BODY SYSTEMS HD - GI

#separator:tab #html:true What are examples of eating disorders?- anorexia nervosa - bulimia nervosa - binge eating disorder - OFSED (other specified feeding and eating disorders) - ARFID (avoidant restrictive food intake disorder) What are the diagnostic features of anorexia nervosa?Diagnostic features of anorexia nervosa 1. active maintenance of low body weight (<85% of expected wt or BMI=or<17) 2. extreme shape & weight concern Types: restricting, binge/purging What are some statistics associated with anorexia nervosa?Anorexia nervosa statistics: - more common in dancers - peak at 15-18yrs - 95% female What are the behavioural signs of anorexia nervosa?Behavioural signs of anorexia nervosa - avoiding food they think is fattening - cutting food into smaller pieces, telling lies about eating habits - excessive exercising - setting high standards and being a perfectionist - depression and anxiety symptoms - may underestimate seriousness of the problem What are the physical signs of anorexia nervosa?Anorexia nervosa physical signs - difficulty sleeping - stomach pains, feeling cold and low body temp, weakness and loss of muscle strength - hair falls out - periods may stop or become irregular - low blood pressure What are the diagnostic features of bulimia nervosa?Diagnostic features of bulimia nervosa 1.recurrent binge eating - large amounts quickly, loss of control 2.compensatory behaviour - vomiting, laxatives, fasting, exercise 3.extreme shape & weight concern binge frequency (1/wk for 3 months) not anorexia nervosa What are the statistics associated with bulimia nervosa?Bulimia nervosa statistics - prevalence in girls aged 18-25 - 95% female - late age of onset - complications of purging, severe psychological effects What are the behavioural signs of bulimia nervosa?Behavioural signs of bulimia nervosa - bingeing, disappearing soon after eating, usually secretive, distorted perception of body weight/shape - associated with depression and low self esteem - feeling anxious and tense - feel loss of self-control over eating - mood swings What are the physical signs of bulimia?Physical signs of bulimia - vomiting - misuse of laxatives and diuretics - enlarged salivary glands - swelling of hands and feet - gastric problems - excessive exercising - stomach pains - feeling bloated - periods stop or are irregular - regular changes in weight What do eating disorders have in common?- behaviour around food - core beliefs and associated concerns - levels of distress What are specific and non-specific risks?Specific - body dissatisfaction risk factors (negative body image) Non-specific - self-regulatory risk factors (low self esteem) What happens in adolescence?Identity is bound to external appearance For girls, high levels of shape/weight concern acted out through food Peer impression management conforming What happens in food and mood regulation?•Day to day eating - mood lifted by consumption of good tasting, high energy food - +ve (-ve?) reinforcement - cravings triggered by -ve mood What happens in eating and emotion in ED?Stopping eating - when external events feel outside personal control e.g. response to an argument - to influence others e.g. to show feelings of distress, defiance, or anger Binge eating and purging - regulate negative emotional states escape from aversive self-awareness reinforcing and self-maintaining What are examples of multi-disciplinary team treatment?•CAMHS Practitioners •Dietitian •Nurses •Pediatricians •Psychiatrists •Psychologists •Specialist Assessment and Treatment •Duty •Supervision •Consultation •Training What are the stages of treatment?- weight management (low weight) - psychological therapies - relapse prevention What are the different types of treatment?"<div><img src=""quizlet-i66HtlNqycXILeBULP18Ng.png""></div>" What is the course of disordered eating?"<div><img src=""quizlet-YC1hJ5.frA3vdd0lzDFjlA.png""></div>" What are methods of accessing treatment?- getting help early - via primary care - access to psychological interventions - specialist CAMHS or adult services - access via GP referral or SPA (CAMHS) - local and national help e.g. beat SUMMARY- food/eating is relevant to EDs - presentation and management - disordered eating - commonplace, co-occurs with other problems - an illness, not a life-style choice - eating disorders may not be the primary problem but develop as a way of managing the problem How many patients are affected by malnutrition?•40% patients malnourished on acute admission •Up to 70% of patients malnourished on discharge What are the effects of poor nutrition?•Normal fit adult -Complete starvation → death in 2 months •After trauma/infection/major surgery -Starvation→ death in 1 month •Acute weight loss of ≥ one third -Impending death What are the consequences of malnutrition?- increased readmission to hospital - reduced muscle power - poor wound healing/pressure sores - reduced immune response - fatigue/depression - prolonged recovery time/hospital stay How is malnutrition assessed?MUST (adults) - Malnutrition Universal Screening Tool - Developed by BAPEN, 2003 - Assessment of malnutrition risk - Assessment of malnutrition What are trigger questions for malnutrition assessment?•Trigger questions: -Has the patient lost weight recently? - -Has the patient noticed a reduction in their appetite? - -Will this admission have an impact on patient's nutritional intake, e.g. multiple injuries, swallowing problems, NBM (Nil By Mouth) What is MUST?•3 measurements -Body Mass Index (BMI) (Weight/Height2) -Recent weight loss (%) -Acute illness with, or likely to be, no nutritional intake for 5 days What are the scoring systems of MUST?"<div><img src=""quizlet-Q1I0n-2C6TlxTuC-sEYeTQ.png""></div>" What are high risk medical conditions associated with artificial feeding?-High risk medical conditions •Swallowing problems •Poor absorption from gut •High nutrient losses •Increased nutritional needs What is unexpected malnutrition?Where someone who is overweight is also malnutrition What are other nutritional assessments?•Clinical •Anthropometric -Tricep skinfold thickness -Mid arm circumference -Mid arm muscle circumference •Biochemical -Poor -Albumin NOT a marker of poor nutrition (but negative acute phase protein) -Can measure levels of vitamins/trace elements etc. What is a nutrition team made up of?•MDT comprising -Nutrition doctors (medical and surgical) -Dietitians -Nutrition nurse specialists -Nutrition pharmacists - -Others - e.g. biochemist What are nutritional requirements?- Calories Equations for each age group and gender and clinical condition - Enough of: Fat Protein Carbohydrate -Electrolytes Vitamins and minerals Who needs artificial nutrition?•Can't eat -Stroke -Head and neck surgery • •Can't eat enough -Burns -Sepsis -Pre-operative malnutrition • •Shouldn't eat -Bowel obstruction -Leaks after surgery -Prolonged paralytic ileus What are oral nutrition supplements?Can provide: • 340 kcal • 20 g protein • Vitamins/minerals (approx a fifth of requirements) What is enteral feeding?nutrients delivered directly to GI tract - needed when persistent and poor oral intake - dysphagia (difficulty in swallowing) - need functioning gut What is parenteral feeding?IV What is short-term enteral feeding?Can provide: • 340 kcal • 20 g protein • Vitamins/minerals (approx a fifth of requirements) What is PEG?-Percutaneous Endoscopic Gastrostomy What is RIG?-Radiologically Inserted Gastrostomy -If cancers in upper GI tract What is TPN?•TPN = Total parenteral nutrition -So actually PN (patients often eat) -Feeding into the vein •Acutely -Patients often on PN solely •Long-term -May be a mixture of oral + PN +/- enteral What are indications for PN?- Inability to establish any other route for nutrition - Inability to meet nutritional requirements via the oral or enteral route -Obstruction -Short Bowel Syndrome (after surgical resections) - Fistulae (abnormal connections, often between bowel and skin) - Complications post-surgery - Prolonged paralytic ileus - Anastomotic leaks What is the composition of parenteral nutrition?•Protein •Glucose •Fats •Electrolytes -Sodium, potassium, calcium, magnesium, phosphate •Vitamins -Fat soluble -water soluble •Trace elements -Zinc, selenium, manganese, copper, iron What are the routes for IV feeding?"<div><img src=""quizlet-h8M5oi8RX7CtALmEH0Ab-g.png""></div>" What is PICC?peripherally inserted central catheter What is a tunnelled central catheter?Central line inserted into chest, line tunnelled through skin. (Hickman line) What are the complications of PN (parenteral nutrition)?- Infection (usually from line) - High blood sugar - may require insulin - Electrolyte disturbance - Abnormal liver tests/liver failure - Refeeding Syndrome What happens in starvation?•↓ insulin secretion •↑ glucagon secretion •Switch from glucose to ketones for energy •Glycogen stores used •Basal Metabolic Rate (BMR) decreases •Brain adapts to ketones •Atrophy of all organs •Reduced lean body mass What are the consequences of starvation?•Deficiency of vitamins and trace elements •Whole body depletion of -Potassium -Magnesium -Phosphate •Impaired cardiac, intestinal and renal reserve • •SERUM electrolytes maintained within normal limits What happens in refeeding?•Increased uptake of: -Glucose -Phosphate -Potassium -(Magnesium also as co-factor) - •Reactivation of Na/K pump -Potassium moves into cells, Na/water out Switch from catabolism to anabolic growth Increased thiamine utilisation What are the consequences of refeeding syndrome?•'Too much too soon' •Patients at risk -Malnourished -No recent intake -Alcoholic •What happens? -Fluid shifts -Electrolyte shifts What are the consequences of NOT refeeding?•Low phosphate •Low potassium •Low magnesium +/- calcium •Low thiamine (Wernicke-Korsakoff's) •High glucose •Cardiac failure, pulmonary oedema and dysrhythmia How should you treat refeeding syndrome?-identify patients at risk -Give pabrinex (iv Vit B and C - thiamine) •Prevents Wernicke's / Korsakoff's -Feed slowly and build up -Daily electrolytes •K, PO4, Mg •Correct abnormalities Outline monitoring longer-term PN•Temperature/pulse/BP + weight daily •Blood sugars 6 hourly •Daily FBC, U&E, Mg, Ca initially •Then 3X week Ca, Mg, Phosphate, LFT •Regular trace elements (Copper, Zinc and Selenium) What is malnutrition a common problem in?It is a common problem in hospitalised patients What is dyspepsia?a broad term used to describe digestion impairment and the associated pain and discomfort of the upper GI tract/ abdomen How is acid production associated with dyspepsia and peptic ulcers?oversecretion of gastric acid can contribute to dyspepsia and peptic ulcers Give two molecules that directly stimulate gastric acid secretion:1) acetylcholine 2) gastrin What cells do acetylcholine and gastrin directly bind to in order to stimulate gastric acid production?parietal cells What molecule indirectly stimulates gastric acid release from ECL cells?histamine What cells are indirectly stimulated by histamine to secrete gastric acid?ECL cells Give the pathway of histamine causing gastric acid release from ECL cells:histamine -> receptors -> activates adenylate cyclase -> ATP to cAMP -> protein kinase A -> protein phosphorylation -> proton pump activated What is the specific ion channel name given to proton pumps:H+/ K+ ATPase What molecular change is initiated when histamine binds to receptors on ECL cells?GsGDP to GsGTP Give two molecules that inhibit gastric acid secretion:1) somatostatin 2) prostaglandin PGE2 How does prostaglandin PGE2 inhibit gastric acid secretion?it binds to a receptor on parietal cells and activates an inhibitory G protein (Gi) which inhibits activation and adenylate cyclase What is the role of goblet cells in stomach lining?producing mucous to protect stomach lining What is the role of parietal cells in stomach lining?producing gastric acid (HCl) What is the role of chief cells in stomach lining?producing pepsinogen What is pepsinogen?inactive form of pepsin What is the role of D cells in the stomach lining?Producing somatostatin What is the role of G cells in the stomach lining?producing gastrin Give to examples of PPI drugs:1) lansoprazole 2) omeprazole What does PPI stand for?proton pump inhibitor How do PPI drugs inhibit gastric acid secretionthey inhibit H+/ K+ ATPase pumps What is the enteric nervous system?large network of neurons surrounding the digestive organs How do H2 blockers inhibit gastric acid secretion?they inhibit histamine binding to ECL receptors What is a vagotomy?treats gastric ulcers not responding to drug therapy by cutting a section of the vagus nerve to reduce stimulating acetylcholine What are the 4 general types of dyspepsia?1) dyspepsia with alarm symptoms 2) uncomplicated/ simple dyspepsia 3) uninvestigated dyspepsia 4) functional dyspepsia What is uncomplicated dyspepsia?dyspepsia without the presentation of red flags What is functional dyspepsia?dyspepsia with no identified structural cause Give 9 dyspepsia alarm symptoms:1) dysphagia - difficulty swallowing  2) haematemesis - vomiting blood 3) melaena - black stools 4) weight loss 5) palpable epigastric mass 6) persistent vomiting 7) family history of gastric cancer 8) odynophagia - painful to swallow 9) dyspepsia onset over 45-55 years What is a peptic ulcer?erosion of the lining of the stomach or duodenum with a fibrin base Other than peptic ulcers, give two other common causes of dyspepsia:1) gastric cancer 2) gastro-oesophageal reflux disease What method is used to treat dyspepsia believed to be linked to H. pylori?test and treat Give 5 symptoms of peptic ulcers:1) epigastric tenderness 2) epigastric pain after eating 3) nausea 4) weight loss 5) anorexia Give the two main causes of peptic ulcers:1) H. pylori 2) NSAIDs Give two rare causes of peptic ulcers mentioned in the lecture:1) Zollinger-Ellison Syndrome 2) Crohn's disease What is Zollinger-Ellison syndrome?rare condition characterized by gastrin-producing tumours in the duodenum and/or pancreas that lead to oversecretion of gastrin, which lead to gastric and duodenal ulcers What treatment is used for H. pylori associated peptic ulcers?PPI and two antibiotics such as amoxicillin and clarithromycin How can H. pylori survived in the acidic stomach environment?it produces urease which converts urea into ammonia and water, neutralising the acidic pH Give 3 non invasive diagnostic methods for H. pylori:1) carbon urea breath test 2) H. pylori serology 3) H. pylori stool antigen Describe how carbon urea breath tests can diagnose H. pylori:C-13 urea is ingested and broken down by any H. pylori producing C-13 CO2, returned to a mass spectrometer Describe how H. pylori serology can diagnose H. pylori:serum is tested for IgG What are the limitations of H. pylori serology:any past H. pylori infections will cause the test to come back positive Describe how H. pylori stool antigen tests can diagnose H. pylori:monoclonal antibodies for H. pyloria antigens are used on stool samples Give 2 invasive H. pylori diagnostic procedures completed during an endoscopy:1) rapid urease test 2) histological examination of biopsy specimens What colour change is observed in the rapid urease test when H. pylori is present?yellow to red How do NSAIDs cause peptic ulcers?they block prostaglandin synthesis via COX enzymes which is associated with mucus production and inhibition of gastric acid secretion Give 3 complications of peptic ulcers:1) perforation 2) bleeding 3) gastric outlet obstruction/ pyloric stenosis What causes gastric outlet obstruction/ pyloric stenosis?fibrosis and scarring What is haematemesis?vomit in blood What is melaena?the production of dark sticky faeces containing partly digested blood What is coffee ground emesis?Partially digested blood that is vomited up Give 6 symptoms of peptic ulcer bleeding:1) haematemesis 2) melaena 3) rectal bleeding 4) tachycardia 5) hypotension 6) coffee ground vomiting Give 6 functions of the GI tract:1) ingestion 2) mechanical processing 3) digestion 4) secretion 5) absorption 6) excretion Which 4 GI tract functions are applicable to the small intestine?1) mechanical processing 2) digestion 3) secretion 4) absorption What is the name of the junction between the duodenum and jejunum?duodenojejunal flexure What is the name of the small, initial region of the small intestine?duodenum What is the name of the large section of the SI that continues from the duodenum?jejunum What is the name of the large section of the SI that continues from the jejunum?ileum What structure connects the small intestine to the large intestine?ileocecal valve What two muscular layers are found in the wall of the SI?1) inner circular layer 2) outer longitudinal layer What is the name of the surface layer of the SI lumen?mucosal layer What are the folds that villi sit on called?pilica circulares What is found in the submucosal layer of the small intestine?mesenteric arteries, veins, nerves, glands and lymphatic vessels What is the name given to the dips between villi in the jejunum and ileum?Crypts of Lieberkuhn What is the role of Crypts of Lieberkuhn?secreting bicarbonate to neutralise acidic matter from stomach and secreting various hormones What is the name given to the dips found between villi in the duodenum?submucosal Brunner's glands What is the brush boarder?the region where microvilli are found on lumen wall What are brush boarder enzymes?integral membrane enzymes associated with the microvilli of the small intestine mucosal cells What is peristalsis?waves on muscular contractions which move contents along the GI tract Give the 3 steps of peristalsis:1) circular muscles contract behind the bolus while circular muscles ahead of the bolus relax 2) longitudinal muscles ahead of the bolus contract, shortening adjacent segments 3) waves of contraction in the circular muscles forces the bolus forward What is segementation?the alternate contraction of neighbouring segments which churn and fragment the bolus and mix content with intestinal secretions What is the role of segmentation in the SI?churning and mixing food with secretions What do MMCs stand for?migrating motor complex What are MMCs?a series of strong, slow peristaltic waves that sweep along the stomach and small bowel True or false: the pyloric sphincter is relaxed during MMCstrue When do MMCs occur?when the gut is relatively empty (every 90 mins) What hormone stimulates MMCs?motilin How many AAs long is motilin?22 What cell secretes motilin?M cells What suppresses motilin secretion?feeding What is the function of MMCs?to clean, prevent reflux and reduce bacterial growth What group of cells secrete hormones in the SI?APUD cells What cells produce CCK?I cells What cells produce secretin?S cells What cells produce bicarbonate in the pancreas?pancreatic duct cells What is the role of mucous secretion in the SI?lubrication True or false: water, electrolytes and vitamins can be absorbed without processestrue What bonds do amylases break?alpha 1,4 bonds Where is amylase produced?Salivary glands, pancreas, small intestine What happens to small chain carbohydrates at the brush boarder?specific enzymes break them down for absorption (e.g sucrase and isomaltase) What protein takes up glucose and galactose?SGLT proteins Describe how SGLT proteins take up glucose and galactose:active transport using Na+ as a cotransporter What provides energy for active transport through SGLT proteins?Na+/ K+ pump on the other side of the cell creating a concentration gradient What protein takes up fructose in the SI?Glut 5 True or false: Glut 5 actively transports fructose in the SIFalse Where does proteolysis begin?stomach What enzyme activates proteases?enterokinases What is the inactive form of trypsin?trypsinogen What are endopeptidases?enzymes that hydrolyse interior peptide bonds (e.g trypsin and elastase) What are exopeptidases?enzymes that hydrolyse one amino acid from the C-terminal of a peptide (carboxypeptidases) How are small AA chains absorbed at the brush boarder?1) membrane bound peptidases