ChemPath: Enzymes and Cardiac Markers

Question 1

Where are most enzymes found?

Answer 1

Intracellularly

Question 2

Why might serum enzymes be elevated?

Answer 2

• infection
• immune mediated/ inflammation- T1DM/ RA
• ischaemia- MI, stroke, ischaemic colitis/ hepatitis
• inherited
• trauma
• toxins- medications, rec drugs
• tumour

Question 3

What are the two types of intracellular enzymes?

Answer 3

• Cytosolic
• Subcellular (within organelles)

Question 4

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

Answer 4

Cytosolic are released first, followed by subcellular

Question 5

In which tissues is ALP present in high concentration?

Answer 5

• Liver- intrahepatic/ extrahepatic BDs
• Bone
• Intestines
• Placenta

Question 6

What is an increase in bone ALP caused by?

Answer 6

Increased osteoblast activity

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, renal osteodystrophy, rickets
• Liver - cholestasis, cirrhosis
• Germ cell tumours

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

Difference between ALT and AST

Answer 11

ALT more specific to liver as higher there but AST found in liver, heart, kidneys

Question 12

Causes of raised ALT- alanine transaminase

Answer 12

hepatic: toxins (alcohol/ paracetamol OD), hepatitis, NAFL, cancer, ischaemia

not used for kidney, pancreatitis or MI diagnosis

Question 13

Why might GGT be elevated?

Answer 13

hepatobiliary: hepatitis, alcoholic liver, cholestatic

enzyme induction: alcoholics, rifampicin, phenytoin, phenobarbitone

pancreas: pancreatitis but better markers

kidney can affect too

Question 14

Why might lactate dehydrogenase be elevated?

Answer 14

found in tissues without mitochondria (anaerobic resp)

WBC: lymphoma

RBC: haemolysis

placenta: germ-cell testicular cancer - seminoma

skeletal muscle: myositis

can be in cardiac and liver injury

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

why might serum amylase be elevated?

Answer 18

• acute pancreatitis, perforated duodenal ulcer, bowel obstruction
• stones/ infection in salivary gland
• macro-amylase (amylase bound to Ig- benign, can do electrophoresis)

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

Describe the manifestations of statin-related myopathy.

Answer 20

Can range from myalgia to rhabdomyolysis

Question 21

List some risk factors for statin-related myopathy.

Answer 21

• 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 22

List some other causes of high CK.

Answer 22

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

Question 23

What are two other uses of enzymes in clinical medicine?

Answer 23

• 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 24

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

Answer 24

CK

AST

LDH

Question 25

Where are myoglobins found within cells?

Answer 25

Cytosol

Question 26

Where is CK-MB found within cells?

Answer 26

Within the mitochondira and nucleus

Question 27

Where are troponins found within cells?

Answer 27

Within the contractile apparatus NOTE: there is also a free cytosolic pool of troponins

Question 28

What factors affect troponin result?

Answer 28

age gender acute or chronic kidney disease number of myocytes injured

Question 29

Causes of elevated cardiac troponin I

Answer 29

primary cardiac injury: * ACS: STEMI/ NSTEMI, angina * myocarditis * cardiomyopathy * aortic dissection secondary cardiac injury: * PE * systemic infection * anaemia - upper GI bleed

Question 30

Describe how troponin levels change with time following an MI.

Answer 30

* Rise at 2-4-6 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- \>50% increase= ACS

Question 31

Outline the diagnostic criteria for MI.

Answer 31

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 32

How are biomarkers used when deciding whether to thrombolyse?

Answer 32

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

Question 33

What are the main biomarkers used in cardiac failure?

Answer 33

* 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 34

When is BNP released?

Answer 34

in response to cardiac overload or muscle stretch

Question 35

How is BNP produced?

Answer 35

from NPPB gene which produces a molecule which is cleaved into NT-proBNP and BNP, which is biologically active blood tests usually measure NT-proBNP as half life 3 hours but BNP can be measured in hospital

Question 36

What drug can falsely increase BNP?

Answer 36

Entresto contains a neprolysin inhibitor which stops break down of BNP, leading to higher levels so NT-proBNP measured instead

Question 37

Define 1 international unit of enzyme activity.

Answer 37

* 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)

Question 38

How can BNP be used in heart failure diagnosis?

Answer 38

ruling out HF + assess long-term prognosis but echo and clinical judgement needed for diagnosis