenomegaly E) Positive direct Coombs test Question 26. Which one of the following statements about hereditary spherocytosis is false? A) It usually shows autosomal dominant inheritance B) Pregnancy can precipitate a megaloblastic crisis C) It may lead to the development of cholesterol gallstones D) Patients should receive treatment with folic acid E) The anaemia may be improved by splenectomy Question 27. Deficiency of which of the following enzymes is associated with haemolytic anaemia? A) Alpha-glucosidase B) Red cell transketolase C) Glucose-6-phosphate dehydrogenase D) Lactate dehydrogenase E) Tyrosine kinase Which of the following diagnoses is most consistent with these results? A) Coeliac disease B) Pernicious anaemia C) Autoimmune haemolytic anaemia D) Hereditary spherocytosis E) Anaemia of chronic disease 94 Question 28. Which one of the following statements regarding sickle-cell disease is true? A) Sickle-cell trait results in an increased susceptibility to falciparum malaria B) The condition shows X-linked inheritance C) Haemoglobin electrophoresis demonstrates a predominance of HbF D) Sickle-cell anaemia is usually accompanied by a reticulocytosis E) With optimal medical care for sicklecell anaemia, life expectancy is unaffected Question 29. Which one of the following is not a clinical manifestation of sickle-cell disease? A) Peripheral neuropathy B) Dactylitis C) Avascular necrosis of the hip D) Splenic infarction E) Pulmonary fat embolism Question 30. A 25-year-old Spanish man is referred to the haematology clinic after a routine full blood count is found to be abnormal. Blood tests reveal the following: Investigations reveal the following: What is the most likely diagnosis? A) Aplastic anaemia B) Chronic myeloid leukaemia (CML) C) Acute myeloid leukaemia (AML) D) Non-Hodgkin lymphoma E) Myelodysplastic syndrome Question 32. A 58-year-old woman is referred to the haematology clinic with an abnormal full blood count. She describes a 6-month history of tiredness, weight loss and shortness of breath. On examination there is marked hepatosplenomegaly but no lymphadenopathy. Investigations reveal the following: What is the most likely diagnosis? A) Alpha-thalassaemia B) Beta-thalassaemia major C) Beta-thalassaemia minor D) Sickle-cell disease E) Congenital sideroblastic anaemia Question 31. A 59-year-old man is referred to the haematology clinic with a 3-month history of progressive lethargy. He complains of recurrent sore throat and has recently noticed bleeding from his gums when he brushes his teeth. He has also noticed that he bruises easily. He appears pale but examination is otherwise unremarkable. 95 What is the most likely diagnosis? A) Hodgkin's disease B) Acute myeloid leukaemia (AML) C) Acute lymphoblastic leukaemia D) Chronic myeloid leukaemia (CML) E) Chronic lymphocytic leukaemia Question 33. Which haematological condition is associated with the Philadelphia chromosome [t(9;22)]? A) Myelofibrosis B) Myelodysplastic syndrome C) Multiple myeloma D) Chronic lymphocytic leukaemia E) Chronic myeloid leukaemia (CML) Question 34. Which one of the following statements about chronic lymphocytic leukaemia (CLL) is false? A) In the majority of cases, the diagnosis is made incidentally following a routine full blood count B) There is a monoclonal proliferation of B lymphocytes C) Hyposplenism is a frequent finding D) The condition is associated with autoimmune haemolytic anaemia E) Chlorambucil may be used as first-line therapy for patients receiving active treatment Question 37. A 69-year-old man describes a 6-month history of lethargy, weight loss and lower back pain. Blood tests reveal the following: Question 35. Which one of the following statements about myelodysplasia is false? A) It predominantly affects elderly individuals B) It often progress to acute myeloid leukaemia (AML) C) Peripheral blood cytopenias are a characteristic feature D) Bone marrow aspiration reveals a hypocellular marrow E) Curative treatment is not possible in the majority of patients Question 36. A 26-year-old man presents with a 6-week history of a painless swelling in his neck. On examination he has painless rubbery cervical lymphadenopathy but no other palpable lymph nodes or splenomegaly. Following lymph node biopsy (see below) the diagnosis of Hodgkin lymphoma is made: What abnormality is shown in the biopsy? A) Auer rod B) Reed-Sternberg cell C) Ringed sideroblast D) Howell-Jolly body E) Burr cell 96 What is the most likely diagnosis? A) Waldenström's macroglobulinaemia B) Multiple myeloma C) Renal cell carcinoma with bony metastases D) Primary hyperparathyroidism E) Non-Hodgkin lymphoma Question 38. The diagnosis of multiple myeloma requires 2 out of 3 diagnostic criteria. Which of the following pairs of results would clinch the diagnosis? A) Presence of serum paraprotein and raised plasma calcium B) Erythrocyte sedimentation rate (ESR) > 100 mm/hr and increased malignant plasma cells in bone marrow C) Raised alkaline phosphatase (ALP) and positive radioisotope bone scan D) Bence Jones protein in urine and lytic lesions on plain X-ray E) Presence of serum paraprotein and widespread lymphadenopathy Question 39. Which one of the following statements regarding polycythaemia rubra vera is false? A) Splenomegaly is a common finding B) Progression to myelofibrosis may occur C) There is an increased risk of ischaemic stroke D) Symptoms are improved by venesection E) Aspirin is contraindicated Question 40. Which condition is characterised by the combination of microangiopathic haemolytic anaemia, neurological signs and renal impairment? A) Idiopathic thrombocytopenic purpura B) Thrombotic thrombocytopenic purpura C) Hereditary haemorrhagic telangiectasia D) Primary thrombocythaemia E) Henoch-Schönlein purpura Question 41. A 74-year-old man is referred to the medical outpatient clinic with a 6-month history of weight loss, fevers and night sweats. He has no significant past medical history. On examination there is painless rubbery 97 cervical, axillary and inguinal lymphadenopathy. There is also palpable hepatosplenomegaly. Blood tests show a mild normocytic, normochromic anaemia. CT confirms the clinical findings and also demonstrates bulky mediastinal and retroperitoneal lymph nodes. What is the most likely diagnosis? A) Chronic myeloid leukaemia B) Multiple myeloma C) Hodgkin's disease D) Non-Hodgkin lymphoma E) Myelofibrosis Question 42. Which one of the following statements regarding disseminated intravascular coagulation (DIC) is false? A) The condition may be precipitated by Gram-negative septicaemia B) Thrombocytopenia is a characteristic finding C) Fibrinogen levels are elevated D) D-dimer levels are elevated E) There is a significant risk of haemorrhage Question 43. All of the following statements about heparin are correct except one. Which is the exception? A) Unfractionated intravenous heparin potentiates the activity of antithrombin B) Severe bleeding secondary to intravenous heparin can be reversed with protamine C) The anticoagulant effect of low molecular weight heparin can be assessed using the activated partial thromboplastin time (APTT) D) Thrombocytopenia is a recognised complication of treatment with heparin E) Heparin exerts its anticoagulant effect more quickly than warfarin Chapter 24 MUSCULOSKELETAL DISORDERS Answers page 221 Question 1. A 70-year-old lady who has recently noticed some hearing difficulty is found to have a greatly increased plasma alkaline phosphatase concentration with normal calcium, phosphate and parathyroid hormone (PTH) levels. What is the most likely diagnosis? A) Osteomalacia B) Rickets C) Renal osteodystrophy D) Paget's disease E) Osteoporosis Question 2. A 76-year-old man with type 2 diabetes and longstanding osteoarthritis of the knees and hips presents to the hospital accident and emergency department with a 72-hour history of progressive pain and swelling of his right knee. He was recently treated by his general practitioner for an episode of cellulitis. On examination, his temperature is 38.5°C and there is a warm, tense effusion with marked tenderness and overlying erythema. Which of the following is the most likely diagnosis? A) Haemarthrosis B) Trauma C) Septic arthritis D) Acute gout E) First presentation of rheumatoid arthritis Question 3. With reference to the patient from the previous question (Q2) who has suspected septic arthritis, which of the following investigations would be of greatest help in confirming the diagnosis? A) Full blood count B) C-reactive protein (CRP) C) X-ray of knee joint D) Joint aspiration E) Ultrasound scan of knee joint 98 Question 4. Which one of the following statements is true with regard to fibromyalgia? A) The erythrocyte sedimentation rate (ESR) is usually elevated B) Symptoms of pain predominantly arise from peripheral joints C) Exacerbations of symptoms are often associated with stressful life events D) Systemic steroids form the cornerstone of treatment E) Muscle biopsy is the definitive investigation Question 5. Which of the following clinical features is least typical of osteoarthritis? A) Joint pain aggravated by activity and relieved by rest B) Involvement of large joints C) Prolonged morning stiffness D) Presence of Bouchard's nodes E) Palpable crepitus over affected joint Question 6. All of the following except one may form part of the management of osteoarthritis. Which is the exception? A) Aerobic and strengthening exercises B) Non-steroidal anti-inflammatory drugs C) Total joint replacement D) Methotrexate E) Provision of a walking stick Question 7. A lady is referred to a rheumatologist by her general practitioner with suspected rheumatoid arthritis. Which one of the following features would not provide support for this diagnosis? A) Morning stiffness lasting more than an hour B) The presence of anti-double-stranded DNA (anti-dsDNA) antibodies on blood tests C) Periarticular osteopenia and marginal erosions on X-ray D) Symmetrical pattern of arthritis E) Duration of symptoms greater than 6 weeks Question 8. All of the following except one are well-recognised extra-articular features of rheumatoid arthritis. Which is the exception? A) Episcleritis B) Pyoderma gangrenosum C) Pericarditis D) Alopecia E) Pulmonary nodules Question 9. A gentleman of 70 with longstanding rheumatoid arthritis is found on a routine blood test to have a white cell count of < 1 × 109/l. He complains of abdominal pain, and on examination you find generalised lymphadenopathy and splenomegaly. Which of the following is the most likely diagnosis? A) Malaria B) Acute lymphatic leukaemia (ALL) C) Felty's syndrome D) Portal hypertension secondary to alcoholic liver disease E) Overwhelming septicaemia Question 10. All of the following clinical features affecting the hands except one are characteristic of rheumatoid arthritis. Which is the exception? A) Bouchard's nodes B) Swan neck deformity C) Piano key deformity D) Subluxed metacarpophalangeal joints E) Rupture of the extensor tendons 99 Question 11. Which one of the following agents is not classified as a diseasemodifying antirheumatic drug (DMARD)? A) Sulfasalazine B) Naproxen C) Penicillamine D) Sodium aurothiomalate (gold) E) Azathioprine Question 12. All of the following except one are documented side-effects of antiarthritic drugs. Which is the exception? A) Renal impairment with ciclosporin B) Pulmonary fibrosis with methotrexate C) Bone marrow suppression with azathioprine D) Keratitis with hydroxychloroquine E) Gastritis with non-steroidal antiinflammatory drugs (NSAIDs) Question 13. All of the following except one are characteristic features of ankylosing spondylitis. Which is the exception? A) Raised erythrocyte sedimentation rate and C-reactive protein B) Strongly positive rheumatoid factor C) Association with HLA-B27 histocompatibility antigen D) Extraspinal features including anterior uveitis and aortic incompetence E) 'Bamboo' spine appearance on X-ray Question 14. Recognised patterns of psoriatic arthritis include all of the following except one. Which is the exception? A) Asymmetric oligoarthritis B) Arthritis mutilans C) Symmetrical polyarthritis D) Atlanto-axial instability E) Distal interphalangeal joint arthritis Question 15. A 50-year-old man presents to his general practitioner with an acute episode of gout. The GP takes a full history and decides that a likely risk factor is one of his medications. Which one of the following drugs would be the most likely candidate? A) Bendroflumethiazide B) Paracetamol C) Perindopril D) Atenolol E) Clopidogrel Question 19. Which one of the following statements regarding osteoporosis is true? A) The most common biochemical profile is a normal serum calcium and phosphate with a raised alkaline phosphatase B) It is less likely to occur in women who have an early menopause C) It is highly unlikely in the absence of symptoms D) Weight-bearing exercise is protective E) Bone mineral density Z-score of less than -2.5 is diagnostic Question 16. All of the following statements about gout are true except one. Which is the exception? A) A typical attack presents with rapid onset of severe pain in a single distal joint B) There is a male preponderance of the disease C) Allopurinol is often used in the treatment of an acute attack D) High alcohol intake is a risk factor for the condition in susceptible individuals E) The monosodium urate crystals deposited within affected joints are negatively birefringent when viewed under polarised light Question 20. Which of the following clinical features is least suggestive of systemic lupus erythematosus (SLE)? A) Raynaud's phenomenon B) Scarring alopecia C) A photosensitive, erythematous malar rash D) Sclerodactyly E) Oral ulcers Question 17. All of the following except one are associated with pseudogout (calcium pyrophosphate dihydrate crystal deposition). Which is the exception? A) Hyperparathyroidism B) Acromegaly C) Wilson's disease D) Haemochromatosis E) Advancing age Question 18. All of the following factors except one would increase the likelihood of a patient developing osteoporosis in later life. Which is the exception? A) Cigarette smoking B) Anorexia nervosa C) Hypothyroidism D) Family history of osteoporosis E) Long-term therapy with oral corticosteroids 100 Question 21. Which one of the following statements is true with regard to the use of bisphosphonates in osteoporosis? A) They inhibit bone resorption B) They have been shown to reduce the risk of fracture in patients with normal bone mineral density C) They reduce the risk of fracture but do not influence bone mineral density D) There is no effective oral preparation E) They stimulate bone formation Question 22. A 46-year-old builder presents to his general practitioner with a 1-week history of back pain. Which one of the following features in his presentation would provide the greatest cause for concern? A) Sudden onset of the pain while lifting a heavy load at work B) A history of intermittent episodes of low back pain in the past C) Pain varying with physical activity but generally relieved by rest D) Difficulty passing urine E) Tenderness of the paraspinous muscles Question 23. Which one of the following conditions is associated with a seronegative arthritis? A) Systemic lupus erythematosus B) Rheumatoid arthritis C) Systemic sclerosis D) Psoriasis E) Sjögren's syndrome Question 24. Which one of the following is not considered a risk factor for development of gastrointestinal ulceration, perforation and bleeding induced by nonsteroidal anti-inflammatory drugs (NSAIDs)? A) Age > 60 years B) Concomitant oral corticosteroid use C) Concomitant respiratory disease D) Past history of peptic ulcer disease E) H. pylori colonisation of the stomach Question 25. Which one of the following is a characteristic feature of Reiter's disease? A) Conjunctivitis B) Subcutaneous nodules C) Strong female preponderance D) Precipitated by streptococcal throat infection E) Positive rheumatoid factor Question 26. Which one of the following statements regarding dual energy X-ray absorptiometry (DXA) bone scanning is incorrect? A) The Z-score compares the patient's bone density to that of an age-matched control B) A T-score of -2.5 is indicative of osteoporosis C) DXA is indicated in patients with an early menopause who have not received hormone replacement therapy D) The preferred measurement sites for bone mineral density are the hip and the lumbar spine E) DXA bone scanning involves the intravenous injection of radioisotope Question 27. A 24-year-old woman with sclerodactyly and symptoms suggestive of Raynaud's phenomenon is diagnosed with systemic sclerosis. Which one of the 101 following statements is true regarding her treatment? A) Calcium channel blockers such as nifedipine may help symptoms of Raynaud's phenomenon B) Angiotensin-converting enzyme (ACE) inhibitors are contraindicated due to the risk of precipitating a hypertensive renal crisis C) Systemic steroids are useful for treating skin changes D) H2-receptor antagonists are more effective than proton pump inhibitors for treatment of oesophageal reflux E) There are no effective oral treatments for pulmonary hypertension Question 28. Which one of the following findings on clinical examination is characteristic of dermatomyositis? A) Weakness of the distal musculature B) Tender nodules on the finger pulps C) A violaceous rash around the eyes D) Nail pitting E) Peripheral oedema Question 29. As the admitting doctor on a general medical ward, you see a patient who has been referred from primary care and is suspected of having dermatomyositis. Which of the following investigations (all of which may support or refute the diagnosis) should you order first? A) Electromyography (EMG) B) Serum creatine kinase (CK) C) Muscle biopsy D) CT chest/abdomen/pelvis E) MRI Question 30. A 23-year-old lady who complains of dry eyes and mouth has a positive Schirmer's test. Serological tests are positive for antinuclear antibody (ANA) and rheumatoid factor. Which of the following is the most likely unifying diagnosis? A) Systemic lupus erythematosus (SLE) B) Sjögren's syndrome C) Conjunctivitis D) Rheumatoid arthritis E) Dehydration Question 31. All of the following statements about Sjögren's syndrome are true except one. Which is the exception? A) There is an association with HLA-B27 B) There is a female preponderance C) Enlargement of the salivary glands is frequently found D) There is an association with other autoimmune diseases such as primary biliary cirrhosis and myasthenia gravis E) There is an increased risk of developing lymphoma Question 32. Which one of the following features is most typical of polymyalgia rheumatica? A) A normal erythrocyte sedimentation rate (ESR) B) Poor response to oral corticosteroid treatment C) Marked muscle wasting D) Muscle stiffness and tenderness E) Mean age of onset of 30 years Question 33. A 75-year-old lady is admitted to the medical admissions unit in the early hours of the morning with a temporal headache, visual disturbance and pain on chewing. On examination, she has decreased visual acuity in her right eye and tenderness over the right scalp. The erythrocyte sedimentation rate (ESR) is 95 mm/hr. Which is the most important action to take? A) Order a CT of the brain B) Request an ophthalmology review in the morning C) Request a temporal artery biopsy D) Give 30 mg of dihydrocodeine for pain relief E) Give 60 mg of prednisolone by mouth Question 34. All of the following statements except one are true of polyarteritis nodosa. Which is the exception? A) Skin manifestations include palpable purpura and livedo reticularis B) There is an association with hepatitis B infection C) It is a large-vessel vasculitis D) Peripheral nerve palsies may be associated E) Severe hypertension is a recognised complication 102 Question 35. With regard to the anatomy of bone, which is the one incorrect statement below? A) The normal skeleton consists of both cortical and trabecular bone B) Cortical bone is formed from Haversian systems C) Osteoclasts are responsible for bone formation D) The most abundant protein in bone is collagen E) Bone is mineralised with calcium and phosphate Question 36. With regard to the anatomy of joints, which is the one incorrect statement below? A) The costochondral joint is an example of a fibrocartilaginous joint B) Synovial joints always include two surfaces covered with articular cartilage C) Articular cartilage has a rich vascular supply D) Synovial fluid is an ultrafiltrate of plasma containing proteoglycans E) The joint capsule is in part formed from ligament Question 37. Plain radiography of joints is often a helpful aid to diagnosis in bone and joint disease. Which is the one incorrect association in the following list of radiographic findings? A) Bony osteophytes and subchondral sclerosis with osteoarthritis B) Diffuse narrowing of the joint space with rheumatoid arthritis C) Soft tissue swelling with septic arthritis D) Looser's zones with osteomalacia E) Osteopenia with Paget's disease of bone Question 38. Which one of the following statements about blood tests often used in rheumatology is incorrect? A) A high titre of rheumatoid factor at first presentation of rheumatoid arthritis is a poor prognostic factor B) Anti-double-stranded DNA (antidsDNA) antibodies are highly specific for systemic lupus erythematosus (SLE) C) Antinuclear antibody (ANA) is a highly sensitive test for SLE D) The serum creatine kinase is often elevated in dermatomyositis E) Serum biochemistry is usually normal in osteomalacia Question 39. A number of weeks after commencing a new tablet for her blood pressure, a 49-year-old lady with hypertension presents to her general practitioner with a photosensitive rash affecting her face and hands and newonset arthralgia. The GP also finds microscopic haematuria on urinalysis and suspects drug-induced lupus. Which of the following medications is most likely to have caused this presentation? A) Atenolol B) Lisinopril C) Minoxidil D) Hydralazine E) Nifedipine 103 Question 40. A 12-year-old boy is brought to clinic by his mother with a rash on his legs that has appeared over the last 3 days. He also complains of pain in his knees and hands, and in the last 24 hours has developed central abdominal pain. Prior to this episode he was entirely well, apart from what his mother describes as a 'cold' 2 weeks ago. On examination, you find a palpable purpuric rash over the buttocks and lower limbs. What is the likeliest diagnosis? A) Still's disease B) Henoch-Schönlein purpura C) Kawasaki disease D) Rheumatic fever E) Juvenile idiopathic arthritis Question 41. With reference to the patient in the previous question (Q40) who has suspected Henoch-Schönlein purpura, which of the following investigations is least likely to contribute to the diagnosis? A) Dipstick and microscopy of urine for red cells B) Urea and electrolytes (U&E) C) Full blood count (FBC) D) Chest X-ray E) Skin biopsy Question 42. Which one of the following conditions is least likely to occur as a complication of Marfan's syndrome? A) Lens dislocation B) Spontaneous pneumothorax C) Aortic dissection D) Mitral valve prolapse E) Pulmonary embolism Chapter 25 NEUROLOGICAL DISEASE Answers page 227 Question 1. The nerve root values corresponding to the biceps tendon reflex are: A) C4/C5 B) C5/C6 C) C6/C7 D) C7/C8 E) C8/T1 Question 2. The myelin sheath surrounding peripheral nerve axons is formed by: A) Astrocytes B) Oligodendrocytes C) Microglial cells D) Schwann cells E) Ependymal cells Question 3. Which of the following neurological deficits is most likely to result from an isolated left temporal lobe lesion in a right-handed individual? A) Expressive dysphasia B) Receptive dysphasia C) Right hemiparesis D) Right hemisensory loss E) Right-sided neglect Question 4. A 63-year-old man attends the neurology outpatient clinic with his wife. His wife reports that for the last few months he has been behaving completely out of character; for instance, he has been shouting and undressing in public. During the consultation he makes inappropriate sexual references. On examination he has a positive grasp reflex. This presentation would fit best with a lesion in which of the following sites? A) Frontal lobe B) Dominant parietal lobe C) Non-dominant parietal lobe D) Dominant temporal lobe E) Non-dominant temporal lobe 104 Question 5. Which disorder is suggested by a 3 cycles/second 'spike and wave' pattern on the electroencephalogram (EEG)? A) Juvenile myoclonic epilepsy B) Childhood absence epilepsy C) Secondary generalised epilepsy D) Sporadic Creutzfeldt-Jakob disease E) Motor neuron disease Question 6. Nerve conduction studies are most likely to be helpful in which of the following conditions? A) Motor neuron disease B) Myasthenia gravis C) Multiple sclerosis D) Carpal tunnel syndrome E) Lambert-Eaton syndrome Question 7. Which of the following imaging modalities is most likely to yield diagnostic information in a patient with suspected multiple sclerosis? A) Plain skull X-ray B) Carotid Doppler ultrasound (duplex) scan C) CT head scan with contrast D) CT head scan without contrast E) MRI head scan Question 8. A 48-year-old man presents to the hospital accident and emergency department with possible meningitis. Which one of the following would not be a contraindication to immediate lumbar puncture? A) Thrombocytopenia B) A Glasgow coma score of 10/15 C) Reduced power in the left leg with an extensor plantar response D) Current treatment with aspirin E) Papilloedema Question 9. Which of the following features is least consistent with the headache of raised intracranial pressure? A) Associated with morning vomiting B) Worsens as the day progresses C) Exacerbated by coughing D) Presence of papilloedema E) Relieved by simple analgesia Question 10. A 33-year-old woman attends her general practitioner with a 4week history of persistent headache. She describes the sensation of a 'tight band' around her head but denies any nausea or visual disturbance. The headache is worse at the end of the day and responds poorly to paracetamol. She has managed to continue working as a shop assistant. What is the most likely diagnosis? A) Temporal arteritis B) Migraine C) Tension headache D) Viral meningitis E) Intracranial space-occupying lesion Question 11. A 25-year-old woman attends hospital with a 12-hour history of intense, throbbing pain on the right side of her head. She has vomited twice and finds it uncomfortable to look at bright light. She gives no history of any visual disturbance or unusual sensations prior to the onset of pain. She has experienced two similar but milder episodes over the last 3 months. What is the most likely diagnosis? A) Subarachnoid haemorrhage B) Migraine C) Viral meningitis D) Intracranial space-occupying lesion E) Cluster headache Question 12. Which of the following drugs is most useful in the treatment of an acute severe migraine attack? A) Sumatriptan B) Propranolol C) Pizotifen D) Sodium valproate E) Amitriptylin 105 Question 13. Which one of the following features is characteristic of cluster headache? A) More frequent in females B) Episodic attacks lasting 12-24 hours C) Patients able to continue normal activities during pain D) Pain is predominantly occipital E) Associated nasal congestion and conjunctival injection Question 14. In a patient presenting with vertigo, which one of the following features most strongly suggests a central rather than peripheral (labyrinthine) cause? A) Episodes provoked by head movement B) Persistent nystagmus C) Tinnitus and distorted hearing D) Positive Hallpike manoeuvre E) Vomiting Question 15. In a patient presenting with a blackout, which one of the following features is most suggestive of a seizure? A) No warning prior to blackout B) Severely bitten tongue C) Urinary incontinence D) Extreme pallor during the unconscious period E) Rapid recovery following the collapse Question 16. A 54-year-old man experiences partial motor seizures characterised by uncontrollable jerking of the right arm and leg. What is the most likely anatomical focus of seizure activity? A) Right pre-central gyrus B) Right post-central gyrus C) Left pre-central gyrus D) Left post-central gyrus E) Left temporal lobe Question 17. Which one of the following is not a cause of partial seizures? A) Astrocytoma B) Cerebral abscess C) Cerebral infarction D) Alcohol withdrawal E) Intracerebral haemorrhage Question 18. A 49-year-old teacher is referred to the medical outpatient clinic following a first seizure. He has no significant past medical history. What advice would you offer him about driving if he lived in the UK? A) He can continue driving provided that he is accompanied at all times B) He can resume driving once established on anticonvulsant therapy C) He should refrain from driving until seizure-free for 3 months D) He should refrain from driving until seizure-free for 1 year E) He should not drive again Question 19. Which of the following drugs is first-line anticonvulsant therapy for primary generalised tonic-clonic epilepsy? A) Phenytoin B) Gabapentin C) Levetiracetam D) Sodium valproate E) Topiramate Question 20. First-line drug treatment for status epilepticus is: A) IV phenytoin B) IV propofol C) IV diazepam D) IV sodium valproate E) IV Phenobarbital Question 21. Which one of the following clinical signs is caused by lower motor neuron lesions? A) Hypertonia B) Muscle fasciculations C) Brisk tendon reflexes D) Clonus E) Extensor plantar responses Question 22. Which one of the following conditions is most likely to be associated with a resting tremor? A) Cerebellar stroke B) Hepatic encephalopathy C) Essential tremor D) Parkinson's disease E) Thyrotoxicosis 106 Question 23. Which one of the following involuntary movements is incorrectly paired with its definition? A) Chorea - jerky, small-amplitude, purposeless movements B) Athetosis - slow writhing movements of the limbs C) Dystonia - involuntary adoption of an abnormal posture D) Hemiballismus - brief, non-purposeful twitching of muscle groups E) Tics - repetitive semi-purposeful movements Question 24. You are asked to examine a 59-year-old man admitted to the neurology ward. Examination reveals loss of joint position and vibration sensation over the right side of the body, with loss of pain and temperature sensation over the left side of the body. There is weakness of the right arm and leg associated with increased tone, brisk reflexes and an extensor plantar. There is no motor deficit on the left side of the body. Cranial nerves, including facial sensation, are intact. What is the most likely cause of these findings? A) Left cerebral hemisphere lesion B) Right-sided cervical spinal cord lesion C) Left-sided cervical spinal cord lesion D) Transverse cervical spinal cord lesion E) Peripheral neuropathy Question 25. You are asked to review a patient with reduced consciousness. He is lying silently with his eyes closed. He makes no response to any verbal prompts but when you apply supraorbital pressure he opens his eyes, makes moaning noises and attempts to remove your hand. These findings are consistent on repeated testing. Based on this data what is his Glasgow Coma Scale score? A) 6 B) 7 C) 8 D) 9 E) 10 Question 26. Which one of the following statements is true of dementia? A) Prominent visual hallucinations suggest Pick's disease B) All patients with severe Alzheimer's disease should receive a trial of anticholinesterase drugs C) Disturbance of language function in the early stages is an indication for brain biopsy D) Recurrent urinary tract infections are a frequent cause E) Imaging of the brain (CT or MRI) should be performed in most patients Question 27. Which one of the following is not a feature of cerebellar disease? A) Ataxia B) Dysarthria C) Hyperreflexia D) Nystagmus E) Dysdiadochokinesis Question 28. Which of the following visual deficits is most likely to occur secondary to a right parietal stroke? A) Right homonymous hemianopia B) Left homonymous hemianopia C) Right homonymous lower quadrantanopia D) Left homonymous lower quadrantanopia E) Left homonymous upper quadrantanopia Question 29. A 34-year-old woman complains of double vision on looking to the right. Eye movement testing confirms diplopia on rightward gaze. Covering the right eye causes disappearance of the outer image. What is the most likely cause of the diplopia? A) Right oculomotor (III) nerve lesion B) Left oculomotor (III) nerve lesion C) Right trochlear (IV) nerve lesion D) Right abducens (VI) nerve lesion E) Left abducens (VI) nerve lesion 107 Question 30. A 74-year-old man complains of headache and double vision. On examination the left eye is looking downwards and abducted with a ptosis. The right eye appears normal. The left pupil is dilated and unresponsive but the right pupil shows normal reactivity to light. What is the most likely site of the lesion? A) Left oculomotor (III) nerve B) Left trochlear (IV) nerve C) Left abducens (VI) nerve D) Left levator palpebrae superioris muscle E) Left constrictor pupillae muscle Question 31. A 68-year-old man with an apical bronchial carcinoma is found to have a partial right ptosis associated with a small right pupil and reduced sweating on the right side of the face. What name is given to this constellation of features? A) Cavernous sinus syndrome B) Horner's syndrome C) Lambert-Eaton syndrome D) Sjögren's syndrome E) Holmes-Adie syndrome Question 32. Which one of the following statements regarding Bell's palsy is false? A) Patients may experience hyperacusis B) Spontaneous recovery occurs in the majority of patients C) Treatment with prednisolone may be of benefit D) The ability to wrinkle the forehead is preserved E) Patients have difficulty closing the eye on the affected side Question 33. Which one of the following is an indication for an urgent CT head scan in a patient presenting with a suspected stroke? A) Previous ischaemic stroke B) Presence of a carotid bruit C) Clinical features of a total anterior circulation stroke D) Treatment with aspirin E) Treatment with warfarin Question 34. Which of the following presentations is least consistent with a diagnosis of transient ischaemic attack (TIA)? A) Monocular blindness B) Facial asymmetry and slurred speech C) Expressive dysphasia D) Loss of consciousness E) Left hemiparesis Question 35. A 73-year-old man presents with a right hemiparesis and expressive dysphasia secondary to an infarct in the territory of the left middle cerebral artery. Blood pressure is 153/82 mmHg, serum cholesterol is 4.4 mmol/l and the ECG shows sinus rhythm with no abnormalities. Which of the following medications is least likely to be of benefit in preventing a further ischaemic stroke? A) Ramipril B) Bendroflumethiazide C) Aspirin D) Warfarin E) Simvastatin Question 36. Which of the following ischaemic stroke patients who have undergone carotid duplex scanning would be most likely to benefit from left carotid endarterectomy? A) Right middle cerebral artery territory infarct with good functional recovery, 75% left carotid artery stenosis B) Left middle cerebral artery territory infarct with good functional recovery, 60% left carotid artery stenosis C) Left middle cerebral artery territory infarct with good functional recovery, 80% left carotid artery stenosis D) Left middle cerebral artery territory infarct with persistent dense right hemiparesis and profound dysphasia, 90% left carotid artery stenosis E) Left cerebellar hemisphere infarct with good functional recovery, 80% left carotid artery stenosis 108 Question 37. A 43-year-old woman attends the hospital accident and emergency department with a 1-hour history of sudden-onset, severe occipital headache. On examination she is photophobic with neck stiffness. What is the most appropriate first-line investigation? A) Skull X-ray B) CT head scan C) CT cerebral angiography D) Lumbar puncture E) Carotid Doppler ultrasound (duplex) scan Question 38. Which one of the following is not a risk factor for cerebral venous thrombosis? A) Oral contraceptive pill B) Dehydration C) Facial erysipelas D) Factor V Leiden deficiency E) Hypercholesterolaemia Question 39. Which one of the following statements regarding multiple sclerosis is true? A) The peak age of onset is between 50 and 60 years B) It is more common in males C) It follows a relapsing and remitting course in the majority of patients D) Impairment of memory is a common presenting feature E) The presence of oligoclonal bands of IgG in cerebrospinal fluid is diagnostic Question 40. Which one of the following treatments is first-line in treating acute relapses of multiple sclerosis? A) Interferon beta B) Methylprednisolone C) IV immunoglobulin D) Plasmapheresis E) Azathioprine Question 41. Which one of the following statements about Alzheimer's disease is true? A) 70% of individuals over the age of 80 years are affected B) Senile plaques and neurofibrillary tangles are characteristic features on brain histology C) Impairment of long-term memory is the earliest feature in the majority of patients D) CT head findings are diagnostic for the condition E) Progression can be halted by early treatment with anticholinesterases Question 42. A 73-year-old man is admitted to hospital with declining mobility. On examination there is a resting tremor affecting the right hand. Muscle tone in the arms is increased. He has difficulty when asked to fasten his buttons. What is the most likely diagnosis? A) Alzheimer's disease B) Parkinson's disease C) Huntington's disease D) Myotonic dystrophy E) Motor neuron disease Question 43. Which one of the following is not a feature of the gait of Parkinson's disease? A) Reduced arm swing B) Wide-based gait C) Impaired balance on turning D) Slow to start walking E) Shortened stride length Question 44. Which one of the following statements regarding the treatment of Parkinson's disease is true? A) Levodopa can be used without a peripheral dopa-decarboxylase inhibitor in many patients B) Young patients with Parkinson's disease should be commenced on levodopa as early as possible C) Levodopa is more effective at relieving tremor than bradykinesia or rigidity D) Dyskinesia secondary to levodopa can be improved by modifying the dosing regimen E) Anticholinergic drugs are contraindicated 109 Question 45. Which one of the following drugs is most likely to cause parkinsonism as a side-effect? A) Amitriptyline B) Diazepam C) Phenytoin D) Fluoxetine E) Haloperidol Question 46. Which one of the following statements regarding Huntington's disease is false? A) It has autosomal recessive inheritance B) It is due to a trinucleotide repeat C) Successive generations are often affected at an earlier age D) Cognitive impairment is a frequent finding E) Genetic screening is available for family members of affected individuals Question 47. A 68-year-old man is referred to the neurology outpatient clinic with a 1-year history of progressive bilateral arm and leg weakness. On examination there is global muscle wasting with muscle fasciculations in the upper arms and thighs. There is generalised muscle weakness, worse distally and on the left. Reflexes are brisk throughout and plantars are extensor. Sensory examination is normal and cranial nerves are intact. What is the most likely diagnosis? A) Myotonic dystrophy B) Motor neuron disease C) Guillain-Barré syndrome D) Cerebrovascular disease E) Myasthenia gravis Question 48. A 34-year-old woman attends the hospital accident and emergency department with a 6-hour history of headache, fever and neck stiffness. On examination she has a temperature of 39.1°C, pulse of 108 bpm, blood pressure of 110/58 mmHg and oxygen saturation of 98% on air. Glasgow Coma Score is 15/15. A purpuric rash is noted over her chest and arms. There is evidence of neck stiffness and photophobia but no focal neurological deficit is identified. What would the most appropriate initial management be? A) Arrange a CT head scan B) Transfer the patient to the ward and perform a lumbar puncture C) Administer IV benzylpenicillin D) Administer IV acyclovir E) Insert a central venous line Question 49. Which one of the following statements regarding poliomyelitis is false? A) The condition is caused by a viral infection B) Upper motor neuron signs predominate C) Physiotherapy is useful in maintaining mobility D) Invasive ventilation may be required E) An effective oral vaccine is available Question 50. A 73-year-old man is brought to the hospital accident and emergency department after experiencing a seizure. His family state that he has been complaining of headaches and nausea for 3 months. His only past medical history is of type 2 diabetes mellitus. A contrastenhanced CT head scan is shown below: What is the most likely diagnosis? A) Subdural haematoma B) Subarachnoid haemorrhage 110 C) Cerebral abscess D) Creutzfeldt-Jakob disease (CJD) E) Herpes simplex encephalitis Question 51. Which one of the following statements regarding tetanus is true? A) The responsible bacterium, Clostridium tetani, infects the spinal cord and brain B) Multiplication of the organism occurs only in areas with good oxygenation C) The typical initial presentation is with headache, fever and drowsiness D) Antibiotics are of no value in treatment E) Tetanus antitoxin should be administered in all suspected cases Question 52. Which one of the following statements regarding Creutzfeldt-Jakob disease (CJD) is false? A) The causative agent is a protein B) Myoclonic jerks are a characteristic feature C) Cognitive function is usually preserved D) Patients with variant CJD are typically younger than those with sporadic CJD E) No curative treatment is available Question 53. Which one of the following statements regarding intracranial neoplasms is true? A) The majority are primary neoplasms B) Primary intracerebral tumours do not, generally, metastasise outside the central nervous system C) CT is superior to MRI for imaging posterior fossa tumours D) Dexamethasone aggravates oedema surrounding cerebral tumours E) Gliomas have a better prognosis than meningiomas Question 54. Which one of the following statements regarding acoustic neuroma is true? A) Conductive deafness is a common finding B) There is an association with tuberous sclerosis C) Cerebellar signs may be present D) CT is the investigation of choice E) Radiotherapy is the treatment of choice Question 55. A 25-year-old woman is referred to the neurology clinic with a 6month history of recurrent headaches. She denies any other symptoms. Her only past medical history is of acne, for which she takes oxytetracycline. On examination she has a body mass index of 34. Fundoscopy reveals papilloedema but neurological examination is otherwise unremarkable. A CT head scan is normal. The cerebrospinal fluid (CSF) opening pressure at lumbar puncture is elevated, but CSF protein, glucose and cell count are normal. What is the most likely diagnosis? A) Normal pressure hydrocephalus B) Cerebral astrocytoma C) Idiopathic (benign) intracranial hypertension D) Subarachnoid haemorrhage E) Cerebellar abscess Question 56. Which of the following drugs is most likely to be effective in the treatment of idiopathic (benign) intracranial hypertension? A) Furosemide B) Bendroflumethiazide C) Spironolactone D) Amiloride E) Acetazolamide Question 57. Which one of the following clinical features is not characteristic of normal pressure hydrocephalus? A) Dementia B) Urinary incontinence C) Headache D) Gait apraxia E) Higher incidence in old age Question 58. A 45-year-old man attends his general practitioner after developing sudden-onset lower back pain while lifting a sofa. He also describes pain shooting down the back of his right leg. On examination the straight leg raise test is positive on the right. Sensation is reduced over the sole and lateral border of the right foot. Plantar flexion of the ankle is weak on the right, and the right ankle jerk is absent. Which nerve root is affected? A) L3 B) L4 111 C) L5 D) S1 E) S2 Question 59. What is the most appropriate first-line treatment for a patient presenting with severe lower back pain secondary to lumbar disc herniation, associated with nerve root compression? A) Bed rest B) Analgesia and early mobilization C) Steroid injection D) Spinal radiotherapy E) Surgical decompression Question 60. A 76-year-old man with metastatic prostate cancer is admitted to hospital with lower back pain and deteriorating mobility. He also describes a 2-day history of urinary incontinence. Neurological examination of the lower limbs reveals bilaterally increased tone with weakness, brisk reflexes and extensor plantars. No deficit is noted in the upper limbs or cranial nerves. There is reduced sensation below his mid-abdomen. What is the most likely cause for the deterioration? A) Cerebral metastases B) Cervical cord compression C) Thoracic cord compression D) Cauda equina syndrome E) Peripheral neuropathy Question 61. Which investigation is most likely to yield useful diagnostic information in suspected cases of spinal cord compression? A) Plain X-ray of the spine B) Spinal CT scan C) Spinal MRI scan D) Nerve conduction studies E) Isotope bone scan Question 62. Which one of the following is least likely to cause peripheral neuropathy? A) Diabetes mellitus B) Chronic alcohol excess C) HIV infection D) Multiple sclerosis E) Vitamin B12 deficiency Question 63. Which one of the following drugs is most likely to cause peripheral neuropathy? A) Amiodarone B) Furosemide C) Haloperidol D) Amoxicillin E) Lansoprazole Question 64. A 54-year-old woman attends her general practitioner with a 2week history of tingling in her right hand. Her symptoms often wake her from sleep. On examination sensation is reduced over the palmar aspect of the right thumb, index and middle fingers and over the radial half of the ring finger. There is weakness of thumb abduction. Which nerve is affected? A) Radial nerve B) Median nerve C) Ulnar nerve D) Axillary nerve E) Musculocutaneous nerve Question 65. Which one of the following statements about Guillain-Barré syndrome is false? A) The condition is often preceded by a diarrhoeal illness B) There is a lower motor neuron pattern of muscle weakness C) Lumbar puncture demonstrates increased cerebrospinal fluid protein with a normal white cell count D) Respiratory muscles are not affected E) IV immunoglobulin reduces the duration of illness 112 Question 66. A 29-year-old woman is referred to the medical outpatient clinic with a 4-month history of intermittent double vision. She also complains of difficulty combing her hair without taking frequent rests. Examination of the upper limbs initially reveals normal power, but this declines with repeated testing. Sensation is normal. What is the most likely diagnosis? A) Duchenne muscular dystrophy B) Oculopharyngeal muscular dystrophy C) Myasthenia gravis D) Chronic fatigue syndrome E) Temporal arteritis Question 67. Which one of the following statements about myasthenia gravis is false? A) The condition is caused by autoantibodies directed against acetylcholine receptors B) The condition may affect respiratory muscles C) The Tensilon test can be helpful in making the diagnosis D) Thymectomy may improve prognosis in patients without thymoma E) The presence of muscle paralysis with fasciculation, sweating and excessive salivation suggests a myasthenic crisis Question 68. Which one of the following features is characteristic of myotonic dystrophy? A) Autosomal recessive inheritance B) Hirsutism C) Delayed relaxation of skeletal muscle D) Calf muscle hypertrophy E) Autoantibodies directed against presynaptic voltage-gated calcium channels at the neuromuscular junction Chapter 26 SKIN DISEASE Answers page 238 Question 1. A 45-year-old gentleman presents with well-demarcated scaly plaques on his scalp, elbows and knees. On examination you also notice some nail abnormalities: What is the diagnosis? A) Lichen planus B) Drug eruption C) Chronic plaque psoriasis D) Atopic eczema E) Pityriasis rosea Question 2. Which one of the following statements regarding psoriasis is incorrect? A) It has a predilection for the extensor surface of the limbs B) It is the only skin disease to demonstrate the Köbner phenomenon C) The Auspitz sign may be demonstrated by lifting a psoriatic scale D) Nail changes include pitting and subungual hyperkeratosis E) Psoriatic pustules are sterile Question 3. Which of the following factors would be least likely to provoke a worsening of psoriasis? A) Beta-blockers B) Lithium C) Penicillin antibiotics D) Stress E) Antimalarial treatment 113 Question 4. Which one of the following systemic agents is not used in the management of psoriasis? A) Methotrexate B) Psoralen C) Ciclosporin D) Acitretin E) Gold Question 5. Which one of the following statements regarding urticaria is incorrect? A) It may be caused by physical agents such as cold and pressure B) Episodes often last longer than 24 hours C) The pathophysiology involves degranulation of mast cells D) Antihistamines may help the condition E) Appropriate investigations would include total IgE and complement levels Question 6. A 15-year-old male presents with a rash consisting of small, scaly salmon-pink macules of raindrop appearance on his back. He gives a recent history of a sore throat. You suspect a diagnosis of guttate psoriasis. Which one of the following organisms is most likely to be associated with this presentation? A) Streptococcus pyogenes B) Trichophyton rubrum C) Proprionobacterium acnes D) Borrelia burgdorferi E) Sarcoptes scabiei Question 7. A 28-year-old woman with type 1 diabetes mellitus presents to the clinic with these yellow waxy-looking plaques on her anterior shin: What is the diagnosis? A) Discoid eczema B) Granuloma annulare C) Psoriasis D) Necrobiosis lipoidica E) Erythema nodosum Question 8. Which of the following statements regarding necrobiosis lipoidica is most accurate? A) The condition only occurs in diabetics B) Severity of the lesion is closely correlated with glycaemic control C) There is an infective component to the pathogenesis D) Topical or intralesional steroids may be useful E) The lesions very rarely ulcerate Question 9. A 68-year-old retired labourer presents with the following lesion on the side of the nose: What is the diagnosis? A) Squamous cell carcinoma B) Nodular melanoma C) Cellulitis D) Actinic keratosis E) Basal cell carcinoma 114 Question 10. Which one of the following statements about basal cell carcinoma is true? A) Deep, penetrating lesions should be treated with cryotherapy B) Metastatic spread to regional lymph nodes occurs early C) Tumour recurrence following treatment carries a poor prognosis D) Most lesions resolve spontaneously E) Local invasion is more common than haematogenous spread Question 11. All of the following features of a mole except one would give cause for concern. Which is the exception? A) Itch B) Bleeding C) Warty texture with 'stuck-on' appearance D) Recent change in shape E) Presence of irregular pigmentation Question 12. Which one of the following statements regarding classification of malignant melanoma is incorrect? A) Lentigo maligna melanoma mainly occurs on the exposed skin of the elderly B) Acral lentiginous melanoma occurs on the palms and the soles C) Superficial spreading melanoma has a radial growth phase D) Amelanotic melanomas are more common than the pigmented variety E) The excision margins of a nodular melanoma are dependent on its Breslow thickness Question 13. All of the following except one are risk factors for development of skin cancer. Which is the exception? A) Dark skin and black hair B) A strong history of sun exposure C) A family history of melanoma D) An outdoor occupation E) The genetic defect, xeroderma pigmentosum Question 14. A 4-year-old girl is brought to the clinic by her mother with a distressing itchy rash on the flexor aspects of her elbows and knees and on her face. She has had a similar rash since early infancy. She takes inhalers for asthma but has not been exposed to any other medications. On examination, you find an erythematous papular rash in the flexures, which is obviously excoriated and has prominent lichenification. Which one of the following is the most likely diagnosis? A) Atopic eczema B) Scabies C) Contact dermatitis D) Psoriasis E) Lichen planus Question 15. Which one of the following would not feature in the management of a child with atopic eczema? A) Greasy emollients B) Topical steroids C) Patient education D) Dithranol E) Avoidance of known irritants Question 16. Involvement of the oral mucous membranes would be an unexpected finding in which one of the following disorders? A) Systemic lupus erythematosus (SLE) B) Pemphigus C) Lichen planus D) Bullous pemphigoid E) Stevens-Johnson syndrome Question 17. With regard to hair loss, which one of the following statements is incorrect? A) Discoid lupus erythematosus causes a non-scarring alopecia