break them into amino acids 2) amino acids are taken up by Na+ linked secondary active transporters What do di and tri peptides require for uptake at the brush boarder?proton linked secondary active transport True or false: a very small proportion of protein is taken up via endocytosistrue What is the role of M cells (not M cells that secrete motilin) in the SI?they are found on Peyer's patches and detect antigens for immune responses What breaks up lipid droplets, increasing their SA?Bile salts What is the name of the process where lipid droplets are broken apart?emulsification How do pancreatic lipases break down triglycerides?they cleave off the outside two fatty acids leaving a monoglyceride and two free fatty acids How do monoglycerides diffuse at the brush boarder?bile salts allow fatty acids to form mixed micelles which can cross the membrane What happens to fatty acids once in SI cells?triglycerides are resynthesized and packaged into chylomicrons which enter lymphatic lacteals What are lymphatic lacteals?lymphatic capillaries Where are conjugated bile salts absorbed?distal ileum How are conjugated bile salts that escape into the colon absorbed?they are deconjugated by bacteria, making them lipophilic and allowing passive reabsorption What aids iron absorption?vitamin c Where is iron absorbed?duodenum and proximal jejunum What brush boarder protein reduces Fe3+ to Fe2+?Dcytb What brush boarder protein cotransports Fe2+ with H+?DMT What aids calcium absorption?Vitamin D Where is calcium absorbed?duodenum What does paracellular mean?between cells True or false: calcium can be absorbed paracellularly at the brush boardertrue Give the 4 fat soluble vitamins:Vitamin A, D, E and K How is vitamin B12/ cobalamin absorbed?intrinsic factor binds once secreted by gastric parietal cells What is the role of the large intestine/ colon?electrolyte balance and final water reabsorption Does the SI secrete acidic or alkaline fluid into the SI?alkaline Give two other common terms for the GI tract:1) alimentary canal 2) digestive tract Approximately how long is the GI tract?8-9m How long is the small intestine (m)?6m Give the 6 key functions of the GI tract:1) ingestion 2) mechanical processing 3) digestion 4) secretion 5) absorption 6) excretion Define 'mechanical processing':crushing and shearing food as well as wetting softening which makes materials easier to propel along the digestive tract Define digestion:the chemical breakdown of food into small organic fragments for absorption by digestive epithelium What is the role of secretion in the GI tract?releasing water, acids, enzymes, buffers and salts by glandular organs and epithelium of the digestive tract Define excretion in relation to the GI tract?removal of indigestible materials and waste products from body fluids What is the medical term for mouth?buccal cavity What is the name of the sphincter found between the stomach and duodenum?pyloric sphincter What are the 3 regions of the small intestine?1) duodenum 2) jejunum 3) ileum What is the name of the sphincter found at the passage connecting the small and large intestineileocecal sphincter What are the 4 regions of the large intestine?1) ascending 2) transverse 3) descending 4) sigmoid What is the caecum?a pouch connected to the junction of the small and large intestines. Where is the appendix located?caecum What is parietal peritoneum?a serous membrane that lines the wall of the abdominal cavity What is visceral peritoneum?peritoneum that covers organs What is the role of peritoneal fluid?provides lubrication and permits organs to move against each other without friction What structure produces peritoneal fluid?peritoneum What is the function of mesenteries?suspends organs, carries vessels and nerves and prevents loops of the gut from getting tangled True or false: mesenteries have fat pads that protect organstrue What 3 branches from the aorta supply to GI tract?1) coeliac artery 2) superior mesenteric artery 3) inferior mesenteric artery What 5 GI structures does the coeliac artery supply?1) stomach 2) spleen 3) gall bladder 4) pancreas 5) liver What 3 GI structures does the superior mesenteric artery supply?1) pancreas 2) small intestine 3) large intestine What 2 GI structures does the inferior mesenteric artery supply?1) large intestine 2) rectum What vessel does most GI blood drain into?hepatic portal vein Where does the hepatic portal vein take blood?to the liver for processing What supplies the liver with oxygenated blood?hepatic artery What are the major layers of the digestive tract from the inside to outside?1) mucosa 2) submucosa 3) muscularis externa 4) serosa True or false: epithelial cells in the GI tract are polarisedtrue What makes epithelial cells polarised?charged proteins are found on the apical side of the cells What is the name of the cell junction that seals the gap between two epithelial cells?tight junction What is the name of the cell junction that connects actin filament bundles across cells?adherens junctions What is the name of the cell junction that connects intermediate fibres between cells?desmosomes What is the name of the cell junction that anchors intermediate filaments in a cell to the extracellular matrix?hemidesmosomes What does paracellular mean?between cells What is primary active transport?Direct use of ATP to carry out active transport. What is secondary active transport?the use of the electrochemical gradient of one molecule to move a second molecule What nervous system innervates the GI tract?enteric nervous system What is the effect of parasympathetic innervation on the GI tract?promotes digestive processes What is the effect of sympathetic innervation of the GI tract?depresses digestive activity Give two examples of plexi found in the enteric nervous system:1) submucosal plexi 2) myenteric plexi What are slow waves?regular oscillations within the resting membrane potential that occur every 3-12 times per minute What cells induce slow waves?Interstitial cells of Cajal What is anorexia nervosa?the active maintenance of a low body weight where BMI is 17 or below What BMI is considered severe anorexia nervosa?below 15 Is anorexia and bulimia more common in males or females?females Give 5 behavioural signs of anorexia nervosa?1) strict dieting 2) depression and anxiety symptoms 3) setting high standards 4) distorted perception of weight/ body shape 5) telling lies about eating Give 6 physical signs of anorexia nervosa?1) severe weight loss 2) irritable and moody 3) hair falls out 4) weakness 5) periods stop 6) downy hair on body What is bulimia nervosa?binge eating and purging What is classified as binge eating?being unable to stop eating whilst feeling bad about it Give 4 examples of purging/ compensatory behaviours associated with bulimia nervosa?1) vomiting 2) using laxatives 3) fasting 4) exercise What is the threshold of binge frequency for bulimia nervosa?1 binge per week for 3 months In what age group is bulimia nervosa most prevalent?18-25 Give 6 behavioural signs of bulimia nervosa:1) purging after binging 2) depression 3) disappearing after eating 4) mood swings 5) feeling guilt of shame after binging 6) distorted perception of weight/ shape Give 6 physical signs of bulimia nervosa:1) fatigue 2) stomach pain 3) gastric problems 4) electrolyte imbalance 5) bloating 6) enlarged salivary glands What is binge eating disorder?significant binge-eating episodes, followed by distress, disgust, or guilt, but without the compensatory purging or fasting that marks bulimia nervosa Give 6 common risk factors for eating disorders:1) perfectionism 2) family history 3) mental health problems 4) being part of a sport/ activity with an emphasis on appearance 5) history of significant dieting 6) exposure to media promoting social comparison What are specific ED risk factors?risk factors associated with weight or shape What are non-specific ED risk factors?risk factors with no association with weight or shape such as trauma Give 3 examples of treatment plans for eating disorders?1) family based treatment- parents are made agents for change 2) physical monitoring 3) cognitive behavioural therapy-enhanced What does MUST stand for?Malnutrition Universal Screening Tool In what 3 instances is MUST used?1) if a patient has recently lost weight 2) if a patient has a reduced appetite 3) if a patient has an issue or injury preventing nutritional intake What 3 factors are used in the MUST test?1) BMI 2) Recent weight loss 3) acute illness or no nutritional intake for 5 days How is BMI calculated?weight in kg/height in meters ^2 What MUST score is considered high?2 and above Give 3 anthropometric nutritional assessments:1) tricep skin fold thickness 2) midarm circumference 3) midarm muscle circumference True or false: blood albumin is a marker for poor nutritionfalse Give the three categories of patients who may need artificial nutrition:1) can't eat (stroke, head/ neck injury) 2) can't eat enough (sepsis, burns) 3) shouldn't eat (bowel obstruction, leaks after surgery) What are the two types of artificial feeding?1) enteral 2) parenteral What is enteral feeding?nutrients delivered directly to GI tract What is parenteral feeding?nutrients delivered into veins True or false: the patient needs a functioning gut for enteral feeding to worktrue Give two methods for short term enteral feeding:1) naso-gastric feeding 2) naso-jejunal feeding What method is used for long term enteral feeding:gastrostomy What is gastrostomy?Insertion of a feeding tube into stomach through an opening in the abdomen What are the two types of gastrostomy?1) PEG 2) RIG What does PEG stand for?percutaneous endoscopic gastrostomy What does RIG stand for?radiologically inserted gastrostomy When is RIG used over PEG?when there is a cancer or other obstruction in the pharynx or oesophagus What does TPN stand for?total parenteral nutrition What does PN stand for?parenteral nutrition When is parenteral nutrition used?when the GI tract is non-functional due to fistulae, obstruction, short bowel syndrome or complications post surgery What parenteral method is used for short term use?insertion into the midline (brachial region) of arm What parenteral method is used for medium term use?peripherally inserted central catheter (feeds into heart) What parenteral method is used for long term use?tunnelled central catheter (runs into heart and out through chest) Give 6 complications associated with artificial feeding (excluding refeeding syndrome):1) pneumothorax 2) sepsis 3) perforated veins 4) infection/ cellulitis 5) high blood sugar (PN) 6) electrolyte disturbance (PN) What is refeeding syndrome?swelling and heart failure after starvation due to low levels of P, K and Mg What minerals are found in low levels in refeeding syndrome?1) magnesium 2) phosphorous 3) magnesium What 3 issues can refeeding syndrome manifest into?1) cardiac failure 2) pulmonary failure 3) dysrhythmia How can refeeding syndrome be prevented? (3)1) slow, progressive feeding 2) Vitamin B and C supplements 3) daily electrolytes Give 6 comorbidities that obesity increases risk for:1) type 2 diabetes 2) hypertension 3) coronary heart disease 4) certain cancers e.g colon 5) osteoarthritis 6) depression What BMI range is considered overweight?25-29.9 What BMI rang is considered obese?30+ True or false: there is no major difference between obesity rates between men and womentrue True or false: obesity rates are higher in less deprived areas of the Englandfalse Other than BMI, name another indicator for obesity:waist circumference Summarise the findings of the 2007 Foresight Report in relation to obesity:1) we live in an obesogenic environment 2) obesity is locked into our lifestyles 3) the pace of technological advancement outstrips human evolution What is meant by an obesogenic environment?obesity is a normal response to an abnormal environment (our environment promotes obesity) What was the name of the 2007 report that researched the causes of obesity?Foresight Report How is weight managed for people with BMIs between 25-40?1) advice on diet, exercise etc 2) oral drugs Give an example of an oral drug used to manage obesity?Orlistat What intervention is considered for those with BMIs over 40?bariatric surgery What considerations should be made when giving weight management advice? (2)1) reasons for motivation 2) how realistic these goals are e.g rates of weight loss, dietary changes, lifestyle and behavioural changes What are the 4 general layers of the anterior abdominal wall?1) skin 2) subcutaneous fat tissue 3) muscle layers (x3) 4) peritoneum What are the three muscle layers found in the anterolateral wall of the abdomen (superficial to deep)?1) external oblique 2) internal oblique 3) transversus abdominis How far is the anterolateral wall from the midline of the abdomen?7/8 cm Why is abdominal subcutaneous tissue a site of notable blood loss during surgery?it has lots of blood vessels running through it In which direction does the external oblique muscle run?inferomedial What is the name of the flattened tendinous sheets that the 3 anterolateral muscles run into in the mid-abdomen?aponeurosis What is the name of the midline structure that aponeuroses meet at in the abdomen?linea alba Why do none of the abdominal aponeuroses attach to bone?the abdomen needs flexibility to distend during eating or pregnancy In which direction does the internal oblique muscle run?superior-medially In which direction does the transversus abdominis run?transversely Where is the transversus abdominis found?below the umbilicus What is the name of the abdominal muscle that found adjacent to the transversus abdominis?rectus abdominis Where is the rectus abdominis found?from the xiphoid process to pubic tubercle in the middle of the abdomen What feature of the rectus abdominis creates the 6-pack effect?tendinous intersections What muscle supports the posterior side of the anterior facing abdominal wall?quadratus lumborum Give 5 functions of the abdominal muscular layers?1) contracting for lateral flexion 2) RA flexes the trunk 3) protection of viscera 4) QL maintains posture 5) can increase intrabdominal pressure for defecation and vomiting Describe the pathway of oxygenated blood from the aorta to the inter and subcostal arteries that supple the abdominal wall:subclavian -> internal thoracic -> superior epigastric -> internal thoracic -> musculophrenic -> inter and subcostal arteries Which inter and subcostal arteries supply the abdominal wall?10, 11, 12 Describe the pathway of oxygenated blood from the aorta to the deep circumflex and superficial epigastric artery:subclavian -> internal thoracic -> superior epigastric -> inferior epigastric -> femoral -> deep circumflex/ superficial epigastric What are intercostal nerves that continue onto the anterior abdominal walls called?thoracoabdominal walls Describe the use of anastomosis in blood supply to the abdominal wall?there is an anastomosis between the superior and inferior epigastric vessels What is the significance of the anastomosis between the superior and inferior epigastric vessels during coarctation of the aorta?a collateral blood supply to the limbs via the femoral artery can be created using the anastomosis Where are thoracoabdominal nerves found?running between the internal oblique and transversus abdominis What 3 structures do the thoracoabdominal nerves innervate?1) skin overlying abdominal muscles 2) muscles of the abdominal wall 3) parietal peritoneum Where do the thoracoabdominal nerves originate from?T7-T11 Where does the subcostal nerve originate?T12 Where do the iliohypogastric and the ilioinguinal nerves originate?L1 What 2 abdominal/inguinal nerves are found at L1?1) iliohypogastric 2) ilioinguinal What is the rectus sheath?aponeuroses of the abdominal muscles forming a fibrous compartment What 3 structures are contained in the rectus sheath?1) rectus abdominis 2) epigastric arteries 3) tips of the thoracoabdominal nerves What structure is found under the transversus abdominis and rectus abdominis layer?transversus fascia What layer is found under the transversus fascia?parietal peritoneum What structures run anterior to the rectus abdominis ABOVE the umbilicus? (2)1) external oblique aponeurosis 2) anterior layer of inferior oblique aponeurosis What structures run posterior to the rectus abdominis ABOVE the umbilicus? (3)1) posterior layer of inferior oblique aponeurosis 2) transversus abdominis aponeurosis 3) peritoneum What structures run anterior to the rectus abdominis BELOW the umbilicus? (3)1) external oblique aponeurosis 2) inferior oblique aponeurosis 3) transversus abdominis aponeurosis What structure runs posterior to the rectus abdominis BELOW the umbilicus? (1)1) peritoneum What is the significance of the arcuate lines?the inferior epigastric vessels perforate the rectus abdominis at the arcuate lines Where are the arcuate lines found?posterior side of the anterior abdominal wall where the epigastric vessels perforate What is the clinical significance of the inguinal triangle of Hesselbach?it contains a depression called the medial inguinal fossa through which direct inguinal hernias protrude through What is the name of the triangle that encloses the medial inguinal fossa?inguinal triangle of Hesselbach Is the inguinal triangle of Hesselbach found on the anterior or posterior face of the anterior abdominal wall?posterior What structure marks the medial side of the inguinal triangle of Hesselbach?rectus abdominis muscles What structure marks the lateral side of the inguinal triangle of Hesselbach?inferior epigastric artery What structure marks the inferior side of the inguinal triangle of Hesselbach?inguinal ligament What is the inguinal region?an area of the abdominal wall that extends from the ASIS to the pubic tubercle What does ASIS stand for?anterior superior iliac spine Is the deep inguinal ring found closer to the ASIS or pubic tubercle?ASIS Is the superficial inguinal ring found closer to the ASIS or pubic tubercle?pubic tubercle What forms the anterior wall of the inguinal canal at the level of the deep inguinal canal?external and internal oblique What forms the posterior wall and roof of the inguinal canal at the level of the deep inguinal canal?transversus fascia What forms the floor of the inguinal canal at the level of the deep inguinal canal?inguinal ligament What forms the anterior wall of the inguinal canal at the level of the superficial inguinal canal?external oblique aponeurosis What forms the posterior wall of the inguinal canal at the level of the superficial inguinal canal?conjoint tendon What is the conjoint tendon?aponeurotic attachments of the conjoining of the internal oblique and transversus abdominis to the pubic tubercle What forms the roof of the inguinal canal at the level of the superficial inguinal canal?medial crus of the external oblique What forms the floor of the inguinal canal at the level of the superficial inguinal canal?lacunar ligament What forms the anterior wall of the inguinal canal at the middle region of the inguinal canal?external oblique aponeurosis What forms the posterior wall of the inguinal canal at the middle region of the inguinal canal?transversus fascia What forms the roof of the inguinal canal at the middle region of the inguinal canal?internal oblique and transversus abdominis What forms the floor of the inguinal canal at the middle region of the inguinal canal?inguinal ligament What is the key content of the inguinal canal in males?spermatic cord What is the key content of the inguinal canal in females?round ligament of the uterus Do direct hernias occur at the level of the superficial or deep inguinal ring?superficial Do indirect hernias occur at the level of the superficial or deep inguinal ring?deep Do direct hernias leave the abdomen medially or lateral to the inferior epigastric vessels?medially Do indirect hernias leave the abdomen medial or laterally to the inferior epigastric vessels?laterally Do direct hernias reach the scrotum?no as the hernial sac is limited by peritoneum