Interpretation of Lab Test Profiles

Ed Uthman, MD

Diplomate, American Board of Pathology

15 Nov 1998

The various multiparameter blood chemistry and hematology profiles offered by most labs represent an economical way by which a large amount of information concerning a patient's physiologic status can be made available to the physician. The purpose of this monograph is to serve as a reference for the interpretation of abnormalities of each of the parameters.

Reference ranges ("normal ranges")

Because reference ranges (except for some lipid studies) are typically defined as the range of values of the median 95% of the healthy population, it is unlikely that a given specimen, even from a healthy patient, will show "normal" values for all the tests in a lengthy profile. Therefore, caution should be exercised to prevent overreaction to miscellaneous, mild abnormalities without clinical correlate.

Units of measurement: America against the world

American labs use a different version of the metric system than does most of the rest of the world, which uses the Système Internationale (SI). In some cases translation between the two systems is easy, but the difference between the two is most pronounced in measurement of chemical concentration. The American system generally uses mass per unit volume, while SI uses moles per unit volume. Since mass per mole varies with the molecular weight of the analyte, conversion between American and SI units requires many different conversion factors. Where appropriate, in this paper SI units are given after American units.

The Analytes

Increase in serum sodium is seen in conditions with water loss in excess of salt loss, as in profuse sweating, severe diarrhea or vomiting, polyuria (as in diabetes mellitus or insipidus), hypergluco- or mineralocorticoidism, and inadequate water intake. Drugs causing elevated sodium include steroids with mineralocorticoid activity, carbenoxolone, diazoxide, guanethidine, licorice, methyldopa, oxyphenbutazone, sodium bicarbonate, methoxyflurane, and reserpine.

Decrease in sodium is seen in states characterized by intake of free water or hypotonic solutions, as may occur in fluid replacement following sweating, diarrhea, vomiting, and diuretic abuse. Dilutional hyponatremia may occur in cardiac failure, liver failure, nephrotic syndrome, malnutrition, and SIADH. There are many other causes of hyponatremia, mostly related to corticosteroid metabolic defects or renal tubular abnormalities. Drugs other than diuretics may cause hyponatremia, including ammonium chloride, chlorpropamide, heparin, aminoglutethimide, vasopressin, cyclophosphamide, and vincristine.

Increase in serum potassium is seen in states characterized by excess destruction of cells, with redistribution of K+ from the intra- to the extracellular compartment, as in massive hemolysis, crush injuries, hyperkinetic activity, and malignant hyperpyrexia. Decreased renal K+ excretion is seen in acute renal failure, some cases of chronic renal failure, Addison's disease, and other sodium-depleted states. Hyperkalemia due to pure excess of K+ intake is usually iatrogenic.

Drugs causing hyperkalemia include amiloride, aminocaproic acid, antineoplastic agents, epinephrine, heparin, histamine, indomethacin, isoniazid, lithium, mannitol, methicillin, potassium salts of penicillin, phenformin, propranolol, salt substitutes, spironolactone, succinylcholine, tetracycline, triamterene, and tromethamine. Spurious hyperkalemia can be seen when a patient exercises his/her arm with the tourniquet in place prior to venipuncture. Hemolysis and marked thrombocytosis may cause false elevations of serum K+ as well. Failure to promptly separate serum from cells in a clot tube is a notorious source of falsely elevated potassium.

Decrease in serum potassium is seen usually in states characterized by excess K+ loss, such as in vomiting, diarrhea, villous adenoma of the colorectum, certain renal tubular defects, hypercorticoidism, etc. Redistribution hypokalemia is seen in glucose/insulin therapy, alkalosis (where serum K+ is lost into cells and into urine), and familial periodic paralysis. Drugs causing hypokalemia include amphotericin, carbenicillin, carbenoxolone, corticosteroids, diuretics, licorice, salicylates, and ticarcillin.

