ChemPath: Enzymes and Cardiac Markers Flashcards

1
Q

What are the two types of intracellular enzymes?

A
  • Cytosolic
  • Subcellular (within organelles)
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2
Q

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

A

Cytosolic are released first, followed by subcellular

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3
Q

In which tissues is ALP present in high concentration?

A
  • Liver
  • Bone
  • Intestines
  • Placenta
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4
Q

What are the most likely sites of pathological ALP increases?

A
  • Bone
  • Liver
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5
Q

What is an increase in bone ALP caused by?

A

Increased osteoblast activity

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6
Q

What are other important biomarkers when ALP is raised?

A
  • LFTs
  • Vitamin D
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7
Q

What technique is used to separate isoenzymes?

A

Electrophoresis

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8
Q

List some physiological causes of high ALP.

A
  • Pregnancy - 3rd trimester (from placenta)
  • Childhood - growth spurt
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9
Q

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

A
  • Bone - Paget’s disease, osteomalacia
  • Liver - cholestasis, cirrhosis
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10
Q

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

A
  • Bone - tumours, fractures, osteomyelitis
  • Liver - infiltrative disease, hepatitis
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11
Q

Where are ALT and AST found

A

ALT specific for liver

AST found in liver, heart, muscle, kidney

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12
Q

What are 2 causes of high GGT?

A
  • Hepatobiliary disease
  • Enzyme induction (specifically in alcoholics)

(can also be produced in pancreas / kindey)

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13
Q

Causes of elevated LDH

A
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14
Q

What are two important clincial implications of LDH levels

A
  • LDH raised in haemolysis
  • Serial LDH levels are taken to assess treatment response in cancers as LDH levels are associated with tumour bulk
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15
Q

Describe the ALP levels in osteoporosis.

A

It is NORMAL unless there is a fracture.

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16
Q

Which markers are used in acute pancreatitis?

A

Amylase

Lipase

17
Q

Where else is amylase found?

A

Salivary glands

NOTE: will be raised in parotitis

18
Q

What is macroamylase

A

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

Request amylase electrophoresis for amylase isoenzymes

19
Q

What are the three forms of creatine kinase?

A
  • CK-MM = skeletal muscle
  • CK-BB = brain
  • CK-MB = cardiac muscle
20
Q

List causes of high CK.

A
  • Muscle damage - rhabdomyolysis, polymyositis/dermatomyositis
  • Myopathy (e.g. Duchenne muscular dystrophy)
  • Drugs e.g. statins
  • MI
  • Severe exercise
  • Physiological (Afro-Caribbeans)
21
Q

Describe the manifestations of statin-related myopathy.

A

Can range from myalgia to rhabdomyolysis

22
Q

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

A

Cardiac

  • STEMI and NSTEMI
  • Myocarditis
  • Aortic dissection
  • Cardiomyopahty

Non-cardiac

  • PE
  • Sepsis
  • Trauma
  • SAH
23
Q

Pathological difference between STEMI and NSTEMI

A

STEMI - Full thickness infarction

NSTEMI - partial thickness infarction

24
Q

What isoform is cardiac troponin

A

Troponin i

25
Q

Describe how troponin levels change with time following an MI.

A
  • 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.

26
Q

What are the main biomarkers used in cardiac failure?

A

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

27
Q

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

A
  • 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
28
Q

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

A
  • BNP released in response volume overload stretching the ventricles
  • BNP stimulates naturesis, thus decreasing blood volume
29
Q

Why we measure NT pro-BNP

A
  • Biologically inactive (cleaved to form BNP)
  • Half-life of 3 hours
  • Marker of BNP production
  • Good at ruling out HF (high negative predictive value)
30
Q

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

A

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

31
Q

At what level of NT-proBNP would trigger additional investigation

A

> 400 pg/mL

32
Q

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

A
  • Km is the concentration of substrate required to reach 50% of enzymes Vmax
  • Low Km means enzymes has high affinity for substrate
33
Q

Define 1 international unit of enzyme activity.

A
  • 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)