Enzymes and Cardiac Markers Flashcards
What is an enzyme?
Substance (usually a protein) that increases rate of a chemical reaction without itself being changed in the process.
What is Km (Michaelis-Menten constant)?
[substrate] at which the reaction velocity is 50% of max.
What do high and low Kms represent?
High Km: weak affinity.
Low Km: strong affinity.
How can enzymes be used to determine organ-specific injury?
Intracellular enzymes are released in response to cellular injury- can be measured in blood
Many tissues express the same enzyme so need to determine which organ is it coming from.
Clinical context can be used.
The enzyme may be predominantly released by 1 tissue after injury (e.g. serum ALT is mostly from liver).
Which organs can be responsible for abnormal ALP?
Intrahepatic or extrahepatic bile ducts: Intra/extrahepatic cholestatic liver disease.
Bone: bone turnover
Placenta: Germ-cell tumours
ALP in Intestine but not used for Ix of bowel disorders
Give 6 causes of bone related rise in ALP
Fracture
Paget’s disease
Osteomalacia/ Rickets
Cancer (primary or metastasis)
1o Hyperparathyroidism with bone involvement
Renal osteodystrophy
Give 4 causes of Intra- and 2 causes of extrahepatic cholestatic liver disease.
Intra: Hepatitis, PBC, PSC, Malignancy
Extra: Choledocholithiasis, bile duct tumour
When is a raised ALP physiological due to growth?
Childhood- bone
Pregnancy (last trimester)- placenta
What is the clinical approach to an unexplained ALP?
- Check LFTs (γ-glutamyl transferase + ALT)
- Check vitamin D
- ALP isoenzymes – performed by electrophoresis test
Why check LFTs when ALP is raised?
Gamma GT + ALT very specific for liver
Why check vitamin D if LFTs are normal when ALP is raised?
If vitamin D is low, can’t absorb phosphate so breakdown bone to release phosphate
How does ALP change through life?
Serum ALP changes as a function of age. There are age-specific cut-off ranges for ALP.
Birth: HIGH due to bone growth
Plateaus just before puberty
Falls when bone growth ceases
What are causes of a raised ALT?
Hepatic:
Hepatitis (viral, alcohol, AI)
Non-alcoholic fatty liver disease
Liver ischaemia
Toxins: Alcohol, Paracetaomol OD
Cancer
Not really used for kidney, pancreas or cardiac since better markers are available.
What are 4 broad causes of a raised γ-glutamyl transferase (γ-GT)?
Hepatobiliary disease
Enzyme induction: upregulated in response to drugs
Pancreas: Pancreatitis (not used for dx, serum amylase is better).
Kidney: Not used in kidney disease because there are better biomarkers (creatinine, eGFR, albuminuria).
What are 3 hepatobilliary causes of a raised γ-glutamyl transferase (γ-GT)?
Hepatitis
Alcoholic liver disease
Cholestatic liver disease
What is a raised γ-glutamyl transferase (γ-GT) not useful for in hepatobiliary disease?
Distinguishing hepatic or biliary disease
ALT:ALP ratio is more useful
What are 4 enzyme induction causes of raised γ-glutamyl transferase (γ-GT)?
Alcoholics (+/- liver disease)
Rifampicin
Phenytoin
Phenobarbitone
(Increased intracellular γ-GT levels so more is released in normal cell turnover)
What are causes of a raised lactate dehydrogenase?
WBC: Lymphoma
RBC: Haemolysis e.g. haemolytic anaemia
Placenta: Germ-cell testicular cancer (seminoma)
Skeletal muscle: Myositis
Liver injury: Hepatic disease but better biomarkers available
Cardiac: Better biomarkers available
What are causes of a raised serum amylase?
Pancreas: Acute pancreatitis, perforated duodenal ulcer, bowel obstruction (causes secondary injury to pancreas).
Salivary gland: Stones, infection (e.g., mumps). Less common, likely present with jaw pain.
What is macro-amylase?
Amylase bound to immunoglobulin, thus too large to be cleared by kidneys. Often benign but causes confusion.
If you suspect this, request amylase electrophoresis for amylase isoenzymes.
Benign
What are causes of a raised creatine kinase?
Skeletal muscle: Rhabdomyolysis, Myositis, polymyositis, dermatomyositis, severe exercise, myopathy (Duchene muscular dystrophy, statins).
Cardiac muscle: Cardiac injury but not used for this purpose (high-sensitivity troponin is better).
In which population is creatinine kinase generally higher?
Individuals of Afro-Carribean descent
What is Troponin I?
In cardiac + skeletal myocytes where it participates in muscle contraction.
3 types of troponin I, T + C in skeletal + cardiac muscle.
Labs do not measure skeletal muscle troponin, labs measure cardiac troponin I or T.
High sensitivity Trop I can be used to diagnose cardiac conditions.
Which primary cardiac injuries can result in an elevated trop I?
Acute coronary syndrome (STEMI, NSTEMI, unstable angina) or ACS
Myocarditis
Cardiomyopathy
Aortic dissection