Increase in serum chloride is seen in dehydration, renal tubular acidosis, acute renal failure, diabetes insipidus, prolonged diarrhea, salicylate toxicity, respiratory alkalosis, hypothalamic lesions, and adrenocortical hyperfunction. Drugs causing increased chloride include acetazolamide, androgens, corticosteroids, cholestyramine, diazoxide, estrogens, guanethidine, methyldopa, oxyphenbutazone, phenylbutazone, thiazides, and triamterene. Bromides in serum will not be distinguished from chloride in routine testing, so intoxication may show spuriously increased chloride [see also "Anion gap," below].

Decrease in serum chloride is seen in excessive sweating, prolonged vomiting, salt-losing nephropathy, adrenocortical defficiency, various acid base disturbances, conditions characterized by expansion of extracellular fluid volume, acute intermittent porphyria, SIADH, etc. Drugs causing decreased chloride include bicarbonate, carbenoxolone, corticosteroids, diuretics, laxatives, and theophylline.

CO2 content
Increase in serum CO2 content for the most part reflects increase in serum bicarbonate (HCO3-) concentration rather than dissolved CO2 gas, or PCO 2 (which accounts for only a small fraction of the total). Increased serum bicarbonate is seen in compensated respiratory acidosis and in metabolic alkalosis. Diuretics (thiazides, ethacrynic acid, furosemide, mercurials), corticosteroids (in long term use), and laxatives (when abused) may cause increased bicarbonate.

Decrease in blood CO2 is seen in metabolic acidosis and compensated respiratory alkalosis. Substances causing metabolic acidosis include ammonium chloride, acetazolamide, ethylene glycol, methanol, paraldehyde, and phenformin. Salicylate poisoning is characterized by early respiratory alkalosis followed by metabolic acidosis with attendant decreased bicarbonate.

Critical studies on bicarbonate are best done on anaerobically collected heparinized whole blood (as for blood gas determination) because of interaction of blood and atmosphere in routinely collected serum specimens. Routine electrolyte panels are usually not collected in this manner.

The tests "total CO2" and "CO2 content" measure essentially the same thing. The "PCO 2" component of blood gas analysis is a test of the ventilatory component of pulmonary function only.

Anion gap
Increased serum anion gap reflects the presence of unmeasured anions, as in uremia (phosphate, sulfate), diabetic ketoacidosis (acetoacetate, beta-hydroxybutyrate), shock, exercise-induced physiologic anaerobic glycolysis, fructose and phenformin administration (lactate), and poisoning by methanol (formate), ethylene glycol (oxalate), paraldehyde, and salicylates. Therapy with diuretics, penicillin, and carbenicillin may also elevate the anion gap.

Decreased serum anion gap is seen in dilutional states and hyperviscosity syndromes associated with paraproteinemias. Because bromide is not distinguished from chloride in some methodologies, bromide intoxication may appear to produce a decreased anion gap.

Hyperglycemia can be diagnosed only in relation to time elapsed after meals and after ruling out spurious influences (especially drugs, including caffeine, corticosteroids, estrogens, indomethacin, oral contraceptives, lithium, phenytoin, furosemide, thiazides, thyroxine, and many more). Previously, the diagnosis of diabetes mellitus was made by demonstrating a fasting blood glucose >140 mg/dL (7.8mmol/L) and/or 2-hour postprandial glucose >200 mg/dL (11.1 mmol/L) on more than one occasion. In 1997, the American Diabetes Association revised these diagnostic criteria. The new criteria are as follows:
  • Symptoms of diabetes plus a casual plasma glucose of 200 mg/dL [11.1 mmol/L] or greater.


  • Fasting plasma glucose of 126 mg/dL [7.0 mmol/L] or greater.


  • Plasma glucose of 200 mg/dL [11.1 mmol/L] or greater at 2 hours following a 75-gram glucose load.

At least one of the above criteria must be met on more than one occasion, and the third method (2-hour plasma glucose after oral glucose challenge) is not recommended for routine clinical use. The criteria apply to any age group. This means that the classic oral glucose tolerance test is now obsolete, since it is not necessary for the diagnosis of either diabetes mellitus or reactive hypoglycemia.

