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CLINICAL ENZYMOLOGY
Dr.MANOJ SINAKHED
1 INTRODUCTION
Enzymes are catalysts that increase the rate or velocity of physiologic reactions. Each and every reaction in our
body takes place with the help of an enzyme. In general, most enzymes are present in cells at much higher
concentrations than in plasma
PLASMA ENZYMES
Enzymes present in plasma can be classified into 2 types
A)Functional Plasma enzymes
B) Non-functional plasma enzymes
Functional plasma enzymes:
• Present in plasma at higher concentration than tissues
• They function in plasma.
• Mostly synthesized by the liver
• Usually decreased in disease conditions
• Eg. Clotting enzymes, lipoprotein lipase
Non-functional plasma enzymes:
• Present in plasma at lower concentration than tissues
• Do not have any function in plasma
• Mostly synthesized by liver, skeletal muscle, heart, brain etc
• Usually increased in disease conditions
• Eg. Creatine kinase, Alanine transaminase etc
• Measurement of these enzymes in plasma can be used to assess cell damage and proliferation i.e. diagnosis
of disease.
ENZYMES IN HEALTH AND DISEASES
Lactate Dehydrogenase
Clinical significance
Normal range of total LDH: 180-360 U/L= 3.1-6.1 μkat/L
1. It is increased in plasma in Myocardial injury, acute leukemias, generalized
carcinomatosis and in acute hepatitis.
2. Estimation of its isoenzymes in more useful in clinching diagnosis between hepatic
disease and Myocardial Injury
3. Moderate increase: skeletal muscle disease: pulmonary embolism: infectious
mononucleosis.
Creatine Kinase
Normal range for total CK:
Male : 46-171 U/L= 0.78-2.90 μkat/L Female: 34-145 U/L= 0.58-2.47 μkat/L
Serum CK activity is greatly elevated in all types of muscular dystrophy.
High values of Ck are noted in viral myositis, polymyositis and similar muscle disease.
However in neurogenic muscle disease, such as:
(a) Myasthenia gravis
(b) (b) Multiple sclerosis
(c) (c) Polimyeltis
(d) (d) Parkinsonism
Aminotransferases/Transaminases
Aspartate Transaminase (AST)
Normal values of AST: Male<35 UNITS FEMALE :<31 UNITS
Alanine Transaminase(ALT)
Normal values of AST: Male<45 UNITS FEMALE :<34 UNITS
Alkaline phosphatase
1. Physiological: There is a gradual increase in the proportion of liver ALP with age: in the elderly the
plasma bone isoenzyme activity may increase slightly.
2. 2. Bone ailment: rickets and osteomalacia
3. 3. Liver disease:
4. 4. Malignancy bone or liver involvement or direct tumor production
LOW LEVEL
• Arrested bone growth
• Hypophosphatasia: an autosomal recessive disorder, associated with rickets or osteomalacia.
Pancreatic enzymes
Amylase:
Normal values of amylase: 28-100 U/L
Causes of Raised Plasma Amylase Activity
Marked increase (five to 10 times the upper reference limit):
• Acute pancreatitis
• Severe glomerular impairment
Moderate increase (up to five times the upper reference limit):
• Perforated peptic ulcer
• Acute cholecystitis z Intestinal obstruction
• Salivary gland disorders like mumps, salivary calculi
Lipase
Normal values: 40-200 U/L
Plasma lipase levels are elevated in acute pancreatitis and carcinoma of the pancreas.
serum amylase is increased in mumps, pancreatic disease or due to some other cause, whereas
lipase is increased only in pancreatitis. Therefore, the determination of both amylase and lipase
together helps in the diagnosis of acute pancreatitis.
Glucose -6-phosphate Dehydrogenase
The reference interval for G6PD on erythrocytes is 8-14U/g Hb
The majority of G6PD – deficient individuals develop hemolysis only when oxidative stress occurs, as
with infections and after ingestion of certain drugs or fava beans. Outside these periods, they are
usually asymptomatic
G6PD deficiency also leads to mild to sever chronic hemolysis, exacerbated by oxidative stress.
Cholinesterase
Normal values for CHE: 4.9-11.9 U/Ml
Measurements of CHE activity in serum are used:
1. as a test of liver function
2. 2. as an indicator of possible insecticide poisoning
Causes of decreased plasma cholinesterase activity
1. Hepatic parenchymal disease (reduced synthesis)
2. 2. Ingestion or absorption through the skin, of such anticholinesterases as organophosphates.
Causes of increased plasma cholinesterase activity
1. Recovery from liver damage (actively growing hepatocytes) 2. Nephrotic syndrome
Acid Phosphatase
Normal range of TR-ACP: 1.5-4.5 U/L
Elevated TR-ACP
(a) Paget disease
(b)(b) Hyperparathyroidism with skeletal involvement
(c) Presence of malignant invasion of bones by cancers
Isoenzymes
Isoenzymes (also known as isozymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction
LDH-Isoenzymes
• The LDH has five Isoenzymes which are:
• LDH-1 (H4) is found mainly in the heart.
• LDH-2 ( H3M1) Reticuloendothelial system.
• LDH-3 (H2M2) is found in the lungs.
• LDH-4 ( H1M3) in the kidney, placenta, and pancreas, and
• LDH-5 ( M4) in liver and striated (skeletal) muscle.
