Sunday, November 11, 2012

Liver function tests (Plasma proteins)


Plasma proteins:

Since liver synthesize almost all the plasma proteins however, albumin, prealbumin, coagulation proteins and immunoglobulins are of diagnostic significance.

Albumin:

This is the major plasma protein synthesized exclusively by liver. Liver produces 12 g of albumin per day. It has half-life of 21 days. It is responsible for maintaining plasma oncotic pressure and binds several hormones, anions, drugs, fatty acids, etc. So, in liver disease albumin decreases although other conditions are also responsible for this like poor dietary intake.  

Prothrombin time and coagulation factors:

Prothrombin time measures the rate at which prothrombin is converted to thrombin in the presence of thromboplastin, calcium, fibrinogen and other coagulation factors (V, VII and IX). In turn thrombin leads to conversion of fibrinogen to fibrin. Prothrombin, V, VII, X, X require vitamin K to become active and are synthesized in liver. PT is replaced by INR. This is derived by dividing the PT of patient by that of control. Thus, normal INR is 1 (<1.2).

In liver disease there is prolonged PT. First, damaged liver cannot synthesize clotting factors. Second, since vitamin K is fat soluble vitamin, it may be deficient due to impaired fat absorption during obstructive jaundice. This is remediable by parenteral administration of vitamin K and return of INR to normal range within 18h indicates obstructive jaundice, failure to respond implies severe parenchymal disease. Since, the half-life of PT is 6h so INR measurement may be reliable indicator of liver damage.

α-Fetoprotein:

This is fetal equivalent of albumin and ceases shortly after birth. This is seen in patient with hepatocellular carcinoma.

α1-Antitrypsin

This is major α1 globulin and responsible for 90% plasma tryptic inhibitory capacity. AAT deficiency is the major cause of chronic liver disease in children.

Transferrin:

This is the major circulating iron binding protein and correlates with total iron binding capacity of plasma. In hereditary haemochromatosis the saturation is between 55% and 100% compared to reference 30-40%. It is also synthesized by liver and has short half life.

Transferrin is glycoprotein containing up to nine terminal sialic acid residues. In healthy individuals the trisialo, tetrasialo and pentasialo forms predominate. Alcohol consumption inhibits glycation of several glycoproteins, including transferrin, in alcoholics plasma transferrin often lacks up to four of these sialic acid residues resulting in asialo –and disialotransferrins, collectively termed carbohydrate deficient transferrin (CDT). CDT measurement has been proposed as a marker of excessive alcohol consumption.

Ceruloplasmin:
 
This copper containing protein in plasma has oxidase activity including ferroxidase activity essential for oxidation of ferrous to ferric form. It has single polypeptide chain with 6 copper atoms but less turnover, thus it is not copper transporter as transferrin that transports iron. It plays an important role in diagnosis of Wilson’s disease since, in this condition, it is virtually absent in plasma.

Acute phase reactants:

In response to tissue damage, there is increase in hepatic synthesis of several proteins, notable CRP, antichymotrypsin, fibrinogen and ceruloplasmin.

Immunoglobulins:

Elevated plasma level is seen during inflammatory process. Globulin = (Total protein – albumin). IgG is elevated in autoimmune hepatitis, IgM in primary biliary cirrhosis, IgA in alcoholic liver disease.

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