ChemPath: Enzymes and Cardiac Markers

Question 1

What are the two types of intracellular enzymes?

Answer 1

• Cytosolic
• Subcellular (within organelles)

Question 2

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

Answer 2

Cytosolic are released first, followed by subcellular

Question 3

In which tissues is ALP present in high concentration?

Answer 3

• Liver
• Bone
• Intestines
• Placenta

Question 4

What are the most likely sites of pathological ALP increases?

Answer 4

• Bone
• Liver

Question 5

What is an increase in bone ALP caused by?

Answer 5

Increased osteoblast activity

Question 6

What are other important biomarkers when ALP is raised?

Answer 6

• LFTs
• Vitamin D

Question 7

What technique is used to separate isoenzymes?

Answer 7

Electrophoresis

Question 8

List some physiological causes of high ALP.

Answer 8

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

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

Where are ALT and AST found

Answer 11

ALT specific for liver

AST found in liver, heart, muscle, kidney

Question 12

What are 2 causes of high GGT?

Answer 12

• Hepatobiliary disease
• Enzyme induction (specifically in alcoholics)

(can also be produced in pancreas / kindey)

Question 13

Causes of elevated LDH

Answer 13

Question 14

What are two important clincial implications of LDH levels

Answer 14

• LDH raised in haemolysis
• Serial LDH levels are taken to assess treatment response in cancers as LDH levels are associated with tumour bulk

Question 15

Describe the ALP levels in osteoporosis.

Answer 15

It is NORMAL unless there is a fracture.

Question 16

Which markers are used in acute pancreatitis?

Answer 16

Amylase

Lipase

Question 17

Where else is amylase found?

Answer 17

Salivary glands

NOTE: will be raised in parotitis

Question 18

What is macroamylase

Answer 18

Immunoglobulin binds to amylase, cannot be cleared by kindeys, thereby causing raised benign raised amylase

Request amylase electrophoresis for amylase isoenzymes

Question 19

What are the three forms of creatine kinase?

Answer 19

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

Question 20

List causes of high CK.

Answer 20

• Muscle damage - rhabdomyolysis, polymyositis/dermatomyositis
• Myopathy (e.g. Duchenne muscular dystrophy)
• Drugs e.g. statins
• MI
• Severe exercise
• Physiological (Afro-Caribbeans)

Question 21

Describe the manifestations of statin-related myopathy.

Answer 21

Can range from myalgia to rhabdomyolysis

Question 22

What are some cardiac and non-cardiac causes of raised troponins

Answer 22

Cardiac

• STEMI and NSTEMI
• Myocarditis
• Aortic dissection
• Cardiomyopahty

Non-cardiac

• PE
• Sepsis
• Trauma
• SAH

Question 23

Pathological difference between STEMI and NSTEMI

Answer 23

STEMI - Full thickness infarction

NSTEMI - partial thickness infarction

Question 24

What isoform is cardiac troponin

Answer 24

Troponin i

Question 25

Describe how troponin levels change with time following an MI.

Answer 25

* Starts to rise at 2 hours post-MI * Peaks at 12 hours * Remains elevated for 5-10 days So, troponins should be measured at 6 hours and 12 hours after the onset of chest pain in a suspected MI. >50% increase or decrease is suggestive of Cardiac injury due to ACS.

Question 26

What are the main biomarkers used in cardiac failure?

Answer 26

NT-proBNP is used to assess ventricular function and can be used to exclude heart failure (high negative predictive value)

Question 27

When should troponin be measured in patient presenting with chest pain?

Answer 27

* First measurement taken on admission, second taken 3 hours after * 50% change between both measurements indicates myocardial injury (even if measurment is within normal range

Question 28

When do the ventricles release BNP and what is its primary effect?

Answer 28

* BNP released in response volume overload stretching the ventricles * BNP stimulates naturesis, thus decreasing blood volume

Question 29

Why we measure NT pro-BNP

Answer 29

* Biologically inactive (cleaved to form BNP) * Half-life of 3 hours * Marker of BNP production * Good at **ruling out** HF (high negative predictive value)

Question 30

Normally you can measure either BNP or NT-proBNP, but in what situation use NT-proBNP over BNP?

Answer 30

Patients taking ARNI will have raised BNP due to the action of the neprolysin inhibitor, their NT-proBNP levels more accurately reflect ventricular wall stress

Question 31

At what level of NT-proBNP would trigger additional investigation

Answer 31

>400 pg/mL

Question 32

What is Km (Michaelis-Menton constant) and what is its significance

Answer 32

* Km is the concentration of substrate required to reach 50% of enzymes Vmax * Low Km means enzymes has high affinity for substrate

Question 33

Define 1 international unit of enzyme activity.

Answer 33

* 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)