• Normally, levels of LDH-2 are higher than those of
the other Isoenzymes
CPK- Isoenzymes
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CLINICAL ENZYMOLOGY.pptx

  • 2. 1 INTRODUCTION Enzymes are catalysts that increase the rate or velocity of physiologic reactions. Each and every reaction in our body takes place with the help of an enzyme. In general, most enzymes are present in cells at much higher concentrations than in plasma
  • 3. PLASMA ENZYMES Enzymes present in plasma can be classified into 2 types A)Functional Plasma enzymes B) Non-functional plasma enzymes Functional plasma enzymes: • Present in plasma at higher concentration than tissues • They function in plasma. • Mostly synthesized by the liver • Usually decreased in disease conditions • Eg. Clotting enzymes, lipoprotein lipase
  • 4. Non-functional plasma enzymes: • Present in plasma at lower concentration than tissues • Do not have any function in plasma • Mostly synthesized by liver, skeletal muscle, heart, brain etc • Usually increased in disease conditions • Eg. Creatine kinase, Alanine transaminase etc • Measurement of these enzymes in plasma can be used to assess cell damage and proliferation i.e. diagnosis of disease.
  • 5. ENZYMES IN HEALTH AND DISEASES
  • 6. Lactate Dehydrogenase Clinical significance Normal range of total LDH: 180-360 U/L= 3.1-6.1 μkat/L 1. It is increased in plasma in Myocardial injury, acute leukemias, generalized carcinomatosis and in acute hepatitis. 2. Estimation of its isoenzymes in more useful in clinching diagnosis between hepatic disease and Myocardial Injury 3. Moderate increase: skeletal muscle disease: pulmonary embolism: infectious mononucleosis.
  • 7. Creatine Kinase Normal range for total CK: Male : 46-171 U/L= 0.78-2.90 μkat/L Female: 34-145 U/L= 0.58-2.47 μkat/L Serum CK activity is greatly elevated in all types of muscular dystrophy. High values of Ck are noted in viral myositis, polymyositis and similar muscle disease. However in neurogenic muscle disease, such as: (a) Myasthenia gravis (b) (b) Multiple sclerosis (c) (c) Polimyeltis (d) (d) Parkinsonism
  • 8. Aminotransferases/Transaminases Aspartate Transaminase (AST) Normal values of AST: Male<35 UNITS FEMALE :<31 UNITS Alanine Transaminase(ALT) Normal values of AST: Male<45 UNITS FEMALE :<34 UNITS
  • 9. Alkaline phosphatase 1. Physiological: There is a gradual increase in the proportion of liver ALP with age: in the elderly the plasma bone isoenzyme activity may increase slightly. 2. 2. Bone ailment: rickets and osteomalacia 3. 3. Liver disease: 4. 4. Malignancy bone or liver involvement or direct tumor production LOW LEVEL • Arrested bone growth • Hypophosphatasia: an autosomal recessive disorder, associated with rickets or osteomalacia.
  • 10. Pancreatic enzymes Amylase: Normal values of amylase: 28-100 U/L Causes of Raised Plasma Amylase Activity Marked increase (five to 10 times the upper reference limit): • Acute pancreatitis • Severe glomerular impairment Moderate increase (up to five times the upper reference limit): • Perforated peptic ulcer • Acute cholecystitis z Intestinal obstruction • Salivary gland disorders like mumps, salivary calculi
  • 11. Lipase Normal values: 40-200 U/L Plasma lipase levels are elevated in acute pancreatitis and carcinoma of the pancreas. serum amylase is increased in mumps, pancreatic disease or due to some other cause, whereas lipase is increased only in pancreatitis. Therefore, the determination of both amylase and lipase together helps in the diagnosis of acute pancreatitis.
  • 12. Glucose -6-phosphate Dehydrogenase The reference interval for G6PD on erythrocytes is 8-14U/g Hb The majority of G6PD – deficient individuals develop hemolysis only when oxidative stress occurs, as with infections and after ingestion of certain drugs or fava beans. Outside these periods, they are usually asymptomatic G6PD deficiency also leads to mild to sever chronic hemolysis, exacerbated by oxidative stress.
  • 13. Cholinesterase Normal values for CHE: 4.9-11.9 U/Ml Measurements of CHE activity in serum are used: 1. as a test of liver function 2. 2. as an indicator of possible insecticide poisoning Causes of decreased plasma cholinesterase activity 1. Hepatic parenchymal disease (reduced synthesis) 2. 2. Ingestion or absorption through the skin, of such anticholinesterases as organophosphates. Causes of increased plasma cholinesterase activity 1. Recovery from liver damage (actively growing hepatocytes) 2. Nephrotic syndrome
  • 14. Acid Phosphatase Normal range of TR-ACP: 1.5-4.5 U/L Elevated TR-ACP (a) Paget disease (b)(b) Hyperparathyroidism with skeletal involvement (c) Presence of malignant invasion of bones by cancers
  • 15. Isoenzymes Isoenzymes (also known as isozymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction LDH-Isoenzymes • The LDH has five Isoenzymes which are: • LDH-1 (H4) is found mainly in the heart. • LDH-2 ( H3M1) Reticuloendothelial system. • LDH-3 (H2M2) is found in the lungs. • LDH-4 ( H1M3) in the kidney, placenta, and pancreas, and • LDH-5 ( M4) in liver and striated (skeletal) muscle. • Normally, levels of LDH-2 are higher than those of the other Isoenzymes