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HEPATIC FAILURE DR.M.H.Mumtaz Topics • Anatomy • Histology • Liver Functions • Liver Function Tests • Liver Failure • Management in ICU ANATOMY Wt . 1.8 - 2 Kg Blood supply = 25 % CO Topography = 2 Lobes subdivided into lobules Rt Lobe =have 2 suspended Lobes Caudate Lobe quadrate Lobe Liver Blood Flow = 1100 -1800 ml / min 25 % CO Hepatic artery = 30 – 40 % = O2 supply = 40 - 55 % = Saturation = 98 % = flow = sphincteric mechanism Total Liver Blood Flow Hepatic Portal vein = 70 % B. flow =50 - 60 % O2 supply = po2 = 50 mm Hg = blood velocity = 9 cm/sec Hepatic arterio-venous reciprocity Liver Blood Flow Blood Flow 1. 2. 3. 4. 5. PCO2 Hepatitis Supine Posture Food Drugs • Beta stimulants • Phenobarbitone • Enzyme inducers Blood Flow 1. 2. 3. 4. 5. 6. IPPV + PEEP Surgery PCO2 , Hypoxia Upright posture Cirrhosis Drugs • alpha stimulants • Beta blockers • Ganglion blockers • Ranitidine • Pitressin • Anaesthetics Histology zone 1 - receives blood with zone 2 - intermediate zone 3 - receives blood with spo2 spo2 Important Liver Functions A. Carbohydrate Metabolism 1. Glycogen synthesis 2. Glycogenolysis 3. Gluconeogenesis Important Liver Functions B. Lipid Metabolism 1. 2. 3. Synthesis of Lipoproteins • Phospholipids • Cholesterol • Endogenous Triglycerides Excretion of breakdown products of cholesterol Ketone synthesis Important Liver Functions C. D. E. F. G. H. Protein Synthesis Vitamin .D metabolism Vitamin A, B, B12. stored in liver Iron store Excretion & Detoxication Reticuloendothelial function Liver Function Tests A. Static Tests B. Dynamic Tests Liver Function (Static )Tests Liver cell damage 1. 2. Liver cell dysfunction 1. 2. 3. Serum Proteins Coagulation factors - PT, APTT Serum Bilirubin Biliary Tract obstruction 1. 2. 3. Transaminases Lactate dehydrogenase Alkaline Phosphatase Gama-glutamyl Transferase Bilirubin Tests Indicating aetiology ROLE OF VIT K LIVER ----------VIT. K WARFARIN -------gamma glutamyl carboxylase ADDS carboxyl group to glutamic acid residue ON Factors, 2nd,7th,9th & 10th. Proteins S,C,&Z ( activation) PROTHROMBIN TIME(PT) HEPARINES ANTITHROMBINS(SERINE PROTEASE INHIBITOR) DEGRADE THROMBIN,F9a, F10a,F12a ( serine proteins) HEPARIN increase adhesion of antithrombins to factors Functional ( Dynamic) Tests 1. Impaired Lactate clearance (lactate level) 2. Clearance of organic substances • 3. Anionic dye – Indocyanine green (ICG) Formation of metabolites • Monoethylglycinxylidid from lidocain (MEGX) Topology of Liver Damage 1. Diffuse Parenchymal damage 2. Periportal damage 3. Pericentral damage Response to injury 1. 2. 3. 4. 5. 6. Necrosis Degeneration Steatosis Regeneration Inflammation Fibrosis ETIOLOGICAL FACTORS 1. NON . INFECTIOUS • • • • 2. Alcohol Drug related Reyes’ Syndrome Pregnancy INFECTIOUS DAMAGE • • • • • Fungal Protozoal Malaria Parasites Liver abscess Aetiology 3. Viral Infections a. Systemic Viral infection • Infectious mononucleosis • cytomegalovirus • Herpes virus • In children ( rubella, adenovirus enterovirus) Aetiology, 3. Viral infections b. Hepatotropic Viruses Hepatitis A virus (HAV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) Delta Hepatitis virus (HDV) Hepatitis E virus ( HEV ) Others – ( F,G…. ? ) 4. Inborn Errors of metabolism • Primary Haemochromatosis • Wilsons’ Disease • Alpha – 1 – Antitrypsin deficiency 5. Tumours • Benign • Malignant LIVER FAILURE MANIFESTATIONS a. Hepatic Manifestations • • b. Jaundice Coagulopathy Extrahepatic Manifestations • • • Encephalopathy Hepato-renal Syndrome Susceptibility to infections MANAGEMENT IN ICU General • • • • • • • Intensive Care Enteral nutrition Stress ulcer prophylaxis Glucose Homeostasis Antibiotic prophylaxis / SDD Control Intracranial Hypertension Albumen Vasopressor for HRS MANAGEMENT Specific Therapy- Antidote Monitoring by. PDR – ICG Extracorporeal Liver Support Transplant Hepatic Encephalopathy Toxic Metabolites ammonia,glutamine ^ ICP Ippv,Mannitol,Hypothermia Hypertonic saline Vasopressors--caution Hepatorenal Syndrome 1, Marked renal vasoconstriction RBF decreased GFR decreased 2,Absence of histological changes 3,Preserved tubular renal function HRS Pathogenesis Portal hypertension/Liver failure 1, Increased level of ; NO, CO. 2, Spanchnic arterial vasodilation 3,Low effective circulating volume 4, Activation of systemic endogenous vasoconstrictors 5, Svere renal vasoconstriction HRS Diagnostic criteria Major criteria CHF +Portal hypertension Low GFR Absence-shock,infection,drug dehydration No improovement after,removal of diuretics, pv expansion Proteinurea <500mg/dl HRS Diagnostic criteria Minor criteria Urine volume<500ml/d Urine sod.excretion<10mmol/l urine osmolality/plasma osm>1 No finding in urine sediment Natremia <130mmol/l All major criteria +a few minor to support HRS TYPES Type 1, Type 2 Rapidly progressive---RF with out rapidly progressive Acute r.failure-------------Refractory ascites HRS Precipitating events spontaneus bacterial peritonitis paracentesis without plasma expan GIT haemorrhage Severe acute alcoholic hepatitis Unknown HRS THERAPY TIPS (transjugular intravenous portosystamic s.) + Albumin,vasoconstrictors MARS (molecular adsorbant recycling system) New therapies -HRS Albumin+trlipressin Albumin+Midodrine+octreotide Albumin+Noradrenaline Extracorporeal Liver Support