Enzymes and Cardiac Markers Flashcards
What is an enzyme
A protein which catalyses one or more specific biochemical reactions
What is clinical enzymology
The application of the science of enzymes to the diagnosis and treatment of disease
How does the concentration of enzymes change after catalysing a reaction
Concentration remains the same before and after the reaction
How can measuring enzyme levels help in diagnosis of pathological conditions
Detects tissue injury - enzymes are intracellular - levels of the intracellular enzymes increase hollowing tissue injury
How are the ranges for normal enzyme level
Small amounts of the intracellular enzymes are routinely detected in plasma as a result of normal cell turnover
What two processes lead to increased plasma levels of enzymes (2)
Leaky membranes - cytosolic enzymes
Cell necrosis - cystosolic and sub-cellular enzymes
What is key when measuring enzyme levels
The timing is crucial - cytosolic first, then sub-cellular
Ignoring optimal diagnostic time windows can lead to misdiagnosis
What are the causes of increased serum enzyme levels (3)
Cell injury
Increased synthesis
Decreased clearance
Where may enzyme levels be measured
In serum to detect injury to a tissue that makes the enzymes (increased levels)
In the tissue to identify abnormalities in or absence of the enzymes, which may cause disease (usually decreased levels)
Most useful when measured in the context of a working clinical diagnosis
How can you localise tissue locatiom of the enzyme
Some enzymes may exist in different forms - iso-enzymes
Individual iso-enzymes are characteristic to particular tissues
Measuring an additional enzyme that is released only by one of the tissues in question
Where is Alkaline Phosphate located (4)
Liver
Bone
Intestine
Placenta
What are increases in ALP most often due to (2)
Liver or bone disease
What bone diseases cause a raised ALP
Associated with increased osteoclastic activity
A 39 year old woman with BMI of 43, presented with elevated alkaline phosphatase and RUQ pain. Your laboratory does not offer iso-enzyme testing. What other enzyme can you measure? (3)
GGT
Electrophoretic separation
Bone specific ALP immunoassay now available
How can liver and bone ALP rises be differentiated (3)
GGT measurement
Electrophoretic separation
Bone specific ALP immunoassay now available
What are the two main causes of raised ALP (2)
Physiological
Pathological
What are the causes of physiological raise of ALP (2)
Pregnancy (Placental ALP) - 3rd trimester
Childhood - especially during growth spurt
What are the causes of pathological raised ALP (4)
> 5 x ULN: bone (Paget’s, osteomalacia), liver (cholestasis, cirrhosis)
<5 x ULN: bone (tumours, fractures, osteomyelitis), liver (infiltrative disease, hepatitis)
What happens to ALP in osteoporosis
NOT increased unless complicated by a fracture
What is amylase used as a marker for
Acute pancreatitis
What are the features of acute pancreatitis
Secreted by exocrine pancreas
High serum amylase activity in acute pancreatitis
Usually > 10 times upper limit of normal
Remember salivary isoenzyme exists
Small increases may be seen in other acute abdomen states
What is the most widely used marker of muscle damage
Creatine Kinase (CK)
What are the three forms of CK and where are they found (3)
CK-MM - skeletal muscles
CK-MB (1 and 2) - cardiac muscles
CK-BB - brain - activity minimal even in severe brain damage
What CK isoform is usually found in normal plasma levels
CK-MM
What are the risk factors for statin related myopathy (4)
Polypharmacy ( fibrates – gemfibrosil, cyclosporin, other drugs metabolised by the CYP 3A4 system)
High dose
Genetic predisposition
Previous history of myopathy with another statin
What are the causes of raised CK (5)
Muscle damage due to any cause Myopthy e.g. Duchenne muscular dystrophy (>10xULN) Myocardial Infarction (>10xULN) Severe exercise (5xULN) Physiological – Afro-Caribbean (<5xULN)
A 45 year old woman with long standing history of high alcohol intake, presents to A&E with severe epigastric pain, which radiates to her back and associated with vomiting. Her pain is partially alleviated by sitting forward. What is the most likely working clinical diagnosis?
Acute pancreatitis.
A 45 year old woman with long standing history of high alcohol intake, presents to A&E with severe epigastric pain, which radiates to her back and associated with vomiting. Her pain is partially alleviated by sitting forward. Which enzyme measurement might be helpful with the diagnosis?
Amylase
An 82 year old women presented with bone pain, history of fractures and bowing of her tibia. Which enzyme measurement might be helpful with the diagnosis?
ALP
A 64 year old man who smokes and has a family history of cardiovascular disease has recently been started on atorvastatin. Three weeks after commencing the tablet, he complains of generalised muscle pain. What is the working clinical diagnosis?
Statin related myopathy
A 64 year old man who smokes and has a family history of cardiovascular disease has recently been started on atorvastatin. Three weeks after commencing the tablet, he complains of generalised muscle pain. What enzyme will help with the diagnosis?
CK
What can enzymes be used as markers of (3)
Markers of therapeutic responses/drug toxicity
AS reagents for measurement of other substances
As markers of tissue damage
What enzyme markers are useful in ACS (3)
Troponin
Myoglobin
CK-MB
What is the best immediate enzyme marker of MI
CK (peaks 1 day)
What enzyme markers can be used for MI (3)
Myoglobin (peaks 2-3 hours)
Cardiac troponin (peaks 1 day)
CK-MB (peaks 1 day)
What is the investigation of choice for MI
Troiponin
What makes troponin a useful marker for MI (3)
Rise 4-6 hours post MI
Peak 12-24 hours post MI
Remain elevated for 3-10 days
When should troponin be measured post-MI (2)
6 hours
12 hours
What is the diagnostic criteria for acute MI
(1) Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) with at least one of the following:
(a) ischemic symptoms
(b) pathologic Q waves on the ECG
(c) ECG changes indicative of ischemia
(d) coronary artery intervention
(2) Pathologic findings of an acute MI
What does current diagnosis of MI still not help with
Regarding decisions regarding thrombolysis
What are the biomarkers of heart failure (2)
Natriuretic peptides: Atrial natriuretic peptide (atria)
Brain natriuretic peptide (ventricles)
What natriuretic peptide is the most useful to exclude heart failure
BNP (assess ventricular function)
A 52 year old man presented to his GP with a history of exercise-induced central chest pain which radiated to his left arm and neck a week ago. As the pain lasted for half an hour, and subsided on rest he decided to not to go to his GP until today. He’s currently pain free, and his ECG at the GP surgery was normal. Which biomarker measurement might be helpful with the diagnosis?
Cardiac Troponins (remain elevated for 3-10 days)
What is 1 international unit (U) of enzyme activity
The quantity of enzyme that catalyses the reaction of one micromol of substrate per minute
What is enzyme activity dependent on (2)
Temperature
pH
