1. Enzymes in Clinical DiagnosisBy
Prof. Dr. Hosny Fouad

2. 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.

3. 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.

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

5. 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.

6. 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.

7. 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

8. 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

9. 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

10. 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

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

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

13. 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

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

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

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

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

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

19. 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.

20. 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.

21. 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).

22. Study Questions
Talk about newest markers for myocardial infarction.