ChemPath: Enzymes and Cardiac Markers Flashcards
Where are most enzymes found?
Intracellularly
What are the two types of intracellular enzymes?
- Cytosolic
- Subcellular (within organelles)
Describe the order of release of intracellular enzymes when cells are damaged.
Cytosolic are released first, followed by subcellular
In which tissues is ALP present in high concentration?
- Liver
- Bone
- Intestines
- Placenta
What is an increase in bone ALP caused by?
Increased osteoblast activity
What technique is used to separate isoenzymes?
Electrophoresis
List some physiological causes of high ALP.
- Pregnancy - 3rd trimester (from placenta)
- Childhood - growth spurt
List some causes of very high ALP (>5 x upper limit of normal).
- Bone - Paget’s disease, osteomalacia
- Liver - cholestasis, cirrhosis
List some causes of moderately raised ALP (< 5 x upper limit of normal).
- Bone - tumours, fractures, osteomyelitis
- Liver - infiltrative disease, hepatitis
Describe the ALP levels in osteoporosis.
It is NORMAL unless there is a fracture.
Which markers are used in acute pancreatitis?
Amylase
Lipase
Where else is amylase found?
Salivary glands
NOTE: will be raised in parotitis
What are the three forms of creatine kinase?
- CK-MM = skeletal muscle
- CK-BB = brain
- CK-MB = cardiac muscle
Describe the manifestations of statin-related myopathy.
Can range from myalgia to rhabdomyolysis
List some risk factors for statin-related myopathy.
- 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)
List some other causes of high CK.
- Muscle damage
- Myopathy (e.g. Duchenne muscular dystrophy)
- MI
- Severe exercise
- Physiological (Afro-Caribbeans)
What are two other uses of enzymes in clinical medicine?
- 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)
List three cardiac enzymes that used to be used as markers of cardiac damage.
CK
AST
LDH
Where are myoglobins found within cells?
Cytosol
Where is CK-MB found within cells?
Within the mitochondira and nucleus
Where are troponins found within cells?
Within the contractile apparatus
NOTE: there is also a free cytosolic pool of troponins
Describe how troponin levels change with time following an MI.
- 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
Outline the diagnostic criteria for MI.
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
How are biomarkers used when deciding whether to thrombolyse?
None of the current biomarkers rise quickly enough to aid decisions regarding thrombolysis (so it is based on clinical findings and ECG)
What are the main biomarkers used in cardiac failure?
- 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)
Define 1 international unit of enzyme activity.
- 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)
