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JAUNDICE Daisy Willans WHATWILLWECOVERTODAY? 1.Liver and gallbladder anatomy 2.Functions of the liver 3.Bile synthesis and bilirubin 4.Aetiology of jaundice (pre-hepatic, hepatic, and post-hepatic causes) 5.Clinical features of jaundice 6.Liver function tests HEPATOBILIARYANATOMY right and left hepatic ducts common hepatic duct cystic duct common bile duct pancreatic duct ampulla of Vater image: https://aneskey.com/liver-anatomy-and-physiology/ SBA1 Which ligament forms the primary separation between the left and right lobes of the liver? a) Caudate b) Coronary c) Falciform d) Quadrate e) Triangular SBA1 Which ligament forms the primary separation between the left and right lobes of the liver? a) Caudate b) Coronary c) Falciform d) Quadrate e) Triangular LOBESANDLIGAMENTS Glisson's capsule 4 lobes Right Left Caudate Porta hepatis Quadrate 4 ligaments Falciform Coronary Triangular x 2 (left and right) image: https://www.britannica.com/science/liver THEGALLBLADDER Concentrates + stores bile produced by the liver Bile released in response to CCK Capacity: 30-50 mL Has 3 parts Body Neck Fundus image: https://www.surgeryjournal.co.uk/article/S0263-9319(14)00208-7/fulltext#relatedArticles BLOODSUPPLY Receives 25% of cardiac output Dual blood supply: 75% portal blood (deoxygenated) 25% hepatic artery proper (oxygenated) central veins → collecting veins → hepatic veins → IVC image: https://ib.bioninja.com.au/options/option-d-human-physiology/d3-functions-of-the-liver/liver-blood-flow.html SBA2 A 55 year-old man develops stenosis of his right hepatic artery after a liver transplant. Which organs/sites are most likely to be affected? a) Liver b) Right lobe of liver c) Right lobe of liver, head of pancreas d) Right lobe of liver, gallbladder e) Right lobe of liver, quadrate lobe SBA2 A 55 year-old man develops stenosis of his right hepatic artery after a liver transplant. Which organs/sites are most likely to be affected? a) Liver b) Right lobe of liver c) Right lobe of liver, head of pancreas d) Right lobe of liver, gallbladder e) Right lobe of liver, quadrate lobe MICROANATOMY Lobules/sinusoids = the structural units of the liver Important cells in the liver: Hepatocytes Kupffer cells Stellate cells images: adapted from Medical Physiology, Boron & BoupaepFUNCTIONSOFTHELIVER synthesis and secretion of bile carbohydrate, fat and protein metabolism detoxification iron and B12 storage BILE Hepatocytes secrete hepatic bile Isotonic, pH 7-8 Contents Bile salts Bile pigments Cholesterol Lecithin Mucus Modified by ductal epithelial cells Concentrated in the gallbladder image: adapted from Human Physiology, Pocock & Richards BILEPIGMENTS Excretory products of the haem portion of haemoglobin Gives bile its colour Also why bruises turn yellow Major pigment = bilirubin Formed from biliverdin in the spleen Not water-soluble, transported with albumin Must be conjugated in the liver Excreted in bile image: https://basicmedicalkey.com/the-liver-3/ HOWDOESJAUNDICEHAPPEN? When concentration of bilirubin in the blood = too high Hyperbilirubinaemia PRE-HEPATIC HEPATIC POST-HEPATIC image: adapted from https://www.chegg.com/learn/biology/anatomy-physiology-in-biology/post-hepatic-jaundice PRE-HEPATICJAUNDICE Excessive haemolysis of RBCs Haemolytic anaemia Malaria DIC Erythrocyte defects: Sickle cell anaemia Thalassaemia ↑unconjugated bilirubin conjugated bilirubin excreted normally SBA3 A 28-year-old woman attends her GP practice for a routine health check. She mentions that her father has liver cirrhosis, and so she would like the GP to assess her liver function. The GP orders LFTs to be done. Looking at her results, what is the most likely diagnosis? Bilirubin 37 (<21) Albumin 45 (35-50) ALT 26 (3-45) ALP 125 (30-150) a) Autoimmune haemolytic anaemia GGT 23 (6-32) b) Chronic alcohol liver disease AST 14 (5-40) c) Common bile duct stone Hb 13.7 g/dL (11.5- d) Gilbert's syndrome 15.5) e) Primary biliary cirrhosis Reticulocyte count 1.2% SBA3 A 28-year-old woman attends her GP practice for a routine health check. She mentions that her father has liver cirrhosis, and so she would like the GP to assess her liver function. The GP orders LFTs to be done. Looking at her results, what is the most likely diagnosis? Bilirubin 37 (<21) Albumin 45 (35-50) ALT 26 (3-45) ALP 125 (30-150) a) Autoimmune haemolytic anaemia GGT 23 (6-32) b) Chronic alcohol liver disease AST 14 (5-40) c) Common bile duct stone Hb 13.7 g/dL (11.5- d) Gilbert's syndrome 15.5) e) Primary biliary cirrhosis Reticulocyte count 1.2%NEWBORNJAUNDICE Type of pre-hepatic jaundice Increased haemolysis of fetal red cells Immature liver cannot cope with increased bilirubin Physiological, harmless More likely to be pathological if occurs in first 24 hours after birth Normally, no treatment needed image: https://www.shutterstock.com/video/search/newborn-photo-therapy HEPATICJAUNDICE Liver is unable to excrete and/or conjugate bilirubin Causes: Cirrhosis Malignancy Viral hepatitis Drugs Wilson's disease ↑unconjugated bilirubin + ↑conjugated bilirubin Unconjugated causes: Gilbert's syndrome Crigler-Najar syndrome SBA4 A 72 year-old man presents to the A&E department. He says over the last few weeks he thinks that the whites of his eyes have become progressively more yellow. On examination he has jaundiced sclera