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Summary 8SM00 – Clinical Chemistry R.F.J.F. Van Doorslaer, 100180419-01-2021
1 LECTURE 1
- e.g. test characteristics, predictive values, concepts
of intracellular and extracellular fluids, volume and
electrolyte homeostasis, blood pressure regulation,
acid base-regulation and blood gas interpretation,
endocrine axes, types and causes of anaemia etc.
1.1 CLINICAL PROCESS
- Pre-analytical phase = pre-analytical consultation:
o Can by measuring in body fluids information be obtained on the (dis)function of cells /
organs clinical chemistry.
o Function of blood as a tissue = haematology
- Analytical phase:
o Specificity
o Interference
o Bias
o (im)precision
- Post-analytical phase:
o Interpretation of test results
o Reference intervals
o Comparison of test results (critical difference)
o Intra – and interindividual variation
o Diagnostic value of tests
o Sensitivity and specificity
o Efficiency and prevalence of disease
1.2 MEDICAL DECISION MAKING
- Reference interval: gives an indication of the range of results that would be found in majority (95%) of
an apparently healthy population
o Same analytical method and instrument
o Samples of apparently healthy persons (students, health personnel, blood donors)
o Considering the factors (sex / age, pre-pubertal / post-menopausal, diet, posture, etc.)
- By definition 5% (2,5% +2,5%) of healthy people fall outside reference interval!
o Collect at least 100 test results for the selected reference population of healthy persons
o Assume a normal (Gaussian) distribution
o The reference interval is now defined as mean +/-2 SD
o This reference interval includes about 95% of the results
- From an analytical point of view a difference between two test results is statistically significant
(p<0.05) if the difference between the two results is more than 2.8 (analytical) standard deviations
(SD).
o To tell whether an analytical difference is also clinically significant, the biological variation
has to be considered.
- Sensitivity = true positives / (true positives + false negatives)
- Specificity = true negatives / (true negatives + false positives)
o Receiver Operating Characteristic Curves
To determine the decision limit in e.g. screening (dichotomizing)
To compare the diagnostic value of tests
Alterations in cut-off values leads to changes in sensitivity and specificity:
1
,Summary 8SM00 – Clinical Chemistry R.F.J.F. Van Doorslaer, 1001804
19-01-2021
• Higher sensitivity = lower specificity.
• Higher specificity = lower sensitivity
o Positive predictive value
positive results in patients with the disease
𝑃𝑃𝑃𝑃 + =
total number of positive test results
o Negative predictive value
negative test results in disease−free persons
𝑃𝑃𝑃𝑃 − =
total number of negative test results
p = prevalence
a = sensitivity
b = specificity
1.2.1 Predictive value steps:
1. Determine sensitivity and specificity of test
2. Assume population with prevalence
3. Fill in the table
4. Check the table
5. Calculate positive / negative predictive values
- Bayesian statistics:
o A priory chance * likelihood ratio = posterior chance
Likelihood ratio is calculated from sensitivity, specificity and prevalence
Positive (disease present) and negative likelihood ratio’s (disease absent) can be
used
- SLIDE 56 PRACTICE PREDICTIVE VALUE TABLE
2
, Summary 8SM00 – Clinical Chemistry R.F.J.F. Van Doorslaer, 1001804
19-01-2021
2 LECTURE 2
2.1 WATER DISTRIBUTION:
- Water is not actively transported in the body
- Freely permeable through the ICF (intracellular fluid) and ECF; distribution determined by osmotic
content of these compartments
- Major contributors to the osmolality of the ECF are sodium and its associated anions (Cl- and HCO3-)
2.2 SODIUM (NA+) DISTRIBUTION
- 4000 mmol of sodium in adult man (70% free exchangeable, remainder complexed in bone)
- Majority of exchangeable sodium is extracellular
- ICF concentration of sodium is 4-10 mmol/L
- Active pumping of sodium from ICF (intracellular fluid) to ECF (extracellular fluid) by Na+, K+, ATPase
2.3 POTASSIUM (K+) DISTRIBUTION
- Potassium mainly intracellularly present in the body.
o Only approximately 2% in ECF (where it is accessible for measurement)
o Because of the effect on membrane excitability, plasma potassium concentration (reference
3.6-5.0 mmol/L) is, nevertheless, important.
- 90% free exchangeable, 10% bound in erythrocytes, bone and brain tissue.
2.4 WATER AND SODIUM HOMEOSTASIS
2.4.1 Water and ECF osmolality
- Changes in water content independent of the amount of solute, will alter osmolality.
- Loss of water from ECF increase in osmolality movement of water from ICF
ECF osmolality will remain slightly increased stimulation of the hypothalamic thirst centre and the
hypothalamic osmoreceptors, which causes release of vasopressin (ADH)
o ADH = antidiuretic hormone= vasopressin
2.4.2 Osmolality regulates ADH concentration
- Relatively small ADH response to small decrease in plasma volume: greater falls cause a massive
increase in ADH secretion
- Vasopressin response to fall in blood pressure is exponential
- Osmolar controls are overridden, tending to defend ECF volume (by water retention) at the expense
of a decrease in osmolality.
2.4.3 Sodium and ECF volume
- ECF volume directly dependent on total body sodium content
- Sodium excretion is dependent on (renal) glomerular filtration and tubular re-absorption.
- RAAS = renin–angiotensin–aldosterone system
- Aldosterone (= steroid hormone, stimulated by RAAS) stimulates sodium re-absorption (antidiuretic
function increases the blood volume and increases the blood pressure)
- Natriuretic peptide hormones also have a role in controlling sodium excretion
3
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