Abdominal
Year 2 Lab Sci:
red = extra
conditions
Breast
Year 2 Lab Sci:
CV
Year 2 Lab Sci:
red = extra
conditions
Endocrine
Year 2 Lab Sci:
red = extra
conditions
Haematological
Year 2 Lab Sci:
red = extra
conditions
Locomotor
In depth
In brief
Gastro-oesophageal reflux
Oesophageal carcinoma
Peptic ulcer
Gastric carcinoma
Acute gastro-intestinal bleed
Pancreatic carcinoma
Inflammatory bowel disease
Chronic liver failure
Irritable bowel syndrome
Ascites
Infective gastroenteritis
Malnutrition
Acute and chronic pancreatitis
Perforated viscus
Gallstones including bile duct stones
Coeliac disease
Acute hepatitis
Diverticulitis
Appendicitis
Small and large bowel obstruction
Femoral and inguinal hernia
Oesoph: oesophagits, barrett’s oesophagus, oesophageal Ca,
Stomach: gastritis, PUD, gastric Ca,
SI: coeliac disease, carcinoid (endocrine cell) tumour
LI: appendicitis, diverticular disease, polyps, neoplasia and staging
IBD: Crohn’s and UC
GB: cholecystitis, chollithiasis
Pancreas: pancreatitis, pancreatic Ca
List disorders that may cause:
Dysphagia, haemoatemesis, intestinal obstruction, peritonitis, malabsorption
Abscess
Fibrocystic disease/change
Ductal papilloma
Breast carcinoma (inc staging)
Fibrocystic change, breast Ca, fibroadenoma, lipoma, radial scar; principles of breast screening and triple
assessment; List disorders that can cause breast lumps
Myocardial infarction/ acute coronary syndrome
Valvular heart disease
Angina
Right ventricular failure
Atrial fibrillation
Sub-acute bacterial endocarditis
Essential hypertension
DVT
Left ventricular failure
Congestive cardiac failure
IHD, endocarditis, valvular heart disease, congenital heart disease (ASD, VSD, Fallot’s), cardiomyopathy
(basic aetiology/effects), aneurysm, hypertension, atherosclerosis, vasculitis
Disorders that can cause: left and right sided heart failure
Diabetes (type 1 and 2)
Parathyroid adenoma
Hypo- and hyperthyroidism
Hyperparathyroidism
Goitre
Addison's disease = primary hypoadrenalism
Thyroid nodule
Cushing's syndrome
Thyroid: goitre, Ca, thyrotoxicosis, myoedema
Adrenal: Cushing’s, Addison’s, Conn’s, adrenal Ca
Pituitary: Ca, hypopituitism
Parathyroid: hyper and hypoparathyroidism
Iron deficiency anaemia
Lymphoma
Macrocytic anaemia
Iron deficiency anaemia, (causes at diff ages), megaloblastic anaemia (B12 and folate deficiency),
haemolytic anaemia , sickle cell, thalaseemias, polycythaemia (1°, 2°, relative), aplastic anaemia
Myeloid and lymphoid leukaemias, lymphomas, myeloma, myeloproliferative diseases, clotting times,
haemophilia, von Willebrand’s disease
Osteoarthritis
Rheumatoid arthritis
Gout
Septic arthritis
Prolapsed disc
Year 2 Lab Sci:
Osteoporosis, osteomalacia, metabolic bone disease, Paget’s disease, osteosarcoma, giant cell tumour
Mental Health
Depression
Anxiety
Alcohol dependence
Self-harm
Somatisation
Delirium
Dementia
Psychosis
Delusion
Hallucination
Neck lumps
Cervical lympadenopathy (ALL, AML,CML, CLL)
Parotid and Salivary gland swellings
Neurological
Stroke and TIA
Proximal myopathy
Sub-arachnoid haemorrhage
Multiple sclerosis
Peripheral neuropathy
Epilepsy/seizures
Meningitis
Migraine and tension headache
Parkinson's disease/ Parkinsonism
Cerebrovascular disease, intracranial haemorrhage, meningitis, AD, MS, cerebral Ca, raised ICP (causes and
Year 2 Lab Sci:
effects), dementia (causes), stroke (causes)
Renal tract
Urinary tract infection
Bladder carcinoma
Pyelonephritis
Renal carcinoma
Hydronephrosis
Urinary tract stones
Acute renal failure/acute kidney injury
Chronic renal failure
Benign prostatic hypertrophy
Prostate carcinoma
Year 2 Lab Sci:
Kidney: glomerulonephritis, pyelonephritis, renal Ca, AKI (causes and effects), CRF (causes and effects),
red = extra
nephrotic syndrome (causes and effects)
conditions
Bladder: cystitis, bladder Ca; List DD of haematuria
Respiratory
Acute asthma
Pulmonary fibrosis
Chronic obstructive pulmonary disease
Bronchial carcinoma
Pneumothorax
Unilateral pleural effusion
Lobar pneumonia
Pulmonary embolus
PE, pneumonia, TB, ARDS, sarcoidosis, bronchiectasis, COPD, pulmonary hypertension, occupational lung
Year 2 Lab Sci:
disease, asthma, fibrosing alveolitis, cancers, pleural mesothelioma
Vascular
Peripheral vascular disease
Femoral embolism
Abdominal aortic aneurysm
Varicose veins
Female genital tract In year 4
M genital tract
Testis: neoplasms (teratoma, seminoma, British classification); Prostate: BPH, prostate Ca
Viral hepatitis, steatohepatitis, alcoholic liver disease, 1° biliary cirrhosis, sclerosing cholangitis, ascending
cholangitis, hepatocellular Ca, (causes and effects of haemochromatosis, haemosiderosis, α-1 AT
Liver
deficiency, Wilson’s disease)
Skin
Dermatitis, malignant melanoma, SCC, BCC
Multisystem
AIDS, SLE, DM, rheumatoid disease, polarteritis nodosa, scleroderma
How are cytological samples collected? Advantages and disadvantages of cytology; What diagnoses can be made from
cytological samples at different body sites? Plus chemical pathology questions, haematology guide
Abdominal
Disorder– core
How common is it
Core symptoms
Screening questions
to ask
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Complications
Differential
diagnosis
GORD
‘Heartburn’ (burning, retrosternal) aggrevated by bending, stooping or lying down which ↑ acid
exposure; related to meals; relieved by antacids; pain on drinking alcohol or hot liquids; poor relation
between heartburn and oesophagitis – psychosocial issues play a big role; Regurgitation of food into the
mouth, especially on lying flat or bending; Waterbrash (excess salivation) or bile regurgitation;
Odynophagia (pain on swallowing due to ?oesophagitis or ulceration) and nocturnal asthma
Factors associated with GORD:
Pregnancy; obesity; fat, chocolate or alcohol ingestion; large meals; smoking; drugs (anti-muscarinics,
Ca2+ blockers, nitrates); after treatment for achalasia; hiatus hernia
Mechanisms to prevent GORD:
Some GOR is normal.
Lower oesophageal sphincter is tonically contracted and relaxes only to allow food to pass
Intra-abdominal segment of oesophagus acts like a flap valve
Mucosal rosette formed by folds of gastric mucosa and contraction of diaphragm
Rapid clearance of oesophagus by 2° peristalsis, gravity and bicarbonate
Isolated cases don’t need investigation. If dysphagia, >55yo, >4weeks, persistent symptoms despite
treatment, weight ↓, then investigate
 Upper GI endoscopy: if oesophagitis or Barrett’s oesophagus present then GORD confirmed
 Intraluminal monitoring: 24-hr intraluminal pH monitoring; excessive refulx = pH <4 for >4% of the
time; should also be a good correlation between pH and symptoms
1. Lifestyle:
a. Encourage: weight loss, smoking
cessation, raise bed head, small
regular meals
b. Avoid: hot drinks, alcohol, eating
<3hrs before bed, drugs that slow
motility (nitrates, anticholinergics,
TCA) or that damage the mucosa
(NSAIDS, bisphosphonates)
2. Drugs:
a. Alginate-containing antacids
(Gaviscon/ Magnesium trisilicate):
10mL/8hrs, OTC
b. Prokinetic agents: metocloperamide
?helpful as ↑ gastric emptying
c. H2-receptor antagonist: cimetidine,
acid suppression and OTC
d. PPI: omeprazole; best treatment for
all but mild cases; inhibit gastric
hydrogen/potassium-ATPase; pts who
do not respond to PPIs are said to
have NERD (non-erosive refulx
disease) when endoscopy is normal
3. Surgery: Nissen fundoplication:
indications are unclear but include
severe symptoms, intolerance of
medication, desire not to take meds, expense of meds, concern of long-term s/e; pts who do not
respond to PPIs or those with a functional bowel disease should not have surgery
1. Peptic stricture: in pts >60yo; symptoms are intermittent dysphagia for solids which worsens over a
long time period; may need endoscopic dilatation and long-term PPIs
2. Barrett’s oesophagus: (epithelium metaplasia: squamous→columnar, ‘velvety’ appearence);
3. Oesophageal adenocarcinoma
4. Oesophagitis or ulcers
5. Hernia:
a. Sliding hiatus (80%): gastro-oesophageal junction and part of stomach slides through the hiatus
in diaphragm; >30% of 50yo; produces no symptoms – all symptoms are due to reflux
b. Rolling/ para-oesophageal (20%): gastro-oesophageal junction remains below diaphragm but a
bulge of stomach herniates up into chest alongside oesophagus - ?painful
Oesophagitis (corrosives, NSAIDs); infection (CMV, herpes, Candida); DU; gastric ulcer, cancer; heart
pain (crushing, gripping, radiates to left arm, worse with exercise, dyspnoea)
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Peptic ulcer disease (PUD) and dyspepsia
Duodenal ulcers (DU) affect 10-15% of adults and are 2-3x more common than gastric ulcers
H. pylori:
Slow-growing spiral G-ve flagellate urease-producing bacteria; colonises the mucous layer of gastric
antrum; 80-90% prevalence in developing countries; 20-50% in developed countries; infection highest in
low-income groups; infection usually acquired during childhood (unsure how) and persists for life unless
treated.
Pathogenesis of H pylori:
Not fuly understood; binds to Lewis antigen by BabA adhesion to gastric mucosal cells and causes
gastritis; expresses cytotoxic-associated protein (CagA) and vacuolating toxin (VacA) genes; CagA
product is injected into epithelial cells via a pilus; changes cell morphology, replication, apoptosis; VacA
is a pore-forming protein which ↑ host cell permeability, induces apoptosis and ↓ IR
Results from infection: antral gastritis; peptic ulcers (GU and DU); gastric cancer
Very common in elderly; ↓ rates in young but ↑ in females; more prevalent in developing countries
due to high H. pylori infection rates; can be present with damage via NSAIDs/ Zollinger-Ellison syndrome
Burning epigastric pain; variable relationship to food; DU pain classically occurs at night (and entire
day), is worse when pt is hungry (relieved by eating); may be relieved by antacids/ milk; nausea may
accompany pain; anorexia and weight loss may occur esp with GUs; accompanying back pain suggests
penetrating posterior ulcer; GU = pain on eating; DU = pain when hungry
ALARM symptoms: anaemia, weight loss, anorexia, recent onset of progressive symptoms, melaena/
haematemesis; swallowing difficulty
Tender epigastrium; supraclavicular nodes = Gastric Ca
Pathology:
Peptic ulcers are due to a break in the superficial epithelial cells penetrating down to the muscularis
mucosa; there’s a fibrous base and inflammatory reaction (erosions are just superficial breaks in the
mucosa).
DUs: common on duodenal cap;
95% pts are infected with H. pylori in the antrum (antral gastritis); cure of infection heals the ulcer and
stops DU recurrence; mechanism for DU formation unclear as only 15% of pts with H.pylori develop DU;
RF: H. pylori infection; NSAIDs; smoking impairs mucosal healing; ↑ acid secretion (and gastric
emptying as lowers duodenal pH); virulence factors; ↓ inhibition of acid secretion (H. pylori ↓
somatostatin –ve feedback on gastrin); ↓ bicarb secretion due to H. pylori; blood group O
GUs RF: common on lesser curvature of stomach in elderly
80% have H. pylori infection; NSAIDs; smoking; reflux of duodenal contents; delayed gastric emptying;
stress; associated with gastritis affecting the body of the stomach (not just antrum which is antral
gastritis); ↓ gastric mucosal protection due to cytokine production by the infection
Diagnosis of H pylori infection:
 Non-invasive:
1. Serological tests: detect IgG
antibodies; 90% sensitive and 83%
specific; not useful for confirming
eradication as may take up to 1 year
to fall by 50% or current infection!
2. 13C-urea breath test: quick, reliable,
screening test; ingest 13C-urea which
is broken down by urease and the
13
CO2 is then exhaled and measured;
97% sensitive and 96% specific
3. Stool antigen test: immunoassay
using mAb for qualitative detection of
H pylori
 Invasive (endoscopy):
1. Biopsy urease test: gastric biopsies
are added toa substrate containing
urea and phenol red; if H pylori
present, releases ammonia (2NH3)
which causes colour change from
yellow to red as pH ↑.
2. Culture:
3. Histology: Giemsa staining sections of gastric mucosa obtained at endoscopy
 Investigation of suspected PUD:
Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
Complications
DD
If >55yo or ALARM symptoms refer for urgent endoscopy (exclude cancer); if on NSAIDs then stop; in
other cases do:
 Simple ant-acids and anti-reflux mechanisms (raise bed, not eating <3hrs before bed, stop alcohol)
 Symptoms still present: test for H pylori and eradicate if present (if previous DU, no H pylori test is
needed before eradication therapy begun); if not present then give PPI and review in 4 weeks
Untreated, symptoms of DU relapse and remit spontaneously over many years due to the onset of
atrophic gastritis and a ↓ in acid secretion
Surgery for PUD: now only used in complications to control bleeding or perforation (partial
gastrectomies and vagotomies used to be performed but not anymore)
Eradication therapy = triple therapy
Successful in 90% pts and reinfection is uncommon at 1% in developed countries; eradication failure in
developing countries is ↑ as compliance may be poor, metronidazole resistance is ↑ (used extensively
for parasitic infections) and reinfection is more common
Two Abx (to kill bacteria) + one PPI (treat symptoms) is the standard treatment eg omeprazole 20mg,
clarithromycin 500mg, amoxicillin 1g all BD; metronidazole, bismuth, tetracycline are also used
sometimes
 Haemorrhage: see acute upper GI bleed
 Perforation of peptic ulcer: ↓ frequency; DUs perforate > GUs, usually into peritoneal cavity;
surgery usually performed to close the perforation and drain the abdomen
 Malignancy: distal gastric adenocarcinoma is H pylori associated; also, 70% of pts with gastric B cell
lymphoma have H pylori infection
 Gastric outflow obstruction: obstruction may be prepyloric, pyloric or duodenal; obstruction
occurs due to active ulcer with surrounding oedema or because an ulcer has healed and scarred
area; now uncommon (Crohn’s, cancer of pancreatic head are more common; adult hypertrophic
pyloric stenosis v rare); main symptom is projectile vomiting large volume, ?undigested bits of last
meals
Non-ulcer dyspepsia; DU; duodenitis; gastritis; GU; gastric malignancy; GORD; oesophagitis
Disorder– core
Core symptoms
Signs
Biological
causes/risk factors
Management
e.g. overall plans,
referrals to other
services
Acute upper GI bleed
Usually: haematemesis and melaena (due to any bleed proximal to the right colon).
 Melaena: upper GI bleed
 Bright unaltered blood, massive vols with shock: massive upper GI bleed
 Dark blood and clots w/o shock: lower GI bleed
Signs of shock if severe
Peptic ulceration is commonest cause;
NSAIDs can produce ulcers and
anticoagulation = bigger bleed
RF for rebleed or death: age, evidence of
co-morbidity (HF, IHD, renal disease,
malignant disease); presence of shock,
endoscopic diagnosis, ulcer with active
bleed, clinical signs of CLD; bleeding
associated with liver disease is often from
varices; splenomegaly suggests portal
hypertension
If significant GI bleed within last 48hrs, send to hospital.
In many cases, no treatment necessary as only small blood loss (and 85% pts stop bleeding
spontaneously) within 48hrs
Immediate management:
1. History and examination. Note co-morbidity
2. Monitor the pulse and blood pressure half-hourly
3. Take blood for Hb, urea, electrolytes, LFTs, coagulation screen, group and crossmatching (2 units
initially)
4. Establish intravenous access – 2 large bore i.v. cannulae; central line if brisk bleed
5. Give blood transfusion/colloid if necessary. Indications for blood transfusion are:
a. SHOCK (pallor, cold nose, systolic BP < 100 mmHg, pulse > 100 b.p.m.)
b. haemoglobin < 10 g/dL in patients with recent or active bleeding
6. Oxygen therapy by face mask
7. Keep nil by mouth until urgent endoscopy in shocked patients/liver disease performed
8. Continue to monitor pulse and BP
9. Re-endoscope for continued bleeding/hypovolaemia
10. Surgery if bleeding persists
11. Also, stop NSAIDs, aspirin and warfarin, send to ICU
12. Prepare for resuscitation
Scoring systems to assess risk or rebleeding or death (Rockall) and need for intervention (Blatchford)
SRH = spurting artery, active oozing, fresh or organised blood clot, black spots = ↑ chance of rebleed
1.
Specific conditions
Prognosis
Blood volume: to restore to normal; best via transfusion of red cell concentrates through IV
cannulate; plasma expanders or 0.9% saline given until blood is available; transfusion must be
monitored as overloading can lead to HF (use pulse rate and venous pressure as guides); Hb is poor
indicator for transfusion as anaemia does not develop immediately as haemodilution has not taken
place (but if pt has Hb <10g/dL and has either bled recently or is bleeding then transfusion normally
indicated)
2. Endocopy: will usually make a diagnosis; performed within 24hrs of bleed; pts with Rockall score of
0-1 may be discharged and endoscoped the next day; otherwise, following resuscitation, urgent
endoscopy in pts with shock, ?varices or continued bleeding; detection of cause in 80% cases
a. Varices fixed with banding
b. Bleeding ulcers and those with SRH: treat with two haemostatic methods: usually inject
with adrenaline and thermal coagulation or endoscopic clipping
c. Antral biopsies to look for H pylori
d. A-c ↓ chance of rebleed but do not improve mortality
3. Drug therapy: after diagnosis, omeprazole (PPI) to all pts with an ulcer as ↓ need for surgery
though does not improve mortality rates
4. Uncontrolled or repeated bleeding: repeat to find bleeding site and treat; surgery if persistent/
uncontrollable bleedeing
Chronic peptic ulcer: eradication of H pylori started asap; continue PPI for 4/52 to ensure ulcers heals
Gastric carcinoma: most of these pts don’t have large bleeds
Oesophageal varices:
Mallory-Weiss tear: linear mucosal tear at the oesophagogastric junction and produced by sudden ↑ in
intra-abdo pressure: after bout of coughing or retching; most bleeds are minor and stop spontaneously
Bleeding after percutaneous coronary intervention (PCI): in 2% pts undergoing PCI; 5-10% mortality
Mortality remained same for past years at 5-12% due to ↑ elderly with co-morbidities
Disorder– core
How common is it
Acute lower GI bleed
Massive bleeds are rare and usually due to diverticular disease or ischaemic colitis; small bleeds =
haemorrhoids or anal fissures
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
1.
2.
Proctoscopy: eg anorectal disease: haemorrhoids
Flexible sigmoidoscopy or colonoscopy: eg IBD, cancer, ischaemic colitis, diverticular disease,
angiodysplasia
3. Angiography: vascular abnormality eg angiodysplasia; test of last resort
If pt is <45yo and isolated bleeding, DRE and flexible sigmoidoscopy only required as probability of a
significant proximal lesion is v low unless a stong Fx of colorectal cancer at a young age
Most acute lower GI bleeds start and stop spontaneously; if they don’t stop and pt is haemodynamically
unstable then follow immediate steps as for acute upper GI bleed; surgery rarely required.
Disorder– core
How common is it
Who does it affect
Inflammatory bowel disease (IBD)
Crohn’s, UC (also, microscopic ulcerative, microscopic lymphocytic, microscopic collagenous colitis)
CD: annual incidence of 4-10/100,000 and prevalence of 27-100/100,000; varies between countries
UC: annual incidence of 6-15/100,000 and prevalence of 80-150/100,000
World-wide distribution but more in northern Europe, UK and north America
Affected by race and ethnic origin: ↑ CD in Hispanic and Asian people vs white people; ↑ rates in Jews.
Rates change with migration too (high rates in those who have migrated to industrialised countries/
areas eg ↑ in Hong Kong than middle China). CD M:F = 1:1.2, age 26yo; UC M:F = 1.2:1 age 34yo onset
Core symptoms
CD
Mainly: Diarrhoea (80% cases) usually with
blood, abdo pain (?colicky), weight loss
Malaise, lethargy, anorexia, nausea, vomiting,
low-grade fever; no symptoms in 15% pts,
steatorrhoea if small bowel disease
May present acutely (as RIF pain mimicking
appendicitis) or insidiously
UC
Mainly: Diarrhoea (66%) with blood (90%) and
mucus, ?lower abdo discomfort (30-60%)
Malaise, lethargy, anorexia, weight loss (1540%), aphthous ulcers, blood mixed with stool,
tenesmus, urgency
Ileocolic is commonest for CD
Signs
CD
Weight loss and general ill-health, aphthous
mouth ulcers, normal abdo exam with ?RIF pain
and mass
Anus may have oedematous anal tags, fissures or
perianal abscesses
Biological
causes/risk factors
UC
Usually normal. Abdo may be distended slightly,
usually no anal signs. DRE = blood present
Extraintestinal manisfestations: muco-cutaneous: oral ahpthoid ulcers, pyoderma gangrenosum,
erythema nodosum; ocular: iritis/uveitis, episcleritis, retinitis; renal: kidney and bladder stones;
haemoatological: anaemia, leucocytosis, thrombocytosis, PE; systemic: amyloidosis, vasculitis
Unknown but three main co-factors:
1. Genetics:
a. Familial: +ve Fx is highest independent RF; 1/5 and 1/6 pts with CD and UC respectively
have a 1st degree relative with IBD
b. ↑ concordance in monozygotic vs dizygotic twins (CD > UC); polygenic disease, inc HLA
genes on chromosome 6
2. Environment:
a. Good domestic hygiene ↑ CD risk (poor and large families in crowded conditions have ↓
risk of developing CD); ↑ prevalence of H. pylori in developed countries too; a ‘clean’
environment = bowel not exposed to microorganisms (esp helminthic parasites) =
‘untrained’ for minor infections
b. Lifestyle: breast feeding may be protective; no evidence for dietary factors; pts with CD are
more likely to be smokers but ↑ risk of UC if non-smoking!; adverse life events/
psychosocial factors eg stress and depression ↑ relapses; appendicectomy is protective
for against UC development but may result in more aggressive CD
3. Host immune responses:
a. Alteration of bacterial flora: more anaerobic bac in CD and aerobic in UC
b. Disrupted toll-like receptor signalling
c. Intestinal mucosal invasion by bacteria eg E. coli in CD
d. Defective chemical barrier or intestinal defensins
e. Impaired mucosal barrier
Pathology
CD
All GIT, esp terminal ileum and ascending
colon; rectum involved in 50% cases
Affects
Macroscopic
Microscopic
Strictures
Inflammation
Crypt
abscesses
Goblet cells
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Skip lesions (patchy)
Small bowel thickened, deep ulcers and
fissures in mucosa, cobblestone
appearance, fistulae and abscesses in
colon, aphthoid ulceration is early feature
Granulomas present in 50-60%: noncaseating epithelioid cell aggregates with
Langhans’ giant cells
Common
Transmural/ deep
Uncommon
Present
UC
Rectum always involved (proctitis),
colon, appendix and terminal ileum
(backwash ileitis)
Continuous
Mucosa is reddened, inflamed and
bleeds easily, ulcers may be present if
severe with adjacent mucosa appearing
as inflammatory polyps
Mainly mucosal, with inflamm cells in
lamina propria; no granulomas
Uncommon
Superficial
Common
Depletion
CD
UC
Bloods: anaemia (normocytic, normochromic) of Bloods: ?iron deficiency anaemia, ↑ WCC, ESR
chronic disease, ↑WCC, ESR and CRP ↑,
and CRP ↑, LFTs abnormal, pANCA may be +ve
hypoalbuminaemia if severe disease, ?abnormal
LFTS, pANCA –ve
Stool cultures always done if diarrhoea present to rule out infective cause
Radiology: barium follow-through or CT with oral Imaging: plain AXR with an US if moderatecontrast if suspect CD; findings are asymmetrical severe attack; extent of disease determined by
alteration in mucosal pattern with deep
air distribution in colon and presence of colonic
ulceration and areas of strictures; skip lesions;
dilatation
plain ABX if presenting acutely
Colonoscopy if colonic involvement suspected
Colonscopy: should not be performed if severe
except in pts presenting acutely: may find mild
attack due to risk of perforation, but otherwise
patchy ulcers (aphthoid) or full-blown
useful for defining extent and activity of disease,
cobblestone appearance
and excluding onset of carcinoma in pts with
>10years of disease
High-resolution US and CT: define thickness of
bowel wall
Disease activity: use Hb, WCC, inflamm markers
ESR CRP platelet count and serum albumin
CD: aim is to induce then maintain remission
Stop smoking
Symptomatic treatment if mild CD:
Diarrhoea: loperamide, codeine phosphate, co-phenotrope
Treat anaemia accordingly if iron or B12 (nb severe disease = normocytic, normochromic and will
improve if pts improves); EPO may be required
Pts with moderate-severe colitis are treated as for UC
UC: pt-focussed IBD clinics
Treatment Biological
e.g. specific drugs
1.
CD:
a.
b.
c.
Induction of remission:
i. glucocorticoids useful in moderate-severe attacks of CD (oral prednisolone 3060mg/day)
ii. enteral nutrition; efficacy independent of nutritional status; low fat diets best
iii. infliximab: anti-TNF-α monoclonal Ab induces remission in
corticosteroid/immunosuppressive resistant pts and helps maintain it; infusion
reactions may occur via host Ab against infliximab Ab.
Maintenance of remission
i. Azathioprine, 6-mercaptopurine, methotrexate, mycophenolate mofetil; rate of
relapse on discontinuation of drugs is ~70%!
Surgery: ~80% pts will require surgery at some point of their disease but should be
avoided if possible as recurrence in 15%/year is inevitable. Panproctocolectomy and endileostomy (remove rectum, colon and attach ileum to skin surface of stomach) may be
needed => ileostomy is lifelong and has its own problems
2.
UC:
a.
b.
c.
Treatment Psychological
Course and
prognosis
Aminosalicylate (active part is 5-aminosalicylic acid but comes in many preparations);
released in terminal ileum when right pH; mechanism unknown but induce remission in
mild-moderate and maintain remission in all forms of disease
If moderate-severe flare ups in the past 3 years, consider starting azathioprine
Surgery: may be life-saving, curative and eliminates cancer risk; subtotal colectomy with
en ileostomy is common procedure
Ileostomies: mechanical problems, dehydration, psychosexual problems, infertility in men, recurrence
With UC:
Intermittent (<3 relapses/year): 70%; frequent (>3 relapses/year): 15%; chronic UC: 10-15%
1/3 pts with distal inflamm proctatitis due to UC will develop more proximal disease
1/3 will only have a single attack; 1/3 will undergo surgery in 20years
Increased risk of developing colon cancer with both UC and CD; therefore if have UC or CD every 2 years
you are offered a colonoscopy. 1/10 have colorectal cancer within 25 years of UC (lifetime risk of
normal pop is 1/20)
Complications
CD
UC
Toxic megacolon and perforation
Haemorrhage
Stricture (common)
Stricture (rare)
Carcinoma of small and large bowel
Carcinoma of the large bowel
Fistula 30-50% not common in UC)
Short bowel syndrome (repeated resection =
malabsorption due to resection of diseased SI)
Toxic megacolon: severe colitis leads to transverse colon extending and dilating?
Disorder– core
How common is it
Who does it affect
Core symptoms
Biological
causes/risk factors
Irritable bowel syndrome (IBS)
Co-exists with chronic fatigue syndrome, fibromyalgia, temporomandibular joint dysfunction
Most common functional gastrointestinal disorder (FGID); up to 1 in 5 pts report symptoms suggestive
of IBS – only 50% of which will consult doctors and up to 30% of these will be referred to hospital;
annual healthcare costs of £45 million; $8 billion in USA!
F 2x> M = higher anxiety and depression in women; gut more sensitive; women more focussed on
internal events; food and eating have more psychological significance; pelvic region carries more
significance (defecation, urination, sexuality AND pregnancy, childbirth, menstruation); women more
likely to seek medical attention anyway.
Rome III 2006 diagnostic criteria:
In preceding 3 months, there should be at least 3 days per month of recurrent abdominal
pain/discomfort associated with two or more of:
 Improvement with defecation
 Onset associated with a change in frequency of stool (diarrhoea/constipation)
 Onset associated with a change in appearance of stool
Non-GI features: can be more intrusive than classic IBS features
 Gynaecological: Dysmenorrhoea (painful periods), dyspareunia (painful sex), premenstrual tension
 Urinary: Frequency, urgency, nocturia, incomplete emptying of bladder
 Other: back pain, headaches, bad breath, poor sleeping, fatigue
Biopsychosocial interactions that may interact to
cause dysregulation of brain-gut function
Risk Factors/triggers for onset of IBS:
 Affective disorders: depression,
(hypochondrial) anxiety
 Psychological stress and trauma, life events
 GI infection
 Abx therapy
 Sexual, physical, verbal abuse
 Pelvic surger
 Eating disorders
 Female!
 Severity and duration of diarrhoea
Investigations
Management
Treatment Biological
e.g. specific drugs
Subtypes of IBS by predominant stool pattern:
IBS with constipation: hard lumpy stools >25% and loose/watery stools <25% of bowel movements
IBS with diarrhoea: loose/watery stools >25% and hard lumpy stools <25% of bowel movements
Mixed IBS: hard lump stools >25% and loose/watery stools >25% of bowel movements
Unsubtyped IBS: insufficient abnormalty to meet crieteria for IBS-C, -D or -M
Investigations – clinical judgement but if rectal bleeding, nocturnal pain, fever and weight loss and a
suspicion of organic cause of diarrhoea, then yes
Treatment based on current conceptualisation of biopsychosocial model, targeting central and endorgan therapies
End organ treatment
Explore dietary triggers
High fibre diet and fibre supplements for
constipation
Antidiarrhoeal drugs for bowel frequency
Smooth muscle relaxants for pain
Central treatment
Explain physiology and symptoms
Psychotherapy
Hypnotherapy
CBT
Antidepressants
Action
Refer to dietician
Refer to dietician and prescribe ispaghula husk
Loperamide, codeine, co-phenotrope
Mebeverine hydrochloride, dicycloverine
hydrochloride, peppermint oil
Action
At consultation with leaflets
Refer to clinical psychologist
Refer to psychiatrist
Clomipramine in functional diarrhoea, TCAs
(amitriptyline) in IBS-D, SSRIs (paroxetine) in IBS-C
Disorder– core
How common is it
Who does it affect
Core symptoms
Screening questions
to ask
Biological
causes/risk factors
Gastroenteritis
Most common form of acute GI infection, causing diarrhoea +/- vomiting
Especially in developing world; 2.25 million still die/year despite oral rehydration programmes; less
common and less likely to cause death in Western world. Major cause of morbidity in elderly though.
Travellers to developing countries, homosexual men, infants in day care facilities are also at risk
Bacterial gastroenteritis has two broad clinical syndromes: may be some overlap though
1. Watery diarrhoea (usually due to enterotoxins or adherence)
2. Dysentery (usually due to mucosal invasion and damage)
Often no cause found, but ask about food and water taken, cooking methods, time til onset of
symptoms, whether other diners are affected; food poisoning is a notifiable disease in UK
1. Viral: common cause of D and V in young children; rarely seen in adults unless an outbreak in hospital
eg norovirus
2. Bacterial: most common cause of significant adult gastroenteritis
Watery diarrhoea
Dysentery
Bacillus cereus +profuse vomiting
Shigella spp.
Staphylococcus aureus + profuse vomiting
Campylobacter spp.
Vibrio cholerae
Enteroinvasive Escherichia coli (EIEC)
Enterotoxigenic Escherichia coli (ETEC)
Enterohaemorrhagic Escherichia coli (EHEC)
Enteropathogenic Escherichia coli (EPEC)
Yersinia enterocolitica
Campylobacter jejuni
Vibrio parahaemolyticus
Clostridium perfringens
Both: Salmonella, C diff
Organism
Bacillus cereus
Staph. aureus
Incubation
period
1-5 hrs
2-6 hrs
C. perfringens
8-18 hrs
C. botulinum
C. diff
12-36 hrs
1-7 days
Norovirus
12-24 hrs
Salmonella spp.
12-48 hrs
E. coli 0157
1-2 days
Shigella sonnei
Campylobacter
1-3 days
2-5 days
Cryptosporidium
1-2 weeks
Clinical features
Recovery
Sources/ notes
Vomiting, nausea
Violent vomiting, profuse
water diarrhoea, abdo. pain
Diarrhoea, abdo. pain
Rapid
<24 hrs
Rice
Meat
2-3 days
Vomit, paralysis
Blood diarrhoea, abdo pain,
toxic megacolon, hospitalacquired
Nausea, vomiting,
diarrhoea, ↑ contagious
Diarrhoea, abdo. pain
10-14 days
Meat that had a long
time to cool
Processed food
Abx-associated
Diarrhoea (± blood), abdo.
pain, fever
Diarrhoea, abdo. pain
Diarrhoea (± blood), abdo.
pain, fever
Diarrhoea (Protozoan;
problem if HIV +ve)
3-6/7 but
?14/7
10-12 days
7-10 days
3-5 days
Faecal-oral; vomit
infectious,
Meats, egg, poultry
Cattle, contaminated
foodstuffs
Food/ poor hygiene
Milk, poultry, water
Cow to water to man
V cholera
2 hrs-5 days
Water
Rotavirus
1-7 days
D and V, fever, malaise
ETEC
24 hrs
Watery diarrhoea
1-4 days
Salads, water, ice
Mechanisms: cannot distinguish bacterial/viral cause based on clinical evidence alone
1. Mucosal adherence:
a. Most bacteria must adhere to specific receptors in the gut mucosa eg pili, fimbriae; may be
the prelude to invasion or toxin production though EPEC causes diarrhoea just by binding
2. Mucosal invasion:
a. Penetration of intestinal mucosa eg Shigella, EIEC, Campylobacter spp; entry helped by
‘invasins’ which disrupt the cell’s cytoskeleton; destruction of cells causes the symptoms of
dysentery: low volum bloody diarrhoea and abdo pain
3. Toxin production:
a. Enterotoxins: bacteria bind to intestinal epithelium, induce excessive fluid secretion into
bowel lumen causing watery diarrhoea w/o damage to cell (so no blood) eg cholera, ETEC
b. Cytotoxins: damage intestinal mucosa and vascular endothelium sometimes too
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Extra info:
 Salmonella: commensals in bowels of livestock (esp poultry) and in oviducts of chickens (which is
why eggs can be infected); produce enterotoxins and invade mucosa
 Campylobacter (jejuni): bowel commensal of livestock; worldwide; childhood gastroenteritis;
undercooked meat
 Shigella: (S. dysenteriae, S sonnei, S flexneri); spread by poor hygiene
 ETEC: enterotoxins; common in developing countries so cause of travellers’ diarrhoea
 EHEC (usually O157: H7 serotype): also known as verotoxin producing E coli (VTEC); associated with
cattle; outbreaks (Scotland, Japan) associated with contaminated food; secretes Shiga-like toxin 1
affecting vascular endothelial cells in gut and kidney; after some days pts may develop thrombotic
thrombocytopenic prupura or haemolytic uraemic syndrome; treatment is supportive
 Bacillus cereus: 2 toxins; one produces watery diarrhoea, the other is preformed in food and causes
severe vomiting (‘fried rice poisoning’)
 Staph A: some strains produce heat stable (enterotoxin B); due to poor food hygiene; as toxin is
preformed in contaminated food onset of symptoms is rapid
 C diff: causes Abx-associated diarrhoea, colitis and pseudomembranous colitis; G+ve, anaerobic,
spore-forming bacillus; found in normal bowel flora of 3-5% of pop and up to 20% of hospital pts;
produces 2 toxins: toxin A (enterotoxin), toxin B (cytotoxic = bloody diarrhoea); all Abx but esp with
quinolones (ciprofloxacin); begin with 2-30 days of starting Abx; symptoms mild diarrhoea to watery
haemorrhagic colitis and abdo pain; colonic mucosa inflamed and ulcerated and can be covered by
an adherent membrane-like material (psurodmembranous colitis); can lead to death; detect toxins
A or B in stools by ELISA; metronidazole 400mg TDS or vancomycin 125mg QDS; isolation of pts!
Stool sample for microscopy, culture and sensitivity (MC and S). Microscopy: using modified ZN or
auramine stain for Cryptosporidium parvum oocysts and plated out onto a set of culture media.
An exception to this is “travellers’ diarrhoea”, in which single doses of quinolone antibiotics (e.g.
ciprofloxacin) have been shown to be effective in reducing the duration of symptoms from 3-4 to 1-2
days.
Traveller’s diarrhoea = passage of 3 or more unformed stools/day in a resident of an industrialised
country travelling in a developing nation; usually food or water-borne; ~50% affected if stay for 2 weeks
in a tropical country; benign and self-limiting disease but Abx may be given. Commonly caused by ETEC
(70%), Shigella, Salmonela, Campylobacter, viral, Giardia (all 0-15%)
Management
e.g. overall plans,
referrals to other
services
Treatment – bio
Treatment - Social
DD
In children, acute gastroenteritis has a ↑ mortality due to dehydration; death and serious morbidity are
less common but can still occur esp in developing countries and elderly
Oral rehydration solutions (ORS); Abx if systemically unwell, elderly, immunocompromised
For severe symptoms (but not dysentery) give antiemetics (prochlorperazine) and antidiarrhoeals
(codeine or loperamide)
Shigella, Campylobacter and Salmonella: ciprofloxacin 500mg/12hrs PO
Cholera: tetracycline reduces transmission
Look at www.food.gov.uk UK Food Standards Agency (FSA)
Wash and dry hands before/after handling raw foods; separate from ready-to-eat foods; place raw meat
at bottom of fridge; use different chopping boards and utensils; BBQs are very problematic! – heat,
multiple cooks, mixing of raw and cooked foods, absence of hand washing…
UTIs, chest infections in elderly, and malaria at any age may present with acute diarrhoea
Disorder– core
Acute pancreatitis a process that occurs on the background of a previously normal pancreas and can
return to normal after resolution of the episode (chronic = continuing inflammation with irreversible
structural changes)
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
May range from mild and self-limiting to extremely severe with extensive necrosis and haemorrhage; in
severe forms, mortality is 40-50%
Always a differential diagnosis in anyone with upper adbo pain
Epigastric pain, nausea, vomiting; as inflammation spreads through peritoneal cavity the pain becomes
more intense and lead to back pain; attacks may follow alcoholic binge, Hx of gallstones; quite often no
obvious cause
May show little more than a pt in pain with some epigastric tenderness but no systemic abnormalities;
pt may be tachycardia, hypotensive or be oliguric; abdo exam may show widespread tenderness with
guarding and ↓ or absent bowel sounds
Specific signs that support necrotising pancreatitis = Cullen’s and Grey-Turner’s signs (periumbilical and
flank bleeding); gallstone obstruction may also result in jaundice or cholangitis
I GET SMASHED; gallstones and alcohol account for majority of cases
 Idiopathic
 Gallstones
 Ethanol/alcohol
 Trauma
 Steroids
 Mumps (Coxsackie B)
 Autoimmune (+ tumour)
 Scorpion stings
 Hyperlipidaemia/hypercalcaemmia
 ERCP
 Drugs: azathioprine, diuretics, oestrogens, corticosteroids, didanosine
Mechanisms by which necrosis occurs are unknown, but thi is the same end-point for all causes;
possibly leads to ↑ intracellular calcium = activation of capsases and cell death; alcohol changes calcium
homeostasis in pancreatic acinar cells; gallstones block pancreatic drainage leading to pancreatic
hypertension and ↑ cytosolic calcium
1. Bloods:
a. Serum amylase: v sensitive; if it is 3x↑ than upper limit of normal when measured within 24hrs
of onset of pain (NB. These may also cause ↑ in amylase: Leakage of upper GI contents into the
peritoneum: upper GI perforation, biliary peritonitis, intestinal infarction; inherited
abnormalities of amylase: macroamylasaemia); amylase will fall back to normal with 3-5days so
late presentation may result in false –ve diagnosis
b. Urinary amylase: remain elevated over a longer period of time so also diagnostic
c. Serum lipase: ↑, remain so longer than serum amylase but ↓ accuracy and difficult to measure
d. CRP: assess disease severity and prognosis
e. Other baseline levels: FBC, U and E, glucose, LFT, plasma Ca, ABGs at 24 and 48hrs: ?severity
2.
Radiology:
a. CXR: mandatory to exclude gastroduodenal perforation which ↑ serum amylase; may also see
gallstones or pancreatic calcification
b. Abdo US: screening test to identify biliary (gallstone) cause; distal bile duct obstruction difficult
to detect but there will be dilated intrahepatic ducts; stones in the GB can not be used to
diagnose gallstone-related pancreatitis
c. Contrast-enhanced spiral CT: essential in all except mild attacks of pancreatitis; do it after 72hrs
to assess extent of pancreatic necrosis and prognosis info, and complications
d. MRI (MRCP): assess degree of pancreatic damage and identifies gallstones in biliary tree
e. ERCP: treatment measure to remove bile duct stones in gallstone-related pancreatitis
Majority of cases of pancreatitis are mild, but 25% run into complications =>haemodynamic instability
and multiple organ failure; easrly clinical assessment is not sensitive enough to predict severity
1. Modified Ranson and Glasgow criteria for predicting severity: PANCREAS
 PaO2 <8KPa
 Age >55yo