and the transversalis fascia Where do indirect hernias commonly end up?the processes vaginalis (scrotum) Which is more common: indirect or direct hernias?indirect What is another term for a direct hernia?acquired What is another term for an indirect hernia?congenital What are intercostal nerves that continue onto the anterior abdominal walls called?thoracoabdominal walls Where is the pharyngeal tonsil located?posterior wall of nasopharynx Where are the palatine tonsils located?oropharynx Where are the lingual tonsils located?base of tongue What is the name of the bone that the tongue attaches to?hyoid bone What is the role of molars in mastication?grinding food What is the roles of cuspid/ canine teeth in mastication?ripping food apart What is the role of central incisors in mastication?biting food into smaller pieces What is mastication?chewing What are the two key mastication muscles?1) messeter 2) temporalis What is the function of the messeter and temporalis muscles in mastication? (2)1) closing the jaw 2) rocking the jaw from side to side What is the role of the tongue and cheeks in mastication?they move food across teeth What are the three major salivary glands?1) parotid 2) submandibular 3) sublingual Where is the parotid gland located?in front of the ear What is the medical term for jaw?mandible Where is the submandibular gland located?under the jaw Name 4 roles of saliva:1) lubricating food 2) immune defence 3) digestion 4) facilitates taste Describe saliva's role in immune defence:it contains antibacterial enzymes such as lysozymes as well as HCO3- and Ca2+ ions to protect against acid and bacteria What two digestive enzymes does saliva contain?1) ptyalin a-amylase 2) lingual lipase True or false: both the parasympathetic and sympathetic nervous systems stimulate saliva productiontrue How does parasympathetic action affect saliva production?makes it more watery How does sympathetic action affect saliva production?makes it more mucoid What region of the brain regulates the parasympathetic action on saliva production?the saliva centre in the brainstem Give an example of a local stimuli in relation to saliva production:taste/ touch in the mouth Give an example of a central stimuli in relation to saliva production:smell/ sight of food What microstructures produce saliva?salvions Describe the two stage process of salvions producting saliva:1) they produce isotonic fluid containing mainly NaCl, protein and/ or mucous 2) as it passes along the duct, salt reabsorption and HCO3- and K+ secretion leads to a hypotonic, alkaline fluid Which is the largest of the salivary glands?parotid gland What % of saliva is produced by the parotid gland?50% What % of saliva is produced by the submandibular gland?45% What % of saliva is produced by the sublingual gland?5% What gland provides the main secretions of salivary amylase and proline rich proteins?parotid gland What gland provides the main secretions of salivary lysozymes and lactoperoxidase?submandibular gland What gland produces the main secretions of lingual lipase?sublingual Does the sublingual gland produce mucoid saliva, serous saliva or both?mucoid Does the parotid gland produce mucoid saliva, serous saliva or both?serous Does the submandibular gland produce mucoid saliva, serous saliva or both?both What nerve supplies the salivary glands with parasympathetic innvervation?facial nerve (CN VII) What nerve supplies the salivary glands with sympathetic innervation?superior cervical ganglion What sites can ptyalin alpha-amylase break in polysaccharides?alpha 1,4 sites (not alpha 1,6 sites) What is the optimum pH of ptyalin alpha-amylase?pH 7 (denatures at pH 4) How does lingual lipase break down triglycerides?they cleave out the outer fatty acid, leaving diacyl glycerol What is the optimum pH of lingual lipase and what is the significance of this?pH 4, is stable in the stomach What are papillae?groves on the tongue containing taste buds Describe how salty and acidic tastes are transmitted:salty tastes cause an influx of Na+ while acidic tastes cause influxes of H+ ions, causing membrane depolarisation and Ca2+ mediated exocytosis of a neurotransmitter Describe how GPCR-based taste sensors work?sweet, umami and bitter tastes stimulated G protein coupled receptors, causing membrane depolarisation and Ca2+ mediated exocytosis of a neurotransmitter What type of cells are odour receptors?nerve cells Describe the voluntary (first) phase of swallowig:food enters the oral cavity and all passages are patent Describe the pharyngeal (second) phase of swallowing:the nasopharynx closes, the pharynx wall contracts and the epiglottis is pushed by the bolus to meet the larynx Describe the third phase of swallowing:the upper oesophageal sphincter opens and the trachea closes Describe the oesophageal (fourth) phase of swallowing:the upper oesophageal sphincter closes and the bolus descends by peristaltic activity How does the oesophagus help lubricate food?it produces mucous What structures innervate the oesophagus:fibres from the oesophageal plexus What cells line the oesophagus?stratified squamous epithelium How long and wide is the oesophagus?25cm L, 2cm W What is the cephalic phase of digestion?earliest phase of digestion in which the brain prepares the body in anticipation of food What nervous division mediates the cephalic phase of digestion?parasympathetic nervous system Describe the nerve action in the cephalic phase (2):1) Vagus nerve (CN X) controls cephalic GI motility and secretions 2) the facial and glossopharyngeal nerves (CN VII and) stimulate salivary secretion Where does the primitive gut tube extend to and from?oropharyngeal membrane to the cloacal membrane What are the three divisions of the primitive gut tube?1) foregut 2) midgut 3) hindgut Where is the foregut found?mouth to first half of the duodenum Where is the midgut found?second half the duodenum to 2/3 along the transverse colon Where is the hindgut found?distal 1/3 of the transverse colon to the superior 2/3 of the rectum When does cranio-caudal folding take place?3-4 weeks What two embryological structures in the midgut continues with after cranio-caudal folding (weeks 3-4)?1) yolk sac 2) vitelline duct Where is the epithelial lining of the primitive gut tube derived from?endoderm Where is the smooth muscle and connective tissue of the primitive gut tube derived from?visceral mesoderm Where is the visceral and parietal peritoneum of the primitive gut tube derived from?visceral mesoderm What structure suspends the primitive gut tube from the posterior abdominal wall?dorsal mesentery What is a mesentery?a double fold of peritoneum What is the name given to organs that are enclosed by peritoneum mesenteries?intraperitoneal What is the name given to the organs that aren't enclosed in peritoneum?retroperitoneum What is meant by secondary retroperitoneum?an organ that was once intraperitoneal during development but is retroperitoneal upon completion Where is the dorsal mesentery found?from the lower oesophagus to the cloaca Where is the ventral mesentery found?from the lower oesophagus to the first part of the duodenum What two structures does the ventral mesentery form?1) lesser omentum 2) falciform ligament What role do mesenteries play in transport?they carry blood supply, lymphatics and nerve supply What arteries give rise to the arteries of the primitive GI tube?vitelline arteries What artery supplies the foregut?coeliac trunk What artery supplies the midgut?superior mesenteric artery What artery supplies the hindgut?inferior mesenteric artery Describe the formation of the definitive gut lumen:1) week 6: proliferation of the endoderm-derived epithelial lining occludes the gut tube 2) apoptosis of the epithelium occurs over the next two weeks, creating vacuoles 3) vacuoles coalesce to recanalise the gut tube by week 9 4) during this process the epithelium becomes more specialised What is the term used to describe the process of vacuoles forming and coalescing during formation of the definitive gut lumen?recanalisation What can incomplete recanalisation of the gut tube cause?stenosis or atresia What can abnormal recanalisation of the gut tube cause?duplication of the GI track Which region of the GI tract is most affected by abnormalities in recanalisation?ileum How does the foregut split into the pharynx and trachea?it forms the respiratory diverticulum from the tracheoesophageal septum which eventually fuses What causes oesophageal atresia?displacement of tracheoesophageal septum What is oesophageal atresia?separation of the proximal and distal ends of the oesophagus, forming blind ends What is the effect of oesophageal atresia?the foetus cannot swallow amniotic fluid and return it to placental circulation What is the effect of the foetus not being able to swallow placental circulation due to oesophageal atresia?polyhydramnios, a large volume of amniotic fluid causes swelling When does the oesophagus form?week 4 Where is the skeletal muscle in the oesophagus derived from?paraxial mesoderm When does the oesophagus descend rapidly as the stomach descends into the abdomen?weeks 4-7 What is the name given to the hernias that arise when the oesophagus doesn't elongate enough, leaving some of the stomach outside the diaphragm?congenital hiatal hernia What is a congenital hiatal hernia?some of the stomach is positioned outside the diaphragm due to the oesophagus not descending enough When does the stomach appear in development?week 4 What structures suspend the stomach in the abdomen?ventral and dorsal mesenteries Describe the rotation the stomach goes under in weeks 7-8:1) 90 degrees clockwise around the craniocaudal axis causing the lesser curvature to move to the right and the greater curvature to the left 2) rotation around the ventrodorsally axis so that the greater and lesser curvature face caudally and cranially respectively Where is the lesser sac located?posterior to the stomach Where is the greater sac located?Everything that is anterior to the stomach and liver within the peritoneum What is the name of the narrow opening that connects the greater and lesser sacs?epiploic foramen of Winslow Describe the formation of the greater omentum:the dorsal mesentery attached to the greater curvature of the stomach grows and reflects back on itself to form an extension of the lesser sac the ventral and dorsal folds fuse  they then fuse with the mesentery of the transverse colon What is the greater omentum?a large apron-like fold of visceral peritoneum that hangs down from the stomach What is congenital pyloric stenosis?Narrowing of pyloric sphincter caused by hypertrophy of smooth muscle Where is the pyloric sphincter?At the distal (duodenal) end of the stomach What is the effect of congenital pyloric stenosis?restricted gastric emptying resulting in dilatation of the stomach and a pyloric mass What is heterotopic gastric tissue?ectopic gastric tissue in the gut tube due to inappropriate epithelial differentiation What is the effect of heterotopic gastric tissue?the gastric tissue produces acid that results in inflammation, ulceration, scarring and narrowing What are the two origins of the duodenum?1) foregut forms the proximal half 2) mid-gut forms the distal half When doe the duodenum elongate to form a ventrally projecting C shape?week 4 Is the duodenum intraperitoneal, retroperitoneal or secondarily retroperitoneal?secondary retroperitoneal What makes the duodenum secondarily retroperitoneal?the dorsal mesentery attached to the duodenum degenerates, switching it from intraperitoneal to retroperitoneal What forms the superior limit of the abdominal cavity?thoracic diaphragm What forms the inferior limit of the abdominal cavity?pelvic cavity (continuous) What forms the anterior and lateral limits of the abdominal cavity?abdominal muscles What forms the posterior limit of the abdominal cavity?lumbar vertebrae Where is does the peritoneal cavity sit relative to the abdominal cavity?inside the abdominal cavity What is parietal peritoneum?layers of peritoneum lining the abdominal wall, inferior surface of the diaphragm and the pelvic wall What is visceral peritoneum?layers of peritoneum that specifically cover organs True or false: parietal and visceral peritoneum are continuous with each othertrue What is meant by retroperitoneal?situated outside peritoneum and in contact with the body wall Give an example of a retroperitoneal organ:kidneys What is meant by intraperitoneal?suspended from abdominal wall by a double layered fold of peritoneum Give an example of a intraperitoneal organ?small intestine (jejunum and ilium) Describe the role of the dorsal mesentery during development?the whole gut tube has a dorsal mesentery to separate the gut from the body wall, allowing it to grow longer than the body cavity Describe the mesentery of the transverse colon:the transverse mesocolon positions the transverse colon horizontally across the posterior abdominal wall What structure separates the greater sac into supracolic and infracolic compartments?mesocolic shelf True or false: most mesenteries are derivatives of the dorsal mesentery from developmenttrue Give 3 examples of secondarily retroperitoneal organs:1) ascending colon 2) descending colon 3) duodenum What are the two divisions of the peritoneal cavity known as?1) greater sac 2) lesser sac What are the two divisions of the greater sac known as?1) supracolic compartments 2) infracolic compartments Where is the lesser sac located?posterior to the stomach Where is the falciform ligament found?between liver and anterior abdominal wall Where is the gastrosplenic ligament found?between stomach and spleen Where is the lienorenal ligament found?between the spleen and kidney What structure divides the greater sac into the supracolic and infracolic compartments?transverse colon Give 8 features of the supracolic compartment:1) falciform ligament 2) subphrenic recess 3) coronary ligaments 4) lesser omentum 5) epiploic foramen 6) lienorenal ligament 7) gastrosplenic ligament 8) hepatorenal recess Give 2 features of the infracolic compartment:1) paracolic gutters 2) the mesentery (around small intestine) What are the 4 regions of the large intestine? (in order)1) ascending colon 2) transverse colon 3) descending colon 4) sigmoid colon What are the large groove segments in the colon wall known as?haustra Where is the appendix found on the colon?caecum True or false: the appendix has its own connections with the colonic lumentrue Give the 3 layers of the large intestine wall from the lumen out:1) simple columnar epithelium 2) submucosal layer and vessels 3) muscularis externa What structure separates the ileum from the colon?ileocecal valve When does chyme move through the ileocecal valve?when the ileum is distended When does the ileocecal valve close?when the caecum is distended What is the name given to the contraction of circular muscles in the colon squeezing contents to and fro?haustration What is the name given to organised, peristaltic haustrations?mass movement Describe how mass movements change the shape of hausta:haustra briefly disappear as the movement sweeps by and then reforms Give three examples of regulatory inputs of the colon:1) enteric nervous system 2) enteroendocrine influences such as 5-HT and peptide YY 3) gastrocolic and orthocolic reflexes What is a gastrocolic reflex?increased secretory and motor functions of the stomach result in increased colonic motility What is a orthocolic reflex?increased colonic motility after standing up or moving around What is the ileal break triggered by?presence of undigested lipid in the distal ileum causing the proximal colon to release peptide YY What is the effect of the ileal break?gastric emptying and small bowel peristalsis is slowed What carries out digestion in the colon?bacteria Give 5 examples of molecules digested by bacteria in the colon and their products:1) urea and amino acids -> ammonia 2) conjugated bile acids -> unconjugated bile acids 3) fibre -> short chain fatty acids 4) primary bile acids -> secondary bile acids 5) bilirubin -> urobilinogen and stercobilins Describe how short chain fatty acids (SCFAs) are absorbed in the colon:secondary active transport with Na+-linked co-transport Describe how salts are absorbed in the colon:by ENaC channels which allow transcellular sodium transport while Cl- diffuses paracellularly with water What stimulates salt absorption in the colon?aldosterone What is a secretagogue?a substance that promotes secretion What are the key secretagogues for chloride in the colon?cAMP and Ca2+ How do cholera, E. coli and C. difficile toxins cause secretory diarrhoea through their interactions with Cl- ions?1) cholera and E. coli toxins increase cAMP 2) C. difficile toxins increase Ca2+ both of these are secretagogues of Cl-, resulting in water moving into the lumen What 3 things control the balance of K+ secretion in the colon?1) plasma [K+] 2) aldosterone 3) cAMP Describe the process of defaecation:1) faeces enter rectum, increasing pressure which triggers reflex relation of the internal anal sphincter 2) a small amount of faeces enter the anus, allowing anal sampling 3) the external anal sphincter contracts 4) the rectosigmoid angle increases upon sitting/ squatting and upon relaxation of the puborectalis muscle 5) the external sphincter and pelvic floor muscles relax, opening the way 6) raised intra-abdominal pressure provides motive force <div>The front of this card is blank. <a href='https://anki.tenderapp.com/kb/card-appearance/the-front-of-this-card-is-blank'>More information</a></div><div>The front of this card is blank. <a href='https://anki.tenderapp.com/kb/card-appearance/the-front-of-this-card-is-blank'>More information</a></div> What is intraluminal digestion?Pancreatic enzyme secretion and emulsification by bile salts What is terminal digestion?enzymatic hydrolysis at the brush boarder of the small intestine What is trans-epithelial transport?transport across, into, and through intestinal epithelial cells What does disturbance in electrolyte absorption cause?osmotic diarrhoea Describe how cholera causes diarrhoea:-cholera toxins act on enterocytes, -activating CFTR channels -move large amounts of Cl-, Na_ and HCO3- into the lumen which water follows What are enterocytes?intestinal absorptive cells What is the brush border?microvilli from epithelial cells lining the small intestine What two food groups are further digested at the brush boarder?1) peptides 2) alpha-dextrins and disaccharides Describe how lactose intolerance causes diarrhoea:-deficiencies in brush boarder lactase -lactose cannot be broken into glucose and galactose, -lactose remains in the lumen, drawing water out Why does lactose intolerance cause bloating?bacteria ferments the sugars Describe how fat is absorbed in the small intestine:bile salts form micelles with long chain fatty acids, allowing them to diffuse across the brush boarder Where is the micelle left behind after fat absorption in the SI?in the chymen  Where are bile salts mostly reabsorbed?terminal ileum Which route of circulation is used to recycle bile salts?enterohepatic circulation What is the term for fatty stools?Steatorrhoea Give 3 key identifying characteristics of steatorrhoea:1) foul smelling 2) oily 3) floats in pan/ hard to flush What are 3 common causes of steatorrhoea?1) coeliac disease 2) pancreatitis 3) cholestatic liver disease Describe the effect fat malabsorption has on vitamin uptake:vitamins A, D, E and K are fat soluble so deficiencies in these vitamins may occur (A Dick) What 4 vitamins are fat soluble?A, D, E, K What vitamin is crucial for calcium absorption?vitamin D What two bone issues arise from calcium malabsorption?1) osteoporosis 2) osteomalacia What is osteoporosis?reduced bone desnity What is osteomalacia?normal amount of bone with reduced mineral content What bone issue arises if osteomalacia manifests during the period of bone growth?rickets What does a deficiency in vitamin A cause?xerophthalmia What is xeropthalmia?dry eyes What does a deficiency