B) Exclamation mark hairs are pathognomonic of alopecia areata C) Vitiligo, autoimmune thyroid disease and trisomy 21 are all associated with alopecia areata D) Alopecia totalis describes complete loss of scalp hair with preservation of body hair E) Androgenetic alopecia may occur in both males and females 115 Question 18. A 19-year-old woman presents with this erythematous, painful, nodular eruption on the anterior aspect of both shins: Which of the following steps is least appropriate in her initial work-up and management? A) Chest X-ray B) Full drug history C) Antibiotics D) Antistreptolysin O (ASO) titre E) Simple analgesia Question 19. Which one of the following statements concerning the definitions of skin lesions is incorrect? A) Vesicles are less than 5 mm in diameter B) Papules are solid elevations of skin less than 5 mm in diameter C) Macules are usually raised D) Telangiectasia are visibly dilated small cutaneous vessels E) Excoriation is the result of scratching Question 20. Which one of the following skin conditions is not typically itchy? A) Lichen planus B) Atopic eczema C) Dermatitis herpetiformis D) Bullous impetigo E) Psoriasis Question 21. Which one of the following is not associated with photosensitivity? A) Thiazide diuretics B) Tetracycline antibiotics C) Amiodarone D) Hydroxychloroquine E) Atenolol Question 22. All of the following statements regarding staphylococcal scalded skin syndrome (SSSS) are correct except one. Which is the exception? A) The causative organism is Staphylococcus aureus B) Clinical features include fever, skin tenderness and erythema C) Patients are usually over the age of 18 years D) Blisters arise from a split in the skin below the stratum corneum E) Intravenous antibiotics are an important part of initial management Question 23. Which one of the following nail changes is matched correctly with its associated condition? A) Koilonychia Folate deficiency B) Onycholysis Psoriasis C) Leuconychia Fibrosing alveolitis 116 D) Beau's lines Lichen planus E) Clubbing Atrial septal defec Question 24. Which one of the following is not a cause of porphyria cutanea tarda? A) Alcohol excess B) Haemochromatosis C) Genetic defect D) Diabetes mellitus E) HIV Question 25. The following are all recognised precipitants of erythema multiforme except one. Which is the exception? A) Mycoplasma infection B) Digoxin C) Herpes simplex infection D) Penicillin antibiotics E) Underlying malignancy PART 2 ANSWERS 117 Chapter 1 GOOD PRESCRIBING Question 1. A) It causes adverse effects at doses close to the usual therapeutic range Explanation: It is easier to think of a 'narrow' therapeutic index: that is, there is a narrow range between the dose necessary to have an effect and the dose necessary to cause toxicity. Question 2. B) On average, tow sever exacerbations will be prevented for every 50 patients treated for 1 year with the new inhaler. Explanation: The NNTB expresses the number of patients who must be treated with a drug to obtain a single beneficial outcome over a given time: in this case, to prevent a severe acute asthma exacerbation during treatment for 1 year. A is false because some patients may experience benefits other than the prevention of a severe exacerbation. At first glance it may appear that B and C are both true. Looking at B, it is correct to say that the effect of a drug on the first 25 patients treated should, on average, be the same as the effect on the next 25, so if we treat 50 patients we will prevent, on average, two severe exacerbations. However, C is one step too far; we cannot infer from a trial lasting only 1 year that the benefit will be identical in subsequent years. In the words of the philosopher Francis Bacon, 'The subtlety of nature is many times greater than the subtlety of argument.' The only way to find out if C is true is to do another experiment, one that lasts for 2 years. Question 3. E) 50 Explanation: The absolute risk of lifethreatening haemorrhage is 2% in the placebo group (20/1000) and 4% in the treatment group (40/1000). Thus, with respect to life-threatening haemorrhage, 118 the absolute increase in harm in the treatment group = 4% - 2% = 2% = 0.02. The number needed to harm (i.e. the number of patients that need to be treated to produce one additional life-threatening haemorrhage) is the inverse of this: 1/0.02 = 50 Question 4. A) Taking this drug for 5 years will reduce your chance of a heart attack by 15% Explanation: The only true statement is A. Relative risk (RR) for a given outcome is calculated as: risk with treatment/risk without treatment. The principles underlying the absolute and relative risk reductions and the number needed to treat are explained in the link below. Question 5. E) The dose-response curve for Potentol lies to the left of the curve for Weakol Explanation: The potency of a drug is merely a description of how much of it is required to have a given effect. Thus, the more potent drug will have the same effect at smaller doses, but the maximum effects and adverse effects of the two drugs could be the same. A more potent drug gives a response at a lower dose; therefore the dose-response curve is shifted to the left. Question 6. C) Digoxin Explanation: Digoxin is extensively excreted via the kidneys and has a narrow therapeutic index, so severe toxicity can occur at usual doses in a patient with renal impairment. Paracetamol and simvastatin are relatively safe in renal insufficiency. Larger doses of furosemide are often required to achieve an adequate diuresis in renal insufficiency, although clearly furosemide and other diuretics should be avoided altogether if the cause of renal impairment is hypovolaemia. Question 7. D) Allopurinol and azathioprine Explanation: Allopurinol inhibits xanthine oxidase, preventing the breakdown of a metabolite of azathioprine, mercaptopurine. This leads to an effective overdose of azathioprine, which can cause bone marrow suppression, resulting in neutropenia and potentially catastrophic immune compromise. The dose of azathioprine should be reduced by 75% if allopurinol is co-prescribed. Paracetamol 500 mg plus dihydrocodeine 10 mg (codydramol) is available in a combined formulation. Digoxin and warfarin are commonly prescribed together in atrial fibrillation. Trimethoprim plus sulfamethoxazole are used in combination (as co-trimoxazole) in the treatment of Pneumocystis carinii (jirovecii) pneumonia. Some calcium channel blockers increase ciclosporin blood concentrations, but there is no interaction of ciclosporin with ß- blockers 119 Question 8. B) The route of administration of the drug Explanation: The essential elements of a drug prescription outside hospital can be found in the link below. Question 9. A) Patient's date of birth Explanation: All of the other components are essential legal requirements for prescriptions for controlled drugs Question 10. B) Amiodarone Explanation: A loading dose of amiodarone achieves a more rapid effect. Question 11. D) 0.5 Explanation: Relative risk (RR) for a given outcome is calculated as: risk with treatment divided by risk without treatment = 20/40 = 0.5. Chapter 2 MOLECULAR MECHANISMS OF DISEASE Question 1. D) Neutrophils Explanation: The DNA in most human cells is packaged into 22 pairs of autosomal chromosomes, and one pair of sex chromosomes (XX in females and XY in males), giving a total of 46. Exceptions are gametes (sperm and ova) which have 23 chromosomes, red blood cells which are anucleate, and platelets which are formed by cell fragmentation and contain no DNA. Question 2. B) Formation of messenger RNA from DNA by RNA polymerase Explanation: A gene is a region of DNA which encodes a specific protein. Transcription refers to the creation of RNA from cellular DNA; translation is the synthesis of protein from RNA. Question 3. C) Chloride transport through channels on the cell membrane Explanation: Cystic fibrosis is an autosomal recessive condition which predominantly affects the lungs but also has consequences in the pancreas, gut and male reproductive system. Mutation of the CFTR gene results in defective chloride transport through channels in the cell membrane. In the lungs, this leads to the accumulation of thick respiratory secretions and superadded infection. Question 4. C) Noradrenaline (norepinephrine) Explanation: Steroids (e.g. glucocorticoids, mineralocorticoids, sex steroids), thyroid hormones, and vitamins A and D mediate their effect by binding to intracellular receptors. The activated receptors act as transcription factors and regulate gene expression. Catecholamines (e.g. adrenaline/epinephrine and noradrenaline/norepinephrine) do not 120 influence gene expression but rather bind to G-protein-linked receptors on the cell surface, and transmit their signal via second messenger systems. Question 5. C) The cell membrane remains intact Explanation: Apoptosis refers to programmed cell death in which cells undergo 'suicide'. The process is critical for cell turnover and tissue remodelling, and occurs from embryogenesis through to old age. It is mediated by the activation of specific genes. The cell membrane remains intact despite cell death; toxic cellular enzymes are therefore not released, in contrast to necrosis, and there is no inflammatory response. The apoptotic cell is removed by phagocytosis. Cell death in any ischaemic process such as myocardial infarction involves necrosis rather than apoptosis. Question 6.C) 50% Explanation: Huntington's chorea is an autosomal dominant disorder and so only one abnormal copy of the gene is required to cause the disease. Children with one affected parent therefore have a 50% chance of inheriting the abnormal gene from that parent. Non-identical (dizygotic) twins are formed by the fusion of two separate sperm with two separate ova; genes are acquired independently from both parents and the risk of disease is 50% for each child. Identical (monozygotic) twins have the same genetic composition, and so if one twin has inherited the abnormal gene then so must the other. This highlights the importance of family counselling before genetic testing. Question 7. D) Haemochromatosis autosomal dominant Explanation: Haemochromatosis is a disorder characterised by iron overload and is inherited as an autosomal recessive trait. It is caused by mutation in the HFE gene, and the carrier frequency of the abnormal gene in the general population is 10%. Clinical expression usually occurs earlier in males than in females, as menstrual blood losses protect against iron overload. Question 8. E) Trisomy 21 Explanation: Clinical features of Down's syndrome include learning difficulties, congenital heart disease, characteristic facies and a single palmar crease. 121 Question 9.E) Familial breast/ovarian cancer Explanation: Familial breast and ovarian cancer is a familial cancer syndrome with autosomal dominant inheritance associated with mutations in the BRCA1 or BRCA2 genes. Question 10.B) Congenital adrenal hyperplasia Explanation: Congenital adrenal hyperplasia is an autosomal recessive disorder due to a defect in one of the enzymes involved in steroid biosynthesis. The most common abnormality is a deficiency of 21-hydroxylase, resulting in variable deficiencies of glucocorticoids and mineralocorticoids. Adult polycystic kidney disease has autosomal dominant inheritance, although the rarer infantile polycystic kidney disease is autosomal recessive. Question 11. D) Secondary amenorrhoea Explanation: Turner's syndrome (45,XO) is a chromosomal disorder that affects only females. Affected individuals never menstruate (i.e. primary amenorrhoea) and are infertile. Secondary amenorrhoea, on the other hand, refers to the cessation of periods in a female who has previously menstruated. Other features of Turner's syndrome include widely spaced nipples, a wide carrying angle and the absence of secondary sex characteristics. Question 12. D) A son would be unaffected and a daughter would have a 100% chance of being a carrier Explanation: The abnormal gene in haemophilia A lies on the X chromosome, and the condition is inherited as an Xlinked recessive trait. In this example, the prospective father has the abnormal gene on his X chromosome, and the mother has two normal X chromosomes. A son would inherit the Y chromosome (not the abnormal X chromosome) from the father, and so could not inherit the haemophilia gene. A daughter would inevitably inherit the abnormal X chromosome from the father, and a normal X chromosome from the mother. She would therefore be a carrier for haemophilia A. Female carriers often exhibit no clinical features, although slightly reduced levels of factor VIII may result in a mild bleeding disorder. 122 Question 13. C) Penetrance Explanation: Penetrance describes the proportion of individuals with an abnormal genotype who exhibit clinical disease. Penetrance varies for different conditions, and is often affected by the interaction of genetic and environmental factors. Some conditions (e.g. Huntington's disease) have very high penetrance. Anticipation is the development of disease at a younger age and with greater severity in successive generations; this phenomenon is often seen in conditions caused by triplet repeats (e.g. myotonic dystrophy). Genomic imprinting refers to the development of a different phenotype depending on whether the abnormal gene was inherited from the mother or father. Translocation is the exchange of genetic material between two different chromosomes; for instance, the t(9,22) translocation (the Philadelphia chromosome) is strongly associated with chronic myeloid leukaemia. Lyonisation is the random inactivation of one of the two X chromosomes in the female fetus, and explains why female carriers of X-linked recessive conditions (e.g. haemophilia A) can exhibit mild clinical disease if the normal copy is inactivated in some cells. Question 14. B) Von Hippel-Lindau disease Explanation: Von Hippel-Lindau disease is a familial cancer syndrome with autosomal dominant inheritance. It occurs due to mutation in the VHL gene. Chapter 3 IMMUNOLOGICAL FACTORS IN DISEASE Question 1. E) T lymphocytes Explanation: The immune system is broadly divided into innate defences and adaptive responses. Innate defences are non-specific, fast response systems that do not exhibit memory; the acquired (or adaptive) immune response is targeted against the specific antigen, and changes in specificity and magnitude after initial exposure (memory). T lymphocytes are an essential component of the acquired immune response Question 2. B) Neutrophils Explanation: Neutrophils play an important role in the initial stages of infection, killing microorganisms directly and non-specifically amplifying the immune response. T and B cells form part of the adaptive immune response which is more specific, but slower to respond. Question 3 A) C-reactive protein (CRP) Explanation: C-reactive protein (CRP) is an acute phase protein which increases within hours of infection and falls rapidly on resolution. Levels may increase up to ×1000 normal, making it a useful test for monitoring treatment response. Complement levels may rise as part of an acute phase response, but do not exhibit the same magnitude of response as CRP (×2-4-fold). In addition, complement may be consumed during infection, making it an unreliable indicator of treatment response. Immunoglobulin levels rise much more slowly in response to infection (days to weeks), making these a less useful indicator. 123 Question 4. C) T-lymphocyte deficiency Explanation: This is a typical presentation of T-lymphocyte deficiency, which can cause increased susceptibility to viral, fungal and mycobacterial infections. The most common cause of T-lymphocyte deficiency worldwide is HIV infection. Question 5. A) Complement deficiency Explanation: Formation of the membrane attack complex of complement is essential in defence against Neisseria meningitides and other encapsulated bacteria. Question 6. D) Cryoglobulinaemia Explanation: The combination of joint pain, microscopic haematuria and a purpuric rash is suggestive of small-vessel vasculitis. In patients with hepatitis C, this is most commonly caused by cryoglobulin deposition. Autoimmune thrombocytopenia can cause a purpuric rash but does not commonly cause microscopic haematuria or joint pain. More on Cryoglobulinaemia Question 7. D) Anticardiolipin antibodies Explanation: Anticardiolipin antibodies are associated with recurrent fetal loss and arterial and venous thrombosis. Patients with primary or secondary antiphospholipid syndrome may have a positive lupus anticoagulant in addition to, or instead of anticardiolipin antibodies, but this cannot be assessed in patients on warfarin. Question 8. D) Antibody deficiency Explanation: Recurrent bacterial infection of the upper and lower respiratory tract with end organ damage is a common presentation of patients with primary antibody deficiency. Common organisms include Haemophilus influenzae and Streptococcus pneumoniae. Question 9. B) Vaccination with live attenuated vaccines Explanation: Live vaccines should always be avoided in immunocompromised patients (and patients in whom immune deficiency is suspected) because of the risk of iatrogenic infection. Question 10. A) Thymus Explanation: DiGeorge syndrome is a congenital disorder characterised by thymic aplasia. Normally, T lymphocytes mature in the thymus; in the absence of a thymus, T cells fail to mature and patients are susceptible to fungal, viral and mycobacterial infections. Patients with DiGeorge syndrome also have failure of parathyroid development, but this causes abnormal calcium metabolism and does not lead to immune deficiency. Question 11. B) HLA-B27 Explanation: Patients who carry HLA-B27 are 90 times more likely than other individuals to develop ankylosing spondylitis. Question 12. C) ABO blood transfusion reaction Explanation: Type II reactions are characterised by antibodies to cell surface antigens. In ABO transfusion reactions, 124 anti-blood group antibodies bind to blood group determinants on the surface of red cells and cause cell killing. Question 13. A) CREST syndrome Explanation: If you have difficulty remembering the various associations between autoantibodies and connective tissue disorders you are certainly not alone! However, specific autoantibody profiles can provide useful diagnostic information and are favourites with postgraduate examiners. The CREST variant of scleroderma is associated with anti-centromere antibodies (which can be remembered because they both begin with 'c'). In contrast, the diffuse variant is commonly associated with anti-Scl70. Question 14. E) Sjögren's syndrome Explanation: Anti-Ro/La antibodies are associated with Sjögren's syndrome and systemic lupus erythematosus (SLE). Drug-induced SLE is associated with antihistone antibodies. Question 15. B) Wegener's granulomatosis Explanation: Wegener's granulomatosis is commonly associated with the presence of a c-ANCA, and is often also associated with antibodies to proteinase 3. ChurgStrauss syndrome is associated with pANCA. Question 16. A) Extracellular deposition of insoluble proteins Explanation: The amyloidoses are characterised by the extracellular deposition of insoluble protein complexes. Chapter 4 ENVIRONMENTAL AND NUTRITIONAL FACTORS IN DISEASE Question 1. E) Incidence of the disease Explanation: Incidence of a disease (often confused with prevalence) refers to the number of new cases occurring in the population at risk during a defined period of time. Prevalence is determined by both the incidence and the duration of the disease. Question 2. A) 5 Explanation: The relative risk is the incidence in the exposed population divided by the incidence in the unexposed population. In this case, that means 150 cases per 3000 people living in village X versus 30 cases per 3000 people living remote from the nuclear power plant: (150/3000)/(30/3000) = 150/30 = 5 Question 3. D) Ulcerative colitis Explanation: Smoking tobacco dramatically increases the chances of developing a large number of diseases, including A, B, C and E. However, it has been noted in observational studies that smokers with ulcerative colitis appear to have fewer flares in their disease. Question 4. C) NRT plus behavioural support Explanation: NRT plus behavioural support leads to rates of abstinence at 6 months of up to 12%. In the absence of any intervention, the rate of success is only of the order of 2%. Question 5. A) The oxyhaemoglobin dissociation curve moves to the right Explanation: The oxyhaemoglobin curve describes the relationship between the amount of O2 bound to haemoglobin and the partial pressure of oxygen. In response to the reduction in partial pressure of oxygen at high altitude and the resulting fall in arterial oxygen saturation, a number of physiological adaptations occur. These 125 develop over a few days and include increased production of 2,3-DPG and erythropoietin. Epo increases red cell production while 2,3-DPG shifts the oxyhaemoglobin curve to the right, thereby decreasing the affinity of the haemoglobin molecule for oxygen (therefore oxygen is 'off-loaded' to the tissues more readily). Hyperventilation occurs, rather than hypoventilation, stimulated by hypoxic drive. Question 6. C) High-altitude pulmonary oedema Explanation: This is a fairly classical description of high-altitude pulmonary oedema (HAPE). The most important treatments are immediate descent and administration of oxygen. Question 7. B) Visual loss Explanation: Acute mountain sickness is a common syndrome in travellers to altitudes of > 3000 m; it comprises headache, fatigue, anorexia, nausea and vomiting, difficulty sleeping and dizziness. Visual loss, as well as behavioural change, confusion and loss of consciousness, is more likely to be seen as part of the rare and life-threatening syndrome, high-altitude cerebral oedema (HACE). Question 8. C) Metabolic alkalosis Explanation: Near-drowning is inevitably characterised by hypoxaemia and a metabolic acidosis. Acute lung injury results from inhalation of water, leading to a ventilation-perfusion mismatch. This tends to resolve over 48-72 hours unless infection supervenes. Other complications of near-drowning include haemoptysis, hypotension, dehydration and cardiac arrhythmias, in addition to hypothermia. Question 9. D) Linoleic acid Explanation: NSP is, in its simplest terms, the natural packaging of plant foods. By definition, dietary fibre cannot be digested by human enzymes. It therefore passes into the colon, improving transit and preventing constipation. Linoleic acid is a polyunsaturated fatty acid, i.e. a lipid rather than a carbohydrate. Question 10. C) 9 kcal Explanation: Fat is the most energy-dense component of the human diet, providing 9 kcal/g. This compares with carbohydrate and protein, both of which provide 5 kcal/g. Alcohol has a calorific value of 7 kcal/g. Question 11. C) Some essential amino acids cannot be obtained from vegetarian diets, necessitating the use of supplements Explanation: While the biological value of protein of animal origin is generally higher than that of vegetable origin, a suitable combination of different vegetable sources can provide the full range of essential amino acids with a sufficient protein nutritive value. This is known as the complementary value of proteins, and is the basis on which adequate protein may be obtained from a vegan or vegetarian diet without the use of supplements. Question 12. E) Feeding via a central (subclavian or internal jugular) line carries a higher risk of sepsis than feeding via a percutaneous endoscopic gastrostomy (PEG) tube Explanation: Hospitalised patients are at high risk of nutritional deficiency; their requirements are often increased by illness, and yet their capacity to consume an adequate diet may be impaired. Many therefore require some form of nutritional support. Whenever possible, the enteral route should be used as this preserves the integrity of the mucosal barrier, reducing the risk of bacteraemia. 'Supplement' drinks should be used to support, not replace, a normal diet. With parenteral 126 nutrition, hyperosmolar solutions (which are required in those patients with high nutritional needs) may be administered only into central veins, as they would cause thrombophlebitis if administered peripherally. Although aspiration pneumonia is a recognised complication of feeding by nasogastric tube, feeding via a central line carries a higher overall risk of infection. Question 13. B) Combined oral contraceptive pill Explanation: Weight gain is a wellrecognised side-effect of oestrogen therapy. Metformin may lead to minor weight reduction and is usually the most appropriate first-line drug treatment for glycaemic control in obese patients with type 2 diabetes. Sibutramine is one of the drug treatments available for obesity and reduces food intake through ß1adrenoceptor and 5-hydroxytryptamine receptor agonist activity in the central nervous system. Question `14. E) Obese people have a higher basal metabolic rate than lean people Explanation: Obesity is defined as a BMI > 30 (weight in kilograms divided by height in metres squared). One of the few 'benefits' of smoking is that it protects against obesity, although of course it has many other adverse effects. There are a number of potentially reversible causes of obesity, including hypothyroidism, Cushing's syndrome and insulinomas, which should be considered, particularly if the patient gives a history of having recently begun to gain substantial weight for the first time or at a faster rate than previously. Although approximately 60% of variation in BMI is attributable to genetic factors, the genetic basis for obesity remains poorly understood. Single mutations in a few genes (e.g. leptin) do cause severe childhood obesity but in the vast majority it is a polygenic disorder. The basal metabolic rate of obese individuals is actually higher than that of lean subjects. Question 15. C) Osteoporosis Explanation: Obesity has adverse effects on both mortality and morbidity. However, it protects against osteoporosis by increasing both mechanical stress on bones and sex steroid synthesis in adipose tissue. Question 16. A) Bariatric gastric surgery Explanation: All of the interventions above can be used in the appropriate circumstances as part of the management of obesity. Bariatric surgery is the most effective in the short and long (10-year) term, although it also has significant risks of complications. Question 17. D) Vitamin C Explanation: Vitamin C is water-soluble. This means that a large proportion of the vitamin C content of vegetables and fruit is lost when these foods are boiled in water. Question 18. B) Vitamin B2 (riboflavin) Beri-beri Explanation: A deficiency in vitamin B1 (thiamin) causes beri-beri. This manifests in three different forms: • infantile, occurring in the breastfeeding children of thiamin-deficient mothers • dry or neurological beri-beri, characterised by peripheral neuropathy and wrist/foot drop • wet beri-beri, characterised by generalised oedema, due to congestive cardiac failure. Deficiency in vitamin B2, riboflavin, is very rare because it is found in many food types. When deficiency does occur, it mainly affects the tongue and lips, manifesting as glossitis, angular stomatitis and cheilosis. Question 19. A) Vitamin C Explanation: Elderly people who are socially and geographically isolated may not have ready access to fresh fruit and vegetables, the most abundant source of vitamin C (ascorbic acid). This vitamin is important in the formation of collagen; 127 when it is deficient, defective collagen formation impairs healing of wounds, causes capillary haemorrhage and reduces platelet adhesiveness (normal platelets are rich in ascorbate). This manifests clinically as perifollicular and petechial haemorrhages, easy bruising, swollen gums which bleed easily, and occasionally gastrointestinal bleeding. Ascorbic acid is also a powerful reducing agent, which converts the ferric form of iron found in the diet to the more readily absorbable ferrous form, thereby increasing body iron absorption. Question 20. C) Fluoride Discoloration of teeth Explanation: There are about 16 essential inorganic elements in the human diet. It is chronic excessive intake of fluoride (e.g. > 10 ppm in the water supply) that causes discoloration of teeth, via a process known as fluorosis. Fluoride increases the resistance of enamel to acid attack and protects against dental caries. A national policy of fluoridating the water in the Republic of Ireland was introduced in the 1950s, following which the country's edentulous rate fell by more than 60%. The addition of traces of fluoride (at 1 ppm) to public water supplies is now widespread practice. Question 21. B) Increased skinfold thickness over the triceps Explanation: In addition to body mass index, a useful measurement in the assessment of nutritional status is skinfold thickness over the triceps; this is decreased in malnutrition due to loss of subcutaneous fat. This measurement can be subtracted from mid-arm circumference to estimate muscle mass. Many of the clinical features of starvation represent physiological adaptations to undernutrition. For example, it is disadvantageous to have children born to an undernourished mother and into a famine environment, so reproductive function is suppressed as part of the physiological response to undernutrition. Chapter OF 5 PRINCIPLES INFECTIOUS DISEASE Question 1. C) Prions are highly complex structures consisting of > 100 different proteins Explanation: Prions are the simplest of all infectious agents, consisting of a single protein molecule which can catalyse a change in a host protein. Viruses only contain one type of genetic material, either DNA or RNA, and require a host cell (either prokaryotic or eukaryotic) in order to reproduce. Fungal cells have a defined nucleus, in contrast to bacteria, whose nuclear material is not organised into a specific organelle. Question 2. D) Hepatitis A Needlestick injury Explanation: In contrast to hepatitis B and C, which are transmitted by sexual contact, blood transfusions and needlestick injuries, hepatitis A is spread by the faecal-oral route. Question 3. A) Pertussis Explanation: All of the above apart from pertussis are live attenuated vaccines and should not cause infection in the immunocompetent recipient. However, they should be given with caution or avoided in those who are immunosuppressed or pregnant, or who have an acute infection. Inactivated vaccines include pertussis, HiB (Haemophilus influenzae type B), and pneumococcal. The 'awkward one' in this classification system is poliomyelitis, for which both a live attenuated and an inactivated form exist. The Salk form is inactive (remember the 'k' in Salk is also in killed) and the Sabin form is live. Question 4. D) MMR (measles, mumps, rubella) vaccine Explanation: With the exception of the MMR vaccine, all of the above should be 128 given to children at the age of 2 months or as soon as possible thereafter, as natural immunity declines. MMR is given during the second year of life. Uptake of this vaccine has declined in recent years following reports of a link between receipt of the vaccine and the development of autism. These claims are without foundation, but have unfortunately shaken public confidence in the vaccine. Question 5. A) Yearly receipt of the polyvalent flu vaccine Explanation: Asplenic patients have heightened susceptibility to encapsulated organisms such as Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. While the flu vaccine is not contraindicated in asplenic patients, it provides protection against a viral infection, and is, therefore, not mandatory. All asplenic patients should have prophylactic antibiotics prior to dental procedures, as there is a risk of disseminated infection. Daily penicillin prophylaxis is also a standard recommendation. All asplenic patients should be encouraged to carry a card or wear a MedicAlert bracelet explaining their condition. Question 6. E) Meningococcal meningitis Explanation: Certain diseases which are thought to have important implications for public health are classified as 'notifiable', meaning that notification of cases to the local public health authority is compulsory. This is so that outbreaks of highly contagious conditions can be recognised, and appropriate measures put in place to control further spread of the condition. In the UK both meningitis (of any cause) and meningococcal sepsis are notifiable. Question 7. C) Neisseria gonorrhoeae Direct microscopy Explanation: Strategies for identifying micro-organisms can be broadly categorised into direct demonstration (e.g. microscopy with or without appropriate staining), molecular diagnostic methods (e.g. PCR) and immunodiagnosis (e.g. ELISA, Western blot, immunofluorescence). Strep. pyogenes is most commonly identified on culture, hepatitis B is identified initially by immunodiagnosis, and if positive, viral load is subsequently determined by PCR. Gonococcus is most often identified on microscopic examination of biological fluid such as urine or urethral discharge (Gram-negative diplococci); sensitivities may subsequently be determined on culture. Mycobacterium tuberculosis is also identified initially by microscopy aided by the use of Ziehl-Neelsen staining. Candida albicans may be identified either on direct microscopy or on culture of biological fluids. Question 8. C) Ciprofloxacin Inhibits DNA gyrase, thereby blocking DNA replication Explanation: Knowledge of how antibiotics work is important for understanding their spectrum of activity and mechanisms of resistance. Question 9. A) Minimum inhibitory concentration (MIC) is the lowest concentration of an antibiotic required to inhibit 50% of the colonies of a particular organism Explanation: The MIC is the lowest concentration of an antibiotic required to inhibit 90% of the colonies of a particular organism. 129 Question 10. D) Prevention of gas gangrene in a patient with a contaminated wound Flucloxacillin Explanation: The recommended prophylaxis for gas gangrene is benzylpenicillin 600 mg 6-hourly for 5 days or metronidazole 500 mg 8-hourly for 5 days. Although chicken pox is common in childhood and the vast majority survive without sequelae, it is an important cause of mortality in newborn infants and in severely immunocompromised patients. Both groups should therefore receive varicella immune globulin if they have been exposed to the virus. The rationale behind endocarditis prophylaxis prior to dental procedures is that transient bacteraemia, from organisms commensal to the mouth, often develops following invasive dental procedures and may colonise damaged or artificial heart valves, leading to endocarditis. Question 11. C) Most patients with established allergy to benzylpenicillin are also allergic to cephalosporins Explanation: Approximately 10% of penicillin-sensitive patients are allergic to cephalosporins, although anaphylaxis to second- and third-generation cephalosporins is exceedingly rare, even in the presence of established penicillin allergy. Beta-lactam antibiotics are bactericidal, meaning that they kill bacteria. They act by inhibiting synthesis of the bacterial cell wall, which is essential for survival of bacteria in osmotically challenging environments. Question 12. C) Clarithromycin Explanation: Clarithromycin is a macrolide antibiotic useful in the treatment of infections caused by Gram-positive, rickettsial, chlamydial and Mycoplasma infections. Had Legionella, another 'atypical' organism, been identified as the cause (best diagnosed by polymerase chain reaction detection of the Legionella antigen in urine), then rifampicin would be an appropriate antibiotic to add. Question 13. A) IV ceftriaxone and metronidazole Explanation: The history suggests the possibility of an aspiration pneumonia, and empirical antibiotic therapy must therefore cover Gram-negative organisms and anaerobes in addition to the usual causes of community-acquired pneumonia. Anti-anaerobic activity will be provided by metronidazole while ceftriaxone, a third-generation cephalosporin, has excellent Gram-negative activity as well as providing Gram-positive cover. Given the history of recent stroke and possible aspiration, the method of administration of the antibiotic may be of importance, and the IV route may be the most appropriate. Question 14. D) Hepatotoxicity Explanation: Aminoglycoside antibiotics are highly nephrotoxic, an effect potentiated by concomitant administration of vancomycin, cisplatin, amphotericin B or contrast media. The ototoxicity results from the enhanced cellular penetration demonstrated by aminoglycosides in the hair cells in the cochlea. Hearing damage and vertigo tend to be permanent. Aminoglycosides impair neuromuscular transmission and should not be given to patients with myasthenia gravis. Larger doses given rapidly by the IV route may result in a transient myasthenic syndrome in those with normal neuromuscular function. Gastrointestinal upset is a relatively common adverse effect but hepatotoxicity does not occur. In order to avoid important complications, serum levels of the aminoglycosides must be checked on a regular basis, and the dosing regimen adjusted to ensure that toxic levels are not reached. Question 15. B) It has potent antiGram-negative properties, but little or no anti-Gram-positive activity Explanation: Fluoroquinolones such as ciprofloxacin have excellent oral bioavailability, a large volume of distribution and good intracellular penetration (the drug concentrates in phagocytes, facilitating its distribution). 130 Although newer quinolones such as moxifloxacin and levofloxacin have enhanced anti-Gram-positive activity, ciprofloxacin has excellent anti-Gramnegative activity with little or no antiGram-positive activity. Side-effects of this drug are infrequent and generally mild. Its oral bioavailability, as mentioned above, is excellent, but is impaired by coadministration of food, antacids, ferrous sulphates and multivitamins. Question 16. E) They have good oral bioavailability Explanation: No useful oral absorption of glycopeptide antibiotics is achieved, and administration is always by the IV route (except in the treatment of Clostridium difficile diarrhoea). The anaphylactoid reaction caused by rapid histamine release from mast cells in response to a rapid infusion of vancomycin is known as 'red man' syndrome. Nephrotoxicity is another potential side-effect, the risk of which is greatly reduced by monitoring of antibiotic serum levels to ensure that toxic concentrations are not reached. No antibiotic in this class has any significant activity against Gram-negative organisms but both vancomycin and teicoplanin are useful against MRSA. Question 17. D) Ketoconazole Nephrotoxicity Explanation: Ketoconazole is an oral antifungal agent that can cause hepatotoxicity. 'Grey baby syndrome' describes the dose-dependent cyanosis and circulatory collapse that occur in infants due to inability to conjugate chloramphenicol and excrete it in urine. All tetracycline antibiotics bind to metallic ions in bones and teeth, causing discoloration, and therefore should be avoided in children and in pregnancy. Tetracyclines also photosensitise and patients should be warned about this and advised to use sun-screen. Erythromicin causes a cholestatic jaundice in some patients, which abates when the drug is stopped. Chapter 6 AGEING AND DISEASE Question 1. D) Increased insulin secretion Explanation: Ageing is a normal physiological process and effects are seen in several organ systems. They do not usually interfere with organ function under normal conditions, but reserve capacity is reduced and so organ failure can be precipitated by minor illness. Pancreatic _cell function declines with age, resulting in reduced insulin secretion. Question 2, D) Omeprazole Explanation: Falls are an extremely common presentation in elderly patients and are often multifactorial. Sedative drugs (e.g. benzodiazepines, antipsychotics, antidepressants), opiates and diuretics are common culprits. Polypharmacy in itself is also a risk factor. Proton pump inhibitors are generally well tolerated and cause relatively few sideeffects. Question 3. E) Bisphosphonate therapy Explanation: Elderly patients who present with recurrent falls are often frail with multiple medical problems. The annual risk of falling increases linearly with the number of risk factors, from 8% with no risk factors to 78% with four or more. In patients who experience recurrent falls, osteoporosis prophylaxis with calcium and vitamin D supplements, and treatment of established osteoporosis with bisphosphonates are important considerations that may reduce the risk of fracture. 131 Question 4. C) Stop amlodipine Explanation: Postural hypotension (drop in BP of > 20 mmHg systolic or > 10 mmHg diastolic on standing from supine) is a cause of dizziness and falls, and is often related to medication. This patient has a documented postural BP drop, and a trial without amlodipine (a dihydropyridine calcium channel blocker) would be reasonable. Neither simvastatin nor metformin causes postural hypotension and there is no compelling reason to stop the drug. Fludrocortisone is a mineralocorticoid that causes salt and water retention, which can be used to treat postural hypotension; however, it can precipitate heart failure and should be used with caution when withdrawal of hypotensive medication fails to resolve the problem. Question 5. D) Alzheimer's disease Explanation: Almost any acute illness can present with confusion in the elderly; examples include infections, vascular events, metabolic derangements and drugs (particularly opioid analgesics and sedatives). Alzheimer's disease causes chronic cognitive impairment rather than acute confusion. On the other hand, acute cerebrovascular events may occur in vascular dementia and can cause acute confusion. Question 6. E) Laxatives may be helpful Explanation: Urinary incontinence affects 15% of women and 10% of men aged over 65. It should never be considered to be due to ageing alone and requires investigation. Causes of incontinence include severe constipation (treatable with laxatives) and hypercalcaemia. Catheterisation should not generally be considered as first-line treatment but may be needed in refractory cases or if there is local skin damage. Question 7. B) 24-hour ambulatory ECG Explanation: The self-limiting nature of this patient's symptoms, together with the absence of a postural element or other associated symptoms, suggests that transient arrhythmias may be the cause. Ageing is associated with an increased incidence of sinoatrial disease. Furthermore, this patient is on ratelimiting treatment in the form of a _blocker. A 24-hour ambulatory ECG 132 would therefore be the most useful initial test. Echocardiography may be helpful if there are clinical signs of valvular disease or an abnormal ECG. CT brain scans are useful if cerebrovascular disease or mass lesions are suspected, but these tend not to present with episodic lightheadedness alone. Question 8. C) Chronological age Explanation: Decisions about the appropriate level of intervention in elderly patients depend on individual circumstances and often require careful thought. Multiple comorbidities, likely tolerance of interventions, patient and family wishes, and advance directives ('living wills') should all be borne in mind. Many elderly people remain fit and active into their nineties, whereas others become severely disabled by illness in their seventies; 'biological' age is therefore generally more useful than 'chronological' age in making decisions about treatment. Chapter CARE AND 7 CRITICAL EMERGENCY MEDICINE Question 1. E) 250 ml of gelofusine over 15 minutes Explanation: The falling blood pressure, urine output and central venous pressure, combined with thirst and tachycardia, are highly suggestive of hypovolaemia. The diagnosis can be confirmed and partly treated by giving a rapid fluid challenge with gelofusine or saline. O-negative blood is precious and administration is associated with a higher complication rate, so it should be conserved for acutely lifethreatening emergencies. Question 2. C) Left atrial pressure Explanation: As direct measurement of left atrial pressure is not practical, PAWP is used as a surrogate. Question 3. B) Systemic arterial pressure Explanation: Central venous pressure (CVP) or right atrial pressure (RAP) is often measured in critically ill patients to help guide intravascular fluid replacement. Accurate interpretation of CVP values requires a knowledge of the physiological factors that influence it. Central venous pressure is largely determined by the combination of: • intravascular volume • venous tone • pulmonary artery pressure (and right ventricular function) • intrathoracic pressure. Systemic arterial pressure does not directly affect right atrial pressure but may affect it indirectly, through altering one of the above parameters. For example, persistent systemic hypertension may lead to left heart failure, which in turn may lead to increased pulmonary artery pressure, ultimately resulting in a rise in right atrial pressure. 133 Question 4. B) Pulmonary embolism Explanation: Interpreting these data may initially seem daunting. However, a logical approach to the causes of shock leads to the correct answer. There are a limited number of problems that can cause shock. We can immediately rule out the 'distributive' causes (septic, anaphylactic and neurogenic) because we know that cardiac output is low. This leaves hypovolaemic, cardiogenic and obstructive causes. Hypovolaemia is less likely because the CVP is high. CVP represents right atrial pressure, whereas PAWP represents left atrial pressure. Cardiogenic shock tends to affect both ventricles, so both CVP and PAWP would be elevated. The fact that PAWP is low and CVP is high suggests some kind of obstruction between the right and left ventricles. This pattern is typical of the haemodynamic compromise caused by massive pulmonary embolus. If you found this question tricky, try having a look at the link below. There is another question on shock later in the chapter to test your understanding. Question 5. A) 1 ml of 1 in 1000 adrenaline Explanation: Adrenaline (epinephrine) is one of the few drug doses that it is important to memorise, because there won't be much time to check when you need to use it. Low volumes are used for intramuscular injections, and in true anaphylaxis the dose is 1 mg. If it is given intravenously, it is more likely to cause arrhythmia, so the dose is titrated in 0.1 mg boluses by an experienced doctor. What mass of adrenaline is in 1 ml of each of the solutions listed? The system seems unnecessarily complex but can be easily understood by memorising one key fact: that all dose strengths refer to grams per millilitre. Thus, 1 in 1000 is 1 gram in 1000 millilitres = 1 gram/litre = 1 mg/ml. This is the concentrated solution for intramuscular injection in anaphylaxis. Likewise, 1 in 10 000 has 1 gram in 10 000 millilitres = 0.1 grams/litre = 0.1 mg/ml. This is the concentration found in minijet syringes on cardiac arrest trolleys. In the context of a cardiac arrest, it is given as a 10 ml bolus. In other situations, it is normally titrated in 1 ml boluses. Finally, 1% means 1 gram in 100 millilitres = 10 grams/litre = 10 mg/ml. Question 6. B) Noradrenaline (norepinephrine) Explanation: Noradrenaline (norepinephrine) acts primarily in the peripheral vasculature, causing intense vasoconstriction, with relatively little direct effect on the heart. Its major clinical use is in hyperdynamic sepsis, when there is low systemic vascular resistance and blood pressure despite a high cardiac output. In these circumstances vasoconstriction is desirable to restore BP, even at the expense of a small reduction in cardiac output. Dobutamine and dopexamine are sometimes called 'ino-dilators', since they increase cardiac contractility whilst simultaneously causing systemic vasodilatation. Sodium nitroprusside and GTN are both nitric oxide donors that cause profound systemic vasodilatation. 