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The liver Lec.8 Bioc. 416 ` The liver is a metabolically active organ responsible for many vital life functions. The primary functions of the liver are: • Bile production and excretion • Excretion of bilirubin, cholesterol, hormones, and drugs • Metabolism of fats, proteins, and carbohydrates • Enzyme activation • Storage of glycogen, vitamins, and minerals • Synthesis of plasma proteins, such as albumin, and clotting factors • Blood detoxification and purification The location of the liver Places of the metabolic activity in the liver - The liver is composed of hepatocyte (parenchymal cell) and non-parenchymal cells, such as kuppfer cell, sinusoidal endothelial cell, stellate cell Bilirubin metabolism • Bilirubin is derived mainly from haem moiety of haemoglobin molecules. • Mainly produce from the old RBC’s • Iron in haem is reutilized and the tetrapyrrole ring degraded to bilirubin • Myoglobin bilirubin • Cytochromes bilirubin • Unconjugated bilirubin(not water soluble) • It is transported in the bloodstream bound to albumin). • In the liver (hepatocyte) bilirubin is transported to the smooth endoplasmic reticulum. • It extracted through the bile ducts to the gut. • Then bilirubin is converted to urobilinogen. • Urobilinogen is oxidized to stercobilin which extract in the stool. • Unconjugated bilirubin (95%) normally present in the plasma. • In health bilirubin is not detectable in urine. • Jaundice (yellow discoloration of tissues due to bilirubin deposition) is a frequent feature or liver disease. • Clinically detecting more than 50µmol/L in plasma bilirubin that means Jaundice Biochemical assessment of liver function Bilirubin • Unconjugated hyperbilirubinaemia: - In the absence of liver disease it is due to haemolysis or Gilbert’s syndrome. - In haemolysis increased production of bilirubin.(exceed the capacity of liver to remove and conjugate pigment) • Conjugated hyperbilirubinaemia: -Due to leakage of bilirubin from hepatocytes or biliary system into the bloodstream. - Water soluble Conjugated bilirubin is excreted in the urine deep orange brown color. - Complete biliary obstruction No bilirubin reaches the gut No stercobilin and the stool are pale in color. Plasma enzymes • • • • The following enzymes are not specific indicators of liver diseases. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT)* Alkaline phosphatase (ALP) Gama -glutamyl trancferase (GGT) • ↑ aminotransferase activities reflect cell damage. • In colestasis(lack of bile flow) plasma ALP activity ↑ • ↑ in plasma activity of aminotransferase and ALP associate liver diseases Plasma proteins • Albumin is synthesized in the liver. • Its concentration in the plasma reflects the functional capacity of the organ. • Plasma albumin conc. ↓ in chronic liver diseases. • Its conc. is normal in early stages of acute hepatitis due to its half life ~ (20 days) • Prothrombin, or factor II, is one of several clotting factors produced by the liver. Adequate amounts of vitamin K are needed to produce prothrombin. • Prothrombin time (PT) is a blood test that measures how long it takes blood to clot. • The prothrombin time is a test of plasma clotting activity. • It reflects the activity of vit. k dependent clotting factors. • ↑ in prothrombin time i.e. acute liver disease. • Prolonged prothrombin time may also vit k deficiency. Detecting of some liver diseases: • Chronic liver disease lead to: ↑ immunoglobulins, ↑ in plasma total protein • In alcoholic liver disease ↑ plasma IgA. • In autoimmune hepatits ↑ IgG • In biliary cirrhosis ↑ IgM • Viral infection detected by measuring viral antigen and antibodies. Non-biochemical investigation of hepatobiliary disease • Ultrasound examination (gallstones) • Cholangiography (biliary system) • Endoscopic retrograde Cholangiography for hepatic tumours • CT and MRI demonstrate space- eccupying lesions.