Subject: Lab Test Interpretation (monthly posting, 40K, version 2.03)
Date: 4 Jan 1996 22:11:52 GMT
Summary: This is a fairly encyclopedic source for assistance in
 interpreting many of the routine lab tests found in commonly
 ordered blood work profiles. It is aimed primarily at med students
 and residents, but others with some general background in human
 physiology may find it useful.
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Version: 2.03 8/11/95
Archive-name: pathology/lab-test-interpretation
Posting-Frequency: monthly

              INTERPRETATION OF LAB TEST PROFILES

                Ed Uthman, MD (uthman@domi.net)

            Diplomate, American Board of Pathology

The various multiparameter blood chemistry and hematology profiles 
offered by most commercial 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. Because normal 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 fall within the "normal" range of all the tests in 
a lengthy profile. Therefore, caution should be exercised to prevent 
overreaction to miscellaneous, mild abnormalities without clinical 
correlate.

SODIUM

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. 

POTASSIUM

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.

CHLORIDE

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 concentration rather than dissolved CO2 gas (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. 

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. 

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.

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.

GLUCOSE

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). Generally, fasting blood glucose >140 mg/dL and/or 2h 
postprandial glucose >200 mg/dL demonstrated on several occasions is 
suggestive of diabetes mellitus; OGTT is usually not required for 
diagnosis. 

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 red top 
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 (gray-top) tube.

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.

CREATININE

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
carbon tetrachloride

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.

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, catacholamines, 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 phosphorous by interference with the assay.

CALCIUM

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 to relation to serum albumin 
concentration. True decrease in the physiologically active ionized form 
of Ca++ occurs in many situations, including hypoparathyroidism, vitamin 
D deficiency, chronic renal failure, Mg++ 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. 

ALKALINE PHOSPHATASE

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.

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.

ALT (SGPT)

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] 

AST (SGOT)

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.

GGTP (GAMMA-GT)

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.

BILIRUBIN

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  papverine
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].

ALBUMIN

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 Waldenstrm'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.

IRON

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 (incl.  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.

The iron assay is one of the less reliable tests on screening panels, so 
any abnormalities should be followed with other inquiry concerning iron 
metabolism (history of blood loss, alcohol consumption, lab tests for 
TIBC, ferritin, etc) before undertaking therapeutic interventions.

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 (incl. 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 "free 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 with decreased FTI is seen in hypothyroidism. Early 
cases of hyperthyroidism may be expressed only by increased thyroid 
stimulation hormone (TSH) with normal FTI. Early cases of hypothyroidism 
may be expressed only by increased TSH with normal FTI.

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 mortality in the 30-50 year age group. Cardiovascular 
mortality increases 9% for each 10 mg/dL increase in total cholesterol 
over the baseline value of 180 mg/dL. Approximately 80% of the adult 
male population has values greater than this, so the use of the median 
95% of the population to establish a normal range (as is traditional in 
lab medicine in general) has no utility for this test. Excess mortality 
has been shown not to correlate with cholesterol levels in the >50 years 
age group, probably because of the depressive effects on cholesterol 
levels expressed by various chronic diseases to which older individuals 
are prone.

HDL-cholesterol is "good" cholesterol, in that risk of cardiovascular 
disease decreases with increase of HDL. One way to assess risk is to use 
the total cholesterol/HDL-cholesterol ratio, with lower values 
indicating lower risk. The following chart has been developed from ideas 
advanced by Castelli and Levitas, Current Prescribing, June, 1977. It 
should be taken with a large grain of salt substitute: 

                              Total cholesterol (mg/dL)
                  150    185   200  210   220   225   244   260   300
               ------------------------------------------------------
            25 | ####  1.34  1.50  1.60  1.80  2.00  3.00  4.00  6.00
            30 | ####  1.22  1.37  1.46  1.64  1.82  2.73  3.64  5.46
            35 | ####  1.00  1.12  1.19  1.34  1.49  2.24  2.98  4.47
HDL-chol    40 | ####  0.82  0.92  0.98  1.10  1.22  1.83  2.44  3.66
 (mg/dL)    45 | ####  0.67  0.75  0.80  0.90  1.00  1.50  2.00  3.00
            50 | ####  0.55  0.62  0.66  0.74  0.82  1.23  1.64  2.46
            55 | ####  0.45  0.50  0.54  0.60  0.67  1.01  1.34  2.01
            60 | ####  0.37  0.41  0.44  0.50  0.55  0.83  1.10  1.65
            65 | ####  0.30  0.34  0.36  0.41  0.45  0.68  0.90  1.35
           >70 | ####  ####  ####  ####  ####  ####  ####  ####  ####

The numbers with two-decimal format represent the relative risk of 
atherosclerosis vis-a-vis the general population. Cells marked "####" 
indicate very low risk or undefined risk situations. Some authors have 
warned against putting too much emphasis on the total-chol/HDL-chol 
ratio at the expense of the total cholesterol level.

Triglyceride level is risk factor independent of the cholesterol levels. 
Triglycerides are important as risk factors only if they are not part of 
the chylomicron fraction. To make this determination in a 
hypertriglyceridemic patient, it is necessary to either perform 
lipoprotein electrophoresis or visually examine an overnight-
refrigerated serum sample for the presence of a chylomicron layer. The 
use of lipoprotein electrophoresis for routine assessment of 
atherosclerosis risk is probably overkill in terms of expense to the 
patient.

LDL-cholesterol (the amount of cholesterol associated with low-density, 
or beta, lipoprotein) is not an independently measured parameter but is 
mathematically derived from the parameters detailed above. Some risk-
reduction programs use LDL-cholesterol as the primary target parameter 
for monitoring the success of the program.

TRIGLYCERIDES

Markedly increased triglycerides (>500 mg/dL) usually indicate a 
nonfasting patient (i.e., one having consumed any calories within 12-14 
hour period prior to specimen collection). If patient is fasting, 
hypertriglyceridemia is seen in hyperlipoproteinemia types I, IIb, III, 
IV, and V. Exact classification theoretically requires lipoprotein 
electrophoresis, but this is not usually necessary to assess a patient's 
risk to atherosclerosis [See "Assessment of Atherosclerosis Risk," 
above]. Cholestyramine, corticosteroids, estrogens, ethanol, miconazole 
(intravenous), oral contraceptives, spironolactone, stress, and high 
carbohydrate intake are known to increase triglycerides. Decreased serum 
triglycerides are seen in abetalipoproteinemia, COPD, hyperthyroidism, 
malnutrition, and malabsorption states.

WBC (White Blood Cell) COUNT

The WBC is really a nonparameter, since it simply represents the sum of 
the counts of granulocytes, lymphocytes, and monocytes per unit volume 
of whole blood. Automated counters do not distinguish bands from segs; 
however, it has been shown that if all other hematologic parameters are 
within normal limits, such a distinction is rarely important. Also, even 
in the best hands, trying to reliably distinguish bands from segs under 
the microscope is fraught with reproducibility problems. Discussion 
concerning a patient's band count probably carries no more scientific 
weight than does a medieval theological argument.

RBC (Red Blood Cell) COUNT

The RBC count is most useful as raw data for calculation of the 
erythrocyte indices MCV and MCH [see below]. Decreased RBC is usually 
seen in anemia of any cause with the possible exception of thalassemia 
minor, where a mild or borderline anemia is seen with a high or 
borderline-high RBC. Increased RBC is seen in erythrocytotic states, 
whether absolute (polycythemia vera, erythrocytosis of chronic hypoxia) 
or relative (dehydration, stress polycthemia), and in thalassemia minor 
[see "Hemoglobin," below, for discussion of anemias and erythrocytoses].

HEMOGLOBIN, HEMATOCRIT, MCV (Mean Corpuscular Volume), MCH (Mean 
Corpuscular Hemoglobin), MCHC (Mean Corpuscular Hemoglobin 
Concentration)

Strictly speaking, anemia is defined as a decrease in total body red 
cell mass. For practical purposes, however, anemia is typically defined 
as hemoglobin <12.0 g/dL and direct determination of total body RBC mass 
is almost never used to establish this diagnosis. Anemias are then 
classed by MCV and MCHC (MCH is usually not helpful) into one of the 
following categories:

    1.  Microcytic/hypochromic anemia (decreased MCV, decreased MCHC)

           Iron deficiency (common)
           Thalassemia (common, except in people of Germanic, Slavonic,
                       Baltic, Native American, Han Chinese, Japanese
                       descent)
           Anemia of chronic disease (uncommonly microcytic)
           Sideroblastic anemia (uncommon; acquired forms more often
                                 macrocytic)
           Lead poisoning (uncommon)
           Hemoglobin E trait or disease (common in Thai, Khmer,
                      Burmese,Malay, Vietnamese, and Bengali groups)

     2.  Macrocytic/normochromic anemia (increased MCV, normal MCHC)

           Folate deficiency (common)
           B12 deficiency (common)
           Myelodysplastic syndromes (not uncommon, especially in older
                       individuals)
           Hypothyroidism (rare)

     3.  Normochromic/normocytic (normal MCV, normal MCHC)
           The first step in laboratory workup of this broad class of
           anemias is a reticulocyte count. Elevated reticulocytes
           implies a normo-regenerative anemia, while a low or 
           "normal" count implies a hyporegenerative anemia:

            A. Normoregenerative normocytic anemias (appropriate
                                          reticulocyte response)
                   Immunohemolytic anemia
                   G-6-PD deficiency (common)
                   Hemoglobin S or C
                   Hereditary spherocytosis
                   Microangiopathic hemolytic anemia
                   Paroxysmal hemoglobinuria

            B. Hyporegenerative normocytic anemias (inadequate
                                         reticulocyte response)
                   Anemia of chronic disease
                   Aplastic anemia*

*Drugs which have caused aplastic anemia include the following:

amphotericin    sulfonamides      phenacetin        trimethadione
silver          chlordiazepoxide  tolbutamide       thiouracil
carbamazepine   chloramphenicol   tetracycline      oxyphenbutazone
arsenicals      chlorpromazine    pyrimethamine     carbimazole
acetazolamide   colchicine        penicillin        aspirin
mephenytoin     bismuth           promazine         quinacrine
methimazole     chlorothiazide    dinitrophenol     ristocetin
indomethacin    phenytoin         gold              trifluoperazine
carbutamide     perchlorate       chlorpheniramine  streptomycin
phenylbutazone  primidone         mercury           meprobamate
chlorpropamide  thiocyanate       tripelennamine

The drugs listed above produce marrow aplasia via an unpredictable, 
idiosyncratic host response in a small minority of patients. In 
addition, many antineoplastic drugs produce predictable, dose-related 
marrow suppression; these are not detailed here.

POLYCYTHEMIA

Polycythemia is defined as an increase in total body erythrocyte mass. 
As opposed to the situation with anemias, the physician may directly 
measure rbc mass using radiolabeling by chromium-51, so as to 
differentiate polycythemia (absolute erythrocytosis, as seen in 
polycythemia vera, chronic hypoxia, smoker's polycythemia, ectopic 
erythropoietin production, methemoglobinemia, and high O2 affinity 
hemoglobins) from relative erythrocytosis (as seen in stress 
polycythemia and dehydration). Further details of the work-up of 
polycythemias are beyond the scope of this monograph.

RDW (Red cell Distribution Width)

The red cell distribution width is a numerical expression which 
correlates with the degree of anisocytosis (variation in volume of the 
population of red cells). Some investigators feel that it is useful in 
differentiating thalassemia from iron deficiency anemia, but its use in 
this regard is far from universal acceptance. The RDW may also be useful 
in monitoring the results of hematinic therapy for iron-deficiency or 
megaloblastic anemias. As the patient's new, normally-sized cells are 
produced, the RDW initially increases, but then decreases as the normal 
cell population gains the majority.

PLATELET COUNT

Thrombocytosis is seen in many inflammatory disorders and 
myeloproliferative states, as well as in acute or chronic blood loss, 
hemolytic anemias, carcinomatosis, status post-splenectomy, post-
exercise, etc.

Thrombocytopenia is divided pathophysiologically into production defects 
and consumption defects based on examination of the bone marrow aspirate 
or biopsy for the presence of megakaryocytes. Production defects are 
seen in Wiskott-Aldritch syndrome, May-Hegglin anomaly, Bernard-Soulier 
syndrome, Chediak-Higashi anomaly, Fanconi's syndrome, aplastic anemia 
(see list of drugs, above), marrow replacement, megaloblastic and severe 
iron deficiency anemias, uremia, etc. Consumption defects are seen in 
autoimmune thrombocytopenias (including ITP and systemic lupus), DIC, 
TTP, congenital hemangiomas, hypersplenism, following massive 
hemorrhage, and in many severe infections.

GRANULOCYTES

Granulocytes include neutrophils (bands and segs), eosinophils, and 
basophils. In evaluating numerical aberrations of these cells (and of 
any other leukocytes), one should first determine the absolute count by 
multiplying the per cent value by the total WBC count. For instance, 2% 
basophils in a WBC of 6,000/uL gives 120 basophils, which is normal. 
However, 2% basophils in a WBC of 75,000/uL gives 1500 basophils/uL, 
which is grossly abnormal and establishes the diagnosis of chronic 
myelogenous leukemia over that of leukemoid reaction with fairly good 
accuracy.

Neutrophilia is seen in any acute insult to the body, whether infectious 
or not. Marked neutrophilia (>25,000/uL) brings up the problem of 
hematologic malignancy (leukemia, myelofibrosis) versus reactive 
leukocytosis, including "leukemoid reactions." Laboratory work-up of 
this problem may include expert review of the peripheral smear, 
leukocyte alkaline phosphatase, and cytogenetic analysis of peripheral 
blood or marrow granulocytes. Without cytogenetic analysis, bone marrrow 
aspiration and biopsy is of limited value and will not by itself 
establish the diagnosis of chronic myelocytic leukemia versus leukemoid 
reaction.