134 Question 7. D) Pulmonary artery wedge pressure (PAWP) < 15 mmHg Explanation: The four defining characteristics of ARDS are: hypoxaemia, bilateral infiltrates on chest X-ray, PAWP < 15 mmHg (this rules out left ventricular failure as the cause of the pulmonary pathology) and decreased lung compliance. Question 8. A) Diamorphine overdose Explanation: The others are all common causes of type 1 respiratory failure in the critically ill. Diamorphine overdose decreases respiratory drive, which decreases ventilation, which allows CO2 to accumulate. Question 9. B) Pulmonary oedema secondary to left ventricular failure (LVF) Explanation: CPAP is an effective treatment to improve oxygenation in LVF. It does not increase ventilation (the volume of air shifted in and out of the lungs) so it is not a good treatment for disorders characterised by hypoventilation, such as COPD, narcotic drug overdose and neuromuscular disorders. These patients may benefit from bi-level positive airway pressure, which does support ventilation. Drug overdose patients are not normally treated in this way because they are at risk of aspiration pneumonitis, so the airway must be protected with a cuffed endotracheal tube. CPAP is contraindicated in acute severe asthma as it worsens hyperexpansion, so decreasing ventilation, which may be fatal. Question 10. C) Arterial bicarbonate (HCO3-) must be lower in the second ABG Explanation: The first ABG shows normal acid-base status and significant hypoxia on air. The second ABG shows a metabolic acidosis, and the patient is still very hypoxic despite receiving 40% O2. The PaO2 should have increased but it has hardly changed at all, so pulmonary gas exchange has probably worsened in the second ABG. The metabolic acidosis is easy to diagnose without being told the HCO3-. PaCO2 has decreased but the patient is acidaemic. These H+ ions must have come from somewhere but they have not come from CO2. Thus, there must be a metabolic acidosis. Question 11. D) Hyponatraemia Explanation: Hyponatraemia is particularly likely to cause coma when its onset is acute. The other options do not directly obtund consciousness. Question 12. C) Disseminated intravascular coagulation (DIC) Explanation: Systemic sepsis may provoke DIC, a potentially life-threatening coagulopathy. This characteristically consumes fibrinogen, platelets and clotting factors, and leaves the circulating blood lacking in adequate clotting factors to support normal clotting. This leads to abnormal bleeding and prolonged APTT and PT. Question 13. D) Mild hyperventilation to reduce PaCO2 to 4-4.5 kPa Explanation: Intracranial pressure must be prevented from rising in head injury patients. Simple measures, such as a 30° head-up tilt, and tight control of fluid balance to prevent dehydration or fluid overload, are believed to help. PEEP should be avoided, since it reduces venous return from the brain, potentially increasing intracranial pressure in headinjured patients. Current evidence suggests 135 that maintaining PaCO2 at the low end of the normal range is the best management for control of intracranial pressure. This causes mild cerebral vasoconstriction but not enough to cause cerebral ischaemia. Normal saline is used to prevent plasma sodium falling below 140 mmol/l. Question 14. D) Pneumonia Explanation: Ranitidine reduces gastric acid secretion and is used to prevent stress ulceration. However, its use does increase the development of ventilator-associated pneumonia in patients on long-term ventilation. Question 15. C) Central venous catheterisation Explanation: This patient is almost certainly going to require aggressive fluid resuscitation. Monitoring his central venous pressure (CVP) will help to guide the rate of intravascular fluid replacement and may help to reduce the risk of precipitating pulmonary oedema. There is no clear indication for ventilatory support in this patient; he is sufficiently alert to communicate his symptoms, and his SpO2 is 96% on air. Inotropes should not be started at this point because adequate volume resuscitation has not been achieved. There is no indication at present for haemofiltration. Diuretics are likely to be counterproductive since he already appears to be fluid-deplete. Question 16. B) Septic shock Explanation: Hypovolaemia and cardiogenic and obstructive shock are all associated with a low cardiac output. Shock with a high cardiac output may be caused by sepsis, anaphylaxis, neurogenic shock and vasodilating drugs. There is no history of rash, bronchospasm, angioedema or sudden circulatory collapse, so we can rule out anaphylaxis. Likewise, there is no history of spinal cord injury or administration of a large dose of a vasodilating drug. Chapter 8 POISONING Question 1. C) Organophosphate insecticides Explanation: These are the classic acute features ('toxidrome') of organophosphate poisoning. A full description of the syndrome is found in the link below. Cholinergic symptoms are a prominent feature of organophosphate poisoning. A popular mnemonic for cholinergic symptoms is 'sludge': Salivation lacrimation Urination diarrhoea gastrointestinal cramps semesis Question 2. D) Ensure a patent airway Explanation: The priority in a patient with poisoning is the same as in any acutely unwell patient: assessment of the airway, breathing and circulation (ABC). Assessing the airway is usually a simple matter of asking the patient to speak, but requires a more detailed assessment in the unconscious patient. If there are any signs of compromise, a chin lift or jaw thrust should be performed. All of the other measures are appropriate, but ultimately futile if the airway is not patent. Question 3. E) Aspirin Explanation: Aspirin is widely available and dangerous in overdose, so it is important to understand the key features of the management of salicylate poisoning. Only a few drugs are 'able' to be removed by haemodialysis and most of them can be remembered easily: Question 4. B) Ethanol Explanation: With the exception of ethanol, all of the drugs listed bind to activated charcoal. It is usually only of benefit if given within an hour of ingestion, although repeated doses can be used for theophylline, quinine, 136 carbamazepine and dapsone poisoning. Some drugs, particularly small molecules and ions, are poorly adsorbed by activated charcoal. Question 5. D) N-acetylcysteine Explanation: Intravenous infusion of Nacetylcysteine is the standard treatment for paracetamol overdose in the UK. Methionine is a suitable oral alternative. Question 6. E) Communicate with the mother to be certain of the timing of the overdose and to identify possible coingestants Explanation: Even in large doses in highrisk patients, paracetamol overdose is often asymptomatic in the first 24 hours. The coma, hypotension and bradycardia cannot be explained by paracetamol alone and the most likely explanation is concomitant overdose of another drug (probably opiates or benzodiazepines). Activated charcoal is not recommended for patients presenting more than 1 hour after paracetamol overdose. Nacetylcysteine can cause anaphylactoid reactions; it is effective if given in the first 10 hours after overdose, so it is safer to wait for a paracetamol level before starting treatment. Vitamin K has no place in the acute management of paracetamol overdose. In fact, giving vitamin K would be counterproductive because the prothrombin time is used to monitor progress and potential need for liver transplantation. Paracetamol levels less than 4 hours after overdose are uninterpretable. Question 7. C) Ecstasy (MDMA) Explanation: The presentation includes the classic features of ecstasy (MDMA) abuse. GHB causes sedation and coma, and LSD is a hallucinogen with relatively low intrinsic toxicity. Question 8. B) Naloxone Explanation: Although this presentation may be due to an overdose of opiates or benzodiazepines, the specific benzodiazepine antagonist flumazenil is rarely used, as it can precipitate seizures and lethal cardiac arrhythmias. On the other hand, naloxone, an opioid antagonist, is relatively safe although, following administration, the patient may wake up very quickly and become agitated or violent, especially if too much is given too quickly. Aim to titrate to a Glasgow coma score of 13-14. Question 9. E) Digoxin Explanation: This is a classic description of digoxin toxicity, which due to dependence on renal clearance and a narrow therapeutic index, can occur without intentional overdose. The yellowing of vision is known as xanthopsia. Verapamil overdose can cause vomiting and bradycardia but no visual disturbance. Quinine overdose causes visual disturbance, deafness, and nausea and vomiting. With large overdoses, cardiac effects can occur, including impaired conduction and tachyarrhythmias. It does not cause the classic 'reverse-tick' ECG changes seen with digoxin toxicity. Fluoxetine is relatively safe in overdose; the major sideeffect of selective serotonin reuptake inhibitors (SSRIs) is gastrointestinal upset. Question 10. D) Methanol poisoning Explanation: There is a raised anion gap metabolic acidosis. This indicates the presence of large quantities of an unmeasured anion, such as salicylate, ketone bodies, lactate or metabolites of methanol. So, with the exception of ethanol, all of the options listed could cause this acidosis. DKA is unlikely with a normal glucose, and if CO poisoning were 137 the cause of the acidosis, the lactate would be elevated. A raised anion gap metabolic acidosis is a classic feature of advanced salicylate poisoning, but methanol poisoning is more likely in this case, as it often causes blindness and is a common cause of poisoning in alcoholics. Methanol poisoning is managed by administration of ethanol or 4-methylpyrazole (4MP), which competitively inhibits alcohol dehydrogenase and thus limits formation of toxic metabolites such as formate, which cause blindness. Question 11. E)Glucagon Explanation: N-acetylcysteine and methionine both replenish hepatic glutathione to protect the liver from the effects of paracetamol toxicity; calcium gluconate is used in overdose with calcium channel blockers; naloxone is effective in opioid overdoses. IV glucagon and adrenaline (epinephrine) are used if needed in overdoses with _-blockers Question 12. A) Iron Explanation: Desferrioxamine is a chelating agent used in severe iron poisoning. Question 13. B) Diamorphine Explanation: Opiate overdoses cause small 'pinpoint' pupils and respiratory depression. Overdose with tricyclic antidepressants, alcohol, cocaine, amphetamine or antihistamines can cause large pupils. Benzodiazepines such as temazepam cause respiratory depression, but do not cause small pupils. Question 14. E) Co-ingestion of ecstasy (MDMA) Explanation: Malnourishment and anorexia deplete the liver of protective glutathione. Alcohol, phenytoin and several other drugs induce hepatic enzymes that increase the rate of conversion of paracetamol to highly toxic metabolites Question 15. D) Treat if the total 24hour dose was more than 150 mg/kg Explanation: In a 'staggered overdose' such as this, a paracetamol level is uninterpretable and cannot reliably be used to guide treatment. Instead, the quantity of drug ingested per kg of body weight is used as a guide. The patient does not belong to a high-risk group so the dose to determine the need for treatment will be 150 mg/kg/24 hours. poison are ineffective and, indeed, are potentially harmful. Other investigations may be necessary, but should not be prioritised ahead of antivenin administration. For a full discussion on the assessment and management of snake-bite victims, see the link below. Question 16. C) Lithium Explanation: All of the other drugs listed can cause severe bradycardia in overdose. Question 18. D) Amitriptyline Explanation: Overdose with tricyclic antidepressants such as amitriptyline, alcohol, cocaine, amphetamines or antihistamines can cause large pupils. Opiate and organophosphate overdoses cause small pupils. Question 17. A) Inject 0.02 ml of salinediluted antivenin subcutaneously and observe the injection site for 10 minutes Explanation: Anaphylactic reactions to antivenins are common and potentially lethal. Sadly, tourniquets and aspiration of Question 19. A) Aspirin Explanation: The management of overdose with aspirin, paracetamol or iron is determined by the blood concentration, the time since the overdose was taken and the clinical features. 138 Chapter 9 MEDICAL PSYCHIATRY Question 1. A) Mania Explanation: Characteristic features of mania which may be apparent in the mental state examination include restlessness, excess energy, elated mood, 'pressure of speech' (rapid speech that is difficult to interpret), 'flight of ideas' (flitting rapidly between loosely related topics) and grandiose thoughts (e.g. patients may believe they are particularly gifted or have special powers). Question 2. C) Constipation Explanation: Somatic symptoms may dominate the clinical picture in anxiety disorders. Diarrhoea is far more common in anxiety than constipation, as evidenced by the queue outside the toilets before final medical examinations! Question 3. E) Age under 45 Explanation: Although deliberate selfharm is more common in women than in men and in young adults than the elderly, completed suicide is more common in men and those over the age of 45. Question 4. A) Impaired cognition and drowsiness Explanation: Impairment of cognition and consciousness, particularly in a medical inpatient, would point to delirium as the cause of these hallucinations. Important causes to consider would include infection, metabolic disturbance, hypoxia, alcohol withdrawal and drug side-effects. The nature of the hallucinations is also of diagnostic value as auditory hallucinations suggest a functional psychosis such as schizophrenia, while hallucinations in other modalities (especially vision) suggest an organic cause such as delirium 139 or temporal lobe epilepsy. Pressure of speech is characteristic of mania while a flat affect is suggestive of depressive disorder. Delusions are a strong pointer towards a psychotic disorder. Question 5. C) It is rarely used due to the high incidence of serious side-effects Explanation: Despite its negative image amongst the general public, ECT remains a highly useful treatment for severe depressive disorder, particularly when complicated by psychosis or risk of starvation. It is now remarkably safe, has very few side-effects and is of proven efficacy in severe depressive disorder. Question 6. C) Electroconvulsive therapy Explanation: Electroconvulsive therapy is reserved for the treatment of severe depressive disorder. Psychological treatments such as graded exposure, cognitive behavioural therapy and relaxation techniques have an important role in the management of anxiety disorders. Beta-blockers help to alleviate the somatic symptoms of anxiety. Benzodiazepines are effective anxiolytics in the short term but readily lead to dependence and so are not a long-term treatment option. Where drug treatment is required, an antidepressant with anxiolytic properties such as citalopram is the treatment of choice. Question 7. C) Monoamine oxidase inhibitors Explanation: These drugs are now rarely prescribed in the UK but it is still important to know of this potentially dangerous interaction. Question 8. E) Treatment should be continued for at least 6 months to reduce the high risk of relapse Explanation: Cognitive behavioural therapy and interpersonal therapy are as effective as antidepressants in the treatment of mild to moderately severe depression, although the latter are preferred for severe depression. The various classes of antidepressant are equally effective and hence choice is largely dictated by tolerability of sideeffects and toxicity in overdose. SSRIs and newer antidepressants such as venlafaxine cause less troublesome side-effects and are less dangerous in overdose than tricyclics. Although three-quarters of patients respond to drug treatment, it commonly takes up to 4 weeks for improvement to occur and response within the first 2 weeks is unusual. It is vital to explain this to patients on initiating treatment to maximise treatment concordance. Question 9. D) Diabetes mellitus Explanation: Lithium is the drug of choice for the maintenance treatment of bipolar disorder. It has a narrow therapeutic range, meaning there is only a small difference between the required therapeutic dose and the dose at which toxicity develops. Features of lithium toxicity include tremor, nausea, vomiting and convulsions. Side-effects, as opposed to toxic effects, occur even when levels remain within the therapeutic range, particularly with long-term treatment. These include renal impairment, hypothyroidism, nephrogenic diabetes insipidus (not diabetes mellitus) and weight gain. Lithium is highly teratogenic and must never be prescribed in the first term of pregnancy. 140 Question 10. B) Poverty of speech Explanation: First-rank symptoms are characteristic of schizophrenia and carry high diagnostic value. Poverty of speech, although not a first-rank symptom, is a feature of chronic schizophrenia, along with other 'negative symptoms' such as blunted mood and apathy. More information on the diagnosis of schizophrenia can be found in the link from the next question. Question 11. D) Ingestion of amphetamines within the last 24 hours Explanation: Although the possibility of schizophrenia should still be considered, recent drug misuse strongly suggests an organic psychosis, which is one of the main differentials of schizophrenia. Question 12. D) Driving under the influence of alcohol Explanation: Alcohol consumption associated with psychological, physical and social problems constitutes harmful use. Alcohol dependence is a more restricted term, the criteria for which are shown in the link below. Question 13. D) Wernicke's encephalopathy Explanation: The combination of confusion, ataxia and nystagmus suggests Wernicke's encephalopathy. Other eye signs, including ophthalmoplegia and ptosis, may also feature. Question 14. C) High-dose intravenous thiamin (Pabrinex) Explanation: Wernicke-Korsakoff syndrome is a rare but important effect of chronic alcohol misuse caused by deficiency of thiamin (vitamin B1). In Wernicke's encephalopathy there is an acute presentation with confusion, ataxia, nystagmus and ophthalmoplegia. This condition is reversible but without prompt treatment it may progress to Korsakoff's syndrome: severe and irreversible loss of short-term memory with consequent inability to make new memories. Treatment of Wernicke's and prevention of 141 Korsakoff's requires the immediate administration of high-dose thiamin, usually in intravenous form (Pabrinex). IV dextrose may precipitate or exacerbate Wernicke's and must not be given before adequate thiamin replacement in a patient in whom the diagnosis is suspected. Question 15. C) Self-induced vomiting or purgation Explanation: Recurrent bouts of binge eating followed by vomiting, purgation or dieting are a feature of bulimia nervosa rather than anorexia nervosa. Chapter 10 ONCOLOGY Question 1. D) Human papillomavirus and oesophageal cancer Explanation: Human papillomaviruses 16 and 18 are associated with cervical intraepithelial neoplasia (CIN) and subsequent cervical carcinoma, not with oesophageal cancer. The detection of CIN by cervical smear testing forms the basis of the UK screening programme for cervical cancer. Question 2. A) Early menarche Explanation: Risk factors for breast carcinoma include advancing age, early menarche, late menopause, postmenopausal obesity, personal or family history of breast malignancy, inheritance of BRCA 1 or 2 genes, some benign breast conditions (e.g. lobular carcinoma in situ, atypical hyperplasia), prolonged use of hormone replacement therapy, previous radiotherapy for Hodgkin lymphoma and smoking. Early full-term pregnancy reduces the risk. Fibrocystic breast change is a benign condition which results in increased breast lumpiness and tenderness, but is not associated with breast cancer. In MEN there is an increased risk of malignancy in endocrine glands; for example, in MEN I, tumours affect the pancreas, pituitary and parathyroids. Question 4. B) Alpha-fetoprotein (AFP) and bladder carcinoma Explanation: Tumour markers detected in the blood can help in the diagnosis of certain types of cancer, but due to lack of specificity are often more useful in monitoring response to treatment and identifying relapse. Alpha-fetoprotein (AFP) may be elevated in hepatocellular carcinoma and testicular cancers. Question 5. B) Take blood cultures and start broad-spectrum antibiotics immediately Explanation: Neutropenic sepsis (fever of 38°C for over 1 hour in a patient with a neutrophil count < 1.0 × 109/l) is most often a complication of chemotherapy and is a life-threatening emergency. Urgent treatment with appropriate broad-spectrum IV antibiotics is essential and must not be delayed pending results of cultures and Xrays. G-CSF can be used in selected cases to stimulate white blood cell production, but is not the initial treatment and should only be given on specialist advice. If the patient develops septic shock she may well require invasive monitoring, but this is unnecessary in the current context. Question 3. B) Acanthosis nigricans Explanation: Non-metastatic manifestations of lung cancer include finger clubbing, neurological problems (e.g. Eaton-Lambert syndrome, cerebellar signs) and excess hormone secretion (ADH resulting in hyponatraemia, ACTH leading to Cushing's syndrome, and parathyroid hormone (PTH)-related peptide causing hypercalcaemia). Acanthosis nigricans, a velvety thickening and pigmentation of the major flexures, particularly the axillae, is associated with tumours of the upper gastrointestinal tract. Question 6. C) Spinal MRI scan 142 Explanation: The rapid onset of bilateral upper motor neuron signs in a patient with prostatic carcinoma is strongly suggestive of spinal cord compression secondary to metastatic disease and is an oncological emergency. Other important clues in the history and examination would be sphincter disturbance or sensory loss. Spinal MRI is the investigation of choice to identify cord compression. CT is useful to look at bony structures, but has poorer resolution than MRI for soft tissues such as the spinal cord and nerve roots. Nerve conduction studies and electromyography are used in the assessment of peripheral neuropathies and myopathies. Question 7 A) Intravenous saline Explanation: Hypercalcaemia in malignancy can occur due to metastatic bone disease or as a non-metastatic manifestation secondary to parathyroid hormone (PTH)-related peptide production by tumour cells. The resulting osmotic diuresis often renders patients severely dehydrated. Treatment with large volumes of intravenous saline corrects the fluid deficit and lowers serum calcium over a period of hours. Bisphosphonates (e.g. pamidronate) lower serum calcium over a few days and can be given following rehydration in severe cases. Forced diuresis (using saline and furosemide) and calcitonin are occasionally used in very ill patients. Calcium gluconate is used in the treatment of hypocalcaemia. Question 8 D) Superior vena caval obstruction Explanation: This patient has features of superior vena caval obstruction (SVCO), which is usually due to malignancy (e.g. lung cancer, lymphoma). Obstruction of the SVC leads to facial suffusion and 143 oedema of the upper body. Veins on the chest wall become prominent as collateral channels open up. Treatment options for SVCO include radiotherapy and stenting. Question 9 B) Dexamethasone Explanation: The CT scan shows multiple cerebral metastases associated with cerebral oedema; these are causing midline shift. The steroid dexamethasone reduces oedema and is therefore the initial treatment of choice. Palliative radiotherapy is often the next step, but there is little evidence for this. Surgery in the presence of multiple metastases and oedema would not be appropriate. There is little evidence to support the use of chemotherapy. Question 10 D) Peripheral neuropathy Explanation: Ionising radiation mediates its effect by causing damage to DNA. Tumour cells and healthy cells are both affected, resulting in a range of adverse effects. Neuropathies are associated with various chemotherapeutic agents but not typically with radiotherapy, although it can cause a brachial plexopathy. Question 11 E) It exerts its effect by acting as an oestrogen receptor antagonist Explanation: Tamoxifen is an oestrogen receptor antagonist and should be considered as adjuvant therapy in all women with breast cancer expressing oestrogen receptors (ER); it has no role in ER-negative breast cancer. Tamoxifen is a hormonal treatment, not a chemotherapeutic agent, and is therefore not associated with bone marrow suppression. Chapter CARE AND 11 PALLIATIVE PAIN MANAGEMENT Question 1. D) Has a better response to non-steroidal anti-inflammatory drugs (NSAIDs) than tricyclic antidepressants Explanation: Neuropathic pain is typically described as burning, stabbing or pulsing. It often responds favourably to tricyclic antidepressants and anticonvulsants, but suboptimally to opioids and NSAIDs. Question 2. B) Liver capsule pain Opioids Explanation: Liver capsule pain is caused by stretching of the capsule due to hepatic enlargement. It is usually associated with a tender, palpably enlarged liver. It responds well to corticosteroids but is poorly responsive to both NSAIDs and opioids. Question 3. A) Replace codeine with a strong opioid such as morphine Explanation: The WHO analgesic ladder dictates that analgesia should be prescribed that is appropriate for the severity of the pain, and increased until the pain is controlled. For severe pain not controlled by a combination of weak opioid (codeine) and non-opioids (paracetamol and NSAIDs), as in this case, the appropriate step is to give the patient a full trial of strong opioids in place of the weak opioid. It is an important principle of the ladder that patients should not move 'sideways', i.e. change from one drug to another drug of similar potency. At each step of the analgesic ladder adjuvant agents (such as anticonvulsants for neuropathic pain) should be considered. However, the pain in this case is unlikely to be neuropathic and a strong opioid is definitely indicated. 144 Question 4. D) Respiratory depression is more likely to be a problem in acute dosing than with patients on regular opioids Explanation: Nausea and vomiting occur initially but usually settle after a few days. Dry mouth, rather than excessive salivation, is a common side-effect. Laxative agents are often prescribed routinely in patients starting strong opioids to prevent problems with constipation. Respiratory depression can be treated with the opioid antagonist, naloxone. Opioids can cause dose-related sedation and drowsiness in patients of all ages, although elderly patients tend to be more sensitive. Question 5. D) Change from CR morphine to regular IR morphine at a lower equivalent dose and also prescribe 'as required' doses of IR morphine Explanation: The patient developed opioid toxicity as a result of the steep increase in her morphine dose. Whenever the opioid requirements of a patient with continuous pain are unclear (e.g. starting strong opioid for the first time, inadequate pain control or adjusting dose in light of toxicity), the correct process is as follows: • Prescribe IR oral morphine 4-hourly. • In addition, prescribe an 'as required' dose of the same strength to be given when the patient has pain that is not controlled by the regular prescription (breakthrough pain). • Review adequacy of pain control, requirement for breakthrough analgesia and presence of side-effects daily. 145 • Increase the regular 24-hour dose by the sum of the breakthrough doses over the previous 24 hours (unless there are significant problems with side-effects). • Only when the correct dose has been established should the patient be converted to a longer-acting preparation such as CR oral morphine or a transdermal fentanyl patch. In the above case the patient may benefit from switching to an alternative strong opioid once the correct dose has been established. It would also be important to ensure adequate hydration and appropriate use of adjuvant agents. Question 6 B) Metoclopramide Explanation: Metoclopramide is contraindicated in the presence of colic because of its prokinetic effect. Chapter 12 INFECTIOUS DISEASES Question 1. C) Unpasteurised milk Leptospirosis Explanation: Leptospirosis (Weil's disease) is caused by infection with the spirochaete, Leptospira interrogans, which enters humans by direct contact, often through swimming in water contaminated with rat urine. Mosquitoes may transmit dengue fever, filiariasis and, most importantly, malaria. Hepatitis B may be contracted from contaminated blood products, unprotected sexual intercourse and the use of intravenous drugs. Brucellosis and salmonellosis may be contracted through drinking unpasteurised milk. Question 5. D) Infants are protected for the first 6 months of life by passive immunity from maternal antibodies Explanation: The incubation period in measles is 14 days. Koplik's spots are pathognomonic of measles but appear on the internal buccal mucosa not the retina. Bacterial pneumonia complicates the disease in around 4% of cases and accounts for many measles-related deaths, but antibiotics should not be given unless there is clinical evidence of superinfection (see evidence-based medicine box in link). Vaccination after recovery is pointless, as survival of infection confers life-long immunity. Question 2. C) Giardiasis Explanation: The flagellate protozoon, Giardia lamblia, colonises the small bowel, where it may cause diarrhoea, abdominal discomfort and malabsorption. Question 6. A) Rubella Myocarditis Explanation: Rubella infection in early pregnancy may lead to severe congenital malformation but rarely causes complications in childhood, with most cases being subclinical. Infection with human erythrovirus 19 (previously known as parvovirus B19) transiently depresses bone marrow function. This is usually mild but, in individuals with reduced red cell lifespan (e.g. spherocytosis), it may lead to life-threatening anaemia. Question 3. B) Cutaneous larva migrans Explanation: The history and description of the rash are classical for cutaneous larva migrans (CLM), which is caused by the dog hookworm, Ancylostoma caninum. The foot is the most common site, but lesions of CLM may also be seen on the breasts, buttocks and elbows. Treatment options include albendazole and ivermectin. Question 4. D) Tuberculosis Explanation: Eosinophils play an important role in combatting helminths, phagocytosing immune complexes and modulating type 1 hypersensitivity reactions. Eosinophilia is therefore most commonly seen with parasitic infections and allergy. Tuberculosis causes a monocytosis. 146 Question 7. C) Varicella zoster virus Explanation: The clinical description and rash are typical of shingles, caused by herpes zoster. The virus remains dormant in the dorsal root ganglion of sensory nerves and can be reactivated at any time. Question 8. E) It is caused by a DNA poxvirus Explanation: Smallpox has been eradicated world-wide since 1980, when WHO coordinated a successful vaccination campaign. Since eradication, the vaccine is no longer routinely used but is still available. The disease has a 30% mortality rate. In contrast to chickenpox, the rash is worst on the face and extremities. Smallpox has recently returned to media prominence due to concern over its potential as a bioterrorist weapon. Question 9. A) Infectious mononucleosis Explanation: The symptoms, clinical findings, lack of travel history and age group all point towards a diagnosis of infectious mononucleosis, caused by the Epstein-Barr virus. Question 10. D) The peak incidence of acquisition is in the sixth decade Explanation: The first peak in virus acquisition is in early childhood, when it is passed readily in communal environments such as nurseries and school. The second peak occurs in teenage years. In most cases primary infection is asymptomatic, but carriers often continue to excrete virus for months or years. Serious consequences of the infection usually occur in the immunosuppressed, in whom it may cause CMV retinitis, and in pregnant women, when there is a 40% risk of spread to the fetus, 10% of whom will have serious neurological sequelae. Question 11. D) Dengue Explanation: Despite the apparent compliance with chemoprophylaxis, it would be vital to consider the diagnosis of malaria in this and any other patient recently returned from an endemic area who has a fever. Such patients should have urgent thick and thin blood films sent to look for the Plasmodium falciparum parasite. Nevertheless, by far the more likely diagnosis in this scenario would be dengue fever, considering the recent travel history, mosquito bites and the symptoms described. The mosquito, Aedes aegypti, is 147 the principal vector, and the incubation period is 2-7 days, with the rash appearing between days 3 and 5 of the symptomatic infection. A more serious form of the infection, dengue haemorrhagic fever, can also occur, particularly in children in South-east Asia. Question 12. E) Norovirus Explanation: Norovirus (Norwalk agent) is the cause of many of the outbreaks of 'winter vomiting disease' that close wards in hospitals each winter in the UK. After a 48-hour incubation period, the virus causes a vomiting illness that lasts 2-3 days. Question 13. C) Hepatitis Explanation: Staph. aureus is a normal commensal of human skin, but can cause serious infection when it breaches this barrier. This is particularly so if foreign material is present: for example, in prosthetic joints and cannulae. Question 14. B) Staphylococcal toxic shock syndrome Explanation: Staphylococcal toxic shock syndrome is a life-threatening condition that presents with high fever, systemic upset, a generalised erythematous blanching rash and haemodynamic compromise, before progressing rapidly to multi-organ failure. It is caused by infection with certain strains of Staphylococcus aureus that produce a toxin known as toxic shock syndrome toxin 1 (TSST1). A major aetiological factor is the use of vaginal tampons, particularly when they are not removed in a timely fashion, as Staph. aureus can grow in and around the tampon with subsequent liberation of TSST1. In the case above, the diagnosis of meningococcal sepsis would also have to be considered. Question 15. E) Haemolytic uraemic syndrome Explanation: Scarlet fever most often results from uncomplicated streptococcal pharyngitis or tonsillitis. Various streptococcal species, including the viridans group, may be responsible for endocarditis. In rheumatic fever, antibodies generated in response to infection with certain strains of group A streptococci cross-react with cardiac myosin and sacrolemmal membrane proteins, leading to inflammation in the endocardium, myocardium and pericardium. An immune-mediated reaction following streptococcal infection may also lead to glomerulonephritis but haemolytic uraemic syndrome is a consequence of infection with certain strains of E. coli, most notably E. coli O157. Question 16. A) Pyoderma gangrenosum Explanation: Brucellae are intracellular organisms that can survive within the body for long periods of time, causing nonspecific symptoms and signs in various organ systems. The acute phase of the illness is marked by high swinging temperature, rigors and lethargy. Physical findings that are non-specific include lymphadenopathy and splenomegaly. Brucellosis may cause erythema nodosum but is not associated with pyoderma gangrenosum. Question 17. E) Erythema chronicum migrans Explanation: Erythema chronicum migrans is the rash associated with Lyme disease, caused by infection with spirochaetes of the genus Borrelia. The main vector is the tick Ixodes, whose bites transmit the disease to humans. The early disease is localised, manifesting as a skin reaction around the site of the tick bite. The infection may then disseminate to produce widespread systemic effects such as arthralgia, meningitis, cranial nerve palsies and peripheral neuropathy. Late advanced disease produces arthritis, encephalopathy and acrodermatitis chronica atrophicans. 148 Question 18. A) 14-day course of doxycycline Explanation: In the absence of contraindications, a 14-day course of amoxicillin or a tetracycline antibiotic such as doxycycline is indicated. Disseminated Lyme disease may require more prolonged therapy, with up to 30 days of treatment. Where there is neurological involvement (neuroborreliosis), parenteral therapy, usually with a broad-spectrum cephalosporin, is required for 3-4 weeks. Question 19. D) Weil's disease (leptospirosis Explanation: This dramatic presentation with fever, haemorrhages, jaundice, purpura, renal impairment and conjuctival hyperaemia is a classical of Weil's disease, a spirochaetal infection caused by leptospires. These highly motile organisms are shed in the urine of animal hosts, especially rats, and infection may occur during prolonged immersion in contaminated water. The disease is therefore more common is freshwater sports enthusiasts, such as this patient. Meningococcal sepsis must be considered in any patient presenting with fever and purpura, but this man's age and the presence of jaundice and hyperaemic conjuctivae make it less likely. His age also reduces the likelihood of infectious mononucleosis, which does not usually present in such dramatic fashion. Hepatitis A may present with fever, jaundice and raised transaminases, but would not account for some of the other features. Listeriosis tends to affect immunocompromised patients and pregnant women. Question 20. C) Faecal-oral Explanation: Typhoid and paratyphoid fevers (the enteric fevers) are transmitted by the faecal-oral route. It is important not to confuse them with typhus, a rickettsial infection transmitted by ticks. Question 21. B) Refrigeration of food products encourages the growth of heatstable enterotoxins Explanation: Correct storage of food and good food-handling practices limit the incidence of staphylococcal food poisoning. As Staph. aureus is a commensal of human skin (and particularly nasal passages), poor hand hygiene among food servers and handlers is a frequent cause of cases. Nausea and profuse vomiting are the predominant symptoms and are due to production of an enterotoxin by the organism rather than active infection. This explains the rapid onset of symptoms, which first arise 1-6 hours after food ingestion. The enterotoxin is also responsible for the typical rise in neutrophil count. Question 22. E) Entero-invasive E. coli (EIEC) causes symptoms through production of an enterotoxin Explanation: EIEC causes symptoms by direct invasion of the colonic mucosa and presents in a very similar fashion to Shigella dysentery. Approximately 10-15 percnt; of patients with the O157 serotype of EHEC will develop haemolytic uraemic syndrome, characterised by acute renal failure, and intravascular haemolysis. It occurs with greatest frequency in the very young and the very old. Management may include dialysis and/or transfusion. E. coli is also the most common cause of travellers' diarrhoea. Question 23. B) Metronidazole Explanation: A 10-day course of oral metronidazole is first-line therapy for established Cl. difficile infection; oral vancomycin is used if there is no response. Almost all antibiotics predispose to Cl. difficile infection, particularly broadspectrum penicillins (e.g. co-amoxiclav), second/third generation cephalosporins (e.g. cefuroxime) and clindamycin. 149 Question 24. A) Cholera Explanation: The bacterium, Vibrio cholerae, causes acute watery diarrhoea. The stool is typically 'rice water' in nature, consisting of clear fluid with flecks of mucus. This contrasts with the other organisms listed, which may directly invade the mucosa of the small bowel, or produce cytotoxins that damage and ulcerate the mucosa with inflammation, producing a bloody diarrhoea. Question 25. C) Oral rehydration solution (ORS) contains carbohydrate, sodium, potassium and chloride Explanation: Replacement of fluid losses is by far the most important aspect of the management of acute gastroenteritis. The average adult with 48 hours of moderate diarrhoea will be 1-2 litres depleted. Adequate rehydration requires replacement of this deficit and on-going diarrhoeal losses in addition to normal daily fluid requirement. While intravenous replacement may be required for those who cannot keep up with losses by oral intake alone (e.g. in persistent vomiting), the vast majority of cases can be managed with appropriate oral rehydration. ORS contains both electrolytes and a source of carbohydrate to allow absorption to take place. Prolonged bouts of diarrhoea will result in a metabolic acidosis, due to the loss of bicarbonate-rich secretions from the gastrointestinal tract distal to the stomach. Infants with gastroenteritis should definitely continue to breastfeed, as milk is sterile and nutritious, and contains the correct balance of electrolytes. Question 26. B) Diphtheria Explanation: Although diphtheria was eradicated from the developed world in the mid-20th century, it remains an important source of illness in the developing world, and recent years have seen the occurrence of outbreaks in South-east Asia and parts of the former USSR. The 'bull neck' and 'wash-leather' grey-green membrane covering the tonsils are characteristic of the acute presentation. Treatment is threefold, including administration of diphtheria antitoxin, antibiotics (penicillin or erythromycin) and isolation. A streptococcal sore throat will characteristically look red and raw; oral candidiasis is whitish in appearance, and has a predilection for the tongue rather than the tonsils; mumps usually affects a younger age group and may cause a swollen neck, but not the other findings; tonsillar cancer is exceedingly rare and does not really fit with this acute presentation. Question 27. D) Leprosy Explanation: A history of skin lesions and thickened peripheral nerves should lead to strong suspicion of leprosy. About 70% of the world's leprosy patients live in India, so this gentleman's ethnic origin is also a clue. Question 28. C) Microscopy of split skin smears Explanation: Although the diagnosis of leprosy is largely clinical, based on the presence of cardinal features, the finding of acid-fast bacilli in split skin is confirmatory and also useful for monitoring response to treatment. M. leprae still cannot be grown in vitro and neither serology nor PCR testing for leprosy DNA is sensitive enough for diagnostic purposes. Question 29. D) Rifampicin Explanation: Rifampicin is a potent bactericidal for Mycobacterium leprae but should always be given in combination with other antileprotics. Multidrug treatment (MDT) is crucial to treatment success because of the emergence of resistant strains of the bacillus. 150 More than 12 million patients have now been successfully treated with MDT. Question 30. D) Bartonella henselae Explanation: B. henselae causes cat scratch disease, a common benign condition that arises in children and young adults following a scratch from a cat. A vesicle or papule develops at the site of the injury, and subsequently the patient develops lymphadenopathy which may last for up to 4 months after the skin lesion has resolved. Bartonella isolates are sensitive to ß-lactam antibiotics, rifampicin, erythromycin and tetracyclines. Organisms of the Bartonella group may also cause a life-threatening endocarditis, particularly in the homeless, which requires intravenous antibiotics and valve replacement. Question 31. B) Falciparum malaria Explanation: A history of intermittent fevers following return from travel in an endemic area should always arouse suspicion of malaria, the most dangerous form of which is falciparum malaria. Jaundice is common due to a combination of haemolysis and hepatic dysfunction, anaemia develops rapidly and tender hepatosplenomegaly is typical. Infectious mononucleosis could potentially present with similar features but the lack of sore throat, lymphadenopathy or rash and the recent travel history favour malaria. With a corresponding history of unprotected sexual intercourse, the timing would be right for HIV seroconversion illness (2-6 weeks after initial infection), which may present non-specifically with fever and malaise but would not produce anaemia and jaundice. The other two options are highly unlikely. Question 32. C) Nephrotic syndrome Explanation: Infection with Plasmodium malariae but not Plasmodium falciparum may cause glomerulonephritis and nephrotic syndrome in children. Renal complications of falciparum malaria include acute renal failure secondary to acute tubular necrosis, occasionally with Question 33. A) Thin blood film Explanation: A thin blood film allows identification of the species of parasite as well as estimation of parasitic load. Full blood and coagulation screen will commonly reveal abnormalities but are not diagnostic. Culture and serological tests play no role in the diagnosis. Question 34. B) Falciparum malaria is still largely sensitive to quinine Explanation: P. falciparum is now resistant to chloroquine almost worldwide, but not to quinine which is the drug of choice. Mefloquine, not quinine, may occasionally cause severe neuropsychiatric side-effects. Mefloquine or doxycycline chemoprophylaxis should be started 1 week before travel to a malarious area and continued for 4 weeks after. Fansidar has resulted in deaths from both agranulocytosis and Stevens-Johnson syndrome and should not be used for chemoprophylaxis. Question 35. D) Blood tests typically reveal thrombocytosis and neutrophilia Explanation: Characteristically, pancytopenia is found on full blood count, rather than thrombocytosis and neutrophilia. Question 36. B) Cutaneous leishmaniasis Explanation: The history of the lesion, recent travel to an endemic area and biopsy findings of parasites in the dermis all make cutaneous leishmaniasis (CL) by far the most likely diagnosis. The incubation period is typically 2-3 months. Although all of the above are protozoal infections, only CL gives a cutaneous ulcer as described. Question 37. B) Trypanosoma cruzi Explanation: American trypanosomiasis (Chagas disease) commonly occurs in South and Central America, and is transmitted to humans by contact with the faeces of the reduviid bug. Between 10% and 30% of cases with chronic infection develop a cardiomyopathy characterised by cardiac dilatation, varying degrees of atrioventricular block, arrhythmias and 151 sudden death. Question 38. B) Tsetse fly Explanation: The bite of the tsetse fly is painful and often causes local inflammation. Question 39. E) The most common presenting features of acquired toxoplasmosis are fever, photophobia and a non-specific rash Explanation: The most common clinical presentation of toxoplasmosis is with painless enlargement of lymph nodes, particularly cervical nodes. Photophobia and a rash do not normally feature. The risks of transmission to the fetus are greatest in the third trimester; however, the overall incidence and severity of congenital disease are greatest in the first trimester. Question 40. C) Clinically, the disease manifests as diarrhoea alternating with constipation, with the presence of blood and mucus Explanation: Amoebiasis is a form of dysentery, which is spread to humans by ingestion of cysts of E. histolytica in water or uncooked food. Vegetative trophozoite forms emerge from cysts in the large bowel and invade the mucous membrane. The incubation period ranges from 2 weeks to many years. Diagnosis is made by direct microscopy of stools, looking for motile trophozoites. Intestinal amoebiasis responds rapidly to oral metronidazole. Question 41. E) Neutrophilia Explanation: Strongyloidiasis is a disease caused by the nematode Strongyloides stercoralis, which is common in the Far East. It is characterised by a marked eosinophilia. Allergic phenomena, such as urticaria, wheeze and arthralgia, are often seen in conjunction with the gastrointestinal symptoms. Ivermectin is the treatment of choice. Question 42. B) Filiariasis Explanation: Filarial worms are tissuedwelling nematodes; toxins released by the adult worm after dissemination in the human blood stream cause dilatation of the lymphatic vessels, leading to lymphatic dysfunction and the chronic limb manifestation of elephantiasis. In the acute phase, the presentation is as described above, with fever, erythema and tenderness along the course of the inflamed lymphatic vessels and epididymo-orchitis. The treatment of choice is diethylcarbamazine (DEC). Question 43. A) Vision Explanation: Onchocerciasis, otherwise known as river blindness, is the result of infection by the filarial Onchocerca volvulus, transmitted by flies of the genus Simulium. It is endemic in sub-Saharan Africa, where it leaves almost half a million people with visual impairment 152 every year. Eye disease is heralded by itching, lacrimation and conjunctival injection. 'Snowflake' deposits are classically seen at the edge of the cornea. The treatment of choice is ivermectin, which is also in widespread use as a prophylactic agent. Question 44. D) Urticaria Explanation: Urticaria is a manifestation of acute schistosomal infection. Schistosoma haematobium characteristically affects the urinary tract, causing the chronic complications of recurrent urinary tract infections, bladder or ureteric stone formation, and hydronephrosis. The eggs of S. mansoni and S. japonicum are deposited in the liver, where they may lead to portal hypertension and consequent development of splenomegaly, progressive ascites and oesophageal varices. Chapter INFECTION AND 13 HIV THE AIDS Question 1. A) Single-stranded RNA virus Explanation: HIV is a single-stranded RNA virus. It consists of a protein core, surrounded by a lipid membrane which is lined by a matrix protein studded with glycoprotein. The virus requires a host cell (a CD4-positive cell) in order to replicate, and to integrate its own genetic material into that of the host. Question 2. C) Homosexual transmission Explanation: The relative importance of the various modes of HIV transmission shows marked geographical variation. In northern Europe, where blood products are routinely and scrupulously screened for HIV and where highly active antiretroviral therapy (HAART) and needle exchange programmes are more readily available, the main mode of transmission is from men who have sex with men (MSM). In Africa, by contrast, the most frequent modes of transmission are heterosexual and vertical. China and Eastern Europe have a much greater proportion of cases in intravenous drug-users. Question 3. E) Receipt of infected blood products Explanation: Receipt of infected blood or blood products carries a 90% risk of transmission to the recipient. The other transmission risks are: • Vertical transmission 15-40% • Intravenous drug users 0.5-1% • Genital mucous membrane contact 0.20.5% • Non-genital mucous membrane contact < 0.1% 153 Question 4. B) CD4 count falls, viral load rises Explanation: Primary infection with HIV is symptomatic in 70-80% of cases, presenting with symptoms suggestive of a flu-like illness. This coincides with a surge in the plasma HIV-RNA levels to > 1 million copies/ml, and a fall in the CD4 count to 300-400 cells/mm3. Question 5. D) Oropharyngeal candidiasis Explanation: The acquired immunodeficiency syndrome (AIDS) is defined by the development of specified opportunistic infections, tumours etc. (see link below) in a patient with HIV infection. These tend to become manifest with varying degrees of immunosuppression, so that there is a correlation between the CD4 count and the specific diseases likely to occur. Oesophageal but not oropharyngeal candidiasis is considered an AIDSdefining illness. Question 6. A) Patients typically present with profuse, bloody diarrhea Explanation: One of the cardinal features of Cryptosporidium infection is that the diarrhoea is watery and cholera-like, as opposed to bloody. When prolonged, it is an AIDS-defining illness that occurs when the CD4 count falls below 200 cells/mm3. As the cysts are chlorine-resistant, all HIV-infected patients are advised to boil their drinking water. Question 7. E) Toxoplasma Explanation: Toxoplasma is a pathogen of the nervous system, causing spaceoccupying cysts within the brain that lead to focal neurological signs. The typical radiological appearance is of multiple ring-enhancing lesions on contrast CT or MRI of brain. Toxoplasma causes subclinical infection in the immunocompetent individual; it occurs in HIV-positive patients when the CD4 count falls below 100 cells/mm3. All of the other pathogens listed can cause chronic diarrhoea in the immunosuppressed. Question 8. B) A cough productive of green sputum Explanation: Pneumocystis carinii (now renamed jirovecii) pneumonia is an AIDSdefining illness that affects the respiratory tract, causing a dry cough, pyrexia, and breathlessness disproportionate to clinical and radiological signs. Exercise-related desaturation is a common feature. Diagnosis is based on cytology of induced sputum samples or bronchoalveolar lavage, as the organism cannot be cultured. First-line treatment is high-dose co-trimoxazole and steroids. Pneumocystis infection occurs when the CD4 count falls below 200 cells/mm3. Many patients who are HIV-positive with CD4 counts at or below this level will be on prophylactic co-trimoxazole or an alternative. Question 9. C) Deafness and blindness are the most common complications Explanation: Cryptococcus is identified on microscopy of CSF that has been stained with India ink. It is the most common cause of meningitis in late-stage HIV infection, and tends to occur only once the CD4 count has fallen below 100 cells/mm3. The typical signs of meningism are often absent, and the presenting features may be non-specific, with headache, fever, vomiting and mild confusion. Deafness and blindness may result from prolonged elevation of intracranial pressure. Cryptococcus neoformans is a budding encapsulated yeast, and therefore penicillin-based antibiotic regimens are ineffective. 154 Amphotericin given intravenously is the treatment of choice. Once infection has been successfully treated, fluconazole can be given as prophylaxis until immunity has recovered. Question 10. D) Cytomegalovirus (CMV) retinitis Explanation: The symptoms given in the history, along with the time-scale of the visual loss and the physical findings, are all suggestive of CMV retinitis. This is an important disease; although the incidence has plummeted since the introduction of highly active antiretroviral therapy (HAART), the infection is sightthreatening, particularly if the macula is affected. It tends to occur when the CD4 count falls below 50 cells/mm3. Treatment involves the initiation of antivirals for CMV (e.g. ganciclovir, cidofovir) and HAART, if not already instituted. Visual loss may result if treatment is not started promptly. Question 11. E) Kaposi's sarcoma Explanation: Options A-C form part of the differential diagnosis of HIV-related skin disease but do not fit well with this presentation. Although HIV-associated lymphoma may cause lymphadenopathy and hepatosplenomegaly, it would not account for the cutaneous appearances described and tends to occur with lower CD4 counts (median CD4 count at diagnosis is 50 cells/mm3). Kaposi's sarcoma, an AIDS-defining disease, is a tumour that affects cutaneous, oral and visceral sites. It may follow an indolent or a fulminant course, with visceral involvement often following cutaneous disease. The pattern of disease mirrors the CD4 count, with accelerated disease more common in those with low CD4 counts. Question 12. A) Cranial nerve palsies Explanation: The neurological sideeffects of NRTIs tend to affect peripheral rather than central nerves. All drugs in this class act by incorporating themselves into the host DNA, inhibiting further lengthening of the complementary strand to the viral RNA template. NRTIs form one of the cornerstones of highly active antiretroviral therapy (HAART, most usually two NRTIs and a protease inhibitor). Below is a list of side-effects paired with the drug with which they are most strongly associated: • Pancreatitis ddI • Anaemia Zidovudine (ZDV) • Peripheral neuropathy d4T, ddI, ddC • Lipoatrophy d4T, ZDV Question 13. D) They improve the lipid profile of most patients by lowering total cholesterol and low-density lipoprotein (LDL), and by raising highdensity lipoprotein (HDL) Explanation: Protease inhibitors are associated with a worsening of lipid profile, causing a rise in total cholesterol and LDL, and a fall in HDL in 30-50% of patients. This effect, combined with the insulin resistance also caused by PIs, leads to an overall increased risk of ischaemic heart disease in these patients. The other major side-effect of PI therapy is fat redistribution, characterised by peripheral fat wasting (cheeks, temples, limbs and buttocks) and central adiposity. 