Neutrophils: WCC > 15 x 109
Calcium <2mmol/L
Renal function: urea >16mmol/L
Enzymes: LDH >600IU/L; AST >200IU/L
Albumin <32g/L
Sugar: blood glucose >10mmol/L
Presence of 3 or more points within first 48hrs = severe acute pancreatitis = transfer to ITU
80% sensitivity for a severe attack, but only 48hrs post presentation
2. Avute physiology and chronic health evaluation (APACHE) score: used to predict severity in a
number of diseases, and is adjusted for age and other chronic health problems
Very sensitive even within first 24hrs of presentation.
Physiological: temp, HR, RR, mean arterial pressure, GCS, BMI (↑ BMI = ↑ severity risk)
Lab: PaO2, arterial pH, serum Na, K, Cr, haematocrit, WCC
Score 0-4 (normal-abnormal)
Management
e.g. overall plans,
referrals to other
services
Prognosis and
Complications
Similar regardless of cause; score pts within 24hrs and again at 72hrs
VACCINES
 Vital signs monitoring (O2): determine need for O2 therapy; give anticoagulant too
 Analgesia/Abx: analgesia: pethidine and tramadol for immediate post-presentation pain control, or
pt-controlled system (eg fentanyl); morphine/diamorphine best avoided as theoretically could ↑
pancreatic ductular hypertension by causing Sphincter of Oddi contraction; prophylactic broadspectrum Abx (cefuroxime) ↓ risk of infective complications and are given from the outset
 Catheter/ calcium gluconate (if necessary)
 Cimetidine (H2 receptor)
 IV access and fluids
 NBM/Nutrition; total parenteral: needed as ↓ chance of oral feeding for a few weeks
 Empty gastric contents (nasogstric tube): nasogastric suction prevents abdominal distension and
vomitus so the risk of aspiration pneumonia
 Surgery if required/ senior review
If gallstone-related pancreatitis and bile duct obstruction, sphincterotomy and stone extraction best; if
no evidence of bile duct obstruction then perform only if severe pancreatitis; if less severe then ?MRCP
Prognosis: mild-moderate: normal recovery with no long-term sequelae; episodes may reccur
If more severe pancreatitis, pancreatic insufficiency for both exocrine (malabsorption) and endocrine
(diabetes) result.
Prognosis after 7 days correlates with extent of pancreatic necrosis, assessed by CT. extensive necrosis
(>50%) = ↑ risk of complications and further surgery may be needed
Complications = PAIN
 Peripancreatic fluid collections/ Pseudocyst: peripancreatic fluid collections are common but most
resolve spontaneously; if fluid collection surrounded by granulation tissue = pseudocyst and are not
fully formed until 6/52 after onset of illness; small <6cm pseudocysts resolve spontaneously but
bigger ones may cause infection, intraperitoneal bleeding or gastric outlet obstruction =>
endoscopic drainage
 Abscesses
 Infection: biggest concern; may develop into sepsis so hence prophylactic Abx; may require surgical
resection of necrotic pancreas
 Necrosis
Disorder– core
How common is it
Chronic pancreatitis
Who does it affect
Core symptoms
In developed countries, alcohol causes 60-80% cases
Epigastric pain radiating through to the back; may be episodic, with short periods of severe pain, or
chronic unremitting. Exacerbations may follow ingestion of alcohol but no direct relationship; anorexia
common, weight loss
In the absence of pain, malabsorption (eg steatorrhoea) or diabetes due to exocrine and endocrine
insufficiency often presenting features; jaundice due to bile duct obstruction may also occur
Features/ symptoms
of presentation in a
primary care setting
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Complications
DD
Same causes as for acute pancreatitis, but also:
1. Tropical chronic pancreatitis: children and young adults; aetiology unknown
2. Hereditary chronic pancreatitis: autosomal dominant, variable penetrance; trypsinogen gene
mutations => 100x ↑ risk of cancer
3. Autoimmune chronic pancreatitis: middle-aged men; anti-nuclear factor and ↑ IgG4.
4. Cystic fibrosis: almost all pts with CF usually from birth
5. Tumours: benign/malignant
Common pathway:
Inappropriate activation of enzymes within the pancreas; chronic alcohol ↑ trypsinogen relative to its
inhibitor and as its autocatalytic, unopposed enzyme actitivyt results
In a pt with known alcohol abuse and typical pain, few investigations are needed.
Serum amylase and lipase: rarerly raised if chronic pancreatitis
Faecal elastase: abnormal in the majority of pts with moderate-severe pancreatitis
PABA
Transabdo US: initial assessment
Contrast-enhanced spiral CT: in presence of pancreatic calcification, a dilated pancreatic duct is
characteristic of chronic pancreatitis
1. If alcohol-related chronic pancreatitis, abstinence will help though this is unproven.
2. Abdo pain: NSAIDs and tramadol for symptomatic relief if episodic flare ups; if chronic unremitting
then this may be inadequate and risk of addiction; amitriptyline (TCA) may be used; spontaneous
pain improvement occurs within 6-10year period for 60% pts
3. Steatorrhoea: pancreatic enzyme supplements, with an acid suppressor (so the pancreatic enzymes
can reach past the stomach); no justification to ↓ fat intake as this may cause malnutrition
4. Diabetes: ?rapid progression from oral hypoglycaemic agents to insulin
Pancreatic pseudocyst, a fluid collection surrounded by granulation tissue
Intra- or retroperitoneal cyst rupture, bleeding or cyst infection may occur
Pancreatic malignancy; consider if short history and localised ductular abnormality
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Other tumours
Pancreatic adenocarcinoma:
1. Lesions of the head
2. Lesions of the body and tail
10/100,000 with no increase in past 20years; 5th most common cause of death in Western worl
Incidence ↑ with age, majority of pts are >60yo; 60% cases are male
Carcinoma of the head or the ampulla of Vater: presents earlier with obstruction of the bile duct
therefore pt is jaundiced, and these are usually painless PAINLESS JAUNDICE (though pain my come
with progressive cancer)
Carcinoma of the body or tail: presents with abdo pain and non-specific symptoms eg anorexia and
weight loss, pain is dull and radiates through to the back; characteristic = partial pain relief if sitting
forward; jaundice may present later but infrequent
Carcinoma of the head of the pancreas: jaundice, excoriations (scratch marks) secondary to cholestasis;
gallbladder may be palpable (Courvoisier’s sign); central abdo mass with hepatomegaly if malignant
Carcinoma of body or tail: often no physical signs
Other signs: may be thrombo-embolic phenomena, polyarthritis, skin nodules (latter due to fat necrosis)
96% of pancreatic cancers are adenocarcinoma in type and most are of ductal origin
Smoking: 2x ↑
Naphthalamine (petroleum product)
Chronic pancreatitis is precancerous; trypsinogen gene mutations = 100x ↑ (hereditary chronic
pancreatitis)
K-ras mutations in 90% cases; others include p16, p53, SMAD4…accumulation of genetic precursors is
associated with progressive premalignant ductual histological changes, called pancreatic intraepithelial
neoplasia (PanINs); classified 1A, 1B, 2, and 3.

