Enzymes and Cardiac Markers Flashcards

1
Q

What is an enzyme?

A

A substance (usually a protein) that increases the rate of a chemical reaction without itself being changed in the overall process.

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2
Q

What is Km (Michaelis-Menten constant)?

A

The Michaelis-Menten constant or Km = [substrate] at which the reaction velocity is 50% of the maximum.

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3
Q

What do high and low Kms represent?

A

High Km indicates weak affinity.

Low Km indicates strong affinity.

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4
Q

How can enzymes be used to determine organ-specific injury?

A

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).

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5
Q

What are reasons for an abnormal ALP?

A

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
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6
Q

What is the clinical approach to an unexplained ALP?

A
  • Check LFTs (γ-glutamyl transferase and ALT)
  • Check vitamin D
  • ALP isoenzymes – performed by electrophoresis test
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7
Q

How does ALP change through life?

A

Serum ALP changes as a function of age. There are age-specific cut-off ranges for ALP.

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8
Q

What are causes of a raised ALT?

A

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.

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9
Q

What are causes of a raised γ-glutamyl transferase (γ-GT)?

A

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).

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10
Q

What are causes of a raised lactate dehydrogenase?

A

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

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11
Q

What is the structure of lactate dehydrogenase?

A

LDH has two monomers – M and H – which combine in various proportions to form 5 isoenzymes.

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12
Q

What are causes of a raised serum amylase?

A

Pancreas: Acute pancreatitis, perforated duodenal ulcer, bowel obstruction (causes secondary injury to pancreas).

Salivary gland: Stones, infection (e.g., mumps).

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13
Q

What is macro-amylase?

A

Amylase bound to immunoglobulin, often benign but causes confusion.

If you suspect this, request amylase electrophoresis for amylase isoenzymes.

Benign

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14
Q

What are causes of a raised creatine kinase?

A

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).

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15
Q

In which population is creatinine kinase generally higher?

A

Individuals of Afro-Carribean descent

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16
Q

What is Troponin I?

A

Located within cardiac and skeletal myocytes where it participates in muscle contraction.

There are 3 types of troponin I, T and C found in troponin isoforms are found in skeletal and 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.

17
Q

Which primary cardiac injuries can result in an elevated trop I?

A

Acute coronary syndrome (STEMI, NSTEMI, unstable angina) or ACS

Myocarditis

Cardiomyopathy

Aortic dissection

18
Q

Which secondary cardiac injuries can result in an elevated Trop I?

A

Pulmonary embolism or PE

Systemic infection

19
Q

Which factors can affect the trop result?

A

Age

Gender

Acute or chronic kidney disease

Time of test

20
Q

How should the use of trop be incorporated into clinical practice?

A
  1. When did the chest pain begin?
  2. Take troponin I on admission
  3. Take 2nd troponin 3 hours later

50% increase or decrease suggestive of cardiac myocyte injury.

21
Q

How long after injury does trop stay elevated?

A

Troponin I begins to rise at 2-4 hours.

Peaks 12 hours (range 8-28 hours).

Returns to normal 5-10 days later.

22
Q

What is a normal trop?

A

Male <35 ng/L
Female <16 ng/L