in vitamin B2 cause?angular stomatis What is angular stomatis?dry, red cracked skin around mouth What does a deficiency in vitamin B1 cause?Beriberi and Wernickes What does beriberi cause?muscle wasting, fatigue, and mental disturbances What is Wernickes?alterations of consciousness What does a deficiency in vitamin B6 cause?Polyneuropathy What is polyneuropathy?Widespread, symmetrical effects on PNS What does a deficiency in vitamin B12 cause?pernicious anaemia What does a deficiency in vitamin C cause?Scurvy What does a deficiency in vitamin D cause?osteomalacia and rickets What does a deficiency in vitamin E cause?haemolytic anaemia and bleeding disorders What does a deficiency in vitamin K cause?haemorrhaging What molecule does vitamin B12/ folate depend on for absorption?intrinsic factor Where is a vitamin 12/ intrinsic factor complex absorbed?terminal ileum How does folate/ vitamin B12 cause macrocytic anaemia?folate is required for thymidylate synthesis and the production of DNA in red blood cells, so a lack of this results in large RBCs What form is iron found once absorbed?transferrin What is coeliac disease?an inflammatory condition of the small intestine mucosa -induced by an autoimmune reaction to gluten protein What is the effect of coeliac disease on the small intestine mucosa?villous atrophy (decrease in size) Give 7 presentations of coeliac disease:1) diarrhoea 2) bloating 3) chronic iron deficiency anaemia 4) osteoporosis/ malacia 5) abdominal pain 6) reduced fertility 7) nutritional deficiencies How does coeliac disease cause diarrhoea? (2)1) villous atrophy = less absorption = lumen is concentrated = water enters 2) inflammation increases the rate of flow through the SI = even less absorption Give two serological tests used to help diagnose coeliac disease:1) EMA test 2) tTG antibodies Other than serological tests, what other investigation can be used to diagnose coeliac disease?duodenal biopsy via GI endoscopy How many the SI lining look during a duodenal endoscopy?ridges on the wall Give _ ways to manage coeliac disease:1) gluten should be removed from the diet 2) nutritional vitamins and minerals should be given 3) bone density should be monitered What is pancreatic insufficiency?Reduced delivery of pancreatic enzymes to the duodenum Describe how cystic fibrosis results in pancreatic insufficiency:reduced enzyme and HCO3- secretion as ducts are blocked with mucous Describe how chronic pancreatitis results in pancreatic insufficiency:regions of the gland are irreversibly destroyed and altered due to chronic inflammation Give 3 tests for chronic pancreatitis:1) faecal elastase (white spots on stool) 2) ultrasound/ CT 3) plain abdominal X-ray How is chronic pancreatitis managed? (4)1) Creon (capsules containing pancreatic enzymes) 2) giving vitamin supplements 3) pain relief 4) stop alcohol consumption Give 4 broad causes of chronic pancreatitis:1) alcohol 2) congenital 3) auto-immune 4) genetics What is cholestatic liver disease?impairment of bile formation What is primary sclerosing cholangitis?Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts, presenting as jaundice Describe how bacterial overgrowth in the gut can cause deficiencies:bacteria can deconjugate bile salts, making fat absorption difficult and they can also metabolise and remove vitamin B12 Give 5 broad components of the innate immune response:1) cells such as macrophages, neutrophils, dendritic cells etc 2) cytokines 3) antimicrobial peptides 4) pattern recognition receptors 5) components from the compliment cascade What does PRR stand for?pattern recognition receptors What are pattern recognition receptors?"antigen recognition receptors receptors located on cells involved in innate resistance.  recognize two types of molecular patterns: molecules that are expressed by infectious agents, either on their surface or released as soluble molecules (pathogen-associated molecular patterns, or PAMPs) or products of cellular damage (damage-associated molecular patterns, or DAMPs)" What is the role of PRRs?altering the immune system of invasion What are the two physical divisions of PRRs?1) cell surface and intracellular receptors 2) fluid-phase soluble molecules Describe the mechanism of antigen presentation by APCs:-antigens are internalised  -broken into peptides -associate with class 2 molecules  -brought to the cell's surface Describe how APC antigen presentation can trigger an immune system:- if peptides foreign - recognised by T cells - T cells activated - produce cytokines needed by T and B cells Give the 4 broad types of lymphocytes:1) B lymphocytes 2) Cytotoxic T lymphocytes (CD8) 3) Helper T lymphocytes (CD4) 4) suppressor T lymphocytes What are epitopes?antibody binding sites What is the role of CD4 T helper lymphocytes?secrete cytokines which control the immune response Why is the gut a major site of infection?it's a major site of contract with foreign antigens and the external environment What are the two key functions of the GI immune system?1) protection 2) tolerance What does GALT stand for?gut associated lymphoid tissue During child birth, how is the baby first exposed to bacteria?vaginal secretions Describe how breast milk is a source of prebiotics:insulin-type fructans lead to lactobacillus and bifidobacterial colonising - stimulates intestinal host defences and maturation of the mucosal immune system Describe how commensal bacteria flora can help protect the GI system from pathogens:gut flora competes for resources with invading pathogens Describe the typical path of C. difficile infections:antibiotics kill some of our natural flora, allowing the invading pathogen to make footholds in the epithelium Its toxins that mucosal injury causing RBCs and neutrophils to leak into the gut Where are stem cells found in the epithelial barrier of the gut?near the base of the crypts of Lieberkhun How does the epithelial barrier of the small intestine protect from infection? (4)1) it prevents penetration by microorganisms 2) contains goblet cells which mucins 3) contains enterocytes which have cilial and mechanical action to remove poorly adhered microbes 4) enterocytes produce IgA, lysozymes and defensins Where are mucosal lymphoid follicles found in the GI tract?Peyers patches in the lower part of the small intestine Where are leukocytes found in the gut lining?lamina propria What is the role of M (microfold) cells?the take up antigens and pass them onto professional M cells What are M (microfold) cells?modified enterocytes that cover lymph nodules of lamina propria and are adapted for antigen uptake Where do B cells differentiate in the GI system?mesenteric lymph nodes Describe how dendritic cells contribute to oral tolerance:they sample gut microflora Where are intraepithelial lymphocytes found?between interstitial epithelial cells Intraepithelial lymphocytes are mainly which type of lymphocyte?Cytotoxic T cells (CD8+) that produce IL-2 and interferon gamma Where are lamina propria lymphocytes found?in loose lamina propria tissue under the epithelium Lamina propria lymphocytes are mainly which type of lymphocyte?Helper T cells (CD4+) Give 3 types of helper T cells found in the GI tract?1) Th 1 (acts on intracellular pathogens) 2) Th 2 (acts on allergens and parasites) 3) T 17 (acts on mucosal pathogens) What is the main antibody of the GI tract?IgA How does IgA defend the GI tract from invading pathogens? (3)1) it prevents attachment of bacteria or toxins epithelia 2) they neutralise viruses and toxins 3) enhances non-specific defence mechanisms such as lactoperoxidase True or false: IgA is a dimertrue Where is most (95%) of ATP produced?mitochondria Describe the permeability of the outer membrane of the mitochondria:freely permeable to small molecules and has no ionic or electrolyte gradients What is the inner mitochondrial membrane folded into?christae Describe the permeability of the inner membrane of the mitochondria:permeable to a small number of molecules via specific transporters and is a good electrical insulator True or false: the inner membrane and christae of the mitochondria contain more proteins than lipidstrue What is the area inside the inner membrane of the mitochondria called?matrix What does the matrix of mitochondria contain?a wide range of enzymes involved in the Krebs cycle, fatty acid oxidation and the urea cycle as well as other proteins, cofactors, lipids, ribosomes and DNA Where does the link reaction take place?mitochondrial matrix What enzyme catalyses the link reaction?pyruvate dehydrogenase Give two examples of cofactors used by pyruvate dehydrogenase during the link reaction:1) Mg2+ 2) lipoic acid Give the equation for the link reaction:Pyruvate + NAD + CoA -> Acetyl CoA + reduced NAD + CO2 What vitamin is pyruvate dehydrogenase reliant on?vitamin B2/ thiamine When is pyruvate dehydrogenase inhibited?when energy levels are high How many molecules of NADH are produced by the Krebs cycle per molecule of glucose?6 How many molecules of FADH2 are produced by the Krebs cycle per molecule of glucose?2 How many molecules of CO2 are produced by the Krebs cycle per molecule of glucose?4 How many molecules of ATP are produced by the Krebs cycle per molecule of glucose?2 What is the input molecule in the Krebs cycle?Acetyl CoA What are the two main stages of the Krebs cycle?1) synthesis of a 6-C compound (citrate) into a 4-C compound (succinyl CoA) 2) oxidation of a 4-C compound to regenerate oxaloacetate which initiates another round of the cycle What controls the Krebs cycle?the amount of energy found in the cell indicated by levels of ATP, acetyl CoA and NADH Describe how ATP metabolism differs in diabetic individuals:they cannot use glucose effectively in the absence of insulin so glycolysis is inhibited. Therefore, pyruvate levels are low and instead, malate and oxaloacetate are removed from Krebs to form glucose. Additionally, fatty acids are mobilised from adipose tissue and are oxidised to acetyl CoA. Ketones also have to be synthesised What are the two stages of oxidative phosphorylation?1) electron transport 2) ATP synthesis Where does oxidative phosphorylation occur?inner mitochondrial membrane Where are electrons in the electron transport chain derived from?NADH and FADH2 What are the names of the 4 proteins in the electron transport chain?complex I, II, III and IV How do electrons move down the electron transport chain?from one protein complex to the next What happens to electrons once they reach complex IV?they are donated to oxygen, reducing it to H2O How is energy produced by the electron transport chain?each reduction at each complex releases energy What is the energy produced by the electron transport chain used for?pumping protons across the inner mitochondrial membrane Fill in the gaps: from each pair of electrons from NADH, a total __ H+ are translocated10 How many protons can move through complexes I and III at once?4H+ How many protons can move through complex IV at once?2H+ How is ADP transported into the mitochondria?antiporters in the inner mitochondrial membrane move it into the matrix How are phosphate molecules transported into the mitochondria?antiporters paired with H+ How many protons have to move across the inner membrane for the synthesis of 1 ATP molecule?4 How is NADH moved across the inner membrane of the mitochondria?it is oxidised to NAD+ and later reduced in the matrix back to NADH What are uncouplers?weak acids that can associate with protons in the inter-membrane space and can dissipate the H+ gradient so electron transport can continue without ATP synthesis Where are uncouplers found in new-borns?brown adipose tissue (as thermogenin) Describe how thermogenin is activated in low temps:when temperature drops, noradrenalin leads to increased concentrations of free fatty acids in cytosol which activates thermogenin How does thermogenin increase temperatures?it acts as an uncoupler, keeping the electron transport chain going to produce heat, uncoupled from ATP synthesis Give 7 functions of lipids:1) storage of energy as adipose tissue 2) insulation and cushioning of vital organs 3) phospholipids and sterols in cell membranes 4) transporting fat-soluble vitamins 5) essential fatty acids act as precursors 6) cholesterol is involved in production of steroid hormones 7) cholesterol is also involved in bile salt production Give two examples of steroid hormones:1) testosterone 2) aldosterone What groups of molecules are omega-3 and -6 precursors for?1) leukotrienes 2) thromboxane 3) lipoxins Are leukotrienes and thromboxane anti or pro inflammatory?pro-inflammatory Are lipoxins anti or pro inflammatory?anti-inflammatory What is another term for omega-6?linoleic acid What structures are used to package absorbed lipids?chylomicrons Where are chylomicrons made?intestinal epithelial cells Where are chylomicrons first released and where do they end up?lymphatic circulation -> thoracic duct -> subclavian vein -> liver Describe the course of lipids once in the liver?1) cholesterol synthesis 2) packaged into VLDLs which carry lipids to peripheral tissues 3) packaged into LDL What enzyme breaks down chylomicrons for energy production or storage?lipoprotein lipase What enzyme breaks down triglycerides in peripheral tissues?hormone sensitive lipase True or false: fatty acids cannot cross the blood brain barrier so cannot be used directly by brain tissuetrue What molecule do long chain fatty acids (>12C) require to cross the membrane?carnitine What molecule inhibits carnitine transport of lipids across cell membranes?malonyl CoA When do levels of malonyl CoA fall?during fasting What is the activated form of a fatty acid?fatty acyl-CoA What enzyme allows fatty acyl CoA to bind to carnitine for transport?carnitine palmitoyl transferase I What is formed when fatty acyl CoA binds to carnitine?acyl carnitines How are acyl carninites transported across cell membranes?via carnitine carrier proteins What enzyme regenerates fatty acyl CoA and carnitine from acyl carnitine once molecules have crossed the membrane?carnitine palmitoyl transferase II What is the name of the process that releases energy from fatty acids in mitochondria?beta-oxidation Where does beta oxidation occur?mitochondria Describe the key phase of beta-oxidation: (3)1) spiral process produces acetyl CoA, NADH and FADH2 2) acetyl CoA enters the Krebs cycle, producing more NADH and FADH2 3) NADH and FADH2 can be used in the electron transport chain Fill in the gaps: the overall reaction of beta-oxidation produces ___ x ATP from each molecule of _____________108, palmitoyl CoA When is Malonyl CoA produced?when insulin levels are high What enzyme does malonyl CoA inhibit?carnitine acyl transferase I When are ketone bodies formed?during fasting and in uncontrolled diabetes Where does synthesis of ketone bodies take place?mitochondria of liver cells What are ketone bodies formed from?excess acetyl CoA Describe how cholesterol uptake in cells is mediated?LDL binds to receptors on the cell surface and are taken up - therefore, a lack of receptors will prevent LDL uptake What controls LDL receptor synthesis?the level of cholesterol in the cell Give the 5 step pathway of cholesterol biosynthesis, starting with acetyl CoA:acetyl CoA -> mevalonate -> isoprene -> squalene -> lanosterol -> cholesterol Where in cells does cholesterol biosynthesis take place?cytosol and smooth endoplasmic reticulum What enzyme plays the largest role in regulating cholesterol synthesis?HMG CoA reductase How does high insulin levels influence cholesterol synthesis?high insulin levels indicate energy availability so increase synthesis True or false: high levels of cholesterol inhibit further synthesis of cholesteroltrue How do high levels of cholesterol inhibit further synthesis?it inhibits the transcription factor SREBP that enhances HMG-CoA reductase transcription True or false: humans cannot break down cholesteroltrue How are trans fats formed?hydrogenation of unsaturated fatty acids Why are trans fats regarded as the most unhealthy of fats?they raise LDL levels while lowering HDL levels What is the role of HDL?it returns cholesterol from peripheral cells to the levels What causes a build up of cholesterol in the blood stream in familial hypercholesterolaemia?lack of LDL receptors What causes Tangier disease?lack of HDL receptors Describe the formation of atherosclerosis: (5)1) damage to endothelium cells allows LDL to access the subintimal space of artery walls 2) LDL becomes oxidised and are internalised by macrophages becoming foam cells 3) accumulation of foam cells creates bulging in the vessel wall called an atherosclerotic plaque 4) a fibrous collagen cap is formed over the accumulating lipids 5) the plaque constricts the lumen which may restrict blood flow How can atherosclerosis result in thrombosis?a continued inflammatory response induces macrophages to produce proteinase enzymes which degrade the cap, which eventually ruptures, exposing the interior How is Alzheimer's related to lipid abnormalities?accumulation of A-beta peptides causes Alzheimers What is steatohepatitis?The accumulation of fat in the liver causing an inflammatory reaction What are the two types of steatohepatitis?1) alcoholic steatohepatitis 2) non-alcoholic steatohepatitis Describe how alcohol can cause steatohepatitis:alcohol can disturb the balance of fatty acid synthesis, inhibiting fatty acid oxidation and activating excess triglyceride synthesis What is the most common cause of non-alcoholic steatohepatitis?insulin resistance leading to secretions that stimulate increased fatty acid synthesis What is IBD?a group of diseases characterised by chronic relapsing and remitting inflammation with unknown aetiology What are the two main types of IBD?1) Crohn's disease 2) Ulcerative colitis True or false: IBD has no curetrue Describe the general cause of IBD:poor or lost tolerance to particular antigens causes an immune response with abnormally activated CD4+ Th cells, leading to chronic tissue damage What is the largest independent risk factor for IBD?positive family history Where is ulcerative colitis found?colon and rectum Where is Crohn's disease found?anywhere in the GI tract but mainly the ileum and colon In which histological layers is ulcerative colitis found?mucosa/ submucosa In which histological layers is Crohn's disease found?transmural (all of them) Which form of IBD is supposedly improved with smoking?ulcerative colitis Which form of IBD is associated with peri-anal disease, fistulae and abscesses?Crohn's disease Give 8 examples of extra-intestinal manifestations of IBD1) pancreatitis 2) erythema nodosum (swollen fat) 3) osteoporosis 4) uveitis (swelling of uvea- coloured part of eye) 5) peripheral arthritis 6) pyoderma gangrenosum (skin ulcers) 7) primary sclerosing cholangitis - inflammation of the bile duct 8) thromboembolic events Give 4 examples of investigations used to diagnose IBD:1) markers for inflammation e.g CRP/ calprotectin in blood or stool 2) sigmoid/ colon/ gastroscopy with biopsies 3) barium studies/ CT/ MRI scans What is ulcerative colitis localised in the rectum called?proctitis What is ulcerative colitis localised in the rectum, sigmoid and descending colon known as?left-sided colitis What is ulcerative colitis found in the entire colon called?pancolitis Give 5 common symptoms of ulcerative colitis:1) diarrhoea with blood and mucous 2) urgency 3) abdominal pain and cramps 4) nocturnal symptoms 5) urgency Give 4 clinical signs of ulcerative colitis:1) tender abdomen 2) tachycardia 3) pyrexia (fever) 4) extra-intestinal manifestations Fill in the gap: IBD is an a______________ conditionautoimmune Give the sequence of drugs used to treat Crohn's disease with increasing severity:5-ASA, systemic steroids, azathioprine, TNF antagonists, surgery How can 5-ASA and other IBD drugs be administered topically?enema Give the sequence of drugs used to treat ulcerative colitis with increasing severity:5-ASA, systemic steroids, azathioprine, ciclosporin, surgery How can sulphasalazine treat