155 Question 14. E) Low incidence of drug rashes Explanation: Rash/drug eruption is a major class-specific side-effect of NNRTIs, up to and including manifestations as severe as StevensJohnson syndrome. The action of this class of drug is to inhibit the action of reverse transcriptase by binding near to the active enzyme site. NNRTIs have a half-life of > 24 hours, allowing for once-daily dosing. Their incorporation into a HAART regime involves combination with two NRTIs. The other major disadvantage of NNRTIs is the potential for development of crossresistance to all drugs in the class, through a single mutational change. Other sideeffects include dizziness, vivid dreams, insomnia, poor concentration and depression. Question 15. B) Toxoplasmosis Erythromycin Explanation: Appropriate prophylaxis for toxoplasmosis would be co-trimoxazole. The decision to institute prophylaxis is generally dependent on CD4 levels, in that prophylaxis will be started when the CD4 count falls to a level at which the patient is deemed to have much greater susceptibility to that particular infection. For example, for Pneumocystis carinii pneumonia, the indication to commence co-trimoxazole is when the CD4 count falls below 200 cells/mm3 Chapter TRANSMITTED 14 SEXUALLY INFECTIONS Question 1. D) Trichomonas vaginalis Explanation: There are approximately 340 million curable STIs reported on a yearly basis to the World Health Organization, of which 170 million cases represent Trichomonas vaginalis. Chlamydia is responsible for 92 million cases, gonorrhoea for 62 million cases, and syphilis for 12 million cases. In the UK, the most common treatable STIs are chlamydia and gonorrhoea. It is important to remember that some STIs, especially chlamydial infection, may remain silent for many years and therefore go undiagnosed. Question 2. D) Gonorrhoea Explanation: The presence of Gramnegative diplococci on a smear of urethral exudate makes gonococcal urethritis the most likely diagnosis; culture may subsequently confirm the organism. Note that if a patient has been sexually active with two new partners in the past month, then the likelihood of an STI is increased. Question 3. D) Swab of the contents of a vesicle Explanation: The most likely diagnosis in the above case is genital herpes, which is diagnosed by sending swabs of vesicular fluid or ulcers for polymerase chain reaction examination for detection of herpes simplex virus (HSV) DNA. Although HSV-2 is classically associated with anogenital herpes, HSV-1 is found in about 50% of cases in the UK, as well as being the most common strain found in orolabial herpes. 156 Question 4. B) HPV 16 and 18 Explanation: HPV 16 and 18 have been linked to neoplasia of the genital tract. HPV 6 and 11 are the relatively benign strains that cause anogenital warts. Question 5. E) Chlamydial infection Explanation: The most commonly diagnosed curable STI in the UK is chlamydia, with 100 000 new cases detected each year. Chlamydia is far more frequently diagnosed than the next most common curable STI, gonorrhoea, with 22 000 cases reported each year. Chlamydia is usually asymptomatic, but may cause symptoms of pelvic inflammatory disease such as those described above. In either scenario, it may eventually cause damage to the Fallopian tubes, and subsequently infertility or ectopic pregnancy. Other rare complications in either sex include conjunctivitis and Reiter's syndrome. Question 6. A) Trichomoniasis Explanation: Motile flagellate protozoa seen on a wet mount of vaginal material are diagnostic of trichomoniasis. The organism involved is Trichomonas vaginalis, and the treatment of choice is metronidazole. Question 7. E) Syphilitic chancre Explanation: A chancre is an indurated ulcer, which is the primary lesion of syphilis; it occurs in the first days of symptomatic infection. It begins as a dull red macule, which becomes papular and eventually ulcerates. Draining lymph nodes may also become enlarged but are painless. The chancre is usually located on the penis in men or on the labia in women. Chancres may also occur on the vaginal wall and on the cervix. In 10% of cases, extra-genital sites such as fingers, lips, tongue and nipple may be involved. Secondary syphilis occurs 6-8 weeks after the chancre, when the treponemes have disseminated to produce multi-system disease. Question 8. D) Webbed neck Explanation: Congenital syphilis is associated with a number of stigmata, many of which are eponymous. The 157 chances of ever encountering any of these signs in clinical practice are infinitesimally small but some of them do still appear in postgraduate examinations! Webbed neck is, of course, associated with Turner's syndrome. Question 9. B) Vaginal candidiasis Explanation: The clinical picture best fits candidiasis. Options A, C and E would be unlikely in a woman of this age who is not sexually active, and the history would not fit with any of these. Although TSS could occur in this patient, it would present in an entirely different way. A further clue to the diagnosis lies in the fact that the patient is on long-term antibiotic therapy for acne; this would, of course, predispose her to candidal infection, as the antibiotics disrupt the natural flora of the female genital tract, allowing overgrowth of pathogens such as Candida albicans. Chapter BIOCHEMISTRY 15 CLINICAL AND METABOLISM Question 1. B) 15 litres Explanation: In a typical adult male, total body water is around 40 litres and constitutes around 60% of overall body weight. The majority of this, around 25 litres, is contained within cells (the intracellular fluid compartment). The bulk of the remaining 15 litres (the extracellular fluid compartment) is found within the interstitial fluid between cells and only a small proportion of this (3 litres) comprises plasma. Question 2. C) Potassium Explanation: The dominant cation in the intracellular fluid (ICF) compartment is potassium while the dominant cation in the extracellular fluid (ECF) compartment is sodium. The major force maintaining the difference in cation concentration between the ICF and ECF is the activity of the sodium-potassium pump, integral to all cell membranes. Question 3. B) High potassium Explanation: Haemolysis during or after collection of a blood sample causes contamination of the plasma compartment by intracellular components. As potassium is the dominant cation within the intracellular fluid compartment, this leads to a spuriously high plasma potassium concentration. In clinical practice this is one of the most common explanations for the finding of a high plasma potassium concentration and it is usually prudent to repeat the test, particularly if the result is unexpected. True hyperkalaemia is, however, a life-threatening emergency and treatment should not be delayed pending the result of a repeat sample if significant ECG changes are present. 158 Question 4. A) Sodium Explanation: Since the great majority of the body's sodium content is located in the ECF, total body sodium is a principal determinant of ECF volume. Importantly, when sodium balance is disturbed, any tendency for plasma sodium concentration to change is usually corrected by the osmotic mechanisms controlling water balance. Consequently, disorders in sodium balance present chiefly as altered ECF volume (hyper- or hypovolaemia) rather than altered sodium concentration. Question 5. B) 65% Explanation: Around 65% of the filtered sodium load is reabsorbed in the proximal tubule, a further 25% in the thick ascending limb of the loop of Henle and some 6% in the early distal tubule. Sodium handling in the late distal tubule and collecting duct is under the influence of aldosterone, which can increase reabsorption over the range of 2-3% of the filtered sodium load. A further small component (< 1%) occurs in the medullary collecting duct; this component is inhibited by atrial natriuretic peptide. A knowledge of the processes mediating sodium reabsorption and the factors which regulate it is essential for understanding disturbances of extracellular fluid volume and their management. Question 6. C) Bradycardia Explanation: Tachycardia, not bradycardia, is a clinical feature of hypovolaemia. Question 7. D) Increased release of atrial natriuretic peptide Explanation: Atrial natriuretic peptide (ANP) is one of several neurohumoral mediators that act to inhibit sodium reabsorption, contributing to natriuresis (increased urinary sodium excretion) during periods of sodium and volume excess. Release of ANP is reduced in response to loss of sodium and water. Activation of the renin-angiotensinaldosterone system is the most important neurohumoral response to salt and water depletion. Question 8. E) Addison's disease Explanation: Addison's disease is a cause of sodium and water depletion and may present with features of profound hypovolaemia. Note that in normal health a number of physiological mechanisms serve to match urinary sodium excretion closely to sodium intake, such that excess sodium intake does not lead to hypervolaemia. Various disease states may, however, impair these mechanisms or render them counterproductive, triggering a sequence of events that ultimately results in sodium and water excess (see link below). An awareness of these events is important both for understanding the pathophysiology of hypervolaemia in various clinical conditions and for providing a rational basis for treatment. Question 9. C) Loop of Henle Explanation: All diuretics act by inhibiting sodium reabsorption at some point in the nephron. Furosemide belongs to the potent class of 'loop diuretics' which inhibit sodium reabsorption in the thick ascending limb of the loop of Henle by blocking the apical Na,K,2Cl transporter. The link below is very useful for understanding the mechanisms by which different classes of diuretic achieve both their therapeutic effects and their sideeffects. 159 Question 10. B) Hyponatraemia Explanation: Treatment with either thiazide or loop diuretics may produce a wide range of metabolic abnormalities, though these are frequently subclinical. Both may lead to hyponatraemia through excess sodium loss with relative retention of water, especially in high vasopressin (ADH) states such as congestive heart failure. Note that the effect of loop and thiazide diuretics on calcium excretion differs, with the former increasing urinary calcium excretion and the latter reducing it. Thus a thiazide diuretic may lead to mild hypercalcaemia, not hypocalcaemia. Question 11. E) Diuretic therapy Explanation: Hyponatraemia (Na < 135 mmol/l) is a common electrolyte abnormality but it is easily misunderstood. This is because disturbances in sodium balance are manifest principally as changes in ECF volume status (hypo- or hypervolaemia) rather than changes in plasma sodium concentration (the plasma sodium concentration is often normal). Abnormalities of plasma sodium concentration are, instead, usually due to disturbances of body water content. Thus in all cases of hyponatraemia there is retention of water relative to sodium and the most useful guide to the underlying cause is assessment of the ECF volume status (which in turn reflects total body sodium). In hypovolaemic hyponatraemia (e.g. diuretic therapy, diarrhoea and vomiting) there is a sodium deficit with a relatively smaller water deficit; in euvolaemic hyponatraemia (e.g. SIADH, primary polydipsia) there is water retention alone with no change in total body sodium; and in hypervolaemic hyponatraemia (e.g. congestive cardiac failure, nephrotic syndrome) there is sodium retention with relatively greater water retention. Hyperlipidaemia is an artefactual cause of apparent hyponatraemia. Question 12. D) Syndrome of inappropriate ADH secretion (SIADH) Explanation: The pointers towards a diagnosis of SIADH in this case are: • no features on examination of hypo- or hypervolaemia (i.e. euvolaemic hyponatraemia) • urinary osmolality that is inappropriately high for the plasma osmolality. (In the face of a plasma osmolality of 250 mmol/kg, the urine should be maximally dilute ( 50 mmol/kg) and should certainly not have an osmolality greater than plasma.) Diabetes insipidus is a cause of hypernatraemia rather than hyponatraemia due to inadequate production of ADH. Question 13. D) Fluid restriction of 11.5 litres per day Explanation: Patients with SIADH have normal total body sodium but an excess of water (euvolaemic hyponatraemia). The most appropriate treatment is therefore not to increase sodium intake but to restrict water intake. Demeclocycline may be a useful second-line treatment if the rise in plasma Na with fluid restriction is inadequate. An important general point regarding the management of hyponatraemia is that the rate of correction of the plasma Na should be determined by the rate of onset of the hyponatraemia. An over-rapid correction in chronic hyponatraemia may lead to large water shifts out of neurons and consequent irreversible brain damage (central pontine myelinolysis). Question 14. B) Carbamazepine Explanation: SIADH has many underlying causes including tumours, intracranial pathology, pulmonary disorders and a variety of drugs. Carbamazepine is a well-recognised and common cause of drug-induced SIADH. Question 15. D) Peaked T wave Explanation: Hyperkalaemia is a dangerous electrolyte abnormality requiring prompt attention as it may lead to ventricular arrhythmias and asystolic cardiac arrest. Early ECG changes include 160 peaking of the T wave and flattening or loss of the P wave. A more serious change is broadening of the QRS complex that often heralds an impending serious arrhythmia. Flattened T waves, ST depression and U waves are all changes associated with hypokalaemia. Question 16. C) Conn's syndrome Explanation: The corticosteroid hormone, aldosterone, is the most important factor in adjusting potassium secretion to match potassium load. It acts on the nephron to stimulate both potassium and hydrogen ion secretion and increase sodium reabsorption, effectively conserving sodium at the expense of potassium and hydrogen. The altered potassium excretion usually acts to maintain tight control of plasma potassium concentration within the narrow normal range. In Conn's syndrome there is excess production of aldosterone by a unilateral adrenocortical adenoma, resulting in primary hyperaldosteronism. This leads to hypertension through excess sodium and water retention, usually accompanied by hypokalaemia through excessive potassium secretion, and metabolic alkalosis. All of the other options would be more likely to result in hyperkalaemia. Question 17. C) Ramipril Explanation: ACE inhibitors such as ramipril inhibit the conversion of angiotensin I to angiotensin II. One of the effects of angiotensin II is to stimulate aldosterone production in the zona glomerulosa of the adrenal cortex. The major function of aldosterone is to promote reabsorption of sodium in the late distal tubule and collecting ducts of the kidney at the expense of potassium and hydrogen. Thus a reduction in aldosterone activity will lead to decreased potassium secretion and decreased sodium reabsorption, explaining why ACE inhibitors (and aldosterone antagonists such as spironolactone) may lead to hyperkalaemia and reduced body sodium. Question 18. E) Calcium gluconate Explanation: All of the above treatments have a role in the management of hyperkalaemia but calcium gluconate is used to stabilise myocardial conductive tissue membranes in severe hyperkalaemia (usually only in the presence of significant ECG changes) and not to lower plasma potassium concentration. Inhaled _2 agonists (e.g. salbutamol) and intravenous glucose and insulin (e.g. 50 ml of 50% dextrose with 5 units Actrapid) act by shifting potassium into cells, whereas dialysis and calcium resonium remove potassium from the body. All medical students and junior doctors should be familiar with the management of hyperkalaemia, as severe hyperkalaemia is a life-threatening but reversible medical emergency. Question 19. E) Renal tubular acidosis Explanation: The anion gap is the difference between the main measured cations (Na and K) and anions (Cl and HCO3) in plasma. It is composed mainly of phosphate, sulphate and negative charges on plasma proteins. The normal value of the anion gap is around 15 mmol/l. Renal tubular acidosis and diarrhoea are the two most common causes of a normal anion gap acidosis. Sepsis may lead to tissue hypoxia and a consequent lactic acidosis; salicylate poisoning typically produces an initial respiratory alkalosis followed by a raised anion gap metabolic acidosis. Both diabetic ketoacidosis and starvation ketosis result in accumulation of acidic ketone bodies. 161 Question 20. C) Metabolic alkalosis Explanation: More on Patterns of acidbase disturbance Question 21. A) Gastric outlet obstruction Explanation: The patient has a hypochloraemic, hypokalaemic metabolic alkalosis with paradoxically acidic urine. This fairly classical pattern of biochemical disturbance is seen with persistent severe vomiting, as might occur with gastric outlet obstruction. The factors that contribute are explained in detail in the link below. Essentially, large quantities of sodium, chloride, potassium and hydrogen ions, as well as water, are lost in the vomit. The overriding response of the kidney is salt and water conservation, principally through increased aldosterone release. This maintains the alkalosis and hypokalaemia, as sodium is conserved at the expense of hydrogen and potassium ions. Thus the most effective method of correcting the alkalosis is intravenous sodium chloride (with potassium supplementation) to interrupt the volumeconserving mechanisms and allow the kidney to excrete excess alkali in the urine. Question 22. E) High-density lipoprotein Explanation: Reverse cholesterol transport refers to the transfer of cholesterol from cholesterol-laden cells to the liver (for excretion) and cholesterolrequiring tissues. This protects peripheral tissues (including blood vessel walls) from excessive cholesterol accumulation. Highdensity lipoprotein (HDL) is primarily responsible for reverse cholesterol transport and low levels of HDL cholesterol are associated with increased risk of atherosclerosis. Question 23. C) Eruptive xanthomas Explanation: Xanthelasma and corneal arcus are fairly non-specific signs of hyperlipidaemia seen in a variety of lipid disturbances and the elderly. On the other hand, xanthomas of the Achilles or extensor digitorum tendons are highly suggestive of familial hypercholesterolaemia (moderate to severe hypercholesterolaemia resulting from an autosomal dominantly inherited mutation of the LDL receptor gene). Although a correlation exists between hypertriglyceridaemia and risk of coronary heart disease, hypercholesterolaemia is a far more important risk factor and more closely associated with the development of cardiovascular disease. Eruptive xanthomas, as well as lipaemia retinalis and hepatosplenomegaly, may be found in severe hypertriglyceridaemia. Question 24. C) They inhibit endogenous cholesterol synthesis Explanation: The primary action of statins is to inhibit endogenous synthesis of cholesterol in the liver. This leads to upregulation of the LDL receptor and hence increased clearance of LDL cholesterol from the circulation. The incidence of rhabdomyolysis is very low, less than 1%. 162 Studies have demonstrated significant reduction in stroke as well as coronary heart disease. The lipid response includes a mild increase in HDL cholesterol, whilst the decrease in triglyceride is usually less than that in LDL. Question 25. B) Bullae on sun-exposed areas of skin Explanation: The porphyrias are disorders of the haem biosynthetic pathway that can be broadly divided into two categories according to pattern of presentation: • Non-acute or cutaneous porphyrias (e.g. porphyria cutanea tarda) are characterised by photosensitive skin manifestations that occur due to excess production and accumulation of porphyrins in the skin. • Acute or neurovisceral porphyrias (e.g. acute intermittent porphyria) present with acute episodes of abdominal pain and features of autonomic dysfunction (e.g. hypertension, tachycardia, constipation), often in conjunction with neuropsychiatric manifestations and/or acute neuropathy (usually motor). There are no skin manifestations in acute intermittent porphyria. Chapter AND URINARY 16 KIDNEY TRACT DISEASE Question 1. E) Renal artery stenosis Explanation: A bruit over one of the renal arteries may raise suspicion of renal artery stenosis, though it is neither a sensitive nor a specific sign. Other situations in which the diagnosis may be suspected include significant deterioration of renal function after starting an angiotensin-converting enzyme (ACE) inhibitor or the finding of significant renal impairment in a patient with widespread vascular disease elsewhere. Question 2. C) Diabetic nephropathy Explanation: Diabetic nephropathy is not a cause of enlarged kidneys but is one of the most common causes of chronic renal failure, often with small shrunken kidneys. Question 3. D) 500 ml Explanation: The minimum urine volume required to remove the daily solute load in maximally concentrated urine is 300-500 ml. Higher volumes are clearly preferable in health. Question 4. C) Malnutrition Explanation: Urea is excreted by the kidneys, so levels rise following a reduction in GFR. However, serum urea concentration is an imperfect guide to renal function since it is also influenced by several other parameters. As urea is a byproduct of protein catabolism, its production and serum levels are increased by high-protein diets or catabolic states. Upper gastrointestinal haemorrhage is effectively a large protein meal while malnutrition is a cause of low protein intake. Urea is also reabsorbed, to a variable extent, in the renal tubules; dehydration increases the proportion of filtered urea that is reabsorbed and therefore causes a rise in blood levels 163 independent of production or GFR. Question 5. A) Negative exponential Explanation: The importance of understanding this relationship is clear from the graph in the link below. A large fall in GFR may occur before serum creatinine is elevated outside the normal range. Question 6. B) Glucose Explanation: Glucose is freely filtered at the glomerulus and reabsorbed actively in the proximal tubules. Glycosuria results when the capacity of proximal reabsorption is saturated, because of either high serum glucose or low reabsorption capacity (low renal threshold). Large proteins such as albumin and fibrinogen, as well as cells, are not normally filtered. Question 7. E) Post-streptococcal glomerulonephritis Explanation: Red cell casts are characteristic of glomerular bleeding (the casts are formed in the renal tubules) and a common finding in cases of poststreptococcal glomerulonephritis. The other options listed cause bleeding from lower down in the urinary tract and do not lead to the formation of casts. Question 8. B) Reduced muscle bulk Explanation: Creatinine is freely filtered in glomeruli and not reabsorbed in tubules, so that serum creatinine is an index of glomerular filtration rate (GFR). Under normal circumstances, creatinine is released from muscle at a fairly constant rate, so the greater a patient's muscle bulk, the more creatinine he or she will produce. Changes in serum creatinine levels are therefore a better guide to renal function than a single one-off value. It is important to note that patients with significant renal impairment may well have a serum creatinine within the normal range, particularly if frail or malnourished. Because urea is a by-product of hepatic protein metabolism, liver failure, protein catabolism and dietary protein intake have a much bigger effect on urea concentration than creatinine. A significant upper gastrointestinal bleed is equivalent to a large protein meal and will likewise lead to increased urea production. Question 9. A) Detection of urothelial malignancy Explanation: Renal ultrasound has superseded IVU for many purposes and is usually the first-line investigation for renal imaging. However, IVU provides excellent definition of the collecting system and ureters and remains superior to ultrasound for detecting stones and urothelial tumours. Question 10. D) Dimercaptosuccinic acid (DMSA) isotope renogram Explanation: DMSA scans allow quantification of each kidney's relative contribution to renal function and can detect the presence of scarring. In general, the other investigations listed yield little functional information regarding the kidneys. Question 11. B) Kidneys < 60% normal size Explanation: Small shrunken kidneys are difficult to biopsy and usually indicate irreversible chronic renal disease. Consequently, complications are more frequent and results rarely helpful. Far 164 from being a contraindication, acute renal failure is one of the most common indications for renal biopsy. Haematuria may also be an indication, especially if associated with proteinuria or renal impairment. Antiplatelet drugs (aspirin etc.) and anticoagulants, but not ACE inhibitors, should be omitted for elective biopsies; indeed, uncontrolled hypertension is a contraindication to biopsy. Question 12. A) Escherichia coli Explanation: E. coli is by far the most common cause of community-acquired UTI. The other options listed occur with greater frequency in the hospital setting, although E. coli remains the most prevalent. Question 13. E) Rhabdomyolysis Explanation: All of the options listed could conceivably account for deteriorating renal function accompanied by dipstick-positive haematuria, but the absence of red cells on microscopy is characteristic of myoglobinuria occurring as a consequence of rapid muscle breakdown. This patient is at risk of rhabdomyolysis from having lain on the floor for 24 hours. Question 14. C) Cystoscopy and renal ultrasound Explanation: The priority in persistent haematuria is to exclude an anatomical bleeding lesion. This is particularly important in older patients who are at greater risk of malignancy. IVU may be considered if cystoscopy and ultrasound fail to reveal a cause, as it provides detailed imaging of the ureters. It would be unusual for prostate cancer or urinary tuberculosis to present with isolated macroscopic haematuria as the only symptom. Similarly, the absence of additional symptoms, lack of proteinuria and presence of normal renal function do not provide evidence of inflammatory renal disease or an indication for renal biopsy. Question 15. E) Microalbuminuria Explanation: Microalbuminuria is usually the earliest sign of renal dysfunction in diabetes mellitus and is associated with an increased risk of cardiovascular events in people without diabetes. It is not detected on standard urine dipstick tests and must therefore be specifically screened for in diabetic patients using ultra-sensitive sticks and/or through formal measurement of the urinary albumin:creatinine ratio. Question 16. E) Focal segmental glomerulosclerosis Explanation: This is a very high level of proteinuria. More than 3 g/24 hrs is in the 'nephrotic' range and is invariably caused by glomerular disease. Focal segmental glomerulosclerosis is a relatively common cause of nephrotic syndrome; the other disorders listed affect the urinary tract distal to the glomerulus. Question 17. E) Hypercholesterolaemia Explanation: Nephrotic syndrome describes the consequences of heavy urinary protein loss. The most characteristic manifestation is generalised oedema from a combination of decreased serum oncotic pressure (hypoalbuminaemia) and avid renal sodium retention (secondary hyperaldosteronism due to decreased intravascular volume). Other wellrecognised features, which are explained in the link below, include marked hypercholesterolaemia, hypercoagulability and increased susceptibility to infection. Question 18. D) Hypocalcaemia Explanation: Causes of polyuria are: • excessive fluid consumption (polydipsia) • osmotic diuresis (e.g. in diabetes mellitus due to hyperglycaemia) • reduced secretion of antidiuretic hormone (cranial diabetes insipidus) • resistance of the renal tubules to the actions of antidiuretic hormone (nephrogenic diabetes insipidus). Nephrogenic diabetes insipidus has a number of underlying causes including interstitial renal disease, lithium therapy, hypokalaemia and hypercalcaemia (which 165 also causes an osmotic diuresis). Cranial diabetes insipidus is often idiopathic but may occur secondary to head injury or an intracranial tumour. Question 19. A) Urge incontinence Explanation: Anticholinergics reduce detrusor muscle tone and may give symptomatic relief to patients with urge incontinence. Stress incontinence is a common problem, particularly in multiparous women, but anticholinergics are not usually effective. Treatment is with physiotherapy to strengthen pelvic floor musculature and, in severe cases, surgery. Question 20. E) Atenolol Explanation: Beta-blockers are a common cause of erectile dysfunction. Sildenafil (Viagra) is a phosphodiesterase 5 inhibitor used as a treatment for erectile dysfunction. Fluoxetine is a selective serotonin reuptake inhibitor in common use as an antidepressant. Interestingly, in a randomised, double-blinded trial, valsartan appeared to boost sexual performance in middle-aged Italian males. Question 21. D) Bilateral small kidneys on renal ultrasound Explanation: The other options given here (haematuria, proteinuria, oliguria, dehydration and hyperkalaemia) may all be present in either acute or chronic renal failure. In some cases it may be difficult to determine the rate of onset of the renal problem, but radiological evidence of shrunken kidneys usually indicates chronic disease. Question 22. B) Ibuprofen Explanation: Non-steroidal antiinflammatory drugs such as ibuprofen have been shown to increase the risk of contrast nephropathy. Intravenous fluid and N-acetylcysteine are thought to have a protective role. Question 23. D) Amoxicillin Explanation: Furosemide is a loop diuretic and bendroflumethiazide (formerly known as bendrofluazide) is a thiazide diuretic. They are particularly potent in combination and will impair renal sodium and water reabsorption, exacerbating hypovolaemia and hypoperfusion. Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, which will prevent the compensatory constriction of efferent renal arterioles. Diclofenac, a nonsteroidal anti-inflammatory drug, will prevent the compensatory dilatation of renal resistance arteries. Both of these drugs worsen renal failure in patients with critically impaired renal perfusion. Question 24. A) Promotes water reabsorption from urine Explanation: The medullary concentration gradient is a key mechanism of water reabsorption, enabling the production of highly concentrated urine. It is often lost in acute tubular necrosis (ATN) and this can lead to a 'diuretic phase' in which an inappropriately large volume of urine is produced during recovery from ATN. Question 25. E) Haemodialysis Explanation: Severe hyperkalaemia may lead to life-threatening arrhythmias, and resistant hyperkalaemia in the context of acute renal failure is one of the strongest indications for dialysis. Calcium gluconate may also be appropriate treatment here but is not used to lower serum potassium; rather it acts to stabilise the myocardium and should be given if the hyperkalaemia is accompanied by ECG changes. Sodium bicarbonate would be of little benefit as the patient is not acidotic, and the other conservative measures listed are unlikely to achieve a sufficient reduction in serum potassium. 166 Question 26. C) Bilateral nephrostomies Explanation: Nephrostomies are radiologically inserted drains that allow urine to drain directly from the renal pelvis and thereby decompress obstructed urinary systems. Most patients with post-renal acute renal failure will recover with relief of the obstruction without the need for renal support and, from the information given, there is no compelling indication for urgent renal replacement therapy here. Fluid restriction is not indicated and, indeed, fluid supplementation may be required once the obstruction is relieved as patients often experience a 'postobstructive diuresis'. Retroperitoneal fibrosis causes ureteric obstruction, so catheterisation would be unhelpful and potentially dangerous as the bladder is likely to be empty. Question 27. C) Reduced phosphate Explanation: Hyperphosphataemia is typical in chronic renal failure due to a combination of reduced phosphate excretion and secondary hyperparathyroidism. The elevated PTH occurs as an 'appropriate' physiological response to hypocalcaemia (hence secondary hyperparathyroidism), which in turn is due to deficiency of active (1Vhydroxylated) vitamin D. Declining renal function is associated with metabolic acidosis that should be treated with sodium bicarbonate. Hypercholesterolaemia is very common in patients with chronic renal failure (particularly with significant proteinuria) and may contribute to the greatly increased risk of cardiovascular events in these patients. Question 28. E) Complications of erythropoietin include hypertension and hypercoagulability Explanation: In patients with significant anaemia, plasma erythropoietin (EPO) should be elevated; a level within the normal range is therefore inappropriately low and indicates inadequate EPO production. The target haemoglobin level is around 100-120 g/dl; significantly higher targets may be associated with increased cardiovascular mortality. Iron deficiency is a common contributing factor to anaemia in chronic renal failure and a cause of suboptimal response to EPO; transferrin saturation should therefore be maintained above 20%. Human recombinant EPO is currently only available in intravenous and subcutaneous preparations. Hypertension and hypercoagulability are both wellrecognised side-effects of EPO. Platelet function is actually impaired in chronic renal failure ('uraemic platelets') and this is accompanied by an increased bleeding tendency. Question 29. B) Angiotensin-converting enzyme (ACE) inhibitors Explanation: Aggressive control of blood pressure is very important in patients with chronic renal disease, both to slow the deterioration in renal function and to reduce the risk of cardiovascular complications such as myocardial infarction and stroke. All of the above drugs may be used for this purpose; however, ACE inhibitors are antiproteinuric and have been shown to have 'renoprotective effects' independent of blood pressure lowering. Question 32. D) Anaemia Explanation: Dialysis essentially replaces the functions of urine - excretion of solutes and excess fluid, control of acid-base and removal of toxins - but it does not replace the endocrine functions of the kidney, such as production of erythropoietin and metabolism of vitamin D. Question 30. D) Enhanced platelet function Explanation: Cardiovascular disease is by far the leading cause of death in patients with chronic renal failure. Hypertension occurs in approximately 80% of patients and is a major risk factor for myocardial infarction, stroke and heart failure. Hypercholesterolaemia is very common and may also contribute to accelerated atherosclerosis. Anaemia is an independent predictor of left ventricular hypertrophy. Patients with chronic renal failure often have a heavily calcified arterial tree and this may be so severe as to cause limb ischaemia. 167 Question 31. A) 1L-hydroxylase Explanation: One of the functions of the kidney is conversion of the inactive form of vitamin D (25-hydroxycholecalciferol) to its active metabolite (1,25 dihydroxycholecalciferol) by the enzyme 1V-hydroxylase. Diminished activity of this enzyme leads to deficiency of active vitamin D, resulting in hypocalcaemia and secondary hyperparathyroidism (see link below). Hyperphosphataemia then occurs from a combination of the secondary hyperparathyroidism and reduced renal phosphate excretion. Accumulation of aluminium often occurs in dialysis patients and may be associated with a wide range of pathology. Question 33. D) Symptomatic fluid shift is less common with PD than HD Explanation: Peritoneal dialysis is less efficient than haemodialysis and must be performed more often. However, fluid shifts are less rapid, so peritoneal dialysis is less likely to cause symptoms associated with hypotension such as lightheadedness and cramps. Abdominal scarring from previous surgery may make peritoneal dialysis impossible, but will not affect haemodialysis. Question 34. B) Active anti-glomerular basement membrane (GBM) disease Explanation: Active anti-GBM disease is considered an absolute contraindication to renal transplant because of the likelihood of recurrence in the transplanted kidney. Transplantation is routinely offered to patients in their fifties in most centres. Previous skin cancer is not directly relevant if the lesion has been successfully removed. However, 50% of Caucasian renal transplant patients develop skin malignancy within 15 years of transplantation, so patient 'D' must be advised to present early with any suspicious lesions. Some patients with chronic renal failure and diabetes mellitus may be suitable for simultaneous pancreas and kidney transplantation. Question 35. D) Renal artery stenosis Explanation: The response of the kidney to a reduction in renal perfusion pressure (such as occurs with flow-limiting stenosis in a renal artery) includes activation of the renin-angiotensin-aldosterone system through increased renin production. The resulting rise in angiotensin II concentration mediates constriction of the efferent arteriole and thereby maintains glomerular perfusion pressure distal to the stenosis. ACE inhibitors abolish this compensatory mechanism and may precipitate a marked reduction in glomerular filtration rate; close monitoring of renal function is therefore essential on starting any patient on an ACE inhibitor or angiotensin receptor blocker. Question 36. B) Membranous nephropathy Explanation: Membranous nephropathy is the most common cause of nephrotic syndrome in adults. In contrast, anti-GBM disease, post-streptococcal glomerulonephritis and small-vessel vasculitis tend to cause a 'nephritic' pattern of clinical findings. Acute tubular necrosis causes renal interstitial dysfunction and usually presents with acute renal failure. 168 The link below provides a simple and memorable summary of the spectrum of clinical presentations of glomerulonephritis. Question 37. C) Goodpasture's disease (anti-glomerular basement membrane (anti-GBM) disease) Explanation: As the name suggests, rapidly progressive glomerulonephritis (RPGN) may lead to a rapid deterioration in renal function over days to weeks. It is usually associated with the histological appearance described as focal segmental necrotising glomerulonephritis or Question 38. A) Minimal change nephropathy Explanation: Minimal change disease remits, in most cases, with corticosteroid therapy. In contrast, the other conditions listed characteristically exhibit a poor response to steroids. Question 39. E) Sensorineural deafness Explanation: Alport's syndrome is an Xlinked recessive disorder that may present with new renal failure in adulthood. It is associated with sensorineural deafness and ocular abnormalities. Question 40. E) Renal cell carcinoma Explanation: APKD is not associated with an increased risk of renal cancer. The liver may be massively enlarged but liver failure is unusual. Subarachnoid haemorrhage occurs in 10% of patients. Question 41. B) Alpha-adrenoceptor blockers Explanation: Alpha-adrenoceptor antagonists (e.g. tamsulosin) are used to improve urinary flow in BPH. All of the other options are precipitants of acute urinary retention. Question 42. A) Lytic bony metastases Explanation: Bone is by far the most common site of metastatic deposits in prostate cancer but these characteristically produce osteosclerotic rather than osteolytic lesions on plain X-ray. Bony involvement may also be indicated by an isolated rise in alkaline phosphatase and 'hotspots' on radioisotope bone scans. In practice, high levels of PSA (> 100 ng/ml) are highly suggestive of distant bony metastases. In prostate cancer the gland is usually enlarged and feels hard and irregular, often with obliteration of the median sulcus. However, it is worth noting that 10-15% of tumours are not palpable on rectal examination. 169 Question 43. B) Adrenaline (epinephrine) Explanation: Renal adenocarcinomas may secrete a wide variety of peptides that can produce a range of systemic effects. Adrenaline (epinephrine) is not usually secreted by renal adenocarcinoma, but may be secreted by a phaeochromocytoma; these two tumours may coexist in the von Hippel-Lindau syndrome. Question 44. D) Penicillamine Explanation: All of the agents listed above are potentially nephrotoxic through a variety of mechanisms (see link below) but penicillamine is a rare cause of membranous nephropathy. Chapter 17 CARDIOVASCULAR DISEASE Question 1. D) Large systolic waves are associated with tricuspid regurgitation Explanation: The internal jugular vein drains directly into the right atrium and the height of the pulse reflects right atrial pressure. It should be viewed with the patient at 45 degrees. Abdominal compression causes the JVP to rise (hepato-jugular reflux). This may aid identification of the pulsation and help distinguish it from an arterial pulsation. As a waves are caused by atrial systole, they are absent in atrial fibrillation. Question 2. D) Right coronary artery Explanation: The right coronary artery supplies the AV node in 90% of individuals, and supplies the sinoatrial node in 60%. It also supplies the inferior aspect of the heart. Inferior myocardial infarction is therefore often associated with transient sinus bradycardia and AV block. Question 3. A) Left anterior descending artery Explanation: Although the exact coronary anatomy varies greatly between individuals, the left anterior descending artery normally gives branches to the anterior part of the septum and the anterior wall and apex of the left ventricle. Question 4. D) Cholinergic nerve fibres act on the sinoatrial node to slow heart rate Explanation: Sympathetic stimulation increases heart rate (positively chronotropic) and force of contraction (positively inotropic) via _1-adrenoceptors. Beta2-receptors are found predominantly in the vasculature where they mediate vasodilatation. Parasympathetic fibres run in the vagus nerve and act to slow heart rate (negatively chronotropic) through 170 effects on the sinoatrial and atrioventricular nodes but do not influence force of contraction. Parasympathetic effects are mediated by acetylcholine and are therefore also termed 'cholinergic'. Question 5. B) Evaluation of unstable angina Explanation: Stress tests are contraindicated in the presence of unstable angina, decompensated heart failure and severe hypertension. Question 6. C) Exertional breathlessness and throat tightness Explanation: Myocardial ischaemia can sometimes present with breathlessness rather than chest pain. A sensation of throat tightness often accompanies this. Epigastric discomfort after eating could represent inferior wall ischaemia but is more likely to be dyspeptic. Wheeze is a feature of bronchospasm and not myocardial ischaemia. Accompanying paraesthesia would suggest hyperventilation syndrome. Exertional palpitation would suggest either an exercise-related arrhythmia or possibly anaemia. Question 7. B) Hypercholesterolaemia Explanation: The abnormality shown in the picture is xanthelasma, which, along with tendon xanthomas and corneal arcus, is a clinical manifestation of hypercholesterolaemia. Eruptive xanthomas would be more suggestive of hypertriglyceridaemia. Question 8. B) Exercise ECG Explanation: The exercise tolerance test (stress ECG) is highly useful in patients with symptoms suggestive of angina. It may help to confirm or refute the diagnosis as well as identify patients with high-risk features. Such patients may require further evaluation with coronary angiography. Question 9. C) Spironolactone Explanation: The goal of secondary prevention is to reduce the risk of future adverse events such as myocardial infarction. This entails measures to correct modifiable risk factors such as smoking cessation, weight loss, optimal blood pressure control and lipid-lowering therapy, as well as antiplatelet therapy. Although both an ACE inhibitor and a statin are clearly indicated in this patient to correct hypertension and hypercholesterolaemia respectively, recent trial data suggest that all patients with vascular disease benefit from angiotensinconverting enzyme (ACE) inhibition and that all patients with coronary heart disease should receive statin therapy irrespective of serum cholesterol. Spironolactone is an aldosterone antagonist beneficial in the treatment of severe chronic heart failure and also as a diuretic, particularly in cirrhotic patients with ascites. Question 10. E) Recurrent pulmonary emboli Explanation: Repeated pulmonary thromboembolic events may lead to increased pulmonary vascular resistance, pulmonary hypertension and ultimately right heart failure. The other disorders present more commonly with left-sided heart failure. Note, however, that chronically elevated left atrial pressure will also lead to pulmonary hypertension, so any cause of left heart failure may eventually result in concurrent right ventricular failure. 171 Question 11. C) Fine bi-basal crepitations Explanation: A raised JVP and pitting oedema may accompany the marked salt and water retention in left heart failure but are also characteristic findings in right heart failure. Isolated right heart failure does not lead to pulmonary venous congestion. Hepatomegaly and ascites are features of severe right heart failure. Question 12. C) Displaced apex beat Explanation: A displaced apex beat suggests left ventricular enlargement. In acute de novo heart failure there is no time for left ventricular dilatation and hence the finding of a displaced apex beat implies chronic, underlying cardiac pathology. The other features listed are all simply manifestations of acute heart failure. Question 13. B) Amlodipine Explanation: Peripheral oedema is a common side-effect of dihydropyridine calcium channel blockers, such as amlodipine and nifedipine, as they lead to increased capillary permeability. Question 14. E) Heavy proteinuria Explanation: A raised jugular venous pressure and hepatomegaly are both signs of chronic heart failure. Severe chronic heart failure is a catabolic state and commonly causes weight loss and muscle wasting (cardiac cachexia). Hyponatraemia may be caused by diuretic therapy but is also a feature of severe heart failure. Heavy proteinuria of greater than 3.5 g/day suggests nephrotic syndrome. Question 15. B) Ramipril Explanation: The mineralocorticoid hormone aldosterone acts to conserve salt and water at the expense of potassium (and hydrogen ions) in the distal convoluted tubule and collecting ducts of the kidney. The principle stimulus to aldosterone production is angiotensin II. Thus agents that inhibit the renin-angiotensinaldosterone system (e.g. ACE inhibitors, angiotensin receptor blockers) or the actions of aldosterone (e.g. spironolactone) may lead to hyponatraemia and hyperkalaemia. Loop diuretics such as furosemide typically cause hypokalaemia. Question 16. C) Beta-blockers Explanation: Although a useful treatment in patients with chronic stable heart failure, _-blockers must be avoided in patients with acute or decompensated heart failure due to their negatively inotropic effects. The other treatments listed are all commonly used to good effect in the management of acute pulmonary oedema. Question 17. C) Dry cough Explanation: As well as converting angiotensin I to angiotensin II, the angiotensin-converting enzyme (ACE) is also responsible for breakdown of bradykinin, a vasodilating peptide. Increased bradykinin levels may be responsible for the dry cough associated with ACE inhibitors. As shown in the link below, ARBs do not interfere with bradykinin metabolism and are much less likely to cause cough. Unfortunately they share all of the more serious adverse effects of ACE inhibitors such as renal dysfunction and electrolyte disturbance. 172 Question 18. D) Loop diuretics Explanation: Loop diuretics are first-line treatment to relieve symptoms in patients with chronic heart failure but have not been shown to improve outcomes. It would be ethically difficult to conduct a heart failure trial in which diuretics were withheld. The other agents listed have all been shown to reduce cardiovascular mortality and morbidity in patients with chronic heart failure in large-scale randomised controlled trials. The treatment of chronic heart failure is a topic of major importance and a comprehensive guide, including the evidence base for treatments, is provided in the link below. Question 19. B) Transient ischaemic attack Explanation: Transient loss of consciousness is due to temporary global cerebral dysfunction from either cerebral hypoperfusion (syncope) or generalised electrical discharge (seizure). Transient ischaemic attacks, by definition, produce focal cerebral dysfunction and the term should not be applied to patients presenting with blackouts. Basilar ischaemia can cause loss of consciousness but is very uncommon. Cardiac syncope occurs with arrhythmia or structural heart disease. The former is usually due to profound bradycardia (e.g. Stokes-Adams attack) or ventricular tachyarrhythmias. The latter commonly occur with exertion (e.g. severe aortic stenosis), when profound hypotension results from a combination of reduced cardiac output and fall in peripheral vascular resistance. In carotid sinus syndrome, hypersensitivity of the carotid baroreceptors causes inappropriate vasodilatation, provoking recurrent episodes of blackout or altered consciousness. Question 20. E) Rapid recovery (< 1 min) following the collapse Explanation: Events immediately before, during and after a blackout may provide useful clues to the cause. Cardiac syncope often occurs without any warning (e.g. Stokes-Adams attack) or may be preceded by chest pain, palpitation or lightheadedness (e.g. tachyarrhythmia). A history of aura preceding the blackout suggests seizure but is frequently lacking, perhaps due to post-ictal retrograde amnesia. For this reason a lack of premonitory symptoms is a fairly poor discriminator between the two. Urinary incontinence and brief twitching activity are often taken as evidence of seizure but may actually occur with any cause of blackout. Cyanosis during the unconscious period suggests seizure, while extreme 'death-like' pallor is characteristic of cardiac syncope. A rapid recovery with full reorientation within 1 minute is very suggestive of cardiac syncope and virtually excludes seizure, which is characterised by prolonged confusion, drowsiness and disorientation. Question 21. E) Defibrillation Explanation: The rhythm strip shows ventricular fibrillation characterised by completely chaotic electrical activity. The only effective treatment is defibrillation. If delivered immediately this will restore cardiac output in more than 80% of patients, but the chances of successful outcome fall by around 10% with each minute's delay. Question 22. B) Atropine Explanation: In a cardiac arrest scenario, atropine should be administered as a single dose of 3 mg when the rhythm is either asystole or pulseless electrical activity with an electrical rate of less than 60 beats per minute. Question 23. B) Mitral stenosis Explanation: The classical low-pitched rumbling diastolic murmur of mitral stenosis is often very difficult to hear and a loud first heart sound may be the most prominent auscultatory finding. 