and skin. He has recently started growing vegetables in his garden, and shows you a picture of his prized carrots. He puts recent weight loss down to his increased vegetable consumption. What is the most likely reason for his jaundice? Bilirubin 136 (<21) a) Acute pancreatitis Albumin 38 (35-50) ALT 57 (3-45) b) Carotenaemia c) Acute cholecystitis ALP 245 (30-150) GGT 90 (6-32) d) Biliary colic AST 40 (5-40) e) Carcinoma of head of the pancreas SBA4 A 72 year-old man presents to the A&E department. He says over the last few weeks he thinks that the whites of his eyes have become progressively more yellow. On examination he has jaundiced sclera and skin. He has recently started growing vegetables in his garden, and shows you a picture of his prized carrots. He puts recent weight loss down to his increased vegetable consumption. What is the most likely reason for his jaundice? Bilirubin 136 (<21) a) Acute pancreatitis Albumin 38 (35-50) ALT 57 (3-45) b) Carotenaemia c) Acute cholecystitis ALP 245 (30-150) GGT 90 (6-32) d) Biliary colic AST 40 (5-40) e) Carcinoma of head of the pancreas POST-HEPATICJAUNDICE Obstructive jaundice Causes: Gallstones Strictures/tumours of bile duct Pancreatic tumours (usually the head) Primary biliary cirrhosis Primary sclerosing cholangitis ↑conjugated bilirubin SBA5 A 25 year-old man presents in your GP clinic complaining of feeling tired, and itchy all of the time. Upon looking at him he appears yellowish, so you perform some liver function tests which show normal unconjugated bilirubin, increased conjugated bilirubin but you cannot read the urobilinogen as it has been missed off. Blood tests reveal that he is negative for AMA and positive for pANCA. Given the type of jaundice the patient is suffering from, what would you expect his urine and stools to look like? a) Normal urine, pale stools b) Dark urine, pale stools c) Normal urine, normal stools d) Light urine, pale stools e) Light urine, normal stools SBA5 A 25 year-old man presents in your GP clinic complaining of feeling tired, and itchy all of the time. Upon looking at him he appears yellowish, so you perform some liver function tests which show normal unconjugated bilirubin, increased conjugated bilirubin but you cannot read the urobilinogen as it has been missed off. Blood tests reveal that he is negative for AMA and positive for pANCA. Given the type of jaundice the patient is suffering from, what would you expect his urine and stools to look like? a) Normal urine, pale stools b) Dark urine, pale stools c) Normal urine, normal stools d) Light urine, pale stools e) Light urine, normal stoolsSTOOL&URINECHANGESCLINICALFEATURES Yellow skin/sclera Pruritus Fatigue Abdominal pain Weight loss Vomiting Fever Pale stools Dark urine image: https://patient.info/digestive-health/abnormal-liver-function-tests-leaflet/jaundice LFTS Alanine transaminase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase (ALP) Gamma-glutamyltransferase (GGT) Bilirubin Albumin Prothrombin time (PT) image: https://geekymedics.com/interpretation-of-liver-function-tests-lfts/ ALTANDALP Alanine transaminase (ALT) ↑[ALT] in hepatocytes Specific for hepatocytes, released in hepatocellular injury Alkaline phosphatase (ALP) Found in liver, bile duct and bone tissues ↑synthesis in response to cholestasis SBA6 You are a junior doctor on the surgical assessment ward and have been asked to see a middle-aged male patient. The patient has right upper quadrant abdominal pain, radiating to his right shoulder. The patient is nauseous, jaundiced and has a temperature of 38.5°C. He does not smoke but reveals that he considers himself a heavy drinker. You review the liver function tests and blood tests which have been done on the patient. What is the most likely diagnosis? Bilirubin 45 (<21) Albumin 41(35-50) ALT 39 (3-45) ALP 330 (30-150) a) Acute cholecystitis GGT 90 (6-32) b) Acute alcoholic hepatitis AST 30 (5-40) c) Cholelithiasis WCC - elevated d) Hepatocellular ischaemia e) Pancreatitis serum lipase + amylase - normal SBA6 You are a junior doctor on the surgical assessment ward and have been asked to see a middle-aged male patient. The patient has right upper quadrant abdominal pain, radiating to his right shoulder. The patient is nauseous, jaundiced and has a temperature of 38.5°C. He does not smoke but reveals that he considers himself a heavy drinker. You review the liver function tests and blood tests which have been done on the patient. What is the most likely diagnosis? Bilirubin 45 (<21) Albumin 41(35-50) ALT 39 (3-45) ALP 330 (30-150) a) Acute cholecystitis GGT 90 (6-32) b) Acute alcoholic hepatitis AST 30 (5-40) c) Cholelithiasis WCC - elevated d) Hepatocellular ischaemia e) Pancreatitis serum lipase + amylase - normal ASTANDGGT Aspartate aminotransferase (AST) Released from hepatocytes, skeletal and cardiac muscle Gamma-glutamyltransferase (GGT) ↑ suggests biliary epithelial damage + bile flow obstruction Sometimes↑in response to alcohol and drugs (e.g. phenytoin) ↑GGT alongside ↑ALP = cholestatic picture OTHERS Albumin Protein produced by hepatocytes Measures synthetic function of liver Half life = ~20 days ↓indicates chronic damage Prothrombin time Time taken for blood to clot Liver synthesises clotting factors ↑indicates reduced hepatic function image: https://teachmephysiology.com/immune-system/haematology/coagulation/