Transabdo US: initial investigation in most pts; in presence of bile duct obstruction, this will confirm
dilated intrahepatic bile ducts and a mass in the head of the pancreas; overlying bowel gas makes
detection of carcinoma in body and tail at 60%
 Contrast enhanced spiral CT: confirm presence of a mass and defines vascular supply/ invasion/
lymph node involvement/ metastases
 Laparoscopy: pre-op assessment
 ERCP:
 Percutaneous needle biopsy: discouraged if chance of cure as may cause spread into peritoneum
 Tumour markers: CA19-9 ahs 80% sensitivity but a high false +ve rate; progressive elevation over
time is often diagnostic and can be used to monitor treatment success
5-year survival is 2-5%; surgery is the only chance of long-term survival; 20% of all cases have a localised
tumour suitable for resection but in an elderly population many of these people can’t undergo the
surgery as it’s too risky
Majority of cases: palliative care: as jaundice is very debilitating and causes pruritis, malaise, lethargy,
stents (endoprostheses) are excellent
Radiotherapy results often poor but 5-fluorouracil ↑ short-term survival if severe case
1. Cystic tumours: 75% will be pseudocysts, but 25% are true cystic neoplasms: difficult to distinguish
a. Serous cyst adenomata: (cystademona) multiple small cystic cavities lined by cuboidal glycogenrich cells; occur in elderly; asymptomatic; malignant transformation is rare; ?compressive
b. Mucinous cyst adenomata: 50-60yo women only; pancreatic body and tail; 20% are malignant
at presentation, more likely to produce symptoms
c. Intraductal papillary mucinous tumour (IPMT): arise from either main pancreatic duct or its
branches; 60-70yo men; pancreatic pain common but may be incidental
 Resection of cystic lesions desirable to avoid malignancy potential
2. Neuroendocrine tumours:
a. Insuinloma:
b. Gastrinoma: 1/1000 cases of duodenal ulcers; hypersecretion of gastric acid secondary to
gastrin secretion by the pancreas (Zollinger-Ellison syndrome); diagnosis = ↑ gastrin; high dose
PPIs help
c. VIPoma: endocrine pancreatic tumour produces vasoactive intestinal polypeptide causing
severe secretory diarrhoea (Verner-Morrison syndrome); watery diarrhoea + hypokalaemia +
metabolic acidosis; treat with glucocorticoids
d. Glucagonoma: rare α-cell tumours causing migratory necrolytic dermatitis, weigth loss, DM,
DVT, anaemia, hypoalbuminaemia; diagnose by ↑ serum glucagon; mets are common
e. Somatostatinoma: rare malignant D cell tumours cause DM, gallstones and diarrhoea; diagnose
by ↑ serum somatostatin and resection is treatment
f. Non-functioning neuroendocrine tumours: local mass effect with pain, weight loss and bile
duct obstruction; often large with many mets at presentation; palliative care/surgery only
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Complications
Coeliac disease: disorder of small intestine causing malabsorption
Up to 1% of the population affected, though many are clinically silent
Presents at any age; peak period of diagnosis is in 50s; F>M
Many are asymptomatic (silent) and present due to abnormal bloods eg ↑ MCV or iron deficiency in
pregnancy; tiredness, malaise, angular stomatitis and mouth ulcers associated with anaemia most
common; diarrhoea, steatorrhoea, abdo discomfort, bloating or pain, weight loss = severe disease
Few and non-specific; related to anaemia and malnutrition
Inflammation of the mucosa of the proximal SI that improves when gluten is withdrawn from the diet
and relapses when gluten is reintroduced.
Gluten is the entire protein content of the cereals wheat, barley and rye. Prolamins (gliadin from wheta,
hordeins from barley and secalins from rye) are the damaging agents. They have high glutamine and
proline content so are resistant to digestion by pepsin and cymotrypsin so remain in the intestinal
lumen causing inflammatory responses.
 Immunology: gliadin is deaminated by transglutaminase which makes it more immunogenicl binds
to antigen-presenting cells, interacts with CD4+ T cells in lamina propria, which produce inflamm
cytokines IFN-γ. T cells interact with B cells to produce antibodies. Enterocytes also release IL-15
activating intraepithelial lymphocytes. Metalloproteinases => damage
 Inheritance: inherited component but unsure what mode; 10-15% of 1st degree relatives will ahev
the condition; 70% concordance rate inidentical twins. HLA-DQ2 and 8 are associated with it; >90%
pts have HLA-DQ2 vs 30% gen population
 Environmental: ?breast-feeding and age of introduction of gluten into diet; rotavirus infection in
infancy ↑ risk
1. Duodenal biopsy essential as treatment involves a life-long diet change = expensive and socially
limiting
2. Histology: villous atrophy and crypt hyperplasia with chronic inflammatory cells in lamina propria;
↑ intraepithelial lymphocytes
3. Serology: persistent diarrhoea, folate or iron deficiency, a Fx of coeliac
disease and other autoimmune dieases; >90% sensitivity for endomysial and
anti-tissue transglutaminases antibodies
4. HLA typing: absence of HLA-DQ2 and 8 has a high –ve predictive value
Others:
1. Haematology: anaemia in 50% cases; folate deficiency causing macrocytosis;
iron deficiency due to malabsorption of iron common (vit B12 deficiency is
rare)
2. U and Es: if severe coeliac’s, may cause osteomalacia (low Ca2+ and high
phosphate) and hypoalbuminaemia
3. AXR: dilatation of the SI with slow transit
4. Bone dexa scan: risk of osteoporosis so should be done on all pts
1. Replacement minerals and vitamins (iron, folic acid, vit D, Ca2+)
2. Gluten-free diet for life: improvement within days-weeks; morphological improvement in months;
oats are often tolerated well; meats, dairy, fruit and veg are naturally gluten-free
a. Usual cause of failure to respond to diet is poor compliance
3. Pneuomococcal vaccines every 5 years (because of splenic atrophy)
1. Unresponsive coeliac disease: often no cause found but the following may be cause:
a. Enteropathy-associated T cell lymphoma (EATCL)
b. Ulcerative jejunitis: presents as fever, abdo pain, perforation, bleeding; full-thickness biopsy
necessary for diagnosis; treat with steroids and immunosuppresives (azathioprine)
c. Oesophageal carcinoma:↑ incidence unrelated to during of the disease
2. Tetany, osteomalacia, gross malnutrition with peripheral oedema; ↑ incidence of autoimmune
diseases (DM, Sjogren’s syndrome, thyroid disease), IBD, 1° biliary cirrhosis, CLD, ILD, epilepsy
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Screening questions
to ask
Jaundice/ icterus
Young person – drugs, alcohol, sex
Elderly - carcinoma
Abdominal pain in pts with biliary obstruction by gallstones; general malaise
Signs of acute and chronic liver disease
Hepatomegaly: smooth and tender in hepatitis and extrahepatic obstruction; nodular and irregular in
malignancy
Splenomegaly: indicates portal hypertension when signs of CLD are present
Ascites: cirrhosis and malignancy (including ovarian)
Palpable gall bladder: carcinoma of the pancreas
Generalised lymphadenopathy: lymphoma
Cold sores: herpes simplex virus hepatitis
PC:
How long has the pt had jaundice?
Onset (acute/chronic); progressive (cancer/ stones) /fluctuating (stones)
Ask about colour of stools/urine.
Ask about itching as bilirubin deposited in skin is an irritant.
Ask about abdominal pain
Ask about fever(sweating and rigor suggest ascending cholangitis – infection of bile ducts); Charcot’s
triad =jaundice, RUQ pain, fever
Outbreak in a community? Suggests hepatitis A
Weight loss? Cancer/CLD
Vomited? Acute hepato-biliary disease; Ca of pancreas
Easy bruising? Low bile salts = low fat uptake = low vit K uptake = low factors 2, 7, 9, 10
PMH:
Ever had it or gallstones in the past? Even if cholecystectomy, can get gallstones in CBD; recent RUQ
pain?; any history of cholangitis?
Any operations in the past? (cause a stricture)
See your GP for any long-term conditions? autoimmune disease(SLE ass autoimmune hepatitis/IBD)
Blood transfusions(pre-1991: Hep B/C risk);
DH: past 2-3 months especially
Drugs may cause liver damage – check BNF;
paracetamol O/D; metformin inc wind and changes bowel
SH:
Smoking
Alcohol
Country of origin
Recent consumption of shellfish: HAV infection
Recent IVDU, tattoos, injections:
Unprotected sex (men with men, female prostitution = HBV infection)
Travel (exotic infections, Hep A can be acquired through seafood; hydatid amongst sheep in Wales)
occupation(sewage workers: leptospirosis; sheep farmers: hydatid disease; Drs: hep B/C)
Biological
causes/risk factors
FH:
recurrent jaundice in family = congenital condition? Some haemolytic diseases are
hereditary(hereditary spherocytosis = autosomal dominant)
Detectable clinically when serum bilirubin is >50µmol/L (3mg/dL)
1. Pre-hepatic:
 Haemolytic jaundice - ↑ bilirubin load for the liver cells:
 Due to ↑ breakdown of RBC = haemolytic anaemia; often mild jaundice; unconjugated bilirubin is
not water soluble and so will not pass into the urine; ↑ bilirubin but other LFTs ar normal
 Congenital hyperbilirubinaemia – defects in conjugation:
 Unconjugated: Gilbert’s syndrome (familial hyperbilirubinaemia; asymmptomatic; 2-7% of
population; low activity of UDP-glucoronyl transferase); Criger-Najjar syndrome (less/absent UDPglucoronyl transferase)
 Conjugated:Dubin-Johnson syndrome (autosomal recessive; low activity of excretion of bilirubin
glucoronide); Rotor’s syndrome
2.

Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Hepatic/hepatocellular (also invariably cholestatic!):
Intrahepatic cholestasis: failure of bile secretion: viral hepatitis; drugs; alcoholic hepatitis; cirrhosis;
pregnancy; congenital disorders;
3. Post-hepatic/obstructive (cholestatic): dark urine and pale stools and bilirubin is conjugated
 Extrahepatic cholestasis: due to large duct obstruction of bile flow at any point in biliary tract distal
to biliary canaliculi: common duct stones; carcinoma of bile duct/ head of pancreas/ ampulla;
biliary stricture; sclerosis cholangitis; pancreatic pseudocyst
Jaundice is not a diagnosis and always needs investigartion
Bloods: LFTs and viral markers for HAV, HBV, HCV in high-risk groups;
Hepatitis: serum AST or ALT tends to be high in early disease
Extrahepatic obstruction: ALP is high with small ↑ in aminotransferases
Long-standing liver disease: prolonged PT and low albumin
Haemolytic jaundice: bilirubin ↑ and other LFTs are normal
Raised WCC: infection = cholangitis nb leucopenia in hepatitis
US: exclude extrahepatic obstruction (dilated bile ducts) and indicate level of obstruction; and show
cause of obstruction in all pts with tumours and 75% of pts with gallstones
FNAC:
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Differential
diagnosis
Gallstones
25% in people >60yo
Present at any age but uncommon <30yo; ↑ with age and 2-3x ↑ in females; more common in
Scandanavia, South America, native N Americans and less common in Africans and Asians
90% are asymptomatic; increasingly detected incidently; over a 10year period, 20% will cause
symptoms and 10% have complications
Gallstones do not cause dyspepsia, fat intolerance, flatulence, or vague upper GI symptoms; chances of
a fat, fair, female in her 40s have gallstones are the same for the rest of the population.
1. Biliary/ gallstone colic: epigastric/RUQ pain due to temporary obstruction of cystic duct or CBD by
a stone migrating from the GB; pain radiates to right shoulder/tip of scapular; normally severe and
crescendo-like; high fatty food intake; common during mid-evening/early hours of morning; nausea
and vomiting if severe attack;
2. Acute cholecystitis: stones cause 95% cases; obstruction results in ↑ GB secretions = ↑ GB
distension = compromise vascular supply = inflammatory and immune response; initial pain
presentation as above but soon localises specifically over RUQ due to parietal involvement due to
inflammatory process (local peritonitism, fever, ↑ WCC)
3. Obstructive jaundice due to stone in CBD: presents with biliary colic = RUQ pain, fever and
jaundice (=Charcot’s triad);
4. Cholangitis: bile duct infection causing RUQ pain, jaundice, rigors
Murphy’s sign: plce 2 fingers on RUQ; ask pt to breathe in; causes pain and stops breathing as imflamed
GB impinges on fingers; only +ve if not present in LUQ
Two types of gallstones:
1. Cholesterol gallstones: 80% cases in Western world; due to cholesterol crystallisation into stones
and depends on cholesterol supersaturartion of bile relative to bile salts and phospholipids,
crystallisation-promoting factors in bile and motility of GB; majority of cholesterol uptake is from
diet (20% synthesised in vivo)
2. Bile pigment stones:
o Black: calcium bilirubinate and calcium carbonate/phosphate; seen in 40-60% of pts with
haemolytic conditions eg sickle cell anaemia and hereditary spherocytosis
o Brown: calcium salts of fatty acids and calcium bilirubinate; almost always found in the presence
of bile stasis and/or biliary infection; common cause of recurrent stones
Bloods:
 Stone in GB neck or cystic duct: probably no
changes; maybe ↑ CRP
 CBD obstructon/ cholangitis: ↑ ESR and CRP; raised
serum bilirubin with mild ↑ in ALP, γ-GT, AST, ↑
prothrombin time due to loss of vit K absorption
 Pancreatitis: ↑ serum amylase
US: look for
 Gallstones in GB, neck or cystic duct;
 Focal tenderness over the underlying GB
 Thickening of GB wall (may also be seen in portal
hypertension, acute viral hepatitis, ↓ albumin)
 In CBD obstruction: dilatation of intrahepatic biliary radicles; 50% stones in distal CBD are missed
Biliary scintigraphy: isotopes taken up by hepatocytes and excreted into bile; delineate biliary tree;
absence of cysti duct and GB filling provides evidence for acute colecystitis
1. Laparoscopic cholecystectomy for all with symptomatic GB stones; converted to an open
laparotomy in 5% cases; Acute colecystitis: initially conservative; nil by mouth; IV fluids; opiate
analgesia; IV Abx; then lap cholecystectomy; if pt fails to respond to initial conservative therapy,
consider empyema or grangrene of GB and do an urgent US
a. Post-cholecystectomy syndrome: RUQ pain months after operation; related to functional bowel
disease with hepatic spasm or hypertension of Sphincter of Oddi
2. Stone dissolution and shock wave lithotripsy: infrequently used unless pt is not fit for operation;
dissolution if pure cholesterol stones but high recurrence rate and poor efficacy;
3. If suspect CBD obstruction: if LFTs worsening, can do MRCP, but ERCP with sphincterotomy offers
therapeutic option, then ?cholecystectomy
Biliary colic DD: Irritable bowel syndrome (spasm of hepatic flexure); carcinoma of the right side of the
colon; atypical PUD; renal colic; pancreatitis
Acute cholecystitis: perforated PUD; intrahepatic abscess; basal pneumonia; MI; acute pancreatitis
CBD obstruction: cholangitis can occur in 1° slcerosing cholangitis; malignancy; Mirizzi’s syndrome
(stone in cystic duct compresses bile duct); if no jaundice then ?biliary colic
Acute hepatitis (parenchymal liver damage) can be caused by many agents.
Chronic hepatitis is any hepatitis lasting >6monoths
Disorder– core
How common is it
Vrial hepatitis
Hep A: most common viral hepatitis; world-wide; epidemics; seen in autumn; affects children and
young adults;
 spread by faeco-oral route arising from ingestion of contaminated food or water (shellfish,
overcrowding, poor sanitation);
 common in travellers or institutions
 no carrier state; notifiable disease
Hep B: world-wide (360million carriers); 1% carriers in USA and UK, 20% in Africa and East; spread by:
 Vertical transmission: mother to child in utero, during birth, soon after birth; most common route
world-wide; this is related to the HBV replicative state of the mother (90% HbeAg+, 30% HbeAg−ve)
and is uncommon in Africa where horizontal transmission (sib to sib) is common. HBV is not
transmitted by breast feeding.
 Horizontal transmission: esp in children through minor abrasions or close contact with others; HBV
can survive on toys, toothbrushes
 IVDU (blood transfusions, tattoos, acupuncturists, drugs users)
 Sex esp in men with men (25% in USA); virus found in semen and saliva
Hep C: world-wide (240million carriers); 0.02% prevalence in healthy blood donors in N Europe, 6% in
Africa;
 virus transmited by blood and blood products so was common in haemophiliacs pre-1991;
 limited role for sexual transmission
 Vertical transmission can occur but is very rare
 Close contact transmission is extremely rare
 20% cases = unknown mode of transmission
Hep D:
 IVDU, but can affect all risk groups as for Hep B
 Exists only with HBV; co-infection or superinfection of HBV and HDV is clinically indistinguishable
Core symptoms
Hep E:
 Transmitted enterally by contaminated water
 30% of dogs, pigs and rodents carry the virus
 Epidemicas occur; no carrier state and does not progress to CLD; mortality of fulminant hepatic
failure in 1-2%, 20% in pregnant women
Hep A:
 Prodromal: fever, malaise, anorexia, nausea, arthralgia, distaste for cigarettes!
 After 1-2wks: jaundice develops but symptoms improve; urine becomes dark, stools pale
(intrahepatic cholestasis); hepatmegaly and splenomegaly in 10% cases, lymphadenopathy is
occasionally seen with a transient rash in some
 3-6wks: jaundice ↓ and illness resolves
Hep B:
 Subclinical in many cases
 When HBV infection is acquired perinatally: acute hepatitis does not usually occur due to ↑
immunological tolerance but virus persists in >90%; if there is an acute clinical episode then the
virus is cleared in >99% cases
 Clinical picture same as for HAV, but more severe;
 Extra-hepatic features too: a serum sickness-like immunological syndrome may be seen = rashes
(urticaria or mac-pap rash) and polyarthritis, arteritis, glomerulonephritis
Hep C:
 Most are asymptomatic
 10% have mild flu-like illness with jaundice and a ↑ in aminotransferases
 Extra-hepatic features: arthritis, glomerulonephritis associated with cryoglobulinaemia, and
porphyria cutanea tarda
Biological
causes/risk factors
Pathology for acute hepatitis:
 Most changes are v similar regardless of the cause.
 Hepatocytes show degenerative changes (swelling, cytoplasmic granularity, vacuolation), undergo
necrosis (becoming shrunken, eosinophilic Councilman bodies) and are rapidly removed.
 Extent of damage variable amongst individuals with same aetiology: single and small groups of
hepatocytes die (spotty or focal necrosis), or multiacinar necrosis involving a substantial part of the
liver (massive hepatic necrosis) resulting in fulminant hepatic failure.
Hep A: RNA viurus
Picornavirus, replicates in the liver, excreted in the bile and then faeces for ~2wks before onsent of
symptoms and for 7days after
Hep B: DNA virus
The complete infective virion or Dane particle
is a 42 nm particle comprising a nucleocapsid
(27 nm) surrounded by an outer envelope of
surface protein (HBsAg). HBV not directly
cytopathic – damage is caused by host rather
than HBV (via T cells and HLA class I
molecules)
Hep C: RNA virus
Of Flaviviridae family
Hep D: incomplete RNA virus
Activated by the presence of HBV so it is
unable to replicate on its own
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Hep E: RNA virus
Hep A
 Bloods:
 LFTs: ↑ AST, ALT (within a couple of weeks) and bilirubin; AST and ALT remain high for upto
6months after jaundice subsided; ALP is usually <300IU/L
 FBC: leucopenia with relative lymphocytosis; PT prolonged in severe cases; ↑ ESR
 Viral markers: antibodies to HAV: IgG AB are common in >50yo but anti-HAV IgM = acute infection
Hep B:
 Bloods: as above
 Viral markers: antibodies to HBV: HBsAg is present from 1-6months after exposure; HbeAg also
looked for; anti-HBc IgM is diagnostic.
Hep C:
 Bloods: AST: ALT <1:1 until cirrhosis develops
 Viral markers: antibodies to HCV: anti-HCV AB; HCV-PCR
Treatment Biological
e.g. specific drugs
Hep D:
 Viral markers: antibodies to HDV: anti-HDV AB
Hep A:
 Treatment: supportive: rest and dietary measures are unhelpful; avoid alcohol; corticosteroids
have no benefit; admission to hospital is not usually necessary
 Prevention: good hygiene; HAV resistant to chlorination but is killed by boiling water for 10mins
 Active immunisation: with Harvix Monodose, an inactivated protein derived from HAV; given to
people travelling to endemic areas, pts with CLD, haemophiliacs; AB persist for 1 year; immunity
for 10years so need a booster injection
 Passive immunisation: normal Ig is used if exposure to HAV is <2wks
Hep B:
 Treatment: supportive: avoid alcohol; treat symptoms; combined prophylaxis (vaccine and Ig)
should be given to staff with needle-stick inuries, all newborn babies of HBsAg-poisitive mothers
 Prevention: avoid RF (don’t share needles and avoid needle-stick injuries, have safe sex);
vaccination is available and should be done in all high-risk groups (all healthcare personnel;
members of emergency and rescue teams; morticians and embalmers; children in high-risk areas;
people with haemophilia; patients in some psychiatric units; patients with chronic kidney disease/
on dialysis units; long-term travellers; homosexual and bisexual men and prostitutes).
 Active immunization: uses a recombinant yeast vaccine produced by insertion of a plasmid
containing the gene of HBsAg into a yeast. 3 injections (at 0, 1 and 6 months) are given into the
deltoid muscle; this gives short-term protection in over 90% of patients.
Hep C: Treatment: Interferon-α has been used in acute cases to prevent chronic disease.
Course and
prognosis
Hep D and E: Treatment: No effective treatment
Hep A: excellent; most make a
complete recovery; mortality in young
adults is 0.1% but ↑ with age; death is
due to fulminant hepatitis necrosis
=> get better or die
Hep B (pic): majority of pts recover
completely, with fulminant hepatitis
occurring in 1%; some go on to
develop chronic hepatitis, cirrhosis,
HCC or inactive HBV infection;
complete eradication of HBV is
probably rare
=> chronic infection possible
Hep C: 90% develop CLD; cirrhosis
develops in 20–30% within 10–30
years and of these patients between
7% and 15% will develop
hepatocellular carcinoma.
=> chronic infection likely
Hep D: complicated by super or co-infection with HBV. Fulminant hepatitis can follow.
Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis and hepatocellular carcinoma world-wide
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
Course, prognosis
and complications
Differential
diagnosis
Appendicitis
Most common surgical emergency. Lifetime incidence = 6%
Rare before 2yo; not commoner in pregnancy but ↑ fetal mortality
Abdominal pain – periumbilical which then localises to the RIF within a few hours
Also may be: anorexia, nausea, vomiting, constipation usual though diarrhoea may occur
Variations: boy with vague abdo pain who won’t eat his favourite food
Nb pain migrates because of referred pain and embryological origin:
Gut
Division
Somatic referral
Arterial supply
Foregut proximal-2nd part of duodenum
Upper abdo
Coeliac axis
Midgut
2nd part of duodenum-2/3
Middle abdo
Superior
transverse colon
mesenteric
Hindgut 2/3 transverse colon to distal
Lower abdo
Inferior
mesenteric
 Early inflamm: irritates walls of appendix so referred to middle abdo = umbilical
 Inflamm progress and irritates the parietal peritoneum: pain at McBurney’s point
Visceral peritoneum and viscus have no somatic innervations hence referred pain
 General: tachycardic, fever, furred tongue, lying still, coughing hurts, shallow breaths
 RIF: ?mass, guarding due to localised peritonitis, rebound + percussion tenderness, PR painful on
right.
 McBurney’s point: 2/3 from umbilicus to R ASIS.
 Rovsing’s sign (more pain in RIF than LIF when pressed)
 Psoas sign: pain on extending hip if retrocaecal appendix
 Obturator (Cope) sign: pain on flexion and internal rotation of right hip as appendix in close
relationship to obturator internus.
 In men: do PR: painful on the right
 In women: do PV: +ve cervical excitation = ?salpingitis
Most commonly occurs when lumen of appendix becomes obstructed with faecolith; can also become
obstructed due to lymphoid hyperplasia or filarial worms; gut organisms then invade the appendix wall
Hygiene hypothesis: impaired ability to prevent invasion brought about less exposure to pathogens
Don’t rely on tests as may be unhelpful or cause delay; may be wrong half the time though!
 Bloods: ↑ WCC (neutrophil leucocytosis), ESR and CRP
 US: detects an inflamed appendix or mass
 CT: highly sensitive and specific, ↓ appendicectomies, delays possible in emergency
 Surgery: appendicectomy by open or commonly laparoscopically
 Gridion incision over McBurney’s point at 90° to line from umbilicus to ASIS. Lanz incision is
more horizontal in langer’s lines and gives better scar → divide subcutaneous fat and superficial
Scarpa’s fascia. Fibres of ex ob, int ob, transverus abdo divided with muscle splitting incision →
incise pre-peritoneal fat and peritoneum to reveal caecum → mesoappendix divided, ligated
and excised.
 Abx: metronidazole 500mg/8hr and cefuroxime 1.5g/8hr; 1-3 doses IV pre-op ↓ wound infections
Pain normally subsides over a few days and the mass disappears over a few weeks
 Perforation:does not appear to cause later fertility in women; perforation is commoner with ↓ age
reflecting diagnostic difficulty = can lead to localised abscess or generalised peritonitis
 Appendix mass: when an inflamed appendix becomes covered with omentum; do US/CT to exclude
a colonic tumour which can present as early as in 40s; treat conservatively with Abx and NBM first
then interval (ie delayed) appendicectomy
 Appendix abscess: occurs if appendix mass fails to resolve; signs = mass ↑ size and ↑ pain, temp,
pulse, WCC; treat by drainage
 Non-specific mesenteric lymphadenitis – may mimic appendicitis.
 Acute terminal ileitis due to Crohn’s disease or Yersinia infection.
 Gynaecological causes.
 Inflamed Meckel’s diverticulum.
 Functional bowel disease.
 Ectopic pregnancy; UTI; mesenteric adenitis; cholecystitis; diverticulitis; sapingitis; dysmenorrhoea;
Crohn’s; perforated ulcer; food poisoning.
Alvarado score:
Not very good scoring system at helping to diagnose appendicitis:
Migration of pain, nausea/vomiting, anorexia, rebound pain, temp >37.3°C, neutrophil count >75% all
score 1 point; RIF tenderness and WCC >10 x 10 9/L score 2 points; <4 = unlikely; 5-6 = pbserve; >7 = op!
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Screening questions
to ask
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
DD
Small and large bowel obstruction
Mostly due to mechanical block; if bowel doesn’t function = paralytic ileus (occurs after operations and
with peritonitis

