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Biochemistry (MPAS) > Lecture 6: Clinical proteins and enzyme markers > Flashcards

Lecture 6: Clinical proteins and enzyme markers Flashcards

1
Q

Most common reasons for release of plasma enzymes and proteins into blood plasma

A

Tissue damage or cell death (necrosis/apoptosis/autophagy), usually caused by toxins or induced by ischemia.

Increased cell turn over during active growth, tissue repair, or in tumour invasion of normal tissue (as in cancer).

Increased concentrations of enzymes/proteins within cells, because of induction by diseases or drugs.

Duct obstruction. For example, exocrine secretions may be released into the blood, if the normal route of flow is obstructed or damaged

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2
Q

What is a useful clinical marker assay?

A

should be specific and sensitive for a particular tissue or disease. Some of the marker enzymes are expressed as isoenzymes/isomers in different tissues.

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3
Q

Sensitive assay

A

detects the smallest amount of the marker.

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4
Q

Specific assay

A

highly distinguishes between the marker and other undesirable substances.

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5
Q

Precise assay

A

reproducibility of an assay.

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6
Q

Accuracy of assay

A

how close the result is to the “true value”.

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7
Q

Sensitivity vs specificity

A

Often, increasing sensitivity leads to decreased specificity (increased false positive)

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8
Q

What does lactate DH do?

A

involved in anaerobic process of glycolysis

Catalyzes conversion of lactate to pyruvate in glycolytic pathway

Reversible reaction

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9
Q

Isoenzymes of lactate DH

A

composed of five isoenzymes formed from two major subunits, designated as the H (heart) and M (muscle) specific subunits.

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10
Q

Distribution of Lactate DH in tissues

A

Widely distributed in most tissues

The isoenzyme patterns of the tissues depend on the relative amounts of the LDH subunits.

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11
Q

Reaction catalyzed by creatine kinase (CK)

A

Conversion of creatine + ATP to creatine phosphate

Reversible

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12
Q

Which organs is CK specific for?

A

Skeletal and cardiac muscle

Brain also has large amount of CK (uses a lot of energy)

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13
Q

Isoenzymes of CK

A

Muscle (M) and Brain (B) subunits

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14
Q

Cardiac muscle CK

A

MB subunits (CK-2)

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15
Q

Skeletal muscle CK

A

MM (CK-3)

Skeletal muscle specific

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16
Q

Brain CK

A

BB (CK-1)

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17
Q

What happens if you see BB CK in blood?

A

Serious problem

BB should not be in blood because of blood brain barrier

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18
Q

What are troponins?

A

Tn

components of the regulatory contractile protein complex of muscles (cardiac and skeletal muscles).

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19
Q

Three types of troponins

A

Troponin T - tropomyosin bindnig

Troponin I - inhibitory actin binding

Troponin C - calcium binding

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20
Q

Solubility of troponins

A

Insoluble

When there is damage, you will see the soluble form

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21
Q

Distribution of aspartate and alanine aminotransferases

A

Widely distributed

Abundant in liver

ALT is present in most tissues

AST is more abundant than ALT

22
Q

Activity of ALT and AST in liver

A

Similar activity

23
Q

Activity of alkaline phosphatase (ALP)

A

group of enzymes with maximum activity in the pH range 9.0 – 10.5.

Hydrolytic enzymes, remove phosphate

24
Q

Distribution of ALP

A

liver

bone

placenta

intestine.

25
Q

Tissue distribution of alpha amylase

A

present mostly in the pancreas and salivary glands and smaller amounts in other tissues.

26
Q

Reaction of alpha amylase

A

breakdown of starch/carbohydrate polymers into sugar.

27
Q

Excretion of alpha amylase

A

The salivary and pancreatic amylase isoenzymes are usually filtered at the glomeruli in the kidneys.

28
Q

Distribution of gamma-glutamyl transferase (GGT)

A

found mainly in the kidney, liver biliary tract and pancreas.

29
Q

Function of GGT

A

cell surface protein contributing to the extracellular catabolism of glutathione, an antioxidant

30
Q

LDH levels in disease

A

Heart and bone barrow: H subunits

Skeletal muscle: M subunits

Lung, brain, kidney and pancreas: both

31
Q

What is abnormal CK associated with?

A

Skeletal and cardiac muscle damage, muscular dystrophy, intramuscular injection

BB is hardly ever detected in plasma

BUT in the absence of MM (skeletal) or MB (cardiac) isotopes, brain damage will be considered

32
Q

Detection of cardiac troponins (Tn)

A

Cardiac troponins are very sensitive and highly specific (97% sensitivity and specificity) for detecting even a minimal amount of myocardial damage.

Elevations of cardiac troponin can occur without elevation of total CK and CK-MB

33
Q

What troponins are used in assays?

A

cTnI and cTnT are more used than cTnC

Interpretation of cTnI and cTNT are similar

34
Q

What biochemical markers are best for detecting myocardial infarction?

A

Troponins

cardiac specific cTnI is best

35
Q

What does increase in AST or ALT in blood indicate?

A

leakage from damaged hepatocytes.

Also present in cardiac and skeletal muscle

36
Q

Where are AST and ALT mainly used?

A

investigations of patients with liver diseases and suspected myocardial infarction and muscular dystrophy.

37
Q

What is ALP used for in diagnoses?

A

Diagnoses of liver and bone diseases.

Used in standard liver function tests

38
Q

When will amylase be elevated?

A

Acute pancreatitis

Lipase will also be high

Used for differential diagnosis of severe abdominal pain of sudden onset.

39
Q

What can GGT be used for?

A

Liver function testing

Associated with cell membranes

40
Q

How to distinguish between LDH iso forms

A

LDH isoenzymes have different electrophoretic mobility, physical and chemical properties.

Heart specific enzymes are present for one or two days after a chest pain

41
Q

Indications of muscle disease

A

CK, AST, LDH and ALT activities may be increased

42
Q

Cardiac troponins in detection of MI

A

Best at detecting MI

More specific than CK-MB

After MI, cardiac troponins increase within four hours and remain increased for several days

Not good for continuous monitoring

43
Q

Troponin I

A

Highly specific and sensitive for MI

44
Q

When is AST measured?

A

Used in patients with liver disease, suspected MI and muscular dystrophy

45
Q

When is ALT measured?

A

Measured for hepatocellular damage, since it is more liver specific than AST.

46
Q

What does elevated ALP indicate?

A

ALP activity is usually increased when there is cholestasis and not when there is hepatocellular damage.

increased in bone disease, such as in Paget’s disease, rickets and osteomalacia, where there is increased osteoblastic activity,

It is also elevated in hyper parathyroidism.

It is also used as tumor markers.

47
Q

When is amylase increased?

A

Intestinal infarction or perforation.

Peritonitis (inflammation of peritoneum)

48
Q

When do GGT and ALP increase in parallel?

A

when there is cholestasis in liver disease (obstruction of bile flow) .

49
Q

What is increase in GGT stimulated by?

A

Cholestasis in liver disease

Alcohol and drug use (ex: anti epileptic drugs)

50
Q

How can GGT help identify tissue of origin for ALP in plasma?

A

GGT is not raised in bone diseases, but is raised in liver.

So if ALP is high, but GGT is not, it is probably bone disease

51
Q

Release of markers in MI

A

See figure

52
Q

Why do enzyme activities and protein levels vary?

A

Due to their rate of release

Biochemistry (MPAS) (10 decks)

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