8SM00 - Summary of Lectures

Summary 8SM00 – Clinical Chemistry R.F.J.F. Van Doorslaer, 1001804
19-01-2021



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