Vomiting with relief, nausea and anorexia; profuse if upper gut obstruction (faeculent vomiting =
fermentation of the intestinal contents in established obstruction ; found when there is a colonic
fistula with the proximal gut)
 Colicky abdominal pain: seen in early obstruction and may be absent in long-standing obstruction
 Constipation: proximal obstruction = may not be absolute, distal obstruction = absolute
 Abdominal distension: ↑ with progression of problem; distension is above the obstruction (with ↑
secretion of fluid into the distended bowel)
 Inspection: distension of abdomen
 Palpation: ↑ tenderness = ?strangulation
 Auscultation: active tinkling bowel sounds(mechanical block); absent sounds(paralytic ileus)
 Examine hernial and rectal orifices:
1. Is the obstruction small or large bowel?
o SI: vomiting occurs earlier, distension is less and pain is higher in the abdomen; AXR essential as
shows central gas shadows but no gas in the LI; fluid levels are seen on an erect film
o LI: pain is more constant, felt over distended caecum; AXR shows gas proximal to block but not
distal ie in the rectum (unless you have done a PR exam); caecum and ascending colon are
distended
o Nb on AXR a sigmoid volvulus = inverted U loop that looks like a coffee bean.
2. Is there an ileus or mechanical obstruction?
o Ileus = no pain and bowel sounds are absent
3. Is the bowel strangulated?
o There is a localised, sharper and more constant pain than the central colicky pain of the
obstruction; peritonism is a cardinal sign; fever and ↑ WCC and other signs of mesenteric
ischaemia; strangulation can lead to gangrene, perforation and peritonitis
Mechanical:
Obstruction can be simple (1 point), closed loop (volvulus), strangulated (blood supply compromised
and pt more ill than you expect)
 Common: constipation, hernias, adhesions (80% in adults), tumours
 Rare: Crohn’s; gallstone ileus; intussusception; diverticular stricture; TB; volvulus (gastric, caecal,
sigmoid); foreign body.
 SI: adhesions, hernias, Crohn’s, intersusception, extrinsic involvement of cancer
 LI: carcinoma of colon, sigmoid volvulus, diverticular disease
Paralytic Ileus: functional obstruction = adynamic bowel due to the absence of normal peristaltic
contractions. Causes: abdo surgery, pancreatitis, spinal injury, hypokalaemia, hyponatraemia, uraemia,
drugs (tricyclics)
Pseudo-obstruction: like mechanical but with no cause found. Acute colonic pseudo-obstructionOgilvie’s syndrome. Predisposing factors: peurperium, pelvic surgery, trauma.
Sigmoid volvus: bowel twists on its own mesentery
 AXR: distended loops of bowel proximal to the obstruction (see above for description)
 Water-soluble (Gastrografin) enema: may help to demonstrate the site of the obstruction.
 CT: can localize the lesion accurately and is the investigation of choice = dilated, fluid-filled bowel
 Colonoscopy: may induce a perforation
General principles: depends on site, onset and completeness of obstruction
Ileus and incomplete: manage conservatively
LI, complete and strangulation: surgery
Immediate action: ‘drip and suck’
NGT and IV fluids (isotonic saline with K+)to rehydrate and correct electrolyte imblanace (being NBM
does not give adequate bowel rest as the intestines can produce up to 9L fluid/day)
Further imaging:
Surgery: necessary for volvulus and strangulation; small bowel obstruction 2° to adhesions should rarely
lead to surgery
 Pts with Crohn’s may have recurrent episodes of intestinal obstruction: managed conservatively.
 Pts with volvulus = use flexi sig to un-kink the bowel
 Critically ill pts may have a defunctioning colostomy put in
Renal calculi, gallstones
Disorder– core
How common is it
Signs
Femoral and inguinal hernias
The protrusion of a viscus or part of a viscus through a defect of the wall of its containing cavity into an
abnormal position (any structure passing through anotherso ending up in the wrong place)
 Irreducible: part of bowel that cannot be pushed back into the right place (this does not mean they
are necessarily obstructed or strangulated)
 Incarceration: contents of hernia sac are stuck inside by adhesions.
 Obstructed: when GI contents cannot pass through = classic obstruction symptoms and signs
appear!
 Strangulated: if ischaemia occurs.
Inguinal hernia: most common hernia
Age groups: femoral > common in middle aged to elderly females.
Look for previous scars; feel both sides (more common on R); examanine external genitalia; is the lump
visible; is it reducible; is it a scrotal lump; ask pt to cough (*); if no lump visible palate for cough
impulse; repeat exam with pt standing; Cannot get above (behind/around) a hernia
1. (*) inguinal hernias appear inferiomedial to the external ring
 Distinguishing between Direct Vs indirect: (not of clinical relevance as surgery repair is the same)
occlude deep inguinal ring with 2 fingers, ask pt to cough or stand, if the hernia does not protrude it
is an indirect hernia; if it pops out it is direct (nb gold standard is via surgery and relationship to
inferior epigastric vessels: indirect =lateral ie through deep inguinal ring; direct =medial and not
through deep inguinal ring)
2. Femoral: Neck of hernia felt inferior and lateral to pubic tubercle (inguinal are superomedial)
Indirect
Common (80%) esp men
Can strangulate
Biological
causes/risk factors
Direct
Less common (20%)
Rarely strangulate
Reduce easily
Femoral
F>M
Frequently strangulate
Don’t reduce easily
Inguinal Hernias (direct//indirect)
 Indirect: pass through the deep/internal inguinal ring and if large extend through the
superficial/external inguinal ring.
 Direct: push directly forward through the posterior wall of the inguinal canal into a defect.
 Deep ring: midpoint of the inguinal ligament, 1cm above femoral pulse.
 Superficial ring: a split in external oblique aponeurosis, superior and medial to pubic tubercle.

Inguinal Canal: floor- inguinal ligament, lacunar ligament medially; Roof- fibres of transversalis,
internal oblique; Anterior- External oblique aponeurosis and internal oblique for lateral 1/3;
posterior- laterally transversalis fascia; medially conjoint tendon.
Femoral hernia
 Bowel enters the femoral canal, presenting as a mass in the upper thigh, or above inguinal ligament
where it points down the leg whereas an inguinal hernia points towards the groin. Likely to be
irreducible and strangulate due to canal’s borders.


Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
DD
Complications
Femoral Canal: anterior- inguinal ligament; medial- lacunar ligament; lateral- femoral vein;
posterior- pectineal ligament and pectineus; canal contains fat and Cloquet’s node.
RF: male; chronic cough; constipation; urinary obstruction; heavy lifting; ascites; past abdominal
surgery;
Irreducible hernias:
If called to a long-standing hernia that is now irreducible and painful
Try reducing yourself (to prevent strangulation and bowel necrosis): use the flat of your hand and direct
hernia below and up towards the contralateral shoulder
Repairs:
Advise to diet if overweight ans top smoking pre-op
Surgery: Mesh techniques (Lichtenstein repair): sutures both anterior and posterior walls of canal. Or
laparoscopic repair (but not recommended). Recurrence is <2%
Return to work and driving after ≤2wks is ok, but 4wks rest advised
Femoral: Herniotomy: ligation and excision of sac, herniorrhaphy: repair of hernia defect.
Inguinal: hydrocele, lymph node swelling, abscess, saphena varix, varicocoele, undescended teste
Strangulation leading to ischaemia. Obstruction
Description
Epidemiology
Cause
Risk Factors
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Description
Epidemiology
Cause
Risk Factors
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Oesophageal Carcinoma
20% occur in the upper part, 50% in the middle, 30% in the lower part. They may be squamous cell or
adenocarcinomas (incidence ↑)
Prevalence:<5/100 000 Australia; >100 Iran
Age groups:
Diet, alcohol excess, smoking, achalasia, Pulmmer-Vinson syndrome, obesity, diet low in vit A&C,
nitrosamine exposure, reflux oesophagitis +/- Barrett’s (44 fold ↑ risk of adenocarcinoma if severe reflux
>10yrs
Presentation
Dysphagia; weight↓; retrosternal chest pain; lymphadenopathy.
From upper 1/3: Hoarseness; cough;
Causes of dysphagia: mechanical: stricture, gastric Ca, lung Ca, retrosternal goitre…Motility: achalasia,
myasthenia gravis, bulbar palsy…
Management
Barium swallow, CXR, oesophagoscopy with biopsy
Survival rates are poor without treatment. If localised radial curative oesophagectomy can be tried.
Gastric Carcinoma
Poor prognosis and non-specific presentation.
Spread is local, blood, transcoelomic (ovaries)
Incidence: adenocarcinoma at gastro-oesophageal junction ↑ in west; distal and body Ca ↓ sharply
23/100 000 UK; geographical variations: Japan, eastern Europe ↑↑↑
Age groups: M:F 2:1
Borrman Classification: 1. Polypoid/fungating 2. Excavating 3. Ulcerating and raised 4. Linitis plastic
(leather bottle lie uniform thickening)
Pernicious anaemia; blood group A; H.pylori; atrophic gastritis; adenomatous polyps; lower social class;
smoking; diet (high nitrate, high salt, low vit C); nitrosamine exposure; E.cadherin abnormalities.
Presentation
Dyspepsia (>1month & >50yrs demands investigation), weight ↓, vomiting, dysphagia, anaemia.
Epigastric mass, hepatomegaly, jaundice, ascites, large left supraclavicular node (Virchow’s), acanthosis
nigrans
<10% overall 5yr survival. 20% after radical surgery
Management
Gastroscopy + ulcer edge biopsies
Surgery, chemo
Cisplatin
Description
Epidemiology
Cause
Risk Factors
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Pancreatic Carcinoma
Typical pt is male over 60.
Prevalence: Uk incidence ↑; <2% of all Ca, 6500 deaths/yr
Age groups: male >60yrs
Mostly ductal adenocarcinomas (met early, present late). 60% arise in the head, 25% body, 15% tail, few in
ampulla of Vater
95% have mutations on the KRAS2 gene
Smoking, alcohol, carcinogens, DM, chronic pancreatitis, possibly high fat diet.
Presentation
Tumours of the head of the pancreas present with painless obstructive jaundice. 75% of tumours in
tail/body present with epigastric pain radiating to the back relieved by sitting forward.
All: anaemia, weight ↓, diabetes, acute pancreatitis.
Rare: thrombophlebitis migrans (arm vein becomes sore and swollen then a leg vein), Ca 2+ ↑, portal
hypertension.
Jaundice, palpable gall bladder, epigastric mass, hepatomegaly, splenomegaly, lymphadenopathy, ascites.
Mean survival <6months. 5yr survival <2%. After whipples 5yr 5-14%.
Management
Most present with mets so <10% suitable for radical surgery.
Surgery: Whipple’s (pancreatoduodenectomy)
Drugs
Chronic Liver Failure
Description
Epidemiology
Cause
Prevalence:
Age groups:
Infections: Viral Hepatits (esp B,C, CMV), yellow fever, leptospirosis.
Drugs: paracetamol O/D; Toxins: amanita phalloides mushroom, carbon tetrachloride; Vascular: Budd-Chari
synd; Other: alcohol, primary biliary cirrhosis, cirrhosis, haemochromatosis, autoimmune hepatitis, alpha-1antitrypsin deficiency, Wilson’s disease.
Risk Factors
Presentation
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Jaundice, hepatic encephalopathy, fetor hepaticus (smells like pear drops), asterixis, constructional apraxia
(can’t draw a 5 point star).
Signs of chronic liver disease suggest an acute-on-chronic failure.
Infection, Gi bleed
Leads to encephalopathy as ammonia builds up, passes to brain, astrocytes convert glutamate →glutamine,
which causes an osmotic imbalance causing cerebral oedema.
Management
ITU
Description
Epidemiology
Cause
Ascites
Presence of fluid in the peritoneal cavity due to:
 Renal sodium and water retention as a result of arterial vasodilation and ↓effective blood volume.
 Portal hypertension: local hydrostatic pressure → ↑hepatic and splanchnic lymph production and
transudation into peritoneal cavity.
 Low serum albumin: (due to poor synthetic liver production) contributes to ↓ plasma oncotic
pressure.
Prevalence:
Age groups:
Malignancy*; Infection* (esp TB); ↓Albumin (nephrosis); CCF, pericarditis; Pancreatitis*; Myxoedema.
Ascities with portal hypertension: Cirrhosis; Portal Nodes; Budd-Chiari syndrome*; IVC or portal vein
thrombosis.
Risk Factors
Presentation
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Description
Epidemiology
Cause
Risk Factors
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Massive stomach
Shifting dullness; fluid thrill
Fat, fluid, flatus, foetus, faeces.
Management
Aspirate ascetic fluid (paracentesis) for cytology, culture, protein level (>30g/L in diseases marked *) with a
21G needle in RIF
↓dietry Na
Spironolactone: aldosterone antagonist- lose Na
Diverticulitis
Diverticulum is an out pouching of the mucosal layer of the gut wall through the muscle layer, usually at
sites of entry of perforating arteries. Diverticulosis= diverticular present. Diverticular disease= they are
symptomatic. Diverticulitis= inflammation of a diverticulum.
Prevalence: 50% have diverticular by 50yrs
Age groups:
95% sigmoid colon, due to lack of dietary fibre leads to ↑intraluminal pressures force the mucosa to
herniate through the muscle layers of the wall at weak points
Western diets low in fibre, age, obesity, smoking, NSAIDs.
Presentation
Diverticulosis: altered bowel habit +/- left sided colic, relieved by defecation, nausea and flatulence
Diverticulitis: pyrexia, WCC ↑, CRP/ESR ↑, tender colon +/- localised peritonism,
Pelvic abscess, colorectal Ca
Haemorrhage: common, can be severe, abruptly and painless or abdo pain, spontaneously stops.
Management
PR, sigmoidoscopy, barium enema, colonoscopy, CT
NBM, IVI
Analgesia, antibiotics, antispasmodics: mebeverine.
Cardiovascular
Disorder– core
How common is it
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Acute coronary syndromes include: unstable angina and an evolving MI specifically, ST-elevation
myocardial infarction (STEMI), non-ST elevation MI (NSTEMI)
UA
NSTEMI
STEMI
History Angina with ↑ frequency,
Chest pain for
Chest pain for >20mins
unpredictability or at rest;
>20mins
chest pain <20mins
ECG
Normal, ST depression or T
ST depression or As for NSTEMI + ST ↑ (>2mm in 2
wave changes
T wave inversion consecutive chest leads or >1mm
in 2 limb leads); ?new LBBB
Troponin Normal
↑
↑
5/1000 in UK for STEMI
Chest pain lasting >20mins often unresponsive to GTN, radiates to neck and down left arm often
associated with nausea, sweating, dyspnoea and palpitations; elderly and diabetic pts may present with
atypical symptoms of dyspnoea, fatigue, syncope, epigastric pain, pul oedema, acute confusional state,
stroke, diabetic hyperglycaemic attacks, oliguria
Distress, pallor, sweaty, thready pulse (↑) and BP (↓) changes, 4th heart sound
Pathophysiology same for each of three causes: plaque rupture, thrombosis, inflammation; plaque
grows and grows in a vessel wall, suddenly ruptures so platelets bind and cause >70% narrowing of
artery = chest pain; downstream ischaemia = NSTEMI/UA; 100% block = infarct = STEMI
ACS may rarely be due to emboli, coronary spasm, or vasculitis
Rupture of a plaque can produce prolonged occlusion leading to myocardial necrosis within 15-30 mins;
subendocardial myocardium is affected first, then subepicardial myocardium
Two key questions: is there ST elevation? is there troponin rise?
ECG: in 20% may be normal; classically = tall T waves, ST-elevation, new left bundle branch block within
hours of an acute Q wave…T wave inversion and development of pathological Q waves over the next
few days; other ACS = ST depression and T wave inversion are highly suggestive of ACS
Bichemical markers:
 Creatinine-kinase-MB: was until recently the standard marker for myocyte death but not used now
as low levels in serum of normal people and in pts with skeletal damage (falls, trauma, seizures),
prolonged exercise, myositis, Afro-Caribbeans, hypothermia, hypothyroidism
 Cardiac troponin: mAb against troponin-T (peaks at 12-24hrs) and -I; complex is made up of 3
proteins (I, T, C) that are situated with tropomyosin on the thin actin filament; troponin-T attaches
the complex to tropomyosin; troponin-C binds calcium during excitation-contraction coupling;
troponin-I inhibits the myosin binding site on the actin; not found in normal people (v sensitive);
has prognostic value and determines medical therapy given
 If troponin-T is normal >6hrs after onset of pain and ECG normal, risk of missing a MI is tiny at 0.3%!
 Myoglobin: may be useful for a rapid diagnosis of an ACS as it’s released early in an MI but nnot
specific for ACS (also found in muscle!)
Diagnosis: 2 of 3 present: chest pain/typical history; ECG changes; cardiac enzyme rise
Risk Stratification:
Use Thombolysis in Myocardial Infarction (TIMI)
score or Global Registery of Acute Coronary
Events (GRACE) prediction score
Initial risk: determined by complications of the
acute thrombosis
Long-term risk: defined by clinical risk factors;
age; prior-MI or bypass surgery; diabetes; HF;
biological markers eg CRP can also be used in
stratification
High risk pts: for progression to MI or death
require urgent coronary angiography
Low risk pts: manage with aspirin, clopidogral,
β-blockers and nitrates
 Mortality = 50% of deaths occur within 2hrs
of onset of symptoms; and 50% 1-month
mortality in community vs 6% in hospitals
Immediate treatment:
ROMANCE (or MONAC)
 Reassure
 Oxygen







DD
Morphine – 10mg IV; anxiolytic,
vasodilatory + anti-emetic
Aspirin – 300mg
Nitrates – GTN
Clopidogrel – 300mg
Enoxaprin (2.5mg)
ECG: STEMI = send for 1° (rush to cath lab)
PCI; if no PCI centre nearby then TPA/
streptokinase; If NSTEMI = elective PCI after
48-72hrs stabalisation (earlier = ↑
mortality) with ACE-I, β-blockers, statin,
LMWH
Pre-hospital: ambulance. 300mg aspirin to
be chewed and GTN sublingual; analgesia:
morphine 5mg IV + metoclopramide 10mg
(not IM due to risk of bleeding with
thrombolysis)
 Hospital: O2 nasal cannula 2-4L/min,
morphine and anti-emetic, aspirin, brief
history/risk factors and examination, IV
access, blood for markers (and FBC,
biochemistry, lipids, glucose), 12-lead ECG,
 ACS (NSTEMI):
o β-blocker: atenolol 5mg IV (unless
contraindicated eg asthma)
o LMW heparin (enoxaparin)
o Nitrates
o High-risk pts (persistent or recurrent ischaemia, ST depression, DM, raised troponin): GP IIb/IIIa
antagonist and urgent angiography and PCI (percutaneous coronary intervention eg angioplasty)
within 90 minutes; consider clopidogrel for 12 months
o Low-risk pts (no further pain, flat/inverted T waves, normal ECG, normal troponin levels)
discharge if repeat troponin is –ve. Arrange a stress test and ?angiogram
 ACS (STEMI):
o Thrombolysis or nowadays primary angioplasty
o β-blocker: atenolol 5mg IV (unless contraindicated eg asthma)
o ACE-I within 24hrs of acute MI, esp if evidence of LV dysfunction or HR
 Subsequent management:
o Bed rest for 48hrs, continuous ECG monitor
o Daily examination of heart, lungs and legs for complications
o Daily 12-lead ECG, U and E, cardiac enzymes for 2-3days
o Prophylaxis against VTE with heparin until mobile; if large anterior MI, consider warfarin for 3
months against systemic embolism from LV mural thrombus; continue daily 75-150mg aspirin
indefinitely; aspirin ↓ vascular events (MI, stroke, vascular death) by 29%
o Start a β-blocker to ↓ pulse to <60 for at least 1 year; ↓ mortality from all causes by 25%
o Continue ACE-I in all pts
o Start a statin even if normal cholesterol levels
o Address modifiable factors: smoking, exercise, co-morbidities eg DM, HTN, hyperlipidaemia
o Exercise ECG: helps with risk stratification
 Post-MI follow up at 6/52:
o Any more chest pain? Smoking cessation; medications: statin (↑ dose as also anti-inflamm
props): atorvastatin 80mg ON (so total chol <4 and LDL <2); β-blocker (↓ workload, ↑ cardiac
filling as longer time in diastole, mild vasodilatory); ACE-I (↓ BP, ↓ afterload, prevent adverse
cardiac remodelling), aspirin lifelong, clopidogrel for 1 years; check P (as want to get β-blocker
and ACE-I to max dose w/o BP problems), cardiac rehab, ECG, echo (if LV dysfunction then give
diuretic: furosemide for symptoms only, spironolactone/ epleronone (↓ gynaecomastia) for ↑
prognosis and symptoms)
o General advice on a cardiac rehabilitation programme: 1/5 lives saved; if uncomplicated,
discharge after 5-7 days; return to work after 2 months except air-line pilots, air-traffic
controllers, divers (drivers of public service or heavy goods vehicles may be able to return to
work). Diet; exercise; avoid intercourse for 1 month; avoid air travel for 2 months
Angina, pericarditis, myocarditis, aortic dissection, PE, oesophageal reflux or spasm
Complications


