Clinical Enzymology Flashcards
Why do we measure enzymes?
Detection of suspected disease at pre-clinical stage
Confirmation of suspected disease and assessing severity
Localisation of disease to organs
Characterisation of organ pathology
Assessing the response to therapy
Organ function assessment
Assessing genetic susceptibility to drug side effects
Detection of inherited metabolic disease
Detection of vitamin deficiencies
What factors determine enzyme activities in serum/ plasma?
age
gender
pregnancy
race
time of day
genetics
drugs
disease process, progress and treatment e.g. surgery
What processes trigger the release of enzymes from cells?
Hypoxia – loss of oxygen supply due to occlusion, or inadequate oxygenation, or loss of oxygen carrying capacity
Cellular damage due to chemicals, drugs
Physical damage due to trauma, surgery, burns, radiation etc.
Immune disorders – anaphylaxis, autoimmune disease etc
Microbiological agents – bacteria, viruses, fungi, protozoa, helminths
Genetic defects – many, e.g. Duchenne’s Muscular Dystrophy
Nutritional disorders – protein-calorie, vitamin, mineral deficiency
How are enzymes analysed in lab?
fixed time- measuring at end point
continous- meausring throughout
measure of end product using spectrophotometry
electrophoresis- measure type
What are the problems with enzyme measurement?
Not specific i.e. can be found in more than one tissue in the body.
Particular requirements – temperature, pH etc.
Assays must be optimised
Describe alkaline phosphatase? (ALP)
Hydrolase class
Catalyses the cleavage of orthophosphate from orthophosphoric monoesters under alkaline conditions
Present as isoenzymes
Bone
Liver
Kidney
Intestine
Placenta
Describe creatine kinase? (CK)
Catalyses formation of ATP from ADP and creatine phosphate in muscle.
3 isoenzymes
CK-MM
CK-BB
CK-MB
Measured as total CK as a marker of skeletal muscle damage
Causes of raised CK?
Acute muscle injury
Surgical operations
Vigorous exercise
Rhabdomyolysis
Chronic neuromuscular disease e.g. Duchenne muscular dystrophy
Acute myocardial infarction
Statins
Macro-CK
Describe Thiopurine S-methyltransferase? (TPMT)
Metabolises immunosuppressant Azothioprine
Different genetic variants affect activity
If activity of this enzyme are low, patient at risk of toxicity
If activity of this enzyme are high, patient may need higher dose
Describe alpha galactosidase?
Glycoside hydrolaseenzymethat hydrolyses the terminal alpha-galactosylmoietiesfrom glycolipids and glycoproteins
Fabry disease – lysosomal storage disorder
X-linked disorder but also causes problems for females carrying a copy of an affected gene
Features include
Pain in hands and feet
Angiokeratomas
Decreased sweating
Corneal opacity
GI problems
Hypertrophic cardiomyopathy
Renal failure
Describe cholinesterases?
Group of enzymes which aid the function of the central nervous system
What are the who main kinds of cholinesterases?
Acetylcholinesterase
Butyrlcholinesterase
Describe butyrlcholinesterases?
Found in serum, liver , pancreas, heart, white matter of brain
Function is the process and metabolizing of drugs
Purpose of lab measurement is for a patient with a history of prolonged apnoea or paralysis post anaethesia
Describe acetylcholinesterases?
Found in erythrocytes, lungs , spleen , nerve endings, grey matter of brain
Function is to break down acetylcholine to help transmit nerve signals across nerve endings
purpose of lab measurement is occupational monitoring and acute exposure to organophosphate pesticides
