Enzymes and cardiac markers

Question 1

What is the Michaelis Menten constant (Km)?

Answer 1

Substrate conc at which the reaction velocity is 50% of the maximum rate of reaction

Question 2

In which order are cystolic and sub-cellular enzymes released?

Answer 2

Release of cytosolic enzymes happens first, followed by release of sub-cellular enzymes (as they leak out of cells after necrosis)

Question 3

Where can enzymes be measured?

Answer 3

Enzymes can be measured in the SERUM (i.e. in injury) or the TISSUE (abnormalities)

Question 4

Name 2 physiological causes of raised ALP

Answer 4

Normal bone growth!

• 3rd trimester of pregnancy (from placenta)
• Childhood growth spurts

Question 5

Name 2 pathological causes of raised ALP <5x the upper limit

Answer 5

Bone – tumours, fractures, osteomyelitis

Liver – infiltrative disease, hepatitis (doesn’t go up nearly as much as AST/ALT)

Question 6

Name 2 pathological causes of raised ALP >5x the upper limit

Answer 6

• Bone – Paget’s disease, osteomalacia

- Liver – cholestasis, cirrhosis

Question 7

Which enzyme is elevated in acute pancreatitis?

Answer 7

Amylase

Question 8

Which enzyme is low in chronic pancreatitis?

Answer 8

Faecal elastase

Question 9

What biomarker is used in IBD?

Answer 9

Faecal calprotectin- indicates inflammation

Question 10

What are the 3 forms of creatine kinase?

Answer 10

Three forms (they are dimers containing either M (muscle) and B (brain) subunits):

• CK-MM = skeletal muscles (responsible for almost the entire normal plasma activity)
• CK-MB = cardiac muscle
• CK-BB = brain (activity is minimal even in severe brain damage)

Question 11

What is creatine kinase a marker of?

Answer 11

Muscle damage

Question 12

What condition is caused by statins and causes a raised CK-MM?

Answer 12

Statin-related myopathy

Question 13

Causes of a raised CK

Answer 13

• Muscle damage due to any cause
• Myopathy (e.g. Duchennes) >x10 Upper Limit
• Myocardial infarction >x10 UL
• Severe exercise 5x UL
• Physiological (Afro-Caribbean <5x UL

Question 14

Give two other uses of measuring enzymes

Answer 14

• Markers of therapeutic response or drug toxicity
  E.G. measurement of TPMT activity before starting patients on thiopurine drugs such as azathioprine
• As reagents for measurement of other substances
  E.G. glucose oxidase is used to measure glucose in plasma

Question 15

Which enzyme is the best to measure following MI?

Answer 15

Troponins

Question 16

Which enzymes are the cytosolic and sub-cellular enzymes in the myocardium?

Answer 16

Myoglobin = cytosolic enzyme (rise quickly)

CK-MB = sub-cellular (mitochondria and nuclei)

Question 17

When do troponins…
a) rise
b) peak
…post MI?

Answer 17

a) 4-6 hours

b) 12-24 hours

Question 18

How long do troponins remain elevated following MI?

Answer 18

3-10 days

Question 19

When should troponins be measured in someone with chest pain?

Answer 19

At 6 hours and again at 12 hours after onset of chest pain

Question 20

If after 12-24 hours if there is no rise in troponin, has someone had an MI?

Answer 20

Almost certainly NOT

Question 21

What are the diagnostic criteria for MI?

Answer 21

Diagnostic Criteria for Acute MI = either of the following:

Typical rise and gradual fall in troponin or more rapid rise and fall in CK-MB with at least one of the following:

• Ischaemic symptoms
• Pathological Q waves on ECG
• ECG changes of ischaemia
• Coronary artery intervention

Pathological findings of an acute MI

Question 22

Are cardiac biomarkers enough to diagnose MI when deciding about thrombolysis? Why?

Answer 22

No.

None of the current cardiac biomarkers rise quickly enough to aid decisions regarding thrombolysis (therefore it is decided based on clinical findings and ECG findings)

Question 23

What are the markers of cardiac failure?

Answer 23

Natriuretic peptides (NP):

• Atrial NP (secreted by atria)
• Brain NP (secreted by ventricles) used for:
  Assess ventricular function
  To exclude heart failure in a clinical setting (highly sensitive)