Diagnosis of gestational diabetes mellitus (GDM) is slightly different. The screening test, performed between 24 and 28 weeks of gestation, is done by measuring plasma glucose 1 hour after a 50-gram oral glucose challenge. If the plasma glucose is 140 mg/dL or greater, then the diagnostic test is performed. This consists of measuring plasma glucose after a 100-gram oral challenge. The diagnostic criteria are given in the table below.

Time Glucose (mg/dL) Glucose (mmol/L)
Fasting 105 5.8
1 hour 190 10.5
2 hours 165 9.2
3 hours 145 8.0

In adults, hypoglycemia can be observed in certain neoplasms (islet cell tumor, adrenal and gastric carcinoma, fibrosarcoma, hepatoma), severe liver disease, poisonings (arsenic, CCl4, chloroform, cinchophen, phosphorous, alcohol, salicylates, phenformin, and antihistamines), adrenocortical insufficiency, hypothroidism, and functional disorders (postgastrectomy, gastroenterostomy, autonomic nervous system disorders). Failure to promptly separate serum from cells in a blood collection tube causes falsely depressed glucose levels. If delay in transporting a blood glucose to the lab is anticipated, the specimen should be collected in a fluoride-containing tube (gray-top in the US, yellow in the UK).

In the past, the 5-hour oral glucose tolerance test was used to diagnose reactive (postprandial) hypoglycemia, but this has fallen out of favor. Currently, the diagnosis is made by demonstrating a low plasma glucose (<50 mg/dL[2.8 mmol/L]) during a symptomatic episode.

Urea nitrogen (BUN)
Serum urea nitrogen (BUN) is increased in acute and chronic intrinsic renal disease, in states characterized by decreased effective circulating blood volume with decreased renal perfusion, in postrenal obstruction of urine flow, and in high protein intake states.

Decreased serum urea nitrogen (BUN) is seen in high carbohydrate/low protein diets, states characterized by increased anabolic demand (late pregnancy, infancy, acromegaly), malabsorption states, and severe liver damage.

In Europe, the test is called simply "urea."

Increase in serum creatinine is seen any renal functional impairment. Because of its insensitivity in detecting early renal failure, the creatinine clearance is significantly reduced before any rise in serum creatinine occurs. The renal impairment may be due to intrinsic renal lesions, decreased perfusion of the kidney, or obstruction of the lower urinary tract.

Nephrotoxic drugs and other chemicals include:

antimony arsenic bismuth cadmium
copper gold iron lead
lithium mercury silver thallium
uranium aminopyrine ibuprofen indomethacin
naproxen fenoprofen phenylbutazone phenacetin
salicylates aminoglycosides amphotericin cephalothin
colistin cotrimoxazole erythromycin ampicillin
methicillin oxacillin polymixin B rifampin
sulfonamides tetracyclines vancomycin benzene
zoxazolamine tetrachloroethylene ethylene glycol
acetazolamide aminocaproic acid aminosalicylate boric acid
cyclophosphamide cisplatin dextran (LMW) furosemide
mannitol methoxyflurane mithramycin penicillamine
pentamide phenindione quinine thiazides

Deranged metabolic processes may cause increases in serum creatinine, as in acromegaly and hyperthyroidism, but dietary protein intake does not influence the serum level (as opposed to the situation with BUN). Some substances interfere with the colorimetric system used to measure creatinine, including acetoacetate, ascorbic acid, levodopa, methyldopa, glucose and fructose. Decrease in serum creatinine is seen in pregnancy and in conditions characterized by muscle wasting.

BUN:creatinine ratio
BUN:creatinine ratio is usually >20:1 in prerenal and postrenal azotemia, and <12:1 in acute tubular necrosis. Other intrinsic renal disease characteristically produces a ratio between these values.

The BUN:creatinine ratio is not widely reported in the UK.

Uric acid
Increase in serum uric acid is seen idiopathically and in renal failure, disseminated neoplasms, toxemia of pregnancy, psoriasis, liver disease, sarcoidosis, ethanol consumption, etc. Many drugs elevate uric acid, including most diuretics, catecholamines, ethambutol, pyrazinamide, salicylates, and large doses of nicotinic acid.

