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

BILP
* Bone
* Intestine
* Liver (bile ducts)
* Placenta

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4
Q

What is an increase in bone ALP caused by?

A

Increased osteoblast activity

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5
Q

What technique is used to separate isoenzymes?

A

Electrophoresis

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6
Q

List some physiological causes of high ALP.

A
  • Pregnancy - 3rd trimester (from placenta)
  • Childhood - growth spurt
  • Afro-caribbean patient
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7
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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8
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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9
Q

Describe the ALP levels in osteoporosis.

A

It is NORMAL unless there is a fracture.

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10
Q

Which markers are used in acute pancreatitis and how many xUL is significant?

A

Amylase >x10UL

Lipase >3x UL

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11
Q

Where else is amylase found?

A

Salivary glands

NOTE: will be raised in parotitis / mumps

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12
Q

What are the three forms of creatine kinase?

A
  • CK-MM = skeletal muscle
  • CK-BB = brain
  • CK-MB = cardiac muscle
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13
Q

List some risk factors for statin-related myopathy.

A
  • 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)
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14
Q

List some causes of high CK.

A
  • Muscle damage (rhabdomyolysis)
  • Myopathy (e.g. Duchenne muscular dystrophy)
  • MI
  • Statins
  • Severe exercise
  • Physiological (Afro-Caribbeans)
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15
Q

List 5 cardiac enzymes that are elevated in MI/cardiac damage

A

Myoglobin
Troponin
CK-MB
AST
LDH

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16
Q

Where is CK-MB found within cells?

A

Within the mitochondira and nucleus

17
Q

Describe how troponin levels change with time following an MI.

A
  • 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
18
Q

Outline the diagnostic criteria for MI.

A
  1. 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
  1. or Pathological findings of acute MI
19
Q

What are the main biomarkers used in cardiac failure?

A
  • 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)
20
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)

21
Q

What is Km (the Michaelis-Menten constant)?

A

Km = [substrate] at which the reaction velocity is 50% of the maximum (Vmax50)

  • High km indicates weak affinity
  • Low km indicates strong affinity
22
Q

When should troponins be measured for dx of an MI?

A

6h and 12h after onset of chest pain

23
Q

At what levels of BNP can you exclude or diagnose HF?

A

<100 = exclude HF
>400 = diagnose HF

24
Q

Explain what NTpro-BNP vs BNP is and its use?

A

Pro-BNP is cleaved into NTpro-BNP and BNP

BNP is unstable, needs lab analysis within 6h which is not realistic in some settings e.g. primary care

NTpro-BNP is more stable, allowing more time for analysis, and is more sensitive

25
Q

What are the most specific liver enzymes for liver damage?

A

ALT and GGT

26
Q

How can you tell if a rise in ALP is due to liver pathology?

A
  • If ALP rise is accompanied by a rise in GGT -> liver pathology is indicated
  • Electrophoresis separation
  • Bone specific ALP immunoassays
27
Q

What abnormality on LFTs would you see in a paracetamol OD

A

ALT in the 1000s