Enzymes and Cardiac Markers Flashcards
What is 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 (Michaelis-Menten constant)?
The Michaelis-Menten constant or Km = [substrate] at which the reaction velocity is 50% of the maximum.
What do high and low Kms represent?
High Km indicates weak affinity.
Low Km indicates strong affinity.
How can enzymes be used to determine organ-specific injury?
Released in response to cellular injury. Many tissues express the same enzyme so need to determine which organ is it coming from.
The clinical context can be used. The enzyme may be predominantly released by one tissue after injury (e.g., serum ALT is mostly from the liver).
What are reasons for an abnormal ALP?
Intrahepatic or extrahepatic bile ducts: Intra- or extrahepatic cholestatic liver disease.
Bone:
- Fracture
- Paget’s disease
- Osteomalacia
- Rickets
- Cancer (primary or metastasis)
- 1o Hyperparathyroidism with bone involvement
- Renal osteodystrophy
- Childhood (physiological)
Placenta:
- Pregnancy (last trimester)
- Germ-cell tumours
What is the clinical approach to an unexplained ALP?
- Check LFTs (γ-glutamyl transferase and ALT)
- Check vitamin D
- ALP isoenzymes – performed by electrophoresis test
How does ALP change through life?
Serum ALP changes as a function of age. There are age-specific cut-off ranges for ALP.
What are causes of a raised ALT?
Hepatic:
- Hepatitis (viral, alcohol)
- Non-alcoholic fatty liver disease
- Liver ischaemia
- Paracetaomol overdose
Not really used for kidney, pancreas or cardiac since better markers are available.
What are causes of a raised γ-glutamyl transferase (γ-GT)?
Hepatobiliary disease:
- Hepatitis
- Alcoholic liver disease
- Cholestatic liver disease
Enzyme induction: Alcoholics (with or without liver disease), rifampicin, phenytoin, phenobarbitone.
Pancreas: Pancreatitis (but γ-GT not used for diagnosing pancreatitis, serum amylase is better).
Kidney: Not used in kidney disease because there are much better biomarkers (creatinine, eGFR, albuminuria).
What are causes of a raised lactate dehydrogenase?
White blood cells: Lymphoma
Red blood cells: Haemolysis
Placenta: Germ-cell testicular cancer (seminoma)
Skeletal muscle: Myositis
Liver injury: Hepatic disease but better biomarkers available
Cardiac: Better biomarkers available
What is the structure of lactate dehydrogenase?
LDH has two monomers – M and H – which combine in various proportions to form 5 isoenzymes.
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).
What is macro-amylase?
Amylase bound to immunoglobulin, 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 (Deuchene muscular dystrophy, statins).
Cardiac muscle: Cardiac injury but not used for this purpose (high-sensitivity troponin is better and used instead).
In which population is creatinine kinase generally higher?
Individuals of Afro-Carribean descent