Decreased serum uric acid level may not be of clinical significance. It has been reported in Wilson's disease, Fanconi's syndrome, xanthinuria, and (paradoxically) in some neoplasms, including Hodgkin's disease, myeloma, and bronchogenic carcinoma.

Inorganic phosphorus
Hyperphosphatemia may occur in myeloma, Paget's disease of bone, osseous metastases, Addison's disease, leukemia, sarcoidosis, milk-alkali syndrome, vitamin D excess, healing fractures, renal failure, hypoparathyroidism, diabetic ketoacidosis, acromegaly, and malignant hyperpyrexia. Drugs causing serum phosphorous elevation include androgens, furosemide, growth hormone, hydrochlorthiazide, oral contraceptives, parathormone, and phosphates.

Hypophosphatemia can be seen in a variety of biochemical derangements, incl. acute alcohol intoxication, sepsis, hypokalemia, malabsorption syndromes, hyperinsulinism, hyperparathyroidism, and as result of drugs, e.g., acetazolamide, aluminum-containing antacids, anesthetic agents, anticonvulsants, and estrogens (incl. oral contraceptives). Citrates, mannitol, oxalate, tartrate, and phenothiazines may produce spuriously low phosphorus by interference with the assay.

Hypercalcemia is seen in malignant neoplasms (with or without bone involvement), primary and tertiary hyperparathyroidism, sarcoidosis, vitamin D intoxication, milk-alkali syndrome, Paget's disease of bone (with immobilization), thyrotoxicosis, acromegaly, and diuretic phase of renal acute tubular necrosis. For a given total calcium level, acidosis increases the physiologically active ionized form of calcium. Prolonged tourniquet pressure during venipuncture may spuriously increase total calcium. Drugs producing hypercalcemia include alkaline antacids, DES, diuretics (chronic administration), estrogens (incl. oral contraceptives), and progesterone.

Hypocalcemia must be interpreted in relation to serum albumin concentration (Some laboratories report a "corrected calcium" or "adjusted calcium" which relate the calcium assay to a normal albumin. The normal albumin, and hence the calculation, varies from laboratory to laboratory). True decrease in the physiologically active ionized form of Ca++ occurs in many situations, including hypoparathyroidism, vitamin D deficiency, chronic renal failure, magnesium deficiency, prolonged anticonvulsant therapy, acute pancreatitis, massive transfusion, alcoholism, etc. Drugs producing hypocalcemia include most diuretics, estrogens, fluorides, glucose, insulin, excessive laxatives, magnesium salts, methicillin, and phosphates.

Serum iron may be increased in hemolytic, megaloblastic, and aplastic anemias, and in hemochromatosis, acute leukemia, lead poisoning, pyridoxine deficiency, thalassemia, excessive iron therapy, and after repeated transfusions. Drugs causing increased serum iron include chloramphenicol, cisplatin, estrogens (including oral contraceptives), ethanol, iron dextran, and methotrexate.

Iron can be decreased in iron-deficiency anemia, acute and chronic infections, carcinoma, nephrotic syndrome, hypothyroidism, in protein- calorie malnutrition, and after surgery.

Alkaline phosphatase (ALP)
Increased serum alkaline phosphatase is seen in states of increased osteoblastic activity (hyperparathyroidism, osteomalacia, primary and metastatic neoplasms), hepatobiliary diseases characterized by some degree of intra- or extrahepatic cholestasis, and in sepsis, chronic inflammatory bowel disease, and thyrotoxicosis. Isoenzyme determination may help determine the organ/tissue responsible for an alkaline phosphatase elevation.

Decreased serum alkaline phosphatase may not be clinically significant. However, decreased serum levels have been observed in hypothyroidism, scurvy, kwashiokor, achrondroplastic dwarfism, deposition of radioactive materials in bone, and in the rare genetic condition hypophosphatasia.

There are probably more variations in the way in which alkaline phosphatase is assayed than any other enzyme. Therefore, the reporting units vary from place to place. The reference range for the assaying laboratory must be carefully studied when interpreting any individual result.

