1 Serum Enzymes in Disease Dr. Essam H. Aljiffri

2 Myocardial Infarction Necrosis of the myocardium leads to the release into the circulation of tissue enzymes, particularly; CK, AST and LDH (HBD), these are released from the heart and cleared from the circulation at different rates.

3 Myocardial Infarction The first to rise is CK, activities being raised within 6 h of myocardial infarction. Total CK reaches a peak at h, slightly later than the maximum activity of CK-MB isoenzyme. In uncomplicated cases, CK returns to normal in 3 days.

4 Myocardial Infarction Serum AST rises more slowly, reaching a maximum activity at about 48h and returning to normal in 4-5 days. No significant elevations in HBD are seen for the first 24 h; values reach a maximum at about 3 days and remain elevated for up to 8 days.

5

6 Myocardial Infarction CK and HBD are useful indicators of myocardial infarction, and are more specific than AST. CK from skeletal muscle may be raised following an intramuscular injection, chest compression for resuscitation or electrical defibrillation.

7 Muscle Disease Skeletal muscle is a rich source of several enzymes including CK, AST, ALT, aldolase and LDH. The measurement of total CK activity is the most widely used enzyme in the investigation of muscle damage. This being increased most frequently and showing the highest activities in diseases particularly muscular dystrophies.

8 Muscle Disease Muscular Dystrophy The muscular dystrophies are a group of genetically determined disorders of muscle.  Duchenne muscular dystrophy is an X-linked recessive disorder caused by an abnormal dystrophin gene and characterized by progressive weakness of muscles from the age of 5 years.

9 Muscle Disease Muscular Dystrophy Raised serum CK activities occur before the onset of clinical symptoms and values greater than 10 times the upper limit of normal.  Becker's muscular dystrophy is a form of muscular dystrophy, affected males sometimes reaching reproductive age.

10 Muscle Disease Toxic Myopathies Many drugs and chemicals may produce local or generalized muscle damage. Intramuscular injections may cause muscle damage by two mechanisms, trauma and effect of the agent being injected. The latter may be caused by analgesics, a possible cause of elevated CK activity which should be considered in cases of suspected myocardial infarction.

11 Muscle Disease Malignant Hyperpyrexia Malignant hyperpyrexia is a serious toxic myopathy, this usually follows general anaesthesia and in some cases have been described after the administration of muscle relaxants. High serum CK activities are seen during attacks.

12 Muscle Disease Traumatic Myopathies Causes of trauma to muscles in release of enzymes include surgery, intramuscular injections and post- exercise changes. Serum CK values usually return to normal within 48 h of a single intramuscular injection. Vigorous exercise of short duration and prolonged moderate exercise may produce elevations in serum CK, particularly in untrained athletes.

13 Liver Disease One of the transaminases is used as an indicator of hepatocellular damage, ALT being more specific for this purpose than AST. Increase synthesis of alkaline phosphatase and GGT in biliary cells are seen in cholestasis

14 Bone Disease ALP Level usually very high in Paget's disease of the bone (greater than 10 times the upper limit of normal). Both primary and secondary bone tumours can cause increases in alkaline phosphatase, typically up to five times the upper limit of normal.

15 Enzymes in Urine Enzymes appear in urine from two sources: by filtration of plasma and, by leaking from cells lining the urinary tract. Amylase is normally detected in urine, while other serum enzymes are too large to cross the glomerulus.

16 Enzymes in Urine Several enzymes derived from renal tubular cells have been investigated as indicators of tubular damage, particularly:  alkaline phosphatase  N­acetyl-beta-glucosaminidase (NAG),  ALT and,  GGT.

17 Haematological disorders Red cell enzymes activities may be abnormal because of an inherited deficiency or due to acquired disease. Many inherited defects such as:  haemolytic disease,  spherocytosis or,  methaemoglobinaemia

18 Haematological disorders Genetic examples due to defective enzyme activity of glucose-6-phosphate dehydrogenase (G6PD). Synthesis of G6PD is controlled by an X-linked gene and therefore males predominantly are affected.

19 Haematological disorders Haemolytic anaemia may also be caused by other enzyme defects including those affecting:  pyruvate kinase,  glutathione synthetase,  hexokinase and,  enzymes of the glycolytic pathway.

20 Haematological disorders Elevated serum LDH activities (owing to increases in HBD) are found in various acquired haematological disorders including:  megaloblastic anaemias and,  leukaemias.

21 Tissue Enzymes The estimation of tissue enzymes is usually in the investigation of inherited metabolic diseases, often being done on biopsy specimens from specific tissues.