M. Desmond Burke

Hepatic function testing.

The clinical situation determines the choice of hepatic function tests. Alkaline phosphatase (ALP) and aspartate aminotransferase (GOT) tests serve to detect disease, and when used in combination with a gammaglutamyl transferase (GGTP) test, to exclude it. The combination of ALP, GOT, bilirubin, lactate dehydrogenase (LDH), albumin, globulin, and GGTP tests is useful for routine differential diagnosis. Prothrombin time indicates severity of disease. Interpretation is facilitated by attention to ALP or GOT predominance; the relationship of LDH, ALP, and bilirubin; and the ratio of GGTP to ALP. Abnormalities on routine tests frequently do no more than point out the need for more definitive procedures.

Laboratory tests basic concepts and realistic expectations

Ordering and interpreting laboratory tests take familiarity with the concepts of normal limits, specificity, sensitivity, and prevalence. The relative importance of these test properties for clinical decisions is presented.

Cost-effective laboratory testing

The increased utilization of diagnostic procedures has prompted interest in cost-effective laboratory testing. Clinically useful tests-useful in the sense that the patient benefits-are cost effective. The choice of test(s) is determined by the risks and benefits of proposed management. In practice, the first step in cost-effective laboratory testing is to define the clinical problem; the next step is to choose the test(s) that minimize the risks of making a false diagnosis. The choice will depend on whether sensitivity, specificity, or both are needed to decrease diagnostic uncertainty to the extent that management does more good than harm.

Cholesterol, triglyceride, and lipoprotein studies: Strategies for clinical use

Epidemiologic evidence links high levels of low density lipoprotein (LDL) cholesterol and low levels of high density lipoprotein (HDL) cholesterol to increased risk of coronary heart disease. There is no evidence--yet--that lowering LDL and raising HDL alleviate that risk. Testing should be limited to those subgroups of the population at greatest risk. Total cholesterol and triglyceride determinations are the tests of choice for initial evaluation. HDL should be determined before instituting long-term treatment for hypercholesterolemia.

Principles of therapeutic drug monitoring.

Biochemical monitoring is generally advised for drugs that are potentially toxic, have a narrow therapeutic range, or are prescribed for life-threatening disease. Monitoring should not be attempted until the serum concentration reaches a plateau, or steady state, and sampling must be timed carefully. Besides incorrect timing, various technical, therapeutic, and patient factors can account for results outside the therapeutic range.

Hypoglycemia: Strategies for laboratory investigation

Hypoglycemia recently has become somewhat of a fad diagnosis, often misguidedly used to explain such vague complaints as chronic anxiety and lack of pep. True symptomatic hypoglycemia is of two types: reactive, which may follow gastric surgery, and fasting, most commonly associated with alcoholism, hepatic disease, pituitary or adrenal insufficiency, or tumor. Test strategies for documenting hypoglycemia, differentiating the two types, and identifying the cause are presented here.

Diabetes mellitus: Test strategies for diagnosis and management

Fasting plasma glucose determination is the test of choice for diagnosis of diabetes. Glucose tolerance testing should be reserved for patients with borderline fasting values or possible diabetic complications and those suspected of having gestational diabetes. Strict attention to patient variables is essential if glucose tolerance testing is to be of value. The diagnosis of diabetes should be reserved for those patients with symptoms and unequivocal hyperglycemia, those with fasting plasma glucose values of 140 mg/dl or more repeatedly, and those with glucose tolerance test values of 200 mg/dl or more at two hours and at least one other time.

Clinical enzymology 2. Test strategies and interpretation of results.

The greatest usefulness of enzyme determinations is in diagnosis and management of hepatic, cardiac, pancreatic, and skeletal muscle diseases. They occasionally are useful in patients with malignant or hematologic conditions. As a rule, enzyme determinations are sensitive enough for normal values to exclude disease but are too nonspecific for abnormal values to confirm disease. Exceptions to this rule are determination of the MB isoenzyme of creatine kinase, the flipped lactate dehydrogenase isoenzyme pattern, and calculation of the ratio of amylase clearance to creatinine clearance.

Blood gas measurements.

pH and blood gas measurements are used to detect and monitor ventilation, oxygenation, and acid-base disturbances. The blood sample must be drawn anaerobically and transported in ice water to the laboratory. Partial pressure of carbon dioxide in arterial blood (PaCO2) reflects alveolar ventilation; partial pressure of oxygen in arterial blood (PaO2) reflects oxygen loading. The alveolar-arterial PO2 gradient (PA-aO2) distinguishes hypoxemia due to hypoventilation from that due to inefficent pulmonary gas exchange. The demand status of the cardiovascular system and the hemoglobin value reflect oxygen delivery to tissues. The relationship among pH, PaCO2, and bicarbonate concentration, when interpreted in the light of clinical findings, specifies the type and duration of acid-base disturbance.

Electrolyte studies 2. Potassium, chloride, and acid-base

Hypokalemia plus elevated carbon dioxide (CO2) content usually indicates renal or gastrointestinal potassium (K+) loss. Hypokalemia plus decreased CO2 content usually means intestinal K+ loss. Hyperkalemia is common in metabolic acidosis and oliguric renal failure. With hemolysis or thrombocytosis, serum K+ concentration may be elevated while plasma concentration is normal. A CO2 value less than 18 mmole/liter suggests metabolic acidosis; a value greater than 30 mmole/liter suggests metabolic alkalosis.