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Dr Gihan Gawish Liver - Anatomy and Physiology Largest organ in the body Three basic functions • Metabolic • Secretory • Vascular Major function • Excretion of waste products from bloodstream by excretion into bile Dr Gihan Gawish Liver - Anatomy and Physiology Location • Upper right quadrant • Four lobes made up of hepatocytes • phagocytic cells Blood supply • One major vein - portal vein • One major artery - hepatic Dr Gihan Gawish Liver - Anatomy and Physiology Functions of liver • Blood glucose concentration • Protein metabolism • Fat metabolism • Storage functions • Drug metabolism • Ammonia conversion Dr Gihan Gawish Metabolic Profile of the Liver The primary function of the liver is to regulate the metabolism. It metabolizes the intake of carbohydrates, fats, and proteins. It accomplishes this function by working closely with other systems such as lymphatic system, circulatory system, as and endocrine system. In order for the liver to metabolize the fats, carbohydrates, and proteins, it must be healthy and free of any diseases. Dr Gihan Gawish Bile Production Liver produces and secretes a product called bile. This is what makes it possible for metabolize the intake of fats, proteins, and carbohydrates. This fluid is a very important presence in the body due to the fact that it aids in the elimination of contaminants in the body, such as drugs. The bile system is also responsible for re-circulating red blood cells. Dr Gihan Gawish BILIRUBIN PRODUCTION Heme proteins myoglobin, cytochromes (20 to 25%) Hemoglobin (70 to 80%) Erythroid cells Heme ferritin apoferritin (250 to 400 mg/day) 3 [O] Heme oxygenase 3+ Fe + CO Biliverdin NADPH + H+ Biliverdin reductase NADP+ Bilirubin Dr Gihan Gawish albumin indirect unconjugated pre-hepatic BILIRUBIN PROCESSING albumin-Bilirubin albumin hepatocyte ligandin ligandin-Bilirubin 2 UDP-glucuronate ER UDP-Glucuronyl transferase 2 UDP Bilirubin diglucuronide bile (gall bladder) Dr Gihan Gawish direct conjugated post-hepatic BILIRUBIN EXCRETION Bilirubin diglucuronide 2 glucuronate liver Bacterial enzyme Intrahepatic urobilinogen cycle Bilirubin 8H Bacterial enzyme kidneys intestines Urobilinogen Urobilin urine Stercobilin feces kidneys Bacterial enzymes Stercobilinogen Dr Gihan Gawish DEGRADATION OF HEME TO BILIRUBIN 75% is derived from RBCs P450 cytochrome In normal adults this results in a daily load of 250-300 mg of bilirubin Normal plasma concentrations are less then 1 mg/dL “unconjugated” bilirubin Hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion NORMAL BILIRUBIN METABOLISM Uptake of bilirubin by the liver is mediated by a carrier protein (receptor) Uptake may be competitively inhibited by other organic anions On the smooth ER, bilirubin is conjugated with glucoronic acid, xylose, or ribose Glucoronic acid is the major conjugate catalyzed by UDP glucuronyl tranferase “Conjugated” bilirubin is water soluble and is secreted by the hepatocytes into the biliary canaliculi Converted to stercobilinogen (urobilinogen) (colorless) by bacteria in the gut Oxidized to stercobilin which is colored Excreted in feces Some stercobilin may be re-adsorbed by the gut and re-excreted by either the liver or kidney Failure to Produce Bile It is possible for a type of liver disease to cause the liver to stop the secretion of bile. When this happens, the liver loses the capability to metabolize the fats, carbohydrate, and proteins. The only way fats can be absorbed into your blood system is if bile is present. This is why it would be impossible for the body to absorb the fat-soluble vitamins without bile. Dr Gihan Gawish HYPERBILIRUBINEMIA Increased plasma concentrations of bilirubin (> 3 mg/dL) occurs when there is an imbalance between its production and excretion Recognized clinically as jaundice Dr Gihan Gawish Diagnoses of Jaundice Red Blood Cell System Another important function the liver performs is that it cleanses the body from the damaged, or old, red blood cells. The liver will also store iron in your body, as well as breakdown hemoglobin. This is the reason why many people who suffer from liver disease may suffer from anemia. Dr Gihan Gawish Hepatitis Inflammation of the liver Viral hepatitis is the most common type A, B, C, D and E Noninfectious hepatitis may be caused by drugs and chemicals Dr Gihan Gawish Hepatitis – Clinical Manifestations Preicteric or Prodromal phase • Precedes jaundice • Lasts 1 – 21 days • Maximal infectivity for hepatitis A • Symptoms Anorexia, right upper quadrant pain, constipation or diarrhea, malaise, fever, headache, arthralgias, weight loss Dr Gihan Gawish Lab Tests Elevated Alkaline phosphatase Decreased albumin Elevated with bone and liver Increased prothrombin Elevated SGOT/AST Blood ammonia level disorders Elevated SGPT/ALT Elevated serum globulin time • Increased due to decreased metabolism of ammonia to urea by the liver Elevated LDH Dr Gihan Gawish