1 CLINICAL CHEMISTRY-2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE ONE Dr. Essam H. Aljiffri

2  Introduction  Normal hepatic function Carbohydrate metabolism Amino acid and protein metabolism Lipid metabolism Bile acid metabolism Conjugation and detoxification

3 Assessment of hepatic function Bilirubin metabolism Jaundice Neonatal jaundice Congenital defects in bilirubin transport Serum enzymes in liver disease Plasma proteins in liver disease

4 Liver diseases Acute viral hepatitis Chronic viral hepatitis Hepatic cirrhosis Hepatocellular and acute- (fulminant) hepatic failure Hepatic malignancy Toxic liver damage

5  Gallstones  Investigation of liver disease  Case histories Case 1 Case 2 Case 3

6 Introduction The liver plays a key role in the intermediary metabolism of carbohydrates and fats. The major organ of detoxification and excretion of lipid-soluble substances, including the major metabolite of haem metabolism, bilirubin.

7 Introduction Other roles include the synthesis of plasma proteins which have a variety of functions. Bile acids, necessary for fat digestion and absorption, are also synthesized and excreted by the liver.

8 Structure of the Liver - The liver contains two major cell types, hepatocytes or parenchymal cells which comprise about 60% of the liver, and Kupffer cells which form part of the reticuendothelial network and comprise approximately 30% of the liver mass.

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10 Normal Hepatic Function

11 Normal Hepatic Function -Carbohydrate Metabolism Hepatic glucose output maintains blood sugar levels between meals, the principal sources of glucose being hepatic glycogen (glycogenolysis) and gluconeogenesis (from lactate, alanine and glycerol). The liver also converts galactose and fructose to glucose.

12 Normal Hepatic Function Amino Acid Metabolism Amino acids derived from the diet and the breakdown of tissue proteins are transported to the liver. Some are transaminated or deaminated to keto- acids, while others are metabolized to urea and ammonia.

13 Normal Hepatic Function Amino Acid Metabolism The liver also synthesizes most proteins found in plasma, except the immunoglobulins which are produced by lymphoid tissue.

14 Proteins measured in the investigation of disease

15 Normal Hepatic Function Lipid Metabolism The liver plays an active role in lipid metabolism, it removes chylomicron remnants from the circulation and synthesizes very-low-density lipoproteins (VLDL). Intermediate-density lipoprotein (IDL) is converted to low-density lipoprotein (LDL) by hepatic lipase and there is a high density of LDL receptors on hepatocytes

16 Normal Hepatic Function Lipid Metabolism Precursor particles of HDL are synthesized in the liver, as is lecithin cholesterol acyl transferase (LCAT), the enzyme which converts precursor to functional HDL particles. Further hepatic roles in lipid metabolism include the production of ketone bodies from non-esterified fatty acids (NEFA), cholesterol excretion into bile and hydroxylation of vitamin D to form 25- hydroxycholecalciferol.

17 Normal Hepatic Function Bile Acid Metabolism The primary bile acids are cholic acid and chenodeoxycholic acid which are synthesized only in the liver, from cholesterol. They are secreted in bile and most are reabsorbed through enterohepatic circulation, hepatic synthesis of bile acids being regulated by the amount returning to the liver.

18 Normal Hepatic Function Bile Acid Metabolism Gut bacteria dehydroxylate the primary bile acids producing the secondary acids, deoxycholic and lithocholic acids. Deoxycholic acid is reabasorbed and enters the enterohepatic circulation, while most lithocholic acid is excreted in the stools.

19 Bile Acid Metabolism

20 Normal Hepatic Function Conjugation and Detoxification Bilirubin conjugation and excretion, and other substances metabolized and excreted by the liver include steroid hormones and drugs.