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Which condition is associated with a marked increase in plasma creatine kinase activities?
Salivary gland disorders can cause a marked increase in serum amylase levels.
False
What enzyme breaks down starch and glycogen in the serum?
amylase
A marked increase in plasma amylase activity may indicate conditions like acute pancreatitis and __________.
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Match the following causes of increased amylase activity with their corresponding types:
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Which of the following conditions can cause a marked increase in plasma AST activity?
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Alanine aminotransferase (ALT) is also known as glutamate oxaloacetate aminotransferase (GOT).
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Name one organ where both AST and ALT are present in high concentrations.
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A marked increase in plasma ALT activity may indicate __________.
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Match the enzyme with its corresponding activity:
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What condition is most likely diagnosed in the presented clinical scenario?
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Enzymology refers to the study of enzymes present exclusively in the plasma.
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What does ALP stand for in the context of serum enzyme tests?
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The enzyme activity in plasma may be ______ than normal due to cell damage or increased cell turnover.
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Match the enzymatic activity to its possible reason for elevation:
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Which of the following enzyme activities is normally found at low levels in serum?
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Isoenzyme determination can enhance diagnostic accuracy in enzymology.
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What is indicated by an increase in enzyme levels in plasma?
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What is a marked increase in plasma total LDH activity associated with?
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LDH1 is primarily associated with the liver.
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Name one condition that can lead to a slight increase in LDH activity.
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The isoenzyme LDH4 has __________ significance.
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Match the following isoenzymes of LDH with their primary source or elevation condition:
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Which laboratory enzyme isoform predominates in cardiac muscle?
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CK-3 isoenzyme is predominant in the brain.
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What type of macroenzyme is associated with autoimmune disease like rheumatoid arthritis?
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Study Notes
Enzymes
- Enzymology is the study of enzymes in body fluids, commonly used for diagnosis and monitoring of conditions
- Measuring plasma enzyme activity has limits, as it lacks specificity
- Isoenzymes, differing molecular variants of enzymes, and measuring multiple enzymes improve diagnostic accuracy
- Functional plasma enzymes are present at all times in circulation, performing physiological functions in the blood
- Non-functional plasma enzymes lack specific function in plasma, and function inside cells
- Non-functional enzymes are released during normal cell turnover
- Low levels are present in serum, but levels rise in tissue injury, helping diagnose the site and extent of injury
Steady-state of Enzyme Activity
- Normally, plasma enzyme activity indicates a steady-state
- The rate of enzyme entry into plasma equals the rate of enzyme removal
Enzyme Activity Abnormalities
- Higher than normal plasma enzyme activity can be due to:
- Proliferation of cells, increasing cell turnover or damage
- Increased rate of cell turnover or damage
- Increased enzyme synthesis (induction)
- Reduced clearance from the plasma
- Lower than normal plasma enzyme activity can be due to:
- Reduced enzyme synthesis, congenital deficiency, or inherited variants with low biological activity
- Presence of macroenzymes, high-molecular-weight forms of native enzymes, often complexed with immunoglobulins, common in autoimmune diseases
Clinically Important Plasma Enzymes
Aminotransferases
- Transfer amino groups from one molecule to another
- Two important aminotransferases are aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
Aspartate Aminotransferase (AST)
- Also known as glutamate oxaloacetate aminotransferase (GOT)
- Catalyzes the transfer of an amino group from aspartate to α-ketoglutarate, forming oxaloacetate and glutamate
- Found in high concentrations in:
- Cardiac muscle
- Erythrocytes
- Skeletal muscle
- Liver
- Kidneys
Causes of Raised Plasma AST Activity
- Artefactual: In vitro release from RBC due to hemolysis
- Marked increase (greater than 5-10 times the upper reference limit or URL): Note: URL is the reference range for AST activity.
- Circulatory failure with shock and hypoxia
- Myocardial infarction
- Acute viral or toxic hepatitis
- Moderate to slight increase (less than 5 times URL):
- Cirrhosis
- Liver tumors
- Skeletal muscle disease
Alanine Aminotransferase (ALT)
- Also known as glutamate pyruvate aminotransferase (GPT)
- Catalyzes the transfer of an amino group from alanine to α-ketoglutarate, forming glutamate and pyruvate
- Found in high concentrations in:
- Liver
- Skeletal muscle
- Kidneys
- Cardiac muscle
Causes of Raised Plasma ALT Activity
- Marked increase (greater than 5-10 times URL): Note: URL is the reference range for ALT activity.