173 Question 24. E) Atrial septal defect Explanation: In atrial septal defect there is a left to right shunt because left atrial pressure exceeds right atrial pressure. The resulting increase in right ventricular stroke volume prolongs right ventricular ejection time and hence pulmonary valve closure - accounting for the wide splitting. The split between the sounds does not vary with respiration because the septal defect equalises pressures between the left and right side of the heart throughout the respiratory cycle. The increased right ventricular stroke volume may also produce a systolic flow murmur over the pulmonary valve. Question 25. D) Atrial fibrillation Explanation: A fourth heart sound is due to atrial contraction against a stiff left ventricle and is therefore not present in atrial fibrillation. Question 26. C) Mitral regurgitation Explanation: In contrast to a fourth heart sound, which is always pathological, a third heart sound may be a normal physiological finding (e.g. in young adults or pregnancy). The combination of a third heart sound and soft first heart sound may occur in mitral regurgitation or heart failure. Question 27. D) Aortic regurgitation Explanation: The murmurs of VSD, tricuspid regurgitation and pulmonary stenosis all occur in systole. Mitral stenosis typically produces a mid-diastolic murmur. The soft early diastolic murmur of aortic regurgitation is best heard with the patient sitting forward in held expiration and is often described as 'the absence of silence' following the second heart sound. The link below provides a comprehensive guide to the evaluation of heart murmurs. Question 28. B) Raised intracranial pressure Explanation: Raised intracranial pressure is associated with hypertension and bradycardia. Question 29. C) Atrial flutter Explanation: Vagal manoeuvres, such as carotid sinus massage or Valsalva manoeuvre, slow conduction through the AV node and may terminate AV nodal reentry tachycardia or reveal flutter waves (as in this case) in atrial flutter. Question 30. A) Bisoprolol Explanation: Beta-blockers are the drug of choice to prevent occasional paroxysms of AF and are particularly useful when there is associated hypertension (as in this case), ischaemic heart disease or cardiac failure. Verapamil and digoxin are both used as rate-limiting agents in persistent AF but are not effective for preventing paroxysms. ACE inhibitors are effective antihypertensives but have no antiarrhythmic properties. Amiodarone is associated with troublesome side-effects that restrict its use to those in whom other measures have failed. Question 31. D) Subtherapeutic INR Explanation: Therapeutic anticoagulation for at least 4 weeks before and 4 weeks after elective DC cardioversion is essential to minimise the risk of cerebral embolism. All of the other factors listed would reduce the chance of a successful long-term outcome from cardioversion but are not, in themselves, contraindications. In patients with relapse following previous DC cardioversion, anti-arrhythmic therapy may reduce the risk of further recurrence and help maintain sinus rhythm. Question 32. E) Amlodipine Explanation: Digoxin and _-blockers are both suitable options for rate control in atrial fibrillation. The other three options listed are calcium channel blockers (CCBs). The non-dihydropyridine CCBs (e.g. verapamil) act predominantly by slowing conduction at the AV node and exert powerful rate-limiting effects. 174 On the other hand, the dihydropyridine CCBs (e.g. amlodipine, nifedipine) act on the peripheral vasculature to produce vasodilatation. These agents are used mainly as antihypertensives and may actually cause reflex tachycardia. Diltiazem exerts both rate-limiting and vasodilating properties and may be used for rate control in AF. Question 33. C) Atrioventricular (AV) nodal re-entrant tachycardia Explanation: Adenosine transiently blocks conduction through the AV node and may therefore terminate AV nodal reentrant tachycardia. It may be of diagnostic value in atrial flutter as the slowing of conduction often reveals flutter waves but does not cardiovert this rhythm. It can also be of use in distinguishing between ventricular tachycardia and a supraventricular tachycardia with aberrant conduction. Vagal manoeuvres such as carotid sinus massage also slow or transiently block AV conduction and may be tried before adenosine. Question 34. C) Wolff-Parkinson-White syndrome Explanation: The resting ECG shows a short PR interval and slurred upstroke of the QRS complex (known as a delta wave), suggesting an accessory pathway between the atria and ventricles. The presence of an accessory pathway in association with symptoms is known as Wolff-Parkinson-White syndrome. Question 35. D) Catheter ablation of accessory pathway Explanation: Percutaneous catheter ablation of the accessory pathway is the treatment of choice in patients with symptomatic Wolff-Parkinson-White (WPW) syndrome. It is important to note that both digoxin and verapamil should be avoided in WPW as they shorten the refractory period of the accessory pathway. Amiodarone prolongs the refractory period and can be used as prophylactic therapy but is associated with troublesome long-term side-effects and is less effective than catheter ablation. Question 36. C) Presence of capture and fusion beats on ECG Explanation: A history of ischaemic heart disease (particularly previous myocardial infarction) and a QRS duration of > 140 ms both favour the diagnosis of VT. However, capture and fusion beats (see link below) are pathognomonic of VT and therefore the best answer. Other features that favour VT are extreme left axis deviation (not right axis), lack of response to carotid sinus massage/IV adenosine and evidence of atrioventricular dissociation. Note: VT is by far the most common cause of a broad complex tachycardia and if there is any doubt, manage as VT. Question 37. B) IV amiodarone Explanation: In any patient with VT the priority is to determine if there is a cardiac output. Pulseless VT is managed as a cardiac arrest in the same way as ventricular fibrillation. In patients with a cardiac output the next step is to establish if there is haemodynamic compromise (e.g. systolic BP < 90; features of shock), in which case the appropriate treatment is urgent DC cardioversion (under general anaesthetic unless unconscious). Patients, such as the one above, who tolerate the arrhythmia well may be treated in the first instance with IV amiodarone or, less commonly, IV lidocaine. They must be monitored closely for signs of deterioration with full resuscitation facilities nearby. Question 38. C) Torsades de pointes Explanation: Torsades de pointes literally means 'twisting points' and the ECG above shows the characteristic pattern of rapid irregular complexes that seem to oscillate around a fixed central axis. Question 39. D) Prolonged QT interval Explanation: Torsades de pointes is a complication of prolonged QT interval. 175 Question 40. C) Clarithromycin Explanation: Macrolide antibiotics are a well-known cause of QT interval prolongation, should be avoided in patients with long QT syndrome, and should not be used with other drugs known to cause QT prolongation, such as amiodarone and sotalol. Question 41. A) Magnesium Explanation: IV magnesium should be given in all cases. Class III antiarrhythmics, such as amiodarone and sotalol, prolong the QT interval and may exacerbate the situation. Question 42. D) Third-degree (complete) heart block Explanation: Third-degree AV block (complete heart block) results from complete failure of conduction at the AV node. Atrial impulses occur as usual, giving rise to normal P waves. The AV block results in a bradycardic ventricular escape rhythm, usually associated with wide QRS complexes due to the abnormal activation of the ventricles. In some cases, the escape rhythm can arise from the AV node itself (nodal escape) and a narrowcomplex bradycardia develops. There is no relationship between atrial and ventricular activity on the ECG (AV dissociation). Question 43. D) Dual-chamber pacemaker Explanation: This patient has a double indication for pacemaker. Patients with symptomatic bradyarrhythmias associated with atrioventricular block should receive permanent pacemakers. In addition, patients with complete heart block may derive prognostic benefit from pacemaker implantation, even in the absence of symptoms. Question 44. A) Nephrotoxicity Explanation: Digoxin has a narrow therapeutic range and is predominantly renally excreted. Consequently renal impairment may lead to digoxin toxicity and any of features B-E, but nephrotoxicity does not result from digoxin toxicity. Question 45. C) Lipid-rich core Explanation: Complications of atherosclerotic plaque rupture, notably myocardial infarction, stroke and acute limb ischaemia, are the most common cause of premature death in the developed world. Understanding the mechanisms that lead to plaque instability and developing novel therapeutic strategies to reduce the risk of rupture are therefore areas of major importance. Question 46. B) Raised high-density lipoprotein (HDL) cholesterol Explanation: Elevated HDL cholesterol is protective against atherosclerosis. Raised low-density lipoprotein (LDL) cholesterol and, to a lesser extent, triglycerides increase the risk of atherosclerosis. Question 47. E) Chest pain and 1-2 mm downward-sloping ST depression in inferior leads during stage 1 of the Bruce protocol Explanation: The most convincing ECG evidence of myocardial ischaemia is the demonstration of reversible ST segment depression or elevation that corresponds with the timing of the patient's symptoms. Horizontal and downward-sloping ST depression usually indicate myocardial ischaemia, while upward-sloping ST depression is less specific. Of the above scenarios, D and E would both constitute a positive test, but in E there is ischaemia at low workload - a high-risk finding and therefore an indication for coronary angiography. In scenario D, ischaemia occurs only at high workload and effort tolerance is good, both of which are reassuring features. A rise in pulse and BP are normal haemodynamic responses to exercise, whereas a fall in BP during a stress test is a high-risk finding. 176 The test result in scenario C should be classed as 'inconclusive'; coronary angiography may provide useful diagnostic information but other forms of stress test could also be considered (see link). Question 48. A) Clopidogrel Explanation: Clopidogrel is an antiplatelet drug used in patients intolerant of aspirin. It reduces the risk of adverse events such as myocardial infarction in patients with stable angina but does not relieve symptoms. The combination of aspirin and clopidogrel is also used in the management of acute coronary syndromes and after percutaneous coronary intervention. A comprehensive discussion of anti-anginal drugs can be found in the link below. Question 49. B) Persistent ST segment elevation on ECG Explanation: Although unstable angina may be associated with transient ST elevation, the presence of persistent ST elevation in the context of ischaemicsounding chest pain suggests an acute ST elevation myocardial infarction. Other causes of ST elevation include pericarditis and a left ventricular aneurysm (usually a long-term complication of a large anterior myocardial infarction). Question 50. C) Elevated serum cholesterol Explanation: Elevated serum cholesterol is a risk factor for the development of coronary artery disease and should be addressed as part of a secondary prevention strategy, but it is not a marker for adverse outcomes in patients with acute coronary syndromes. Question 51. D) Aspirin, clopidogrel and low molecular weight heparin Explanation: The link below includes the evidence base for this combined treatment. Additional treatment with a glycoprotein IIb/IIIa inhibitor (e.g. abciximab, tirofiban) may further improve outcomes in refractory cases, particularly in the context of percutaneous coronary intervention. Question 52. E) Coronary angiogram Explanation: This patient with unstable angina has failed to settle with medical therapy and has several high-risk features including recurrent pain at rest, ECG changes and an elevated troponin. He should therefore undergo coronary angiography with a view to revascularisation through either percutaneous coronary intervention or, if appropriate, bypass surgery. Question 53. B) Acute anterior myocardial infarction Explanation: The ECG shown was actually taken from a 48-year-old man who had developed severe chest pain 6 hours earlier. It shows acute full-thickness anterior myocardial infarction. He has ST elevation in leads I, aVL and V2-V6, and has already developed Q waves in leads V3-V5. Question 54. D) IV metoprolol Explanation: This patient has uncontrolled hypertension which is a relative contraindication to thrombolysis. If thrombolysis is the reperfusion strategy of choice for this patient, then urgent control of blood pressure is required before initiating therapy. This could be achieved with either sublingual nifedipine or IV metoprolol (oral ACE inhibitor would take too long to have an effect). In patients without contraindications (e.g. heart failure or bradycardia) intravenous _blockers relieve pain, reduce arrhythmias and improve short-term mortality, making them the best option here. Large-scale trials in acute MI have shown no survival benefit from use of magnesium or calcium channel blockers. 177 Primary percutaneous coronary intervention (PCI) is an alternative reperfusion therapy to thrombolysis that is resource-intensive but produces better outcomes. It is used in patients in whom thrombolysis is contraindicated. In some countries, it is supplanting thrombolysis as the first-line reperfusion treatment for ST elevation MI. The term 'rescue PCI' refers to the use of PCI in patients for whom thrombolysis has failed to achieve reperfusion. Question 55. B) IV atropine Explanation: The admission ECG shows acute inferolateral myocardial infarction (MI). Inferior MI is often complicated by sinus bradycardia and transient atrioventricular (AV) block, due to ischaemia of the sinus node and AV node respectively. The correct initial treatment for symptomatic sinus bradycardia is atropine 0.6 mg IV repeated, if necessary, to a maximum of 3 mg. AV block may also respond to atropine or resolve with reperfusion but, if symptomatic, may require temporary pacemaker insertion. A permanent pacemaker is very rarely needed as the block almost always resolves within 7-10 days. Question 56. E) Isosorbide mononitrate Explanation: In addition to lifestyle modifications, and in particular smoking cessation, the first four agents listed form the core of secondary prevention following acute MI. Aspirin reduces the risk of further infarction and other vascular events by 25% and _-blockers reduce long-term mortality by 25%. The benefits of ACE inhibitors and statins following MI extend to patients with preserved left ventricular function and serum cholesterol levels within the normal range. Isosorbide mononitrate offers no prognostic benefit but might improve symptoms in patients who continue to experience exertional angina post-infarction. Question 57. B) Night pain Explanation: Chronic lower limb ischaemia manifests as two distinct clinical entities: intermittent claudication (IC) and critical limb ischaemia (CLI). The latter is by far the more dangerous condition; it is almost always due to severe multi-level disease and carries a high risk of limb loss and mortality within a matter of months. Night pain is one of the cardinal features of CLI. Diminished pedal pulses are a common finding in both IC and CLI and the presence of a bruit provides no information on disease severity. ABPI, on the other hand, is a simple but useful guide to severity. A ratio of 0.8 is typical of IC; it is usually < 0.5 in CLI. Question 58. C) Previously undiagnosed atrial fibrillation Explanation: An obvious embolic source such as atrial fibrillation would increase the probability of embolism, particularly if it were a new finding, as the patient would almost certainly not be anticoagulated. All of the other features listed would favour thrombotic occlusion of a previously diseased artery. Question 59. D) New early diastolic murmur Explanation: Type B dissections may involve the descending aorta and aortic arch but, by definition, spare the ascending aorta. A new early diastolic murmur suggests aortic regurgitation and hence involvement of the aortic root. Question 60. A) Hyperlipidaemia Explanation: The pathogenesis of essential hypertension is poorly understood but all of the factors listed other than hyperlipidaemia (which is a risk factor for atherosclerosis) are contributing environmental factors. 178 Question 61. E) Addison's disease Explanation: The vast majority (95%) of patients with hypertension have no specific underlying pathology but in a small proportion of patients the elevated blood pressure may be due to endocrine disease, renal disease, drugs or coarctation of the aorta. Addison's disease (primary adrenal insufficiency) frequently presents with hypotension. Question 62. D) Thiazide diuretic Explanation: Thiazide diuretics (e.g. bendrofluazide) or calcium channel blockers are recommended first-line therapy for elderly patients with hypertension. Question 63. C) Calcium channel antagonist Explanation: See Guide to management of hypertension Question 64. C) Acute rheumatic fever Explanation: This teenage patient has evidence of recent streptococcal infection (ASOT > 200 U/ml), pericarditis and mitral regurgitation, making rheumatic fever the most likely diagnosis. Question 65. E) Flitting polyarthritis Explanation: The diagnosis of acute rheumatic fever is based on the revised Jones criteria, and requires evidence of recent streptococcal infection as well as two or more major manifestations, or one major and two or more minor manifestations. This patient already has sufficient evidence of streptococcal infection in the form of elevated antistreptolysin O titres so a positive throat swab is incorrect. He currently fulfils one of the major criteria ('carditis') and cardiac dilatation would simply provide further evidence of this criterion. Fever and a prolonged P-R interval are both minor criteria so neither one would be sufficient for diagnosis. Flitting polyarthritis is another of the major criteria (seen in 75% of patients) and would therefore clinch the diagnosis. The revised Jones criteria are included in the link below. Question66. D) Mitral stenosis Explanation: The signs listed are typical of mitral stenosis, as is the history of slowly progressive symptoms. Atrial fibrillation is an extremely common complication owing to left atrial enlargement. Aortic regurgitation typically causes an early diastolic murmur and large volume pulse. Question 67. E) Loud pulmonary component of second heart sound (P2) Explanation: A loud S1, opening snap and tapping apex beat are all classical signs of mitral stenosis. The presence of a pansystolic murmur radiating to the axilla would suggest concomitant mitral regurgitation. Clinical findings suggestive of pulmonary hypertension include a loud P2 and parasternal heave (right ventricular hypertrophy), signs of tricuspid regurgitation (secondary to right ventricular dilatation) such as systolic waves in the jugular venous pulse and, ultimately, signs of right ventricular failure such as pitting oedema and ascites. Question 68. B) Concomitant mitral regurgitation Explanation: Mitral balloon valvuloplasty is the treatment of choice for patients who fulfil the necessary criteria. The presence of mitral regurgitation is a contraindication. Question 69. E) Congenitally bicuspid mitral valve Explanation: This one is a bit of a trick question, as the normal mitral valve is bicuspid. A congenitally bicuspid aortic valve (usually tricuspid) may predispose to either aortic stenosis or regurgitation. 179 Question 70. B) Third heart sound (S3) Explanation: Atrial fibrillation, pulmonary congestion and pulmonary hypertension (loud P2 and right ventricular heave) commonly complicate both mitral stenosis and regurgitation. A third heart sound is caused by rapid filling of the left ventricle during diastole; therefore, its presence effectively excludes significant mitral stenosis but is characteristic of mitral regurgitation. Question 71. E) Slow-rising carotid pulse Explanation: A slow-rising pulse is a characteristic finding in aortic stenosis, often accompanied by a narrow pulse pressure, heaving but non-displaced apex beat and a soft A2. In general, left-sided heart murmurs are louder in expiration; right-sided heart murmurs are louder in inspiration. Question 72. A) Syncopal episodes Explanation: Reduced valve area and a high pressure gradient across the valve are both indicators of severity in aortic stenosis, but the presence of symptoms is by far the most important indication for valve replacement. Question 73. B) Acute aortic dissection Explanation: Bounding pulses, a wide pulse pressure and displaced apex beat are characteristic of severe chronic aortic regurgitation due to left ventricular dilatation and increased stroke volume consequent upon chronic volume overload of the left ventricle. Syphilitic aortitis, rheumatic heart disease, Marfan's syndrome and ankylosing spondylitis are all well-recognised causes. However, in acute aortic regurgitation (e.g. secondary to involvement of aortic root in acute aortic dissection) there is no time for compensatory hypertrophy and dilatation of the ventricle. The apex beat is therefore not displaced and the clinical picture tends to be dominated by features of heart failure and hypotension. Question 74. A) Viridans streptococci Explanation: Streptococci of the viridans group are the most common cause of native valve endocarditis, accounting for 30-40% of cases. They tend to cause subacute endocarditis with a presentation like the one described above. In contrast, Staph. aureus endocarditis usually presents as a severe acute febrile illness. It is a common organism in IV drug misusers, often affecting right-sided valves. Coagulase-negative staphylococci, such as Staph. epidermidis, are frequent culprits in prosthetic valve endocarditis. Coxiella burnetti is the causative agent in Q fever, a cause of culture-negative endocarditis. Question 75. D) Benzyl penicillin and gentamicin Explanation: In this patient with subacute endocarditis, streptococci are the most likely causative agents and, therefore, combined treatment with benzyl penicillin and gentamicin is the best choice of empirical therapy. The management of infective endocarditis, including rationale for choice of antibiotic, is described in the link below. Question 76. D) Vegetations on echocardiography Explanation: See Modified Duke criteria 180 Question 77. C) Patent ductus arteriosus Explanation: More on Patent ductus arteriosus Question 78. A) Ventricular septal defect Explanation: This patient has developed Eisenmenger's syndrome and therefore the original underlying abnormality must have involved a left-right shunt, e.g. ventricular septal defect or patent ductus arteriosus. In patent foramen ovale there is a connection between the left and right side of the heart but no significant shunt. The other options, in isolation, are not associated with shunting of blood and are not causes of cyanotic heart disease. Question 79. D) Patent ductus arteriosus Explanation: More on Tetralogy of Fallot Question 80. A) Tuberculosis Explanation: The patient has symptoms and signs of severe right heart failure with no obvious features of left heart failure, a normal-sized heart and heavy calcification of the pericardium. The diagnosis is constrictive pericarditis. In a patient from West Africa the most likely underlying diagnosis would be tuberculosis. This is a common presenting feature of AIDS in West Africa and he should be offered HIV testing. Haemochromatosis and trypanosomiasis may both cause a cardiomyopathy. Chapter 18 RESPIRATORY DISEASE Question 1. C) PaCO2 of 5.8 kPa Explanation: The other features all suggest a severe asthma attack but only answer C is a life-threatening feature. Patients with acute severe asthma should have a depressed PaCO2 on account of the increased alveolar ventilation. Even a normal PaCO2 is a sign that the patient is struggling to overcome the obstruction to airflow and, perhaps, beginning to tire from the effort of breathing. In this case the PaCO2 is at the high end of the normal range and, in addition to other appropriate measures, the intensive treatment unit should be alerted. Question 2. B) Chronic obstructive pulmonary disease (COPD) Explanation: This lifelong smoker has an obstructive ventilatory defect that is not reversible by inhaled bronchodilators. Her lungs are hyperexpanded and there is no clinical evidence of pulmonary oedema or fibrosis. Question 3. B) Compensated respiratory acidosis Explanation: The results show a respiratory acidosis (high PaCO2) that is completely offset by a metabolic alkalosis (high HCO3-), so that the overall pH of the blood is normal. By far the most likely explanation for this is chronic type II respiratory failure with metabolic compensation. The only theoretical alternatives are complete respiratory compensation for metabolic alkalosis or concomitant but unrelated respiratory acidosis and metabolic alkalosis. In practice, the former does not occur and the latter is extremely unlikely. 181 Question 4. D) Smoking cessation Explanation: Smoking cessation is one of the very few interventions shown to prolong life in COPD. Nebulised and inhaled ß2-agonists provide symptomatic relief but do not influence prognosis. Oral steroids are useful in the treatment of acute exacerbations but have no role in maintenance treatment; inhaled steroids may reduce the number of acute exacerbations and hospital admissions in patients with severe disease and frequent exacerbations. Tiotropium is a once-daily inhaled anticholinergic treatment which improves both symptoms and effort tolerance but, like ß2-agonists, has not been shown to reduce mortality. Question 5. D) Transfer to a critical care environment and consider endotracheal intubation by an experienced anaesthetist Explanation: The likely diagnosis is acute epiglottitis. The acute onset makes noninfectious causes of stridor, such as tumour compression of the trachea, less likely, so a CT would be of limited use. In epiglottitis, the problem is the potential for sudden airway occlusion. Nebulised bronchodilators will offer no benefit, while arterial blood gas analysis is unlikely to provide much useful information and may exacerbate the situation by distressing the patient. Examination of the throat is extremely dangerous and should be avoided. The patient must be managed with intravenous antibiotics in facilities appropriate for endotracheal intubation if necessary. Question 6. C) Stony dull percussion note at left base Explanation: The patient has a moderate to large left-sided pleural effusion which will manifest clinically as reduced expansion of the left hemithorax accompanied by stony dullness to percussion, reduced or absent breath sounds, and reduced or absent vocal resonance over the left base and mid-zone. Large effusions can cause tracheal and mediastinal shift although, from the chest X-ray, there does not appear to be any tracheal deviation in this case. Question 7. D) Pleural aspiration Explanation: The patient has a unilateral pleural effusion. The most helpful investigation in establishing the cause will be evaluation of the pleural fluid obtained by simple aspiration. The appearance of the fluid should be noted (e.g. bloodstained, purulent) and it should then be sent for biochemical, microbiological and cytological analysis. Question 8. B) Parapneumonic effusion Explanation: The pleural effusion is an exudate. We know this because the pleural fluid protein is more than half the plasma protein content and also because the pleural fluid LDH is > 60% of the plasma LDH (see Light's criteria in the link below). Nephrotic syndrome and cardiac failure cause transudative effusions. Acute pancreatitis is highly unlikely in the absence of either abdominal pain or a raised serum amylase. Thoracic duct occlusion causing chylothorax is very rare and the pleural aspirate would have a milky rather than serous appearance. The diagnosis of parapneumonic effusion is further supported by the patient's confusion, the raised white cell count and the low pH of the pleural fluid. Establishing the cause of a pleural effusion is a commonly encountered problem in clinical practice and more information can be found in the link below. 182 Question 9. A) Psychogenic hyperventilation Explanation: Psychogenic hyperventilation is, to a large extent, a diagnosis of exclusion, and alternative possibilities such as pneumothorax and particularly pulmonary embolism should always be considered. However, there are several pointers towards the diagnosis here, most notably the inability to take a deep breath, history of recurrent episodes, absence of chest signs and reassuring oxygen saturations. The hyperventilation causes a respiratory alkalosis that may lead to paraesthesiae in the hands and feet and carpopedal spasm - both useful distinguishing features. Question 10. B) Rusty, golden yellowcoloured sputum Explanation: Pneumocystis carinii pneumonia (PCP) (caused by Pneumocystis jirovecii) typically presents with a dry, non-productive cough; rustybrown spit is a classical finding in pneumococcal pneumonia. PCP is a common and life-threatening infection in AIDS sufferers. At presentation, dyspnoea, fever and a dry cough are usual. The dyspnoea is out of proportion to the chest X-ray changes; indeed, many patients have a normal chest X-ray and most have no focal abnormalities on chest auscultation. Induced sputum is the diagnostic test of choice for PCP. Clinical findings suggestive of HIV infection, such as oropharyngeal candidiasis or oral hairy leukoplakia, would also raise suspicion. Question 11. E) Intravenous aminophylline Explanation: This patient has several features to suggest this is an acute severe asthma exacerbation (respiratory rate > 25/min, heart rate > 115, PEF < 50% predicted, inability to speak in sentences) and she should be managed accordingly. Options A-D are all key steps but intravenous aminophylline should only be used in patients who fail to respond to these and other measures (e.g. intravenous magnesium) and, even then, usually under specialist supervision. More information on assessment of asthma severity can be found in Q1 and further details of the management of asthma exacerbations in the link below. Question 12. C) Refer to the intensive treatment unit for consideration of mechanical ventilation Explanation: The patient has deteriorated significantly despite maximal medical therapy and this is now a life-threatening asthma attack (PEF < 33% predicted, high alveolar/arterial oxygen gradient, rising PaCO2, quiet breath sounds, exhaustion). She is likely to require intubation and mechanical ventilation imminently and should be referred to ITU without delay. Note that, although non-invasive ventilation may be useful in exacerbations of COPD, it has no role in the management of acute severe asthma. Likewise, in acute asthma, the presence of a high or rising PaCO2 must not be taken as an indication to reduce oxygen concentration but rather as a warning of deterioration and possible need for intubation and mechanical ventilation. Question 13. D) Anticholinergic Explanation: Ipratropium is an anticholinergic bronchodilator. Tiotropium is a newer, once-daily preparation. Nebulised ipratropium forms part of the treatment of acute severe asthma but its main use is in the management of COPD. 183 Question 14. D) Viral pneumonia Explanation: Viral pneumonia is very unlikely to have lasted several months and would be associated with chest X-ray changes. The other options in this question are reasonable differential diagnoses for a patient with a persistent cough, although bronchogenic carcinoma must also be considered, particularly in smokers. Cough may be the dominant symptom in asthma with little or no breathlessness or wheeze. Question 15. B) Aggressive fluid resuscitation is necessary immediately Explanation: Community-acquired pneumonia is by far the likeliest diagnosis here; non-specific elevation of D-dimer occurs in a number of conditions other than pulmonary embolism, including pneumonia. She has severe sepsis with evidence of haemodynamic compromise and requires prompt, aggressive fluid resuscitation, ideally with monitoring of both urine output and central venous pressure; she may require inotropic support and invasive ventilation if her condition does not improve. Current British Thoracic Society guidelines specify four markers of severity in community-acquired pneumonia, known as the CURB score: • confusion • urea > 7 mmol/l • respiratory rate > 30/min • low BP (systolic < 90 mmHg or diastolic < 60 mmHg). This patient has all four markers and is undoubtedly in the severe category. She requires immediate treatment with intravenous third-generation cephalosporin and macrolide; it is inappropriate to delay pending the results of cultures. Her management should be supervised in a high-dependency or intensive care unit. Management on a general medical or general respiratory ward is inappropriate for someone this ill. Question 16. B) Pulmonary embolism Explanation: The sudden onset of symptoms, pleuritic chest pain and lack of change in sputum favour the diagnosis of pulmonary embolism over infective exacerbation of COPD. She also has a risk factor for thromboembolism in the form of oestrogen-containing hormone replacement therapy. One would expect chest X-ray changes in acute left ventricular failure or pneumonia; psychogenic hyperventilation should not be considered as a diagnosis in the presence of hypoxia. Question 17. A) Computed tomography pulmonary angiogram (CTPA) Explanation: In a patient with preexisting lung disease such as COPD, in whom a pulmonary embolism (PE) is suspected, CTPA is undoubtedly the investigation of choice. A V/Q scan may be hard to interpret, as existing lung disease may cause perfusion defects and the majority of such cases are reported as 'indeterminate'. Echocardiography may help in the urgent diagnosis of massive PE in patients with circulatory collapse by identifying features of acute right heart strain, but is less likely to be helpful in this situation. The value of D-dimer is the high negative predictive value conferred by a low result. It is, however, non-specific and a positive D-dimer, no matter how high, would not confirm the diagnosis. HRCT is mainly used in the assessment and diagnosis of diffuse interstitial lung disease and bronchiectasis. Question 18. B) Percussion and auscultation of the lung fields Explanation: The most likely diagnosis is tension pneumothorax, which can and must be diagnosed on clinical examination. Reduced breath sounds and hyper-resonant percussion note on the affected side confirm the diagnosis, and immediate needle thoracocentesis should be performed. 184 Question 19. C) Fibrotic lung disease Explanation: These are all classical findings in pulmonary fibrosis. Cystic fibrosis presents at an earlier age; however, severe bilateral bronchiectasis might explain the findings, although the crackles would tend to be coarse. Question 20. A) Larynx and central airways Explanation: A useful fact to help understand examination findings. Question 21. D) Three lobes on the right, two on the left Explanation: This crucial fact is essential for correct interpretation of all lung imaging. Question 22. C) Sarcoidosis Explanation: The skin lesion described is characteristic of erythema nodosum. The combination of erythema nodosum, arthralgia, constitutional symptoms and isolated BHL on chest X-ray is highly suggestive of sarcoidosis. Question 23. D) Reduced midexpiratory flow indicates collapse of small intrathoracic airways Explanation: The loop shows the classical pattern of intrathoracic small airways obstruction, as seen in chronic obstructive pulmonary disease (COPD). Large airway obstruction limits peak inspiratory and/or peak expiratory airflow (depending on the site of obstruction), producing a plateau on the loop. Vital capacity is frequently reduced in obstructive ventilatory defects, but the proportional reduction in forced expiratory volume in 1 second (FEV1) is greater, giving a reduced FEV1/vital capacity (VC) ratio. The loop shows that peak expiratory flow is reduced. At a given lung volume, the limitation of flow is much greater during expiration than inspiration, indicating dynamic collapse of the small intrathoracic airways. Question 24. E) Functional residual capacity Explanation: A full explanation of all of the above terms and uses of respiratory function tests in clinical practice can be found in the link below. Question 25. A) Chest X-ray Explanation: Pneumothorax should be excluded in any apparent acute severe asthma exacerbation, especially when there are supportive clinical findings. Question 26. A) Long-term oxygen therapy Explanation: Long-term domiciliary oxygen therapy has been shown to improve survival in selected patients with COPD. Question 27. D) Calcification on chest X-ray Explanation: Calcification may be found in malignant tumours, particularly on CT, but more often it indicates a granuloma, perhaps from old tuberculosis. Question 28. C) Protuberant mandible Explanation: A recessed mandible is associated with airway obstruction during sleep. Question 29. B) Arterial blood gas (ABG) analysis Explanation: The most likely cause of this patient's deterioration is type II respiratory failure. An ABG is essential to confirm this, assessing the severity and guiding further management. Question 30. E) Mechanical ventilatory support Explanation: This patient is in extremis and at high risk of imminent cardiac arrest because of hypoxia. Her normal bicarbonate shows that this is an acute not a chronic deterioration, therefore probably reversible. Her oxygen must not be reduced, but unfortunately increasing it is unlikely to be enough to save her, particularly as this may further decrease her respiratory drive. The best solution is mechanical ventilatory support, which can be delivered by non-invasive bi-level ventilation or by intubation in an ITU. Question 31. E) Severe kyphoscoliosis Explanation: Type I respiratory failure refers to hypoxia (PaO2 < 8 kPa) with a normal or low PaCO2 (i.e. failure of oxygenation) and is primarily caused by ventilation-perfusion mismatch. 185 Type II respiratory failure is hypoxia (PaO2 < 8 kPa) in the presence of hypercapnia (PaCO2 > 6.6 kPa) and is due to inadequate ventilation (not 'blowing off' sufficient CO2). It is important to bear in mind that any cause of type I respiratory failure may progress to type II if exhaustion supervenes. Question 32. C) A trial of itraconazole should be considered Explanation: The most likely diagnosis is allergic bronchopulmonary aspergillosis (ABPA), caused by a hypersensitivity reaction to Aspergillus fumigatus. Common manifestations include fever, breathlessness, cough productive of bronchial casts and worsening of asthmatic symptoms, which may be accompanied by radiographic evidence of transient diffuse pulmonary infiltrates and lobar or segmental pulmonary collapse. Other characteristic features include an elevated peripheral blood eosinophilia (> 0.5 × 109/l), positive skin test to an extract of A. fumigatus, serum precipitating antibodies to A. fumigatus and an elevated total serum IgE. Fungal hyphae of A. fumigatus may be seen on microscopic examination of sputum (which will be rich in eosinophils). The optimum maintenance therapy for ABPA is uncertain. Regular therapy with low-dose oral corticosteroid therapy (prednisolone 7.5-10 mg daily) is prescribed to suppress the immunopathological responses and prevent progression to tissue damage. Therapy with itraconazole may be beneficial in some patients. As this patient has never smoked and lobar collapses have occurred in two different sites, lung cancer is unlikely. Question 33. B) Non-steroidal antiinflammatory drugs Explanation: Non-steroidal antiinflammatory drugs and ß-blockers are the drugs most frequently implicated in exacerbations of asthma. Beta-agonists and leukotriene receptor antagonists are used in the management of asthma. Question 34. B) A 20% improvement in forced expiratory volume in 1 second (FEV1) following administration of a bronchodilator Explanation: All of these may be present in an asthmatic patient, but only B clinches the diagnosis according to current criteria. Asthma is a very common disease, so a knowledge of the diagnosis is essential. Question 35. B) Addition of long-acting ß2-adrenoceptor agonist Explanation: It is always important in this situation to check inhaler technique, adherence to treatment and avoidance of aggravating factors first before increasing drug therapy. Long-acting inhaled ß2agonists (e.g. salmeterol) are first choice of add-on therapy for patients whose symptoms are inadequately controlled on regular inhaled corticosteroid and an asrequired short-acting ß2-agonist. Asthma treatment is guided by a stepwise treatment model, based on good clinical evidence and detailed in the link below. Question 36. C) 76-year-old ex-smoker with bilateral pitting oedema to knees and maximum PaO2 of 7.7 kPa on two ABGs 3 weeks apart Explanation: Criteria for LTOT are based on two sets of ABG measurements taken at least 3 weeks apart in clinically stable patients on optimal medical therapy. To qualify, patients must have stopped smoking and demonstrate either: • PaO2 < 7.3 kPa (and FEV1 < 1.5 litres) • PaO2 7.3-8 kPa plus pulmonary hypertension, peripheral oedema or nocturnal hypoxaemia. Only the patient in C meets these requirements. LTOT is one of the few treatments that favourably alters prognosis in COPD. More information can be found in the link below. Question 37. A) Autosomal recessive Explanation: The gene for CFTR (cystic fibrosis transmembrane conductance regulator) is on the long arm of chromosome 7. A defect in the genes encoding CFTR from both parents is required for clinical disease. 186 Interestingly, heterozygotes (who have one normal and one abnormal CFTR gene) appear to have some protection from fluid loss in gastroenteritis such as cholera. Question 38. B) Amiodarone Explanation: See list of Drug-induced respiratory diseases Question 39. B) Tuberculosis Explanation: Caseating granulomas are a classic finding in tuberculosis, which is often discovered after a 'cryptic' presentation such as this, particularly in the elderly. Question 40. C) Right upper lobe collapse Explanation: This chest X-ray has the classic appearance of right upper lobe collapse. The link below shows the chest X-ray features associated with collapse of the other lobes. Question 41. B) Small-cell bronchogenic carcinoma Explanation: Lobar collapse in a smoker is commonly due to lung cancer. Of the various histological subtypes of bronchial carcinoma, small-cell carcinoma most commonly causes hyponatraemia through ectopic inappropriate secretion of antidiuretic hormone (ADH). Question 42. C) Squamous carcinoma Explanation: Squamous cell cancers may cause hypercalcaemia by secreting ectopic parathyroid hormone (PTH). Small-cell carcinomas commonly secrete antidiuretic hormone (ADH) and adrenocorticotrophic hormone (ACTH). Question 43. A) Continued cigarette smoking Explanation: Cigarette smoking is a contraindication to domiciliary oxygen therapy but this is on the grounds of safety (oxygen is a fire hazard). It is not a contraindication to surgical resection of bronchial carcinoma. Question 44. E) Asthma Explanation: Asthmatic patients often have relatively normal lung function at rest so asthma is not usually associated with chronic hypoxaemia and the majority of patients have normal pulmonary artery pressures. In contrast, the other conditions listed cause progressive pulmonary hypertension, which is associated with increased complications and mortality. Question 45. D) Rheumatic fever Explanation: Connective tissue disorders may lead to pulmonary fibrosis and a variety of other respiratory complications. Rheumatic fever may cause pleurisy or a pleural effusion, but not fibrosis. Question 46. E) Intravenous endothelin Explanation: Endothelin is a potent pulmonary vasoconstrictor. The endothelin receptor antagonist bosentan has shown some promising results in pulmonary hypertension. Question 47. B) The most likely diagnosis is silicosis Explanation: This history and the chest X-ray appearances are highly suggestive of silicosis. Silicosis results from the inhalation of crystalline or free silica, usually in the form of quartz. Occupations at risk include stonemasons, sandblasters and miners. Silica is highly fibrogenic and even when exposure to dust ceases, the 187 disease is often progressive. The patient should, therefore, be removed from the offending environment as soon as possible. Enlargement of the hilar glands with an 'egg-shell' pattern of calcification is said to be a characteristic chest X-ray appearance but is uncommon and nonspecific. The appearances described are not those of miliary tuberculosis; however, it should be remembered that patients with silicosis may be at increased risk of tuberculosis - so-called 'silicotuberculosis'. The recognition of occupational lung disease should prompt screening of the workplace to identify other affected individuals. Question48. B) The clinical scenario could be explained by bleomycin toxicity Explanation: It is correct to consider a diagnosis of PCP; however, induced sputum is generally the investigation of choice. Bronchoalveolar lavage may be considered as a second-line investigation. In this case induced sputum samples for PCP and cytomegalovirus were negative and the most likely diagnosis was bleomycin-induced pneumonitis. Lung function tests classically show a restrictive defect and patients typically desaturate on exertion. HRCT will confirm the presence of interstitial inflammation but is not usually diagnostic. Chapter 19 ENDOCRINE DISEASE Question 1. B) Thyroid-stimulating hormone (TSH) Explanation: The thyroid is the only tissue which makes significant physiological use of iodine. The functional unit of the thyroid gland is the follicle, consisting of central colloid surrounded by follicular epithelial cells. Inorganic iodide is trapped and transported into these cells and organified by the enzyme thyroid peroxidase; thereafter the iodine is bound to thyroglobulin protein. This iodinated molecule is cleaved to release the thyroid hormones thyroxine (T4) and triiodothyronine (T3). T4 can be converted to either T3 or rT3 in peripheral tissues. A dietary iodide intake greater than 100 µg per day is necessary for thyroid hormone synthesis. Thyroid-stimulating hormone (TSH, thyrotrophin) is a glycoprotein released from the anterior pituitary which stimulates the whole process, and is subject to negative feedback from T4 and T3. TSH does not contain iodine. The antiarrhythmic drug amiodarone contains large amounts of iodine. Question 3. E) Toxic thyroid adenoma Explanation: In toxic adenoma there is increased isotope uptake by the adenoma. However, excessive thyroxine production by the adenoma inhibits pituitary thyroidstimulating hormone (TSH) secretion so that the remainder of the thyroid gland is suppressed, resulting in negligible isotope uptake. In toxic multinodular goitre there is patchy uptake by the hyperfunctioning nodules. Thyroiditis is associated with low isotope uptake by the thyroid as the follicular cells are not functioning normally during a temporary inflammation of the gland. (The excess thyroid hormone is released from stores within the follicle, rather than synthesised de novo.) Thyroid malignancies are not usually associated with derangements of thyroid function and are visible as 'cold' (low-uptake) areas on a scintigraphy scan. Medullary carcinoma arises from the parafollicular C cells which produce calcitonin. A very useful guide to establishing the diagnosis in thyrotoxicosis is provided in the link below. Question 2. C) Graves' thyrotoxicosis Explanation: The raised T4 with undetectable TSH levels indicates primary thyrotoxicosis. The most common cause of thyrotoxicosis is the autoimmune condition, Graves' disease. TSH receptor antibodies are very rare in patients without autoimmune thyroid disease and their presence therefore confirms the diagnosis. Note, however, that 5-20% of patients with Graves' disease are negative for these antibodies; had the result been negative rather than positive, this would not have excluded the diagnosis of Graves' disease and further tests (thyroid scintigraphy) might have been required. Question 4. B) Lid lag Explanation: Lid retraction (visible sclera above the iris) and lid lag (delay in downward movement of the upper eyelid during downgaze) can occur with all causes of thyrotoxicosis. They result from the effect of increased sympathetic activity on the levator palpebrae superioris muscles. The other listed ocular features are only seen in Graves' disease, although their presence is unrelated to the severity of the thyrotoxicosis. Ophthalmoplegia and diplopia result from swelling and eventual fibrosis of the extraocular muscles. Other features specific to Graves' are pretibial myxoedema and thyroid acropachy (finger clubbing). 188 Question 5. D) Thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) Explanation: Stimulating TRAb antibodies are responsible for stimulating the TSH receptors and causing thyrotoxicosis. Occasionally, blocking TRAb antibodies cause episodes of hypothyroidism in patients with autoimmune thyroid disease. Routine assays cannot distinguish stimulating from blocking antibodies but TRAbs are present in up to 95% of patients with Graves' disease and are rare in patients with other forms of thyroid disease. Question 6. B) Propranolol Explanation: Thyrotoxicosis is an important cause of atrial fibrillation (AF). Of the agents listed above, the nonselective _-blocker propranolol is best for AF associated with hyperthyroidism and is also useful for many other symptoms of hyperthyroidism (particularly tremor) which are mediated by increased sympathetic activity. Ventricular rate in thyrotoxic patients with AF characteristically responds poorly to digoxin. Prolonged use of amiodarone can lead to hyper- or hypothyroidism. Acute DC cardioversion is reserved for those patients who are haemodynamically compromised by the rapid ventricular rate. Two other key elements of this patient's management will be definitive treatment of her thyrotoxicosis and anticoagulation (thromboembolic complications are particularly common in thyrotoxic AF). Question 7. D) Hyperprolactinaemia Explanation: The most common causes of hypothyroidism in the UK are autoimmune disease (including Hashimoto's thyroiditis) and thyroid failure following thyroidectomy or radio-iodine therapy. Transient thyroiditis (e.g. de Quervain's thyroiditis, post-partum thyroiditis) is often associated with an initial thyrotoxic phase, followed by transient hypothyroidism. Although Graves' disease usually causes hyperthyroidism, the thyroid-stimulating hormone (TSH) receptor antibodies can sometimes have a blocking effect rather than a stimulatory one, resulting in hypothyroidism. 189 Hyperprolactinaemia does not cause hypothyroidism but may occur as a result of primary hypothyroidism due to increased hypothalamic thyrotrophinreleasing hormone (TRH) secretion (TRH stimulates prolactin release). Question 8. C) Start treatment with thyroxine Explanation: This patient has primary hypothyroidism, as indicated by the low T4 level with raised TSH. She has clinical symptoms of hypothyroidism and treatment with thyroxine is required. The positive anti-thyroid peroxidase antibody result suggests an autoimmune cause such as Hashimoto's disease. Imaging of the thyroid gland is unlikely to provide any additional information, and such cases can generally be managed in the primary care setting. Carbimazole is used in the treatment of hyperthyroidism. Question 9. B) Normal ageing Explanation: As phenytoin and rifampicin are liver enzyme inducers, they increase metabolism of thyroxine, often necessitating an increase in the thyroxine dose. In coeliac disease there is malabsorption, so a higher dose of oral thyroxine may be required. Pregnancy is associated with increased levels of thyroid-binding globulin; a greater proportion of thyroid hormone is therefore bound to protein, and an increased thyroxine dose may be needed to maintain the same levels of free active thyroid hormone. Ageing leads to a reduction in thyroxine clearance and smaller doses of thyroxine are often required. Question 10. D) Give IV triiodothyronine and IM hydrocortisone Explanation: Myxoedema coma is a rare presentation of hypothyroidism. It has a 50% mortality rate and needs urgent treatment even before biochemical confirmation of the diagnosis. IV triiodothyronine replacement is required. Unless it is clear that the patient has primary hypothyroidism (e.g. thyroidectomy scar), hydrocortisone should also be administered to cover the possibility of coexisting corticosteroid deficiency due to hypothalamic or pituitary disease. In hypopituitarism, administration of thyroid hormone in advance of hydrocortisone replacement can be dangerous, as the increase in metabolic rate may precipitate an adrenal crisis. Supportive measures (e.g. oxygen, IV fluids and rewarming) are also important, but the bradycardia is appropriate to her slow metabolic rate and is likely to respond to hormone replacement. Question 11. A) Facial nerve injury Explanation: Complications of subtotal thyroidectomy are rare. A hoarse voice or change in voice quality can result from damage to the recurrent laryngeal branch of the vagus (X) nerve, but there is no risk of injury to the facial (VII) nerve. Around 25% of patients become hypothyroid following surgery and require temporary treatment with thyroxine, but permanent hypothyroidism is rare. Transient (10%) or permanent (rare) hypocalcaemia can occur due to damage to the parathyroid glands or their blood supply, and careful monitoring of serum calcium is important during the post-operative period. Exacerbation of Graves' ophthalmopathy is thought to be a complication of radio-iodine treatment (not surgery), and prophylactic therapy with corticosteroids reduces this risk. Question 12. C) The risk of relapse is greater than 30% within 2 years of stopping the drug Explanation: The antithyroid drugs carbimazole and propylthiouracil act by inhibiting the iodination of tyrosine and thereby reducing thyroid hormone synthesis. 