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?
- Liver
- Bone
- Intestines
- Placenta
What are the most likely sites of pathological ALP increases?
- Bone
- Liver
What is an increase in bone ALP caused by?
Increased osteoblast activity
What are other important biomarkers when ALP is raised?
- LFTs
- Vitamin D
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
Where are ALT and AST found
ALT specific for liver
AST found in liver, heart, muscle, kidney
What are 2 causes of high GGT?
- Hepatobiliary disease
- Enzyme induction (specifically in alcoholics)
(can also be produced in pancreas / kindey)
Causes of elevated LDH
What are two important clincial implications of LDH levels
- LDH raised in haemolysis
- Serial LDH levels are taken to assess treatment response in cancers as LDH levels are associated with tumour bulk
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 is macroamylase
Immunoglobulin binds to amylase, cannot be cleared by kindeys, thereby causing raised benign raised amylase
Request amylase electrophoresis for amylase isoenzymes
What are the three forms of creatine kinase?
- CK-MM = skeletal muscle
- CK-BB = brain
- CK-MB = cardiac muscle
List causes of high CK.
- Muscle damage - rhabdomyolysis, polymyositis/dermatomyositis
- Myopathy (e.g. Duchenne muscular dystrophy)
- Drugs e.g. statins
- MI
- Severe exercise
- Physiological (Afro-Caribbeans)
Describe the manifestations of statin-related myopathy.
Can range from myalgia to rhabdomyolysis
What are some cardiac and non-cardiac causes of raised troponins
Cardiac
- STEMI and NSTEMI
- Myocarditis
- Aortic dissection
- Cardiomyopahty
Non-cardiac
- PE
- Sepsis
- Trauma
- SAH
Pathological difference between STEMI and NSTEMI
STEMI - Full thickness infarction
NSTEMI - partial thickness infarction
What isoform is cardiac troponin
Troponin i
Describe how troponin levels change with time following an MI.
- 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.
What are the main biomarkers used in cardiac failure?
NT-proBNP is used to assess ventricular function and can be used to exclude heart failure (high negative predictive value)
When should troponin be measured in patient presenting with chest pain?
- 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
When do the ventricles release BNP and what is its primary effect?
- BNP released in response volume overload stretching the ventricles
- BNP stimulates naturesis, thus decreasing blood volume
Why we measure NT pro-BNP
- Biologically inactive (cleaved to form BNP)
- Half-life of 3 hours
- Marker of BNP production
- Good at ruling out HF (high negative predictive value)
Normally you can measure either BNP or NT-proBNP, but in what situation use NT-proBNP over BNP?
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
At what level of NT-proBNP would trigger additional investigation
> 400 pg/mL
What is Km (Michaelis-Menton constant) and what is its significance
- Km is the concentration of substrate required to reach 50% of enzymes Vmax
- Low Km means enzymes has high affinity for substrate
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)