- Circulatory failure with shock and hypoxia
- Acute viral or toxic hepatitis
- Moderate to slight increase (less than 5 times URL):
- Liver cirrhosis
- Liver tumors
Lactate Dehydrogenase (LDH)
- Catalyzes the reversible conversion of lactate to pyruvate using NAD+ as a cofactor
- Found in many tissues, including:
- Skeletal muscle
- Kidneys
- Brain
- Cardiac muscle
- Liver
- RBCs
Causes of Raised Plasma Total LDH Activity
- Artefactual: In vitro hemolysis
- Marked increase (greater than 5-10 times URL): Note: URL is the reference range for LDH activity.
- Circulatory failure with shock and hypoxia
- Myocardial infarction
- Some hematological disorders: Megaloblastic anemia, acute leukemia, and lymphomas
- Moderate to slight increase (less than 5 times URL):
- Viral hepatitis
- Malignancy of any tissue
Isoenzymes of LDH
- Five main isoenzymes can be detected by electrophoresis: LDH1 to LDH5
- Each isoenzyme consists of two different kinds of polypeptide chains, designated as H and M
- Isoenzyme and tissue distribution:
- LDH1: H4 - Heart - Elevated in Myocardial Infarction (MI)
- LDH2: H3M1 - Heart, Kidney, RBCs - Elevated in MI and hemolytic anemia
- LDH3: H2M2 - Widely distributed - Elevated in malignancy of many tissues
- LDH4: H1M3 - Widely distributed - Little diagnostic significance
- LDH5: M4 - Liver, Skeletal muscle - Elevated in skeletal muscle and liver diseases
Creatine Kinase (CK)
- Catalyzes the reversible phosphorylation of creatine to creatine phosphate, using ATP
- Found in high concentrations in:
- Skeletal muscle
- Cardiac muscle
- Brain
Isoenzymes of Creatine Kinase
- Three principal isoenzymes: BB, MB, and MM
- Each isoenzyme consists of two polypeptide chains: B (brain) or M (muscle)
- Isoenzyme and tissue distribution:
- BB (CK-1): Predominant in brain
- MB (CK-2): Predominant in cardiac muscle
- MM (CK-3): Predominant in skeletal muscle
Other Forms of CK
- Mitochondrial CK: Found in hepatic disease, certain tumors, and critically ill patients
- Type 1 Macroenzyme: Associated with autoimmune disease, like rheumatoid arthritis, thought to be CK complexed with IgG
- Type 2 Macroenzyme: An oligomer of mitochondrial CK
Causes of Raised Plasma Creatine Kinase Activities
- Marked increase (greater than 5-10 times URL): Note: URL is the reference range for CK activity.
- Dermatomyositis and polymyositis
- Shock and circulatory failure
- Myocardial infarction
- Moderate to slight increase (less than 5 times URL):
- Muscle injury
- Physical exertion
- After an intramuscular injection
- Hypothyroidism
- Certain drugs: statins, ciclosporin, cocaine
Amylase
- Breaks down starch and glycogen
- Serum amylase originates mainly from the pancreas (P-isoamylase) and salivary glands (S-isoamylase)
- Can also be extracted from other tissues: gonads, Fallopian tubes, skeletal muscle, and adipose tissue
- Excreted in urine due to its low molecular weight
Causes of Raised Plasma Amylase Activity
- Marked increase (greater than 5-10 times URL): Note: URL is the reference range for amylase activity.
- Acute pancreatitis
- Severe glomerular impairment
- Diabetic ketoacidosis
- Perforated peptic ulcer
- Moderate to slight increase (less than 5 times URL):
- Other acute abdominal disorders: acute cholecystitis, intestinal obstruction
- Salivary gland disorders: mumps, salivary calculi
- Decreased amylase activity:
- Chronic pancreatic disease
Macroamylasaemia
- High plasma amylase activity due to low renal excretion of a macroenzyme form, despite normal glomerular function
- Symptomless, thought to be the enzyme bound to IgA, forming a complex with a molecular weight of about 270 kDa
Lipase
- Derived from the pancreas, more specific for pancreatic pathology
- Longer half-life than amylase, making it more useful for diagnosis of late-presenting acute pancreatitis
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