ChemPath: Enzymes and Cardiac Markers

Question 1

Where are most enzymes found?

Answer 1

Intracellularly

Question 2

What are the two types of intracellular enzymes?

Answer 2

• Cytosolic
• Subcellular (within organelles)

Question 3

Describe the order of release of intracellular enzymes when cells are damaged.

Answer 3

Cytosolic are released first, followed by subcellular

Question 4

In which tissues is ALP present in high concentration?

Answer 4

• Liver
• Bone
• Intestines
• Placenta

Question 5

What is an increase in bone ALP caused by?

Answer 5

Increased osteoblast activity

Question 6

What technique is used to separate isoenzymes?

Answer 6

Electrophoresis

Question 7

List some physiological causes of high ALP.

Answer 7

• Pregnancy - 3rd trimester (from placenta)
• Childhood - growth spurt

Question 8

List some causes of very high ALP (>5 x upper limit of normal).

Answer 8

• Bone - Paget’s disease, osteomalacia
• Liver - cholestasis, cirrhosis

Question 9

List some causes of moderately raised ALP (< 5 x upper limit of normal).

Answer 9

• Bone - tumours, fractures, osteomyelitis
• Liver - infiltrative disease, hepatitis

Question 10

Describe the ALP levels in osteoporosis.

Answer 10

It is NORMAL unless there is a fracture.

Question 11

Which markers are used in acute pancreatitis?

Answer 11

Amylase

Lipase

Question 12

Where else is amylase found?

Answer 12

Salivary glands

NOTE: will be raised in parotitis

Question 13

What are the three forms of creatine kinase?

Answer 13

• CK-MM = skeletal muscle
• CK-BB = brain
• CK-MB = cardiac muscle

Question 14

Describe the manifestations of statin-related myopathy.

Answer 14

Can range from myalgia to rhabdomyolysis

Question 15

List some risk factors for statin-related myopathy.

Answer 15

• Polypharmacy (in particular, fibrates and cyclosporin and other drugs metabolised by CYP3A4)
• High dose
• Genetic predisposition
• Previous history of myopathy with another statin
• Vitamin D deficiency (increased risk of statin intolerance)

Question 16

List some other causes of high CK.

Answer 16

• Muscle damage
• Myopathy (e.g. Duchenne muscular dystrophy)
• MI
• Severe exercise
• Physiological (Afro-Caribbeans)

Question 17

What are two other uses of enzymes in clinical medicine?

Answer 17

• Markers of therapeutic response and drug toxicity (e.g. TPMT activity should be measured before starting thiopurines (e.g. azathioprine))
• Reagents to measure other substances (e.g. glucose oxidase is used to measure plasma glucose)

Question 18

List three cardiac enzymes that used to be used as markers of cardiac damage.

Answer 18

CK

AST

LDH

Question 19

Where are myoglobins found within cells?

Answer 19

Cytosol

Question 20

Where is CK-MB found within cells?

Answer 20

Within the mitochondira and nucleus

Question 21

Where are troponins found within cells?

Answer 21

Within the contractile apparatus

NOTE: there is also a free cytosolic pool of troponins

Question 22

Describe how troponin levels change with time following an MI.

Answer 22

• Rise at 4-6 hours post-MI
• Peaks at 12-24 hours
• Remains elevated for 3-10 days
• So, troponins should be measured at 6 hours and 12 hours after the onset of chest pain in a suspected MI

Question 23

Outline the diagnostic criteria for MI.

Answer 23

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
• ECG changes suggestive of ischaemia
• Coronary artery intervention

Pathological findings of acute MI

Question 24

How are biomarkers used when deciding whether to thrombolyse?

Answer 24

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

Question 25

What are the main biomarkers used in cardiac failure?

Answer 25

• ANP - from the atria
• BNP - from the ventricles
• BNP is used to assess ventricular function and can be used to exclude heart failure (high negative predictive value)

Question 26

Define 1 international unit of enzyme activity.

Answer 26

• Quantity of enzyme required to catalyse a reaction of 1 µmol of substrate per minute

NOTE: activity is affected by assay conditions such as pH and temperature (so reference ranges may differ between laboratories)