Lactate dehydrogenase (LD or "LDH")
Increase of LD activity in serum may occur in any injury that causes loss of cell cytoplasm. More specific information can be obtained by LD isoenzyme studies. Also, elevation of serum LD is observed due to in vivo effects of anesthetic agents, clofibrate, dicumarol, ethanol, fluorides, imipramine, methotrexate, mithramycin, narcotic analgesics, nitrofurantoin, propoxyphene, quinidine, and sulfonamides.

Decrease of serum LD is probably not clinically significant.

There are two main analytical methods for measuring LD: pyruvate->lactate and lactate->pyruvate. Assay conditions (particularly temperature) vary among labs. The reference range for the assaying laboratory must be carefully studied when interpreting any individual result.

Many European labs assay alpha-hydroxybutyrate dehydrogenase (HBD or HBDH), which roughly equates to LD isoenzymes 1 and 2 (the fractions found in heart, red blood cells, and kidney).

Increase of serum alanine aminotransferase (ALT, formerly called "SGPT") is seen in any condition involving necrosis of hepatocytes, myocardial cells, erythrocytes, or skeletal muscle cells. [See "Bilirubin, total," below]
Increase of aspartate aminotransferase (AST, formerly called "SGOT") is seen in any condition involving necrosis of hepatocytes, myocardial cells, or skeletal muscle cells. [See "Bilirubin, total," below] Decreased serum AST is of no known clinical significance.
Gamma-glutamyltransferase is markedly increased in lesions which cause intrahepatic or extrahepatic obstruction of bile ducts, including parenchymatous liver diseases with a major cholestatic component (e.g., cholestatic hepatitis). Lesser elevations of gamma-GT are seen in other liver diseases, and in infectious mononucleosis, hyperthyroidism, myotonic dystrophy, and after renal allograft. Drugs causing hepatocellular damage and cholestasis may also cause gamma-GT elevation (see under "Total bilirubin," below).

Gamma-GT is a very sensitive test for liver damage, and unexpected, unexplained mild elevations are common. Alcohol consumption is a common culprit.

Decreased gamma-GT is not clinically significant.

Serum total bilirubin is increased in hepatocellular damage (infectious hepatitis, alcoholic and other toxic hepatopathy, neoplasms), intra- and extrahepatic biliary tract obstruction, intravascular and extravascular hemolysis, physiologic neonatal jaundice, Crigler-Najjar syndrome, Gilbert's disease, Dubin-Johnson syndrome, and fructose intolerance.

Drugs known to cause cholestasis include the following:

aminosalicylic acid androgens azathioprine benzodiazepines
carbamazepine carbarsone chlorpropamide propoxyphene
estrogens penicillin gold Na thiomalate imipramine
meprobamate methimazole nicotinic acid progestins
penicillin phenothiazines oral contraceptives
sulfonamides sulfones erythromycin estolate

Drugs known to cause hepatocellular damage include the following:

acetaminophen allopurinol aminosalicylic acid amitriptyline
androgens asparaginase aspirin azathioprine
carbamazepine chlorambucil chloramphenicol chlorpropamide
dantrolene disulfiram estrogens ethanol
ethionamide halothane ibuprofen indomethacin
iron salts isoniazid MAO inhibitors mercaptopurine
methotrexate methoxyflurane methyldopa mithramycin
nicotinic acid nitrofurantoin oral contraceptives papaverine
paramethadione penicillin phenobarbital phenazopyridine
phenylbutazone phenytoin probenecid procainamide
propylthiouracil pyrazinamide quinidine sulfonamides
tetracyclines trimethadione valproic acid

Disproportionate elevation of direct (conjugated) bilirubin is seen in cholestasis and late in the course of chronic liver disease. Indirect (unconjugated) bilirubin tends to predominate in hemolysis and Gilbert's disease.

Decreased serum total bilirubin is probably not of clinical significance but has been observed in iron deficiency anemia.

Total protein
Increase in serum total protein reflects increases in albumin, globulin, or both. Generally significantly increased total protein is seen in volume contraction, venous stasis, or in hypergammaglobulinemia.

