Human Biochemistry, Volume 2 - Murray R. 1993

Appendix
Chemical Composition of Blood and Body Fluids

Quantitative Assessment of Laboratory Data

The results obtained in a clinical laboratory when determining the concentration or amount of a substance in a sample reflect the capabilities of the respective method, as well as the quality of Reagents and equipment.

The accuracy of a method refers to the degree of closeness between the obtained value and the "true" value (for example, a known concentration in a control sample). The reproducibility of a method is characterized by the dispersion of values obtained from the analysis of multiple aliquots of a single sample. The reliability of a method is determined by its accuracy and reproducibility.

Reproducibility depends on A number of factors: The complexity of the method, the stability and quality of reagents, the accuracy of the primary standard, the reliability of the equipment, and the experience of the technical personnel. Every laboratory is responsible for verifying the reproducibility of its Methods. It is assessed by the magnitude of the standard deviation from the mean obtained during repeated analyses of the same sample. For instance, the reproducibility in determining serum Cholesterol in a good laboratory typically averages ±5 mg%. It is known that the 95% confidence interval equals ±2 standard deviations, which in this case corresponds to ±10 mg%. Thus, any result is considered true if it falls within these boundaries (20 mg%). Therefore, a serum cholesterol level of 200 mg% means that the true value lies between 190 and 210 mg%. When determining serum potassium with an error of ±0.1 mmol/L (1SD), the test results of samples from the same specimen may differ by ±0.2 mmol.

A result of 5.5 mmol indicates that the true value lies within the range of 5.3–5.7. This means that when analyzing different aliquots of the same sample, results of both 5.3 and 5.7 mmol/L may be obtained; both fall within the test's reproducibility limits.

Physicians should receive information from the laboratory regarding the potential measurement error for each method, as this allows them to judge whether a given patient's test results have genuinely changed.

Interpretation of Laboratory tests

Normal values are defined as those that fall within two standard deviations of the mean value of the parameter in question within a normal (healthy) population. Such values characterize 95% of the healthy population. There are numerous factors that influence test results, including age, race, gender, environment, body posture, diurnal and other cyclic fluctuations, the timing of sample collection (fasting or postprandial), dietary habits, medication use, and the level of physical activity.

Normal values may vary depending on the analytical method, as well as the conditions of sample collection and storage. In every laboratory, all stages of analysis must be strictly regulated and standardized to ensure that the results can be interpreted correctly.

When interpreting laboratory data, the patient's clinical condition must be taken into account. A low concentration of a substance, such as serum sodium, may result from either a true deficiency or "dilution." Deviations from the norm may be linked not only to the Specificity of a disease but also to the administration of certain medications. For example, elevated serum uric acid may be caused by Gout or may be a consequence of chlorothiazide or antineoplastic therapy. When evaluating a test result, it is absolutely essential to have at hand a list of medications that could affect the outcome of that specific test.

The method of sample collection is of critical importance. Improperly collected 24-hour urine, Blood hemolysis, The Use of an inadequate anticoagulant, insufficiently clean glassware, or a malfunctioning analyzer can all serve as sources of analytical error.

Note: If unusual or markedly abnormal results are obtained, the possibility of error must be ruled out before making any decisions regarding patient Treatment. Consultation with a specialist in the field is strongly recommended.

Effect of Diet and Posture on Blood Substance Concentrations

A. Diet. Blood is typically drawn for analysis in the fasting state after an 8–12 hour fast. With rare exceptions, drinking Water is permitted.

If blood is drawn 3–4 hours after breakfast, the resulting standard test values will differ from the fasting levels. If blood is drawn 3–4 hours after lunch, the parameters deviate to an even greater extent. Accurate determination of serum or plasma triglycerides requires a 10–14 hour fast.

B. Posture. The plasma volume measured in an individual who has been lying down for several hours is 10–15% greater than that of a person who has been changing posture or standing for about an hour. This means that blood concentration measurements in a person who has been lying down for more than an hour will be lower than those obtained after walking.

