1. Dr Gihan Gawish

2. 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

3. 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

4. Liver - Anatomy and Physiology Functions of liver Blood glucose concentration Protein metabolism Fat metabolism Storage functions Drug metabolism Ammonia conversion Dr Gihan Gawish

5. 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

6. 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

7. BILIRUBIN PRODUCTION Heme (250 to 400 mg/day) Heme oxygenase Biliverdin reductase Hemoglobin (70 to 80%) Erythroid cellsHeme proteins myoglobin, cytochromes (20 to 25%) Biliverdin Bilirubin NADPH + H + NADP + 3 [O] Fe 3+ + CO apoferritinferritin indirect unconjugated pre-hepatic albumin Dr Gihan Gawish

8. BILIRUBIN PROCESSING albumin-Bilirubin ligandin Bilirubin diglucuronide ER hepatocyte UDP-Glucuronyl transferase albumin ligandin-Bilirubin bile (gall bladder) direct conjugated post-hepatic 2 UDP-glucuronate 2 UDP

9. Dr Gihan Gawish BILIRUBIN EXCRETION Bilirubin diglucuronide Intrahepatic urobilinogen cycle Stercobilinogen Bacterial enzymes Bilirubin Bacterial enzyme2 glucuronate Bacterial enzyme Urobilinogen 8H liver Urobilin kidneys urine Stercobilinfeces kidneys intestines

10. DEGRADATION OF HEME TO BILIRUBIN P 450 cytochrome  75% is derived from RBCs  In normal adults this results in a daily load of 250-300 mg of bilirubin  Normal plasma concentrations are less then 1 mg/dL  Hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion “unconjugated” bilirubin

11. 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

12. Dr Gihan Gawish 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.

13. 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

15. Diagnoses of Jaundice

16. 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

17. 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

18. 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

19. Lab Tests  Elevated Alkaline phosphatase  Elevated with bone and liver disorders  Elevated SGOT/AST  Elevated SGPT/ALT  Elevated serum globulin  Elevated LDH  Decreased albumin  Increased prothrombin time  Blood ammonia level Increased due to decreased metabolism of ammonia to urea by the liver Dr Gihan Gawish