190 Since episodic relapse and remission is the most common pattern in the natural history of Graves' thyrotoxicosis, carbimazole is usually given for 12-18 months in the anticipation that the disease will be in remission when the drug is discontinued. However, thyrotoxicosis recurs in at least 50% of patients within 2 years of stopping treatment. Subtotal thyroidectomy or radioactive iodine therapy may then be preferred. Agranulocytosis is a rare side-effect of carbimazole, occurring in 0.2% of patients; patients are therefore advised to undergo urgent testing of their full blood count in the event of a sore throat or fever. Although carbimazole and propylthiouracil are only excreted in small amounts in breast milk, propylthiouracil is thought to be safer. Question 13. A) Medullary carcinoma Explanation: Medullary carcinoma arises from the parafollicular C cells of the thyroid. Tumour cells secrete calcitonin, and serum levels can be used to monitor response to treatment. The condition presents in middle age with a firm thyroid mass, and treatment is by total thyroidectomy. Thyroid function tests are normal and there is no role for radioiodine therapy. Question 14. B) Carbimazole Explanation: 'Differentiated' (papillary and follicular) thyroid carcinomas usually present as palpable nodules for which the initial investigation of choice is fine needle aspiration cytology. They are usually treated by total thyroidectomy followed by a large dose of 131iodine to ablate any residual thyroid tissue. Subsequent long-term treatment with thyroxine at a dose sufficient to suppress thyroid-stimulating hormone (TSH) secretion is required, and recurrence can be detected by secretion of thyroglobulin into the blood. Papillary and follicular carcinoma have 20-year survival rates of 95% and 60% respectively. Question 15. D) Autoimmune gonadal failure Explanation: In hypogonadotrophic hypogonadism there is deficiency of follicle-stimulating hormone (FSH) and luteinising hormone (LH), the gonadotrophins. This may be due to structural disease of the pituitary or hypothalamus (e.g. pituitary adenoma), or to 'functional' gonadotrophin deficiency secondary to other influences (e.g. chronic illness, stress, malnutrition, excessive exercise). Primary gonadal failure, on the other hand, is associated with elevated gonadotrophin levels due to a loss of negative feedback (hypergonadotrophic hypogonadism). Question 16. B) Women with an intact uterus should receive both oestrogen and progesterone Explanation: Oestrogen replacement in post-menopausal women reduces vasomotor symptoms (e.g. hot flushes, sweats) and prevents osteoporotic fractures. There is, however, an increased risk of breast and endometrial cancer, thromboembolic disease, ischaemic heart disease and stroke. For these reasons, HRT should not be continued long-term, and many authorities recommend that treatment is only continued beyond the age of 50 if there are unacceptable symptoms of oestrogen deficiency. In women with an intact uterus, unopposed oestrogen therapy is more likely to cause endometrial malignancy; combined cyclical treatment with progesterone is therefore recommended to induce regular withdrawal bleeds. Question 17. A) Bromocriptine Explanation: High serum prolactin levels may be physiological (e.g. stress, pregnancy) or pathological. Prolactin secretion from the anterior pituitary is normally inhibited by dopamine from the hypothalamus. Pituitary tumours can cause hyperprolactinaemia by directly secreting prolactin (prolactinoma) or by compressing the infundibular stalk and thereby interfering with the inhibitory effect of dopamine. Anti-dopaminergic drugs (e.g. antiemetics and antipsychotics) can also cause high prolactin levels. 191 Bromocriptine, on the other hand, is a dopamine agonist used in the treatment of prolactinoma. Primary hypothyroidism leads to increased hypothalamic thyrotrophin-releasing hormone (TRH) secretion by negative feedback, which in turn stimulates prolactin release from the pituitary. Question 18. C) Gliclazide Explanation: PCOS is associated with insulin resistance and obesity. Weight loss and treatment with insulin-sensitising drugs such as metformin are beneficial; gliclazide is a sulphonylurea which enhances insulin secretion but not insulin sensitivity, and has no role in PCOS. The combined oral contraceptive pill enables cyclical delivery of oestrogen and progesterone, which regulates menstrual cycles and improves hirsutism by suppressing androgen production from the ovary. Cyproterone acetate is an androgen receptor antagonist (which also has progesterone agonist effects) and is useful in combating hirsutism in PCOS. Question 19. E) Low follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels Explanation: Turner's syndrome affects 1 in 2500 females and is usually associated with the 45XO karyotype. Ovarian development during gestation is abnormal. The ovaries are therefore unable to produce adequate oestrogen, and the loss of negative feedback leads to elevated levels of FSH and LH. The short stature responds in part to growth hormone therapy. Question 20. C) There is an increased incidence of gynaecomastia Explanation: Klinefelter's syndrome affects 1 in 1000 males and is usually associated with the 47XXY karyotype. There is dysgenesis and subsequent fibrosis of the seminiferous tubules, and affected individuals usually have small, firm testes. Tall stature (due to androgen deficiency and failure to close the epiphyseal growth plates) is common, and growth hormone treatment is not required. Impaired testicular function results in androgen deficiency, which in turn leads to elevated follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels due to loss of negative feedback (hypergonadotrophic hypogonadism). The lack of androgens leads to gynaecomastia, failure of development of secondary sex characteristics and infertility. Question 21. D) Alpha-fetoprotein (AFP) Explanation: Teratomas often secrete Vfetoprotein (AFP), and both teratomas and seminomas secrete _-human chorionic gonadotrophin (_-HCG); serum levels of these tumour markers are potentially useful in diagnosis and prognosis. Question 22. B) It inhibits 1Lhydroxylation of vitamin D in the kidney Explanation: PTH is a polypeptide hormone secreted by the parathyroid glands in response to low serum calcium levels. Its actions lead to an increase in serum calcium. This is mediated by increased calcium resorption from bone and increased renal absorption of calcium. Vitamin D derived from sunlight and from the diet initially undergoes 25hydroxylation in the liver to 25-hydroxyvitamin D, which then undergoes 1Vhydroxylation in the kidney to form active 1,25-dihydroxy-vitamin D. PTH stimulates the latter step. Activated vitamin D increases gut absorption of calcium, thereby further increasing calcium levels. 192 Question 23. B) Secondary hyperparathyroidism Explanation: Primary hyperparathyroidism is usually due to a parathyroid adenoma, but can be due to parathyroid hyperplasia or, in rare cases, parathyroid carcinoma. Elevated parathyroid hormone (PTH) levels result in hypercalcaemia. Secondary hyperparathyroidism occurs as a response to hypocalcaemia (e.g. in chronic renal failure), and calcium levels are therefore normal or low. Prolonged secondary hyperparathyroidism can ultimately lead to autonomous PTH hypersecretion with consequent hypercalcaemia (tertiary hyperparathyroidism). Malignancy can lead to elevated serum calcium due to bony metastases, paraneoplastic phenomena (mediated by PTH-related peptide, e.g. in squamous cell bronchial carcinoma) or myeloma. Question 24. C) Hyperparathyroidism, medullary thyroid carcinoma, phaeochromocytoma Explanation: MEN syndromes are rare autosomal dominant disorders characterised by tumours or hyperplasia in multiple glands. Differentiated thyroid cancers (e.g. follicular carcinoma) are not a feature. Option A describes MEN type 1, and option E describes von Hippel-Lindau syndrome. Question 25. C) Low calcium, high phosphate, low parathyroid hormone Explanation: This patient has hypoparathyroidism resulting from damage to the parathyroid glands during her thyroidectomy. Since the net effect of parathyroid hormone (PTH) is to increase serum calcium and decrease phosphate, this results in hypocalcaemia and hyperphosphataemia. Carpopedal spasm is a manifestation of tetany and is characteristic of hypocalcaemia. In carpal spasm, the metacarpophalangeal (MCP) joints are flexed and the interphalangeal (IP) joints extended. Other features of low calcium include tingling in the hands and feet and around the mouth, stridor and seizures. Chvostek's and Trousseau's signs may be positive. Question 26. A) Osteophyte formation Explanation: Hyperparathyroid bone disease is now rare thanks to earlier use of surgical parathyroidectomy. Osteitis fibrosa cystica results from bone resorption by osteoclasts with subsequent fibrous tissue deposition within the lacunae. Bone mineral density is reduced and subperiosteal erosions and terminal resorption can be seen in the phalanges. Calcium pyrophosphate crystal deposition within the articular cartilage (especially the knees) leads to chondrocalcinosis and pseudogout. Osteophytes are a characteristic radiological finding in osteoarthritis. The overnight dexamethasone suppression test involves administration of 1 mg of the synthetic glucocorticoid dexamethasone at bedtime with measurement of plasma cortisol as soon as practicable after waking the next morning. In healthy individuals, endogenous adrenocorticotrophic hormone (ACTH) secretion is inhibited and plasma cortisol is therefore suppressed to < 60 nmol/l. Failure to suppress endogenous cortisol secretion is consistent with Cushing's syndrome. Alternative screening tests include measurement of cortisol in a 24-hour urine sample or of cortisol:creatinine ratio in an overnight urine sample. Question 27. B) Cushing's syndrome Explanation: Cushing's syndrome is caused by excessive glucocorticoid levels, which may be exogenous or endogenous in origin. Addison's disease results from primary adrenocortical insufficiency. In Conn's syndrome there is excess mineralocorticoid secretion by an adrenal adenoma. Phaeochromocytoma arises from a tumour of catecholamineproducing enterochromaffin cells, most commonly from the adrenal medulla. Question 30. B) Low blood pressure, low sodium, high potassium Explanation: In Addison's disease there is primary adrenocortical insufficiency. Mineralocorticoid (aldosterone) deficiency leads to hypotension, hyponatraemia and hyperkalaemia. Glucocorticoid (cortisol) deficiency causes hypotension and hyponatraemia. Patients can present with chronic features (e.g. fatigue, weight loss, anorexia) or with an acute adrenal crisis associated with circulatory collapse. The latter is a medical emergency requiring urgent treatment with IV fluids and hydrocortisone. Question 28. D) Chronic glucocorticoid therapy Explanation: Prolonged administration of glucocorticoids in supra-physiological quantities (e.g. in patients with asthma or inflammatory bowel disease) is the most common cause of Cushing's syndrome. In patients who have not received glucocorticoid therapy, pituitary adenoma is the most common cause (Cushing's disease). Question 29. C) Overnight dexamethasone suppression test Explanation: The first step is to establish whether or not the patient has Cushing's syndrome; further investigations are then required to determine the cause. Random plasma cortisol levels are unhelpful in view of the diurnal variation in cortisol secretion. 193 Question 31. E) Spironolactone Explanation: In Conn's syndrome there is an aldosterone-secreting adrenal adenoma. Aldosterone promotes sodium and water retention and increases renal potassium excretion. High mineralocorticoid levels therefore result in hypertension and hypokalaemia. The diuretic spironolactone is a mineralocorticoid receptor antagonist and is therefore first-line treatment. Surgical resection of the diseased adrenal gland is usually recommended. Question 32. B) Phenoxybenzamine Explanation: The clinical features and investigation findings are consistent with phaeochromocytoma. Hypertension results from excessive secretion of catecholamines (adrenaline/epinephrine and noradrenaline/norepinephrine) from the tumour. Initial antihypertensive treatment is with the V-blocker, phenoxybenzamine. If the V-blockade induces a marked reflex tachycardia or if there is persistent hypertension, then a _blocker can be added. A _-blocker must not be given before an V-blocker, as blockade of _2-receptors (which have a vasodilatory action when activated) can result in unopposed V-mediated vasoconstriction and precipitate a hypertensive crisis. Question 33. D) Administration of exogenous insulin Explanation: Endogenous insulin is cosecreted with C-peptide (both are formed from the cleavage of pro-insulin from the pancreas). High insulin levels associated with low C-peptide levels during hypoglycaemia therefore indicate an exogenous origin of the insulin. The family history of diabetes in this patient suggests that she may have access to a relative's insulin at home. In insulinoma and sulphonylurea ingestion, the hyperinsulinaemia is endogenous and Cpeptide levels are therefore also elevated. Hypoglycaemia in alcohol excess and hypopituitarism is not due to increased insulin secretion; insulin and C-peptide levels are therefore low. Question 34. D) 5-hydroxytryptamine (5-HT) Explanation: Carcinoid syndrome is caused by ectopic production of the vasoactive hormone 5-HT by a carcinoid tumour. Clinical manifestations include flushing, wheezing and diarrhoea, as well as cardiac valvular abnormalities. The most common site of carcinoid tumours is the small bowel, but for carcinoid syndrome to occur, the vasoactive hormones must gain access to the systemic circulation. Since hormones secreted into 194 the portal circulation are metabolised by the liver, carcinoid syndrome usually occurs only when such tumours have spread to the liver or outside the GIT. Question 35. C) Cranial diabetes insipidus Explanation: Diabetes insipidus is characterised by the production of large volumes of dilute urine. It is secondary to deficient production/release of ADH by the hypothalamus/posterior pituitary (cranial diabetes insipidus) or to reduced responsiveness of the renal tubules to ADH (nephrogenic diabetes insipidus). In healthy individuals, water deprivation leads to increased ADH secretion. This causes increased water retention by the kidneys with the resultant formation of concentrated urine (> 600 mOsm/kg) and maintenance of normal plasma osmolality (280-290 mOsm/kg). In diabetes insipidus, the kidneys are unable to retain water despite water deprivation. Plasma therefore becomes concentrated (> 300 mOsm/kg) and the urine is not maximally concentrated (i.e. it is < 600 mOsm/kg). In cranial diabetes insipidus (ADH deficiency) the urine does concentrate after administration of the ADH analogue DDAVP, but in nephrogenic diabetes insipidus (ADH resistance) there is a minimal response to DDAVP. Question 36. A) Oral GTT. Explanation: This patient has acromegaly. It is caused by excessive growth hormone (GH) secretion by a pituitary adenoma. The diagnosis is confirmed by measuring plasma GH levels during an oral glucose tolerance test; in normal subjects plasma GH suppresses to < 2 mU/l, but fails to do so in patients with acromegaly. It is important to evaluate the other pituitary hormones (including thyroid function tests) and to image the pituitary (MRI scan); however, as in most circumstances in endocrinology, scanning is usually performed after the biochemical diagnosis has been established. Insulin tolerance tests may be used to diagnose GH deficiency (not GH excess). Chapter 20 DIABETES MELLITUS Question 1. D) Decreased glycogenolysis Explanation: Insulin is an anabolic hormone, and its secretion increases in response to a rise in blood glucose. Its actions are to reduce blood glucose levels and promote energy storage (therefore only D is true), inhibit ketogenesis, and increase fat and protein synthesis. Question 2. E) Addison's disease Explanation: Growth hormone, catecholamines, corticosteroids and glucagon are all counter-regulatory hormones, as they respond to the stress of hypoglycaemia and oppose the actions of insulin. They may all therefore cause diabetes when present in excess, e.g. in acromegaly, phaeochromocytoma or Cushing's syndrome. Addison's disease involves immune destruction of the adrenals, resulting in reduced glucocorticoid production, and so blood glucose levels tend to be low. In haemochromatosis, pancreatic iron overload can impair insulin secretion, leading to diabetes. Question 3. E) Concordance rates between monozygotic twins are greater than 90% Explanation: Type 1 diabetes is mediated by autoimmune destruction of the insulinproducing ß-cells in the pancreas. Treatment with insulin is therefore essential to prevent uncontrolled hyperglycaemia and ketoacidosis. The condition is thought to be triggered by environmental factors (e.g. viral infection) in genetically susceptible individuals. However, concordance between monozygotic twins is only 35% in type 1 diabetes, compared with rates approaching 100% in type 2 diabetes. Type 1 diabetes is associated with other autoimmune conditions, including pernicious anaemia, 195 Addison's disease and thyroid disease. Question 4. C) Ketoacidosis is a common complication Explanation: Diabetic ketoacidosis develops in type 1 diabetes because of severe insulin deficiency, but is rarely a feature of type 2 diabetes, as sufficient insulin secretion to suppress lipolysis is usually retained. Type 2 diabetes has a much higher prevalence and is a major risk factor for cardiovascular disease. Unlike type 1 diabetes, it is often asymptomatic and detected incidentally. One of the characteristics of type 2 diabetes is insulin resistance. The combination of type 2 diabetes, hypertension, hyperlipidaemia and central obesity constitutes the metabolic syndrome, also known as the insulin resistance syndrome, which strongly predisposes to ischaemic heart disease. Question 5. D) Explain to the patient that she has diabetes mellitus Explanation: The World Health Organization (WHO) criteria for diagnosing diabetes mellitus are shown in the link below. C-peptide is the connecting peptide which links the A and B chains of insulin, and is secreted from the islet ßcells with insulin in equimolar concentrations. It can be measured in the assessment of hypoglycaemia to establish whether excess insulin originates from an exogenous or endogenous source and, occasionally, to determine endogenous insulin secretory reserve in a patient with diabetes; however, it is not used to make the diagnosis of diabetes. Question 6. C) A low renal threshold for glucose in an otherwise healthy individual Explanation: The most common cause of glycosuria is a low renal threshold for glucose, which results in glucose 'spilling over' into the urine. This is most often found in pregnancy and in young people. In some healthy individuals there is a rapid rise in blood glucose after meals, which can exceed the renal threshold and lead to transient glycosuria. Pyelonephritis can lead to protein, blood, nitrites and leucocytes in urine, but not typically glucose. Question 7. D) Measuring glycated haemoglobin (HbA1C) Explanation: Glycated haemoglobin (HbA1C) is formed by the non-enzymatic attachment of glucose to haemoglobin. Measurement of HbA1C provides an estimate of glycaemic control over the lifespan of red blood cells. (Red cells have a lifespan of 120 days, but the turnover of the pool in the circulation means that HbA1C reflects blood glucose over the previous 8 weeks.) The target level is usually 7% or less, as this reduces the risk of developing microvascular complications. Pre-prandial blood glucose measurements are useful to patients at home for monitoring glycaemic control and adjusting insulin doses. Assessment of urine glucose is of limited value since it varies according to the renal threshold. Question 8. A) Administration of intravenous insulin and intravenous saline Explanation: In diabetic ketoacidosis (DKA), severe insulin deficiency leads to hyperglycaemia and the generation of ketone bodies. The hyperglycaemia results in glycosuria and an osmotic diuresis, through which patients can become severely dehydrated. The initial priorities in managing DKA are therefore administration of intravenous saline and insulin. 196 Although serum potassium levels are often initially high, patients are usually depleted in total body potassium, and intravenous infusion of potassium should be given once potassium falls below 5.0 mmol/l. Sodium bicarbonate is rarely needed, may be dangerous and should be administered only under expert supervision. Central venous access may be required to assist with fluid management, but is not the most urgent step. Antibiotic therapy would be required if there was evidence of overt infection as the precipitating cause of the DKA. Question 9. B) Subcutaneous heparin should be administered within the first 24 hours Explanation: Hyperosmolar non-ketotic hyperglycaemia (HONK) principally affects patients with type 2 diabetes. It is characterised by severe hyperglycaemia and marked dehydration, but patients are not acidotic because ketone production is not increased. Smaller doses of insulin are required than for treatment of diabetic ketoacidosis. There is a high risk of thromboembolic complications in HONK due to the severe dehydration, and low molecular weight heparin should therefore be given. Question 10. B) Kussmaul breathing Explanation: Sweating and tachycardia are stimulated by sympathetic activation in hypoglycaemia. Confusion and altered consciousness result from neuroglycopenia. Kussmaul breathing (air hunger) is a feature of diabetic ketoacidosis as a response to the metabolic acidosis. Question 11. D) Oral carbohydrate Explanation: Although the accuracy of blood glucose strip testing kits is variable, this patient has clinical features and a glucose reading consistent with hypoglycaemia, so prompt treatment is required. If a patient is conscious and able to swallow, then oral carbohydrate is the treatment of choice. If not, then IV dextrose or IM glucagon should be administered. Laboratory samples should be obtained (for glucose, insulin, Cpeptide, toxicology drug screen) before treatment in patients with unexplained suspected 'spontaneous' hypoglycaemia, as this avoids potentially complex attempts to reproduce the hypoglycaemia later. However, hypoglycaemia in diabetic patients who are treated with insulin or with a sulphonylurea is probably related to their treatment. Question 12. E) Stop metformin and commence intravenous insulin Explanation: Studies suggest that strict glycaemic control in the peri-infarct period improves long-term prognosis after an MI. This is usually achieved with insulin, often in the form of an intravenous infusion (sliding scale). The study most often cited is the DIGAMI study (diabetes mellitus, insulin glucose infusion in acute myocardial infarction), which showed a reduction in mortality of 25% in patients treated with an insulin infusion, compared with standard treatment over a follow-up period of 3.5 years (though this has not been confirmed in subsequent studies). Oral anti-diabetic agents are usually discontinued until the recovery period after MI. Metformin in particular should be withheld because of the small risk of lactic acidosis in the event of impaired systemic perfusion. 197 Question 13. C) Insulin alone Explanation: The development of diabetes during pregnancy is associated with increased maternal and fetal morbidity and mortality. Hyperglycaemia can result in teratogenic effects and macrosomia. Strict blood glucose control with insulin is therefore important. Oral anti-diabetic agents may be harmful to the fetus and should not be given during pregnancy. Question 14. D) Start an intravenous infusion of dextrose and insulin in place of the patient's usual therapy Explanation: Adequate control of hyperglycaemia is important in the perioperative period. For type 2 diabetic patients undergoing minor operations, it is reasonable to place them first on the operating list and to omit their morning oral anti-diabetic agent or insulin until after the operation. However, for type 2 diabetic patients undergoing major surgery, and for all type 1 diabetic patients, blood glucose should be controlled by means of an intravenous insulin infusion. Question 15. B) Metformin Explanation: Sulphonylureas (e.g. gliclazide) act by stimulating endogenous insulin secretion. A major side-effect of this class of drug is weight gain, and so they would not generally be considered first-line treatment in obese patients. Metformin (a biguanide) works by increasing insulin sensitivity and does not cause weight gain, so is a better choice in this patient. Thiazolidinediones (e.g. rosiglitazone, pioglitazone) also act by improving insulin sensitivity, but are not usually prescribed as first-line treatment. Insulin treatment is sometimes required in type 2 diabetes, but tends to be initiated when glycaemic control with oral agents is suboptimal. Question 16. C) They are particularly useful in diabetic patients with left ventricular dysfunction Explanation: The thiazolidinedione class of drugs, also known as glitazones or TZDs, includes rosiglitazone and pioglitazone. They act by binding to a nuclear receptor called peroxisome proliferator-activated receptor-W (PPAR-W), particularly in fat cells. This results in altered expression of genes involved in metabolism and thereby enhances insulin sensitivity. Insulin secretion itself is not affected. They are useful in obese patients with type 2 diabetes, in whom insulin resistance is often severe. Although they do cause weight gain, this is usually in subcutaneous rather than intra-abdominal adipose tissue and is therefore thought to be metabolically 'benign'. They have few side-effects, but can cause salt and water retention, and are therefore contraindicated in heart failure. Question 17. D) Glipizide N hypoglycaemia Explanation: Sulphonylureas (e.g. gliclazide, glipizide) stimulate insulin secretion and hence cause weight gain and can induce hypoglycaemia. Metformin increases insulin sensitivity and does not cause hypoglycaemia, but frequently causes nausea and diarrhoea. It is also contraindicated in patients with renal impairment, liver dysfunction, symptomatic heart failure and sepsis because of the risk of lactic acidosis. Question 18. A) Ischaemic heart disease Explanation: Macrovascular disease is the major cause of mortality in diabetes, particularly myocardial infarction and stroke. Macrovascular disease also causes significant morbidity in the form of coronary heart disease, cerebrovascular disease and peripheral vascular disease. Microvascular complications include diabetic retinopathy, nephropathy and neuropathy. Their incidence is related to poor glycaemic control and causes serious morbidity but is not the major cause of death. 198 Question 19. C) Flame haemorrhages Explanation: Flame haemorrhages are a feature of hypertensive retinopathy but are not usually a feature of diabetic retinopathy. Hard exudates (due to leakage from abnormal capillaries), blot and dot haemorrhages, and cotton wool spots (caused by areas of retinal ischaemia) are found in both diabetic and hypertensive retinopathy. Microaneuryms and venous beading occur in diabetic retinopathy. Question 20. D) Venous beading with cotton wool spots Explanation: Microaneurysms, dot haemorrhages and hard exudates are features of background diabetic retinopathy. The finding of hard exudates near the macula indicates diabetic maculopathy, which is sight-threatening. Venous beading, cotton wool spots and intra-retinal microvascular abnormalities (IRMAs) occur in pre-proliferative disease. New vessel formation (neovascularisation) is the key feature of proliferative diabetic retinopathy. Rupture of these vessels can result in pre-retinal haemorrhage. Papilloedema is a feature of grade IV hypertensive retinopathy but may also be seen in other conditions, including raised intracranial pressure. The classification of retinopathy is detailed in the link below. Question 21. C) Regular follow-up in the diabetic clinic but no referral to ophthalmology Explanation: Background retinopathy requires regular fundoscopy to identify progression but is not in itself an indication for ophthalmology referral. Patients with pre-proliferative and proliferative retinopathy should be referred urgently to ophthalmology for further assessment and consideration of retinal laser photocoagulation. Progression of retinopathy is related to poor glycaemic control and elevated blood pressure, and so anti-diabetic agents and antihypertensives should not be stopped. Question 22. C) Ramipril Explanation: Diabetic nephropathy is a major cause of end-stage renal failure. Its development is related to poor glycaemic control. The presence of microalbuminuria heralds the development of overt nephropathy. The risk of progression can be reduced by good glycaemic control and aggressive treatment of elevated blood pressure. Angiotensin-converting enzyme (ACE) inhibitors provide greater benefit from equal blood pressure lowering than other antihypertensive agents. They reduce intra-glomerular pressure and urinary protein excretion and are therefore the preferred agents in patients with microalbuminuria. Question 23. E) It is typically associated with painful foot ulcers Explanation: Like all diabetic microvascular complications, the development of neuropathy can be prevented or delayed by good glycaemic control. Sensory, motor and autonomic nerves can all be affected, but patients are often asymptomatic, particularly in the early stages. Sensory neuropathy classically gives rises to a 'glove and 199 stocking' distribution of sensory loss distally. Motor involvement can cause progressive proximal muscle weakness, commonly accompanied by severe pain. Motor and sensory function of individual cranial and peripheral nerves can also be affected (mononeuropathy and mononeuritis multiplex). Peripheral sensory neuropathy can ultimately result in grossly deforming neuroarthropathy of the feet (Charcot joint) due to loss of pain sensation. Although neuropathy can give rise to foot ulcers, these are typically painless (unlike ischaemic ulcers). Question 24. D) Gastroparesis Explanation: Autonomic neuropathy can affect sympathetic or parasympathetic nerves. Gastroparesis in patients being treated with insulin can predispose to poor glycaemic control and hypoglycaemia, because of unpredictable matching between carbohydrate absorption and plasma insulin concentrations. Fast-acting insulin analogues should be avoided. Agents that promote gastric emptying, such as metoclopramide, may be helpful. Chapter 21 ALIMENTARY TRACT AND PANCREATIC DISEASE Question 1. E) Rounded mass Explanation: The other findings are all characteristic of an enlarged spleen. Question 2. A) Trypsin Explanation: Amylase is involved in carbohydrate digestion. Lipase cleaves long chain triglycerides, yielding fatty acids and monoglycerides. Cholecystokinin is a hormone with important effects on gut motility. Pepsin is active in the stomach, not small bowel, where it plays a modest role in protein digestion. Question 3. C) Glycogen Explanation: More on Carbohydrate digestion and absorption Question 4. D) Increased gastric acid secretion Explanation: In addition to the other factors listed above, CCK suppresses gastric acid secretion. Question 5. D) Oesophageal carcinoma Explanation: The barium swallow shows a long irregular stricture, typical of an oesophageal carcinoma. None of the other options would produce this appearance. Question 6. A) Faecal elastase Explanation: Elastase is a proteolytic enzyme produced by the pancreas. Levels are reduced in pancreatic exocrine failure, though it has low sensitivity for detecting mild disease.Abdominal CT is useful for assessing pancreatic size and structure, but not function. Three-day faecal fat is a test for fat malabsorption. Fasting blood glucose is a test of pancreatic endocrine function. The lactose hydrogen breath test is used in the detection of lactose intolerance. 200 Question 7. B) Helicobacter pylori infection Explanation: Urea breath testing is, in most cases, the best test for detecting H. pylori infection as it is accurate, simple and non-invasive. Bacterial overgrowth and lactose intolerance may be detected by the glucose hydrogen breath test and lactose hydrogen breath tests respectively. Fat malabsorption can be diagnosed by either 3-day faecal fat assessment or the 14 C-triolein breath test. Tests for coeliac disease include coeliac antibodies and small bowel (usually duodenal) biopsy. Question 8. E) Achalasia Explanation: Upper gastrointestinal endoscopy is, in general, the investigation of choice in dysphagia to exclude structural causes and allow biopsy with or without dilatation of any suspicious strictures. However, oesophageal manometry is useful in achalasia where the characteristic pattern of high-pressure, non-relaxing lower oesophageal sphincter with poorly contractile body of oesophagus confirms the diagnosis. Question 9. E) Associated difficulty in swallowing Explanation: Dyspepsia is extremely prevalent and usually does not require investigation, especially in younger patients. In general, upper gastrointestinal endoscopy should be reserved for patients over 55 years old, younger patients unresponsive to empirical treatment or those with 'alarm' features, such as dysphagia, which may point to serious underlying pathology. Question 10. C) Atenolol Explanation: Many antibiotics, analgesics and cytotoxins may lead to vomiting. Sideeffects of atenolol include tiredness, impotence and nightmares, but not vomiting. Question 11. B) Mallory-Weiss tear as the cause of bleeding Explanation: Mortality risk in patients presenting with acute upper gastrointestinal bleed is defined by the 'Rockall risk score' which takes into account age, features of shock, comorbidity, diagnosis and endoscopic findings. Mallory-Weiss tear is the diagnosis associated with the most favourable outcome. Question12. E) Anal fissure Explanation: Anal fissure does not cause severe acute lower gastrointestinal bleeding but rather small amounts of fresh rectal bleeding associated with pain during defaecation. Question 13. C) Blood and mucus in stool Explanation: A colonic aetiology is suggested by cramping lower abdominal pain, blood and mucus in stool, and highfrequency, low-volume stool, often with tenesmus. Question 14. D) Peripheral neuropathy Vitamin C Explanation: Vitamin C deficiency produces bleeding gums, poor wound healing and perifollicular or petechial bruising (scurvy). Peripheral neuropathy may be due to vitamin B12 deficiency. Question 15. E) Verapamil Explanation: Constipation is a side-effect of various calcium channel blockers but particularly verapamil. Diarrhoea is a common side-effect of macrolide antibiotics, especially erythromycin. Likewise, metformin is far more likely to cause diarrhoea than constipation. Sideeffects of digoxin include nausea, vomiting, arrhythmia and disturbed vision, but not constipation. 201 Orlistat is a lipase inhibitor that reduces absorption of dietary fat and is used in the management of obesity. Side-effects include liquid or oily stools and faecal urgency rather than constipation. Question 16. E) Psoriasis Explanation: See list of Causes of oral ulceration Question17. C) Weight loss Explanation: Weight gain may precipitate or aggravate symptoms by increasing intra-abdominal pressure, whereas weight loss may improve symptoms. Question18. D) Patients with the condition should undergo regular endoscopic surveillance with biopsies Explanation: Barrett's oesophagus refers to metaplastic rather than neoplastic change. Although a major risk factor for oesophageal adenocarcinoma, the vast majority of patients do not go on to develop this condition. Neither potent acid suppression nor antireflux surgery has been shown to induce regression or even stop progression of Barrett's oesophagus. Regular endoscopic surveillance is recommended. Question 19. D) Recurrence of symptoms following cessation of medical treatment is common Explanation: The patient is young, is otherwise well, and has a typical history of GORD and no worrying features. He can therefore be treated empirically without need for further investigation. A history of weight gain prior to onset of symptoms is common in GORD and would lend support to the diagnosis. PPIs are superior to H2-receptor antagonists in both relieving symptoms and healing oesophagitis (see the evidence-based medicine box in the link below). Recurrence of symptoms after stopping acid-suppressing therapy is common and some patients require long-term low-dose maintenance therapy. Antireflux surgery is highly effective in alleviating symptoms. Question 20. B) Achalasia Explanation: The barium swallow shows the characteristic appearance of a dilated barium-filled oesophagus with fluid level and distal tapering and a closed lower oesophageal sphincter. Clues in the history include the long duration of symptoms, the easing of swallowing difficulties by drinking liquids, and the intermittent episodes of severe chest pain which are due to oesophageal spasm. Diffuse oesophageal spasm produces transient rather than slowly progressive dysphagia. Myasthenia gravis, as with other neuromuscular causes of dysphagia, tends to be worse for liquids rather than solids. In systemic sclerosis there is usually a history of severe heartburn. An endoscopy may still be necessary to exclude oesophageal carcinoma. Question 21. D) The presence of hoarseness suggests mediastinal invasion Explanation: The overall 5-year survival rate is very poor at 6-9% and even after 'potentially curative' surgery remains only 30%. Endoscopic ultrasound is the most sensitive modality for staging, as CT tends to understage tumours. Dysphagia is classically persistent and progressive and is initially worse for solids. Pain is often absent due to destruction of mucosal innervation by the tumour. Endoscopically directed tumour ablation using laser therapy or stent insertion is the major method of improving swallowing. Mediastinal invasion with involvement of the recurrent laryngeal nerve may cause hoarseness. Question 22. A) Chronic peptic ulcer Explanation: Of the possibilities above, chronic peptic ulcer fits best with the pattern of symptoms. The three characteristics of ulcer pain are the recurrent, episodic nature, a relationship to food and localisation to the epigastrium. Occasional vomiting occurs in about 40%. It is worth noting, though, that the history is actually a poor predictor of the presence of an ulcer. 202 The pain of chronic pancreatitis and mesenteric ischaemia tends to be precipitated rather than relieved by eating, as does the pain of biliary colic, particularly with fatty foods. It would be unusual for Crohn's disease to produce pain well localised to the epigastrium. Question 23. D) The patient should be given specific advice on dietary restriction Explanation: Most peptic ulcers are now cured by H. pylori eradication and acidsuppressing therapy with the result that elective surgery for peptic ulcer disease has become a rare event. No special dietary advice is required, although patients may themselves wish to avoid certain foods they feel aggravate symptoms. If failure to eradicate H. pylori infection occurs with standard triple therapy, the patient should first be asked about compliance with treatment and then offered second-line therapy. Question 24. C) It exclusively colonises gastric-type epithelium Explanation: H. pylori is a Gramnegative spiral-shaped rod. The enzyme 'urease' produces ammonia from urea, thereby raising the surrounding pH and making the environment less hostile for the bacterium. It is true that H. pylori only colonises gastric-type epithelium and is, therefore, only found in the duodenum in association with patches of gastric metaplasia. CagA is one of several wellrecognised virulence factors (see Fig. 22.32 in the link below). Colonisation is associated with depletion of somatostatin (from D cells) but stimulates release of gastrin (from G cells). Question 25. C) Around 40% of patients with duodenal ulcer are infected with H. pylori Explanation: H. pylori infection may be responsible for 60-70% of cases of gastric carcinoma. Around 90% of duodenal ulcer patients and 70% of gastric ulcer patients are infected. The development of a lowgrade lymphoma known as a 'MALToma' is closely associated with H. pylori infection, and superficial MALTomas may be cured by H. pylori eradication. Despite all of the above, only a minority of H. pylori-infected patients develop clinical disease. Question 26. A) Weight gain Explanation: Weight loss rather than weight gain is common. The usual cause is reduced dietary intake due to early satiety from a small gastric remnant. Both diarrhoea and anaemia may be multifactorial. Rapid gastric emptying of food of high osmotic potential may produce large fluid shifts into the small intestine, provoking autonomic symptoms. This is known as 'dumping syndrome'. Question 27. C) Zollinger-Ellison syndrome Explanation: In Zollinger-Ellison syndrome there is severe peptic ulceration from gastric acid hypersecretion due to a gastrin-producing non-ß-cell islet tumour of the pancreas ('gastrinoma'). Ulcers are often multiple and refractory to standard therapy, and may occur in unusual places such as oesophagus or duodenum. It comprises part of the MEN type 1 syndrome. Inactivation of pancreatic enzymes and bile salts by increased acidity in the small intestine can result in diarrhoea (seen in more than one-third of patients) and steatorrhoea. High-dose proton pump inhibitor therapy heals ulcers, alleviates diarrhoea and has largely removed the need for total gastrectomy. 203 Question 28. B) Zollinger-Ellison syndrome Explanation: A reduction in the acidity of the stomach (hypochlorhydria or achlorhydria) appears to increase gastric cancer risk, perhaps by permitting colonisation of the stomach with nitritereducing bacteria which form carcinogenic N-nitroso-compounds from nitrates. Autoimmune chronic gastritis and H. pylori infection may both lead to achlorhydria, unlike Zollinger-Ellison syndrome, which markedly increases gastric acidity. (Although H. pylori infection normally results in normal or increased acid secretion, a proportion of infected individuals become hypochlorhydric or achlorhydric.) Question 29. C) Conn's syndrome Explanation: See list of Disease associations of coeliac disease Question 30. E) Mesenteric ischaemia Explanation: The most common cause of subtotal villous atrophy in the UK is coeliac disease but there are a number of other important causes. Question 31. E) There is an increased risk of T-cell lymphoma Explanation: Patients are intolerant of wheat, rye, barley and, to a lesser extent, oats, but not rice, maize or potatoes. Peak onset is in infancy and early childhood; in adults the highest incidence occurs in the 40-59 age group. Around 50% of patients are asymptomatic and many remain undiagnosed. Metabolic bone disease is less common in patients who stick strictly to a gluten-free diet. There is an increased risk of T-cell lymphoma as well as small bowel carcinoma and squamous carcinoma of the oesophagus, although the absolute risk of developing these malignancies is very low. Question 32. E) Serum amylase Explanation: The above account is classical of acute pancreatitis. Pain radiates to the back in 65% of cases; guarding and rebound tenderness are typically absent in the early stages as the inflammation is retroperitoneal. A markedly elevated serum amylase often confirms the diagnosis, although in difficult cases, ultrasound or CT can help by demonstrating evidence of pancreatic swelling. Abdominal and erect chest Xrays may exclude other conditions such as intestinal obstruction or perforated viscus and an ECG should be performed to exclude atypical presentation of myocardial infarction. C-reactive protein is not helpful diagnostically but is a useful indicator of severity and prognosis. Question 36. D) Recurrent hypoglycaemia Explanation: Hyperglycaemia, due to the development of diabetes mellitus, rather than hypoglycaemia is a common feature of chronic pancreatitis. Question 33. C) Hypocalcaemia Explanation: Hypercalcaemia not hypocalcaemia is a rare cause of acute pancreatitis. By far the two most common aetiologies are alcohol and gallstones. Question 38. D) The liver is a common site for metastatic deposits Explanation: Pancreatic carcinoma has a dismal prognosis; only 15% of tumours are amenable to curative resection and, even in patients who undergo complete resection, 5-year survival is around 20%. Around two-thirds of tumours arise from the head of the pancreas; these frequently involve the common bile duct, resulting in obstructive jaundice. Coeliac plexus neurolysis may be useful in relieving pain, which often proves extremely difficult to control with other measures. Ampullary carcinomas behave less aggressively than pancreatic carcinomas and have a more favourable outlook. Question 34. D) Amylase 1000 U/l (normal range < 100 U/l) Explanation: Although an elevated serum amylase is useful in diagnosing acute pancreatitis, it has no prognostic value. The other parameters listed are included in the Glasgow criteria of adverse prognostic factors. Question 35. B) Enteral feeding should be started at an early stage in patients with severe pancreatitis Explanation: Hypocalcaemia need only be corrected if tetany occurs. Thromboprophylaxis is advised. The greatest benefit from emergency ERCP occurs in patients who have ascending cholangitis (see EBM Box 22.58 in the link below). Opiate analgesia is required in nearly all cases. Nutritional support, preferably by the enteral route, forms an important part of the management of acute pancreatitis. 204 Question 37. D) Carcinoma of pancreas Explanation: This is a fairly typical presentation of pancreatic carcinoma (apart from the vanishingly rare sign of palpable gallbladder). The diagnosis will be confirmed with abdominal ultrasound or CT. According to 'Courvoisier's law', a palpable gallbladder in a jaundiced patient is unlikely to be due to gallstones, and is usually the result of distal biliary obstruction by a carcinoma of the head of pancreas. Question39. E) Inflammation limited to the mucosa Explanation: There are several important pathological differences between ulcerative colitis (UC) and Crohn's disease (CD), including but not confined to the following: • UC only involves the colon, while Crohn's disease can involve any part of the gastrointestinal tract from mouth to anus. • In UC inflammation is confluent and more severe distally (thus it invariably involves the rectum but may spread proximally to involve the remainder of the colon). In CD changes are patchy with areas of inflammation interrupted by islands of normal mucosa. (This may produce the characteristic 'skip lesion'.) • In UC the inflammatory process is superficial, confined to the mucosa and sparing deeper layers of the bowel wall, while in CD inflammation is deep and seen through all layers of the bowel wall. (Deep ulcers may penetrate through the bowel wall to initiate fistulae.) Question 40. B) Cigarette smoking Explanation: Ulcerative colitis is more common in non-smokers and, in fact, cessation of smoking can provoke a relapse of symptoms. Emotional stress, intercurrent illness, non-steroidal antiinflammatory drugs (NSAIDs) and antibiotics are all well-recognised factors which may precipitate flares. Question 41. D) Serum albumin Explanation: Serum albumin is a marker of disease severity in ulcerative colitis but does not contribute to the diagnosis. It is suppressed in any condition producing an acute phase response. Question 42. B) Stool volume 200 g/24 hrs Explanation: Stool volume > 400 g/24 hrs suggests severe disease. These parameters are utilised in clinical practice. 205 Question 43. B) The patient should be treated with intravenous corticosteroids Explanation: Intravenous corticosteroids are given as a constant infusion in the treatment of severe ulcerative colitis. Question 44. C) The patient should be referred for urgent colectomy Explanation: The X-ray shows a grossly dilated colon due to severe ulcerative colitis. Toxic megacolon occurs most commonly during the first attack of colitis and is associated with a high risk of perforation. It is, therefore, an indication for colectomy. Question 45. E) Diarrhoea in ulcerative colitis may be due to enteroenteric fistulae Explanation: Fistulous connections between loops of affected bowel (enteroenteric), or between bowel and bladder (enterovesical) or vagina (enterovaginal) are specific complications of Crohn's disease and do not occur in ulcerative colitis. Patients with extensive active colitis of more than 8 years' duration are at increased risk of colon cancer and should, therefore, have regular colonoscopic surveillance. Question 46. B) Primary sclerosing cholangitis Explanation: Primary sclerosing cholangitis and cholangiocarcinoma are both more common in ulcerative colitis but appear to be unrelated to intestinal disease activity. The other complications listed tend to be more of a problem during active bowel disease. Question 47. C) Corticosteroids are preferred to methotrexate for maintaining remission Explanation: Chronic corticosteroid treatment is avoided due to the high incidence of complications with long-term use and poor efficacy in preventing relapse. All of the other statements are true and are useful learning points. Azathioprine and methotrexate are both used in maintenance of remission. Infliximab is highly effective in inducing remission in active Crohn's but relapse commonly occurs around 12 weeks after treatment. It should therefore be given in combination with either azathioprine or methotrexate. Surgery is not curative in Crohn's disease and repeated surgery may lead to the development of short bowel syndrome. Cigarette smoking is more important than any drug treatment in maintaining remission. Question 48. C) Symptoms disturbing sleep Explanation: Nocturnal symptoms are uncommon in IBS and pain that wakens a patient from sleep is often a useful pointer to organic disease. Other features that would raise doubt as to the diagnosis include rectal bleeding and weight loss. Question 49. D) Reassurance alone may lead to resolution of symptoms Explanation: Anxiety over the possibility of serious organic disease, particularly cancer, is often a major contributing factor to symptoms in IBS and many patients respond to simple explanation and reassurance. Such patients have a far better long-term outlook than those who fail to respond. 