IBD?it suppresses the gut's immune system by inhibiting chemotaxis, T cell proliferation and COX How does azathioprine mediate the gut's immune system?it forms 6-MP which forms 6-thioguanine which -halts immune cell replication and purine biosynthesis -increases apoptosis of mononuclear cells How does methotrexate mediate the gut's immune system?it inhibits folate metabolism and has anti-inflammatory effects via the inhibition of other enzymes. It results in decreased IL 2, 6 and 8 production as well as impaired chemotaxis What is the most common surgery used to treat ulcerative colitis?proctocolectomy with an ileostomy What is metabolism? set of chemical reactions occurring in the body  to extract energy from the environment  use energy to synthesis building blocks What is catabolism?the breakdown of energy rich compounds such as fats, proteins and carbohydrates (break down) What suffix do catabolic pathways always end in?lysis What is anabolism?the synthesis of complex molecules from simpler ones, generally requiring energy (build up) What suffix do anabolic pathways always end in?genesis What are the two metabolic forms of carbohydrates?glucose and fructose What is the metabolic form of lipids?free fatty acids Why is it fats provide a very dense energy store?they don't bind to water and contain little oxygen How are lipids stored?as fatty acids, primarily in adipose tissue  lipids cannot be synthesised back to?glucose Why are proteins not an ideal source of energy?most amino acids are stored as functional proteins What does liver convert amino acids into?glucose What two amino acids found in muscle tissue can be exported for gluconeogenesis?alanine and glutamine What are the three levels of metabolic regulation?1) hormonal 2) substrate 3) allosteric Describe substrate control of metabolism:the relative ability of any given substrate has a large impact on which pathways are activated Describe allosteric control of metabolism:"-inhibition or activation of an enzyme -by a small regulatory molecule  -at a site (allosteric site) other than the active site" What is the body's most important factor in regulating metabolism?blood glucose concentration What is the physiological range for blood glucose conc?4.5-8mM (120mg/ 100ml plasma) Describe the metabolic requirements of the brain:blood brain barrier limits what food stuffs can get across brain is heavily reliant on plasma glucose conc However, can use ketone bodies during times of fasting/ starvation Describe the metabolic requirements of erythrocytes: no mitochondria -  energy from anaerobic glycolysis - inefficient. BUT they have low metabolic demands left over pyruvate and lactate = back to liver for gluconeogenesis Describe the metabolic requirements of adipose tissue:"High glucose conditions = insulin to promote uptake of glucose and conversion to triglycerides. Low glucose conditions = glucagon converts stored triglycerides to free fatty acids and glycerol" Describe the metabolic requirements of the liver:high glucose conditions = insulin to promote glucose uptake and convert it to glycogen.  Low glucose conditions = glycogen to be released as glucose Describe the metabolic requirements of type 1 skeletal muscle:highly aerobic and adapted to prolonged, modest activity uses fatty acids as an energy source Describe the metabolic requirements of type 2b skeletal muscle: Anaerobic glycolysis - few mitochondria.  Fatigue quickly - explosive performance Describe the metabolic requirements of type 2a skeletal muscle:contains some mitochondria -  glycogen can provide energy but at lower exercise levels, fatty acids are the main energy soruce Describe the metabolic requirements of cardiac muscle:highly aerobic with many mitochondria. The main energy source is fatty acids but it can also use lactate or ketone bodies Give the general formula for carboohydrates:Cx(H2O)n What is the characteristic functional group of carbohydrates?carbonyl (C=O) What value should blood glucose lie around?5mM What transporter brings glucose into cells?GLUT4 Describe how electron movement in aerobic respiration produces energy:electrons are transferred from C or H to an O atom and as O is more electronegative the electrons lose potential energy, releasing it Why are carbohydrate and fats so high in energy relative to proteins?they have a lot of electrons associate with hydrogen What are the 3 NET products of glycolysis?1) x2 ATP 2) x2 NADH 3) x2 pyruvate Describe the Link reaction:Pyruvate enters the mitochondrial matrix and is decarboxylated and dehydrogenated and bonds with coenzyme A to form acetyl CoA What are the 2 key products of the Link reaction per molecule of glucose?1) x2 acetyl CoA 2) x2 NADH Give the 8 steps of the Krebs cycle:"1) acetyl CoA joins with oxaloacetate to form citrate 2) citrate is isomerised to form isocitrate 3) isocitrate is oxidised to form alpha-ketoglutarate producing NADH 4) alpha-ketoglutarate is oxidised to succinyl-CoA producing NADH 5) succinyl-CoA is converted to succinate producing ATP 6) succinate is oxidised to fumarate producing FADH2 7) fumarate is hydrate and forms malate 8) malate is oxidised to oxaloacetate producing NADH <img src=""c7052763740cb431d8e989fa55460816cc5a074c.png""> " What are the four products of the Krebs cycle per molecule of gluocse?1) x6 CO2 2) x6 NADH 3) x2 FADH2 4) x2 ATP Describe the electron transport chain: (3)1) NADH and FADH2 are oxidised to produce electrons which move from each protein complex in the inner mitochondrial membrane, releasing energy 2) this energy is used to pump H+ ions against their gradient into the intermembrane space, creating an electrical gradient 3) H+ can pass through ATP synthase via chemiosmosis, producing ATP from ADP Give the flow chart for anaerobic respiration of gluocse:glucose -> pyruvate -> ethanol/ lactic acid What molecule is anaerobic respiration's redox balance linked to?glyceraldehyde-3-phosphate What molecule is used to store glucose?glycogen What is a glycan?polysaccharide of a glycoconjugate (glycolipid, glycoprotein etc) Describe how glycogen is synthesised:1) glucose-6-phosphate is converted to glucose-1-phosphate and UDP glucose is synthesised 2) glycogenin primers help elongate chains and the intersection of branch points What are the linkages called in glycogen?alpha-1,4 linkages What are the branch points in glycogen called?alpha-1,6 linkages What enzyme plays a chief role in glycogen synthesis?glycogen synthase Describe glycogen breakdown in the liver and kidneys:1) glycogen phosphorylase removes glucose units to produce glucose-1-phosphate which is then converted back to glucose-6-phosphate which can enter glycolysis Describe how fatty acids can be synthesised from sugars:citrate is used to produce acetyl CoA which goes onto form malonyl CoA using ATP and acetyl CoA carboxylase How does insulin affect glycolysis?upregulates glycolysis and downregulates gluconeogenesis How does glucagon affect glycolysis?Glucagon inhibits glycolysis in the liver (inhibits glucose breakdown) and increases glycogenolysis (break down of glycogen) to release glucose in the blood Name the three layers of muscular lining in the stomach from the outside in:1) longitudinal muscle 2) circular muscle 3) oblique muscle What is the name of the upper hump of the stomach located adjacent to the lower oesophageal sphincter?fundus What is the cardia of the stomach?where oesophagus enters What is the name of the sphincter the separates the stomach from the duodenum?pyloric sphincter Where is the antrum of the stomach?between body and pylorus Where is the pylorus located?The bottom portion of the stomach where food exits What is the name given to the folded ridges of the stomach wall?rugae Which side of the stomach can the lesser curvature be found?right What side of the stomach can the greater curvature be found?left What is the role of the lower oesophageal sphincter and cardia? (4)1) helps prevent reflux 2) controls entry of food 3) regulates belching 4) secretes mucous and HCO3- What is the role of the fundus and body of the stomach? (2)1) responsible for creating tonic force during emptying 2) secretes H+, intrinsic factor, mucous, HCO3- and pepsinogens What is the role of the antrum and pylorus of the stomach?1) mixing, grinding and sieving food 2) regulating emptying 3) secretes mucous mucous and HCO3- How does the stomach adjust its accommodation of foodstuffs?stretch sensors in the stomach lining signal via the vagus which acts on the enteric nervous resulting in relaxation and dilation of the fundus and body of the stomach Describe the role of the antral pump in the stomach:the antral pump is adapted to only allow thin liquids to pass through the pyloric sphincter, forcing thicker material to be churned and ground until its smooth enough to be passed to the duodenum Fill in the gap: particles larger than _-_mm cannot pass through the pyloric sphincter1-2mm How does the duodenum halt gastric emptying when it anticipates filling?it detects delivery of acid, amino acids and lipids, stimulating the release of CCK, secretin and GIP which decrease motility What two substances do mucous cells secrete?1) mucin 2) HCO3- What is another term for parietal cells?oxyntic cells What two substances do parietal cells secrete (and where)?1) HCl 2) intrinsic factor (in the fundus and body of the stomach) What do G cells secrete?gastrin Where are G cells most commonly found?antral and pyloric glands What is another term for chief cells?peptic cells What do chief cells secrete?pepsinogen What type of gastrin is mostly secreted in the antrum?G17 What type of gastrin is mostly secreted in the duodenum?G34 What receptors do gastrin molecules bind to?CCK-B What stimulates gastrin release? (2)1) detection of amino acids 2) cephalic or gastric stretch induced parasympathetic activity (ACh) What inhibits gastrin release?H+ and somatostatin What is the main action of gastrin?stimulates acid secretion What cells produce and secrete somatostatin?D cells What stimulates somatostatin release?luminal H+ What inhibits somatostatin release?vagal stimulation (ACh) What is the effect of somatostatin?acts on G cells to inhibit the release of gastrin Describe the resting state of parietal cells:few folds due to a lack of tubulovesicles fusing with the membrane Describe the active state of parietal cells:many canaliculi due to tubulovesicles fusing with the membrane What pump is used by parietal cells to secrete H+?H+/K+ ATPase What two molecules stimulates parietal cells to pump out H+ ions?1) gastrin 2) ACh Why do mucous cells also secrete HCO3-?to protect the epithelial layer of the stomach from acidic pHs What is the role of intrinsic factor?it binds to cobalamin (vitamin B2) in the small intestine, aiding uptake What cells secrete intrinsic factor in the stomach?parietal cells What 4 molecules stimulate chief cells to secrete pepsinogens?1) gastrin 2) secretin 3) H+ 4) ACh Describe the action of pepsins in the stomach?act as endoproteases, cutting within the peptide chain What is the optimum pH for pepsins in the stomach?pH 2-3 (denatured above pH 5-7 i.e. in the small intestine) Describe the action of gastric lipase:cleaves out a outer fatty acid off triglycerides, leaving a diacyl glycerol What is the optimum pH of gastric lipase?pH 4 What is the name of the amylase enzymes found in the stomach?ptyalin alpha-amylase Describe the action of ptyalin alpha-amylase:cleaves polysaccharides into dextrins or disaccharides What is the optimum pH of ptyalin alpha-amylase and how can it function in the stomach?pH 7, it operates in the fundus and body of the stomach where there is a lot of food which hasn't mixed with acid yet Which region of the brain centrally controls vomiting?area postrema (in medulla) Define retching:involuntary rhythmic diaphragmatic and abdominal contractions Fill in the gap: vomiting is characterised by r______ peristalsis and retching followed by displacement of the c_____ into the thorax and the opening of the lower and upper _______ sphinctersretrograde, cardia, oesophageal What does satiety mean?feeling full How many AAs make up ghrelin?28 What cells produce ghrelin?neuroendocrine cells in the stomach When is ghrelin secreted?when the stomach is empty What is the affect of ghrelin?stimulates appetite What is an orexigenic agent?a substance that stimulates appetite What is an anorexigenic agent?a substance that suppresses appetite Give 6 examples of anorexigens produced by the gut and pancreas:1) CCK 2) Insulin 3) GLP-1 4) Peptide YY 5) Oxyntomodulin 6) Somatostatin True or false: nutrients like glucose and amino acids can act as anorexigenstrue What tissue produces leptin and adiponectin?adipose What is the function of leptin?induces satiety by stimulating insulin secretion What is the function of adiponectin?induces satiety by stimulating insulin secretion Give 2 examples of cytokines that inhibit insulin and leptin:1) TFN-alpha 2) IL-6 Where in the brain are all central and peripheral messages surrounding appetite collected?nucleus of the solitary tract Where in the brain does the nucleus of the solitary tract project to?arcuate nucleus Where is the satiety centre located?ventromedial nucleus Where is the hunger centre located?lateral hypothalamic area Give two examples of anorexigenic neurone secretions:1) POMC 2) CART Give two examples of orexigenic neurone secretions:1) AGRP 2) NPY What molecule is used to fuel RBCs during starvation?glucose What two molecules are used to fuel the brain during starvation?1) glucose 2) ketone bodies What two molecules are used to fuel the liver during starvation?1) glucose 2) fatty acids What two molecules are used to fuel skeletal muscles during starvation?1) fatty acids 2) ketone bodies What two molecules are used to fuel adipose tissue during starvation?1) glucose 2) fatty acids Give 7 traits of extreme starvation:1) diminished respiratory capacity 2) loss of heat-generating capacity 3) muscle fatigue 4) muscle wasting 5) death from respiratory/ cardiac failure or infection 6) slow heart rate 7) apathy What BMI can be classified anorexia nervosa?<17.5 What is a normal BMI range?18.5-24.9 What is an underweight BMI?<18.5 What is an overweight BMI?25-29.9 What is an obese BMI?over 30 Give 9 potential physiological consequences of obesity:1) osteoarthritis 2) non-alcoholic fatty liver disease 3) hypertension 4) sleep apnoea 5) infertility 6) endometrial, breast and colon cancer 7) gall stones 8) type 2 diabetes 9) metabolic syndrome Give the 5 traits of metabolic syndrome (of which you need 3 of for a diagnosis):1) obesity (waist circumference) 2) type 2 diabetes 3) hypertension 4) low HDL cholesterol 5) high plasma triglycerides What is meant my ectopic fat?fat around viscera such as the liver, skeletal muscles and heart How does ectopic fat alter metabolic profile?it is less responsive to insulin and exists in a hyper-lipolytic state meaning it produces free fatty acids What is the effect of ectopic fat producing free fatty acids?it makes the liver less sensitive to insulin and impairs beta cell release What causes chronic inflammation in obese people?ectopic fat produce pro-inflammatory cytokines Describe how cytokines from ectopic fats can lead to atheroma and CVS disease:cytokines cause the production of reactive oxygen species which paired with dyslipidaemia, increases CVS disease and atheroma Neuropeptide Ystimulates hunger - acts within the hypothalamus alpha-melcanocyte stimulating hormonesupresses hunger - acts within the hypothalamus  Peptide YYreleased from the colon to supress hunger what time of hormone is growth hormonea protein hormone when is growth hormones secreted at higher levelduring deep sleep Give 3 examples of organs derived from out=-pocketings of the foregut:1) liver 2) gall bladder 3) pancreas Where dot he liver, gall bladder and pancreas all develop from?diverticulum of the cranial half of the duodenum In which week does the liver appear as an out pocketing of the future duodenum?week 3 What is the name of the out pocketing that goes onto form the liver?hepatic diverticulum How does the bile duct form from the developing liver?the connections between the hepatic diverticulum and duodenum narrows to form the bile duct What is the name of the embryological structure that goes onto form the diaphragm?septum transversum What structure does the hepatic diverticulum pentrate through?septum transversum What do the endodermal cells in the liver bud differentiate into?hepatocytes Where are haematopoietic and Kupffer cells derived from?mesoderm of the septum transversum What two structures are formed by the liver protruding into the ventral mesentery?1) falciform ligament 2) lesser omentum In what week of development does the liver protrude through the ventral mesentery?week 6 How is the bare area of the liver formed?when the liver protrudes through the ventral mesentery, it pushes against the developing diaphragm, causing it to lose some of its peritoneal covering Which surface of the liver is the bare area on?cranial surface Where is the visceral peritoneum of the liver derived from?mesoderm on the liver surface Where are the coronary ligaments found?around the margins of the bare area Where are the left and right triangular ligaments found?at the ends of the coronary ligaments at the lateral edges of the liver Why does the liver make up a greater % of body weight in foetuses?the liver is involved in haematopoiesis which stops after birth as bone marrow takes over During what week of development does a ventral outgrowth from the gall bladder and cystic duct?week 3 Is the outgrowth that forms the gall bladder and cystic duct dorsal or ventral in position?ventral When does the liver start to produce bile?week 12 Why is the first bowel movement of a new born green?bile is released into the GI tract in foetuses What is the first, dark green bowel movement of new borns called?meconium How does neonatal jaundice arise?the immature liver does not have sufficient glucuronosyltransferase to conjugate bilirubin What the severe complication of neonatal jaundice called?kernicterus How can kernicterus lead to brain damage?unconjugated bilirubin can cross the blood-brain barrier What is used to treat neonatal jaundice?phototherapy How does phototherapy treat neonatal jaundice?it oxidised bilirubin to a water soluble form that can be easily excreted by the new born What is biliary atresia?narrowing of the bile or hepatic duct caused by failed recanalisation How can biliary atresia be distinguished from neonatal jaundice?an infant with biliary atresia won't respond to phototherapy What causes duplication of the gall bladder?an extra endodermal out-pocketing during weeks 5 and 6 When does the dorsal bud of the pancreas develop?week 4 Where is the ventral bud of the developing pancreas found?caudal to the developing gall bladder Describe the development of the pancreas:two buds (ventral and dorsal) form and fuse as the duodenum rotates 90 degrees, carrying the ventral bud dorsally During which week of development does the ventral and dorsal buds of the pancreas fuse?week 6 What regions of the pancreas does the dorsal bud give rise to?1) head 2) body 3) tail What regions of the pancreas does the ventral bud give rise to?ucinate process Where are the connective tissues and blood vessels of the pancreas derived from?mesoderm What regions of the primitive ventral and dorsal pancreatic buds form the main pancreatic duct?the distal portion of the dorsal pancreatic duct and all of the ventral pancreatic duct What regions of the primitive ventral and dorsal pancreatic buds form the accessory pancreatic duct?proximal portion of the dorsal pancreatic duct Where does the main pancreatic duct enter the duodenum?Ampulla of Vater (major duodenal papilla) Where does the accessory pancreatic duct enter the duodenum?minor duodenal papilla What is an annular pancreas?Developmental malformation in which the pancreas forms a ring around the duodenum with risk of duodenal obstruction What causes an annular pancreas?a bilobed