o
o
o
o
o



o
o
o

o
o
o


Cardiac arrest or unstable angina
Heart failure (LVF)/cardiogenic shock = inadequate organ perfusion: poor prognostic feature; use
Killip classification;
Killip I – no crackles and no 3rd heart sound
Killip II – crackles in <50% of lung fields or a 3rd heart sound
Killip III – crackles in >50% of the lung fields
Killip IV – cardiogenic shock
Treat using diuretics and IV GTN; sit pt up; CPAP (pushes fluid out of alveoli into interstitium)
Myocardial rupture and aneurismal dilatation: rupture of free wall of left ventricle = tamponade =
death; is usually an early and catastrophic event via haemodynamic collapse and cardiac arrest; left
ventricular aneurysm develops 4-6 weeks post MI and presents with LVF, angina, recurrent
VT/systemic embolism with persistent ST elevation on ECG
Ventricular septal defects: occur in 1-2% pts with STEMI but v high 12-month unoperative
mortality of 92%
Mitral regurgitation: due to mitral valve prolapsed (papillary muscle MI/ chordae tendinae
rupture/ ischaemia of papillary muscle; ?transoesophageal echocardiography (TOE) to confirm
cause:
Severe left ventricular dysfunction and dilatation causing annular dilatation of the valve
MI of the inferior wall producing dysfunction of the papillary muscle
MI of the papillary muscles themselves
Cardiac arrhythmias:
VT and VF: common in STEMI and reperfusion; treat VT with β-blockers; early VT (<24hrs) give
lidocaine or amiodarone; late VT (>24hrs) give amiodarone (nb ↓ K+, hypoxia and acidosis all
predispose to arrhythmias and should be corrected)
Atrial fibrillation: occurs frequently
Bradyarrhythmias: sinus bradycardia: treat with atropine
Condution disturbances: very common following MI to develop heart (AV) or bundle branch blocks
Post-MI pericarditis and Dressler’s syndrome: Dressler’s syndrome is recurrent pericarditis, pleural
effusions, anaemia, ↑ ESR, fever, 1-3 weeks after MI; treat with NSAIDs and steroids
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological causes/RF
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Angina pectoris
>1.4 million people in the UK; CAD accounts for 3% of all hospital admissions in the UK; angina has a
prevalence of 2% in the UK and incidence of 1/1000
Heavy/ tight/ gripping chest pain, central/ retrosternal, radiates to jaw and left arm; can range from
mild ache to very severe pain that provokes sweating and fear; often associated with breathlessness;
 Classical/exertional: provoked by physical exertion, especially after meals and in cold windy
weather; pain fades within minutes with rest; some can occasionally ‘walk through the pain’
 Decubitus angina: angina that occurs when lying down; occurs in association with impaired left
ventricle function due to severe CAD.
 Nocturnal angina: occurs at night and may wake the pt from sleep; provoked by vivid dreams;
occurs in pts with critical CAD and ?due to coronary vasospasm
 Variant (Prinzmetal’s) angina: angina without provocation, usually at rest, due to coronary arter
spasm; F>M, ST elevation during pain
 Cardiac syndrome X: good history of angina, +ve exercise test but angiographically normal coronary
arteries; F>M; mycocardium shows abnormal response to stress
 Unstable angina: angina of recent onset (<1month), worsening angina or angina at rest
Usually no findings, though 4th heart sound may be heard; look for signs of anaemia, thyrotoxicosis and
hyperlipidaemia (corneal arcus, xanthelasma, tendon xanthoma)
Pathology: atherosclerosis over years therefore SOBOE; distance walked ↓ over years; angiogram
indicates collateral vessels have grown; these plaques tend not to rupture so although someone with
angina is at slightly ↑ risk to ACS, it will not happen at these plaques
Diagnosis is largely based on a clinical history
 Resting ECG: usually normal between attacks; Q waves indicate old MI; LVH or LBBB may be
present too; during an attack, ST depression and T wave inversion may be present (=ischaemia)
 Exercise ECG: confirms diagnosis and givs indication for severity of CAD; 80% sensitivity and 70%
specificity
 Cardiac scintigraphy: myocardial perfusion scans at rest and exercise
 Echocardiography: assess ventricular wall involvement
 CT coronary angiography: good for diagnosing CAD and exclude other causes eg a PE
 CV MRI: increasingly used
 Coronary angiography: useful in pts where diagnosis is unclear; used mainly to delineate the exact
coronary anatomy in pts considered for revascularisation (CABG or angioplasty); should only be
done when treatment benefits outweigh risk involved (death = <1/1000)
General: prognosis is good (<2% annual mortality); treat underlying problems eg anaemia, diabetes and
HTN; stop smoking; lose weight; change diet; regular exercise;
Medical:
 Prognostic therapies: 75mg OD aspirin ↓ risk
of coronary events in pts with CAD; lipidlowering therapy to be started if total
cholesterol >4.8mmol/L
 Symptomatic treatment: GTN sublingual
spray/ tablet gives pain relief in 5 mintues and
lasts for ~20-30minutes; can be used prior to
activity that provokes angina; no commonly
accepted algorithm for prophylactic therapy
but will consist of β-blockers, Ca2+ antag;
nitrates
Surgery: percutaneous coronary intervention (PCI)
 Percutaenous transluminal coronary
angioplasty (PTCA): dilating coronary artery
stenosis using an inflatable balloon
introduced into the arterial circulation via the
femoral, radial or brachial artery;
 PCI with coated stents: eg immunosuppressants that ↓ cellular proliferation
Problems: risk of death (~1%, need for revascularisation in a year)
 Coronary artery bypass grafting (CABG): autologous veins or arteries are anastomosed to the
ascending aorta and to the native coronary arteries distal to the area of stenosis; ↑ angina
symptoms, exercise tolerance and need for medical therapy, ↑ 10-year survival and less of a need
for revascularisation
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Atrial fibrillation
Very common; 5-10% pts >65yo
1/3 pts after coronary bypass surgery and >1/2 undergoing valvular surgery
Highly variable; in 30% it is an incidental finding; may be asymptomatic or chest pain, palpitations,
dyspnoea, faintness (↓ CO by 20-30%)
Some ↓ in exercise capacity or well-being (but this is only appreciated when sinus rhythm is restored)
Irregularly irregular pulse that is maintained throughout exercise; apical pulse rate is greater than the
radial pulse rate
Rheumatic heart disease, alcohol intoxication, thyrotoxicosis are classic causes of AF; HTN is most
common cause
But any condition that ↑ atrial pressure or muscle mass, atrial fibrosis or inflammation or infiltration of
the atrium may cause AF. hyperthyroidism may cause AF (so TFTs should be checked if unaccounted
AF); others: HF/ischaemia, HTN, MI, PE, mitral valve disease, pneumonia, post-op, low K+ or Mg2+;
rare: cardiomyopathy, constrictive pericarditis, sick sinus syndrome, lung cancer, atrial myxoma,
endocarditis, haemochromotosis, sarcoid; some cases, no cause can be found = ‘lone/idiopathic’ AF
AF is maintained by continuous, rapid (300-600/min) activation of the atria by multiple meandering reentry wavelets. Atria respond electrically to this rate but uncoordinated mechanical action and only a
portion are conducted to the ventricles
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Main classifications:
 Paroxysmal AF: ‘recurring sudden episodes of symptoms' = comes and goes (within 7 days but
usually <2);
 Persistent AF: lasts >7days and is unlikely to revert back to normal without treatment. However,
the heartbeat can be reverted back to a normal rhythm with cardioversion treatment. Persistent AF
tends to be recurrent so it may come back again at some point after successful cardioversion
treatment.
 Permanent AF. This means that the AF is present long-term and the heartbeat has not been
reverted back to a normal rhythm. This may be because cardioversion treatment was tried and was
not successful, or because cardioversion has not been tried. People with permanent AF are treated
to bring their heart rate back down to normal, but the rhythm remains irregular (see below).
Permanent AF is sometimes called established AF.
 ECG = fine oscillations of the baseline (fibrillations or f waves) and absent p waves; QRS is rapid and
irregular; untreated ventricular rate = 120-180/min
 Bloods: TFTs, U and Es, cardiac enzymes
 ?echocardiogram for left atrial enlargement, mitral valve disease, structural abnormalities?
1. Acute AF (<48hrs), very ill, haemodynamically unstable: O2, bloods, cardioversion, if unavailable
then amiodarone, start anticoagulation (heparin)
 When due to alcohol toxicity, chest infection, hyperthyroidism, then treat underlying cause
2. Paroxysmal AF: ‘pill in pocket’ = flecainide prn
3. Chronic AF: neither has been proved superior in terms of mortality or morbidity
1. Ventricular rate control: AV nodal slowing agents (β-blockers or Ca2+ channel blockers (Diltiazem))
and warfarin; if >65yo and ‘primary’ accepted AF; persistent tachycardias; failed previous
cardioversion attempts; if ↑ risk if use antiarrhythmic drugs; AF lasted >1year; on-going reversible
cause (thyrotoxicosis); do ECG to assess whether rate is controlled in elderly/ ambulatory 24hrHolter monitor and exercise stress test if young pt
2. Rhythm control: (by cardioversion and anticoagulation) if symptomatic or CCF, younger pts,
presenting for first time or lone AF, AF is 2° to corrected precipitant; cardioversion = DC shock or by
IV infusion of flecainide or amiodarone (if structural abnormality); works in 80% pts; biphasic better
than monophasic shocks
Main risk of AF is thromboembolic disease (stroke): warfarin ↓ this to 1%/year rather than 4%/year
Anticoagulation: target = INR 2.0-3.0
Indicated in pts with AF and one of the following major or two moderate risk factors: use CHADS2
 Major:
o Prosthetic heart valve; Rheumatic mitral valve disease; History of CVA/TIA
 Moderate:
o Age >75yo; Congestive heart failure; Hypertension; Diabetes mellitus
 CHADS2: congestive heart failure, hypertension, age >75, DM, previous stroke/TIA (scores 2 points)
 Score of 0= give aspirin; 1 = aspirin/warfarin; 2 = give warfarin; Nb Use aspirin if young and no RF.
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Hypertension
Very common – 20-30% of adult population; 40-50% in black Africans
Anyone and everyone, but ↑ in Africans and old people
Often asymptomatic if mild HTN so some pts may not undertsand the need for preventative measures;
Sweating, palpitations, headaches = ?phaeochromocytoma
Severe HTN = ?headaches, epistaxis (nosebleeds), nocturia; SOB due to LVH or HF, whilst angina/
symptoms of peripheral artery disease = ?atheromatous renal artery stenosis
Elevated BP is usually only sign; radio-femoral delay in coarctation of aorta, renal artery bruits in
renovascular disease
Classification of BP levels of the British Hypertension Society
Category
Systolic
Diastolic
Risk of mortality and morbidity ↑ with
Optimal
<120
<80
↑ systolic and diastolic pressures – each
Normal
120-129 and/or <85
measure has a prognositic value too
High normal = preHTN 130-139 and/or 85-89
Hypertension
If at home, then >135/85 = HTN;
Grade 1 (mild)
140-159 and/or 90-99
ambulatory BP monitoring >125/80 =
Grade 2 (mod)
160-179 and/or 100-109
HTN
Grade 3 (severe)
>180
>110
Isolated systolic HTN
Grade 1
140-149
<90
Grade 2
>160
<90
Fundoscopy: necessary for any pt with HTN; grade according to Keith-Wagener classification
 Grade 1: tortuosity of retinal arteries with ↑ reflectiveness (silver wiring)
 Grade 2: grade 1 + A-V nipping produced when thickened retinal arteries pass over retinal veins
 Grade 3: grade 2 + flame haemorrhages and soft exudates (cotton wool) due to small infarcts
 Grade 4: grade 3 + papilloedema (blurring of margins of optic disc)
Grade 3 and 4 = diagnostic of malignant hypertension
Bell-shaped distribution with different levels depending on population studied – esp age, males and
ethnicity; naturally ↑ with age in industrialised countries
1. Essential/Primary/Idiopathic Causes: (95% cases)
a. Genetics: HTN tends to run in families ?due to shared environmental influences
b. Fetal birth weight: low birth weight = ↑ risk of HTN; fetal adaptations to intrauterine
undernutrition with long-term changes in vessel wall structure
c. Lifestyle/environment:
i. Obesity: ↑ risk of HTN in fat people; ensure correct sized cuff is used
ii. Smoking: ↑ risk of HTN
iii. Alcohol: ↑ alcohol consumption = ↑ HTN risk; low alcohol intake = ?↓ risk of HTN
iv. Stress: definite link with acute stress or pain but unsure about chronoic stress
v. Sodium/salt (diet): ?major determinant; ↑ salt = ↑ HTN
vi. Metabolic syndrome: hyperinsulinaemia (DM), glucose intolerance, ↓ HDL,
hypertricgylceridaemia, central obesity, HTN
2. Secondary Causes: (5% cases): specific or treatable cause
a. Congenital:
i. Adrenal hyperplasia; Aortic coarctation; II hydroxylase deficiency
b. Acquired:
i. Renal disease:
a. Diabetic nephropathy; Chronic glomerulonephritis; Adults polycystic kidney disease; Chronic
tubulointerstitial nephritis; Renovascular disease eg renal artery stenosis, CKD
ii. Endocrine diseases:
a. Conn’s syndrome; Adrenal hyperplasia; Phaeochromocytoma; Cushing’s synd; Acromegaly
iii. Drugs: interfere with response of some anti-hypertensives
a. The pill, NSAIDS, Cyclosporin, Steroids
iv. Pregnancy: CO ↑ in pregnancy but as TPR ↓ then normally BP is lower than those not
pregnant; HTN in 10% pregnancies; when detected in 1st trimester or continuing after
pregnancy then usually due to pre-existing HTN; when detected in 2nd trimester (‘pregnancyinduced’) then this normally resolves by term; nb pregnancy-induced HTN + proteinuria = preeclampsia
v. White coat syndrome!
Investigations
Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
Complications
Pathophysiology: remains unclear
 In chronic hypertension, CO normal and an ↑ TPR maintains ↑ BP; resistance vessels (arteries and
arterioles) show structural changes – thickened wall and smaller radius;
 HTN also causes changes in walls of large arteries – thickened, deposition of collagen and calcium =
loss of arterial compliance = more pronounced pressure wave; atheroma also develops
 Pulse wave velocity: measure of arterial stiffness and inversely related to distensability; with each
systolic contraction a pulse is sent down the arterial wall before the blood flows; more rigid wall =
faster the wave travels; not routinely measured
 LVH due to ↑ TPR and so ↑ pressure load (afterload)
 Renal vascular changes: ↓ renal perfusion and GFR so ↓Na+ and H2O excretion; may lead to
activation of RAAS and further Na+ and H2O retention
Routine: ECG (?LVH), urine dipstick for protein/ blood, fasting blood for lipids (total and HDL
cholesterol) and glucose, serum urea, Cr (?kidney problems) and electrolytes (↓ serum K + = ?endocrine
disorder), CXR if coarctation of aorta suspected
Consider in 3 stages: assessment (+2° causes/ RF?), non-pharmacological, pharmacological treatment
If not malignant HTN: reassess investigations; lifestyle advice – BMI <25kg/m2, low-fat/saturated fat
diet, low salt diet <6g/day, ↑ fruit and veg, alcohol within recommended values, 30 mins exercise/day,
stop smoking, ↑ omega-3 with oily fish
Aim: to ↓ risk of HTN complications
A = ACE-I/angiotensi II blocker; C = Ca2+ antag; D =
diuretic (thiazide); try not to combine diuretic with
β-blocker as this will aggrevate diabetes
 Severe HTN: treat unless malignant
 Moderate sustained HTN: if CV complications,
target organ damage, or DM present then
confirm over 4 weeks and treat; if absent, then
measure weekly for 12 weeks and treat if
continually raised/week
 Mild HTN: if CV complications, target organ
damage, or DM present then confirm over 12
weeks then treat; if absent, measure monthly
and treat if continually raised or 10year CVD risk
>20%
 Pre-HTN: (130-139/85-89) assess yearly
 <130/85: assess every 5 years
 Target BP = ~140/85
Young pts ↑ likely to have high renin-HTN, and black pts/>55yo have low renin-HTN
Cerebrovascular disease (6x↑ instroke) and CAD (3x ↑ in cardiac death eg MI or HF) = most common
causes of death; HTN pts also prone to renal failure, PVD and PAD (2x ↑)
Prognosis: depends on BP, age at presentation, target-organ changes (retinal, renal, cardiac), co-
existing RF (high lipids, DM, smoking, obesity, male sex)
Telling a pt: Blood pressure is a measure of how hard your heart has to work to push
the blood around your body. The pressure in your blood vessels depends on how hard
the heart pumps, and how much resistance there is in these vessels. It is thought that
slight narrowing of your blood vessels increases the resistance to blood flow, which
increases the blood pressure. Like if you squeeze the end of a hose pipe the water
comes out more quickly. The exact cause of the slight narrowing of the blood vessels
is not clear. Various factors probably contribute many of these are down to people’s
lifestyle. It’s important we ↓ your BP as a ↑BP gives you a much greater risk of
suffering a stroke and heart attack.
Disorder– core
Who does it affect
Core symptoms and
signs
Screening questions
to ask
Biological
causes/risk factors
Deep vein thrombosis (DVT) = venous thromboembolism (VTE) see pg 444 K/C
Commonly after long periods of immobilisation
Affect 25-50% surgical pts
Individual may be asymptomatic, presenting with features of a PE. 65% leg DVTs are asymptomatic and
they rarely embolise to the lung
 Major presenting feature = calf pain, swelling, redness, warmth, engorged superficial veins, ankle
oedema; Homan’s sing (pain in the calf on dorsiflexion of the foot) may be present but is not
diagnostic and ?should not be tested for as it may dislodge the clot; mild fever.
 If clot in iliofemoral region, may just have severe pain and ?ankle oedema; PEs more frequent with
these type of DVT
 Complete occlusion leads to cyanotic discolouration of the limb and severe oedema.
 Chronic venous obstruction resulting from a DVT presents with a single swollen limb and may lead
to ulceration (post-phlebitis syndrome)
Ask 9 questions in those who present with swollen legs:
Is it both legs? Is she pregnant? Is she mobile? Any trauma? Any pitting? Past disease/medications? Any
pain? Any skin changes? Any oedema elsewhere?
Thrombus = solid mass formed in the circulation from constituents of the blood during life.
A thrombus forms in vein and causes inflammation of the vein wall.
Major causes = stasis and hypercoaguability
Can occur in normal veins; majority in deep veins of leg originating around the valves as ‘red thombi’
(red cells + fibrin); may embolise
Risk factors:
Patient Factors
Disease or surgical procedure
Trauma/ surgery to lower limb, pelvis, hip
Malignancy
Cardiac/ respiratory failure
Recent MI or stroke
Acute medical illness/ infection
IBD
Nephrotic syndrome
Myeloproliferative disorders
Increasing age
BMI >30Kg/m2 (obese)
Varicose veins
Continuous travel for >3hrs in preceeding 4 wks
Immobility/ bedrest >4days
Pregnancy
Previous DVT or PE
Thrombophilia
Antithrombin deficiency
Sickle cell anaemia
Protein C or S deficiency
Central venous catheter
Factor V Leiden
Paraproteinaemia
Prothrombin gene variant
Antiphospholipid antibody/ lupus anticoagulant
Paroxysmal nocturnal haemoglobinuria
Oestrogen therapy inc the pill and HRT
Plasminogen deficiency
DVT occur in 50% pts after a prostatectomy (w/o prophylactic heparin) or following a CVA; 10% of pts
following an MI
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Wells Score for clinical probability of DVTs
Clinical Features
Score
Active cancer (treatment within the last 6 months or palliative)
1
Paralysis, paresis, reent plaster immobilisation of leg
1
Major surgery or recently bedridden >3d in 4wks
1
Local tenderness along distribution of deep venous system
1
Entire leg swollen
1
Calf swelling >3cm compared to asymptomatic leg (measured 10cm below tibial tuberosity) 1
Pitting oedema
1
Collateral superficial veins (non-varicose)
1
Alternative diagnosis more likely than DVT
-2
3 or more: high pretest probability – treat as suspected DVT
1-2: intermediate pretest probability – treat as suspected DVT amd perform compression US
0 points: low pretest probability – perform D-dimer; if raised then treat as suspected DVT
 Clinical diagnosis unreliable so do a D-dimer where sensitivity = 80% (but not specific)
 D-dimer = fibrin degradation product (FDP), a small protein fragment present in the blood after a
clot has been degraded by fibrinolysis. Contains two crosslinked D fragments of the fibrinogen
protein. (nb. Factor 8 crosslinks fibrin proteofibrils at the D fragment site leading to clot formation).
The typical D-dimer containing fragment contains
two D domains and one E domain of the original
fibrinogen molecule.




Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
Prognoss and
prevention
Differential
diagnosis
-ve test rules out thrombosis; therefore done to
exclude thromboembolic disease where
probability is low (DVT, PE, DIC)
+ve test doesn’t rule out thrombosis or other
causes; therefore do US of the leg or lung
scintigraphy/ CT; may start anticoagulation
therapy before/ after tests;
False +ves may be due to liver disease, high
rheumatoid factor, inflammation, malignancy,
trauma, pregnancy, recent surgery, age!
False –ves if test is done too early or late
If raised D-dimer, do compression US (venography is
rarely necessary)
Do thombophilia tests if no risk factors, if recurrent
DVTs or if family history of DVTs
Main aim is to prevent PEs
All thrombi above the knee are treated
Thombi below the knee are commonly treated for 6 weeks
Bed rest until the patient is completely coagulated; then mobilisation and elastic stockings with
graduated pressure over the leg
Stop the pill 4 weeks before surgery
LMWH have replaced unfractionated heparin
Warfarin is started immediately and heparin stopped when INR is in the correct range (2-3 normally)
Warfarin usually continued for ~3 months but 1 month may be long enough if risk factor accountable
Recurrent DVTs = long-term anticoagulation needed.
Anti-coagulants do not lyse the clot already present (this is for thrombolytic therapy)
Destruction of the deep vein valves produces a painful, swollen limb made worse on standing, along
with ankle oedema and ?venous eczema; occurs in 50% pts; elastic stockings for life
Prevention = use LMWH in pts with HF, MI, surgery to leg or pelvis; leg exercises help
Cellulitis
Venous eczema
Ruptured Baker’s cyst
Disorder– core
Core symptoms
Signs
Biological
causes/risk factors
Investigations
Treatment Biological
e.g. specific drugs
Varicose veins
‘My legs are ugly’; pain, cramps, tingling, heaviness or restlessness are often attributed to varicose veins
Oedema; eczema; ulcers; haemosiderin pigment changes (brown); lipodermatsclerosis (skin hardness
from subcut fibrosis caused by chronic inflammation and fat necrosis); on their own, varicose veins
don’t cause DVTs
Blood from superficial veins of the leg drain into deep veins by perforator veins and at the saphenofemoral junction and saphenopopliteal junction; valves prevent backflow of blood from deep to
superficial veins. If vavles become incompetent then venous hypertension and dilatation occurs of the
superficial veins
RF: prolonged standing, obesity, the pill, pregnancy, Fx
Trendelenburgs test; cough impulse; tourniquet test; Perthes test; Doppler US (listen for flow in
incompetent valves when the calf is squeezed; flow lasting >1s = significant reflux)



Differential
diagnosis

o
o

o
o
o
Education: avoid prolonged standing; support stockings; lose weight; regular walks (aid venous
return)
Injection therapy: esp for varicosities below the knee if no gross saphenofemoral incompetence;
sclerosant (ethanolamine) is injected into a multiple sites and the vein compressed over a few
weeks to avoid thrombosis
Surgery: saphenofemoral ligations; multiple avulsions; stripping from groin to upper calf; very
effective long-term
Primary:
Idiopathic
Congenital valve absence (rare)
Secondary:
Obstruction: DVT, fetus, ovarian tumour
Valve destruction: DVT
Arteriovenous malformation: increased pressure
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Differential
diagnosis
Peripheral artery disease (chronic)
7% of middle-aged men and 4.5% of middle-aged women; though they’re more likely to die of a MI or
CVA than lose a leg
1. Intermittent claudication: Most common symptom of PAD; cramp-like pain felt in the legs due to
arterial insufficiency after a relatively constant distance and sooner if uphill; pain disappears after a few
mins of rest+restarts again on exercise; typical felt in the calf due to femoropopliteal disease but may be
felt in thigh/buttock if aorto-iliac disease. Claudication distance = distance pt can walk before pain
starts(often underestimated). Sharp pain, acute onset, pale whole leg, then no pain – most probably due
to thrombosis
Pts may experience similar symptoms in the buttocks and thighs, associated with male impotence = the
‘Leriche syndrome’ Claudication often worse in one leg but can occur in both; relieved by hanging foot
out of bed or standing on a cold floor; if severe then may be ulcers or gangrene
2. Worsening calf pain
3. Rest pain
4. Pain all the time/ at night
Ischaemic changes present

Cold/numb sensation of extremities

Smooth, shiny, dry skin with no hair on legs

Thickened/brittle toenails (trophic changes)

Pale/blue foot

Pallor when extremity raised

Delayed capillary filling

Diminished/absent pedal pulses

Small, circular, painful ulcers over bony prominences

Atherosclerosis is main cause (hence RF=age, males, smoking, DM, hyperlipidaemia, hypertension)

+ve Buerger’s test; ankle BP <50mmHg
Due to atheroslcerosis affecting the aorto-iliac or infrainguinal arteries
RF – same for CV disease; smoking; diabetes; hypercholesterolaemia; hypertension


