NORMAL LIVER FUNCTIONS (Health tips)

Recognition of normal liver functions is necessary to understand the manifestations that develop when liver becomes abnormal due to disease process.

SYNTHETIC FUNCTION (Health tips)  

Protein synthesis

Liver is the principal site of synthesis of all circulating proteins except gamma-globulins, which are produced in the reticuloendothelial system. Plasma contains 6-8 mg/dl of proteins, mainly in the form of albumin, globulin and fibrinogen. Liver also synthesizes complement factors, transferin, haptoglobin, caeruloplasmin, protease inhibitors (a 1-antitrypsin), and a-fetoprotein.

Albumin has half-life of 16-24 days and 10-12g is synthesized daily. Its main functions are to maintain the intravascular colloid osmotic pressure and to transfer water-insoluble substances such as bilirubin, hormone, fatty acids and drugs.

• Albumin synthesis is reduced in chronic liver disease and malnutrition. It can be lost in nephritic syndrome and in protein-losing enterpathy.
• Hypoalbuminemia results in edema.

Coagulation proteins

Liver also synthesizes all coagulation factors (other than factor VIII) such as fibrinogen, prothrombin, factors V, VII, IX, X and XII.

• Deficiency of coagulation factors results in bleeding tendency.

METABOLIC FUNCTIONS

Carbohydrate metabolism

Liver is the main source of plasma glucose as it is the main body storage site for glycogen. In the fasting state glucose is derived from glycogen breakdown of (glycogenolysis) and gluconeogenesis (formation of glucose from amino acids and fatty acids).

• Liver damage can lead to hypoglycemia.

Fat metabolism

Liver synthesizes triglycerides, cholesterol, phospholipids and lipoproteins.

Protein metabolism

In addition to its synthetic function, liver is the central organ in protein catabolism and synthesis of urea formation. Ammonia is produced by the degradation of amino acids that is converted into urea. Urea is secreted by the liver into plasma for excretion by the kidney. This is the major pathway for the elimination of nitrogenous waste.

• Ammonia level becomes high in severe liver disease that is harmful for brain and may lead to hepatic encephalopathy.

EXCRETORY FUNCTION

Liver is responsible for excretion of many substances in the bile.

Bilirubin metabolism

Bilirubin is produced mainly from the breakdown of mature in Kuffer cells of the liver in the reticuloendothelial system. Biliverdin is formed form haem after removal of iron;  this Biliverdin is reduced to form bilirubin. The bilirubin produced unconjugated and water-insoluble, and is transported to the liver attached to albumin. Bilirubin dissociates from albumin and is taken up by the hepatic cells, where it is conjugated red cells with glucuronic acid and is excreted in bile.

• In liver disease there may be obstruction to excretion of bilirubin manifesting as jaundice.

This conjugated bilirubin enters in intestine within bile, and is not absorbed because of its large molecular size in the terminal ileum. Bacterial enzymes hydrolyze the molecule, releasing free bilirubin, which is then reduced to urobilinogen. Some off this is excreted in the stools as stercobilinogen and the remainder is absorbed by the terminal ileum, passes to the liver via enterohapatic circulation and is re-excreted in bile. Urobilinogen bound to albumin enters the circulation and is excreted in the urine via kidneys.

Bile acids metabolism

Bile acids are synthesized in hepatocytes from cholesterol. They are excreted in bile and then pass into the duodenum. Bile acids are detergents, causing fat solubilization that is necessary for absorption of lipids and lipid-soluble vitamins such as vitamin A, D, E and K.

• Decreases excretion of bile salts in liver disease causes:

-          Pruritus (itching)

-          Bleeding disorder: deficiency of vitamins such as vitamin K leads to decreased formation of vitamin K dependent coagulation factors resulting in bleeding tendency.

-          Steatorrhea (fatty stool) due to fat malabsorption.

DETOXIFICATION FUNCTION

Liver plays a vital role in detoxifying nitrogenous compounds derived from intestine, as well as many hormones, drugs and chemicals.

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