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Dr Allister J Grant Consultant Hepatologist University Hospitals Leicester NHS Trust Anatomy &Physiology IVC Portal Vein Hepatic Artery Splenic Vein Gallbladder CBD SMV Anatomy &Physiology Liver Functions Nutrition/Metabolic – stores glycogen (glucose chains) – releases glucose – absorbs fats, fat soluble vitamins – manufactures cholesterol Bile Salts – lipids derived from cholesterol – dissolves dietary fats (detergent) Bilirubin – breakdown product of haemoglobin Liver Functions Clotting Factors – manufactures most clotting factors Immune function – Kupfer cells engulf antigens (bacteria) Detoxification – drug excretion (sometimes activation) – alcohol breakdown Manufactures Proteins – albumin – binding proteins Disease Progression Acute Liver Failure Chronic Liver Disease • <6 weeks duration • >6 months • • • • • • • Cirrhosis leading to Jaundice Encephalopathy Cerebral Oedema Acute Renal Failure Acidosis Hypoglycaemia MOF • Recurrent decompensation – Ascites – Portal Hypertension (variceal bleeding) – Encephalopathy • • • • Low albumin/Malnutrition Hepatorenal syndrome Hyponatraemia Hepatoma Disease Progression 100% Liver function A B Cirrhosis Liver Failure D Years C 24♀ 48hours post POD • ALT 13000 • Alb 35 • Bili 40 • Cr 160 • Urea 24 • INR 3.0 • PT 33 • Glc 3.6 • • • • Ph 7.1 PCO2 3.2 PO2 12.4 BE -6 ALF • • • • • • • • • • Treat the underlying cause Resuscitate - Central access early Give N-Ac regardless of cause Monitor for hypoglycaemia Monitor coagulopathy Antibiotic prophylaxis Stress Ulcers Early elective ventilation for encephalopathy Nutrition Acidosis/ Renal Impairment • Early referral to Hepatology / discuss with Birmingham Liver Unit Mrs W • 48 year old ♀ admitted from a surgical clinic with jaundice and unwell • Unwell for 6 wks after holiday in Mexico • Hx of xs alcohol 30u/wk • No previous jaundice • USS normal size liver and spleen – biliary tree normal OE • • • • Jaundice Drowsy Agitated/Irritable Doesn’t obey commands • No stigmata of CLD • Asterixis No spleen No ascites Mrs W • U&E normal • FBC Normal • • • • 107 736 363 24 • INR 3.7 ALP ALT Bili Alb Causes of Acute Liver Failure • Drugs • Paracetamol (UK) • INH • Halothane • Ecstacy • Wilsons Disease • Viral • Hepatitis A • Hepatitis B • Hepatitis E • Non-A Non-B • Cardiovascular • Ischaemic hepatitis • Budd Chiari • Autoimmune Hepatitis • Reye’s Syndrome • Acute Fatty Liver of Pregnancy Encephalopathy • Grade 1 » » » » Constructional apraxia Poor memory – number connection test Agitation/ irritability Reversed sleep pattern • Grade 2 » Lethargy, disorientation » Asterixis • Grade 3 » Drowsy, reduced conscious level • Grade 4 » Coma Cirrhosis Expanded Portal Tracts (Blue) Signs of Chronic Liver Disease • • • • • • • • • None Asterixis/Flap Relative hypotension Oedema Jaundice/No jaundice Large/Small liver Splenomegaly Gynecomastia Testicular atrophy-loss of secondary sexual characteristics • Impotence Decompensation in Cirrhosis Means the development ofAscites Hepatic Encephalopathy Portal hypertension (variceal haemorrhage) Decompensation in Cirrhosis Means the development ofAscites Hepatic Encephalopathy Portal hypertension (variceal haemorrhage) The Development of Ascites 50% of compensated cirrhotics develop ascites over 10yrs 50% of cirrhotics with ascites will die within 2 yrs (50% 2yr rule for OLTx assessment) The Development of Ascites Peripheral arterial dilatation Reduced effective blood volume Activation of renin-angiotensin-aldosterone system Sympathetic nervous system ADH NaCl Na retention & Water retention Ascites and Oedema Low urinary Na Dilutional hyponatraemia Plasma volume expansion Ascites Schrier et al Hepatol 1988 General Management Ascites and Oedema • Salt restriction • Diuretics spironolactone frusemide • Water restriction if sodium < 125 mmol • Paracentesis diagnostic (SBP, tumour) therapeutic (20% Alb) • DAILY WEIGHTS! Decompensation in Cirrhosis Means the development ofAscites Hepatic Encephalopathy Portal hypertension (variceal haemorrhage) Causes of Encephalopathy INCREASED AMMONIAGENESIS Increased substrate (protein) for ammoniagenesis – – – – Increased protein intake Gastrointestinal bleeding Constipation Dehydration Increased substrate (urea) for ammoniagenesis – Renal failure Increased catabolism of protein – Infection – Hypokalemia – Sepsis Causes of Encephalopathy DECREASED HEPATOCELLULAR FUNCTION – – – – – – – – – Worsened intrinsic liver disease Hypoxia Anaemia Development of hepatocellular carcinoma Dehydration Hypotension Sepsis Drug toxicity Superimposed viral hepatitis Causes of Encephalopathy INCREASED PORTOCAVAL SHUNTING – – – – Portal vein thrombosis Transjugular intrahepatic portosystemic shunt formation Surgical shunt formation Spontaneous shunt formation PSYCHOACTIVE DRUG USE – – – – – Benzodiazepines Ethanol Antiemetics Antihistamines Others General Management Encephalopathy Minimize effects of liver disease Treat precipitants • sepsis • GI bleed • medications (over-diuresis) Avoid sedatives, hypnotics, opiates Lactulose to ensure BO 2x/day Metronidazole/ neomycin Decompensation in Cirrhosis Means the development ofAscites Hepatic Encephalopathy Portal hypertension (variceal haemorrhage) Portal Circulation Oesophageal varices Management of Bleeding Varices • Prevention • Prophylactic Antibiotics • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS Management of Bleeding Varices • Prevention • Prophylactic Antibiotics • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS Fluid Management • • • • • • Crystalloid Colloid Blood Platelets FFP Vitamin K Management of Bleeding Varices • Prevention • Prophylactic Antibiotics • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS Oesophageal varices Bleeding Gastric Varices Variceal Bander Variceal Band Ligation Management of Bleeding Varices • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy• Balloon Tamponade • TIPS Terlipressin 2mg qds i.v Management of Bleeding Varices • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS Sengstaken-Blakemore Tube Complication of SBT Management of Bleeding Varices • Resuscitation • Endoscopy - Band Ligation Sclerotherapy • Pharmacotherapy- Terlipressin • Balloon Tamponade • TIPS The End “All right, let's not panic. I'll make the money by selling one of my livers. I can get by with one “ Doh!