enzymes and cardiac markers Flashcards
definition of an enzyme
a substance (usually a protein) that increases the rate of a chemical reaction without itself being changed in the overall process
what is Km
The Michaelis-Menten constant or Km = [substrate] at which the reaction velocity is 50% of the maximum.
high Km indicates weak binding
low Km indicates strong binding.
Black needed 1 unit to reach Vmax
Red needed 5 units to reach Vmax
Lower the Km the better
what is Km
The Michaelis-Menten constant or Km = [substrate] at which the reaction velocity is 50% of the maximum.
high Km indicates weak binding
low Km indicates strong binding.
Black needed 1 unit to reach Vmax
Red needed 5 units to reach Vmax
Lower the Km the better
what do elevated serum enzymes suggest
diseased organ - because released in response to cellular injury eg:
* Infection (viral, bacterial, fungal)
* Immune mediated/inflammation (hypersensitivity reactions), e.g., T1DM, Asthma, Rheumatoid arthritis
* Ischaemia (MI, Stroke, ischaemic colitis/hepatitis, haemorrhage)
* Inherited
* Trauma
* Toxins (medications, recreational drugs, alcohol)
* Tumour
how do you know which organ the marker is coming from
clinical context
or enzyme released predominantly by one tissue
biochemical markers used for screening
faecal immunochemical test for Bowel cancer;
midnight salivary cortisol or 24-hour urine cortisol for suspected Cushing’s;
TSAT for haemachromatosis,
pre-natal screening tests for down’s syndrome (^hCG, inhibin A, decreased AFP unconjugated oestriol)
what can biochemical tests be used to help with
screening
dx
response to rx- -eg cholesterol levels after starting statins
long term monitoring - AFP in after surgery for liver cancer, HbA1c for Diabetes,
what is isoenzyme testing
An isoenzyme are a group of enzymes that perform the same function but they each group has a slightly different structure, which can be picked up by testing.
what organs produce ALP
intrahepatic or extrahepatic bile ducts
bone
placenta
intestine
-ALP has 4 isoenzymes in 4 different organs, so in each organ ALP carries out the same function but it has a slightly different structure in each organ
bone causes for raised ALP
Fracture,
Paget’s disease,
Osteomalacia, Rickets,
cancer (primary or metastasis),
1o hyperparathyroidism with bone involvement,
renal osteodystrophy
Childhood (physiological)
placenta causes of high ALP
Pregnancy (last trimester) - placenta produces ALP - so increases as placenta gets bigger = physiological
Germ-cell tumours
approach to raised ALP
- Check LFTs
- If LFTs normal, check Vitamin D - if low = reduced absorption of phos from gut -> break down bone to release phosphate, ALP will remove phos from the bone matrix; (low phosphate stimulates 1a renal hydroxylase producing calcitriol and inhibition of FGF23, thereby increasing serum phosphate)
describe the age changes of ALP
At birth, ALP is high because of bone growth, ALP then plateaus until just before puberty in boys and girls and falls to adult levels when bone growth ceases
use of ALT and AST clinically
Used when liver disease is suspected
ALT more specific for liver - but both ALT and AST basically give the same info
AST can come from heart, liver, skeletal muscle or kidney
hepatic causes of raised ALT
Toxins (Alcohol, paracetamol OD)
Hepatitis (viral, alcohol, autoimmune) Non-alcoholic fatty liver disease
Cancer
Ischaemia
causes of raised LDH
haemolytic anaemia - high LDH, low haptoglobin, high K and phos and bilirubin
causes of elevated troponin
when do you measure troponin
two troponin measurements, one on admission and another 1 hour later, and if there is a 50% increase or decrease then this is highly suggestive of dynamic cardiac myocyte injury
trop 1 rises in 2-4 hr from chest pain onset
within a few hours , there is an exponential increase
Trop I remains elevated for 5-10 days
if had MI 7 days ago - trop probs normal - consider in context of hx and ecg
pathway for cardiac chest pain
STEMI = cardiac sounding chest pain + ST elevation show urgently to a senior (needs urgent IP cardio review) don’t wait for troponin
NSTEMI = cardiac sounding chest pain + abnormal ECG + elevated troponins -> urgent senior review (will probably need IP cardio review)
Unstable angina = cardiac sounding chest pain + normal ECG or ST depression or T wave inversion with normal troponins -> urgent senior review, high risk for progression to MI (needs urgent IP cardio review).
Angina = Exertional chest pain relieved by rest or GTN + normal resting ECG + two troponin results that are within the reference range and there is not a 50% change in the results, senior review and probably discharge with outpatient cardiology fu
non-specific chest pain, a normal ECG and troponin is unlikely to have cardiac chest pain – negative predictive value is good
HF dx guidelines
