Enzymes in Clinical Diagnosis By Prof. Dr. Hosny Fouad

Plasma enzymes are of two types: A small group of enzymes secreted into the blood by certain cells e.g. the liver secretes zymogens (inactive form of enzymes) of blood coagulation.

A large group of enzymes are released from cells during normal cell turnover. These enzymes function intracellularly (inside cells) and have no function in the blood. In healthy individuals, the blood levels of these enzymes are constant, as the rate of release from damaged cells into blood is equal to the rate of removal of enzymes from blood.

Elevated enzyme activity in blood indicates tissue damage (due to increased release of intracellular enzymes).

A. Plasma Enzymes as diagnostic tools Diseases that cause tissue damage result in increased release of intracellular enzymes into the plasma. Determination of the level of these enzymes is used for diagnosis of heart, liver, skeletal muscle, etc. The level of these enzymes in plasma correlates with the extent of tissue damage.

The presence of increased levels of some enzymes in plasma is diagnostic to damage of a particular tissue; e.g. The enzyme alanine aminotransferase (ALT) is abundant in the liver and the appearance of elevated levels of ALT in plasma indicates damage to the liver.

Intracellular Distribution of Diagnostic Enzymes Liver Heart Pancreas Salivary Glands Bone Muscle Biliary Tract Prostate LD5 ALT AST LD1 AST CK LPS AMS ALP GGT ACP

DISORDERS DIAGNOSED BY ENZYMES 1) Cardiac Disorders. 2) Hepatic Disorders. 3) Skeletal Muscle Disorders. 4) Bone Disorders. 5) Pancreatic Disorders. 6) Salivary gland diseae (Mumps) 7) Malignancies

Cardiac Disorders: e.g. Acute Myocardial Infarction (AMI). 1) The myocardium becomes ischemic and undergoes necrosis. 2) Cellular contents are released into the circulation. Blood levels of the following enzymes increase: AST LD1 CK

2. Hepatic Disorders Hepatocellular Disorders: (1) Viral hepatitis: Hepatitis B & Hepatitis C. (2) Toxic hepatitis: caused by chemicals & Toxins (e.g aflatoxin, Asp. flavus) Increased levels of the following enzymes : ALT AST LD5

ALP GGT b) Biliary tract disorders: The plasma levels of the following enzymes increase: ALP GGT

3. Skeletal Muscle Disorders Muscle dystrophy. Muscle trauma. Muscle hypoxia. Frequent I.M Injections. The plasma levels of the following enzymes increase: CK AST

4. Bone Disorders: 1) Paget’s Bone Disease: caused by increased osteoclastic activity. 2) Rickets 3) Osteomalacia: The plasma levels of the following enzyme increase: ALP

5. Acute Pancreatitis The plasma levels of the following enzymes increase: Lipase AMS

6. Salivary Gland Inflammation: In Mumps: The levels of -Amylase (AMS) is significantly increased

7. Malignancies Plasma (Acid phosphatase) ACP levels increase in: Prostatic carcinoma. Bone metastatic carcinoma

Pancreatic carcinoma. Bile duct carcinoma. Liver metastasis. b) Plasma levels of Alkaline phosphatase (ALP) increase in: Pancreatic carcinoma. Bile duct carcinoma. Liver metastasis.

c) Plasma levels of Total Lactate dehydrogenase (LDH) increase in: Leukemia Lymphomas. Liver metastasis.

B. Isoenzymes and Heart Diseases Isoenzymes (or isozymes) are a group of enzymes that catalyze the same reaction. However, these enzymes do not have the same physical properties (as they differ in amino acid sequence). Thus, they differ in electrophoretic mobility. The plasma level of certain isozymes of the enzyme Creatine kinase (CK) level is determined in the diagnosis of myocardial infarction.

Many isoenzymes contain different subunits in various combinations. CK occurs in 3 isoenzymes, each is a dimer composed of 2 subunits (B & M): CK1 = BB, CK2 = MB and CK3 = MM, each CK isozyme shows a characteristic electrophoretic mobility.

Myocardial muscle is the only tissue that contains high level of CK2 (MB) isoenzyme. Appearance of CK2(MB) in plasma is specific for heart infarction. Following an acute myocardial infarction,CK2appears in plasma 4-8 hours following onset of chest pain (peak is reached after 24 hours).

Study Questions Talk about newest markers for myocardial infarction.