ChemPath: Enzymes and Cardiac Markers Flashcards
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?
BILP
* Bone
* Intestine
* Liver (bile ducts)
* 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
- Afro-caribbean patient
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 and how many xUL is significant?
Amylase >x10UL
Lipase >3x UL
Where else is amylase found?
Salivary glands
NOTE: will be raised in parotitis / mumps
What are the three forms of creatine kinase?
- CK-MM = skeletal muscle
- CK-BB = brain
- CK-MB = cardiac muscle
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 causes of high CK.
- Muscle damage (rhabdomyolysis)
- Myopathy (e.g. Duchenne muscular dystrophy)
- MI
- Statins
- Severe exercise
- Physiological (Afro-Caribbeans)
List 5 cardiac enzymes that are elevated in MI/cardiac damage
Myoglobin
Troponin
CK-MB
AST
LDH
Where is CK-MB found within cells?
Within the mitochondira and nucleus
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
- or Pathological findings of acute MI
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)
What is Km (the Michaelis-Menten constant)?
Km = [substrate] at which the reaction velocity is 50% of the maximum (Vmax50)
- High km indicates weak affinity
- Low km indicates strong affinity
When should troponins be measured for dx of an MI?
6h and 12h after onset of chest pain
At what levels of BNP can you exclude or diagnose HF?
<100 = exclude HF
>400 = diagnose HF
Explain what NTpro-BNP vs BNP is and its use?
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
What are the most specific liver enzymes for liver damage?
ALT and GGT
How can you tell if a rise in ALP is due to liver pathology?
- If ALP rise is accompanied by a rise in GGT -> liver pathology is indicated
- Electrophoresis separation
- Bone specific ALP immunoassays
What abnormality on LFTs would you see in a paracetamol OD
ALT in the 1000s
