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YR5 Chemical Pathology > Enzymes and Cardiac Markers > Flashcards

Enzymes and Cardiac Markers Flashcards

1
Q

What is an enzyme?

A

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

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2
Q

What is Km (Michaelis-Menten constant)?

A

[substrate] at which the reaction velocity is 50% of max.

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3
Q

What do high and low Kms represent?

A

High Km: weak affinity.

Low Km: strong affinity.

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4
Q

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

A

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).

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5
Q

Which organs can be responsible for abnormal ALP?

A

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

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6
Q

Give 6 causes of bone related rise in ALP

A

Fracture

Paget’s disease

Osteomalacia/ Rickets

Cancer (primary or metastasis)

1o Hyperparathyroidism with bone involvement

Renal osteodystrophy

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7
Q

Give 4 causes of Intra- and 2 causes of extrahepatic cholestatic liver disease.

A

Intra: Hepatitis, PBC, PSC, Malignancy

Extra: Choledocholithiasis, bile duct tumour

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8
Q

When is a raised ALP physiological due to growth?

A

Childhood- bone

Pregnancy (last trimester)- placenta

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9
Q

What is the clinical approach to an unexplained ALP?

A
  1. Check LFTs (γ-glutamyl transferase + ALT)
  2. Check vitamin D
  3. ALP isoenzymes – performed by electrophoresis test
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10
Q

Why check LFTs when ALP is raised?

A

Gamma GT + ALT very specific for liver

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11
Q

Why check vitamin D if LFTs are normal when ALP is raised?

A

If vitamin D is low, can’t absorb phosphate so breakdown bone to release phosphate

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12
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.

Birth: HIGH due to bone growth

Plateaus just before puberty

Falls when bone growth ceases

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13
Q

What are causes of a raised ALT?

A

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.

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14
Q

What are 4 broad causes of a raised γ-glutamyl transferase (γ-GT)?

A

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).

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15
Q

What are 3 hepatobilliary causes of a raised γ-glutamyl transferase (γ-GT)?

A

Hepatitis

Alcoholic liver disease

Cholestatic liver disease

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16
Q

What is a raised γ-glutamyl transferase (γ-GT) not useful for in hepatobiliary disease?

A

Distinguishing hepatic or biliary disease

ALT:ALP ratio is more useful

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17
Q

What are 4 enzyme induction causes of raised γ-glutamyl transferase (γ-GT)?

A

Alcoholics (+/- liver disease)

Rifampicin

Phenytoin

Phenobarbitone

(Increased intracellular γ-GT levels so more is released in normal cell turnover)

18
Q

What are causes of a raised lactate dehydrogenase?

A

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

19
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). Less common, likely present with jaw pain.

20
Q

What is macro-amylase?

A

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

21
Q

What are causes of a raised creatine kinase?

A

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).

22
Q

In which population is creatinine kinase generally higher?

A

Individuals of Afro-Carribean descent

23
Q

What is Troponin I?

A

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.

24
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

25
Q

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

A

Pulmonary embolism

Systemic infection

Anaemia e.g. upper GI bleed

26
Q

Which factors can affect the trop result?

A

Age

Gender M>F

Acute or chronic kidney disease

Number of myocytes injured

Time of test

27
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 h later

50% increase or decrease suggestive of cardiac myocyte injury due to ACS

28
Q

How long after injury does trop stay elevated?

A

Troponin I begins to rise at 2-4h

Peaks 12h (range 8-28h).

Returns to normal 5-10 days later.

29
Q

What is a normal trop?

A

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

30
Q

A 40M presents with abdominal pain. The serum ALT is elevated. What tissue is the ALT most likely coming from?

A

Liver

31
Q

What is LDH associated with in germ cell testicular cancer and lymphoma?

A

Tumour bulk

High LDH = big tumour = poor prognosis

Monitor in remission

32
Q

What must be accounted for to make a diagnosis of cardiac myocyte injury?

A

Hx

Exam

ECG

Troponin

33
Q

A 45F with long hx of high alcohol intake, presents with vomiting and severe epigastric pain radiating to her back, partially alleviated on leaning forward. What is the diagnosis?

A

Acute pancreatitis

34
Q

What is the pathophysiology of STEMI, NSTEMI, unstable and stable angina?

A

Narrowing of the coronary arteries due to atherosclerotic plaque accumulation on a spectrum from 50% narrowing to complete occlusion

STEMI, NSTEMI + UA: admit

SA: outpatients

35
Q

How would you manage a patient with cardiac chest pain and ST elevation in any ECG leads?

A

Urgent cardiology review

Needs coronary revascularisation

Don’t wait for Troponin

Acute total occlusion of a coronary artery- needs to be opened so blood can perfuse heart to avoid HF.

Full thickness necrosis of cardiomyocytes

36
Q

How would you manage a patient with cardiac chest pain, abnormal ECG and elevated troponins?

A

Urgent cardiology review

Partial occlusion- some blood can perfuse the heart so there is partial cardiomyocyte necrosis

If left untreated can progress to STEMI

37
Q

How would you manage a patient with cardiac chest pain, normal ECG/ ST depression or T wave inversion with normal troponins?

A

Urgent cardiology review

At high risk of progression to MI

38
Q

How would you manage a patient with exertional chest pain that is relieved by rest or GTN, with a normal resting ECG, 2 troponin results within the ref ranges and with <50% change in results?

A

Senior review + likely discharge with outpatient cardiology FU

39
Q

How would you manage a patient with non-specific chest pain, normal ECG and normal troponins?

A

Very unlikely cardiac in nature

Negative predictive value of troponins is really good

40
Q

Describe the synthesis of BNP and NT-proBNP

A

Pro BNP has an N terminal + C terminal

Broken down to NT-proBNP + BNP

BNP: biologically active

Release BNP when there is volume overload or the cardiac myocytes are stretched

BNP does to kidney, causing nature’s to offload the volume

41
Q

Describe the use of NT-proBNP

A

BNP half life: 80mins - short + difficult to measure

NT-proBNP half life: 3h- more stable to measure

NT-proBNP produced in equimolar amounts as BNP

NT-proBNP used to exclude HF- if negative unlikely HF

42
Q

Which drug can interfere with BNP measurements, and thus reinforces the importance of measuring NT-proBNP?

A 
Entresto (tx for HF)
Contains Sacubitril (Neprilysin inhibitor)

Neprilysin breaks down BNP

Inhibition of neprilysin causes falsely high BNP

YR5 Chemical Pathology (16 decks)

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