Nadia Bukhari Describe the basic structure and function of the liver Describe the various clinical tests used in liver disease Explain the difference between acute and chronic liver disease Describe the complications of alcoholic liver cirrhosis Describe the various treatments for the complications of alcoholic liver cirrhosis Explain the pharmacokinetics of drugs in liver disease Largest organ in the body Weight ~ 1.5kg Located under the diaphragm Capable or regeneration Blood enters via hepatic artery and portal vein Maintains Homeostasis of Body Regenerate after disease Liver disease affects kinetics of many drugs Ascites, encephalopathy and oesophageal varices ~ Chronic Liver Disease Detoxification Bile Secretion Metabolism Storage Synthesis of Plasma Proteins Acute Self limiting episode E.g paracetamol o/d ; viral infections Chronic Permanent structural changes Long term damage to the liver E.g alcoholic cirrhosis Imaging Techniques Liver Biopsy Liver Function Tests Liver Enzymes Inexpensive Cannot be used independently to make a diagnosis Monitoring progression Monitoring response Bile : Bile Salts Bile Pigments Cholesterol HaemBilirubin Excreted in bile Secreted by Liver Sign of liver disease Due to bilirubin Clinically apparent : >35micromol/l Hepatocellular damage; cholestasis; haemolysis Yellowing of skin and iris ALT more liver specific Released into plasma in hepatocellular damage Indicates liver blockage Released in large amounts in blockage GGT Long half life Good indicator of extent Albumin is synthesised in the liver No/little reduction in acute liver disease Synthesis of prothrombin and other clotting factors Increased prothrombin time Deficiency of vitamin K Early sign Symptoms: Fatigue Weight Loss Pruritus Bleeding from gums Signs Failure of Liver to carry out normal function Finger clubbing Spider naevi Palmer erythema White nails Easy bruising Enlarged liver Increased pressure in portal venous system Collateral veins develop Contributes to ascites and encephalopathy Propranolol Swollen abdomen Accumulation of fluid Reduction in serum albumin Portal hypertension Decrease in aldosterone metabolism Cirrhotic liver unable to metabolise oestrogen Males : gynaecomastia Females: reduction in fertility Cause is unclear ; occurs with significant liver dysfunction Neurotoxic substance such as ammonia brain Ammonia increases the permeability of BBB Altered mental state, asterixis Potential of full reversibility Commonest cause of cirrhosis Induction of inflammatory activity Process is generally reversible STOP DRINKING Delirium Tremens Diazepam IV thiamine Vitamin supplements Pruritus is common and distressing Due to deposition of bile salts within the skin Management depends on severity Antihistamines Ursodeoxycholic acid Anion exchange resins Clotting abnormalities Phytomenadione 10mg daily for 3 days Avoid NSAIDs and anticoagulants Aim: Mobilise the excess fluid by reducing sodium intake Increase renal excretion so that ~0.5kg of body weight is lost per day Diuretics ~ Spironolactone, Furosemide Paracentesis Aim : Reduce amount of ammonia in the circulatory system Protein restriction Lactulose ~ broken down by GI bacteria to form lactic, acetic and formic acids Acidifies colonic contentsionisation of nitrogenous products within the bowel Antibiotics ~ metronidazole and neomycin Upper GI bleeding Aim~ stop or slow down blood loss, treat hypovolemic shock, prevent recurrent bleeding Terlipressin ~ lowers portal venous pressure Balloon Tamponade ~ compresses bleeding varices HEPATIC BLOOD FLOW Reduced Increase in systemic bioavailability of oral drugs which undergo 1st pass High extraction drug E.g propranolol, morphine Used between 10% and 50% PORTOSYSTEMIC SHUNTING 60% of blood supply diverted Increased bioavailabilty REDUCED HEPATIC CELL MASS Severe liver disease little as 30% capacity Consider drugs metabolised by the liver REDUCTION IN PROTEIN BINDING Low serum albumin Important for drugs highly protein bound E.g phenytoin, warfarin Drug free concentration will increase More sensitive to sedative drugs Masking encephalopathy NSAIDS, warfarin aspirin to be avoided