Test results in the same individual change when transitioning from a supine to an upright position: total protein, albumin, calcium, potassium, phosphate, cholesterol, triglycerides, AST, Phosphatases, total thyroxine, hematocrit, erythrocyte count, and Hemoglobin all increase. The most pronounced changes involve total protein, Enzymes (+11%), and calcium (3–4%). In a series of studies, changing from an upright to a supine position was accompanied by a decrease in total protein by 0.5 g%, albumin by 0.4–0.6 g%, calcium by 0.4 mg%, cholesterol by 10–25 mg%, total thyroxine by 0.8–1.8 mcg%, and hematocrit by 49% (due to hemodilution following the return of interstitial fluid into the vascular bed).

Applying a tourniquet for 1 minute instead of 3 resulted in the following changes in results: total protein, +1–5%; iron, +6.7%; cholesterol, 1–5%; AST, +9.3%; bilirubin, +8.4%; whereas decreases were noted in potassium levels by 6% and creatinine by 2.3%.

Validity of Laboratory Tests

The clinical utility of a test is determined by its specificity, sensitivity, and the prevalence of the corresponding disease in the population being tested.

Test sensitivity is judged by the proportion (%) of positive test results among patients with the target disease. For example, the test for phenylketonuria is highly sensitive: positive results are observed in all patients with this condition (100% sensitivity). The carcinoembryonic antigen test has low sensitivity: results are positive in only 72% of patients with advanced Colorectal Cancer and in merely 20% of cases during early stages. Low test sensitivity at the onset of a disease followed by a sharp increase in later stages is characteristic of many pathological conditions.

Specificity is judged by the proportion (%) of negative results among individuals who do not have the target disease. For example, the test for phenylketonuria is highly specificity: testing people without phenylketonuria yields negative results in 99.9% of cases. Conversely, the Specificity of the intestinal carcinoma test is relatively low: among non-smoking patients, There is a 3% false-positive rate (97% specificity); in smokers, the proportion of such results reaches 20% (80% specificity). Certain situations can complicate the assessment of specificity; for instance, serum thyroxine levels are elevated not only in patients with hyperthyroidism but also in women taking oral contraceptives and in pregnant women.

The diagnostic value of a positive test is characterized by the proportion (in %) of true-positive results among all positive results. This indicator is directly related to the probability of the suspected disease.

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Before ordering a biochemical test, one must evaluate whether the sensitivity, specificity, and diagnostic value of the test are adequate for the clinical objectives at hand, and to what extent they can contribute to an accurate Diagnosis and the Selection of an appropriate treatment course.

SI Units (Système International d'Unités)

The General Conference on Weights and Measures developed a coherent system of units that is currently widely adopted.

For clinical Applications, 8 base quantities were selected:

length: metre (m); mass: kilogram (kg);

amount of substance: mole (mol);

time: second (s);

thermodynamic Temperature: kelvin (K);

electric current: ampere (A);

luminous intensity: candela (cd);

catalytic activity:

katal (kat).

The derived quantities include the following:

mass concentration: kilogram/litre (kg/L);

mass fraction: kilogram/kilogram (kg/kg);

volume fraction: litre/litre (L/L);

volume: cubic metre (m³); for clinical use — litre (L);

substance concentration: mole/litre (mol/L);

molality: mole/kilogram (mol/kg);

mole fraction: mole/mole;

pressure: pascal (Pa)—newton/m².

Decimal multiples and submultiples

The terms "per" or "a", such as "per second", are frequently expressed using negative exponents.

Instead of "per second", s^-1 is written; per square metre — m^-2, per kilogram — kg^-1.

Example: cm/s = cm∙s^-1; g/m² = g∙m^-2.

Assuming that the SI system will be adopted in the United States in the coming years, the data presented herein are expressed in both traditional and SI units (in parentheses).