Chapter 67: Enzyme Diagnostics Flashcards

1
Q

Enzyme leakage into the plasma may result from

A
  • Cellular necrosis
  • Membrane damage due to ischemia
  • Increased cellular turnover (normal active growth or malignant disease)
  • Induction of intracellular enzymes which increases the concentration gradient
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2
Q

Enzyme activity is measured as

A
  • Substrate converted per unit time

- Optimal conditions of [S], Temp, pH, [cofactors]

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3
Q

Advantages of UV light absorption

A
  • Reduced NAD or NADP to absorb UV light at 340 nm
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4
Q

If the reactions do not use NAD or NADP - coupled reactions

A
  • Particular tissues involved cannot usually be pinpointed

- Except Alcohol DH (liver) & Acid Phosphatase (prostate)

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5
Q

Isoenzyme assay allows

A
  • Differential diagnosis

- They can be separated and quantified

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6
Q

The absorption spectra of niacin and flavin coenzymes

A
  • Follows rate of reduction of NAD (increase in absorption at 340nm)
  • Follow rate of reduction of FAD (fall in absorbance at 450nm)
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7
Q

Alkaline phosphates (ALP)

A
  • Membrane bound isoenzymes

- Activity varies with both age and sex

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8
Q

Assay of plasma ALP activity is useful for

A
  • Assessing hepatobiliary and bone diseases
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9
Q

Hepatic disease (ALP)

A
  • Obstructed bile flow (cholestasis, pancreatic cancer) = 10x increase in plasma ALP
  • Viral hepatitis = 2x increase in plasma ALP
  • ALP only increases in small amounts following hepatocellular damage
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10
Q

Bone disease (ALP)

A
  • Paget’s disease of bone remodelling affecting the femur and hip of elderly men
  • Pagest’s = plasma ALP increases 25x
  • Ricketts = ALP increases 2-4x
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11
Q

Separation of liver and bone ALP isoenzymes by

A
  • Electrophoresis at pH 8.6
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12
Q

Gamma glutamyl transferase

A
  • Membrane bound enzyme
  • High concentrations in liver and kidney
  • Production is enhanced by drugs and alcohol
  • Used to confirm hepatic origin for ALP elevation
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13
Q

Elevated levels of GGT

A
  • (Often more than 10x) indicate cholestasis and cirrhosis
  • More sensitive than AP and more liver specific
  • Reyes syndrome, MI and acute pancreatitis as well
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14
Q

Some pathological causes of high GGT include

A
  • Hepatitis (often 5x)

- Alcohol abuse (usually less than 5x)

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15
Q

Aspartate transaminase (AST)

A
  • Glutamic oxaloacetic transaminase (GOT)
  • Present in most tissues (primarily skeletal and cardiac muscle, liver and kidney)
  • Mitochondrial and cytoplasmic isoenzymes
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16
Q

In alcoholic liver disease levels of AST

A
  • AST > ALT
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17
Q

Assay of plasma AST (activity coupled to MDH) measures

A
  • Myocardial infarction
  • Acute liver damage
  • Muscular dystrophy
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18
Q

Alanine transaminase (ALT)

A
  • Glutamic pyruvic transaminase (GPT): cytoplasmic enzyme
  • Generally lower concentrations than AST in tissues
  • In the liver the activity of ALT and AST are similar
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19
Q

ALT levels increase > AST early hepatocellular disease

A
  • AST increase is greater in alcohol-related liver disease
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20
Q

Alanine transaminase assay useful for

A
  • Acute liver damage (like viral hepatitis)
  • Monitoring effectiveness of new treatments of liver disease
  • Cardiac failure and muscle disease
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21
Q

De Ritis Ratio (DRR)

A
  • AST/ALT
  • Numerical values may vary
  • May reach 6.0 in alcohol-related liver disease
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22
Q

Increased AST/ALT ratio plasma levels are seen in

A
  • Cirrhosis
  • Liver tumors
  • Obstructive jaundice
  • Burns and shock
23
Q

Creatine kinase catalyzes

A
  • Reversible phosphorylation of creatine by ATP

- Key to phosphagen metabolism

24
Q

Creatine kinase requires

A
  • Mg++, but is inhibited by excess ADP
25
Creatine kinase
- Cytosol of striated muscle, brain, heart tissue | - Exists as a dimer of 2 subunits; M and B (mwt 40,000)
26
Plasma CK levels are proportional to
- Muscle mass
27
Plasma CK assay importance
- Skeletal muscle and heart disease | - Differentiation between skeletal muscle and heart disease necessitates isoenzyme assay
28
Creatine kinase isoenzymes must be distinguished by
- Electrophoresis
29
Elevated plasma creatine kinase levels are seen in
- Muscle disease - Myocardial infarction (10x increase) - Surgery, muscular trauma, heavy exercise, muscle dystrophy (5x increase)
30
Creatine kinase levels of well-trained athletes will be
- Lower than untrained individuals because they secrete smaller amounts
31
All types of muscular dystrophy demonstrate
- Increase in CK (mainly CK3, but maybe CK2)
32
- Diseases of CNS and hypothyroidism show
- 5-fold increase in creatine kinase (CK3)
33
Decrease in plasma CK levels is observed in
- Hyperthyroidism
34
Plasma Cardiac Troponin T is better than
- CK-MB in diagnosis and prediction of heart failure
35
Major sources of amylase
- Salivary glands | - Exocrine pancreas
36
Amylase
- Small protein that filters well | - Measurable in urine
37
Plasma amylase may be
- Normal in chronic pancreatic disease | - Elevated in renal disease
38
Acute pancreatitis
- Caused by gallstones/alcohol | - Elevates plasma amylase (10x) and lipase activity
39
Acute pancreatitis
- Initially managed medically | - Other acute abdomens usually require laparotomy
40
Lactate dehydrogenase (LDH)
- Cytoplasm of the majority of cell types | - Concentration is 500-fold that in the plasma
41
Five distinct isoenzymes of LDH exist (mwt 136kD)
- Tetramers of 4 distinct polypeptide chains | - Polypeptide chain may be 1 of 2 types, H or
42
Five different combinations constitute the LDH isoenzymes
- H4 isoenzyme = LD1 - M4 isoenzyme = LD5 - All 5 found in plasma of healthy individuals
43
All LDH isoenzymes catalyze
- Reversible oxidation of lactate | - NAD functions as the H acceptor in the reaction
44
Plasma levels of LDH isoenzymes
- Healthy: LD2 > LD1 > LD3 > LD4> LD5 | - Changes to this pattern in disease
45
LDH 1 and 2 primarily found in
- Myocardium | - Erythrocytes
46
LDH 3 primarily found in
- Brain | - Kidney
47
LDH 4 and 5 primarily found in
- Liver | - Skeletal muscle
48
Classic plasma LDH changes caused by diseases
- Myocardial infarction | - Hepatic, hemolytic jaundice and other liver disorders
49
Myocardial infarction plasma LDH changes
- LD1 & LD2 are elevated - 8 - 12 hours after pain begins - Peak at 24 - 48 hours - Levels remain elevated for 7-12 days and decline slowly
50
LD1 and LD2 may also be elevated in
- Anemia
51
Specimen hemolysis may generate
- LDH profile that mimics that seen in MI | - cTroponin I now often preferred assay for infarction
52
Plasma LDH in hepatic anoxia, hemolytic jaundice and other liver disorders
- Elevated up to 10x normal - LD5 most elevated (combine results with AST/ALT assay) - Patients with malignant disease (Muscular dystrophy) exhibit elevated serum LDH
53
The most useful enzyme assays are those that can easily be measured
- Spectrophotometrically