206 Question 50. B) Acute small bowel ischaemia Explanation: The rapidity of onset, history of vascular disease and atrial fibrillation (not on warfarin), paucity of abdominal findings despite severe symptoms and metabolic acidosis all point to acute small bowel ischaemia. Given her history of atrial fibrillation, a likely aetiology would be a thromboembolism from the heart. Question 51. E) Stool analysis for Clostridium difficile toxin Explanation: Cl. difficile is the most likely cause of this patient's diarrhoea. It is a very common cause of diarrhoea in hospital inpatients, particularly those > 65 years with comorbid disease who have had recent broad-spectrum antibiotic therapy. Legionella pneumonia can be associated with gastrointestinal upset but the timing certainly favours Cl. difficile infection in this case. Question 52. D) Polyps with a villous architecture carry a higher risk of malignant change than those with tubular architecture Explanation: Nearly all forms of colorectal carcinoma develop from adenomatous polyps, usually over a period of 5-10 years, although certain features such as increased size and villous architecture increase the risk for malignant change. Polyps are usually asymptomatic and are often found incidentally during colonoscopy; when discovered, they should be removed whenever possible to reduce the risk of developing colorectal cancer. Peutz-Jeghers syndrome is characterised by the presence of nonneoplastic hamartomatous polyps in the colon and small bowel (although it is associated with increased risk of certain malignancies, e.g. breast, ovary, colon). Question 53. C) High dietary calcium Explanation: Dietary calcium decreases the risk of developing colorectal cancer as it binds and precipitates faecal bile acids. Question 54.D) Colonoscopy Explanation: The combination of occult gastrointestinal bleeding, weight loss and a palpable right iliac fossa mass in a patient of this age group should lead to strong suspicion of colonic (caecal) carcinoma and should be investigated as a matter of 207 urgency by colonoscopy. Colonoscopy is preferable to barium enema in most instances as it has better sensitivity and specificity and allows biopsy of lesions and polypectomy. If the diagnosis is confirmed then a CT scan may be useful for detecting hepatic metastases. CEA is neither sensitive nor specific for diagnosing colorectal cancer, but in those patients with a raised CEA who go on to have resection of the tumour, it may help in follow-up to detect early recurrences Chapter 22 LIVER AND BILIARY TRACT DISEASE Question 1. B) Production of vitamin K Explanation: Vitamins are, by definition, not synthesised in the human body so an adequate dietary intake and gastrointestinal absorption of vitamin K is essential. Vitamin K is a fat-soluble vitamin and absorption is impaired in obstructive jaundice, resulting in a prolonged prothrombin time which is corrected by vitamin K administration. Question 2. E) It is the primary site of lipolysis in the liver Explanation: Below is a quick reminder of the structure of the hepatic acinus. Question 3. C) Phenytoin Explanation: Phenytoin is a microsomal enzyme-inducing drug; all of this type of drug may cause an isolated increase in the microsomal enzyme GGT. This is a reflection of hepatic enzyme induction and does not necessitate any change to therapy. A list of enzyme-inducing drugs can be found in the link below. It is important to learn them as they have interactions with other drugs, such as reducing the effectiveness of the oral contraceptive pill and increasing the toxicity of paracetamol in overdose. Question 4. A) Viral hepatitis Explanation: This is the classic picture of hepatocellular jaundice. Question 5. E) Raised reticulocyte count Explanation: Part of the bone marrow response to excessive red cell destruction is premature release of reticulocytes, resulting in a reticulocytosis. Nucleated red cell precursors may also appear in the blood. Bilirubinuria and pale stools both suggest cholestatic jaundice. As discussed 208 in the previous question, a predominant rise in ALT suggests a hepatocellular cause. Spider naevi are a pointer towards chronic liver disease. Question 6. D) Factor IX Explanation: The vitamin K-dependent clotting factors are II, VII, IX and X. Noone has ever devised a decent mnemonic for this fact, so you just have to remember it. Here they are again: 2, 7, 9 and 10. (1972) Question 7. E) Prothrombin time (PT) Explanation: Albumin, fibrinogen and most coagulation factors are synthesised in the liver so all of the above tests are, to some extent, dependent on hepatic synthetic function, with the exception of urea which is a by-product of protein metabolism. The prothrombin time changes most quickly in response to an acute liver insult, because of the short half-life of the clotting factors on which it depends. Albumin has a much longer halflife and hypoalbuminaemia is a feature of chronic liver disease. Question 8. A) Chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of 37% Explanation: The conditions required for a safe liver biopsy are included in the link below. There is a risk of causing pneumothorax if the pleura is punctured and, in a patient with severe COPD, this is not only more likely but also potentially catastrophic. Question 9. D) Abdominal ultrasound Explanation: The LFTs show a cholestatic picture. The most useful initial investigation is abdominal ultrasound, particularly to detect biliary obstruction. Should more detailed imaging of the biliary tree prove necessary, then either ERCP or magnetic resonance cholangiopancreatography (MRCP) may be helpful. MRCP (followed if necessary by therapeutic ERCP) is the diagnostic test of choice, as it carries a lower risk of complications than ERCP. A very useful algorithm for the investigation of patients with jaundice is provided in the link below. Question 10. B) Primary biliary cirrhosis (PBC) Antimitochondrial antibody (AMA) Explanation: This is difficult to remember, but genuinely useful because AMA has high sensitivity for PBC, being present in over 95% of cases. Question 11. B) Cholestatic jaundice Explanation: Cholestatic jaundice is the only option here that explains both yellow sclerae and dark urine. Conjugated bilirubin from the liver enters the blood because of a failure of bile flow. As conjugated bilirubin (unlike unconjugated bilirubin) is water-soluble, it is filtered by the kidneys and appears in the urine. More information on cholestatic jaundice, including causes and clinical features, is provided in the link below. Carotenaemia, caused by eating too much carotene, is almost always benign and causes yellowing of the skin but not the sclera. Gilbert's syndrome describes a congenital impairment of glucuronyl transferase, that leads to reduced hepatic uptake of bilirubin from the blood. This therefore causes unconjugated hyperbilirubinaemia, so the sclerae are yellow but the urine is not dark. In contrast, rhabdomyolysis causes large amounts of myoglobin to enter the urine, which can make the urine appear black but does not cause jaundice. Dehydration results in highly concentrated urine but does not cause jaundice. 209 Question 12. E) Ascitic fluid white cell count Explanation: This is a classic presentation of spontaneous bacterial peritonitis, a common and life-threatening complication of cirrhosis. Question 13. B) Spironolactone Explanation: Aldosterone excess, caused by impaired hepatic steroid metabolism, is a key factor in the pathogenesis of ascites in chronic liver disease (explained in the link below). Spironolactone is an aldosterone antagonist, which makes it the best choice to prevent sodium retention in cirrhotic patients. Furosemide (a loop diuretic) is sometimes added to spironolactone to further promote sodium excretion in the urine. Bendroflumethiazide (a thiazide diuretic) is not often used to treat ascites because better drugs are available. Vasopressin is a potent vasoconstrictor and powerfully promotes water retention. It is used in the management of hepatorenal syndrome. Digoxin is not useful in the management of ascites. Question 14. A) Prothrombin time (PT) > 100 secs Explanation: PT is a better predictor of poor outcome than liver function tests, and is used in standard criteria for determining the need for liver transplant. The following two prognostic factors (see the link below) have been shown to confer a > 90% mortality in acute liver failure secondary to paracetamol overdose: • H+ > 50 nmol/l (pH < 7.3) • Creatinine > 300 µmol/l with PT > 100 secs and grade 3 or 4 encephalopathy. Question 15. C) May be balloted Explanation: Distinguishing a grossly enlarged kidney (for example, in polycystic kidney disease) from splenomegaly can be tricky. The correct technique for palpation of the liver and spleen is shown in the link below. Question 16. C) Pruritus is a more common presenting feature than jaundice Explanation: Primary biliary cirrhosis is more common in women by a factor of 9. Pruritus is the most common presenting complaint and may precede jaundice by years. Positive antinuclear antibodies are found in only 15% of cases, whereas antimitochondrial antibodies are of considerable diagnostic value, present in over 95% of patients. Immunosuppressive drugs are not effective, and treatment mainly palliates symptoms until transplant becomes necessary. Although 30% of patients will exhibit disease recurrence in a transplanted liver, this takes years to develop and is not a contraindication to transplant. Question 17. D) Terlipressin Explanation: Terlipressin lowers the portal pressure and is the drug of choice in this scenario. The somatostatin analogue, octreotide, is also useful. Noradrenaline (norepinephrine) and dopamine predominantly cause peripheral vasoconstriction. However, in a patient dying from haemorrhage, fluid replacement, rather than vasoconstriction, is the best method to correct hypotension. Activated protein C is contraindicated in haemorrhage. Question 18. D) Hepatitis D Explanation: Hepatitis D is an incomplete virus and cannot cause infection without concurrent infection with hepatitis B. Question 19. B) It may be spread by the faecal-oral route Explanation: Hepatitis A is not usually spread through blood or conventional sexual contact, and, unlike hepatitis B and C, does not induce a chronic carrier state. A vaccine is available, and immune serum globulin may be useful in the management of outbreaks and immunocompromised or pregnant patients. Anti-HAV antibodies of IgM type may be useful diagnostically. 210 Question 20. E) It may cause cirrhosis Explanation: Hepatitis B is commonly transmitted through blood or sexual contact. The most common route of transmission world-wide is vertical during childbirth; this route of infection carries a much higher risk of chronic infection (see the link below), which may ultimately lead to cirrhosis and hepatocellular carcinoma. A vaccine is given to all health-care staff in the UK. Question 21. E) Anti-HBc IgG and HBsAb Explanation: This is difficult but important to understand. Both the natural history of infection and the serological tests are explained in the link below. A few things are particularly important to commit to memory: a vaccinated patient will only have antibody to the surface protein (content of vaccine) but a patient who is immune (previously exposed and cleared) will have antibodies to the whole virus, i.e. core and surface antibodies. Note that HbsAg is present in chronic infection but, likewise, appears in acute infection; acute infection can be differentiated from chronic infection by the presence of anti-HBc IgM. Question 22. C) It effectively rules out hepatitis B as the cause of his illness Explanation: Anti-HBs is found in the blood of patients who have been successfully immunised against hepatitis B. As a nurse, this patient will have been immunised before taking up employment. If you're still having trouble with interpretation of these serological tests, have another look at the link below Question 23. E) Treatment with interferon is ineffective in chronic infection Explanation: Interferon treatment is effective in some patients with hepatitis B. Question 24. E) Acute infection is usually asymptomatic Explanation: Hepatitis C is only rarely symptomatic in the acute phase, and is often only discovered once cirrhosis has developed. About 80% of infected patients develop chronic infection, which usually progresses ultimately to cirrhosis. Treatment with pegylated interferon and ribavirin can eradicate the virus completely in some patients. Although reinfection almost inevitably occurs after transplant, this treatment may give otherwise terminally ill patients many years of a high quality of life, and should not be withheld for this reason. Question 25. B) There is a genetic predisposition Explanation: Twin studies have revealed a genetic contribution to ALD, although there is at least one obvious environmental factor involved. After a presenting complication of cirrhosis, most patients who become abstinent will be alive after 5 years. Question 26. C) Non-alcoholic fatty liver disease Explanation: Obesity is by far the most common cause of non-alcoholic fatty liver disease, which also shows an association with type 2 diabetes mellitus and the metabolic syndrome. It is the most likely cause in this patient. The introduction of tests to detect and exclude infected blood units has massively reduced the risk of transmission of hepatitis B and other viruses through blood transfusion. The chances of hepatitis B transmission from a unit of blood in the UK in 2002 were around 0.24 per 1 000 000 units. Question 27. A) Co-amoxiclav Explanation: Co-amoxiclav (amoxicillin plus clavulanic acid) may cause a cholestatic hepatitis up to 42 days after a course of treatment has finished. Paracetamol in normal doses can cause liver necrosis, but this only occurs in highrisk patients, such as those with preexisting alcoholic liver disease. 211 Question 28. E) Hereditary haemochromatosis Explanation: The combination of joint pain (caused by chondrocalcinosis), diabetes mellitus ('bronzed diabetes), hepatomegaly and hyperpigmentation is characteristic of hereditary haemochromatosis, one of the most common inherited diseases in northern Europeans. About 90% of patients are male, perhaps due to the protective effect of iron loss with menstruation. Question29. B) Weekly venesection of 500 ml blood Explanation: The complications of haemochromatosis arise because of massive iron overload. The aim of treatment is to remove this excess iron safely, and this is done by weekly venesection until iron levels return to normal. Question30. C) Wilson's disease Explanation: Recurrent acute hepatitis with parkinsonian features and choreoathetoid movements suggest Wilson's disease. The Kayser-Fleischer rings (shown here) around the cornea are pathognomonic but easily missed. Of the other options, hereditary haemochromatosis usually presents later in life with advanced liver disease. The others may cause acute liver failure but do not cause Kayser-Fleischer rings or extrapyramidal manifestations. BuddChiari syndrome is hepatic venous thrombosis, Amanita phalloides is a profoundly hepatotoxic mushroom, and ecstasy (MDMA) is a drug of abuse that may cause liver failure. Question31. A) Penicillamine Explanation: Penicillamine is a copper chelator and is the treatment of choice in Wilson's disease. It removes copper in the urine and confers an excellent prognosis, provided it is commenced before the development of irreversible liver and cerebral damage. Question32. E) Chronic viral hepatitis Explanation: All of these conditions predispose to cirrhosis and hepatocellular carcinoma. Hepatitis B- and C-related cirrhosis is particularly carcinogenic. In chronic hepatitis B infection, but not chronic hepatitis C infection, hepatocellular carcinoma can also occur in the absence of cirrhosis. Question33. C) Acute cholecystitis Explanation: This is a classic presentation of acute cholecystitis. Biliary colic causes pain but not inflammation, and so the pyrexia and leucocytosis make this diagnosis less likely. Acute pancreatitis is highly unlikely, given the normal amylase. Mirizzi's syndrome (a stricture in the common hepatic duct caused by gallstones impacted in the cystic duct) and choledocholithiasis (stones in the bile duct) would be expected to cause abnormal LFTs in a patient with disease severe enough to present with systemic symptoms. Question34. C) Cholecystokinin Explanation: Cholecystokinin secretion is increased after a meal. It promotes satiety, increases pancreatic enzyme secretion, stimulates gallbladder contraction and relaxes the sphincter of Oddi. Question35. A) Recurrent epigastric pain, radiating to the back, lasting 2 hours then subsiding spontaneously Explanation: 'Biliary colic' usually lasts for around 2 hours and occurs intermittently. It is most commonly felt in the epigastrium (70%) or right upper quadrant (20%), and often radiates to the interscapular region or the tip of the right scapula. Of the other options, D is characteristic of dyspepsia and E is suggestive of an acute myocardial infarction. B and C are relatively nonspecific presentations but serious diagnoses such as dissecting thoracic aneurysm and acute pancreatitis must be considered. 212 Question36. B) Abdominal ultrasound scan Explanation: Ultrasound is quick and inexpensive and does not expose the patient to radiation. Stones may be visualised within the gallbladder and bile duct, and dilatation of the bile duct may be seen, indicating distal obstruction of bile flow. Question37. B) Correction of any coagulopathy with fresh-frozen plasma Explanation: The liver is a highly vascular organ and life-threatening haemorrhage may occur following injury to it. Most patients presenting for TIPSS have cirrhosis, and impairment of hepatic synthetic function leading to coagulopathy is common. This is effectively corrected by replacing clotting factors by administering fresh-frozen plasma. Question38. C) Cholestasis and hepatitis are both common presentations Explanation: Alcoholic liver disease is a common cause of substantial suffering, so a good understanding of it is important. It may be detected incidentally in an asymptomatic individual or may present with features of cholestasis, hepatitis or advanced cirrhosis. Alcohol causes several different pathological lesions including macrovesicular steatosis. Fatty liver secondary to alcohol carries a good prognosis and may be reversible with as little as 3 months of abstinence. Cirrhosis is found in only 10% of alcoholics at postmortem. The total amount of alcohol ingested rather than the concentration determines the risk of liver damage. Question39. E) Chronic hepatitis C infection Question 40. D) Hypoglycaemia Explanation: Hypoglycaemia does not precipitate hepatic encephalopathy but is an important differential diagnosis in a patient with liver disease presenting with confusion or drowsiness. Chapter 23 BLOOD DISORDERS Question1. A) They are derived from megakaryocytes Explanation: Red blood cell precursors are called erythroblasts or normoblasts. These nucleated cells divide and acquire haemoglobin. The nucleus is then extruded from the cell. The first non-nucleated red cell is the reticulocyte. Increased red cell production is therefore associated with increased numbers of circulating reticulocytes. Megakaryocytes give rise to platelets. Question2. D) Pneumococcal infection Explanation: Eosinophils have phagocytic potential and are involved in combating parasitic infection. They are also implicated in allergic reactions (e.g. atopic asthma, hay fever, eczema). Bacterial infection typically causes a neutrophilia. Question3. C) Carbimazole Explanation: See list of Drugs causing neutropenia Question4. C) Thalassaemia Explanation: Iron deficiency, thalassaemia and sideroblastic anaemia all cause a microcytosis (reduced red cell size or mean cell volume, MCV). Vitamin B12 or folate deficiency, chronic liver disease, alcohol excess and hypothyroidism cause a macrocytosis (i.e. increased MCV). Question5. B) Cirrhosis Explanation: Target cells have a central area of haemoglobinisation and are seen typically in liver disease, thalassaemia and post-splenectomy. Question6. B) Multiple myeloma Explanation: Chronic myeloid leukaemia, myelofibrosis and malaria may all produce massive splenomegaly. Portal 213 hypertension secondary to cirrhosis of the liver is a common cause of splenomegaly in the UK. Multiple myeloma, a malignant proliferation of plasma cells associated with excess production of a monoclonal immunoglobulin (paraprotein), may produce a diverse array of clinical manifestations but does not cause splenomegaly. Question7. B) Coagulation by the extrinsic pathway is initiated by the interaction of factor VII with tissue factor Explanation: Clotting factors are synthesised in the liver. The coagulation process can be activated by one of two pathways (extrinsic and intrinsic). The extrinsic pathway is thought to be the major physiological mechanism in vivo, and is initiated by the interaction of factor VII with tissue factor. The final step in the cascade is the conversion of fibrinogen to fibrin. Antithrombin, protein C and protein S are natural inhibitors of the clotting system. Antithrombin has inhibitory activity against thrombin and factor Xa. The binding of heparin to antithrombin accelerates this inhibitory activity. Question8. B) Factor V Explanation: Clotting factors are synthesised by the liver. Factors II, VII, IX and X are produced as inactive proteins. They are activated by a carboxylase enzyme which requires vitamin K as a cofactor. In this process, vitamin K is inactivated to an epoxide; it must therefore be reactivated by a reductase enzyme. Warfarin inhibits the latter reaction, reducing the availability of active vitamin K and thereby exerting an anticoagulant effect. Question9. C) It provides an accurate assessment of platelet function Explanation: The prothrombin time (PT) assesses the extrinsic pathway of the coagulation cascade and is prolonged by deficiencies of factors II, V, VII and X. Warfarin leads to prolongation of the PT. The international normalised ratio (INR) is used to monitor warfarin treatment; it is the ratio of the patient's PT to a normal control PT corrected to the international thromboplastin. The activated partial thromboplastin time (APTT) assesses the intrinsic pathway and is prolonged in patients with haemophilia A. Thrombocytopenia and abnormal platelet function lengthen the bleeding time but do not affect the PT or APTT. Question10. B) Haemarthrosis Explanation: Muscle and joint bleeds suggest a coagulation defect. Purpura, prolonged bleeding from superficial cuts, epistaxis, gastrointestinal haemorrhage and menorrhagia suggest thrombocytopenia, abnormal platelet function or von Willebrand's disease. Question11. D) Desmopressin aggravates the tendency to bleeding Explanation: Haemophilia A is an Xlinked recessive condition characterised by factor VIII deficiency. There is a spectrum of severity. Large joint haemarthroses and muscle haematomas are characteristic. Recurrent bleeds into joints can lead to secondary osteoarthritis. Treatment is usually with factor VIII concentrate. Desmopressin (vasopressin, antidiuretic hormone ) can also be used to treat mild bleeds or cover minor surgery in patients with mild haemophilia. 214 Question12. C) Doppler ultrasound scan of the leg Explanation: A patient's clinical risk of having a DVT can be established using the Wells scoring system. Those with a high or medium risk should undergo definitive investigation by Doppler ultrasound or venography. For patients with a low risk, the plasma D-dimer should be measured; a normal level excludes a DVT, but a raised level should prompt ultrasound or venography. A positive D-dimer is not diagnostic of a DVT, but a negative Ddimer in patients at low risk of a DVT essentially excludes the diagnosis. Depending on the clinical context, a thrombophilia screen may be indicated after the diagnosis of venous thrombosis has been confirmed. Question13. E) ABO incompatibility reactions are mediated by complement Explanation: The ABO system comprises four different blood groups: O, A, B and AB. Individuals have antibodies directed against the A or B antigens that are not expressed on their own red cells. Group O blood can therefore be given to all patients, as the infused red cells do not express any AB antigens ('universal donor'), while patients with group AB blood can safely receive blood of all four groups, as they do not have antibodies to either A or B antigens ('universal recipient'). The transfusion of ABOincompatible blood is the main cause of fatal acute transfusion reactions, and the risk is greatest if group A red cells are infused into a group O recipient. The recipient's antibodies bind to antigens on the transfused cells, activating complement. The resulting lysis of red blood cells may lead to disseminated intravascular coagulation and renal failure. Question14. C) Transfusion of RhDnegative blood to an RhD-positive woman may result in production of anti-RhD antibodies Explanation: IgG antibodies to RhDpositive red cells are produced if such cells enter the circulation of an RhD-negative individual (e.g. via blood transfusion or fetomaternal haemorrhage). If an RhDnegative woman is so sensitised and subsequently becomes pregnant with a RhD-positive fetus, then the anti-RhD antibodies can cross the placenta and cause severe anaemia and neurological damage (haemolytic disease of the newborn). Anti-RhD immunoglobulin (anti-D) can be given to RhD-negative pregnant women after potentially sensitising events to prevent the development of endogenous Rhesus antibodies. Question15. D) Give paracetamol and continue transfusion at a slower rate Explanation: Febrile non-haemolytic transfusion reactions are not uncommon. If temperature rises by less than 1.5°C and the patient is otherwise well, then it is reasonable to administer paracetamol and continue the transfusion at a slower rate. Allergic reactions (urticaria, bronchospasm, angio-oedema) should be treated with IV chlorphenamine and hydrocortisone, nebulised salbutamol and IM adrenaline (epinephrine) according to their severity. The transfusion should be stopped, and any unused blood should be returned to the blood bank together with a repeat sample for a 'group and screen' test. Question16. E) Creutzfeldt-Jakob disease (CJD) Explanation: Blood products are routinely screened for HIV, human T lymphotrophic virus (HTLV), hepatitis B and C, and syphilis. Question17. A) Omeprazole Explanation: Iron is absorbed in the upper small intestine. Hydrochloric acid secreted by the stomach helps to maintain iron in the soluble reduced ferrous (Fe2+) state, as opposed to the oxidised ferric (Fe3+) state; the ferrous form is more easily absorbed. 215 Reduced gastric acid secretion following long-term proton pump inhibitor therapy can therefore lead to iron malabsorption. Aspirin causes iron deficiency by increasing gastrointestinal blood loss, not by interfering with its absorption. Question18. C) Upper gastrointestinal endoscopy Explanation: Iron deficiency causes a microcytic, hypochromic anaemia. The most common cause in men and postmenopausal women is gastrointestinal blood loss. This may result from upper or lower gastrointestinal malignancy, peptic ulcer disease, inflammatory bowel disease, diverticular disease, colonic polyps and angiodysplasia. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) can exacerbate any blood loss. The gastrointestinal tract must therefore be investigated by endoscopy (upper gastrointestinal endoscopy and colonoscopy) or barium studies. Question19. C ) Cold agglutinin disease Explanation: Iron deficiency occurs when iron losses or physiological requirements exceed absorption. (see link below). Cold agglutinin disease is a cause of intravascular haemolysis resulting from the development of IgM antibodies to red cells. It can occur transiently in association with Mycoplasma pneumoniae infection or infectious mononucleosis, or may follow a chronic course in patients with underlying lymphoma. Question 20. D) Reduced ferritin Explanation: All of the above typically occur in iron deficiency but plasma ferritin is the best single confirmatory test on account of its high specificity (i.e. a low ferritin is strongly suggestive of iron deficiency). On the other hand, a normal ferritin level does not exclude iron deficiency as levels may be elevated in systemic inflammation (ferritin is an acute phase protein) or liver disease, despite absent bone marrow stores. Question 21. D) It is often due to dietary deficiency Explanation: Vitamin B12 and folate deficiency lead to impaired DNA synthesis. This results in a megaloblastic anaemia associated with a raised mean cell volume (MCV). The blood film shows oval macrocytes and hypersegmented neutrophils. In severe cases there may be peripheral blood cytopenias. Vitamin B12 is absorbed in the terminal ileum. Deficiency may therefore arise from Crohn's disease or surgery affecting this part of the bowel. B12 deficiency is very rarely dietary in origin, only affecting strict vegans. Question 22. B) Nystagmus Explanation: Vitamin B12 deficiency is associated with neurological disease in up to 40% of patients. Peripheral nerve involvement gives rise to a 'glove and stocking' peripheral neuropathy. Spinal cord damage results in subacute combined degeneration of the cord; posterior column involvement causes loss of vibration and joint position sensation (resulting in ataxia), and corticospinal tract damage leads to upper motor neuron signs. In rare cases, chronic B12 deficiency can lead to dementia. Question 23. C) Total body stores are small Explanation: Foods rich in folate include leafy vegetables, fruits and animal protein. Pregnancy is a common cause of folate deficiency, especially in twin pregnancies and hyperemesis gravidarum. Pernicious anaemia is an autoimmune condition in which there is antibody-mediated destruction of gastric parietal cells. This leads to reduced secretion of intrinsic factor and impaired absorption of vitamin B12; folate is unaffected. The Schilling test is helpful in distinguishing B12 deficiency secondary to pernicious anaemia from that resulting from malabsorption. It is, however, rarely performed in practice. Serum folate is very sensitive to dietary intake, and red cell folate provides a more accurate indicator of folate stores. 216 Question 24. D) Hereditary spherocytosis Explanation: The normocytic anaemia, reticulocytosis, elevated bilirubin and elevated LDH suggest a haemolytic process, consistent with either autoimmune haemolytic anaemia or hereditary spherocytosis. The presence of reticulocytes, which are large, accounts for the MCV at the upper end of the normal range. One would expect the direct Coombs test to be positive in autoimmune haemolytic anaemia, making hereditary spherocytosis the more likely diagnosis in this case. The anaemia of chronic disease may cause a normocytic anaemia but would not account for the features suggesting haemolysis. Coeliac disease may lead to anaemia through iron and/or folate malabsorption but both are normal in this case. The normal B12 level excludes pernicious anaemia. Question 25. B) Haemosiderinuria Explanation: Haemosiderinuria occurs when all other mechanisms for 'mopping up' free intravascular haemoglobin have been exhausted and is always indicative of intravascular haemolysis. Earlier features include a fall in haptoglobin levels and formation of methaemalbumin (detected by the Schumm's test). Reticulocytosis and elevated LDH may result from any cause of haemolysis. Splenomegaly may occur in extravascular haemolysis where physiological destruction occurs in the fixed reticulo-endothelial cells in the liver or spleen. Positive direct Coombs test indicates immune-mediated destruction of red cells. Question 26. C) It may lead to the development of cholesterol gallstones Explanation: In most cases of hereditary spherocytosis there is a compensated chronic haemolytic state. However, the condition can be complicated by haemolytic, aplastic or megaloblastic crises. The latter results from folate deficiency, which in turn arises from increased red cell turnover. This can be precipitated by pregnancy, and patients with hereditary spherocytosis should receive folic acid supplements. The hyperbilirubinaemia resulting from haemolysis gives rise to pigment (not cholesterol) gallstones. The spleen is the main site of haemolysis, and splenectomy may therefore improve the anaemia. Question 27. C) Glucose-6-phosphate dehydrogenase Explanation: Glucose-6-phosphate dehydrogenase is essential for the intracellular production of NADPH which protects the red cell against oxidative stress. Deficiency can result in haemolysis. Question 28. D) Sickle-cell anaemia is usually accompanied by a reticulocytosis Explanation: Sickle-cell disease is caused by an amino acid substitution in the beta globin polypeptide chain. The condition is inherited as an autosomal recessive trait. Homozygotes only produce abnormal beta chains which form abnormal HbS (sicklecell anaemia), while heterozygotes make a mixture of normal HbA and abnormal HbS (sickle-cell trait). Individuals with sicklecell trait are usually asymptomatic and may be relatively resistant to falciparum malaria. Patients with sickle-cell disease usually have a compensated anaemia associated with a reticulocytosis. The high reticulocyte count represents the body's attempt to maintain an adequate haemoglobin concentration in the face of red cell sickling. Even with optimal medical care, life expectancy is greatly reduced. Question 29. Peripheral neuropathy Explanation: Hypoxia, dehydration and infection precipitate sickling. This can 217 lead to a vaso-occlusive crisis, where plugging of small blood vessels produces acute severe bone pain (e.g. dactylitis, avascular necrosis of the hip, pain in the limbs or vertebrae). Recurrent sickling in the spleen can cause splenic infarction and ultimately hyposplenism. Bone marrow infarction can result in fat emboli to the lungs and cause pulmonary infarction (sickle chest syndrome). Question 30. C) Beta-thalassaemia minor Explanation: Normal adult haemoglobin (HbA) consists of two alpha and two beta globin chains (V2_2). The thalassaemias are a group of inherited disorders in which there is impairment of globin chain production. In alpha-thalassaemia the alpha genes are deleted; in betathalassaemia (seen most commonly in the Mediterranean area) beta chain production is defective. In beta-thalassaemia major (seen in homozygotes), HbA production is absent or grossly reduced; individuals develop a profound microcytic hypochromic anaemia, and electrophoresis reveals increased levels of HbF (V2W2). Beta-thalassaemia minor (seen in heterozygotes) results in a microcytic blood picture with no clinical manifestations; there is a raised fraction of HbA2 (V2a2). Question 31. C) Acute myeloid leukaemia (AML) Explanation: This patient has a high white cell count associated with anaemia and thrombocytopenia. The hypercellular bone marrow indicates increased white cell proliferation with 'spill over' into the peripheral blood. The excess of immature blast cells of the myeloid lineage suggests a diagnosis of AML. Although white cells are massively increased in number, they are immature and functionally useless. They take up increasing amounts of marrow space at the expense of the normal haematopoietic stem cells. Question 32. D) Chronic myeloid leukaemia (CML) Explanation: This patient has a marked leucocytosis originating from the granulocyte series. The picture is dominated by mature neutrophils. This pattern of granulocyte proliferation with fairly normal cell maturation is consistent with chronic myeloid leukaemia. In some cases, CML may transform into an acute leukaemia (blast crisis phase) characterised by proliferation of immature blast cells. Blast crisis is relatively refractory to treatment and is the major cause of death in patients with CML. Question 33. E) Chronic myeloid leukaemia (CML) Explanation: Around 95% of patients with CML possess the Philadelphia chromosome. This is a chromosomal abnormality characterised by reciprocal translocation of genetic material between chromosomes 9 and 22. The fragment from chromosome 9 carries the abl oncogene and joins the breakpoint cluster region (BCR) on chromosome 22. The resultant BCR ABL chimeric gene codes for a tyrosine kinase that stimulates cell proliferation and plays a causative role in the disease. The development of imatinib, a specific inhibitor of BCR ABL tyrosine kinase activity, has revolutionised the management of CML. Question 34. C) Hyposplenism is a frequent finding Explanation: Chronic lymphocytic leukaemia (CLL) has an insidious onset, and the diagnosis is made incidentally following a routine full blood count in 70% of patients. The condition most commonly arises in the elderly, and is characterised by a monoclonal proliferation of B lymphocytes. Clinical features include symptomatic anaemia, infection, lymphadenopathy, night sweats and weight loss. Splenomegaly and warm autoimmune haemolytic anaemia may also be present. Treatment is generally only required for patients with systemic symptoms, bone marrow failure, progressive lymphadenopathy or splenomegaly. The oral chemotherapeutic agent chlorambucil is usually first-line therapy. 218 Question 35. D) Bone marrow aspiration reveals a hypocellular marrow Explanation: Myelodysplastic syndrome (MDS) comprises a group of haematopoietic stem cell disorders characterised by peripheral blood cytopenias and abnormal-looking (dysplastic) blood cells. The marrow is hypercellular with dysplastic changes. It predominantly affects elderly patients, presenting with symptoms of anaemia, recurrent infections or bleeding. The condition is incurable in most patients, and supportive care with transfusion and antibiotics is the mainstay of treatment. Given time, all forms of MDS will ultimately progress to AML, although the time course to progression is highly variable. Question 36. B) Reed-Sternberg cell Explanation: The characteristic histological abnormality in Hodgkin lymphoma is the presence of ReedSternberg cells - large, malignant lymphoid cells of B-cell origin. Ringed sideroblasts are erythroid precursors in which iron has accumulated in the mitochondria, seen in sideroblastic anaemia. Auer rods are present in acute myeloid leukaemia. Burr cells are irregularly shaped red blood cells typical of uraemia, and Howell-Jolly bodies are nuclear remnants commonly seen postsplenectomy; both are detected on the peripheral blood film. Question 37. B) Multiple myeloma Explanation: Multiple myeloma is a malignant proliferation of plasma cells associated with excess production of a monoclonal immunoglobulin (paraprotein). The plasma cells release cytokines which stimulate osteoclasts and result in bone resorption, bone pain, pathological fractures and hypercalcaemia. Bone marrow involvement can lead to a normocytic anaemia. Paraprotein deposition in the kidneys, hypercalcaemia and dehydration can all contribute to cause renal failure. The erythrocyte sedimentation rate is often elevated. The paraprotein (most often of the IgG subtype) can be measured in plasma and detected by protein electrophoresis. Question 38. D) Bence Jones protein in urine and lytic lesions on plain X-ray Explanation: This is a difficult question but contains a number of useful learning points. The diagnosis of multiple myeloma requires two of the following criteria: • increased malignant plasma cells in bone marrow • serum and/or urinary paraprotein skeletal lesions (characteristically lytic lesions). • Thus, although options A and B would both be highly suggestive of myeloma, only option D satisfies the criteria. Bence Jones protein is an immunoglobulin light chain produced by plasma cells that appears in urine. Hypercalcaemia is a common feature in myeloma, resulting from lytic bony lesions. The ESR may be elevated as a result of increased plasma viscosity from the paraproteinaemia, although it is worth noting that only 5% of patients with an ESR persistently > 100 mm/hr actually have myeloma. Lytic bony lesions, the skeletal hallmark of myeloma, are best detected by skeletal survey and not a radioisotope bone scan; in fact, in the absence of fractures, both plasma ALP and radioisotope bone scan are normal in myeloma. 219 Question 39. E) Aspirin is contraindicated Explanation: Polycythaemia rubra vera (PRV) is a myeloproliferative disorder characterised by an increased red cell mass and elevated haemoglobin concentration. Neutrophil and platelet counts are often also raised. Patients may present with symptoms of hyperviscosity (e.g. headache, dizziness, loss of concentration, lethargy, pruritus). Splenomegaly is common. The hyperviscosity predisposes to arterial thrombosis; aspirin reduces this risk. Venesection reduces red cell mass and relieves hyperviscosity symptoms. Question 40. B) Thrombotic thrombocytopenic purpura Explanation: Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) represent two conditions on a continuum characterised by microangiopathic haemolytic anaemia, the formation of platelet thrombi in the microcirculation and resultant thrombocytopenia. Other features include renal failure and fluctuating neurological signs due to microvascular thrombosis. Question 41. D) Non-Hodgkin lymphoma Explanation: The combination of lymphadenopathy and systemic upset in an elderly patient raises the possibility of non-Hodgkin lymphoma (NHL). Hodgkin's disease usually affects young adults, although there is a second peak at age 50-70. CML is usually associated with a marked leucocytosis and does not typically cause generalised lymphadenopathy. Question 42. C) Fibrinogen levels are elevated Explanation: Disseminated intravascular coagulation (DIC) is triggered by conditions causing exposure of tissue factor with consequent activation of the coagulation system via the extrinsic pathway. Common causes of DIC include Gram-negative septicaemia and antepartum haemorrhage. Intravascular coagulation results in thrombosis with consumption of platelet and coagulation factors. The resultant thrombocytopenia, prolonged prothrombin and activated partial thromboplastin time lead to a haemorrhagic state. Fibrinogen levels are low, and levels of D-dimer (a fibrin degradation product indicating fibrin turnover and breakdown) are raised. Question 43. C) The anticoagulant effect of low molecular weight heparin can be assessed using the activated partial thromboplastin time (APTT) 220 Explanation: Unfractionated IV heparin exerts its anticoagulant affect by enhancing the effect of antithrombin, which itself inhibits the procoagulant activity of factors IIa, VIIa, IXa, Xa and XIa. The level of anticoagulation is monitored using the APTT. Low molecular weight heparins are administered subcutaneously on a once- or twice-daily basis. They augment antithrombin activity against factor Xa and do not affect the APTT. The half-life of IV heparin is around 1 hour, and if a patient bleeds it is usually sufficient simply to discontinue the heparin; in severe cases, heparin can be neutralised with protamine. It takes warfarin takes several days to exert its therapeutic effect, and treatment with heparin is required during this window. Heparin-induced thrombocytopenia (HIT) is a recognised complication, requiring immediate discontinuation of the drug. Chapter 24 MUSCULOSKELETAL DISORDERS Question 1. D) Paget's disease Explanation: Paget's disease is a common condition characterised by increased and disorganised bone remodelling. The biochemical picture is that of a normal calcium, phosphate and PTH, in conjunction with a raised alkaline phosphatase. Osteoporosis (in the absence of a fracture) does not cause any biochemical abnormality. The fact that the lady has been complaining of difficulty in hearing may be significant, as deafness is a clinical feature of Paget's disease. Question 2. C) Septic arthritis Explanation: Although all of the above may cause an acute monoarthritis, septic arthritis is the most likely cause, given the progressive pain, overlying erythema, pyrexia, recent episode of cellulitis (representing a possible portal of entry for infection) and presence of risk factors (diabetes mellitus, pre-existing joint disease, age). With crystal synovitis (urate, pyrophosphate) pain is at its maximum within the first day; progressive pain and overlying erythema should always suggest sepsis. Question 3. D) Joint aspiration Explanation: Although a full blood count, CRP test and X-ray of the joint might provide useful information, only an aspirate of fluid from the knee sent for microscopy, culture and sensitivity can definitively confirm the diagnosis. Blood cultures also identify the organism in around 50% of cases. 221 Question 4. C) Exacerbations of symptoms are often associated with stressful life events Explanation: The principal features of fibromyalgia are multiple sites of regional pain, particularly over the neck and back, and fatigability. In general there is a discrepancy between the level of disability reported by the patient and the physical findings found on examination. Joint disease, neurological deficit, muscle wasting and a raised ESR are not features of fibromyalgia and any of these should prompt a search for an alternative explanation. Treatment is symptomatic and patient education is important, as is the provision of a graded exercise programme. Question 5. C) Prolonged morning stiffness Explanation: Morning stiffness in osteoarthritis tends to be brief, lasting only a few minutes. Thereafter, pain is related to movement and weight-bearing, and relieved by rest. This pattern contrasts markedly with inflammatory arthritides such as rheumatoid arthritis, in which morning stiffness is typically prolonged (lasting longer than an hour) and symptoms are exacerbated by inactivity. Question 6. D) Methotrexate Explanation: Osteoarthritis is extremely common and knowledge of the various aspects of its management is therefore essential. Methotrexate is a diseasemodifying drug used in the treatment of the inflammatory arthritides and has no role in the management of osteoarthritis. Question 7. B) The presence of antidouble-stranded DNA (anti-dsDNA) antibodies on blood tests Explanation: Anti-dsDNA antibodies are highly specific for systemic lupus erythematosus and would therefore make the diagnosis of rheumatoid arthritis unlikely. The presence of rheumatoid factor, on the other hand, would be consistent with the diagnosis and, in common with the other options listed, is included in the American Rheumatism Association diagnostic criteria for rheumatoid arthritis. Because of its low specificity, however, a high titre of rheumatoid factor at presentation has more prognostic value (it suggests a worse prognosis) than diagnostic value. Question 8. D) Alopecia Explanation: All of the above are recognised features of rheumatoid arthritis, with the exception of alopecia. Alopecia is more commonly associated with systemic lupus erythematosus. Question 9. C) Felty's syndrome Explanation: Although an enlarged spleen may potentially be found in any of the above conditions, Felty's syndrome refers to the association of splenomegaly and neutropenia with rheumatoid arthritis and is, therefore, the most likely diagnosis here. It has a peak incidence in the 50-70year-old age group, typically occurring in patients with longstanding disease and a positive rheumatoid factor. In addition to splenomegaly, clinical features include recurrent infections, weight loss, leg ulcers and lymphadenopathy. Question 10. A) Bouchard's nodes Explanation: Bouchard's nodes are posterolateral hard swellings of the proximal interphalangeal joints, characteristically seen in nodal generalised osteoarthritis along with Heberden's nodes (similar swellings arising from the distal interphalangeal joints). 222 Question 11. B) Naproxen Explanation: DMARDs have the potential to reduce target tissue damage in rheumatoid arthritis and may therefore favourably alter the rate of disease progression. Naproxen is a non-steroidal anti-inflammatory drug (NSAID) and, as such, provides symptomatic relief only. Question 12. D) Keratitis with hydroxychloroquine Explanation: All of the above associations are true with the exception of D. At very high doses hydroxychloroquine (though more commonly chloroquine) may cause retinitis (classically a 'bull's eye' maculopathy) and not keratitis (inflammation of the cornea). Question 13. B) Strongly positive rheumatoid factor Explanation: As one of the seronegative spondarthritides (see Box 25.51 in the link below), ankylosing spondylitis has no association with seropositivity for rheumatoid factor. Rheumatoid factor is negative or positive only in low titre. Question 14. D) Atlanto-axial instability Explanation: Psoriatic arthritis may present with a variety of different patterns of joint disease. Atlanto-axial subluxation, however, is a potentially serious manifestation of rheumatoid arthritis and occasionally other conditions (e.g. classic ankylosing spondylitis, Down's syndrome). Question 15. A) Bendroflumethiazide Explanation: Thiazide diuretics such as bendroflumethiazide reduce urinary excretion of uric acid and may therefore lead to hyperuricaemia and eventual urate crystal formation. Other drugs that cause hyperuricaemia include aspirin, ciclosporin, pyrazinamide and alcohol. Question 16. C) Allopurinol is often used in the treatment of an acute attack Explanation: Allopurinol is not used to treat acute gout. Management of acute gout includes appropriate analgesia (often a non-steroidal anti-inflammatory drug), oral colchicine, joint aspiration and intraarticular injection with a long-acting steroid. The most common side-effects of colchicine are nausea and diarrhoea. Definitive diagnosis of gout requires demonstration of negatively birefringent needle-shaped crystals in a joint aspirate when viewed under polarised light. Question 17. B) Acromegaly Explanation: Sporadic, familial and metabolic-associated forms of pseudogout exist. The common feature is deposition of calcium pyrophosphate crystals in the joint (most commonly the knee, followed in frequency by the wrist, shoulder, ankle and elbow), leading to chondrocalcinosis. Acromegaly is associated with a secondary osteoarthritis, but not with pseudogout. Question 18. C) Hypothyroidism Explanation: Hyperthyroidism, not hypothyroidism, is associated with osteoporosis. Question 19. D) Weight-bearing exercise is protective Explanation: Protective factors include weight-bearing exercise, high dietary calcium and late menopause. The biochemical profile in osteoporosis should be entirely normal, and any deviation from this, other than in the context of a fracture (which may cause a rise in alkaline phosphatase), should arouse suspicion of an alternative diagnosis. The diagnosis is based on the T-score, which measures the number of standard deviations difference between the bone mineral density of the patient and the mean of a normal healthy population with peak bone mass. The Zscore is the number of standard deviations from the mean for an age-matched population, which is a less precise predictor of risk of fracture than the Tscore. 223 Question 20. D) Sclerodactyly Explanation: All the skin and mucous membrane conditions listed are associated with SLE except for sclerodactyly, which is a feature of systemic sclerosis. Question 21. A) They inhibit bone resorption Explanation: Bisphosphonates act by adsorbing to bone surfaces and becoming incorporated into the bone matrix. When they are then ingested by osteoclasts in the process of bone resorption, large amounts of the drug are released within the cell, bringing about osteoclast death and a reduction in bone resorption. They have no direct stimulatory effect on bone formation. The increased bone mineral density is thought to be due to decreased removal of minerals from existing bone. Question 22. D) Difficulty passing urine Explanation: The most important lesson from this question is that there are socalled 'red flag signs' (see the link below) which must not be ignored, as they may be indicative of serious underlying pathology. All of the other symptoms described are consistent with simple mechanical low back pain, which is likely to improve with time and simple analgesia. Question 23. D) Psoriasis Explanation: The term 'seropositive' refers to arthritis that associates with an increased prevalence of rheumatoid factor. Psoriasis is one of a family of conditions the seronegative spondarthritides - that manifest arthritis with no such increased association with rheumatoid factor. Rheumatoid factor has low specificity for rheumatoid arthritis and occurs with increased prevalence in a wide range of conditions. Question 24. C) Concomitant respiratory disease Explanation: Comorbidity does not increase the incidence of NSAIDassociated gastrointestinal ulceration, but if a person develops a complication (bleeding, perforation, obstruction) comorbidity, especially cardiovascular disease and diuretic therapy, increases the associated morbidity and mortality. Coprescription of a proton pump inhibitor such as omeprazole can reduce the incidence of NSAID-associated peptic ulceration, and is particularly important to consider in those with any of the risk factors listed above. A past history of peptic ulcer bleeding or perforation is usually taken as an absolute contraindication to oral NSAIDs. Question 25. A) Conjunctivitis Explanation: Reiter's disease is the most common cause of inflammatory arthritis in men aged 16-35. It consists of the classic triad of arthritis, urethritis and conjunctivitis; additional extra-articular features include keratoderma blenorrhagica, nail dystrophy, buccal erosions and circinate balanitis. Precipitants for Reiter's include bacterial infections such as Salmonella or Campylobacter, and also sexually transmitted infections such as Chlamydia, but not streptococcal throat infection. Nodules are a feature of rheumatoid arthritis. Question 26. E) DXA bone scanning involves the intravenous injection of radioisotope Explanation: DXA bone scanning measures the extent to which the passage of X-ray beams through bone is attenuated. Since this is determined by the degree of mineralisation, the relative density of the bone can be calculated. Two scores are calculated; the T-score compares the bone mineral density (BMD) of the subject to that of a healthy young person, and the Z-score to that of an agematched control. 