Diagnostic Value of Enzymes in Various Diseases

Creatine kinase (CK)

How will you define Creatine kinase (CK)?

1. This is a dimeric enzyme that causes the reversible phosphorylation of creatine.
2. CK activity is greatest in striated muscles, the brain, and the heart tissues.
3. The kidney has lower lipase activity.
4. The liver and RBCs have no CK activity.

What are the indications for creatine kinase (CK)?

1. Skeletal muscle disorders.
2. Cardiac muscular diseases.
3. Neuromuscular diseases.
4. Drug and toxin-induced diseases.
5. Metabolic and endocrine conditions.

What are the subunits of creatine kinase?

1. CK-1 is CK-BB.
2. CK-2 is CK- MB.
3. CK-3 is CK – MM.

What are the conditions where creatinine kinase increases?

1. CK enzyme activity increases in skeletal muscles, the cardiovascular system, the brain, and thyroid diseases.
2. CK-MM is increased in:
   1. Muscular atrophy, especially Duchenne’s type.
   2. In progressive muscular dystrophy.
   3. The enzyme level is high in children between 7 to 10 years.
   4. It falls in the older patients.
3. CK-MB is increased in:
   1. It is raised after an acute myocardial infection.

Diagnostic Value of Enzymes in Various Diseases: CK-MB curve in AMI

7. CK-BB is increased in :
   1. It is increased in cerebrovascular diseases.
   2. It increases in the neurosurgical intervention.
   3. In cerebral ischemia.

Gamma-glutamyl transferase (GGT)

How will you define Gamma-Glutamyl Transferase (GGT)?

1. GGT is a membrane-bound enzyme in the liver (cells lining the bile ductuli and canaliculi).
2. GGT is also seen in proximal renal tubules, the brain, the prostate, and the pancreas (ductules and acinar cells).

What are the Indications for the GGT:

1. It is advised for liver diseases.
2. It is advised to limit alcohol intake to prevent liver cell injury.
3. It differentiates liver diseases from bone diseases, where alkaline phosphatase is raised.

How will you explain the pathophysiology of GGT?

1. GGT is responsible for glutathione’s extracellular metabolism (the cells’ main oxidant).
2. Glutathione is its substrate.
3. GGT is present on cell membranes and assists in the transport of amino acids into cells.

GGT role for amino acid transport

4. GGT is mainly present in the liver cells. It is also presented in the biliary tract epithelium.
5. GGT is present in the smooth endoplasmic reticulum of liver cells, and it will be increased in case of increased toxins.
6. GGT is increased in patients when exposed to drugs like barbiturates, warfarin, valproate, Dilantin, methotrexate, and alcohol.
7. A small amount is found in the kidneys, intestine, heart, brain, pancreas, and spleen.
8. There is some activity in the capillary endothelial cells.
9. The serum GGT level increases in the newborn but decreases to the adult level by 4 months.
10. GGT usually does not increase in bone disease, childhood or adolescence, or pregnancy.
11. GGT is raised by acute liver cell damage and biliary tract obstruction.
12. Its half-life is 7 to 10 days.
13. This enzyme originates from the hepatobiliary system.
14. GGT is the best indicator of occult alcoholism.
15. GGT is lower in women than in men. It is significantly higher in African Americans.

What are the Causes of raised GGT?

1. It is raised 2 to 3 times the normal value in heavy drinkers.
   1. It returns to normal after stopping the alcohol in about 3 weeks.
2. It is raised in all forms of liver disease.
3. It is raised in intrahepatic and posthepatic biliary obstruction.
4. The level reaches 5 to 30 times the normal value.
5. This is a more sensitive test for diagnosing obstructive jaundice, cholangitis, and cholecystitis.
6. The rise is earlier than that of other enzymes and persists longer.
7. Moderate elevation, 2 to 5 times, occurs in infectious hepatitis.
8. A high level was seen in primary or metastatic malignancies.
9. A 2 to 5 times increase is seen in fatty liver and drug intoxication.
10. In acute or chronic pancreatitis, GGT levels may be elevated to 5-15 times normal when a hepatobiliary obstruction occurs.
11. GGT is always raised in acute pancreatitis. In chronic pancreatitis, it is raised if there is biliary tract involvement or active inflammation.
12. It is normal in a skeletal disease like Paget’s disease and in bone malignancy, even when alkaline phosphatase is raised.
13. GGT is raised in alcoholic cirrhosis.
14. In 5% to 30% of patients, GGT is raised in acute myocardial infarction. This is due to the proliferation of capillaries and fibroblasts in granulation tissue. The rise is usually reported after 7 to 14 days of the infarction. Usually, elevation starts on the 4th to 5th day and peaks at 8 to 12 days.
15. In pregnancy, in bone diseases, and in childhood, alkaline phosphatase levels increase, but GGT remains normal.

What is the importance of GGT?

1. GGT differentiates from the liver to non-liver cell injury origin when the alkaline phosphatase level is raised.
2. GGT is the best test to confirm that elevated alkaline phosphatase is of hepatic origin.

Lactate dehydrogenase (LDH)

What sample for LDH is needed?

1. It is done in the patient’s serum.
2. A random sample can be used.

What are the Indications for LDH?