ventral pancreatic bud where one bud migrates dorsally and the other ventrally, to surround the duodenum What is ectopic pancreatic tissue?the inappropriate differentiation of endodermal cells into pancreatic tissue ranging from the distal oesophagus to the tip of the primary intestinal loop Where is ectopic pancreatic tissue most commonly found?duodenum and stomach mucosa Describe the symptoms of ectopic pancreatic tissue:usually asymptomatic but large lesions may cause obstructions, ulceration or haemorrhage Which germ layer is the spleen derived from?mesoderm Describe the development of the spleen:it appears as a mesenchymal condensation in the dorsal mesentery and the rotation of the stomach brings the spleen over to the left hand side What is the dorsal mesentery between the stomach and spleen called?gastrosplenic ligament What is the dorsal mesentery between the spleen and kidney called?lienorenal ligament How do accessory spleens come about?additional mesenchymal condensations may occur in the dorsal mesentery Where do accessory spleens usually form?the hilum of the primary spleen What is the physiological range of glucose?4.5-8mM Describe the differences between GLUT-2 and GLUT-4 transporters:GLUT-2 only takes up glucose when it is found at high concentrations while GLUT-4 has a higher affinity and can take up glucose at lower affinities Which is the insulin responsive GLUT transporter?GLUT-4 True or false: GLUT 2 and 4 are both mobile?true What two glucose transporters are found in the apical brush boarder for glucose uptake in the small intestine?SGLT-1 and SGLT-2 What cells produce insulin?beta cells What cells produce glucagon?alpha cells What cells produce somatostain?delta cells Why is it important that the islets of Langerhans are surrounded by blood flow?cells can sample the blood for glucose and respond appropriately What transporters pick up glucose in beta-cells?GLUT-2 Describe how insulin is secreted from beta-cells: (3)1) the cells pick up glucose using GLUT-2 which is metabolised to generate ATP 2) ATP closes the KATP channels, stopping K+ from leaving the cell, depolarising the membrane 3) this stimulates a Ca2+ influx which induces exocytosis of insulin Describe the processing of insulin from pre-hormone to active hormone: (2)1) disulphide bonds are inserted to stabilise the structure of the protein in the endoplasmic reticulum 2) the protein is then cleaved to give A and B chains as well as a free C peptide in the Golgi apparatus Describe the significance of C peptide:it is inactive but can be used as a biomarker for insulin production What is the receptor for insulin?tyrosine kinase How does tyrosine kinase increase cycling of GLUT-4 to cell surfaces?it phosphorylates nearby proteins, activating a complex downstream pathway Give 4 effects of insulin that take place in the liver:1) promotion of glycolysis (converting glucose to glucose-6-phosphate) 2) promotion of lipogenesis (converting glucose to fatty acids using acetyl CoA) 3) promotion of glycogenesis (increased activity of glycogen synthase) 4) inhibition of gluconeogenesis How does insulin promote glycogenesis?it increases the activity of glycogen synthase and inhibits glycogen phosphorylase How does insulin promote glycolysis?it stimulates the conversion of glucose to glucose-6-phosphate Give 4 effects of insulin that take place in skeletal muscle:1) promotion of glycolysis (converting glucose to glucose-6-phosphate) 2) promotion of lipogenesis (converting glucose to fatty acids using acetyl CoA) 3) promotion of glycogenesis (increased activity of glycogen synthase) 4) promotion of protein synthesis Give 3 effects of insulin that take place in adipose tissue:1) increased expression of GLUT-4 2) increased glycolysis 3) increased expression of lipoprotein lipase (releases fatty acids from lipoproteins for fatty acid uptake) What nutrient component stimulates glucagon release from alpha-cells?amino acids What nutrient component inhibits glucagon release from alpha-cells?glucose Describe how glucagon is secreted: (3)1) low glucose levels keep ATP levels in alpha-cells low which keeps K+ATP channels open 2) this causes Ca2+ channels to open 3) the influx of Ca2+ drives exocytosis of glucagon Describe how glucagon secretion is inhibited when blood glucose levels are high:1) high glucose keeps ATP levels elevated in alpha-cells, causing K+ATP channels to close 2) this causes membrane depolarisation so Ca2+ ion channels close 3) exocytosis is inhibited Give 4 effects of glucagon that take place in the liver:1) glucagon inhibits glycolysis to preserve glucose levels 2) glucagon inhibits glycogenesis and promotes glycogenolysis 3) glucagon promotes fatty acid metabolism through beta-oxidation and inhibits fatty acid synthesis 4) glucagon helps with the provision of phosphoenolpyruvate for gluconeogenesis How does glucagon inhibit fatty acid synthesis?it blocks the conversion of acetyl CoA to malonyl CoA How does the liver promote glucose production during exercise?the Cori cycle is activated, converting lactate to pyruvate to glucose How do skeletal muscles change their metabolism during exercise to promote glucose uptake?they undergo glycogenolysis and glucose uptake through increased GLUT-4 expression How does adipose tissue change its metabolism during exercise?adipose tissue undergoes lipolysis and free fatty acids are released into the blood Describe Type 1 Diabetes Mellitus:an autoimmune disease in which beta-cells are destroyed so there is an inability to produce insulin. Blood glucose rises and without GLUT-4 expression, cells cannot take it up Why do glucagon levels increase in diabetes and what is the effect of this?raised blood glucose levels stimulates glucagon secretion leading to lipolysis, proteolysis as well as gluconeogenesis and ketogenesis in the liver Describe Type 2 Diabetes Mellitus:insulin resistance due to receptor down regulation, strongly associated with obesity and cardiovascular disease Give a drug that inhibits gluconeogenesis used in T2 diabetes treatment:metformin Give a drug that enhances insulin sensitivity used in T2 diabetes treatment:pioglitazone Give two drugs that enhance insulin secretion used in T2 diabetes treatment:1) incretins 2) sulphonylurea What does satiety mean?feeling full How many AAs make up ghrelin?28 What cells produce ghrelin?neuroendocrine cells in the stomach When is ghrelin secreted?when the stomach is empty What is the affect of ghrelin?stimulates apeptite What is an orexigenic agent?a substance that stimulates appetite What is an anorexigenic agent?a substance that suppresses appetite Give 6 examples of anorexigens produced by the gut and pancreas:1) CCK 2) Insulin 3) GLP-1 4) Peptide YY 5) Oxyntomodulin 6) Somatostatin True or false: nutrients like glucose and amino acids can act as anorexigenstrue What tissue produces leptin and adiponectin?adipose What is the function of leptin?induces satiety by stimulating insulin secretion What is the function of adiponectin?induces satiety by stimulating insulin secretion Give 2 examples of cytokines that inhibit insulin and leptin:1) TFN-alpha 2) IL-6 Where in the brain are all central and peripheral messages surrounding appetite collected?nucleus of the solitary tract Where in the brain does the nucleus of the solitary tract project to?arcuate nucleus Where is the satiety centre located?ventromedial nucleus Where is the hunger centre located?lateral hypothalamic area Give two examples of anorexigenic neurone secretions:1) POMC 2) CART Give two examples of orexigenic neurone secretions:1) AGRP 2) NPY What molecule is used to fuel RBCs during starvation?glucose What two molecules are used to fuel the brain during starvation?1) glucose 2) ketone bodies What two molecules are used to fuel the liver during starvation?1) glucose 2) fatty acids What two molecules are used to fuel skeletal muscles during starvation?1) fatty acids 2) ketone bodies What two molecules are used to fuel adipose tissue during starvation?1) glucose 2) fatty acids Give 7 traits of extreme starvation:1) diminished respiratory capacity 2) loss of heat-generating capacity 3) muscle fatigue 4) muscle wasting 5) death from respiratory/ cardiac failure or infection 6) slow heart rate 7) apathy What BMI can be classified anorexia nervosa?<17.5 What is a normal BMI range?18.5-24.9 What is an underweight BMI?<18.5 What is an overweight BMI?25-29.9 What is an obese BMI?over 30 Give 9 potential physiological consequences of obesity:1) osteoarthritis 2) non-alcoholic fatty liver disease 3) hypertension 4) sleep apnoea 5) infertility 6) endometrial, breast and colon cancer 7) gall stones 8) type 2 diabetes 9) metabolic syndrome Give the 5 traits of metabolic syndrome (of which you need 3 of for a diagnosis):1) obesity (waist circumference) 2) type 2 diabetes 3) hypertension 4) low HDL cholesterol 5) high plasma triglycerides What is meant my ectopic fat?fat around viscera such as the liver, skeletal muscles and heart How does ectopic fat alter metabolic profile?it is less responsive to insulin and exists in a hyper-lipolytic state meaning it produces free fatty acids What is the effect of ectopic fat producing free fatty acids?it makes the liver less sensitive to insulin and impairs beta cell release What causes chronic inflammation in obese people?ectopic fat produce pro-inflammatory cytokines Describe how cytokines from ectopic fats can lead to atheroma and CVS disease:cytokines cause the production of reactive oxygen species which paired with dyslipidaemia, increases CVS disease and atheroma What structure in the brain regulates hormone release from the anterior pituitary gland?hypothalamus What area of the pituitary secretes GH, ACTH, TSH, FSH/LH and MSH?anterior pituitary Where specifically are glucocorticoids produced?zona fasciculata in the adrenal cortex What hypothalamic hormone is released by the hypothalamus to stimulate the pituitary gland to secrete ACTH?CRH What stimulates the hypothalamus to secrete CRH?stress cytokines What does the pituitary gland release in response to CRH?ACTH What is the effect of ACTH on cortisol production?it increases cortisol production What is the effect of high cortisol levels on the hypothalamus and pituitary gland?production of CRH and ACTH is inhibited via negative feedback Give two types of glucocorticoids:1) cortisol 2) cortisone What molecule are most steroid hormones including glucocorticoids synthesised from?cholesterol Other than glucocorticoids, what other hormone groups are produced by the adrenal cortex?1) mineralocorticoids 2) androgens When is cortisol production highest?30 minutes after waking up What region of the hypothalamus regulates cortisol levels?the suprachiasmatic nucleus What is meant when cortisol is described as diurnal?it is present predominantly during the day True or false: glucocorticoid receptors are present in almost all cells meaning cortisol has an effect on almost all body systemstrue Give two instances where cortisol secretion would increase:1) times of stress 2) during pregnancy (x2-4) Give the four general effects of cortisol:1) reducing inflammation 2) increasing blood glucose levels and availability 3) role in the fight or flight response 4) increases cardiovascular tone Give three ways in which cortisol reduces inflammation:1) suppresses B cell antibody production 2) reduces neutrophil migration 3) stimulates apoptosis of T cells Give 6 ways in which cortisol increases blood glucose levels and availability:1) increases blood glucose availability to the brain 2) increases lipolysis 3) increase gluconeogenesis 4) reduces glycogen synthesis 5) reduces insulin production 6) increases glucagon synthesis What is the name of the disease characterised by adrenal insufficiency?Addison's disease Give 6 symptoms of Addison's disease:1) weight loss 2) weakness and fatigue 3) hypotension 4) reduced body hair 5) hyperpigmentation 6) hypoglycaemia Give 4 causes of Addison's disease:1) malignancies 2) autoimmune issues 3) irradiation 4) pituitary disease What is Addison's crisis?Life threatening emergency caused by sudden withdrawal of cortisol in stressful situations Give 5 signs/ symptoms of Addison's crisis:1) low blood pressure 2) pyrexia 3) vomiting 4) confusion 5) raised blood potassium What is the name of the common stimulation test used to investigate adrenal insufficiency?Synacthen test Describe the synacthen test:ACTH is injected and cortisol levels are taken at 30 and 60 minutes- cortisol levels should increase to 420 at 30 mins How is Addison's crisis treated?IV steroids and fluids What causes Cushing's syndrome?prolonged exposure to high levels of cortisol Give an iatrogenic cause of Cushing's syndrome:too much glucocorticoid medication How does Cushing's disease differ from Cushing's syndrome?Cushing's disease is caused by a pituitary tumour and is ACTH specific Give 6 signs and symptoms of Cushing's syndrome:1) weight gain 2) proximal muscle weakness 3) hypertension 4) striae 5) bruising 6) osteoporosis What does ONDST stand for?over night dexamethasone suppresion test Describe the suppression test for Cushing's:dexamethasone is administered before a patient goes to bed and then a blood test is completed the following morning- cortisol levels should decrease Give 3 treatments used for Cushing's:1) removal of related adrenal or pituitary tumour 2) medication 3) radiotherapy Give an example of a steroidogenesis inhibitor drug:osilodrostat How do steroidogenesis inhibitors such as osilodrostat treat Cushing's?they inhibit the enzyme that catalyses the final step of cortisol synthesis in the adrenal cortex Give an example of a somatostatin analogue drug:pasireotide How do somatostatin analogues such as pasireotide treat Cushing's?they bind to human somatostatin receptors, resulting in inhibition of ACTH secretion Give 3 examples of adrenal steroid inhibitors:1) ketoconazole 2) metyrapone 3) etomidate Give an example of a anti-neoplastic drug used to treat Cushing's:mitotane Fill in the gap: 90% of hormone produced by the thyroid is __ which is later activated to __T4, T3 Describe the synthesis of T3 and T4:1) the thyroid peroxidase enzyme on thyroid epithelium is used for iodination of tyrosine on thyroglobulin 2) two iodotyrosines are then combined to form T3 and T4 What thyroid cells take up iodine for T3 and T4 synthesis?thyroid epithelial cells How is tyrosine produced for T3 and T4 synthesis?its produced from thyroglobulin which is synthesised from thyroid epithelial cells and secreted into the lumen of the colloid follicle Give 3 causes of hypothyroidism:1) iodine deficiency 2) iatrogenic cause 3) autoimmune issues Give 5 common symptoms of hypothyroidism:1) hair loss 2) weight gain 3) tiredness 4) dry skin 5) slow heart beat How is hypothyroidism treated?levothyroxine (T4) Give the 3 main causes of hyperthyroidism:1) Graves/ autoimmune 2) toxic goitres 3) pituitary tumour Give 6 signs and symptoms of hyperthyroidism:1) excess sweating 2) hand tremors 3) rapid heart rate 4) fatigue 5) weight loss 6) heat intolerance Give four treatments for hyperthyroidism:1) anti-thyroid agents like carbimazole 2) beta-blockers 3) radioactive iodine 4) total thyroidectomy Why are foetuses so dependent on maternal thyroxine?in the early stages of development, it is required for neurological development What is another term for growth hormone?somatotropin Where is GH produced?anterior pituitary gland True or false: GH follows the circadian rhythm with max release in the second half of the nighttrue What hypothalamic hormone stimulates GH release?GHRH What hormone inhibits GH release?somatostatin Describe the role of GH in protein metabolism: (2)1) stimulates transcription 2) increases amino acid uptake Describe the role of GH in fat metabolism: (2)1) promotes lipolysis 2) increases fat utilisation Describe the role GH in carbohydrate metabolism: (3)1) promotes gluconeogenesis 2) increases the utilisation of glucose 3) inhibits glycolysis True or false: GH also enhances milk productiontrue How does GH promote linear growth?transforms cartilage into bone and increases bone mass What is the result of hypersecretion of GH in children?gigantism What is the result of hypersecretion of GH in adults?acromegaly Give two features of acromegaly:1) enlargement of hands and feet 2) coarse facial features What is the main cause of GH hypersecretion?pituitary adenoma What suppression test can be used for GH?glucose What blood marker indicates hypersecretion of GH?high IGF-1 (insulin growth factor 1) Give two treatments for GH oversecretion:1) trans-sphenoidal surgery (removing tumour from pituitary) 2) medical therapies such as somatostatin analogues and dopamine receptor analogues What 4 sympathetic nerves supply the GI tract?1) greater splanchnic 2) lesser splanchnic 3) least splanchnic 4) lumbar splanchnics What two groups of parasympathetic nerves supply to GI tract?1) vagus nerve (to the distal third of the transverse colon) 2) pelvic splanchnic (to the hindgut and pelvic organs) Where do the pelvic splanchnic nerves originate from?S2-S4 Where do the autonomic plexuses of the GI tract lie?around the coeliac trunk, SMA and IMA Describe the standard pathway of a sympathetic action potential in the thorax:an impulse travels into the sympathetic chain via the white ramus communicans where it can either synapse to a motor neurone towards a target organ or ascend/ descend along the sympathetic chain Describe the standard pathway of a sympathetic action potential in the abdomen:an impulse travels into the sympathetic chain via the white ramus communicans where instead of synapsing in the ganglion, it just travels straight through to the target organ and later synapses at a prevertebral ganglia Summarise the pathway of sympathetic action potentials in the abdomen: (5)1) synaptic entry at the spinal cord via para-vertebral ganglia 2) travels down preganglionic neurones (T1-L2) 3) synapses at pre-vertebral ganglia around the CT, SMA and IMA 4) travels down post-ganglionic neurones 5) target organ Where does parasympathetic supply of the GI tract originate?pre-ganglionic neurones in the brainstem (vagus) and sacral spinal cord (pelvic splanchnic nerves) Summarise the pathway of parasympathetic action potentials in the abdomen: (4)1) pre-ganglionic neurones (vagus from the brain stem and pelvic splanchnic nerves from S2-S4) 2) synapse close to target organs 3) become post-ganglionic neurones 4) target organs What parasympathetic pre-ganglionic neurones are found in the brainstem that supply the GI system?vagus nerve What parasympathetic pre-ganglionic neurones are found in the sacral spinal cord that supply to GI system?pelvic splanchnic nerves What three neurone types do prevertebral ganglia contain?1) a presynaptic parasympathetic vagal fibre 2) a visceral afferent fibre 3) a presynaptic sympathetic splanchnic fibre What are the names of the three pre-vertebral ganglia associated with the three unpaired visceral arteries?1) coeliac ganglion 2) superior mesenteric ganglion 3) inferior mesenteric ganglion Describe how the autonomic plexuses of the GI tract connect with the rest of the body?the nerve networks surrounding the three unpaired visceral arteries extend to the bifurcation of the aorta, towards the superior hypogastric plexus and joins the inferior hypogastric plexus via hypogastric nerves What vertebral levels cover the nociception of the foregut?T6-T9 What vertebral levels cover the nociception of the midgut?T8-T12 What vertebral levels cover the nociception of the hindgut?T12-L2 What are the two sphincters of the stomach?1) cardiac/ lower oesophageal sphincter 2) pyloric sphincter Explain why the cardiac sphincter is considered a physiological sphincter:it has no thickening of circular muscle Explain why the pyloric sphincter is considered an anatomical sphincter:it is marked by the thickening of circular muscle in the muscularis externa At what vertebral level does the oesophagus pierce the diaphragm?T10 Describe type I (sliding) hiatal hernias:the cardiac region slides through the oesophageal opening Describe type II (rolling) hiatal hernias:the fundus region slides through the oesophageal opening True or false: aortic aneurysms can occlude the IMATrue Where vessel is used as a collateral route when the IMA is occluded by an aortic aneurysm?marginal artery What is sigmoid volvulus?twist in sigmoid colon resulting in obstruction, ballooning and potentially ischaemia What are the 4 key branches of the hepatic portal vein that can differ in formation from person to person?1) left gastric vein 2) splenic vein 3) inferior mesenteric artery (branch of splenic vein) 4) superior mesenteric artery True or false: the hepatic veins and peritoneal ligaments help anchor the livertrue What 3 things does a healthy diet supply us with?1) energy 2) building blocks for metabolism 3) essential nutrients What does EAR stand for on a nutrient requirement curve?estimated average requirement What is EAR?Average amount of a nutrient known to meet the needs of 50 percent of individuals What does LRNI stand for on nutrient requirement curves?lower reference nutrient intake What is LRNI?the amount of nutrient that is considered sufficient for 2.5% of the population - many will require more How many SDs are RNI/ LRNI above/ below EAR?2 What does RNI stand for on nutrient requirement curves?reference nutrient intake What is RNI?the amount of nutrient considered sufficient for 97.5% of the population and used as a standard for health What 2 factors does energy expenditure depend on?1) basic metabolic rate 2) amount and intensity of physical activty Give 3 factors that basic metabolic rate (BMR) depends on:1) age 2) weight 3) sex How much of the eat well guide is taken up by carbohydrates?1/3 How much of the eat well guide is taken up by fruit and vegetables?1/3 How many kcal should the average man eat in a day?2500 kcal How many kcal should the average woman eat in a day?2000 kcal Which out of the following provides the most energy: fats, carbohydrates or proteins?fats In which two structures can glycogen be stored?1) liver glycogen 2) muscle glycogen True or false: proteins and amino acids cannot be storedtrue Approximately how much protein do we need to eat a day?50 g/day Where do we get nitrogen from in our diet?proteins Describe the relationship between nitrogen intake and excretion in healthy adults:nitrogen intake equals nitrogen excretion What is a negative nitrogen balance and when would it occur?where excretion is greater than intake, illness What is a positive nitrogen balance and when would it occur?where nitrogen intake is greater than excretion, growth/ pregnancy What are essential amino acids?amino acids that cannot be synthesised by the body and so must be obtained from the diet What are the 9 essential amino acids?1) methionine 2) valine 3) histidine 4) leucine 5) phenylalanine 6) tryptophan 7) Isoleucine 8) lysine 9) threonine What mnemonic can be used to help recall the 9 essential amino acids?Many Very Happy Little Pigs Take Iced Lemon Tea How many kcal does 1g of fat provide?9 kcal How many kcal does 1g of carbohydrate or protein provide?4 kcal What molecules are cholesterol and fatty acids precursors for?1) hormones 2) prostaglandins True or false: the body can store an unlimited amount of triglycerides in adipose tissuestrue Give 2 examples of food where you'd find lots of saturated fat:meat, diary What % of our dietary energy intake should be taken up by fat?30% What are the two essential fatty acids?linoleic acid (omega 3) and linolenic acid (omega 6) What are non milk extrinsic sugars?added sugars What % of our dietary energy comes from carbohydrates?50% What are vitamins?organic compounds required for normal metabolic function which cannot be synthesised in the body Give the 4 fat soluble vitamins:1) E 2) K 3) A 4) D Give 9 water soluble vitamins:1) B1 2) B2 3) B3 4) B5 5) B6 6) B7 7) B9 8) B12 9) C What is the name of vitamin B1?Thiamine What is the role of Vit B1 (Thiamine)?cofactor in carboxylation What is a deficiency in Vit B1 (thiamine) called?Beri Beri What is Beri Beri?muscle weakness, loss of appetite, nerve degeneration, and oedema What is the name of vitamin B2?Riboflavin What is the role of vitamin B2 (riboflavin)?constituent of FAD cofactor What is the name of vitamin B3?Niacin What is the role of vitamin B3 (niacin)?constituent of NADH cofactor What is a deficiency in vitamin B3 (niacin) called?pellagra What is pellagra?Niacin deficiency (Dermatitis, Diarrhoea , Dementia , Death) What is vitamin B5 called?pantothenic acid What is the role of vitamin B5 (pantothenic acid)?constituent of CoA What is vitamin B7 called?Biotin What is the role of vitamin B7 (Biotin)?prosthetic group carrier for CO2 in carboxylation What is vitamin B6 called?Pyridoxal phosphate What is the role of vitamin B6 (Pyridoxal phosphate)?cofactor for many metabolic processes What is vitamin C called?ascorbic acid What is the role of vitamin C (ascorbic acid)?involved in collagen synthesis What does a deficiency in vitamin C (ascorbic acid) cause?scurvy What is vitamin B9 called?folic acid What is the role of vitamin B9 (folic acid)?DNA synthesis What does a deficiency in vitamin B9 (folic acid) cause?neural tube defects in foetal development What is vitamin B12 called?Cobalamin What does a deficiency in vitamin B12 (Cobalamin) cause?macrocytic anaemia What is the role of vitamin A?vision and transcriptional regulator What is the role of vitamin D?mineralization of bones, immune regulation What does a deficiency in vitamin D cause?rickets in children and osteomalacia in adults What is the role of vitamin E?prevents lipid oxidation in membranes What is the role of vitamin K?cofactor for enzymes which activate clotting factors What are minerals?inorganic elements that have physiological functions What is malnutrition?the inadequate or excess intake of protein, energy and micronutrients What vitamin do vegans commonly become deficient in which can cause anaemia and neurological damage?vitamin B12 Why do vegans commonly become Vit. B12 deficient?it is only found in human sources What structure divides the liver into its right and left lobes?falciform ligament What are the 8 clinical segments of the liver called?couinaud What determines the 8 clinical segments of the liver?vasculature What structure do the left and right hepatic ducts drain into?common hepatic duct What does the hepatic duct drain into?common bile duct What is the name of the duct that connects the gall bladder to the common hepatic duct?cystic duct What is the name of the junction between the common bile duct and the duodenumAmpulla of Vater What are the 4 regions of the pancreas called?1) head 2) neck 3) body 4) tail What pancreatic cells produce insulin?beta islet cells What pancreatic cells produce hormones?hormone secreting iselt cells What pancreatic cells produce enzymes?digestive enzyme secreting cells What are the 3 phases of enzyme secretion?1) cephalic 2) gastric 3) intestinal Describe the cephalic phase of enzyme secretion:when smelling, seeing or tasting food, secretions are stimulated by the vagus nerve, producing water and NaCl rich secretions as well as pancreatic peptide What is the effect of pancreatic peptide during the cephalic phase of enzyme secretion?it stops the duodenum from contracting to keep enzymes there Describe the gastric phase of enzyme secretion:when food reaches the stomach, receptors in detect stretch, stimulating the vagus nerve to release ACh which thus stimulates secretion of enzymes and saline fluid Describe the intestinal phase of enzyme secretion:gastric chyne enters the small intestine and its acidity stimulates the release of secretin from S cells which promotes HCO3- secretion for neutralisation. I cells also release CCK which promotes enzyme secretion What does CCK stand for?cholecystokinin What cells produce CCK?I cells What cells produce secretin?S cells of duodenum How many amino acids are found in CCK?33 What stimulates release of CCK?lipids and proteins arriving in the small intestine What receptors do CCK molecules bind to?CCK-A What receptors do gastrin molecules bind to?CCK-B What are the two main effects of CCK?1) stimulation of pancreatic secretion (enzymes) 2) stimulation of gall bladder emptying (bile) Describe how the action of trypsin can regulate CCK secretion:trypsin acting on proteins can produce monitor peptides that bind to I cell receptors, causing CCK secretion How many amino acids are found in monitor peptides?66 How many amino acids are found in secretin?27 What stimulates secretin secretion?acid in duodenum What is the effect of secretin release?stimulates HCO3- secretion by ductal cells in the pancreas and liver for neutralisation What is the effect of secretin o gastric acid?secretin modestly inhibits gastric acid production What is the name given to inactive protease precursors?zymogens Give 3 examples of protease zymogens:1) trypsinogen 2) chymotrypsinogen 3) proelastase What enzyme converts protease zymogens into their active forms?enterokinases True or false: trypsin activates chymotrypsintrue What is the name given to the enzymes found on the brush boarder that convert smaller peptides into single amino acids?peptidases Give two examples of nucleases:1) deoxyribonuclease 2) ribonuclease Give 3 example of pancreatic lipases:1) pancreatic lipase 2) non-specific esterase 3) prophospholipase A2 True or false: pancreatic alpha-amylase has a very different action of digestion to salivary amylasefalse Describe the secretion of bicarbonate by pancreatic/ bile ducts:secretin stimulates secretion, CFTR channels pump out Cl- ions which are used in antiport secondary active transport for the release of HCO3- What cells produce bile?hepatocytes True or false: 95% of bile is watertrue What organ synthesises bile salts and bile acids?liver What property of bile salts allows them to form micelles?amphipathic Other than bile salts and acids, what are the other components of bile? (4)1) phospholipids 2) cholesterol 3) bile pigments from haemoglobin breakdown 4) inorganic ions Describe and explain the ratio cations and anions in bile:cations exceed anions as bile acids carry a negative charge What do bile salts begin synthesis as?cholesterol How is a bile salt formed from a bile acid?it conjugates with an amino acid e.g. lithocholic acid with taurine What enzyme helps solubilise bilirubin/ urobilinogen?UGT1A1 What product of bilirubin breakdown is excreted in faeces and also processed in urine excretion?urobilinogen Where in the liver lobules will bile be found?bile canaliculi True or false: flow in bile canaliculi is counter-current to flow of blood in the hepatic artery and hepatic portal veintrue What liver cells remove toxins?Kupffer cells How is bile modified as it moves along bile ducts?bicarbonate, salt and water are added What is the name of the sphincter found at the Ampulla of Vater that closes of the duct between the liver/ pancreas to the duodenum?sphincter of Oddi How does bile reach the gall bladder for storage?the sphincter of Oddi closes, causing bile to back up into the gall bladder How does the ball bladder keep bile salts dissolved when you're not eating?it undergoes tonic contractions How is bile released into the duodenum upon eating?the gall bladder contracts, causing relaxation of the sphincter of Oddi What 3 nerves/ hormones regulate the gall bladder?1) vagus nerve 2) splanchnic nerve 3) CCK What makes the fluid in the gall bladder so concentrated?the gall bladder reabsorbs salt and water What gall bladder mechanism prevents precipitation of salts, thus reducing the risk of gall stones?there is a net proton secretion that acidifies the bile What circulation is used to recycle bile salts back to the liver?enterohepatic What role does bacteria play in bile salt recycling?bacteria helps deconjugate bile salts into bile acids What cells produce gastrin?G cells What is the effect of gastrin?stimulates gastric acid secretion Where is motilin produced?M cells of duodenum and jejunum What is the effect of motilin?initiates migrating motor complexes for GI clear-out during fasting How many lobes does the liver have?4 Name all 4 lobes of the liver:1) right 2) left 3) caudate 4) quadrate What ligament separates the right and left lobes of the liver?falciform ligament What ligament separates separates the quadrate lobe of the liver?right triangular ligament What is the name of the region of the underside of the liver not covered by peritoneum?bare area What vessel carries blood from the GI tract to the liver?hepatic portal vein What % of blood entering the liver comes from the hepatic portal vein?75% What % of blood entering the liver comes from the hepatic artery?25% What vessel does deoxygenated blood in the liver pool into?hepatic vein What is the name given to the hexagonal functional units found in the liver?hepatic lobules Describe the structure of hepatic lobules:a single central vein is surrounded by 6 hepatic portal vein branches and 6 hepatic artery branches What structures connect blood vessels in hepatic lobules?sinusoids What is the most abundant cell type in the liver?hepatocytes What is the name of the phagocytic liver cells that aid detoxification?Kupffer cells What is the name of the epithelial cells that line the bile duct?cholangiocytes What is the name of the liver's mesenchymal cells?hepatic stellate cells Other than hepatocytes and Kupffer cells, name four other cells found in the liver:1) hepatic stellate cells 2) liver endothelial 3) cholangiocytes 4) liver infiltration lymphocytes such as B cells What are the two main roles of hepatocytes?1) detoxification 2) fatty acid metabolism Name the 5 major functions of the liver:1) macronutrient metabolism 2) nutrient storage 3) hormone metabolism 4) xenobiotic detoxification 5) bilirubin metabolism excretion Give two ways in which the liver is involved in carbohydrate metabolism:1) gluconeogenesis 2) glycogen synthesis and breakdown Give 3 ways in which the liver is involved in fat metabolism:1) ketogenesis 2) fatty acid, cholesterol and lipoprotein synthesis 3) bile acid synthesis Give 3 ways in which the liver in involved in protein metabolism:1) amino acid synthesis 2) break down of amino acids (urea) 3) plasma protein synthesis Give 3 examples of nutrients stored by the liver:1) glycogen 2) vitamins A, D, E, K and B12 3) iron Give 3 ways in which the liver in involved in hormone metabolism:1) metabolism and excretion of steroid hormones 2) metabolism of polypeptide hormones 3) hydroxylation of vitamin D What is meant by xenobiotic detoxification?metabolism and excretion of alcohol, drugs and other foreign compounds What is the role of bile?emulsifies fat during digestion What molecule is the starting molecule for bile acid synthesis?cholesterol What circulation pathway is used for the recycling of bile salts?enterohepatic circulation What role do bile salts play in the storage of bile?they maintain solubility of bile in the gall bladder Describe how gall stones are formed?too few bile salts or too much cholesterol causes precipitation of cholesterol in the gall bladder What causes cholecystitis?obstruction to the bile duct caused by gallstones or biliary sludge What is the surgical method used to remove the gall bladder?cholecystectomy What are xenobiotics?chemical substances not naturally produced such as alcohol and drugs What enzyme largely drives phase 1 metabolism of xenobiotics?cytochrome P450 Give three examples of cytochrome P450 drugs involved in the metabolism of drugs:CYP1, CYP2, CYP3 What molecules are required as cofactors for cytochrome P450 metabolism of xenobiotics?O2 and NADPH Give the two step breakdown pathway of ethanol in the liver:ethanol -> acetaldehyde -> acetate What two molecules can convert ethanol to acetaldehyde in the liver?1) ADH 2) CYP2E1 What molecule can convert acetaldehyde to acetate during ethanol metabolism in the liver?ALDH Does paracetamol metabolism use phase 1 or 2 metabolism?phase 2 How does paracetamol overdose cause liver failure?a depletion of glutathione allows free NAPQI to react with cell membranes causing hepatic necrosis Describe haem degradation?haem is phagocytosed by Kupffer cells a forming bilirubin What are the three steps of bilirubin metabolism?1) oxidative metabolism with NADPH- cytochrome P450 reductase and haem oxygenase 2) multiple conjugation steps mainly with glucuronic acid, then secreted into the biliary system 3) bacteria converts it to urobilinogen, then urobilin (excreted in urine) and stercobilin (excreted in faeces) What is the key presentation of hyperbilirubinemia?jaundice What is a common method for treating jaundice in infants?phototherapy (photo-oxidation transforms bilirubin to colourless oxidation products) Give 4 chemical markers used in liver function tests:1) ALT/ AST 2) Alkaline phosphate 3) gamma-glutamyl transpeptidase 4) bilirubin Give a prehepatic cause of jaundice:haemolysis Give hepatic cause of jaundice:hepatitis Give two post-hepatic causes of jaundice:cholestasis, carcinoma of the pancreas What is the advised weekly alcohol cap?14 units True or false: it is best to spread your weekly alcohol intake across 3 days or moretrue What advice is given to pregnant women when it comes to alcohol?don't drink at all Where is the liver found?right upper quadrant, below the 4th rib and extending to the 9th Give 6 principle functions of the liver:1) cholesterol metabolism 2) fatty acid metabolism 3) protein synthesis 4) drug metabolism 5) bile formation 6) carbohydrate metabolism 7) ammonia metabolism Give 5 functions of bile:1) cholesterol/ phospholipid homeostasis 2) functional bile acid circulation 3) drug excretion 4) electrolyte balance maintenance 5) conjugated bilirubin excretion Give the 4 major types of liver disease:1) acute hepatitis 2) chronic liver disease 3) extrahepatic biliary obstruction 4) fatty liver disease How is Hepatitis A transmitted?faecal-oral route What type of virus is hepatitis A?RNA virus How does the hepatitis A virus cause damage?it replicates in hepatocytes, causing hepatocyte necrosis and lymphocyte infiltration Give 6 common symptoms/ signs of hepatitis A:1) jaundice 2) dark urine 3) pale stool 4) malaise 5) anorexia 6) abdominal pain What is juandice?yellow skin What is the key clinical feature found with hepatitis A during scans?hepatomegaly What is chronic liver disease?cirrhosis Fill the gaps: chronic liver disease is p________ and p__________permanent, progressive What is cirrhosis?scarring of the liver (fibrosis and nodular regeneration causing changes in lobular architecture) Give 7 causes of chronic liver disease:1) alcohol 2) autoimmune liver disease 3) primary sclerosing cholangitis 4) fatty liver disease 5) primary biliary cirrhosis 6) hepatitis B 7) hepatitis C Give three ways in which cirrhosis causes significant morphological changes to the liver:1) hepatocytes are damaged and function poorly 2) vascular perfusion is disturbed 3) the sinusoidal/ canalicular pathway is disrupted Give 9 clinical signs of cirrhosis:1) ascites 2) jaundice 3) portal hypertension 4) renal failure 5) splenomegaly 6) endocrine abnormality 7) bleeding 8) renal failure 9) hepatocellular carcinoma What is ascites?accumulation of fluid in the peritoneal cavity What is encephalopathy?any disease of the brain What are spider nevi?markings of the skin characterised by a central red spot with deep reddish extensions What disease are spider nevi associated with?cirrhosis What is xanthelasma?Triglyceride build-up (under eye) Describe how portal hypertension can present as vomiting blood?it can cause oesophageal varices which rupture What are oesophageal varices?Dilatations of the lower oesophageal submucosal veins, which may rupture to cause severe haemorrhage What is caput medusae?Varicose enlargement of periumbilical veins of the abdominal wall due to portal hypertension What are the two main causes of extrahepatic biliary obstruction?1) gall stones 2) pancreatic cancer Give 9 clinical signs of extrahepatic biliary