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Florence Bradshaw JaundiceCONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 2CONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 2What is Jaundice? ● Yellowish pigmentation of the skin and sclera ● Caused by the buildup of bilirubin ● Hyperbilirubinaemia (>20mg/L causes jaundice) ● Bilirubin is a product of haem metabolism → hyperbilirubinaemia is haem metabolic dysfunctionBilirubin Metabolism Pre-hepatic - RBCs→ 120 day lifespan - Death→ rupture→ haemoglobin released into circulation - Macrophages phagocytose free haemoglobin - Haem is oxidised to biliverdin (green) - Biliverdin is oxidised to bilirubin (yellow) - As this is not attached to anything, it is unconjugated - Unconjugated bilirubin travels to the liver bound to albuminBilirubin Metabolism Hepatic - Unconjugated bilirubin is attached to glucuronic acid to make conjugated bilirubin - Reason→ bilirubin is now soluble in water and can be excreted - Bilirubin is sent to the gallbladder for storageBilirubin Metabolism Post-hepatic - Bilirubin forms part of bile - Bile is secreted by the gallbladder into the duodenum - Intestinal bacteria: conjugated bilirubin → urobilinogen - Urobilinogen → stercobilinogen → stercobilin - Stercobilin → faeces (brown) - Leftover urobilinogen→ reabsorbed into hepatobiliary circulation - Some reabsorbed urobilinogen is excreted by the kidneys - Converted to yellow urobilinCONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 2How to split the differential Pre-hepatic Hepatic Post-hepatic • Excess production • Due to liver • Also called of haem → dysfunction→ obstructive increased combo of ↓ cholestasis→ destruction of uptake, obstruction in RBCs ↓conjugation, ↓ transport of bile (haemolysis) excretion from liver to gutPre-Hepatic Jaundice • Excess production of haem→ increased destruction of RBCs (haemolysis) • Unconjugated hyperbilirubinaemia • Haemolysis→ intrinsic or extrinsic • Haemolytic anaemia • Hereditary spherocytosis • Sickle cell anaemia • Thalassaemia • Extrinsic • HUSHepatic Jaundice • Due to liver dysfunction→ combo of ↓ uptake, ↓conjugation, ↓ excretion • predominantly as excretion is the rate limiting step • Hepatitis • Viral→ acute or chronic • Non-alcoholic fatty liver • Drug-induced • Autoimmune • Cirrhosis • HepatotoxicityPost-Hepatic Jaundice • Also called obstructive cholestasis→ obstruction in transport of bile from liver to gut • Conjugated hyperbilirubinaemia • Bile stagnates and builds up→ increases concentration of bilirubin in the blood • Lack of bile in stool + increased bile in urine→ pale stool and dark urine • Causes: anything blocking the outflow of b•leBile duct stones • Head of pancreas cancer • PancreatitiscturesCONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 2HPC • Acute or chronic? • Associated symptoms • RUQ pain, nausea, vomititng, pruritus • Fever • Steatorrhoea, dark urine, and pruritus • Weight loss, fever and night sweats • Bronzed skin and signs of DiabetesPMH • Gallstones? • Liver disease? • Haemophilia? • Recent blood transfusion or surgery? • Ulcerative colitis? • Diabetes mellitus? • Emphysema? • Psychosis?DHX Anything that will cause an increase in haemolysis • Intravascular haemolysis (e.g. sulphonamides, aspirin in G6PDH-deficient patients). • Autoimmune, extravascular haemolysis (e.g. methyldopa). • Hepatitis (e.g. paracetamol overdose). • Cholestasis (e.g. co-amoxiclav).SHX • Excessive alcohol consumption? • IVD use? • Unprotected sex or multiple partners? • Foreign travel? • Tattoos?FHX Gilbert’s disease Haemochromatosis Wilson’s disease Sickle cell disease Thalassaemia, Hereditary spherocytosis G6PDH deficiency (X-linked) Cancer?EXAMINATION • abdomen inspection→ Jaundice, distended • Hands→ Leukonychia, palmar erythema, Dupuytren’s contracture, bruising, scratch marks, asterixis (flapping tremor when arms are outstretched and eyes closed) • Face: Scleral icterus, malar erythema • Chest: Spider naevi, gynaecomastia • Abdomen: Hepatomegaly, splenomegaly, ascites (with shifting dullness), caput medusae • Sacrum/feet: Pedal oedemaCONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 2Investigations Bloods Imaging Liver screen! • First line: Abdominal USS Main components: • From there, it will depend on what is • FBCs suspected and if it needs imaging: • U&Es • Cancer→ CT abdomen • LFTs • Bile duct obstruction→ MRCP or • Coagulation ERCP • Hepatitis serology • Hepatitis: No imaging necessary • Iron studies • Cirrhosis: Fibroscan • etc…LFTs Consists of a range of tests Main tests: • AST/ALT → released from hepatocytes → markers of hepatocellular damage • ALP → released from the liver and cholangiocytes. Synthesis increased in response to cholestasis → marker of cholestasis • Gamma-GT → released by cholangiocytes, and is usually raised alongside raised ALP. Together, they support a cholestatic picture. • Albumin → measure of the ‘synthetic function of the liver’ • Prothrombin time → measure of the synthetic function of the liverLFTs If liver function tests are deranged, the pattern of these markers can help determine where the pathology is: • ↑↑ ALT & AST with ↑/↔ ALP → Hepatic picture • ↑↑ ALP with ↑/↔ ALT & AST → Cholestatic pictureInvestigations Bloods Imaging Liver screen! • First line: Abdominal USS Main components: • From there, it will depend on what is • FBCs suspected and if it needs imaging: • U&Es • Cancer→ CT abdomen • LFTs • Bile duct obstruction→ MRCP or • Coagulation ERCP • Hepatitis serology • Hepatitis: No imaging necessary • Iron studies • Cirrhosis: Fibroscan • etc…CONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 21. Obstructive jaundice typically presents with a. Dark urine, normal stools and no pruritus b. Dark urine, acholic stools and pruritus c. Normal urine, normal stools and no pruritus d. Normal urine, normal stools and pruritus e. Normal urine, acholic stools and no pruritus2. What does raised ALP and Gamma-GT suggest? a. Poor synthetic function of the liver b. Increased haemolysis c. Cholestasis d. Raised bilirubin e. Poor coagulation3. What enzyme has reduced activity in Gilbert’s syndrome? a. ALP b. GGT c. Lactate dehydrogenase d. Glucuronosyltransferase e. Biliverdin reductaseCONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 2Hereditary spherocytosis (Pre-Heaptic)Hereditary spherocytosis • Most common hereditary haemolytic anaemia in northern European descent • cell cytoskeletont defect of red blood • The normal biconcave disc shape is replaced by a sphere-shaped red blood cell • RBC survival reduced as destroyed by the spleenPresentation • Failure to thrive • Pallor • Jaundice • Splenomegaly • Fatigue • Family history • Aplastic crisisInvestigations • Osmotic fragility test • “patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests” • EMA binding test and cryohaemolysis test • Electrophoresis analysis of erythrocyte membranesManagment Acute Haemolytic Crisis: • Treatment is generally supportive • Transfusion if necessary Longer Term Treatment: • Folate replacement • SplenectomyAlcoholic Hepatits (Heaptic)Alcoholic Hepatitis Definition→ Inflammation in the liver due to chronic alcohol consumption Causes→ Excess alcohol consumption over an extended period of time • Recommended limit is 14 units/week for both men and women • which is reversible on cessationads to alcohol related fatty liver • If drinking continues, alcoholic hepatitis develops which may be reversible on permanent abstinence •coCAGE questionnairearmful alcohol use • AUDIT testPresentation Mild Severe • Fatigue • Confusion/coma • Ascites • Asterixis • Nausea/vomiting • Jaundice • RUQ pain • Pruritus • Signs of chronic liver diseaseInvestigations • FBC, U+ Es, Clotting Abdominal USS • Fibroscan to assess for degree of • LFTs cirrhosis • Hepatitic picture with ↑ ↑AST/ALT and ↑ yGT • Mildly raised ALP OGD • Assess for oesophageal varices • AST/ALT ratio >2 Liver biopsy • Confirm diagnosis→ when steroid treatment is being consideredManagment Diagnosis → History of significant alcohol intake, with worsening LFTs, elevated bilirubin and onset of jaundice. Confirmed by liver biopsy to be either AH or cirrhosis Management 1. Advise permanent abstinence from alcohol 2. Nutritional support with thiamine and high protein diet 3. Consider steroids 4. Treat complications of cirrhosis 5. Referral for liver transplant→ need to abstain from alcohol for 3 months prior to referralPancreatic Cancer (Post-Hepatic)Pancreatic Caner th 6 most common cancer in Europe 65-75 years old the pancreasocarcinomas which typically occur at the head of Associated with: - Increasing age - Smoking - Diabetes - Chronic pancreatitis - Genes e.g. BRAC2 gene and KRAS gene mutationsPresentation • Painless Jaundice • Pale stools, dark urine and pruritis • Abdominal masses • Non-specific symptoms • Anorexia, weight loss, epigastric pain • Atypical back painInvestigations 1 Line: CT scan (high resolution), US, LFTs Consider: PT, FBCs, CA19-9, PET scanManagment • Less than 20% of cases are suitable for surgery at diagnosis • Whipple's resection → for resectable lesions in the head of the pancreas • Adjuvant chemotherapy • ERCP (+ stent) if palliativeCONTENTS 1. JAUNDICE AND BILIRUBIN 2. DIFFERENTIAL DIAGNOSIS 3. HISTORY AND EXAMINATION 4. INVESTIGATIONS 5. QUIZ NUMBER 1 6. CONDITIONS CAUSING JAUNDICE b. Hepaticatic c. Post-hepatic 7. QUIZ NUMBER 24. What is the most appropriate management of severe alcoholic hepatitis a. Antibiotics b. Fluid therapy c. Lactulose d. Liver Transplant e. Prednisolone5. What organism may cause an aplastic crisis in patients with hereditary spherocytosis a. Staphylococcus aureus b. Group A streptococcus c. Herpes simplex virus d. Parvovirus e. Rotavirus6. What is the diagnostic investigation of choice for pancreatic cancer? a. ERCP b. Abdominal CT Scan c. MRCP d. Percutaneous transhepatic cholangiography (PTC) e. UltrasoundTHANK YOU!REFERENCES 1. Oxford Cases in Medicine and Surgery – Jaundice [BOOK] 2. https://teachmephysiology.com/gastrointestinal-system/liver/bilirubin- metabolism/ 3. https://manualofmedicine.com/topics/gastroenterology/evaluation-of-jaundice/ 4. https://app.pulsenotes.com/presentations/gastrointestinal/notes/jaundice 5. https://bestpractice.bmj.com/topics/en-gb/1143 6. https://www.passmedicine.com/v7/menu.php? – Alcoholic Liver Disease 7. https://bestpractice.bmj.com/topics/en- gb/265?q=Pancreatic%20cancer&c=suggested