1. It is a marker of hemolysis.
2. It is a useful marker of the disease activity in cryptogenic fibrosing alveolitis and extrinsic allergic alveolitis.
3. LDH was the marker of AMI, but is now replaced by Troponin-T.

What are the precautions for LDH?

1. Avoid hemolysis, as this will interfere with LDH estimation.
2. Separate the clot from the serum immediately.
3. Avoid heating the blood sample.

How will you explain the distribution of LDH?

1. LDH is widely distributed in tissues and has a high concentration in the liver, cardiac muscle, kidneys, skeletal muscle, RBCs, and other tissues.
2. Less concentration is found in the lungs, smooth muscles, and the brain.

What are the isoenzymes of LDH?

1. LD-1 is predominant in the heart, muscles, kidneys, and RBCs.
   1. LD-2 is like LD-1.
2. LD-3 is present in various tissues, such as the lung and spleen.
3. LD-4 is more prevalent in the liver and skeletal muscles.
4. LD-5 is more concentrated in the liver and skeletal muscles.
   1. LDH- 5 has isoenzymes:

What is the chemical role of LDH?

1. LDH catalyzes the interconversion of lactate to pyruvate.
2. Lactate dehydrogenase is a hydrogen transfer enzyme that catalyzes the oxidation of L-lactate to pyruvate.

LDH’s role in chemical reaction

3. The optimal pH for LDH-catalyzed pyruvate formation is 8.8-9.8.
4. LDH activity is present in all cells and is found in the cytoplasm.
5. Enzyme levels vary across various tissues.
6. The tissue level is 500 times higher than the serum, so cell leakage increases the serum level.

What are the causes of increased LDH levels?

1. Acute myocardial infarction:
   1. LDH levels rise within 24 to 48 hours of the AMI, peak at 48 to 72 hours, and slowly return to normal over 5 to 10 days.

LDH changes in AMI

1. A moderate increase may be seen in myocarditis and cardiac failure.
2. Severe shock and anoxia.
3. Megaloblastic anemia.
4. In the case of liver disease.
5. In 1/3 of cases of renal disease, such as tubular necrosis and pyelonephritis.
6. In liver metastatic tumor infiltration.
7. LDH-raised values in the urine are seen in glomerulonephritis, diabetic nephropathy, systemic lupus erythematosus, urinary bladder, and kidney malignancies.
8. CSF infiltration by granulocytes increases LDH levels.
9. In bacterial meningitis, LD-4 and LD-5 increase.
10. In cerebrovascular accidents:
    1. Subdural  and subarachnoid hemorrhage increases all isoenzymes of LD, especially LD-3, 4, 5
    2. Where the peak level is reached in 1 to 3 days.
    3. It is not related to xanthochromia.
    4. In CNS tumors, there is an increase in the LD-5 in >9% of the cases and a decreased level of the LD-1: LD-5 ratio.
    5. LD-1: LD-5 ratio <2.5 in the absence of infection or hemorrhage suggests meningeal tumors.
    6. LD-5 in >10% of the cases suggests high-grade malignant tumors.
11. This is normal in angina and pericarditis.

Lipase Enzyme

How will you define lipase?

1. Lipase is a glycoprotein enzyme filtered by glomeruli and completely absorbed by proximal tubules.
2. Lipase is more specific than amylase in pancreatic damage.

How will you discuss the distribution of the lipase enzyme?

1. The pancreas is the main organ for lipase secretion, which goes into pancreatic juice.
   1. Lipase is found in the stomach and intestinal mucosa, but it doesn’t play a significant role in fat processing.
   2. Pancreatic lipase is secreted into the duodenum, where it converts triglycerides into fatty acids.
2. Lipase concentration in the pancreas is 100 times greater than in other tissues.
   1. The difference between amylase in the pancreas and serum is 20,000 times.
   2. A very small amount is found in the serum.
   3. Lipase estimation is difficult and not reproducible, so it is not common in labs.
   4. Lipase hydrolyzes glycerol esters of long-chain fatty acids.

How will you discuss Acute pancreatitis?

1. Lipase enzymes can diagnose it.
2. The serum lipase level rises slightly later than the amylase.
3. The initial rise is seen between 4 and 8 (3 and 6) hours.
4. The peak level is 24 hours (another reference says it occurs after 72 to 96 hours).
5. The peak remains for a longer time.
6. The normal level is seen after 8 to 14 days (7 to 10 days).

lipase level in acute pancreatitis

What are the conditions under which the Lipase level is raised?

1. Acute pancreatitis.
2. Chronic pancreatitis.
3. Acute cholecystitis.
4. Perforating or penetrating peptic ulcer.
5. Obstruction of the pancreatic duct by:
   1. Stones.
   2. Drugs induced.
   3. Partial obstruction with the use of drugs.
6. Small intestinal obstruction.
7. Intestinal infarction.
8. Acute and chronic renal failure with complications.
9. Alcoholism.
10. Diabetic ketoacidosis.
11. Drug-induced acute pancreatitis.

What are the conditions under which the Lipase level decreases?

• It is only observed in the methodology, where interference from Hemoglobin, heavy metals, and calcium ions is present.

What are the conditions where the Lipase level is normal?

1. Values are lower in neonates.
2. Mumps.
3. Macroamylasemia.

Questions and answers: