Hepatic Failure,Tao Wang, PH.D., Associated professor Pathophysiology department Anhui Medical University,2,Introduction and Conception Etiology Hepatic insufficiency Hepatic failure Hepatic encephalopathy (focal point) Hepatorenal syndrome,Hepatic Failure,3,PART I Introduction and Conception,Liver,The largest and most metabolically complex organ,1. The liver,4,2. The liver anatomy,The liver is divided into 2 main lobes, each consisting of many lobules.,These lobules are surrounded by branches of the hepatic artery, which supplies the liver with oxygenated blood.,The portal vein supplies nutrient-rich blood.,Deoxygenated blood from the liver drains into the hepatic veins.,A network of ducts carries bile from the liver to the gallbladder and the small intestine,5,3. The functions of the liver, Substance metabolism, immune function, Hemostasis regulation, production and secretion of bile, Bio-transformation (detoxification),6,4. Hepatic insufficiency,Severe damage in liver cells will result in serious condition, manifesting as jaundice, bleeding, infection, renal dysfunction or encephalopathy, termed all together these syndromes of hepatic insufficiency.,Acute Hepatic insufficiency,Chronic Hepatic insufficiency,7,5. Hepatic failure,Terminal stage of hepatic insufficiency,Hepatic encephalopathy (focal point) Hepatorenal syndrome,Primary clinical manifestations,8,PART II Etiology,1. Biological,2. Physical and chemical,3. Inherited conditions,4. Immune,5. Nutritional causes,Hepatitis virus (such as HBV), bacteria, parasites, etc.,Industrial toxins, some drugs, alcohol, etc.,Idiopathic hemochromatosis, Wilsons disease, etc.,Extent of inflammation and necrosis,9,PART III Hepatic insufficiency,Liver,Various etiology causes,hepatocytes,Non-parenchymal cells,damage,damage,Kupffer cells, hepatic satellite cells, lipocytes, liver associated lymphocytes, hepatic sinusoid endothelial cells,Hepatic insufficiency,10,Syndromes of Hepatic insufficiency,1. Metabolic disorders,2. Water and electrolytes imbalance,3. Disorders in production of bile salts and elimination of bilirubin,4. Impaired kupffer cells function,Carbohydrate Metabolic Disorders Lipid Metabolic Disorders Protein Metabolic Disorders,Hepatic Ascites Electrolytic Metabolic Disorders,11,1. Metabolic disorders,1) Carbohydrate Metabolic Disorders,Carbohydrate Metabolism of liver,To maintain concentrations of glucose in blood within a narrow, normal range.,insulin,A hormone produced by the pancreas that regulates glucose levels in the blood. It is normally produced in response to raised glucose levels following a meal and promotes glucose absorption into the liver and muscle cells (where it is converted into energy).,Excess glucose entering the blood after a meal is rapidly taken up by the liver and sequestered as the large polymer, glycogen,glycogenesis,12,glyconeogenesis,glycogenolysis,when blood concentrations of glucose begin to decline, the liver activates other pathways which lead to depolymerization of glycogen,When hepatic glycogen reserves become exhaused, as occurs when an animal has not eaten for several hours, the hepatocytes , recognize the problem and activate additional groups of enzymes that begin synthesizing glucose out of such things as amino acids and non-hexose carbohydrates.,13,Severe liver disease,Hypoglycemia,Hyperglycemia,Caused by a decrease in functional hepatocyte mass.,When glucogen reserves are depleted: gluconeogenensis impared; inactivation of insulin weaken,Caused by portal-to-systemic shunting,Decrease the postprandial extraction of glucose from protal blood,Some patients may suffer abnormal glucose tolerance,14,1. Metabolic disorders,2) Lipid Metabolic Disorders,Liver is the center of lipid metabolism,Manufacturing 80% of the cholesterol,Synthesizing, storing and exporting triglycerides,Assembling, secreting and taking up lipoprotein particle, such as VLDL, LDL, and HDL.,Severe liver disease,Disturbance of lipid metabolism,Syndromes of fat accumulation (fatty liver),In certain chronic liver disease,Primary biliary cirrhosis,Destruction of bile ducts,Bile flow decrease,Decrease lipid clearance via bile,hyperlipidemia,These patients often develop xanthomas accumulation of cholesterol,16,1. Metabolic disorders,3) Protein Metabolic Disorders,The liver manufactures and secretes many of the protein found in plasma,albumin,Some clotting factors,Some binding proteins,Some hormone precursors,To maintain plasma oncotic pressure,To regulate hemostasis,Steroid and thyroid hormone- binding protein to regulate metabolism,angiotensinogen to regulate blood pressure Insulin like growth factor-1 to regulate growth,17,Other roles of the liver in protein metabolism,Processes of oxidative deamination and transamination,The urea cycle allows nitrogen to be excreted in the form of urea,Severe liver disease,Disturbance of protein metabolism,Decreased conversion of ammonia to urea,Plasma proteins decrease,Elevated ammoni