Clinical usage of enzymes

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Presentation transcript:

Clinical usage of enzymes Diagnosis of myocardial infarction (MI) Diagnosis of bone disease Diagnosis of muscle disorders Diagnosis of acute pancreatitis Diagnosis of metastasizing cancer of the prostate

Diagnosis of myocardial infarction (MI) Myocardial infarct is a necrotic area in the heart caused by a deficient blood flow to that area as a result of a clot in the coronary vessel and/or narrowing of the vessel lumen. When the cardiac cells in the necrotic area die, their intracellular enzymes diffuse out of the cell into tissue fluid and end up in plasma. The enzymes tests that help in the diagnosis of MI are: Creatine kinase (CK), aspartate aminotransferase(AST or GOT), lactate dehydrogenase (LD or LDH), isoenzyme CK-MB, and the isoenzyme of LD.

Aspartate aminotransferase (AST) AST is found in practically every tissue of the body, including red blood cells. It is in high concentration in cardiac muscle and liver, intermediate in skeletal muscle and kidney, and in much lower concentration in other tissues. AST concentration increased shortly after occurrence of MI.

Increased activity of AST The serum activity of AST increased after MI, in liver disorders, in trauma to or in diseases affecting skeletal muscles, after renal infarct, and in various hemolytic conditions. The serum AST activity begins to rise about 6 to12 hours after MI and return back to normal by 4-6 days after infarct.

Lactate dehydrogenase (LD or LDH) Lactate dehydrogenase reversibly catalyzes the oxidation of lactate to pyruvate by transferring hydrogen from lactate to cofactor, NAD. LD is distributed widely in tissues and in high concentration in liver, cardiac muscles, kidney, skeletal muscles, erythrocytes, and other tissues. The LD activity in serum does not rise as much as CK or AST after MI but it does remain elevated for much longer period of time 7-10 days.

Increased activity of LD In myocardial infarction. It may remain elevated for 7-10 days. In liver disease, but other test more sensitive (AST and ALT). Muscle trauma. Renal infarct. Hemolytic diseases. Pernicious anemia.

LD isoenzymes The LD enzyme is composed of 4 subunits. There are different polypeptide chains : M type of skeletal muscle and H type from cardiac muscle. 5 different isoenzymes are possible from this combination: HHHH (LD1from heart muscle, RBC, kidney). MHHH (LD2 also in heart). MMHH (LD3 in lung and other tissues). MMMH (LD4 in many tissues). MMMM (LD5 primary in skeletal muscle and liver).

The serum LD isoenzyme composition of normal individual as % of total and as units

Diagnosis of bone disease Alkaline phosphatase(ALP) Alkaline phosphatase ALP are group of enzymes that split off a terminal phosphate group from organic phosphate ester in alkaline solution(pH 10). ALP is widely distributed in the body and is present in high concentration in bone (osteoblasts, the cells of growing bone), intestinal mucosa, and renal tubule cells.

Alkaline phosphatase(ALP) 20-105u/L Increased concentration Decreased concentration In all bone disorders Paget's disease Osteoplastic tumors with metastasis Hyperparathyroidism (Ca,P) Rickets In liver disease(biliary tree) During trimester of pregnancy In rare congenital defect Hypophosphatasemia In dwarfs. Hypothyroidism In pernicious anemia

Diagnosis of muscle disorders Aldolase The 3 serum enzymes used most frequently for this purpose, in order of their general usefulness, are CK,AST, Aldolase (ALD). ALD convert fructose 1.6 diphosphate into 2 triose phosphate esters, dihydroxy acetone phosphate and glyceraldehyde 3 phosphate. Raised serum ALD level are detectable in all neurogenic muscle atrophy and temporarily raised following muscle trauma, surgery when muscles are cut, and intramuscular injections.

Diagnosis of acute pancreatitis It is difficult to establish the diagnosis of acute pancreatitis without the assistance of lab. tests. The patient usually complains of intense pain in the upper abdomen that could be caused by several different disorders The 2 most commonly tests used for diagnostic purposes are serum amylase and serum lipase

Serum amylase 0.8-3u/L in human, the amylases are enzymes that randomly split the 1,4-glycosidic bonds on the starch chain. Amylases are secreted by the salivary and pancreatic glands into their respective juices, which enter the gastrointestinal tract. The amylases that is normally present in serum is derived from both pancreas and salivary glands. The activity of serum amylase rises following obstruction to flow from either the salivary or pancreatic glands. Acute pancreatitis is caused by: Blockage of the pancreatic ducts. Injury to pancreatic tissue by toxin. Inflammation.(mumps) Trauma. Impaired blood flow to pancreas.

Serum lipase Lipase is an enzyme that hydrolyzes emulsified triglycerides. The pancreas is the principal organ for the production of lipase, which is secreted in pancreatic juice with other digestive enzymes. The serum activity lipase is rapidly elevated in acute pancreatitis, but remains elevated for a longer period of time than amylase.

Serum lipase 28-200u/L Serum lipase activity is elevated in acute pancreatitis and may reach 10-40 folds. The serum lipase activity usually reaches its maximum at 72 to 96 hours after an attack of acute pancreatitis and declines more slowly than does the amylase activity.

Diagnosis of metastasizing cancer of the prostate Cancer of the prostate is common disease that primarily affects elderly men. It is difficult to diagnose in early stages because of the lack of signs and symptoms. Prostate gland is rich in acid phosphatase (ACP), which is present in lower concentration in many tissues (spleen, kidney, liver, bone, blood platelets). ACP acts optimally below pH 6.0. Normal serum has a low activity ACP but in metastasizing carcinoma of the prostate, its activity increases greatly and may rise to 3-15 fold.

Serum acid phosphatase (ACP) 0.2-1.8u/L Increased concentration Decreased concentration Metastasizing carcinoma of prostate. Bone disease (Paget's disease or female breast cancer that has metastasized to bone). After prostate massage. No clinical significance to low concentration of serum ACP