Liver Enzymes

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The liver is the largest internal organ. It is incredibly functionally complex. It carries out more than 500 different functions that include detoxification, protein synthesis and chemical synthesis to aid in digestion. Some of the livers main functions will be talked about. Bile produced by the liver aids in digestion in the small intestine. It breaks down and absorbs fats, cholesterol, and occasionally some vitamins. Bile is produced by the liver and is stored in the gallbladder. The liver also absorbs and metabolizes bilirubin. Bilirubin is caused by the breakdown of hemoglobin in red cells. This can either be extravascular or intravascular hemolysis and can either be normal breakdown as red cells only live for 120 days before being recycled or it can be not normal. The iron that is released by the bilirubin is stored in the liver or the bone marrow that is used to make new red cells. Bilirubin is metabolized to its direct conjugated form where it is excreted by the urine and feces. The liver produces clotting factors. Vitamin K is necessary for some clotting factors to be produced and in order for vitamin K to be absorbed from the diet the liver needs to produce bile. Without the bile clotting factors would not be produced. The liver aids in filtering the blood. It filters and removes different waste material produced from the body as well as exogenous compounds like alcohol and other drugs. The liver also has a immunological function in that it contains Kupffer cells. These Kupffer cells are the macrophages of the liver and are part of the mononuclear phagocyte system that destroy any foreign antigen that enters the liver. The liver produces albumin which is arguably the most important protein in the body. Albumin is used as a transport protein and maintains colloid pressure in the blood vessels. Angiotensinogen is produced by the liver that is used in the angiotensinogen-Renin system in the kidneys that raises blood pressure by vasoconstriction.

Regeneration is a unique feature of the liver. Its important to the body is unmatched and it has evolved the ability of regeneration. Regeneration is the ability for the organ to regrow rapidly as long as it is kept healthy. During this process of regeneration the function of the liver is not compromised. If needed there are a number of compounds that can aid in the regeneration process like hepatocyte growth factor, insulin, epidermal growth factor, IL-6, and even norepinephrine.

Analysis of bilirubin is based on the reaction of bilirubin with a diazotized sulfanilic acid. Three fractions of bilirubin is measured. Conjugated, unconjugated, and delta bilirubin. Delta bilirubin is bilirubin bound to albumin. A fasting sample is preferred and hemolyzed samples should be avoided. Bilirubin is sensitive to light so care should be taken to shield the sample from the light.

Liver enzymes are relatively nonspecific indicators that can indicate tissue destruction in several organs. Alkaline phosphatase is a group of isoenzymes that are found on the membranes of cells in almost every tissue. Alkaline phosphatase can become elevated in many different conditions including bone diseases, puberty, and even in late pregnancy. One important feature of alkaline phosphatase is that the isoenzyme found in bone is the most heat labile. Differentiation in the laboratory includes heating the sample and then remeasuring the alkaline phosphatase and measuring the difference.

Gamma-glutamyltransferase (GGT) is a membrane enzyme that is important in glutathione metabolism. It transfers glutamate to the amino acid peptide chain. GGT is among one of the first enzymes to become elevated in acute liver diseases such as hepatitis. Its important to note that GGT is normal in patients with bone diseases making it one of the most clinically specific of all the liver enzymes. Lactate dehydrogenase is a cytosolic enzyme that interconverts pyruvate and lactate. There are five isoenzymes. Isoenzymes 4 and 5 are increased in viral or toxic hepatitis, biliary obstructions and cirrhosis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) convert aspartate and alanine to oxaloacetate and pyruvate respectively. ALT is very specific for liver pathology. AST is found in liver tissues, but also present in heart and muscle tissue. The AST/ALT ratio is an important factor to look at. A ratio less than 1.0 indicates viral hepatitis. This is an increase in ALT greater than the increase in AST. An AST/ALT ratio greater than 1.0 usually means that the ALT is elevated to a lesser degree than the AST and this can be found in cirrhosis, bile duct obstruction, or metastatic cancer of the liver.

-Caleb

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