Examine the pulses – give estimation of the level of disease.
Measure severity of disease with an ABPI = measurement of cuff pressure at which blood flow is
detectable by a Doppler. May be a fall in ABPI after exercise. Arteries may be incompressible in DM
or renal disease so ABPI will be falsely elevated.
 Angiograms are less commonly used now as Doppler and duplex measurements are so accurate.
Medical
 Assess RF – smoking cessation, chiropody care for pts with DM, use statin for high cholesterol, low
dose-aspirin to reduce MI/stroke risk; supervised exercise program? No drugs for claudication
proven of benefit yet.
Surgical
 Only in those who have had RF addressed and feel symptoms are affecting quality of life.
 Percutaneous transluminal angioplasty via femoral artery; results similar to that of a continued
exercise program; stents/ drug-eluting stents (paclitaxel) may be used.
 Bypass procedures may be used by autologus veins or Dacron; ?efficacy and long-term
effectiveness
 Amputation is severe ischaemia with unreconstructable arterial disease; ?loss of independence as
only 70% below-knee and 30 above-knee amputees achieve full mobility
 Spinal cord claudication (but all pulses are present)
 Knee or hip osteoarthritis
 Peripheral neuropathy (ass with numbness or tingling)
 Popliteal artery entrapment (young pts with normal pulses)
 Venous claudication (bursting pain on walking with a Hx of DVT)
 ‘Buerger’s’ disease (young males, heavy smokers)
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
Treatment Biological
e.g. specific drugs
Complications
DD
Thoracic-abdominal
aneurysm (TAA)
Aortic dissection
Abdominal aortic aneurysm (AAA)
Incidence increases with age, present in 5% of population >60yo; mortality = 125/million in 55-59yo and
2728/million in >85yo
M 5x>F and in ¼ of male children of an affected individual
 Most are asymptomatic and only found on routine abdo exam, AXR or urological investigations
 Rapid expansion or rupture of a AAA may cause severe epigastric pain radiating through to the
back; symptoms of rupture may mimic renal colic, diverticulitis, severe lower abdo/testicular pain
 Gradual erosion of vertebral bodies may cause non-specific back pain; haematemesis due to a
aortoduodenal fistula is rare
Ruptured AAA cause hypotension, tachycardia, massive anaemia and sudden death. May be no overt
signs in an obese pt as AA is retroperitoneal
Pulsatile and expansile abdo mass
Secondary to atherosclerosis is main cause; infection (syphilis, E. coli, Salmonella) and trauma, or
genetic (Marfan’s syndrome, Ehler’s-Danlos syndrome) are other causes
Assess by US, though CT is more accurate and relates anatomical relationship to renal and visceral
vessels
Put in two cannulas; call a vascular surgeon and anaesthetist; treat with ORh –ve blood; keep systolic BP
<100mmHg; take blood for amylase, Hb, crossmatch
Asymptomatic AAA: balance of operative risk and conservative management; UK Small Aneurysm Trial
showed pts with infrarenal AAA did best with an operation if AAA was >5.5cm in diameter, expanding
>1cm/year and symptomatic. Risk of rupture is 25%/year if >6cm but <1% otherwise
 Medical: Control hypertension, stop smoking, lower lipids, US surveillance
 Surgery: open surgery with insertion of a Dacron or Gore-Tex graft; endovascular stent via femoral
artery is a non-surgical approach to AAA repair; laparoscopic surgery is an alternative to open
repairs.
 Prognosis: after repair, normal activity within a few months; elective surgery = 5% morality;
Rupture; thrombosis; embolism (leading to distal ‘trash’); compress nearby structures
Pancreatitis, renal colic, testicular pain (if severe pain radiating through to back but no expansile mass)
 Ascending, arch or descending part of aorta may become aneurysmal. Ascending common in pts
with Marfan’s syndrome or HTN; arch and descending common in atherosclerosis and syphilis.
 Again, found routinely; if rapidly expanding, may cause chest pain radiating to upper back, stridor
(due to compressed bronchial tree), haemoptysis (aortobronchial fistula), hoarse voice
(compression of recurrent laryngeal nerve)
 CT scan for assessment of a TAA; if >6cm then operative repair or stenting appropriate.
 Blood splits the aortic media, usually due to a tear in the intima to begin with.
 Type A: involves aortic arch and aortic valve proximal to left subclavian artery origin (involves
asceding aorta irrespective of site of tear: OHCM)
 Type B: involves the descending thoracic aorta distal to the left subclavian origin
 Severe and central chest pain radiating through to the back and down the arms, mimicking a MI; pt
may be shocked and have neurological symptoms secondary to loss of blood supply to spinal cord;
peripheral pulses absent; renal and lower limb ischaemia?
 CXR: mediastinum widened; confirmed by CT or transoesophageal echocardiography
 Antihypertensive medication; type A = surgery (arch replacement) if fit; type B = manage medically
Disorder– core
Classification
How common is it
Who does it affect
Core symptoms
Signs
Pathophysiology
Cardiac failure; results from any structural or functional cardiac disorder in which the heart is unable to
pump blood at the rate required for normal metabolism; functional, not morphological
1. Forward vs backward failure:
• Backward
– Ventricle fails to pump blood rapidly enough to prevent the atria from overfilling
– Backpressure in the (pulmonary) venous system rises
• Forward
– Ventricle fails to pump enough blood to maintain normal (renal) circulation
– Renin-angiotensin system retains sodium and water
2. Acute vs chronic failure
Clinical picture depends on rate of onset of failure – compensatory mechanisms
• Sudden onset; can occur within mins of a MI
– Myocardial infarction
– Valvular collapse
• Slow onset; years
– E.g. mitral stenosis = valve disease: ↑ pulmonary pressure causing RHF
– Chronic ischaemia
3. Right vs left failure
• Early presentation often predominated by one-sided failure, usually LHF (usually due to ischaemia)
• Late disease affects both sides
• Congestive cardiac failure (CCF) = signs of hypervolaemia = peripheral oedema
• RHF: may be due to chronic obstructive lung disease (emphysema, bronchitis) = ‘cor pulmonale’
• Clinical features are mainly predictable from the pathophysiology
4. High and low output failure:
Low output: cardiac output is ↓ and fails to ↑ normally on exertion. Causes: Pump failure: sys/dia heart
failure (above), ↓HR (βblockers); Excessive preload: mitral regurgitation, fluid overload; chronic
excessive afterload: aortic stenosis hypertension. High output: rare
Commonest complication of all forms of heart disease
↑ age; eg Scotland 7.1/1000 (high) which ↑ to 90/1000 if >85yo; 23million people worldwide affected
LHF:
• Back-pressure causes pulmonary congestion/oedema
• Exertional dyspnoea (sometimes with wheeze/ nocturnal cough, hence old term “cardiac asthma”)
• Haemoptysis – sputum frothy and pink
• Pleural effusions (fluid in pleural cavity): X-ray, percuss (bilateral) = loss of costophrenic angle
• Orthopnoea
• Paroxysmal nocturnal dyspnoea
• Fatigue
RHF:
• ↑ venous pressure in systemic circulation, ↑ JVP (tricuspic regurgitation)
• Gravitational oedema/ ankle oedema/ sacrum when pt is in bed
• Hepatic congestion (‘nutmeg’ liver) so ascites
 Look ill and exhausted, cool peripheries,
cyanosis,
 Displaced apex beat in LVF
 RV parasternal heave in RVF
 3rd and 4th heart sounds; murmurs of
mitral or aortic valve disease
 Elevated JVP
 Tachycardia at rest
 Tachypnoea
 Hypotension
 Bi-basal end-inspiratory crackles/ wheeze
 Ankle oedema
 Ascites
 Tender hepatomegaly in tricuspid regurgitation
1. Heart/pump failure = low CO = peripheral underperfusion ‘arterial underfilling’ = compensatory
haemodynamic changes:
 Ventricular dilatation
 Myocyte hypertrophy
 ↑ collagen synthesis







Biological causes/RF
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Altered myosin gene expression
Altered sarcoplasmic Ca2+-ATPase density
↑ ANP secretion (to counteract the ↑ salt and water retention)
Salt and water retention (RAAS) = ↑
BV
Sympathetic stimulation = ↑ HR,
force of contraction
Peripheral vasoconstriction
Failure due to
1. heart muscle disease (IHD,
cardiomyopathy)
2. restricted filling (constrictive
pericarditis, tamponade,
restrictive cardiomyopathy)
3. inadequate HR: β-blockers,
heart block, post-MI
4. -ve inotropic drugs: eg
antiarrhythmic drugs
How?
As HF continues, these mechanisms are
overwhelmed and become
pathophysiological = cardiac
decompensation; factors involved are:
2. Venous return (preload):
In an intact heart, failure leads to a
reduced blood ejection and ↑ enddiastolic volume, stretching the
myocardial fibres, (normally activating Starling’s law). But in HF, there is a depression of the ventricular
function curve:
 Mild depression: no reduction in CO due to an ↑ venous pressure (hence diastolic volume) and HR,
but ejection fraction is reduced
 Severe depression: CO can only be maintained by massive ↑ in venous pressure and HR; leads to
accumulation of interstitial/ alveolar fluid, hepatic enlargement, ascites, dependent oedema. CO
may be OK at rest but not on exercise.
 Very severe depression: CO depressed despite ↑ venous pressure; inadequate CO is redistributed
to vital organs
 ↑ preload due to mitral regurgitation or fluid overload, poor renal excretion
3. Outflow resistance (afterload):
An increase in afterload ↓ CO, increasing EDV and dilation of ventricles
 ↑ afterload due to aortic stenosis, hypertension
Myocardial contractility (inotropic state):
Temporary SNS activation = compensation mechanism
Chronic SNS activation is deleterious: myocyte apoptosis, downregulation of β-receptors
Neurohormonal and SNS activation: salt and water retention:
The increase in venous pressure that occurs when ventricles fail leads to salt and water retention;
reduced kidney perfusion also leads to salt and water retention which also ↑ venous pressure
Myocardial remodelling:
Left ventricular remodelling – altered size, shape and function; hypertrophy, loss of myocytes and ↑
interstitial fibrosis
Coronary artery disease is commonest cause in western countries
Diagnosis: symptoms and signs of HF AND objective evidence of cardiac dysfunction (at rest)
The underlying cause of HF should be established too
Blood tests FBC, LFT, U and E, cardiac enzymes in acute HF, BNP or N-terminal portion of proBNF
(NPproBNP), TFT
Chest X-ray THINK: ABCDE in LVF = alveolar oedema ‘Bat’s wings’, interstitial oedema Kerley B lines,
cardiomegaly, dilated prominent upper lobe vessels, pleural effusions; also, LA is normally a concave
‘dent’ – this goes and there is a straight diagonal line instead on left heart border
ECG for ischaemia, hypertension or arrhythmia.
Echocardiography cardiac chamber dimension, systolic and diastolic function, regional wall motion
abnormalities, valvularheart disease, cardiomyopathies
Management
Treatment Biological
e.g. specific drugs
Nuclear cardiology Radionucleotide angiography (RNA) can quantify ventricular ejection fraction, single
photon-emission computed tomography (SPECT) or PET demonstrate myocardial ischaemia and viability
in dysfunctional myocardium.
CMR (cardiac MRI) Assessment of
viability in dysfunctional myocardium
with the use of dobutamine for
contractile reserve or with gadolinium
for delayed enhancement (‘infarct
imaging’).
Cardiac catheterization Diagnosis of
ischaemicheart failure (and suitability
for revascularization),measurement
of pulmonary artery pressure, left
atrial(wedge) pressure, left
ventricular end-diastolicpressure.
Cardiac biopsy Diagnosis of
cardiomyopathies, e.g.amyloid,
follow-up of transplanted patients to
assess rejection.
Cardiopulmonary exercise
testingPeak oxygen consumption
(VO2) is predictive of hospital
admissionand death in heart failure. A
6-minute exercise walk is an
alternative.
Ambulatory 24-hour ECG monitoring
(Holter) In-patients with suspected
arrhythmia. May be used in patients
with severe HF or inherited cardiomyopathy to determine if a defibrillator is appropriate (non-sustained
ventricular tachycardia).
Relieving symptoms, prevention and control of disease leading to cardiac dysfunction and HF, slowing
disease progression and improving quality and length of life.
Diuretics: (furosemide, bumetanide, bendroflumethiazide), help prevent fluid overload providing
symptomatic relief for dyspnoea and improve exercise tolerance; limited efficacy for survival rates
ACE-I: (captopril, ramipril), symptomatic relief, improved prognosis, slowed development of HF,
recommended in all pts at risk of developing HF
Angiotensin II receptors (ARA) inhibitors: (losartan), if pts are intolerant of ACEI
Β-blockers: (bisoprolol, carvedilol), improve functional status and reduce CV morbidity and mortality in
pts with HF
Aldosterone antagonists: (spironolactone, eplerone), improve survival rates
Cardiac glycosides: (digoxin), indicated if pts has AF with HF
Vasodilators and nitrates: (isosorbide dintrate, hydralazine), reduce pre-load and afterload, used in pts
intolerant of ACEI and ARA
Revascularisation: efficacy unclear
Treatment - Social
Prognosis
Biventricular pacemaker/ implanted cardioverter-defibrillator: NYHA 3 pts and if systolic HF
Heart transplant: treatment of choice in younger pts with intractable HF and prognosis of <6months; 5
year survival at 75%
Education: counselling of patients and family, emphasizing weight monitoring and dose adjustment of
diuretics, may prevent hospitalization.
Obesity control: maintain desired weight and body mass index.
Dietary modification: avoid large meals; salt restriction; fluid restriction in severe HF; alcohol has a –ve
inotropic effect (slows HR) so moderate consumption allowed
Smoking: stop immediately
Physical activity, exercise training and rehabilitation: bed rest helps with exacerbations of CCF (but
may lead to DVTs if prolonged) – avoid by daily leg exercises, daily heparin injections, elastic stockings;
low-level enduranceexercise (e.g. 20–30 minutes walking three or five times/week) is actively
encouraged in patients withcompensated heart failure in order to reverse ‘deconditioning’of peripheral
muscle metabolism
Vaccination: vaccinated against pneumococcal disease and influenza
Air travel: possible for most patients, subject to clinical circumstances
Sexual activity: pts on nitrates should not to take phosphodiesterase type 5 inhibitors (e.g. sildenafil) as
it may induce profound hypotension
Driving: may continue if no symptoms to distract the driver; symptomatic HF pts can not drive
lorries/buses
Improved over past 10 years but mortality is still at 50% at 5 years; HF is ass with a 4x ↑ risk of stroke
Disorder– core
How common is it
Core symptoms
Signs
Biological
causes/risk factors
Infective endocarditis: endovascular infectio of CV structures – valves, atrial and ventricular
endocardium, large intrathoracic vessels and intrathoracic foreign bodie (prosthetic valves, pacemaker
leads)
Incidence in UK is 6/100,000 but more common in developing countries
Fever + new murmur = infective endocarditis until proven otherwise
Depends on organisms and presence of predisposing cardiac conditions
Low grade-fever and non-specific symptoms common => a high-index of clinical suspicion is needed
Septic signs: fever, rigors, night sweats, malaise, weight loss, anaemia, splenomegaly, clubbing
High clinical suspicion:
 Cardiac lesions: new valve lesion/(regurgitant) murmur due to valve destruction
 Embolic event(s) of unknown origin: emboli may cause abscess in the relevant organ eg RHS
endocarditis may cause pulmonary abscesses
 Sepsis of unknown origin
 Immune-complex deposition:
o haematuria, glomerulonephritis and suspected renal infarction
o Janeway lesions, Osler’s nodes, splinter haemorrhages, Roth spots,
 ‘fever’ plus:
o prosthetic material inside the heart
o other high predisposition for infective endocarditis, e.g. IVDU
o newly developed ventricular arrhythmias or conduction disturbances
o first manifestation of congestive cardiac failure
o positive blood cultures (with typical organism)
o cutaneous (Osler, Janeway, splinter haemorrhages) or ophthalmic (Roth spots) manifestations
o peripheral abscesses (renal, splenic, spine) of unknown origin
o predisposition or recent diagnostic / therapeutic interventions known to result in significant
bacteraemia.
Low clinical suspicion: Fever plus none of the above.
Usually the result of: presence of organisms in the blood + abnormal cardiac endothelium facilitating
there adhereance and growth
Cause of bacteriaemia:
 pt-specific: poor dental hygiene, IVDU, soft tissue infection
 procedure-specific: dental treatment, cannula, heart surgery, pacemakers, valve replacement
 OHCM: UTI, cystoscopy, endoscopy, sigmoidoscopy, resp infection, colon cancer, GB disease, skin
disease, abortion, fractures.
Organisms:
Commonest is Strep viridians (35-50%); others: enterococci, Staph A or epidermidis
Rare causes:HACEK group of G-ve bacteria = Haemophilus, Actinobacilus, Cardiobacterium, Eikenella,
Kingella; fungi: Candida and Aspergillus; also SLE and malignancy can cause it
Pathology
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
Treatment Biological
e.g. specific drugs
Complications


