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IASM + CPRS Practicals > Chemical Pathology > Flashcards

Chemical Pathology Flashcards

1
Q

Rise in Troponin is specific to heart but not specific to cause

A

Non MI myocardial injury:
- myocarditis

Multifactorial myocardial injury:
- pulmonary embolism

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2
Q

Serial measurement of cardiac Troponin

A

0, 3, 6 hours
If initial levels negative —> additional measurements
Still negative —> exclude AMI

Rise is bigger in MI than myocarditis
Chronic heart failure —> no rise/fall

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3
Q

Definition of MI

A
  • Cardiac markers + symptoms / ECG/ imaging/ intracoronary thrombus
  • at least one cardiac marker > 99th percentile of upper reference limit
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4
Q

5 types of MI

A

Type 1: secondary to plaque
Type 2: not due to ACS (coronary spasm, embolism)
Type 3: sudden cardiac death (no biomarker)
Type 4: procedure related (PCI)
Type 5: coronary artery bypass grafting

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5
Q

Approach to cardiac marker abnormality

A
  • Test validity
  • level and trend
  • relationship too symptom
  • exclude non-AMI cause
  • consider AMI cause
  • acute / long term treatment
  • monitoring
Rising may not duet to AMI
Late presentation of MI may not appear to be changing (near peak / gradual down)
Analytical interference (use other instrument)
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6
Q

3 major natriuretic peptide

A

ANP (from atria):
—> response to pressure / volume overload —> natriuresis, oppose RAAS

BNP (from ventricle):
—> response to cardiac wall stretch —> natriuresis, reduce preload
—> BNP + NTproBNP (byproduct)
—> diagnose ***heart failure who present acutely with dyspnea
—> identify cardiac involvement
—> prognostic marker in HF, ACS (high BNP —> poorer prognosis)
—> monitor drug therapy

CNP (vascular endothelium):
—> regulate vascular tone

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7
Q

Criteria for valid Therapeutic Drug Monitoring (TDM)

A
  1. Poor correlation between dose and effect
  2. Narrow therapeutic window
  3. Absence of good clinical marker of effect
  4. Good correlation between plasma concentration and effect
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8
Q

Drugs need TDM

A

Digoxin

  • 2 compartment
  • high volume of distribution —> distribute mainly in tissue
  • blood concentration correlate with effect after 6-8 hours
  • collection time (minimum 8 hours, prefer 12 hours)
  • renal excreted
  • 0.5-2.0 ng/mL (critical value: 2.5)
  • toxicity: arrhythmia, nausea, vomiting
  • **- hypokalaemia, hypomagnesemia, hypercalcemia, impaired renal function enhance toxicity
  • activated charcoal, Digibind (Digoxin-specific antibody), haemodialysis not effective since distribute in tissue
  • immunoassays may not be accurate: Interference: Digoxin-like immunoreactive substance (DLIS), Megdigoxin, steroid, Spironolactone
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9
Q

Pharmacogenetics of Clopidogrel

A
  • pro-drug —> convetered to active metabolite (inhibit ADP P2Y12 and plate activation)
  • 2C19:
    *1 —> wild type
    *2 —> no activity
    3 —> no activity
    (    2 and *3 account for almost all poor metabolisers in Asian)
  • 2 defective copies of allele may not achieve therapeutic effect
    —> increase dose / switch to other drugs
  • 1 defective copy —> increase dose
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10
Q

Urine analysis

A
  1. Macroscopic:
    - colour: red —> haemoglobin, myoglobin, drugs, food
    - turbidity
    - volume
  2. Microscopic:
    - casts (ligh chains)
    - crystals
    - bacterial staining / cultrue
    - chyle (lymph due to inflammation of glomerulus)
  3. Chemical analysis (urine dipstick)
    - limitations: pathologic vs non-pathologic cause of abnormal urine dipstick
    - false-positive vs false-negative
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11
Q

Urine pregnancy test

A

Lower limit of detection (high sensitivity)

Urine hCG: 25 mIU/mL

Blood hCG:

  • Non-pregnant: <5
  • 0.2-1 week: 5-50 mIU/L
  • Every week increase 10x

False positive:

  • early miscarriage
  • missed reaction time (sit for too long —> do not wait till +ve)
  • drugs: hCG shot for infertility treatment
  • faint evaporation line
  • abuse of drugs
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12
Q

