ChemPath: Enzymes and Cardiac Markers Flashcards
Where are most enzymes found?
Intracellularly
Why might serum enzymes be elevated?
- infection
- immune mediated/ inflammation- T1DM/ RA
- ischaemia- MI, stroke, ischaemic colitis/ hepatitis
- inherited
- trauma
- toxins- medications, rec drugs
- tumour
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- intrahepatic/ extrahepatic BDs
- 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, renal osteodystrophy, rickets
- Liver - cholestasis, cirrhosis
- Germ cell tumours
List some causes of moderately raised ALP (< 5 x upper limit of normal).
- Bone - tumours, fractures, osteomyelitis
- Liver - infiltrative disease, hepatitis
Difference between ALT and AST
ALT more specific to liver as higher there but AST found in liver, heart, kidneys
Causes of raised ALT- alanine transaminase
hepatic: toxins (alcohol/ paracetamol OD), hepatitis, NAFL, cancer, ischaemia
not used for kidney, pancreatitis or MI diagnosis
Why might GGT be elevated?
hepatobiliary: hepatitis, alcoholic liver, cholestatic
enzyme induction: alcoholics, rifampicin, phenytoin, phenobarbitone
pancreas: pancreatitis but better markers
kidney can affect too
Why might lactate dehydrogenase be elevated?
found in tissues without mitochondria (anaerobic resp)
WBC: lymphoma
RBC: haemolysis
placenta: germ-cell testicular cancer - seminoma
skeletal muscle: myositis
can be in cardiac and liver injury
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
why might serum amylase be elevated?
- acute pancreatitis, perforated duodenal ulcer, bowel obstruction
- stones/ infection in salivary gland
- macro-amylase (amylase bound to Ig- benign, can do electrophoresis)
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)
- Polymyositis, dermatomyositis
- 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
What factors affect troponin result?
age
gender
acute or chronic kidney disease
number of myocytes injured
Causes of elevated cardiac troponin I
primary cardiac injury:
- ACS: STEMI/ NSTEMI, angina
- myocarditis
- cardiomyopathy
- aortic dissection
secondary cardiac injury:
- PE
- systemic infection
- anaemia - upper GI bleed
Describe how troponin levels change with time following an MI.
- Rise at 2-4-6 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- >50% increase= ACS
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)
When is BNP released?
in response to cardiac overload or muscle stretch
How is BNP produced?
from NPPB gene which produces a molecule which is cleaved into NT-proBNP and BNP, which is biologically active
blood tests usually measure NT-proBNP as half life 3 hours but BNP can be measured in hospital
What drug can falsely increase BNP?
Entresto contains a neprolysin inhibitor which stops break down of BNP, leading to higher levels so NT-proBNP measured instead
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)
How can BNP be used in heart failure diagnosis?
ruling out HF + assess long-term prognosis but echo and clinical judgement needed for diagnosis