50% of cases occurs on normal valves and presents with HF
Endocarditis on abnormal valves = sub-acute course: RF = cardiac lesions, valves disease, IVDU,
PDA, VSD; endocarditis acquired ‘early’ = acquired at time of surgery and presents within 60 days
(poor prognosis); ‘late’ = acquired haematogenously
Investigations:
 Bloods: FBC (normocytic normochromic anaemia and polymorphonuclear leucocytosis); U and E
(renal dysfunction common in sepsis); LFTs (↑ALP?); CRP and ESR ↑
 Blood cultures: most important; 3 samples (6 bottles) from different venepuncture sites
 Urine dipstick: proteinuria and haematuria often
 ECG: evidence of MI (emboil) or conduction defects; new AV block = ?abscess formation
 CXR: evidence of HF or in RHS endocarditis, pulmonary emboli or abscesses
 Echo: TTE (transthoracic echo) or TOE (transoesophageal echo); TOE ↑ sensitivity (90% vs 60%) for
aortic root abscess formation and prosthetic valve endocarditis; a –ve echo does not exclude
endocarditis
Criteria for diagnosis: modified Duke criteria
Major criteria:
 Positive blood culture:
o Typical organism in 2 separate cultures or
o Persistently +ve blood cultures eg 3, 12hrs apart
 A +ve serological tests for Q fever
 Endocardium involved:
o +ve echo (vegetations, abscess, new partial dehiscence of prosthetic valve)
o New valvular regurgitation (change in murmur not sufficient)
Minor criteria:
 Predisposition (cardiac lesions, IVDU)
 Fever >38°C
 Vascular/immunological signs
 +ve blood culture that do no not meet major criteria
 +ve echo that does not meet major criteria
Diagnosis = 2 major + 1 minor; 1 major + 3 minor; all 5 minor
Without treatment, mortality reaches 100%; with treatment there is still significant morbidity/mortality
Long-course (4-6wks) of Abx: penicillins are fundamental to treatment so allergies compromise
prognosis; can use vancomycin or teicoplanin instead but not as good
 Empirical: awaiting results (and don’t suspect Staph): Penicillin 1.2 g 4-hourly, gentamicin 80 mg
12-hourly
 Enterococci: Ampicillin/amoxicillin 2 g 4-hourly, gentamicin 80 mg 12-hourly
 Strep: Penicillin 1.2 g 4-hourly, gentamicin 80 mg 12-hourly
 Staph: suspect if IVDU, recent IV devices, heart surgery, acute infection): Vancomycin 1 g 12-hourly,
gentamicin 80–120 mg 8-hourly
Consider surgery if: HF, valve obstruction, repeated emboli, fungal endocarditis, persistent
bacteraemia, myocardial abscess, unstable infected prosthetic valve
Persistent fever: think: perivalvular extension of infection and possible abscess formation; nosocomial
infection (UTI, venous access site); PE (2° RHS endocarditis or prolonged hospitalisation)
Endocrine
Disorder– core
How common is it
Classification
Who does it affect
Core symptoms –
defined by WHO
Diabetes mellitus type 1 (IDDM): syndrome of chronic hyperglycaemia due to relative insulin deficiency
Diabetes mellitus type 2 (NIDDM): syndrome of chronic hyperglycaemia due to relative insulin
resistance
Affects >120million people worldwide, estimated to affect 370million people by 2030;
Type 1: 16-20% incidence in UK; 2-3% increase/year; highest in N European countries
Type 2: 2-3% prevalence in UK, lifetime risk of 15%; common in all populations
Primary (idiopathic): most cases
Secondary (known cause): 1-2% of all cases, but often treatable
Type 1: usually juvenile onset but can come on at any age; concordance in identical twins is only 30% =
environmental influences must exist but is HLA DR3 and DR4-linked
Type 2: much more prevalent, possibly due to better longevity and diagnosis; 4 main determinants =
increasing age, obesity (↑ risk 80-100x), ethnicity and Fx; higher in Asians, >40yo but teenagers are
increasingly being diagnosed with it due to poor diet control/no exercise, M>F; >50% concordance in
identical twins = strong genetic component - polygenic; T2DM is associated with central obesity,
hypertension, hypertriglyceridaemia, low HDL-cholesterol, modest ↑ in pro-inflammatory markers (ie
the metabolic syndrome)
Diagnosis:
1. symptoms + one abnormal result
2. no symptoms + two abnormal random results
3. glucose tolerance test (if ?borderline or gestational diabetes)
Fasting plasma glucose > 7.0mmol/L (126mg/dL)
Random plasma glucose > 11.1mmol/L (200mg/dL)
GTT: plasma glucose > 11.1mmol/L
To perform GTT: fast overnight. Measure venous glucose (whole blood values lower). Give 75g of
glucose in 300mL water for adult (1.75g glucose/Kg body weight for child) in the morning. Measure
venous glucose 2hrs after the drink. >11.1 at 2hrs = DM diagnosis
HbA1C or capillary glucose should not be used to diagnose DM; glycosuria on a urine dipstick may be a
normal finding
Impaired fasting glucose: fasting plasma glucose >6.1mmol/L but <7mmol/L = ?lower risk of progression
to DM than IGT
Type 1: weight loss, persistent hyperglycaemia despite diet and medications; presence of autoAB, islet
cell AB, anti-glutamic decarboxylase antiAB, ketonuria on urine dipstick
Type 2: often asymptomatic or will present with micro/macrovascular complications.
Classic triad: young people present with a 2-6 week history
Weight loss (due to fluid depletion and ↑ breakdown of fat and muscle due to insulin deficiency)
Polyuria (hyperglycaemia causes osmotic diuresis); ketonuria may also be present in young people
Thirst (due to resulting loss of fluids and electrolytes)
Signs
Feature/ symptoms
of presentation in a
general hospital
setting
Clinical findings: evidence of weight loss and dehydration, breath may smell of ketones (pear drops),
vascular complications inc diabetic retinopathy
Ketoacidosis; weight loss
Type 1 is associated with other autoimmune conditions
Complications of DM:
 Macrovascular: prevalent in the West as a whole
o Stroke: ↑ x2
o MI: ↑ x3-5
o Amputation for foot gangrene: ↑ x50
o Tackle hypertension, smoking, lipid abnormalities
o Due to a number of possible causes including: ?stemming from SOD overproduction in
mitochondria due to hyperglycaemic state
 Non-enzymatic glycosylation of proteins (eg Hb, collagen, LDL ad tubulin in peripheral nerves) =
accumulation of AGE (advanced glyscosylated end)-productions = cause injury and
inflammation
 Polypol pathway: metabolism of glucose to sorbitol and fructose by aldose reductase =
changes in vascular permeability, cell prolif and capillary structure
 Abnormal microvascular blood flow impairs supply of blood and nutrients
 Microvascular: specific to DM; manifest 10-20 years after diagnosis
o
Retinopathy grade
Peripheral retina
Background
diabetic/nonproliferative
Pre-proliferative
Proliferative
Advanced
Central retina
Maculopathy
Retina: ~1/3 pts develop eye problems; commonest cause of blindness in <65yo
 Diabetic retinopathy: 20% pts will have changes after 10 years, 80% after 20 years
 Type 1: rapid progression to proliferative retinopathy
 Type 2: progression is slower and (para)macular region affected most often: macular oedema;
can go on to develop proliferative retinopathy
Retinal abnormality (cause)
Action needed
Dot haemorrhages: 1st sign; development of capillary microaneurysms
Blot haemorrhages: (leakage of blood into deeper retinal layers (superficial
haemorrhages on the ganglion cell layer and outer plexiform layer)
Hard exudates: exudation of plasma rich in lipids and protein (?old cotton wool
spots)
Venous beading/loops: indicate capillary non-perfusion; beading occurs as the vein
passes through an area of ischaemia; venous loops result from closure of the vein at
the margin of an area of capillary non-perfusion
Intraretinal microvascular abnormalities: new blood vessels growing within the
retina (healing process), no symptoms evident
Multiple cotton wool spots: microinfarcts within the retina and the spot itself is
made up of axoplasmic debris; debris is removed by macrophage to leave cytoid
bodies (little white dots); may be due to HTN (resolve quickly) or DM
New blood vessel formation: due to widespread capillary non-perfusion (ischaemia).
If they grow on the pupil margin and then at the angle of the anterior chamber, they
will give rise to ↑ intraocular pressure (thrombotic glaucoma); if capillary growth
extends across the macula, then loss of central vision will result
Preretinal or subhyaloid haemorrhage: preretinal = new blood vessel comes through
the retina at the margin of capillary closure – prone to bleed (preetinal haemorrhage
= boat-shaped haemorrhage; lies on inferior half of retina)
Vitreous haemorrhage: further bleeding from a preretinal blood vessel, blood seeps
into the vitreous = loss of vision
Retinal fibrosis: ince new vessels have grown, they undergo evolution with collagen
tissue growing along the margins of the capillary = fibrotic traction bands;
Traction retinal detachment: fibrotic traction bands may pull on the retina = ↑
haemorrhage and retinal detachment = loss of vision
Annual
screening
Aneurysms ↑ in number and leak = fluid accumulates in the retina; if aneurysms are
localised they are associated with fat and protein deposition (circinate retinopathy);
oedema extending into the macula = loss of central vision. Final outcome = large
exudative plaque in central macular area
Non-urgent
referral to
ophthalmologist
o
o
o
o
o
Non-urgent
referral to
ophthalmologist
(fluorescein
angiography;
aggressive
control of
glucose
Urgent referral
to
ophthalmologist;
laser therapy
Urgent referral
to
ophthalmologist
 Cataracts: develops earlier in DM; changes in blood sugar cause osmotic changes in the lens =
refractive error (becomes hypermetropic); commonly resolves with control of blood sugar,
though a ‘snowflake cataract’ is acute and doesn’t resolve
 External ocular palsies: 3rd and 6th nerve; recover spontaneously
Renal glomerulus: (diabetic nephropathy); affects 30% of pts diagnosed when <30 yo; rising
incidence as type 2 DM ↑
 Glomerular damage: 1st functional abnormality = renal hypertrophy with ↑GFR. Over time,
afferent arteriole vasodilates ↑ intraglomerular pressure = damages glomerulus, leading to
sclerosis and thickening of basement membrane; but disruption of protein cross=-links
which makes BM a good filter disintegrate so proteinuria results
 Ischaemia due to hypertrophy of afferent and efferent arterioles; leads to hyalinization of
vessels and ischaemia of kidney
 Ascending infection (UTIs); may occur due to autonomic neuropathy causing bladder stasis
(which makes it easier for infections to start up in damaged kidney tissue)
Nerve sheaths: (diabetic neuropathy)
Vascular cause: occlusion of vasa nevorum (doesn’t explain diffuse symmetrical pattern of some
neuropathies)
Metabolic cause: hyperglycaemia => ↑sorbitol and fructose in Schwann cells => disrupt
structure and function of nerves (delayed conduction via segmental demyelination; later axonal
death)
Symmetrical mainly sensory polyneuropathy: loss of vibration (pain (deep then superficial) and
temperature sensation of feet; later ‘walking on cotton wool’; loss of balance; complications =
unrecognised trauma, blisters due to ill-fitted shoes, ulceration
Acute painful neuropathy: burning/crawling pains in the feet, shins and thigh; worse at night;
pressure from bedclothes intolerable; may develop after insulin started; remits spontaneously
after 3-12 months;
o Mononeuropathy and mononeuritis multiplex: any nerve can be affected by diabetic
mononeuritis; onset is abrupt and painful; eg isolated 3rd and 6th nerve palsies; usually resolve
over 3-6 months
o Diabetic amyotrophy: older men; painful, asymmetrical wasting of quads/shoulders; babinski
reflex may develop, resolves with time
o Autonomic neuropathy: symptomatic autonomic neuropathy is rare;
 CV: tachycardia due to loss of PSNS, postural hypotension due to loss of SNS; warm foot with
bounding pulse sometimes seen due to peripheral vasodilation
 GIT: vagal damage = gastroparesis (and vomiting); autonomic diarrhoea at night
 Bladder: loss of tone, incomplete emptying, stasis (predispose to UTIs) = result in painless,
atonic, distended bladder; intermittent self-catheterisation needed
 Erectile dysfunction: very common; incomplete erection to total failure; retrograde ejaculation;
causes = anxiety, depression, alcohol excess, gonadal failure, atheroma in pudendal arteries,
hypothyroidism; treat with PDE type 5 inhibitors
 Diabetic foot ulcers: 10-15% pts develop them at some point; responsible for 50% diabetic-admission
to hospital; ischaemia, infection and neuropathy lead to tissue necrosis => amputation
Diabetic Ketoacidosis:
Type 1: Insulin deficiency due to destruction of pancreatic β-cells (which normally secrete insulin); islet
Ag = insulin, glutamic acid decarboxylase (GAD), protein tyrosine phosphatise (IA-2): appear years
before clinical presentation
Type 2: less insulin secretion and insulin resistance due to β-cell dysfunction; ass with obesity, lack of
exercise and calorie excess; typically progresses from impaired glucose tolerance or impaired fasting
glucose
All pts should be encouraged to live as normal life as possible. Most pts will experience periods of not
coping, of helplessness, of denial and acceptance fluctuating over time.
 Impossibility to take a ‘holiday’ from DM
 Concessions of sympathy often denied as presence is not visible
 Treatment is complex and demanding – trade-offs between short and long-term well-being
 Embarrassing loss of control over personal behaviour can occur if miscalculation of insulin dose
 Risk-taking behaviour (eg emotional eating) has greater impact on someone with DM
 Poor self image
 Eating disorders: 30-40% young women with Dm have an eating disorder
 Non-compliance as with all illnesses: between ¼-1/5 tablets not consumed within treatment period;
insulin omission in young women due to concerns of weight gain
 Need to inform DVLA and insurance companies after diagnosis; wise to inform family and friends in
case of hypoglycaemia; not allowed to work as driver of heavy goods/ public service vehicles, at
heights, as a pilot, with dangerous machinery in motion, barred from police and armed forces
Type 1: associated with other autoimmune diseases (HLA DR3 and DR4 linked)
Types 2: 25-50% pts already have some form of vascular complications at the time of diagnosis
Overview: genetic predisposition in T2DM, but whether it develops or not is largely lifestyle-dependent;
established DM can be reversed by successful diet control + ?bariatric surgery; DM is mostly
preventable
Medications and patient education are key to management
Patient Education:
Improved glycaemic control; depends on cooperation of pt = depends on understanding of risks of DM
and benefits of good glycaemic control (+ keeping lean, stopping smoking, looking after their feet)
Diet: should be no different than for someone w/o DM
Protein: 1g/Kg bodyweight
Fat: < 35%: avoid processed foods (crisps, chocolate, processed meats)
Carbs: 40-60% intake, slow-burning (low-glycaemic index) best – pasta better than potatoes
Encourage sweetners not sugars (squash, cordials OK), limit fruit juices, cakes, biscuits
Low sugar intake, high fibre, 5 fruit and veg/day, alcohol not forbidden (but be aware it may cause
delayed hypoglycaemia), <6g salt/day
Exercise: any increase to be encouraged; participation in formal exercise programmes is best
o
Biological
causes/risk factors
Psychosocial
implications of the
disorder
e.g. job, social
circumstances,
activities of daily
living
Management
e.g. overall plans,
referrals to other
services
Treatment Psychological
Measuring metabolic control of DM:
1. Urine dipstick: if pt doesn’t perform home blood glucose testing; if dipstick is persistently –ve and
there are no symptoms of hypoglycaemia, then assume DM is well controlled.
Treatment Biological
e.g. specific drugs
see drug profiles
Differential
diagnosis
Gestational DM
Metabolic
syndrome
(syndrome X)
Problems: urine glucose lags behind blood glucose; mean renal threshold is ~10mmol/L but the range is
wide (7-13), and it changes with age; urine tests give no guidance re: blood glucose levels below the
renal threshold. Also checks for proteinuria (hence diabetic nephropathy)
2. Home capillary blood glucose testing: 4 samples on 2 days/week note record them in a diary
3. Glycosylated Hb (HbA1C): glycosylation of Hb is a 2-step process; covalent bond forms between
glucose molecule and terminal valine of β-chain of Hb; rate depends on prevailing [glucose] and
provides an index of average blood glucose concentration over the lifetime of the Hb molecule =
~6weeks; glycosylated Hb is expressed as a % of total Hb (standardized range 4-6.2%); not good if RBC
lifespan is reduced or abnormal Hb or thalassaemia present
4. Glycosyalted proteins (fructosamine): index of control over last 2-3weeks; glycosylated albumin is
the major constituent; useful in pts with anaemia or in pregnancy (when RBC turnover changeable)
Targets:
HbA1C <7.5% to reduce risk of microvascular complications; only some pts will reach targets, and it’ll be
harder as DM progresses
Does it matter? YES!
Diabetes Control and Complications Trial: even though 40% pts had blood glucose above non-DM range,
there were 60% reduction in progression to retinopathy, nephropathy by 30%, neuropathy by 20% over
7-year period. Risk = hypoglycaemia
Medications should be prescribed once lifestyle changes are in place. They will not succeed alone in
obtaining good glycaemic control. Tablets will be needed if satisfactory metabolic control is not
achieved within 4-6 weeks.
Control CV risks with ACE-I, a statin, and low-dose aspirin
Type 1: Pt will always need insulin (short-acting, long-acting, inhaled forms available)
Type 2: 3 main drugs; may need insulin after some time once pancreas destroyed
1. biguanide (metformin)
2. sulfonylureas (tolbutamide, glibenclamide, glipizide, gliclazide, chlopropamide)
3. thiazolidinediones (‘glitazones’)
Others: intestinal enzyme inhibitors, orlistat, rimonbant, gastric banding or bypass surgery (marked
obesity unresponsive to 6/12 intensive dieting and graded exercise
Approach to management:
Discuss lifestyle changes and compliance at every stage. As T2DM progresses, β-cell failure will mean
glucose control will deteriorate over time requiring pre-emptive and progressive escalation in therapy.
Most pts on tablets will need insulin in time (consider early if HbA1C > 8% or >7% if concurrent CV
risks): initially insulin at night
Secondary diabetes:
Drug-induced: corticosteroids, thiazide diuretics, atypical antipsychotics, β-blockers, antiretroviral
protease inhibitors
Pancreatic disease: chronic pancreatitis, pancreatectomy (where >90% pancreas has been removed),
trauma, pancreatic destruction (hereditary haemochromatosis, CF), carcinoma of the head of panreas
Endocrine: Cushing’s disease, acromegaly, thyrotoxicosis, phaeochromocytoma, glucagonoma
Insulin receptor abnormalities: acanthosis nigricans, congenital lipodystrophy, glycogen storage disease
Genetic syndromes: Friedreich’s ataxia, dystrophia myotonica
Insulin resistance causes: obesity (↑ the rate of release of non-esterified FA causing post-receptor
defect’s in insulin’s actions), pregnancy, renal failure, polycystic ovarian syndrome, Asians, acromegaly,
CF, Werner’s syndrome, TB drugs, Cushing’s, metabolic syndrome (central obesity, hyperglycaemia,
hypertension, dyslipidaemia (high TG, low HDLs)
Glucose intolerance that develops during pregnancy; usually remits following delivery; typically
asymptomatic; treated with diet and insulin (doesn’t cross placenta so no affect on congenital
abnormalities) during pregnancy; no consensus concerning harmful levels of blood glucose to baby;
complications of hyperglycaemia = stillbirth; mechanical problems in birth canal owing to fetal
macrosomia; hydramnios; pre-eclampsia; ketoacidosis during pregnancy = 50% fetal mortality; baby
more prone to hyaline membrane disease (nenonatal respiratory distress syndrome); neonatal
hypoglycaemia (maternal glucose crosses placenta but insulin does not, so baby secrete insulin to cope
but when the cord is cut hypoglycaemia results) => these are complications due to hyperglycaemia in 3 rd
trimester
Poor glycaemic control at the time of conception = risk of major congenital malformations
Collection of both non-lipid and lipid RF of metabolic origin; insulin resistance is the underlying
mechanism: obesity leads to insulin resistance due to non-esterified FA causing post-receptor defects in
insulin’s action; also gene mutations in insulin receptor.
Increased insulin resistance in obesity, Asian origin, pregnancy, acromegaly, polycystic ovaries, CF,
ataxia telangiectasia, acute and chronic RF, Prader-Willi syndrome, Wener’s syndrome, rifampicin,
isoniazid
Two different bodies make recommendations for a diagnosis:
1. National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III: >3 RF
2. International Diabetes Federation (IDF): large waist plus any other two RF
Defining Level NCEP ATP III
Any three of these:
Defining criteria IDF
Large waist plus any two:
Central (abdominal) obesity*
waist circumference
men > 102 cm (>40 in)
women > 88 cm (>35 in)
men > 94 cm (> 37 inches)
women > 80 cm (> 32 inches)
if South Asian
 Male >= 90 cm
 Female >= 80 cm
if Chinese
 Male >= 90 cm
 Female >= 80 cm
high-density lipoprotein
cholesterol
men <1.0 mmol/L (<40mg/dL)
women <1.3 mmol/L
(<50mg/dL)
men < 1.0 mmol/L (40 mg/dL)
women <1.3 mmol/L (50
mg/dL)
triglycerides
>= 1.7 mmol/L (>= 150mg/dL)
>= 1.7 mmol/L (>=150 mg/dL)
blood pressure
>= 130/85 mmHg
>= 130/85 mmHg
fasting plasma glucose
>= 6.6 mmol/L (>=110mg/dL)
>= 5.6 mmol/l (>=100 mg/dL)
Risk Factor
Central obesity is better correlated to metabolic syndrome than high BMI
Treatment is:
Weight reduction; increased physical activity (lowers VLDL, BP, and insulin resistance and beneficial
effects on CV function); hypertension and TG-lowering treatments; reduce alcohol, smoking and
lowering monosaturated fat intake
Disorder– core
How common is it
Classification
Who does it affect
Core symptoms
Signs
Features/ symptoms
of presentation in a
primary care setting
Biological
causes/risk factors
Goitre
Can be felt in up to 9% of population
Thyroid cancers: ¾ affect women, presenting initially as thyroid nodules, 400 deaths annually in UK
Most commonly recognised by friends and family as a cosmetic defect; majority painless; large goitres
can cause dysphagia and difficulty breathing = compression of oesophagus or trachea.
A small goitre may be visible on swallowing (note size, shape, consistency, mobility and whether a lower
edge can be palpated. Ask about medications (esp iodine-containing preparations) and radiation
exposure
 Puberty and pregnancy may produce a diffuse increase in size of the thyroid.
 Pain in a goitre may be caused by thyroiditis, bleeding into a cyst or (rarely) a thyroid tumour.
 Excessive doses of carbimazole or propylthiouracil will induce goitre.
 Iodine deficiency and dyshormonogenesis (see above) can also cause goitre.
Questions to ask:
1. Is thyroid smooth or nodular?
2. Is the pt euthyroid, thyrotoxic or hypothyroid?
a. Smooth, non toxic goitre: Endemic (iodine deficiency); congenital; tyroiditis; physiological;
Hashimoto’s thyroiditis;
b. Smooth, toxic: Graves’ disease
3. Any nodules? Many or one? If >4cm = likely to be cancer
Diffuse:
 Simple: no clear cause; usually smooth and soft;?ass with thyroid growth stimulating Ab
 Autoimmune: Hashimoto’s thyroditis and thyrotoxicosis (Graves disease) are both ass with a firm,
diffuse goitre of variable size
 Thyroiditis: acute tenderness/pain in a diffuse swelling = acute viral thyroiditis (de Quervain’s
disease). May produce transient clinical hyperthyroidism with a serum ↑ in T4.
Nodular:
 Multinodular: most common, esp in older people; pt is usually euthyroid; may cause oesophageal
or tracheal compression and laryngeal palsy (hence coarse)
 Solitary: Single thyroid lump: common problem but difficult in diagnosis – should always be
treated as malignant (5% risk), though the majority of these are cysts, adenoma, benign (and
probably the largest nodule of multinodular thyroid) or malignant
 Fibrotic: (Reidel’s thyroiditis): rare, produces a ‘woody’ gland, irregular and hard so difficult to
differentiate between malicnancy; ass with systemic symptoms of inflammation and ↑
inflammatory markers
Malignancy: rapid enlargement, ass lymph node involvement, painful; RF = previous irradiation, lonhstanding iodine deficiency and a Fx. Lung and bones are most common sites for metastases.
Cell type
Papillary
Frequency
70%
Behaviour
Young people
Follicular
20%
Middle-aged, F>M
Medullary
5%
Anaplastic
Lymphoma
<5%
2%
Familial (MEN syndrome)
or sporadic 80%
F:M 3:1; elderly
F:M 3:1; elderly
Spread
Local nodes, lung and bone; good prognosis
esp If young
Mets to bone/ lung early via blood; good
prognosis if resectable
May produce calcitonin; local and mets;
poor prognosis
V poor prognosis;
Present with stridor or dysphagia;
aggressive; ?responsive to radiotherapy
Anterior triangle:
 Submandibular region: submandibular stones
 Pulsatile: carotid aneurysm; tortuous carotid artery; chemodectoma
 Non-pulsatile:
o Midline: dermoid cyst; thyroid goitre; thyroglossal cyst; pharyngeal pouch
o Not-n-midline: brachial cyst
Posterior triangle:
 Cystic hygroma
 Cervical rib
 Subclavian artery aneurysm
 Pancoast’s tumour
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc





Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
Thyroid function tests – TSH plus free T4 or T3.
Thyroid antibodies – to exclude autoimmune aetiology.
Ultrasound with fine needle aspiration = (cytology) – good for demonstrating cystic or solid lumps;
multinodular thyroid may be demonstrated if only a solitary nodule can be palpated. FNA has a 5%
false-negative rate
Chest and thoracic inlet X-rays to detect tracheal compression and large retrosternal extensions in
patients with very large goitre or clinical symptoms.
Thyroid scan (125I or 131I) can be useful to distinguish between functioning (hot) or nonfunctioning (cold) nodules. A hot nodule is only rarely malignant; however, a cold nodule is
malignant in only 10% of cases and FNA has largely replaced isotope scans in the diagnosis of
thyroid nodules.

Indications for surgery:
1. If possibly malignant/ pt considers FNA false-negative rate high
2. Cosmetic reasons
3. Compressive effects on oesophagus or trachea
Papillary and Follicular (differentiated): thyroidectomy (total/partial) with radioactive iodine (RAI)
ablation of residual thyroid post-op; pts are treated with suppressive doses of levothyroxine = T4
(suppress TSH)
Anaplastic (undifferentiated): do not respond to RAI and external radiotherapy only offers brief respite.
Medullary (MTC): arise from calcitonin-producing C cells; ass with multiple endocrine neoplasia type 2
(MEN2); 25% pts diagnosed with MTC have RET protoncogene mutation = genetic and family screening
?necessary; perform phaeochromocytoma screen pre-op; total tyroidectomy and wide lymph-node
excision needed; tumour invasion likely.
Most tumours are minimally active hormonally (but may produce thyroglobulin which can be detected
and used as a tumour marker to guide risk of recurrence)
Adrenal glands
Anatomy and function: 8-10g; outer cortex with 3 zones (reticularis, fasciculata and glomerulosa) producing steroids – 3 types,
and an inner medulla that synthesizes, stores and secretes catecholamines (see adrenal medulla).
Medulla is in the middle and the cortex is the covering. Blood supply is from cortex to medulla.
Glasses feel right, make good sight
Zona glomerulosa
mineralocorticoids (aldosterone) aldosterone is a mineralcorticoid
Zona fasciculate
glucocorticoids (cortisol) cortisol is a corticosteroid
Zona reticularis
sex steroids (DHEA and other weak androgens)
Types of steroid:
1. Glucocorticoids:
Mainly effect carb metabolism; act on intracellular type 2
corticosteroid receptors and combine with coactivating proteins
to bind the glucocorticoid response element (GRE) in specific
regions of DNA to cause gene transcription.
Secretion controlled by the HPA axis:
 Hypothalamus release CRH due to circadian rhythm,
stress and other stimuli.
 CRH travels down portal system ACTH release from the
 anterior pituitary (ACTH is derived from the
prohormone pro-opiomelanocortin (POMC)).
 ACTH contains melanocyte-stimulating hormone
(MSH)-like sequences = causes pigmentation if high
levels
 ACTH causes release of cortisol from adrenals.
 Cortisol (and exogenous steroids) cause –ve feedback on hypothalamus and pituitary gland to inhibit CRH/ACTH
release.
 The set-point of this system clearly varies through the day according to the circadian rhythm, and is usually overridden
by severe stress.
 Following adrenalectomy or other adrenal damage (e.g. Addison’s disease), cortisol secretion will be absent or reduced;
ACTH levels will therefore rise.
Catabolic actions on muscles
Other hormone effects are modified
Repair processes and collagen synthesis in bone and soft tissues are inhibitied
They facilitate requirements of daytime activity and are needed for the stress response
Influence glucose homeostasis
2. Mineralocorticoids:
Mainly effect the extracellular balance of Na+ and K in the distal convoluted tubule of kidneys.
Zona glomerulosa = produces aldosterone
Act on intracellular type 1 corticosteroid receptor
Mineralocorticoid secretion is mainly controlled by the renin–angiotensin system (see p. 1023).
Unlike cortisol, mineralocorticoids and sex steroids do not cause negative feedback on the CRH/ACTH axis.
3. Sex steroids (androgens):
Have relatively weak intrinsic androgenic activity until metabolised to testosterone or dihydrotestosterone in the periphery.
Disorder– core
Who does it affect
Core symptoms
Signs
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Addison’s disease (primary hypoadrenalism) addison’s is inadequate adrenocorticoids
Rare; incidence of 3-4million/year and prevalence of 40-60/million; F>M; linked to autoimmune disease
(90% in UK) but in countries with a ↑ prevalence of HIV/AIDS, TB is an ↑ cause.
Vague and non-specific: weight loss, anorexia, malaise, weakness, fever, depression,
impotence/amenorrhoea, nausea/vomiting, diarrhoea, confusion, syncope from postural hypotension,
abdo pain, constipation, myalgia, joint or back pain.
Pigmentation (esp of new scars and palmar creases): dull, slaty, grey-brown predominant sign in >90%
cases, buccal pigmentation, postural hypotension: due to hypovolaemia and Na loss is also present in
80-90% cases due to mineralocorticoid deficiency), weight loss, general wasting, dehydration, loss of
body hair
Destruction of the entire adrenal cortex = ↓ glucocorticoid, mineralocorticoid and sex steroid
production. ↓ cortisol levels leads to ↑ CRH and ACTH, the latter causing hyperpigmentation.
Autoimmune adrenalitis results from destruction of adrenal cortex by autoantibodies with 21hydroxylase as the common antigen.
Causes:
 Autoimmune disease (90% cases)
 Degenerative (amyloid)
 Drugs (ketoconazole)
 Infections (TB <10% in the UK, HIV)
 Secondary (low ACTH); hypopituitarism, surgical removal
 Others – adrenal bleeding (meningococcal septicaemia, venography)
 Neoplasia (secondary carcinoma)
 Schilder’s disease (adrenal leucodystrophy)
Secondary hypoadrenalism arises due to:
1. hypothalamic-pituitary-disease (inadequate ACTH production)
2. long-term steroid therapy leading to HPA suppression
Investigation is urgent as soon as Addison’s is suspected.
If pt is seriously ill/hypotensive, take a blood sample (to measure cortisol for later), give 100mg
hydrocortisone IM and saline IV.
 Single cortisol measurements are of little value, although a random cortisol below 100 nmol/L
during the day is highly suggestive, and a random cortisol > 550 nmol/L makes the diagnosis
unlikely (but not impossible).
 The short ACTH stimulation test
 A 0900 h plasma ACTH level – a high level (> 80 ng/L) with low or low-normal cortisol confirms
primary hypoadrenalism.
 A long ACTH stimulation test can also exclude adrenal suppression by steroids or ACTH deficiency.
 Electrolytes and urea classically show hyponatraemia, hyperkalaemia and a high urea, but they can
be normal.
 Blood glucose may be low, with symptomatic hypoglycaemia.
 Adrenal antibodies are present in many cases of autoimmune adrenalitis.
 Chest and abdominal X-rays may show evidence of tuberculosis and/or calcified adrenals.
 Serum aldosterone is reduced with high plasma rennin activity.
 Hypercalcaemia and anaemia (after rehydration) are sometimes seen. They resolve on treatment,
but are occasionally the first clue to the diagnosis.
ACTH Test
Measure
Normal test
result or positive
suppression
Use and explanation
Short
Tetracosactide
250µg IV/IM at
time 0
Plasma cortisol
at time 0 and
30min
Cortisol at 30min
>600nmol/L
To exclude primary adrenal failure
Confirms hypoadrenalism but does not
differentiate Addison’s disease from
ACTH deficiency or iatrogenic
suppression (via steroids)
Long
Depot
tetracosactide 1mg
IM at time 0
Plasma cortisol
at time 1, 2, 3,
4, 5, 8, 24hours
Maximum
>100nmol/L
Rise >550nmol/L
To demonstrate or exclude adrenal
suppression via steroid or ACTH
deficiency
Short synacthen test:
Stimulation test for adrenal insufficiency
Y not try the long synacthen test or depot synacthen test if secondary adrenal insufficiency?
No rise in serum cortisol in response to synacthen in hypoadrenal pts
Used to Ascertain the the adrenals are functioning normally after a prolonged course of corticosteroids
Checks the amount of cortisol in the body
Synacthen is tetracosactrin, the first 24 amino acids of ACTH
Used in the diagnosis of hypoadrenalism
Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
THE A D CRISIS
Tachycardia
Hypotension
Eyes are sunken
Abdo pain and anorexia
Dizziness (esp
postural)/dehydrated
Cramps
Rigid abdomen
Increased calcium
Serums sodium is low
Ill pt with a fewver who is
vomiting
Skin turgor is lost
Treat acute hypoadrenalism as an emergency
Long-term treatment: replace glucocorticoid and mineralocorticoid ; treat TB if cause.
Glucocorticoid
 Hydrocortisone 20–30 mg daily (10 mg on
waking, 5 mg at 1200 h, 5 mg at 1800 h) or
 Prednisolone 7.5 mg daily (5 mg on
waking, 2.5 mg at 1800 h); rarely:
 Dexamethasone 0.75 mg daily (0.5 mg on
waking, 0.25 mg at 1800 h)


Good control = clinical well-being and
restoration of normal, but not excessive,
weight AND
normal cortisol levels during the day while
on replacement hydrocortisone (cortisol
levels cannot be used for synthetic
steroids).
Mineralocorticoid
 Fludrocortisone 50–300g daily

Treatment - Social
Acute Addison’s disease:

Clinical context: hypotension, hyponatraemia,
hyperkalaemia, hypoglycaemia, dehydration,
pigmentation often with precipitating infection,
infarction, trauma or operation. The major
deficiencies are of salt, steroid and glucose.