224 Both T- and Z-scores refer to numbers of standard deviations from the mean. Osteoporosis is defined as a T-score of < 2.5. The preferred sites for measurement are the lumbar spine and the hip. DXA scans should not be confused with isotope bone scans, which involve the intravenous injection of radioisotope. Question 27. A) Calcium channel blockers such as nifedipine may help symptoms of Raynaud's phenomenon Explanation: The dihydropyridine calcium channel blockers help prevent vasospasm and are a useful treatment for Raynaud's phenomenon. An ACE inhibitor is an important prophylactic agent in reducing the risk of development of a hypertensive renal crisis, particularly in patients who have diffuse cutaneous disease, who are most at risk of this complication. Other useful treatments include proton pump inhibitors for oesophagitis (which is often severe) and the oral endothelin antagonist bosentan for pulmonary hypertension. On the other hand, no agent is known to improve the cutaneous manifestations of the disease. Question 28. C) A violaceous rash around the eyes Explanation: Recognised cutaneous features of dermatomyositis include a violaceous rash around the eyes, Gottron's papules over the proximal interphalangeal and distal interphalangeal joints, periorbital oedema and abnormal nailfold capillary loops. Weakness of proximal musculature is a cardinal feature. Question 29. A) There is an association with HLA-B27 Explanation: HLA-B27 is strongly associated with ankylosing spondylitis. Sjögren's is associated with HLA-B8 and HLA-DR3. Question 30. B) Sjögren's syndrome Explanation: The case described fits best with a diagnosis of Sjögren's syndrome. Although the serology would be compatible with both SLE and rheumatoid arthritis, the description of keratoconjunctiva sicca (dry eyes) and xerostomia (dry mouth) and the combination of both positive rheumatoid factor and ANA are typical of Sjögren's. Question 31. A) There is an association with HLA-B27 Explanation: HLA-B27 is strongly associated with ankylosing spondylitis. Sjögren's is associated with HLA-B8 and HLA-DR3. Question 32. D) Muscle stiffness and tenderness Explanation: Polymyalgia rheumatica is a disease of older people; patients are almost always over 55 years, but there is a mean age of onset of 70. The ESR is invariably elevated. There is a rapid and dramatic response to systemic corticosteroids, with most patients experiencing relief of symptoms within 72 hours of first dose. The most common complaint is of muscle stiffness and there is often marked muscle tenderness but no muscle weakness. Muscle weakness and wasting suggest primary muscle disease such as polymyositis. Question 33. E) Give 60 mg of prednisolone by mouth Explanation: The history and exam findings detailed above are absolutely classical for temporal or giant cell arteritis. This is a large-vessel vasculitis affecting, predominantly, the branches of the temporal and ophthalmic arteries. It is sight-threatening, and the correct treatment once the diagnosis is suspected is immediate administration of high-dose oral corticosteroid. Such steroid treatment will not alter any histological abnormalities obtained on temporal artery biopsy if this procedure is undertaken within 1-2 weeks. 225 Question 34. C) It is a large-vessel vasculitis Explanation: Polyarteritis nodosa (PAN) is a rare vasculitis of small and mediumsized (not large conduit) vessels, which predominately affects men, is ANCAnegative and may have a number of manifestations, including arteritis of the vasa nervorum, leading to peripheral neuropathy, abdominal pain, fever and severe hypertension secondary to renal infarctions. Hepatitis B is a risk factor for development of PAN, and incidence of PAN is higher in places such as Alaska where the infection is endemic. Question 35. C) Osteoclasts are responsible for bone formation Explanation: All of the above are true with the exception of option C; osteoclasts are responsible for bone resorption (C for chewing away at the bone), osteoblasts are responsible for bone formation (B for building up bone). Question 36. C) Articular cartilage has a rich vascular supply Explanation: The major learning point here is that articular cartilage is avascular. Question 37. E) Osteopenia with Paget's disease of bone Explanation: X-rays in Paget's disease commonly show a mixed picture of osteosclerosis and focal osteolysis, but not osteopenia. All of the other radiological features described are true. Question 38. E) Serum biochemistry is usually normal in osteomalacia Explanation: Osteomalacia is commonly associated with low serum calcium and phosphate, accompanied by elevated alkaline phosphatase. In contrast, osteoporosis is associated with normal serum biochemistry. Options B and C highlight the difference in the sensitivity and specificity of tests. ANA has a high sensitivity for lupus (almost 100%), so if a person tests negative for ANA this virtually excludes the diagnosis. (High sensitivity is a desirable quality in a good screening test.) Anti-dsDNA antibodies, however, provide a highly specific test for lupus, meaning that if a person tests positive for anti-dsDNA antibodies, then the diagnosis is almost certainly lupus. Unfortunately, anti-dsDNA has low sensitivity for lupus. Question 39. D) Hydralazine Explanation: Hydralazine, along with procainaminde, isoniazid, minocycline and chlorpromazine, can cause a drug-induced lupus syndrome that commonly presents as skin rash and arthralgia. Renal involvement is less common in druginduced lupus than in primary lupus, but can occur. 226 Question 40. B) Henoch-Schönlein purpura Explanation: The combination of arthritis, abdominal pain and purpura in a patient of this age suggests a diagnosis of Henoch-Schönlein purpura. The condition often follows an upper respiratory tract infection. Question 41. D) Chest X-ray Explanation: A chest X-ray is the least likely to aid diagnosis. A skin biopsy, although invasive, would confirm the diagnosis by demonstrating on immunofluorescence IgA deposition in the vessel walls. The serum IgA levels are also often raised. Henoch-Schönlein purpura may cause an acute nephritis leading to haematuria and/or renal failure, thus U&E and urinalysis are important. An FBC should be checked in all cases of purpura to exclude the possibility of thrombocytopenia (low platelet count). Question 42. E) Pulmonary embolism Explanation: Cardiovascular complications are the leading cause of death in patients with Marfan's, particularly aortic dissection which accounts for 27-48% of deaths. There is no increased risk of pulmonary embolism. Chapter 25 NEUROLOGICAL DISEASE Question 1. B) C5/C6 Explanation: The biceps and supinator jerks both correspond to the C5/C6 nerve roots. Question 2. D) Schwann cells Explanation: The myelin sheath surrounding axons is essential for rapid conduction of the action potential. Myelin is formed by Schwann cells in the peripheral nervous system, and by oligodendrocytes in the central nervous system (CNS). Astrocytes form the structural framework for neurons within the CNS. Microglia are specialised macrophages. Astrocytes, oligodendrocytes and microglial cells are collectively known as glial cells. Ependymal cells line the cerebral ventricles. Question 3. B) Receptive dysphasia Explanation: The language centres are located in the dominant hemisphere. The left hemisphere is dominant in almost all right-handed individuals and 50% of lefthanded individuals. Lesions to Broca's area within the frontal lobe cause expressive dysphasia; damage to Wernicke's area in the temporal lobe results in expressive dysphasia. Question 4. A) Frontal lobe Explanation: The frontal lobe is responsible for personality, emotional control and social behaviour, and lesions here commonly present with disinhibited or antisocial behaviour. Associated physical phenomena may include 'frontal release signs', i.e. primitive reflexes such as grasp reflex, rooting reflex and palmomental response. 227 Question 5. B) Childhood absence epilepsy Explanation: Absence epilepsy (formerly known as petit mal) is a form of generalised epilepsy encountered in childhood and is characteristically associated with a 3 cycles/second 'spike and wave' pattern on EEG. Individuals develop altered awareness and often have a staring appearance lasting for only a few seconds, followed by rapid recovery. Question 6. D) Carpal tunnel syndrome Explanation: The principal use of nerve conduction studies is to identify damage to peripheral nerves, determine whether such damage is focal (e.g. carpal tunnel syndrome) or diffuse (e.g. polyneuropathy such as Guillain-Barré syndrome), and establish if it is predominantly axonal or demyelinating in nature. Electromyography (rather than nerve conduction) is abnormal in motor neuron disease and myasthenia gravis. Multiple sclerosis is a disease of the central rather than the peripheral nervous system. Question 7. E) MRI head scan Explanation: Although there is no specific test for multiple sclerosis, the demonstration of patchy demyelination of white matter within the central nervous system may assist in the diagnosis. MRI is far more sensitive than CT in detecting soft tissue abnormalities and is therefore the investigation of choice. Question 8. D) Current treatment with aspirin Explanation: Lumbar puncture is contraindicated in the presence of raised intracranial pressure, as the procedure can result in the downward shift of intracranial contents into the spinal canal (coning). Lumbar puncture should therefore not be performed if there is papilloedema, a reduced level of consciousness or focal neurological signs that may suggest an underlying space-occupying lesion. It is also contraindicated in the presence of a bleeding tendency (e.g. thrombocytopenia, disseminated intravascular coagulation, treatment with warfarin). Aspirin treatment is not a contraindication. Question 9. B) Worsens as the day progresses Explanation: Headache due to raised intracranial pressure tends to be maximal on waking in the morning, and improves or resolves through the day as the upright posture reduces intracranial pressure. It often responds well to simple analgesia. Question 10. C) Tension headache Explanation: Tension headache is extremely common and often follows a chronic course. The pain is usually generalised and becomes more noticeable as the day progresses. Although it responds poorly to analgesia, individuals are typically able to continue with their daily activities. 228 Question 11. B) Migraine Explanation: The history of severe, throbbing, episodic, unilateral headache associated with nausea, vomiting and photophobia in a patient of this age is highly suggestive of migraine. 'Classical' migraine consists of a triad of paroxysmal headache, nausea and vomiting, and an 'aura' of focal neurological events. However, many patients experience paroxysmal headache (with or without vomiting) without aura; this is termed 'common' migraine. When present, the aura is most often visual, consisting of shimmering zigzag lines ('fortification spectra'). Question 12. A) Sumatriptan Explanation: Avoidance of obvious precipitants may prevent migraine attacks. Acute migraine may respond to simple analgesics (e.g. paracetamol) and antiemetics. Severe attacks can be treated with one of the 'triptans' (e.g. sumatriptan); these are 5-hydroxytryptamine agonists that cause vasoconstriction of the extracranial arteries, which are thought to be dilated in migraine. The other agents listed can all be used to prevent recurrent migraines but are not useful during an acute attack. Question 13. E) Associated nasal congestion and conjunctival injection Explanation: Typical cluster headache comprises episodic severe, unilateral, periorbital pain. It is associated with unilateral lacrimation, nasal congestion and conjunctival injection. Episodes characteristically last 30-90 minutes and can occur daily for a few weeks, followed by respite for several months before recurrence of another 'cluster'. The condition is five times more common in men than women. Question 14. B) Persistent nystagmus Explanation: Disorders affecting either the vestibular nucleus in the brain stem or its central connections are distinguished from disorders of the labyrinth by the persistence of both vertigo and nystagmus. Positionally induced central vertigo persists for as long as the head position is maintained, as does the accompanying nystagmus. In contrast, peripheral positional vertigo (and any associated nystagmus) fatigues quite quickly if the inducing position is maintained. This phenomenon of fatigability is seen with the Hallpike maneouvre (see the link below). This test is positive in benign paroxysmal positional vertigo - a condition, more common in the elderly, which causes brief episodes of vertigo with certain head movements. Severe vertigo lasting a few days associated with vomiting and ataxia is characteristic of labyrinthitis. Ménière's disease, another cause of paroxysmal labyrinthine vertigo, usually presents initially with tinnitus and distorted hearing. Question 15. B) Severely bitten tongue Explanation: Determining the cause of a collapse can be difficult and obtaining a witness account is crucial. Details of the events immediately before (prodrome) and after (recovery) provide useful clues. Vasovagal syncope is typically preceded by lightheadedness, sensations of heat, tinnitus and dimming of vision. A history of aura preceding the blackout suggests seizure but is often lacking (perhaps due to post-ictal retrograde amnesia). Cardiac syncope (e.g. Stokes-Adams attack) frequently occurs without any warning. With regard to the event itself, urinary incontinence and brief twitching of limbs are non-specific features that may occur during any syncopal attack. On the other hand, cyanosis and tongue biting are more specific to seizure and the finding of a severely bitten tongue after loss of consciousness is pathognomonic of a generalised seizure. Extreme 'death-like' pallor is characteristic of cardiac syncope. A prolonged recovery phase characterised by confusion, headache, drowsiness or amnesia strongly suggests seizure. 229 Question 16. C) Left pre-central gyrus Explanation: Partial (focal) seizures result from paroxysmal discharge of neurons in a focal area of the cerebral cortex. The clinical manifestations depend on the area of cortex involved. Involvement of the pre-central gyrus (frontal lobe, motor cortex) causes partial motor seizures affecting the contralateral side of the body, while post-central gyrus (parietal lobe, sensory cortex) activity leads to partial sensory seizures. Occipital foci result in partial visual seizures, and temporal lobe foci can cause rhythmic smacking of the lips or alterations of perception (e.g. déjà vu). Partial seizures are classified as simple partial if consciousness remains intact, and complex partial if consciousness is altered. Any partial seizure may subsequently spread to the rest of the brain, resulting in a tonicclonic phase (secondary generalisation). Question 17. D) Alcohol withdrawal Explanation: Alcohol withdrawal causes generalised seizures. The other listed conditions cause focal cerebral pathology and can therefore result in partial seizures; these may become secondarily generalised. Individuals with partial seizures should undergo brain imaging to identify focal structural defects. Question 18. D) He should refrain from driving until seizure-free for 1 year Explanation: Patients should be advised to inform the Driver and Vehicle Licensing Authority (DVLA) of their seizure and to refrain from driving until they are fit-free for 1 year. Question 19. D) Sodium valproate Explanation: Anticonvulsant treatment should generally be considered after two seizures have occurred. The majority of patients can be controlled with monotherapy. Sodium valproate is firstline treatment for primary generalised epilepsy; carbamazepine is the usual drug of choice for partial seizures. Question 20. C) IV diazepam Explanation: Status epilepticus describes prolonged seizure activity or recurrent seizures without full recovery of consciousness between attacks. It usually refers to generalised tonic-clonic seizures and is a medical emergency. Question 21. B) Muscle fasciculations Explanation: Muscle wasting and fasciculations are manifestations of lower motor neuron lesions (anterior horn cell, motor root, nerve plexus or peripheral nerve). All of the other options listed are signs of upper motor neuron pathology (motor cortex or corticospinal tracts). Question 22. D) Parkinson's disease Explanation: Parkinson's disease is characteristically associated with a 'pillrolling' tremor which is most pronounced at rest. The tremor of thyrotoxicosis is best detected by asking the patient to hold the arms outstretched (i.e. sustained posture). Cerebellar lesions cause an intention tremor which worsens as the hand approaches a fixed target (identified using the 'finger-nose' test). A flapping tremor (asterixis) is observed with metabolic derangements such as hepatic encephalopathy and hypercapnia; holding the arms outstretched with hyperextended wrists leads to intermittent flapping of the hands. Question 23. D) Hemiballismus - brief, non-purposeful twitching of muscle groups Explanation: Hemiballismus refers to dramatic, flinging movements of the limbs. These are usually unilateral, and result from vascular lesions of the subthalamic structures. The definition given in option D is that of myoclonus. Question 24. B) Right-sided cervical spinal cord lesion Explanation: This patient has BrownSéquard syndrome, caused by a unilateral spinal cord lesion. 230 Fibres conveying joint position and vibration sensation enter the spinal cord at the posterior horn and pass without synapsing into the ipsilateral dorsal columns, from where they ascend to the brain stem. They synapse with secondorder neurons in the gracile and cuneate nuclei, which then cross the midline and ascend to the thalamus. Pain and temperature sensory fibres, on the other hand, enter the spinal cord and synapse with second-order neurons. These cross the midline at the level of entry and then ascend in the contralateral spinothalamic tract to the thalamus. A unilateral cord lesion will therefore cause ipsilateral loss of joint position and vibration sensation, with contralateral loss of pain and temperature below the level of the lesion. Ipsilateral upper motor neuron signs develop due to involvement of the ipsilateral corticospinal tracts. Question 25. D) 9 Explanation: •Eye-opening To pain = 2 •Motor response Localises = 5 •Verbal response Incomprehensible sounds = 2 The Glasgow Coma Scale provides a tool for objectively assessing a patient's level of arousal and response to stimuli. It is particularly useful for monitoring trends in the level of consciousness. Question 26. E) Imaging of the brain (CT or MRI) should be performed in most patients Explanation: Anticholinesterases (e.g. donepezil) may produce modest improvements in cognitive function in selected patients with mild or moderate Alzheimer's disease. Prominent visual hallucinations would be more suggestive of Lewy body dementia than Pick's disease. Infections (e.g. urinary tract infection, pneumonia) can cause acute confusion (delirium) and can lead to decompensation in patients with dementia, but are not in themselves a cause of dementia. Brain imaging should be performed to exclude potentially treatable pathology (e.g. cerebral tumour, chronic subdural haematoma), but brain biopsy is very seldom required. Question 27. C) Hyperreflexia Explanation: Features of cerebellar pathology include ataxia, incoordination of limb movements (e.g. past pointing), intention tremor, dysdiadochokinesis (inability to perform alternating movements), dysarthria and nystagmus. Question 28. D) Left homonymous lower quadrantanopia Explanation: The anatomy of the visual pathways is shown in the link below. Lesions anterior to the optic chiasm cause visual field defects restricted to one eye, while lesions posterior to the chiasm cause homonymous field defects affecting the contralateral side of the visual field in both eyes. From the lateral geniculate body in the thalamus, lower fibres running in the temporal lobe represent the upper part of the field, while upper fibres in the parietal lobe represent the lower part of the field. A right parietal lesion will therefore cause a left homonymous lower quadrantanopia. Question 29. D) Right abducens (VI) nerve lesion Explanation: Horizontal diplopia on rightward gaze implies a problem with right eye abduction (right VI nerve stimulates lateral rectus) or left eye adduction (left III nerve stimulates medial rectus). A useful tip to remember is that the outer image always arises from the paretic eye; the lesion here must therefore be within the right VI (abducens) nerve or its nucleus. Question 30. A) Left oculomotor (III) nerve Explanation: The trochlear (IV) nerve supplies the superior oblique muscle, while the abducens (VI) nerve supplies lateral rectus. All other extraocular muscles are innervated by the oculomotor (III) nerve. This nerve also supplies levator palpebrae superioris (which keeps the upper eyelid open) and the constrictor pupillae muscle (which mediates papillary constriction in response to light). Third nerve palsies therefore lead to ptosis with a dilated unreactive pupil, and the eye rests in a 'down and out' position due to unopposed activity of the lateral rectus and superior oblique muscles. 231 A Painful third nerve palsy is classical of a posterior communicating artery aneurysm. Question 31. B) Horner's syndrome Explanation: Sympathetic nerve fibres originating in the hypothalamus pass down the brain stem and cervical cord to emerge at T1, then return back up to the eye in association with the internal carotid artery and supply the dilator pupillae muscle to stimulate pupil dilatation. Lesions of the sympathetic pathway (e.g. due to locally invasive apical lung tumour) therefore result in a unilateral small pupil associated with a partial ptosis and reduced sweating on that side (Horner's syndrome). Question 32. D) The ability to wrinkle the forehead is preserved Explanation: The term 'Bell's palsy' refers to an isolated idiopathic facial nerve (VII) palsy. There is lower motor neuron weakness on the affected side, with a facial droop and an inability to wrinkle the forehead. Other features include difficulty closing the affected eye, reduced tear and saliva secretion, and reduced taste sensation. Hyperacusis may occur if the nerve to stapedius (a branch of the facial nerve) is involved. Preservation of the ability to wrinkle the forehead on the affected side indicates an upper motor neuron pattern of facial weakness. Question 33. E) Treatment with warfarin Explanation: Patients who are anticoagulated with warfarin or who have a non-iatrogenic coagulopathy require urgent imaging of the brain to rule out the possibility of an intracerebral haemorrhage. Question 34. D) Loss of consciousness Explanation: The definition of a TIA is the rapid onset of a focal neurological deficit, of presumed vascular origin, that resolves within 24 hours. It also includes transient monocular blindness due to vascular occlusion in the retina (amaurosis fugax). Basilar ischaemia can cause loss of consciousness but is very uncommon and, as a general rule, the diagnosis of TIA should not be made in patients who present with episodes of syncope, dizziness or confusion as these do not reflect focal cerebral dysfunction. The evidence to support surgery in symptomatic patients with moderate (5069%) stenosis and asymptomatic patients with severe stenosis is less conclusive, as these patients have a smaller benefit/risk ratio than patients with severe symptomatic stenosis. Patients with stenosis of < 50% do not benefit from carotid endarterectomy, irrespective of symptoms. Finally, a patient with severe residual disability would gain little benefit from preventing a further stroke within the same territory and may have a greater risk of surgical complications. Question 35. D) Warfarin Explanation: In addition to lifestyle modifications, antiplatelet, lipid-lowering and antihypertensive therapy forms the cornerstone of secondary prevention for most patients with an ischaemic stroke. Recent large-scale randomised trials have demonstrated the benefit of statins and antihypertensives in these patients, even with blood pressure and cholesterol levels within the 'normal' range. There is no net benefit in prescribing anticoagulants after ischaemic stroke to patients in sinus rhythm. The evidence base for stroke secondary prevention is included in the link below. Question 37. B) CT head scan Explanation: The clinical signs and symptoms in this patient are suggestive of a subarachnoid haemorrhage. An emergency head CT scan is essential. About 15% of patients with a subarachnoid haemorrhage will have a normal CT scan; in these cases, a lumbar puncture should be performed 12 hours following the onset of headache to look for xanthochromia (breakdown products of red blood cells). Question 36. C) Left middle cerebral artery territory infarct with good functional recovery, 80% left carotid artery stenosis Explanation: Carotid endarterectomy reduces the risk of stroke in patients with severe stenosis of the internal carotid artery but carries a significant risk of perioperative mortality and stroke. Decisions on whether to operate must, therefore, be based on a careful benefit/risk analysis. The absolute reduction in risk of future stroke is greatest for symptomatic patients with 70-99% stenosis and, in general, outweighs the risk of surgical complications. Importantly, symptomatic patients are defined as patients with a TIA or non-disabling stroke in the territory of the carotid artery on the same side as the stenosis in the preceding 6 months. 232 Question 38. E) Hypercholesterolaemia Explanation: Cerebral venous thrombosis is uncommon. Hypercholesterolaemia and hypertension are risk factors for arterial thromboembolic disease, but not for venous occlusion. Question 39. C) It follows a relapsing and remitting course in the majority of patients Explanation: Multiple sclerosis (MS) is characterised by inflammation and patchy demyelination within the central nervous system (CNS). The condition is more common in females and peak age of onset is between 30 and 40 years. MS can present with diverse neurological features according to the areas of the CNS involved. Optic neuritis (optic nerve), sensory symptoms and leg weakness (spinal cord), and ataxia (cerebellar fibres) occur frequently but intellectual function is usually preserved until the later stages of the disease. Most patients experience a relapsing-remitting course, while 20% have primary progressive MS. Although there is no single diagnostic investigation, plaques of CNS demyelination can be seen on MRI. The presence of oligoclonal bands of IgG in the cerebrospinal fluid is consistent with (but not specific for) a diagnosis of MS. Question 40. B) Methylprednisolone Explanation: Pulsed high-dose steroids (methylprednisolone) reduce the duration of relapses by means of their antiinflammatory effect. Interferon beta is an immune modulator which reduces the number of relapses by 30%. Azathioprine also has some effect in reducing relapses and improving long-term outcome. Plasmapheresis and IV immunoglobulin are occasionally used in severe disease. Question 41. B) Senile plaques and neurofibrillary tangles are characteristic features on brain histology Explanation: Alzheimer's disease is the most common cause of dementia, affecting 5% of the population over 65 years of age and 30% over 80. Histology from the brain typically reveals senile plaques (containing amyloid) and neurofibrillary tangles. Although both short- and longterm memory are affected, defects in the former are generally more obvious and occur earlier. CT head scan typically shows cerebral atrophy, but there are no specific appearances that are pathognomonic for Alzheimer's disease. Treatment with anticholinesterase drugs may lead to modest improvements in cognitive function in selected patients but they do not halt progression of the disease. Question 42. B) Parkinson's disease Explanation: Parkinson's disease is an idiopathic condition characterised by depletion of dopaminergic neurons in the substantia nigra. It is classically composed of the triad of tremor, rigidity and bradykinesia. A fine resting tremor is usually first seen in the fingers and thumb, and is characteristically 'pill-rolling' in nature. Rigidity (increased muscle tone) causes stiffness and a flexed posture. Coexistent tremor causes cogwheel rigidity. Bradykinesia (slowness of movement) is manifest by slowness of gait and difficulty with tasks such as fastening buttons and writing. Question 43. B) Wide-based gait Explanation: An unsteady wide-based gait (ataxia) is a feature of cerebellar disease. It is also seen in conditions with impaired joint position sensation. 233 Question 44. D) Dyskinesia secondary to levodopa can be improved by modifying the dosing regimen Explanation: The rationale for giving levodopa (a dopamine precursor) in Parkinson's disease is to boost dopamine production in the remaining dopaminergic neurons of the substantia nigra. However, if it is given as monotherapy, more than 90% is decarboxylated peripherally, preventing it from reaching the brain and leading to a high incidence of side-effects. This is overcome by coadministering a peripheral dopa-decarboxylase inhibitor (carbidopa or benserazide). As these do not cross the blood-brain barrier they prevent conversion to dopamine in the periphery but allow it to occur in the brain. Involuntary movements (dyskinesia) are related to long-term use of levodopa therapy. Initiation of levodopa should therefore be delayed until there is significant disability, especially in younger patients. Dyskinesia can be improved by modification of the drug dose and frequency of administration. Levodopa may help tremor in some patients but is generally more effective at relieving bradykinesia and rigidity. Anticholinergic drugs may be useful in treating tremor and rigidity. Question 45. E) Haloperidol Explanation: Neuroleptic agents (e.g. haloperidol, chlorpromazine) and certain anti-emetics (e.g. metoclopramide) have anti-dopaminergic actions and can therefore cause parkinsonism Question 46. A) It has autosomal recessive inheritance Explanation: Huntington's disease is an autosomal dominant disorder characterised by involuntary choreiform movements. Symptoms usually develop in middle age, by which time individuals have often had children. Genetic screening is available for asymptomatic family members after appropriate counselling. Involuntary movements are accompanied by psychiatric symptoms which eventually progress to frank dementia. 234 Question 47. B) Motor neuron disease Explanation: Motor neuron disease is a progressive disorder caused by degeneration of motor neurons in the spinal cord and cranial nerve nuclei, and of pyramidal neurons in the motor cortex. Patients present with muscle weakness, and neurological examination reveals a combination of lower motor neuron (e.g. wasting, fasciculations) and upper motor neuron (e.g. increased tone, brisk reflexes, extensor plantars) signs. Sensation is normal. Involvement of the lower cranial nerves may cause bulbar palsy with dysarthria and dysphagia. Question 48. C) Administer IV benzylpenicillin Explanation: The presence of headache, fever and neck stiffness in association with a purpuric rash is strongly suggestive of meningococcal meningitis. This is a medical emergency requiring resuscitation and immediate treatment with empirical IV antibiotics. Although a lumbar puncture is required, this must not delay antimicrobial therapy. A CT head scan should be performed before lumbar puncture if there are clinical signs of possible raised intracranial pressure (e.g. drowsiness, focal neurological deficit, seizures). Question 49. B) Upper motor neuron signs predominate Explanation: Poliomyelitis is caused by an enterovirus. Involvement of anterior horn cells results in lower motor neuron signs (flaccid weakness, fasciculations, areflexia). Treatment consists of bed rest and physiotherapy. Respiratory muscle involvement may necessitate invasive ventilation via a tracheostomy. Childhood immunisation with an oral vaccine has dramatically reduced the incidence of polio in many countries. Question 50. C) Cerebral abscess Explanation: The CT scan shows a single low-density area with ring enhancement in the right temporal lobe, consistent with a cerebral abscess. There is associated cerebral oedema and midline shift to the left. The condition typically presents over days or weeks with features of raised intracranial pressure, seizures and focal neurological signs. The main differential diagnosis is a cerebral tumour. Question 51. E) Tetanus antitoxin should be administered in all suspected cases Explanation: The bacterium Clostridium tetani is found in soil and usually enters the body through contaminated wounds. It multiplies only in anaerobic conditions, e.g. necrotic tissue. The organism itself remains localised but produces an exotoxin that affects anterior horn cells. The most important early symptom is spasm of the masseter muscles, which causes difficulty in opening the mouth and chewing (trismus or lockjaw). The rigidity spreads to the rest of the body and causes violent convulsions. Treatment comprises IV human tetanus antitoxin to neutralise absorbed toxin, and wound debridement and benzylpenicillin to prevent further toxin production (toxoid). Question 52. C) Cognitive function is usually preserved Explanation: Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy mediated by a prion protein. Spongiform change in the brain is associated with neuronal loss and gliosis in the grey matter. Clinical features include myoclonic jerks and a rapidly progressive dementia. Repetitive slow wave complexes on EEG are characteristic, and life expectancy is reduced to 4-6 months. Question 53. B) Primary intracerebral tumours do not, generally, metastasise outside the central nervous system Explanation: Primary intracerebral tumours do not metastasise outside the central nervous system, even if malignant. 235 However, metastases to the brain can occur from extracranial primary tumours (e.g. lung, breast, gastrointestinal tract). MRI offers better resolution than CT, and is particularly useful for imaging structures in the posterior fossa (brain stem and cerebellum). The steroid dexamethasone reduces oedema surrounding cerebral tumours, and can often lead to an improvement in conscious level. Meningiomas are benign tumours arising from the meninges, whereas gliomas (e.g. astrocytoma) arise from the brain substance; the former are therefore easier to resect completely and carry a better prognosis. Question 54. C) Cerebellar signs may be present Explanation: Acoustic neuroma is a benign tumour arising from the Schwann cells of the VIII (vestibulocochlear) cranial nerve. The condition may arise sporadically or in association with neurofibromatosis type 2. Sensorineural deafness is extremely common. The tumour is located in the cerebellopontine angle; distortion of the cerebellum can therefore lead to ataxia and cerebellar signs in the limbs. As the lesion is situated in the posterior fossa, MRI is the investigation of choice. Treatment is by surgical resection. Question 55. C) Idiopathic (benign) intracranial hypertension Explanation: Idiopathic (benign) intracranial hypertension is characterised by raised intracranial pressure in the absence of a space-occupying lesion or ventricular dilatation. The condition tends to affect young obese women. Other risk factors include drugs (e.g. tetracyclines, vitamin A), Addison's disease and withdrawal of steroid therapy. Patients complain of headache, and papilloedema is usually the only clinical finding. CT of the head is normal and lumbar puncture demonstrates elevated CSF pressure with normal constituents. Question 56. E) Acetazolamide Explanation: Treatment of idiopathic intracranial hypertension includes weight loss and withdrawal of precipitating factors. Other measures to lower intracranial pressure include the carbonic anhydrase inhibitor, acetazolamide, and repeated therapeutic lumbar puncture. Cervical cord compression would produce motor and sensory signs in all four limbs (see the link below). The spinal cord ends at the T12/L1 spinal level; below this hangs a collection of nerve roots called the cauda equina. Lesions compressing the cauda equina therefore only cause lower motor neuron signs in the lower limbs. Question 57. C) Headache Explanation: Normal pressure hydrocephalus is characterised by the triad of gait apraxia, dementia and urinary incontinence. Headache is not a feature. The condition predominantly affects older patients. Question 61. C) Spinal MRI scan Explanation: Spinal MRI is the investigation of choice for identifying compression of the spinal cord or nerve roots. Urgent investigation is required to enable prompt treatment. Soft tissue detail is excellent, and it is often possible to determine the reason for the cord compression (e.g. spinal metastases). This helps guide further therapy in terms of surgery or radiotherapy. Question 58. D) S1 Explanation: Sudden onset of lower back pain while straining, accompanied by 'sciatica' and a positive straight leg raise test, suggests lumbar disc herniation with resultant nerve root compression. The neurological findings described correspond to pressure on the S1 root. Question 59. B) Analgesia and early mobilization Explanation: The vast majority of patients with sciatica recover with a combination of analgesia and early mobilisation. Bed rest retards recovery. Local anaesthetic or steroid injections are useful if there is associated ligamentous injury or joint dysfunction. Surgery is usually considered only if there is no response to conservative treatment or if there is progressive neurological disability. Radiotherapy is useful only in patients with spinal cord or nerve root compression secondary to malignancy. Question 60. C) Thoracic cord compression Explanation: This patient has signs of spinal cord compression, which is likely to be secondary to bony metastases. The presence of bilateral upper motor neuron signs in the legs (spastic paraparesis), with preserved upper limb function and a sensory level on the abdomen, suggests involvement of the thoracic spinal cord. 236 Question 62. D) Multiple sclerosis Explanation: Peripheral neuropathies can affect a single nerve (mononeuropathy) or several discrete nerves (mononeuritis multiplex), or be generalised (polyneuropathy). There are multiple causes, the most common of which are diabetes mellitus, alcohol excess, GuillainBarré syndrome, hereditary neuropathies, vitamin deficiencies and drug toxicity. Question 63. A) Amiodarone Explanation: See list of Drugs causing peripheral neuropathy Question 64. B) Median nerve Explanation: This patient has carpal tunnel syndrome, a mononeuropathy affecting the median nerve. Symptoms are often self-limiting and a wrist splint may provide some relief. More severe or persisting symptoms may require surgical decompression at the wrist. Question 65. D) Respiratory muscles are not affected Explanation: Guillain-Barré syndrome is an acute inflammatory polyneuropathy caused by cell-mediated demyelination of peripheral and cranial nerves. It is often preceded by a respiratory infection or diarrhoeal illness (usually Campylobacter). Patients develop rapidly ascending muscle weakness, starting in the lower limbs and spreading up to the upper limbs. Involvement of the respiratory muscles can lead to respiratory failure and necessitate ventilatory support. The majority of patients make a complete recovery over 3-6 months. Early treatment with IV immunoglobulin or plasma exchange shortens the duration of ventilation and improves prognosis. Question 66. C) Myasthenia gravis Explanation: The fatigable muscle weakness is typical of myasthenia gravis. Symptoms worsen with exercise and as the day progresses. Features include intermittent ptosis, diplopia (due to extraocular muscle involvement), and weakness of chewing, swallowing, speaking and limb movement. There is no sensory deficit. The condition is more common in women and usually presents between the ages of 15 and 50 years. Question 67. E) The presence of muscle paralysis with fasciculation, sweating and excessive salivation suggests a myasthenic crisis Explanation: Myasthenia gravis is caused by autoantibodies directed against acetylcholine receptors in the post- 237 synaptic membrane of the neuromuscular junction. IV injection of the short-acting anticholinesterase edrophonium (the Tensilon test) increases the available levels of acetylcholine and produces a transient improvement in muscle power. Longer-acting anticholinesterases (e.g. pyridostigmine) are used in the treatment of myasthenia. Thymectomy in patients with antibody-positive disease is associated with a better prognosis, irrespective of whether or not a thymoma is present. Sudden, severe weakness in myasthenia may be due to exacerbation of the disease (myasthenic crisis) or excessive treatment with anticholinesterase drugs (cholinergic crisis). Differentiating between the two is vital and the presence of fasciculations, sweating and excessive salivation suggests a cholinergic crisis. Question 68. C) Delayed relaxation of skeletal muscle Explanation: Myotonic dystrophy is an autosomal dominant condition caused by an expanded triplet repeat on chromosome 19. The characteristic finding is myotonia, an abnormality of muscle relaxation. This can be elicited by asking the patient to make a fist and then rapidly straighten the fingers; the latter can only be performed slowly in patients with myotonic dystrophy. Other features include cardiac conduction abnormalities, lens opacities, frontal balding and cognitive impairment. Autoantibodies to presynaptic calcium channels are a feature of Lambert-Eaton myasthenic syndrome. Chapter 26 SKIN DISEASE Question 1. C) Chronic plaque psoriasis Explanation: The picture shows nail pitting and onycholysis (separation of the nail from the nail bed), both of which are classical of psoriasis. Nail changes are common in psoriasis and also include subungual hyperkeratosis. Neither the description nor the clinical photograph would be consistent with any of the other differentials listed. Question 2. B) It is the only skin disease to demonstrate the Köbner phenomenon Explanation: The Köbner phenomenon describes the tendency of a lesion to arise in areas of previous trauma, such as skin biopsy sites and old surgical scars. Although psoriasis does exhibit the Köbner phenomenon, so do a number of other conditions, including lichen planus and vitiligo. Psoriasis classically has a predilection for the extensor surfaces of the limbs. The Auspitz sign is pathognomonic of psoriasis, and describes the minute capillary bleeding that occurs on lifting a psoriatic scale. Nail changes are common and also include onycholysis. The pustules which may feature are sterile. Question 3. C) Penicillin antibiotics Explanation: All of the above have been associated with flares in psoriasis, except for penicillin antibiotics. Although not mentioned above, alcohol intake is described by many patients as an exacerbant of psoriasis. 238 Question 4. E) Gold Explanation: All of the above except gold are used to good effect in the management of refractory psoriasis; gold is a diseasemodifying drug used in rheumatoid arthritis. Psoralens are natural photosensitisers used in combination with long-wavelength ultraviolet A (PUVA) therapy. Question 5. B) Episodes often last longer than 24 hours Explanation: Urticaria refers to an area of focal dermal oedema secondary to an increase in capillary permeability. It is more commonly known by patients as 'hives', and demonstrates a characteristic weal and flare reaction. Episodes, by definition, last less than 24 hours. There are numerous possible precipitants, all of which trigger mast cell degranulation, leading to release of histamine and a range of other inflammatory mediators. Correspondingly, antihistamines improve symptoms but do not abolish them completely. Question 6. A) Streptococcus pyogenes Explanation: Guttate psoriasis often occurs in children and adolescents after a streptococcal sore throat. The fungus T. rubrum is a common cause of ringworm of the trunk. P. acnes is a bacterium which colonises the pilosebaceous ducts in acne and produces pro-inflammatory factors. B. burgdorferi is the causative organism in Lyme disease, one of the features of which is erythema chronicum migrans, an annular skin lesion which spreads, clearing centrally. S. scabiei causes scabies, an intensely itchy dermatosis characterised by 'burrows' in the web-spaces of the hands. Question 7. D) Necrobiosis lipoidica Explanation: The clinical description and the photograph correlate best with the diagnosis of necrobiosis. Skin conditions which occur with greater frequency in diabetics than in the normal population also include acanthosis nigricans and granuloma annulare. Question 8. D) Topical or intralesional steroids may be useful Explanation: Necrobiosis lipoidica occurs with greater frequency but not exclusively in patients with diabetes. There is no correlation between degree of glycaemic control and severity of the skin disease, and although superinfection may occur, no infective organism is implicated in the pathogenesis. The lesions readily ulcerate and subsequently tend to heal slowly. Question 9. E) Basal cell carcinoma Explanation: The appearance of this lesion is classical for a basal cell carcinoma (BCC) or 'rodent ulcer'. These are slow-growing tumours of the basal cell layer of the epithelium that occur most commonly on the face of elderly individuals. Their clinical appearance is characterised by a pearly, telangiectatic edge, with a central ulcer. Question 10. E) Local invasion is more common than haematogenous spread Explanation: Basal cell carcinomas (BCCs) are slow-growing tumours which very rarely metastasise. They are usually removed by surgical excision. Cryotherapy has significant comorbidity when used for anything other than superficial lesions; radiotherapy can be used for larger lesions, but surgery tends to produce the best cosmetic result. Mohs' surgery is a special kind of 'tissue-conserving' surgery, in which excised tissue margins are examined histologically then extended successively by millimeters until they are clear. Although time-consuming, this method ensures that the bare minimum of tissue is taken. 239 Question 11. C) Warty texture with 'stuck-on' appearance Explanation: In assessing any mole, the principal concern is to exclude malignant melanoma. A naevus with a warty, 'stuckon' appearance is much less worrisome than one which demonstrates any of the other features listed. A warty, 'stuck-on' appearance is more suggestive of a seborrhoeic wart, which is a benign epidermal tumour. A useful mnemonic to help remember worrying features in a mole is 'ABCDE' this is explained in the link below. Question 12. D) Amelanotic melanomas are more common than the pigmented variety Explanation: Melanoma is classified into four basic subtypes: superficial spreading, lentigo maligna, nodular and acral lentiginous. The characteristics of each should be known. Amelanotic melanomas (those without pigment) are very rare; careful examination with a dermatoscope will usually reveal a few flecks of colour. Question 13. A) Dark skin and black hair Explanation: The phenotype of red hair and pale skin is associated with an increased risk of skin cancer, due to exposure to ultraviolet radiation in the absence of adequate melanin pigmentation. The corollary of this is that those with dark skin have a relatively reduced risk of developing skin cancer. All of the other factors mentioned are associated with an increased risk of skin cancer. Question 14. A) Atopic eczema Explanation: This history is pretty classical for atopic eczema. The child has an itchy rash in the skin creases, which began within the first 2 years of life, and there is also a history of asthma, one of the atopic spectrum of disorders. (These comprise hay fever, asthma and a tendency towards allergy: for example, to animal dander.) Lichenification describes the skin changes that occur with prolonged periods of scratching and rubbing, resulting in increased skin markings. It is a feature of many skin diseases. Question 15. D) Dithranol Explanation: Dithranol is an anthralin used in the topical treatment of psoriasis. All of the other agents are important elements of the management of childhood atopic eczema. Topical steroids should be used at an appropriate strength for the site to which they are applied; for instance, as a general rule, nothing stronger than 1% hydrocortisone should be applied to the face, where the skin is thinner than the rest of the body. It may necessary to use more potent steroids elsewhere. Question 16. D) Bullous pemphigoid Explanation: The paucity of oral mucous membrane involvement in bullous pemphigoid is one of the key distinguishing features between this condition and pemphigus. Pemphigus and Stevens-Johnson syndrome may feature bullous lesions of the mucous membranes. SLE may feature oral ulceration. Examination of the mouth of a patient with lichen planus may reveal Wickham's striae (a fine white lacy network overlying the buccal mucosa). Question 17. A) Discoid lupus erythematosus causes a non-scarring alopecia Explanation: Discoid lupus causes a scarring alopecia. Alopecia areata describes a non-scarring patchy hair loss which is associated with other autoimmune conditions, including vitiligo and thyroid disease. 240 A more extensive form of hair loss, called alopecia totalis, describes loss of all scalp hair with preservation of body hair. Alopecia universalis describes loss of all scalp and body hair. Androgenetic alopecia may occur in both males and females. Question 18. C) Antibiotics Explanation: The lesions are those of erythema nodosum, a panniculitis (inflammation in the deep dermis and subcutaneous fat). The nodules are characteristically painful, and although there are many infective causes such as tuberculosis and streptococcal infections (hence a chest X-ray and ASO titre would be appropriate investigations), antibiotics do not form part of the management of this condition. There a number of drug causes, and it is particularly important to ask females about oral contraceptive use. Systemic diseases such as sarcoidosis are also associated. Question 19. C) Macules are usually raised Explanation: A macule is a small, flat area of altered colour or texture. Question 20. D) Bullous impetigo Explanation: All of the above rashes are characteristically itchy with the exception of bullous impetigo, which is a staphylococcal infection of skin, common in young children and the immunocompromised. It occurs when the infecting staphylococci produce exfoliatoxin A or B, which causes blistering lesions to arise. Question 21. E) Atenolol Explanation: All the drugs listed above may cause photosensitivity, with the exception of atenolol. None of the drugs in the ß-blocker class are associated with photosensitivity. Question 22. C) Patients are usually over the age of 18 years Explanation: SSSS is a serious exfoliative skin condition that predominantly affects children, particularly neonates. Question 23. B) Onycholysis Psoriasis Explanation: Nail changes are common in psoriasis and include pitting, onycholysis (separation of the nail plate from the nail bed) and subungual hyperkeratosis. Koilonychia (spoon-shaped nails) is a sign of iron deficiency, while leuconychia (whitening of the nails) is a rare manifestation of hypoalbuminaemia. Fibrosing alveolitis may cause clubbing, as may cyanotic congenital heart disease. Beau's lines, transverse grooves in the nails, are a non-specific manifestation of any acute illness. 241 Question 24. D) Diabetes mellitus Explanation: Diabetes is associated with several skin conditions but not porphyria cutanea tarda. Question 25. B) Digoxin Explanation: Erythema multiforme (EM) is characterised by targetoid lesions that have a 'bull's-eye' appearance. Blisters may feature; severe bullous EM is called Stevens-Johnson syndrome.