Smokers tend to have higher granulocyte counts than nonsmokers. The 
usual increment in total wbc count is 1000/L for each pack per day 
smoked.

Repeated excess of "bands" in a differential count of a healthy patient 
should alert the physician to the possibility of Pelger-Huet anomaly, 
the diagnosis of which can be established by expert review of the 
peripheral smear. 

Neutropenia may be paradoxically seen in certain infections, including 
typhoid fever, brucellosis, viral illnesses, rickettsioses, and malaria. 
Other causes include aplastic anemia (see list of drugs above), 
aleukemic acute leukemias, thyroid disorders, hypopitituitarism, 
cirrhosis, and Chediak-Higashi syndrome. 

Eosinophilia is seen in allergic disorders and invasive parasitoses. 
Other causes include pemphigus, dermatitis herpetiformis, scarlet fever, 
acute rheumatic fever, various myeloproliferative neoplasms, 
irradiation, polyarteritis nodosa, rheumatoid arthritis, sarcoidosis, 
smoking, tuberculosis, coccidioidomycosis, idiopathicallly as an 
inherited trait, and in the resolution phase of many acute infections. 

Eosinopenia is seen in the early phase of acute insults, such as shock, 
major pyogenic infections, trauma, surgery, etc. Drugs producing 
eosinopenia include corticosteroids, epinephrine, methysergide, niacin, 
niacinamide, and procainamide.

Basophilia, if absolute (see above) and of marked degree is a great clue 
to the presence of myeloproliferative disease as opposed to leukemoid 
reaction. Other causes of basophilia include allergic reactions, 
chickenpox, ulcerative colitis, myxedema, chronic hemolytic anemias, 
Hodgkin's disease, and status post-splenectomy. Estrogens, antithyroid 
drugs, and desipramine may also increase basophils.

Basopenia is not generally a clinical problem.

LYMPHOCYTES

Lymphocytosis is seen in infectious mononucleosis, viral hepatitis, 
cytomegalovirus infection, other viral infections, pertussis, 
toxoplasmosis, brucellosis, TB, syphilis, lymphocytic leukemias, and 
lead, carbon disulfide, tetrachloroethane, and arsenical poisonings. A 
mature lymphocyte count >7,000/uL is an individual over 50 years of age 
is highly suggestive of chronic lymphocytic leukemia (CLL). Drugs 
increasing the lymphocyte count include aminosalicyclic acid, 
griseofulvin, haloperidol, levodopa, niacinamide, phenytoin, and 
mephenytoin.

Lymphopenia is characteristic of AIDS. It is also seen in acute 
infections, Hodgkin's disease, systemic lupus, renal failure, 
carcinomatosis, and with administration of corticosteroids, lithium, 
mechlorethamine, methysergide, niacin, and ionizing irradiation. Of all 
hematopoietic cells lymphocytes are the most sensitive to whole-body 
irradiation, and their count is the first to fall in radiation sickness.

MONOCYTES

Monocytosis is seen in the recovery phase of many acute infections. It 
is also seen in diseases characterized by chronic granulomatous 
inflammation (TB, syphilis, brucellosis, Crohn's disease, and 
sarcoidosis), ulcerative colitis, systemic lupus, rheumatoid arthritis, 
polyarteritis nodosa, and many hematologic neoplasms. Poisoning by 
carbon disulfide, phosphorus, and tetrachloroethane, as well as 
administration of griseofulvin, haloperidol, and methsuximide, may cause 
monocytosis.

Monocytopenia is generally not a clinical problem.

                               REFERENCES

Tietz, Norbert W., Clinical Guide to Laboratory Tests, Saunders, 1983. 
Friedman, RB, et al., Effects of Diseases on Clinical Laboratory Tests,  
American Association of Clinical Chemistry, 1980
Anderson, KM, et al., Cholesterol and Mortality, JAMA 257: 21762180, 
1987

                                  NOTE

Please send all constructive comments regarding this FAQ to Ed Uthman, 
MD (uthman@domi.net). I am especially interested in 
correcting any errors of commission or omission.

                               DISCLAIMER

This article is provided as is without any express or implied 
warranties.

While every effort has been taken to ensure the accuracy of the
information, the author assumes no responsibility for errors or
omissions, or for damages resulting from use of the information herein.

Copyright (c) 1994, Edward O. Uthman. This material may be reformatted
and/or freely distributed via online services or other media, as long as
it is not substantively altered. Authors, educators, and others are
welcome to use any ideas presented herein, but I would ask for
acknowledgment in any published work derived therefrom. Commercial use
is not allowed without the prior written consent of the author.

version 2.03, 8/11/95

END