Assuming normal CV function, the following are
required:

1L 0.9% saline should be given over 30–60mins with
100 mg of IV bolus hydrocortisone.

Subsequent requirements are several litres of saline
within 24 hours (assessing with central venous
pressure line if necessary) plus hydrocortisone, 100
mg i.m., 6- hourly, until the patient is clinically stable.

Glucose should be infused if there is hypoglycaemia.

Oral replacement medication is then started, unless
unable to take oral medication, initially
hydrocortisone 20 mg, 8-hourly, reducing to 20–30
mg in divided doses over a few days

Fludrocortisone is unnecessary acutely as the high
cortisol doses provide sufficient mineralocorticoid
activity
–
it should be introduced later.
Good control = restoration of serum
electrolytes to normal AND
 blood pressure response to posture (it
should not fall > 10 mmHg systolic after 2 minutes’ standing)
 suppression of plasma renin activity to normal.
Pt advice:
 All patients requiring replacement steroids should:
 know how to increase steroid replacement dose for intercurrent illness
 carry a ‘Steroid Card’
 wear a Medic-Alert bracelet (or similar), which gives details of their condition so that emergency
replacement therapy can be given if found unconscious
 keep an (up-to-date) ampoule of hydrocortisone at home in case oral therapy is impossible, for
administration by self, family or GP.
Disorder– core
How common is it
Who does it affect
Core symptoms
Cushing’s syndrome cortisol is gushing (hyperadrenocorticism)
Cushing’s syndrome: chronic increased free glucocorticoid excess of which 90% are ACTH-dependent
and 10% are ACTH-independent; causes include Cushing’s disease and iatrogenic causes eg steroids
Cushing’s disease: ACTH-dependent pituitary adenoma (pituitary dependent hyperadrenalism)



Pigmentation only occurs with ACTH-dependent causes.
Excess alcohol can cause a Cushingoid appearance (pseudo-Cushing’s syndrome)
Impaired glucose tolerance or diabetes is common.
Features/ symptoms
of presentation in a
primary care setting
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
Usually divided in to two groups:
1. increased circulating ACTH from the pituitary (=Cushing’s disease), or from an ‘ectopic’ nonpituitary ACTH-producing adenoma elsewhere in the body (10%) with resultant glucocorticoid
excess (=ACTH-dependent Cushing’s)
2. a primary excess of endogenous cortisol (25% cases are spontaneous) due to adrenal tumour or
nodular hyperplasia (with subsequent physiological suppression of ACTH). Rare cases are due to
aberrant expression of receptors for other hormones (e.g. glucose-dependent insulinotrophic
peptide (GIP), LH or catecholamines) in adrenal cortical cells (=ACTH independent Cushing’s).
Most cases of obese, hypertensive and hirsute are not Cushing’s.
Confirmation rests on demonstrating inappropriate cortisol secretion, not suppressed by exogenous
glucocorticoids: though these dynamics are often abnormal with obesity and depression.
physical causes etc
How?
 Random cortisol levels are useless.
Dexamethasone Tests
1. Overnight
Take 1mg going to bed
at 2300h
2. ‘48hr Low dose’
0.5mg 6 hourly
8 doses from 0900h on
day 0
3. 48hr High dose’
2mg 6 hourly
8 doses from 0900h on
day 0



Treatment Biological
e.g. specific drugs
Differential
diagnosis
Measure
Plasma cortisol at
0900h next morning
Plasma cortisol at 0900
on day 0 and +2
Normal test result or
positive suppression
Use and explanation
Plasma cortisol
<100nmol/L
O/P screening test.
Higher false +ve rate
Plasma cortisol
<50nmol/L on 2nd
sample
Diagnosis of Cushing’s:
fail to show complete
suppression so high
[cortisol]
Plasma cortisol on day
+2 <50% of that on day
0 suggests pituitary
dependent disease
Pituitary-dependent
diseases suppresses in
about 90% of cases
24-hour urinary free cortisol measurements; simple, less reliable – repeatedly normal values
render the diagnosis most unlikely, but 10% patients with Cushing’s have normal values
Circadian rhythm. After 48 hours in hospital, cortisol samples are taken at 0900 h and 2400 h
(without warning the patient). Normal subjects show a pronounced circadian variation; those with
Cushing’s syndrome have high midnight cortisol levels (> 100 nmol/L), though the 0900 h value may
be normal.
Other tests. If any clinical suspicion of Cushing’s remains after preliminary tests then specialist
investigations are still indicated. These may include insulin stress test, desmopressin stimulation
test and CRH tests.
Untreated Cushing’s syndrome = poor prognosis; death from hypertension, MI, infection, HF.
Metyrapone, a 11β-hydroxylase blocker if often given (sometimes alongside ketoconazole)
Cushing’s disease: pituitary-dependent hyperadrenalism
Removal of tumour recommended (trans-sphenoidal); nearly always leaves the patient ACTH deficient
immediately postoperatively, and this is a good prognostic sign. Result in 80% remission rate. Irradiation
is occasionally used after failed surgery and is results in 60% remission (though children are nearer
80%). Bilateral adrenalectomy is effective as a last resort.
Adrenal adenomas: resect after clinical remission with metyrapone or ketoconazole.
Adrenal carcinomas: aggressive and poor prognosis; reduce tumour bulk surgically. Mitotane is an
adrenolytic drug and may be used.
Nelson’s syndrome: pigmentation (due to high levels of ACTH) ass with enlaging pituitary tumour,
occurring in 20% of cases post-bilateral adrenalectomy for Cushing’s disease. Rare syndrome now that
adrenalectomy rarely performed.
Hyperthyroidism (Thyrotoxicosis)
Description
Epidemiology
Cause
Clinical effect of excess thyroid hormone usually from gland hyper function.
Hypothalamus→ TRH→ant. Pituitary→TSH→Thyroid →T4 (thyroxine) + T3 (triiodothyronine) production.
Peripheral conversion of T4→T3 (more active). Circulate bound to TBG (thyroxine binding globulin),
unbound is active part. Acts to ↑ cell metabolism via nuclear receptors (in almost all cells), important in
growth and development. ↑catecholamine effects.
Prevalence: ♀:♂ 9:1
Age groups:
Grave’s Disease: 2/3 of cases. Typical age 40-60yrs. Circulating IgG autoantibodies bind to G protein
coupled thyrotropin (TRH) receptors causing smooth thyroid enlargement →↑hormone production.
Triggers: stress, infection, childbirth. Assoc with autoimmune dis: vitiligo, DM1, Addison’s.
Toxic Multinodular Goitre: elderly in iodine deficient areas. Nodules secrete T3+4.
Risk Factors
Symptoms
Signs
Presentation
Diarrhoea; weight↓; appetite ↑ (if +++ = paradoxical weight gain); over-active; sweats; heat intolerance;
palpitations; tremor; irritability; labile emotions; oligomenorrhoea +/- infertility.
Rare: psychosis; choreal panicl itch; alopecia; urticaria.
Pulse fast/irreg (AF or SVT); warm moist skin; fine tremor; palmar erythema; thin hair; lid lag; lid
retraction; goitre; thyroid nodules; bruit.
Grave’s Disease: 1. Eye disease: Exopthalamos, opthalmoplegia. 2. Pretibial myxoedema: oedematous
swellings above lateral malleoli. 3. Thyroid acropachy: extreme manifestation clubbing, painful finger and
toe swelling, perioesteal reaction.
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Heart failure, angina, osteoporosis, opthalmopathy, gynaecomastia.
Management
TFT: TSH↓, T4+T3 ↑.
[free T4+T3 are more representative than total levels as the later depends on TBG, the levels of which ↑
in pregnancy, oestrogen therapy (Pill, HRT) and hepatitis, it is ↓ in nephrotic syndrome and malnutrition,
drugs, and chronic liver disease.]
2. Radioiodine. 3. Thyroidectomy- risk of damage to recurrent laryngeal nerve.
1. Βblockers- propranolol for rapid control of Sx.
Titration of Carbminazole to block function.
Hypothyroidism
Description
Epidemiology
Cause
Risk Factors
Symptoms
Signs
Differential
diagnosis
Complications
Investigations
Treatments
Drugs
Clinical effect of lack of thyroid hormone.
Prevalence:4/1000
Age groups: ≥40yrs ♀:♂ 6:1
Autoimmune causes:
Primary atrophic hypothyroidism: Common. Diffuse lymphocytic infiltration of the thyroid, leading to
atrophy (no goitre).
Hashimoto’s Thyroiditis: goitre due to lymphocytic and plasma cell infiltration. Women 60-70yrs.
Other causes: Iodine deficiency (worldwide chief cause); post-thyroidectomy or radioiodine Rx; Drug
induced
Turner’s & Down’s Syndromes; cystic fibrosis; primary billiary cirrhosis, ovarian hyper stimulation
Presentation
Tired; sleepy; lethargic; mood↓; cold-disliking; weight ↑; constipation; menorrhagia; hoarse voice;
↓memory/cognition; dementia; myalgia; cramps; weakness.
BRADYCARDIC: Reflexes relax slowly; Ataxia (cerebellar); Dry thin hair/skin; Yawning/drowsy/coma; Cold
hands; Ascites +/- pitting oedema +/- pericardial/pleural effusion; Round puffy face/obese; Defeated
demeanour; Immobile +/- ileus; CCF
Untreated: heart disease, dementia.
Pregnancy: eclampsia, anaemia, prematurity, ↓birth weight, stillbirth, post-partum haemorrhage.
Management
TFT: TSH ↑, T4↓
Levothyroxine (T4): 50-100µg (Elderly or IHD- 25µg titrate↑)
Amiodarone: iodine rich drug structurally like T4. 2% get significant thyroid problems with it.
Haematology
Anaemia: a ↓ in Hb in the blood below the reference level for the age and sex of the individual; it is not a diagnosis and a cause
must be found
Level of Hb may also change with plasma volume (↓plasma vol = ↑ Hb): dehydration and apparent polcythaemia (↑plasma vol
= ↓Hb, anaemia): pregnancy
 Koilonychia: iron-deficiency
 Jaundice: haemolytic anaemia
 Bone deformities: thalassemia major
 Leg ulcers: sickle cell disease
Types of anaemia classified by MCV:
 hypochromic microcytic with a low MCV
 normochromic normocytic with a normal MCV
 macrocytic with a high MCV
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Screening questions
to ask
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Iron deficiency anaemia, a type of microcytic anaemia
Very!
Fatigue, headaches, faintness, SOB, angina, intermittent claudication, palpitations (anaemia may
exacerbate CV problems esp in the elderly)
Pallor, tachycardia, systolic flow murmur, cardiac failure plus epithelial cell changes induced by ↓ iron:
Koilonychia, brittle nails, atrophy of the papillae on the tongue, angular stomatitis, brittle hair, a
syndrome of dysphagia and glossitis (Plummer–Vinson or Paterson–Brown–Kelly syndrome; see
p. 255 K and C).
Ask about dietary intake, NSAIDs (induce GI bleed), blood in faeces (bleeding bowel/Ca/haemorrhoids),
menstruation duration and number of sanitary towels/tampons used/day (3-5 normal)
 Blood loss: gut, PV, PU, resp tract…anywhere
 Increased demand: pregnancy, growth
 Reduced intake: diet, malabsorption (most common)
Age-specific causes:
 Child: diet, growth, malabsorption
 Young women: menstrual loss, pregnancy, diet
 Old people: bleeding, GI problems (ulcer, malignancy, diverticulitis)
Blood test: 1-2 common ways to prove it
1. FBC, indices (+film): small (microcytic, ↓MCV <80fl), pale (hypochromic, MCH <27pg) cells. There is
poikilocytosis (variation in shape) and anisocytosis (variation in size)
2. Serum ferritin: reflects amount of stored iron; normal = 30–300 g/L (11.6–144 nmol/L) in
males and 15–200 g/L (5.8–96 nmol/L) in females; acute-phase inflamm marker so ↑ in
presence of inflamm or malignant diseases (use serum iron/TIBC/serum ferritin/soluble transferrin
3.
4.
5.
6.
Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
Treatment - Social
Differential
diagnosis



together instead); if ↓ then pt is definitely deficient
ZPP
Serum iron/ TIBC (total iron binding capacity): serum iron ↓ and TIBC ↑if iron deficient
Serum soluble transferrin receptors: ↑ in deficiency; helps distinguish between iron deficiency and
anaemia of chronic diseases
Bone marrow: erythroid hyperplasia with ragged normoblasts seen in iron deficiency, staining using
Perl’s reaction does not show Russian-blue granules of stainable iron like normal (if rings then =
sideroblastic anaemia); useful for complicated cases (?iron deficiency or anaemia of chronic
disease)
Establish there is a low iron
Establish cause
Treat the iron and the cause
Hb level should raise 1g/dL per week; also measure reticulocyte count to assess progress of treatment
Oral iron (ferrous sulphate (200 mg three times daily, a total of 180 mg ferrous iron):
cheap, works, not always useful, hard to tolerate pharmacological doses (n+v); constipation
 IM iron (iron sorbitol): always painful
 IV iron (low molecular weight iron dextran/sucrose): increasingly used (but consider ?poor oral
compliance, continuing haemorrhage, wrong diagnosis); used for pts unable to take oral iron,
chronic disease (IBD), severe malabsorption; iron stores replaced quicker but haematological
response is no different
 Blood transfusion: almost never required unless pt is haemodynamically unwell
 Diet: red meat, baked beans, boiled eggs, sardines/ oily fish, breakfast cereals with added vitamins,
green leafy veg, dried fruit, wholemeal bread, lentils, nuts
 Poor compliance to iron often
Anaemia of chronic disease:
Esp hospital pts, chronic infections (TB) or chronic inflamm disease (IBD, rheumatoid, SLE, polymyalgia
rheumatic, cancers); ↓ release of iron from bone marrow, inadequate EPO response to anaemia,
decreased RBC survival; mechanisms unclear; serum ferritin raised due to inflamm process. Pts do not
respond to iron therapy; anaemia of renal disease responds to synthetic EPO
Sideroblastic anaemia:
Inherited or acquired disorders characterised by refractory anaemias; ring sideroblasts in bone marrow
is diagnostic (there is accumulation of iron in the mitochondria of erythroblasts owing to disordered
haem synthesis forming a ring of iron granules around the nucleus that can be seen with Perls’
reaction); blood film of dimorphic (two types of RBC seen).
Disorder– core
Megaloblastic anaemia (vit B12 or folate deficiency). Presence of erythroblasts with delayed nuclear
maturation due to defective DNA synthesis in the bone marrow.
How common is it
Who does it affect
Biological
causes/risk factors
Vit B 12 or folic acid deficiency or abnormal
metabolism
Ultimately: Block of DNA synthesis due to
inability to methylate dUMP to dTMP. Methyl
group is supplied by the folate coenzyme,
methylene tetrahydrofolate (THF)
 Folate deficiency reduces supply of this
coenzyme.
 Vit B12 also reduces the coenzyme supply
by slowing demthylation of methyl THF to
THF
Other congenital/acquired forms of
megaloblastic anaemia are due to pruine and
pyrimidine interference which inhibit DNA
synthesis
dUMP
dTMP
dHFR
Vit B12: cobalamin
Made by microorganisms. Humans are
dependent on animal sources (meat, eggs, fish,
milk). Average daily diet = 5-30μg, only 2-3 μg
absorbed; we store 2-3mg in the liver and have
two years’ worth of supply.
Methylation of homocysteine to methionine
with simultaneous demethylation of methyl THF to THF.
1) Low dietary intake: vegans
2) Impaired absorption:
a) stomach: pernicious anaemia (main cause), gastrectomy, congenital deficiency of intrinsic
factor
b) small bowel: illeal disease/ resection, bacterial overgrowth, tropical sprue, fish tapeworm
c) pancreatitis/coeliac disease: don’t usually affect vit B12 enough
3) Abnormal utilisation: nitrous oxide, congenital transcobalamin II deficiency
Pernicious anaemia: autoimmune disorder causing atrophic gastritis of parietal cells in gastric mucosa
=> intrinsic factor not released and vit B12 not absorbed. IF transports vit B12 to specific receptors in
illeum for absorption but remains in the lumen itself. 1% vit B12 absorbed if no IF. Common in elderly
(1/8,000 >60yo in UK), F>M, all races but more if white and fair-haired, ass with thyroid disease,
Addison’s disease and vitiligo; high incidence of gastric Ca it pt has PA. Parietal cell AB found in 90% pts
(only 50% with AB vs IF = diagnostic). Parietal cells are replaced with mucin-producing cells. Onset:
insidious anaemia, ?lemon-yellow colour (inc haemolysis causing pallor and mild jaundice); neurological
changes (progressive polyneuropathy of peripheral nerves, symmetrical parasthesiae in fingers and
toes, early loss of vibration and proprioception, progressive weakness and ataxia, paraplegia, dementia,
hallucinations, optic atrophy) if untreated are irreversible; Treatment: corticosteroids can improve
histology. Presents: anaemia but no neuropathy.
Folate:
In diet as polyglutamate form, which are digested to monoglutamate form in upper GIT, and during
absorption these are converted to methyl THF monoglutamate (main form in serum). Found in green
veg (spinach and broccoli) and offal (liver and kidney). Minimal daily requirement of 100 μg. Body’s
reserves of folate are low (10mg). on a deficient diet, folate deficiency develops over ~4/12, but maybe
quicker if poor diet and increased use (alcoholics, ICU pts). Folate acid at the time of conception (before
too!) and for 12/52 of pregnancy reduce neural tube defects
1) Nutritional:
a) Poor intake: old age, poor social conditions, starvation, alcohol excess => main cause
b) Poor intake due to anorexia: GI disease (gastrectomy, coeliac disease, Crohn’s)
2) Antifolate drugs: anticonvulsants (phenytoin, primidone), methytrexate, pyrimethamine,
trimethoprim
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
3) Excess utilization:
a) Physiological: pregnancy, lactation, prematurity
b) Pathological: haematological disease with inc RBC production (haemolysis), malignant disease
with inc cell turnover, inflamm disease, metabolic disease (homocystinuria), dialysis
4) Malabsorption: small bowel disease
Haematology:
 anaemia; MCV >96fL
 peripheral blood film: macrocytes with hypersegmented
polymorphs with 6 or more lobes in the nucleus
 if severe, leucopenia or thrombocytopenia may be present
Bone marrow: large cells, large immauture nuclei, chromatin is finely
dispersed, giant metamyelocytes are frequently seen (twice size of normal
cells and twisted nuclei
Serum bilirubin: may be raised as a result of ineffective erythropoeisis and
premature breakdown of RBC. LDH can also be increased due to haemolysis.
Serum methylmalonic acid (MMA) and homocysteine (HC): raised in B12
deficiency; HC raised in folate deficiency only.
Serum vit B12: usually <160ng/L (which is lower end of normal range)
Serum folate: normally normal or high
Do not recommend blood transfusions for chronic anaemia anymore (may precipitate HF in elderly).
Vit B12 deficiency: IM hydroxycobalamin 1000μg to a total of 5-6mg over 3 weeks, then 1000μg every 3
months forever; or orally 2mg/day; clinical improvement in 48hrs, but polyneuropathy may take 612months
Folate deficiency: 5mg folate daily for ~4months. Treat any underlying cause. Prophylactic folic acid
(400μg daily) is recommended for all women planning pregnancy.
Disorder– core
How common is it
Who does it affect
Core symptoms
Signs
Aplastic anaemia: pancytopenia with hypocellularity (aplasia) of the bone marrow. There are no
leukaemic, cancerous or other abnormal cells in bone marrow or peripheral blood.
Uncommon but serious; more commonly acquired
Anaemia, bleeding, infection; bleeding often predominant initial presentation with bruising with
minimal trauma or blood blisters in the mouth
Ecchymoses, bleeding gums, epistaxis (nosebleeds); mouth infections; lymphadenopathy and
hepatosplenomegaly are rare.
Screening questions
to ask
Features of the
mental state
Features/ symptoms
of presentation in a
primary care setting
Feature/ symptoms
of presentation in a
general hospital
setting
Biological
causes/risk factors
Investigations
e.g. to confirm
diagnosis, exclude
physical causes etc
Management
e.g. overall plans,
referrals to other
services
Treatment Biological
e.g. specific drugs
Due to reduction in pluripotent stem cells AND a fault
with those remaining/IR against them so they’re
unable to re-populate the bone marrow. Absences in
one cell line may occur (eg red cell aplasia)
1) Primary:
a) Congenital: Fanconi’s anaemia
b) Idiopathic acquired: 67% of cases –
?immune causes; activated cytotoxic T cells
cause BM failure
2) Secondary:
a) Chemical: benzene, toluene, glue sniffing
b) Drugs: Abx (chloramphenicol), gold,
penicillamine, phenytoin, carbamezapine,
carbimazole, cytotoxic drugs (busulfan,
doxorubicin)
c) Insecticide:
d) Ionising radiation:
e) Infections: viral hepatitis, EBV, HIV, erythrovirus, TB
f) Paroxysmal nocturnal haemaglobinuria:
g) Other: pregnancy
Other causes of pancytopenia?
Course of aplastic anaemia: spontaneous remission or progressive deterioration with more severe
pancytopenia, haemorrhage and infection.
A bad prognosis (i.e. severe aplastic anaemia) is associated with the presence of two of the following
three features:

109/L

109/L

109/L.
1.
2.
Supportive care while waiting for bone marrow to recover: transfusion?
Treatment to promote bone marrow recovery; if not responsive to therapy, bone marrow
transplant can be considered but onl 30% survival rate in 5 years if from unrelated donor (75-90% if
from sibling)
Main problem/concern is infection; take precautionary measures. If suspectinfection, treat with broadspectrum Abx