obstruction:1) jaundice 2) dark urine 3) vitamin deficiencies 4) steatorrhea 5) weight loss 6) pale stools 7) disturbed lipid metabolism 8) itchy skin 9) pain What causes itching in extrahepatic biliary obstruction?bile salts accumulating in the skin Give 4 common causes of fatty liver disease:1) obesity 2) diabetes 3) drugs 4) alcohol How does the liver appear in fatty liver disease?swollen and rounded What causes liver swelling in fatty liver disease?triglycerides accumulate in hepatocytes True or false: fatty liver disease can cause inflammation and thus, fibrosis and cirrhosistrue What is meant by an essential amino acid?Essential means that it cannot be made inside the body, meaning we need to get them from our diet What is meant by a non-essential amino acid?non-essential means it can be made in the body if the right carbohydrate and essential amino acids are present What nitrogen containing compound uses glycine in its synthesis?haem What nitrogen containing compound uses histamine in its synthesis?histamine What nitrogen containing compound uses tryptophan in its synthesis?serotonin What is the name of the protein deficiency found in children associated with poor growth and lower limb oedema?Kwashiorkor What causes Kwashiorkor?lack of protein Give 6 signs/ symptoms of Kwashiorkor:1) lower limb oedema 2) poor skin condition 3) poor growth 4) susceptibility to infection 5) abdominal bloating 6) change in skin and hair (brittle, dry, brown) At what stage of a child's life is Kwashiorkor most common?during weaning from breast feeding True or false: the body cannot store amino acidstrue Give 4 symptoms of hyperammonaemia:1) tremor 2) vomiting 3) cerebral oedema 4) coma What is hyperammonaemia?impaired conversion of NH3 to urea What are the three steps of removing nitrogen from amino acids for storage?1) transamination 2) deamination 3) urea cycle Describe transamination:the transfer of an amino group from an amino acid to a keto acid: mainly alpha-ketoglutarate forming glutamate What enzyme is used most commonly in transamination?transaminase What cofactor is needed for the action of transaminase?pyridoxal phosphate Where does pyridoxal phosphate come from?active form of vitamin B6 Other than transamination, name two other metabolic processes that pyridoxal phosphate is involved in:1) haem synthesis 2) decarboxylation reactions in neurotransmitter synthesis Describe deamination:the release of ammonia from glutamate, regenerating alpha-ketoglutarate What enzyme is used in deamination?glutamate dehydrogenase What two molecule form carbamoyl phosphate?ammonia and bicarbonate In which step of the ornithine/ urea cycle is urea removed?L-arginine -> ornithine Describe the section of the ornithine cycle that takes place inside mitochondria:the carbamoyl group is transferred to ornithine to form citrulline Describe the section of the ornithine cycle that takes place in cytosol:citrulline goes onto form L-aspartate which forms argininosaccinate which goes on to form L-arginine when fumarate is removed. Finally, urea is removed from L-arginine to form ornithine Where is uric acid derived from?purine nucleotides What is excess uric acid in the blood called?hyperuricaemia What complications can hyperuricaemia cause?depositions of sodium urate crystals causing kidney stones and gout in joints Give two causes of hyperuricaemia:1) poor excretion of uric acid in the kidneys 2) over production of urate Give 4 examples of foods with high purine levels:1) red meat 2) organ meat 3) sea food 4) yeast-containing food Give 3 examples of metabolic pathways that carbon skeletons from amino acids can be fed into:1) Krebs cycle 2) fatty acid and ketone body synthesis 3) gluconeogenesis What is meant by a glucogenic amino acid?can be degraded to glucose precursors What is meant by a ketogenic amino acid?can be degraded to precursors of fatty acids and ketone bodies What is gluconeogenesis and when does it take place?making glucose from non-carbohydrate intermediates during fasting or exercise Where does gluconeogenesis occur?cytosol of liver and sometimes kidney cells Give the 3 precursors that can be used in gluconeogenesis:1) keto acids 2) lactate 3) glycerol Give 5 examples of amino acids that are both glucogenic and ketogenic:1) tryptophan 2) tyrosine 3) threonine 4) isoleucine 5) phenylalanine Give the first major step of gluconeogenesis:pyruvate to phosphoenolpyruvate catalysed by pyruvate kinase Give the second major step of gluconeogenesis:fructose 1,6 bisphosphate to fructose 6 phosphate catalysed by 1,6 bisphosphatase Give the third major step of gluconeogenesis:glucose 6 phosphate to glucose, catalysed by glucose 6 phosphatase How many molecules of ATP does gluconeogenesis require?6 True or false: gluconeogenesis and glycolysis are reciprocally regulatedtrue Give two molecules that inhibit gluconeogenesis:insulin and ADP Give three molecules that activate gluconeogenesis:glucagon, acetyl CoA and citrate Describe how hyperglycaemia can arise in type 1 diabetes patients: (2)1) no insulin is produced, inhibiting glycolysis (insulin is needed to allow glucose to enter muscle and adipose tissue), causing blood sugar to rise 2) the lack of insulin stimulates gluconeogenesis (insulin inhibits gluconeogenesis) causing the liver to synthesise and release glucose. Blood sugar rises further What is the Cori cycle?A process in the liver that regenerates glucose from lactate released by muscles Give the basic word equation for the Cori cycle:2 lactate -> 2 pyruvate -> glucose Describe how alcohol can make us feel hungry:1) ethanol metabolism in the liver produces lots of NADH which lowers NAD+ levels 2) low NAD+ levels prevents the conversion of glycerol to glyceraldehyde 3 phosphate, inhibiting gluconeogenesis 3) this results in hypoglycaemia which can be experienced as feeling hungry What is the HbA1c of a diabetic?>48 mmol/l Give 5 presenting features of diabetes:1) polyuria and polydipsia 2) weight loss and fatigue 3) pruritis valvae and balanitis 4) hunger 5) blurred vision Why does diabetes cause hunger?a lack of insulin prevents hypothalamic uptake of glucose How does diabetes cause blurred vision?altered acuity due to uptake of glucose in the lens What is the peak age of type 1 diabetes?12 years What is the peak age of type 2 diabetes?60 years How is type 1 diabetes different to type 2?it is an autoimmune disease causing beta-cell destruction How is type 2 diabetes different to type 1?its characterised by insulin resistance and subsequent beta-cell dysfunction What is gestational diabetes?Abnormal blood glucose maintenance during pregnancy True or false: while gestational diabetes ceases after birth, 1/3 women will go on to get type 2 diabetes later in lifetrue In which type of diabetes is ketoacidosis a significant risk?type 1 What are the two most notable symptoms in type 1 diabetes?1) weight loss 2) moderate/ large urinary ketones Give 3 examples of microvascular complications of diabetes:1) retinopathy 2) neuropathy 3) nephropathy What is diabetic retinopathy?damage to the blood vessels in the retina What is diabetic neuropathy?nerve damage that occurs because of the metabolic derangements associated with diabetes mellitus What is diabetic nephropathy?Damage to small blood vessels that supply the glomeruli of the kidney What is the key treatment used for type 1 diabetes?insulin therapy What are the two forms of insulin therapy used to treat type 1 diabetes?1) basal bolus injections (once or twice or day) 2) insulin pump What dietary factor is insulin dose dependent on for type 1 diabetes patients?carbohydrate intake What metabolic issue arises if too much insulin is given to a patient?hypoglycaemia Why is hypoglycemia such a dangerous problem?cerebral tissues rely on glucose for fuel so hypoglycaemia can result in comas and irreversible cerebral damage What hormones are released to counter hypoglycaemia and how do they attempt to do this?adrenaline and glucagon, by increasing hepatic glucose output How long does the implanted arm glucose monitor last?2 weeks How does a 'closed loop' glucose administering system work?a continuous glucose monitor communicates with a glucose pump to adjust insulin levels How does type 2 diabetes lead to beta-cell dysfunction?beta-cells of the pancreas try to pump out more and more insulin to counter the high blood glucose levels, resulting in their dysfunction Give 3 examples of macrovascular complications associated with type 2 diabetes:1) myocardial infarction 2) stroke 3) peripheral vascular disease How does a diagnosis of type 2 diabetes affect life expectancy?reduces it by 6-10 years What two types of treatment are used for type 2 diabetes?1) weight loss and exercise plans to reverse hyperglycaemia 2) medication to control blood pressure, blood glucose and lipids How does hyperglycaemia cause increased lipid levels in the blood?glycation of HDL and LDL means they cannot bind with their receptors Describe how alpha-glucosidase inhibitors act as anti-diabetic agents:reduce glucose absorption in the gut Describe how sulphonylureases act as anit-diabetic agents:they force the pancreas to produce more insulin Describe how metformin acts as an anti-diabetic agent:reduces hepatic glucose production Describe how gliflozins act as anti-diabetic agents:they make kidneys lose glucose via urine Give two examples of anti-hypoglycaemic agents:1) SGLT2 inhibitors 2) GLP1-RA Give four examples of anti-diabetic agents:1) alpha-glucosidase inhibitors 2) sulphonylureas 3) metformin 4) glifozins What structure in the brain regulates hormone release from the anterior pituitary gland?hypothalamus What area of the pituitary secretes GH, ACTH, TSH, FSH/LH and MSH?anterior pituitary Where specifically are glucocorticoids produced?zona fasciculata in the adrenal cortex What hypothalamic hormone is released by the hypothalamus to stimulate the pituitary gland to secrete ACTH?CRH What stimulates the hypothalamus to secrete CRH?stress cytokines What does the pituitary gland release in response to CRH?ACTH What is the effect of ACTH on cortisol production?it increases cortisol production What is the effect of high cortisol levels on the hypothalamus and pituitary gland?production of CRH and ACTH is inhibited via negative feedback Give two types of glucocorticoids:1) cortisol 2) cortisone What molecule are most steroid hormones including glucocorticoids synthesised from?cholesterol Other than glucocorticoids, what other hormone groups are produced by the adrenal cortex?1) mineralocorticoids 2) androgens When is cortisol production highest?30 minutes after waking up What region of the hypothalamus regulates cortisol levels?the suprachiasmatic nucleus What is meant when cortisol is described as diurnal?it is present predominantly during the day True or false: glucocorticoid receptors are present in almost all cells meaning cortisol has an effect on almost all body systemstrue Give two instances where cortisol secretion would increase:1) times of stress 2) during pregnancy (x2-4) Give the four general effects of cortisol:1) reducing inflammation 2) increasing blood glucose levels and availability 3) role in the fight or flight response 4) increases cardiovascular tone Give three ways in which cortisol reduces inflammation:1) suppresses B cell antibody production 2) reduces neutrophil migration 3) stimulates apoptosis of T cells Give 6 ways in which cortisol increases blood glucose levels and availability:1) increases blood glucose availability to the brain 2) increases lipolysis 3) increase gluconeogenesis 4) reduces glycogen synthesis 5) reduces insulin production 6) increases glucagon synthesis What is the name of the disease characterised by adrenal insufficiency?Addison's disease Give 6 symptoms of Addison's disease:1) weight loss 2) weakness and fatigue 3) hypotension 4) reduced body hair 5) hyperpigmentation 6) hypoglycaemia Give 4 causes of Addison's disease:1) malignancies 2) autoimmune issues 3) irradiation 4) pituitary disease What is Addison's crisis?Life threatening emergency caused by sudden withdrawal of cortisol in stressful situations Give 5 signs/ symptoms of Addison's crisis:1) low blood pressure 2) pyrexia 3) vomiting 4) confusion 5) raised blood potassium What is the name of the common stimulation test used to investigate adrenal insufficiency?Synacthen test Describe the synacthen test:ACTH is injected and cortisol levels are taken at 30 and 60 minutes- cortisol levels should increase to 420 at 30 mins How is Addison's crisis treated?IV steroids and fluids What causes Cushing's syndrome?prolonged exposure to high levels of cortisol Give an iatrogenic cause of Cushing's syndrome:too much glucocorticoid medication How does Cushing's disease differ from Cushing's syndrome?Cushing's disease is caused by a pituitary tumour and is ACTH specific Give 6 signs and symptoms of Cushing's syndrome:1) weight gain 2) proximal muscle weakness 3) hypertension 4) striae 5) bruising 6) osteoporosis What does ONDST stand for?over night dexamethasone suppresion test Describe the suppression test for Cushing's:dexamethasone is administered before a patient goes to bed and then a blood test is completed the following morning- cortisol levels should decrease Give 3 treatments used for Cushing's:1) removal of related adrenal or pituitary tumour 2) medication 3) radiotherapy Give an example of a steroidogenesis inhibitor drug:osilodrostat How do steroidogenesis inhibitors such as osilodrostat treat Cushing's?they inhibit the enzyme that catalyses the final step of cortisol synthesis in the adrenal cortex Give an example of a somatostatin analogue drug:pasireotide How do somatostatin analogues such as pasireotide treat Cushing's?they bind to human somatostatin receptors, resulting in inhibition of ACTH secretion Give 3 examples of adrenal steroid inhibitors:1) ketoconazole 2) metyrapone 3) etomidate Give an example of a anti-neoplastic drug used to treat Cushing's:mitotane Fill in the gap: 90% of hormone produced by the thyroid is __ which is later activated to __T4, T3 Describe the synthesis of T3 and T4:1) the thyroid peroxidase enzyme on thyroid epithelium is used for iodination of tyrosine on thyroglobulin 2) two iodotyrosines are then combined to form T3 and T4 What thyroid cells take up iodine for T3 and T4 synthesis?thyroid epithelial cells How is tyrosine produced for T3 and T4 synthesis?its produced from thyroglobulin which is synthesised from thyroid epithelial cells and secreted into the lumen of the colloid follicle Give 3 causes of hypothyroidism:1) iodine deficiency 2) iatrogenic cause 3) autoimmune issues Give 5 common symptoms of hypothyroidism:1) hair loss 2) weight gain 3) tiredness 4) dry skin 5) slow heart beat How is hypothyroidism treated?levothyroxine (T4) Give the 3 main causes of hyperthyroidism:1) Graves/ autoimmune 2) toxic goitres 3) pituitary tumour Give 6 signs and symptoms of hyperthyroidism:1) excess sweating 2) hand tremors 3) rapid heart rate 4) fatigue 5) weight loss 6) heat intolerance Give four treatments for hyperthyroidism:1) anti-thyroid agents like carbimazole 2) beta-blockers 3) radioactive iodine 4) total thyroidectomy Why are foetuses so dependent on maternal thyroxine?in the early stages of development, it is required for neurological development What is another term for growth hormone?somatotropin Where is GH produced?anterior pituitary gland True or false: GH follows the circadian rhythm with max release in the second half of the nighttrue What hypothalamic hormone stimulates GH release?GHRH What hormone inhibits GH release?somatostatin Describe the role of GH in protein metabolism: (2)1) stimulates transcription 2) increases amino acid uptake Describe the role of GH in fat metabolism: (2)1) promotes lipolysis 2) increases fat utilisation Describe the role GH in carbohydrate metabolism: (3)1) promotes gluconeogenesis 2) increases the utilisation of glucose 3) inhibits glycolysis True or false: GH also enhances milk productiontrue How does GH promote linear growth?transforms cartilage into bone and increases bone mass What is the result of hypersecretion of GH in children?gigantism What is the result of hypersecretion of GH in adults?acromegaly Give two features of acromegaly:1) enlargement of hands and feet 2) coarse facial features What is the main cause of GH hypersecretion?pituitary adenoma What suppression test can be used for GH?glucose What blood marker indicates hypersecretion of GH?high IGF-1 (insulin growth factor 1) Give two treatments for GH oversecretion:1) trans-sphenoidal surgery (removing tumour from pituitary) 2) medical therapies such as somatostatin analogues and dopamine receptor analogues What does satiety mean?feeling full How many AAs make up ghrelin?28 What cells produce ghrelin?neuroendocrine cells in the stomach When is ghrelin secreted?when the stomach is empty What is the affect of ghrelin?stimulates apeptite What is an orexigenic agent?a substance that stimulates appetite What is an anorexigenic agent?a substance that suppresses appetite Give 6 examples of anorexigens produced by the gut and pancreas:1) CCK 2) Insulin 3) GLP-1 4) Peptide YY 5) Oxyntomodulin 6) Somatostatin True or false: nutrients like glucose and amino acids can act as anorexigenstrue What tissue produces leptin and adiponectin?adipose What is the function of leptin?induces satiety by stimulating insulin secretion What is the function of adiponectin?induces satiety by stimulating insulin secretion Give 2 examples of cytokines that inhibit insulin and leptin:1) TFN-alpha 2) IL-6 Where in the brain are all central and peripheral messages surrounding appetite collected?nucleus of the solitary tract Where in the brain does the nucleus of the solitary tract project to?arcuate nucleus Where is the satiety centre located?ventromedial nucleus Where is the hunger centre located?lateral hypothalamic area Give two examples of anorexigenic neurone secretions:1) POMC 2) CART Give two examples of orexigenic neurone secretions:1) AGRP 2) NPY What molecule is used to fuel RBCs during starvation?glucose What two molecules are used to fuel the brain during starvation?1) glucose 2) ketone bodies What two molecules are used to fuel the liver during starvation?1) glucose 2) fatty acids What two molecules are used to fuel skeletal muscles during starvation?1) fatty acids 2) ketone bodies What two molecules are used to fuel adipose tissue during starvation?1) glucose 2) fatty acids Give 7 traits of extreme starvation:1) diminished respiratory capacity 2) loss of heat-generating capacity 3) muscle fatigue 4) muscle wasting 5) death from respiratory/ cardiac failure or infection 6) slow heart rate 7) apathy What BMI can be classified anorexia nervosa?<17.5 What is a normal BMI range?18.5-24.9 What is an underweight BMI?<18.5 What is an overweight BMI?25-29.9 What is an obese BMI?over 30 Give 9 potential physiological consequences of obesity:1) osteoarthritis 2) non-alcoholic fatty liver disease 3) hypertension 4) sleep apnoea 5) infertility 6) endometrial, breast and colon cancer 7) gall stones 8) type 2 diabetes 9) metabolic syndrome Give the 5 traits of metabolic syndrome (of which you need 3 of for a diagnosis):1) obesity (waist circumference) 2) type 2 diabetes 3) hypertension 4) low HDL cholesterol 5) high plasma triglycerides What is meant my ectopic fat?fat around viscera such as the liver, skeletal muscles and heart How does ectopic fat alter metabolic profile?it is less responsive to insulin and exists in a hyper-lipolytic state meaning it produces free fatty acids What is the effect of ectopic fat producing free fatty acids?it makes the liver less sensitive to insulin and impairs beta cell release What causes chronic inflammation in obese people?ectopic fat produce pro-inflammatory cytokines Describe how cytokines from ectopic fats can lead to atheroma and CVS disease:cytokines cause the production of reactive oxygen species which paired with dyslipidaemia, increases CVS disease and atheroma

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