Urine sample collection

A
  • spot
  • timed (24 hour: first void in morning discarded, subsequent collect every void)
  • midstream
  • Creatinine clearance
  • 24 hour urine collection CrCl:
    urine creatinine x urine volume / plasma creatinine x time
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13
Q

Cerebrospinal fluid

A
  • from Choroid plexus
  • clear fluid with NO cells
  • precious sample
  • procedure for CSF collection
    1. Four tubes under aseptic technique (needle into spine)
    2. Each tube 2-4ml
    3. Send promptly within 1 hour
    4. Do not refrigerate

Analysis:

  • colour/ appearance: blood, turbidity, xanthochromia
  • open pressure measurement
  • chemical analysis (lactate)
  • immunological (antibodies)
  • anatomical pathology (cytology)
  • high protein —> life-threatening —> protein leak through BBB
  • low glucose —> consumed by bacteria
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14
Q

Pleural fluid

A
  • 30ml normally

Chemical analysis:

  • pH
  • LDH
  • protein
  • TAG (chylothorax)

Transudate = total protein < 30g/L

  • **Exudate: (1 of 3 criteria)
  • pleural fluid:serum total protein > 0.5
  • pleural fluid:serum LDH > 0.6
  • pleural fluid LDH > 2/3 upper normal limit of LDH

Pleural adenosine deaminases (ADA) activity: good test

  • Tuberculosis: high
  • Empyema: low
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15
Q

Factors affecting result interpretation

A
  1. Pre-analytical
    - patients factors (correct patients, age, gender, diet, drugs)
    - sampling factors (storage time, sampling time, specimen type)
  2. Analytical
    - correct test on correct specimen
    - performance of test (accuracy, imprecision, sensitivity, specificity)
  3. Post-analytical
    - transcription, computer data uploading
    - appropriate reference interval
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16
Q

Reference interval

A
  • **Reference interval: represent central 95% of reference individuals
  • Values derived from distribution of results obtained from reference population (healthy individuals)
  • usually 2 values (upper and lower reference limit)

Reference individuals —> population —> sample group —> values —> distribution —> limits —> intervals

  • Parametric: Mean +/- 2 SD (95.4% within 2SD, assume Gaussian distribution)
  • Non-parametric: 2.5th and 97.5 percentile (95% included, no assumption of distribution)
17
Q

Blood analyses requiring partitioning of reference intervals

A

Age: Growth hormone
Gender: Testosterone, oestrogen
Posture: Renin, aldosterone
Diet: glucose, TAG

18
Q

Inter vs Intra-individual variation

A

Intra:
- biological variation: e.g. progesterone level
Inter:
- between individuals

Narrow intra-individual variation —> inter-individual less sensitive than intra-individual variation (睇inter-individual無意思, 睇intra-individual先有用)

19
Q

Clinical decision limits

A
  • **- dividing lines between normal and diseased
  • **- consensus value / predictive value
  • usually one value, without confidence interval
  • may change with time (reference intervals will not)
  • can be distinct from reference limits
  • useful for integrating test results for diagnosis and clinical management
  1. Bayesian approach (e.g. Troponin) —> based on:
    - definition
    - pathogenesis
    - sensitivity of test
    - specificity of test
    - prevalence
    - clinical costs for misclassification
  2. Epidemiological approach (e.g. cholesterol, glucose) —> based on:
    - population studies
    - national guidelines / consensus
    - outcomes studies showing different level of survival with concentrations above or below limit
  3. Pathophysiological approach —> based on:
    - critical values —> life threatening situation
    - arbitrary
    - clinical experience
    - without support of statistical mean
20
Q

Positive predictive value, Negative predictive value, Sensitivity, Specificity

A

PPV = True positive / All positive
NPV = True negative / All negative
Sensitivity = True positive / All disease —> ability to pick up all diseased people
—> high sensitivity —> high NPV (very few false negative)
Specificity = True negative / All healthy —> ability to exclude normal people
—> high specificity —> high PPV (very few false positive)

21
Q

Likelihood ratio

A

LR+ = P(+ve test in diseased) / P(+ve test in normal people)
—> Sensitivity / 1-Specificity

LR- = P(-ve test in diseased) / P(-ve test in normal people)
—> 1-Sensitivity / Specificity

22
Q

Receiver Operating Characteristic Curve (ROC)

A

Performance of 2 different tests can be compared
—> by plotting sensitivity against (1-specificity)

  1. Better the test curve lies above and left
  2. Larger AUC

IASM + CPRS Practicals (9 decks)

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