Decrease in serum total protein reflects decreases in albumin, globulin or both [see "Albumin" and "Globulin, A/G ratio," below].

Increased absolute serum albumin content is not seen as a natural condition. Relative increase may occur in hemoconcentration. Absolute increase may occur artificially by infusion of hyperoncotic albumin suspensions.

Decreased serum albumin is seen in states of decreased synthesis (malnutrition, malabsorption, liver disease, and other chronic diseases), increased loss (nephrotic syndrome, many GI conditions, thermal burns, etc.), and increased catabolism (thyrotoxicosis, cancer chemotherapy, Cushing's disease, familial hypoproteinemia).

Globulin, A/G ratio
Globulin is increased disproportionately to albumin (decreasing the albumin/globulin ratio) in states characterized by chronic inflammation and in B-lymphocyte neoplasms, like myeloma and Waldenström's macroglobulinemia. More relevant information concerning increased globulin may be obtained by serum protein electrophoresis.

Decreased globulin may be seen in congenital or acquired hypogammaglobulinemic states. Serum and urine protein electrophoresis may help to better define the clinical problem.

T3 uptake
This test measures the amount of thyroxine-binding globulin (TBG) in the patient's serum. When TBG is increased, T3 uptake is decreased, and vice versa. T3 Uptake does not measure the level of T3 or T4 in serum.

Increased T3 uptake (decreased TBG) in euthyroid patients is seen in chronic liver disease, protein-losing states, and with use of the following drugs: androgens, barbiturates, bishydroxycourmarin, chlorpropamide, corticosteroids, danazol, d-thyroxine, penicillin, phenylbutazone, valproic acid, and androgens. It is also seen in hyperthyroidism.

Decreased T3 uptake (increased TBG) may occur due to the effects of exogenous estrogens (including oral contraceptives), pregnancy, acute hepatitis, and in genetically-determined elevations of TBG. Drugs producing increased TBG include clofibrate, lithium, methimazole, phenothiazines, and propylthiouracil. Decreased T3 uptake may occur in hypothyroidism.

Thyroxine (T4)
This is a measurement of the total thyroxine in the serum, including both the physiologically active (free) form, and the inactive form bound to thyroxine-binding globulin (TBG). It is increased in hyperthyroidism and in euthyroid states characterized by increased TBG (See "T3 uptake," above, and "FTI," below). Occasionally, hyperthyroidism will not be manifested by elevation of T4 (free or total), but only by elevation of T3 (triiodothyronine). Therefore, if thyrotoxicosis is clinically suspect, and T4 and FTI are normal, the test "T3-RIA" is recommended (this is not the same test as "T3 uptake," which has nothing to do with the amount of T3 in the patient's serum).

T4 is decreased in hypothyroidism and in euthyroid states characterized by decreased TBG. A separate test for "T4" is available, but it is not usually necessary for the diagnosis of functional thyroid disorders.

FTI (T7)
This is a convenient parameter with mathematically accounts for the reciprocal effects of T4 and T3 uptake to give a single figure which correlates with free T4. Therefore, increased FTI is seen in hyperthyroidism, and decreased FTI is seen in hypothyroidism. Early cases of hyperthyroidism may be expressed only by decreased thyroid stimulation hormone (TSH) with normal FTI. Early cases of hypothyroidism may be expressed only by increased TSH with normal FTI. Currently, the method of choice for screening for both hyper- and hypothyroidism is serum TSH only. Modern methodologies ("ultrasensitive TSH") allow accurate determination of the very low concentrations of TSH at the phyisological cutoff between the normal and hyperthyroid states.

ASSESSMENT OF ATHEROSCLEROSIS RISK: Triglycerides, Cholesterol, HDL-Cholesterol, LDL-Cholesterol, Chol/HDL ratio

All of these studies find greatest utility in assessing the risk of atherosclerosis in the patient. Increased risks based on lipid studies are independent of other risk factors, such as cigarette smoking.

Total cholesterol has been found to correlate with total and cardiovascular

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