Interpretation of Lab Tests

7/28/2019 Interpretation of Lab Tests

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Test Normal Value Clinical Significance

Acid Phosphatase

(ACP)

0.1 - 5.0 U/dl

values increases in prostatic cancer , some

liver diseases , hyper para thyroidism ,

hemolytic anemia,sickle cell crisis

Values are decreased in Down syndrome

Alkaline phospatase

(ALP)

4 -13 U/dl

Increases in some liver and bone diseases ,

hyper para thyroidism , pregnancy

Decreases in cretinism , growth retardation

,scurvy , achondroplasia

Alpha feto protien

(AFP)

Non pregnant

adult


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Bilirubin

Conjugated :


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,poor dietary intake

Chloride ion (Cl-) 95 - 103 mEq / Lit

Increase in dehydration ,Cushing's syndrome,anemia

Decrease in severe vomiting ,severe burns

,diabetic acidosis ,fever

Cholesterol Total 40 mg/dl

LDL Cholesterol


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ImmunoglobulinIgG

800 - 1801 mg/dlIncrease in infections of all type, liverdisease , severe malnutrition

Immunoglobulin

IgA

113 - 563 mg/dl

Increase in liver cirrhosis , chronic infections

, auto-immune disorders

Decrease in immunologic deficiency states

Immunoglobulin

IgM 54 - 222 mg/dlIncrease in trypanosomiasisDecrease in lymphoid aplasia

ImmunoglobulinIgD

0.5 - 3 mg/dl Increase in chronic infections , myelomas

ImmunoglobulinIgE

0.01 - 0.4 mg/dlIncrease in hay fever ,asthma , anaphylacticshock

Iron ,total 50 - 170 microgram/dl

Increase in liver disease , various anemia

Decrease in iron deficiency anemia

Iron-binding capacity ,

total (TIBC)

300 - 420 microgram

/dl

Increase in iron deficiency anemia , blood loss

,pregnancy ,in women taking birth control pills

Decrease in many chronic diseases , wide spreadcancer , mal nutrition ,nephrotic syndrome

Ketone bodies

Negative

Toxic level

20 mg/dl

Increase in keto acidosis ,fever ,anorexia ,fasting

,starvation ,high fat diet ,low carbohydrate diet ,following vomiting

Lctic acid(Lactate)

Arterial

3 - 7 mg/dl

Venous

5 - 20 mg/dl

Increase during Muscular activity ,congestive

heart failure ,shock ,severe hemorrhage

Lactic dehydrogenase

(LDH)71 - 207 IU/litr

Increase in myocardial infarction ,liver

disease,skeletal muscle necrosis , extensive

cancer

Lipids

Total

400 - 800 mg / dl

Increase in hyperlipidemia , diabetes mellitus,hypothyroidism

Decrease in fat mal absotbtion

Lipids

Cholesterol

150 - 220mg/dl


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Lipids

Triglycerides

10 - 190 mg/dl

Osmolality285 - 295 mOsm/kg

water

Increase in cirrhosis ,congestive hear failure,high protein diet

Decrease in aldosteronism ,diabetes insipidus,hypercalcemia

Oxygen (O2)Arterial

15 - 23 Volume %

Increase in polycythemya

Decrease in chronic obstructive lung disease

Oxygen partial

pressure(pO2)

Arterial

80 - 105 mm Hg

Increase in polycythemia , hyperventilation

Decrease in anemia , insufficient atmosphericoxygen , hypoventilation

pHArterial

7.35 - 7.45

Increase in vomiting ,hyperventilation ,excessive

bicarbonate , lack of oxygen

Decrease in renal failure , diabetic ketoacidosis,

hypoxia , airway obstruction ,shock

Phosphorous , inorganic

(P)

Adults

2.5 - 4.5 mg/dl

Children

4-7 mg/dl

Increase in renal failure hypoparathyroidism

,hypocalcemia , bone tumors , diabeticketoacidosis ,acromagaly

Decrease in hyperparathyroidism ,alcoholism,rickets ,osteomalacia

Protein , Total 6 - 7.8 g/dl

Increase in dehydration ,shock , systemic lupus

erythematosus (SLE) , rheumatoid arthritis (RA), chronic infections , chronic liver disease

Decrease in insufficient protein intake

,hemorrhage, mal absorbtion , diarrhea , chronicrenal failure ,severe burns

Albumin 3.5 - 5.0 g/dl

Globulin 2.3 - 3.5 g/dl

A/G ratio 1.5 : 1 to 2.5 : 1

Reversed A/G may indicate chronic liver disease

, leukemia , Hodgkin's Disease ,Tuberculosis

(TB ),chronic hepetitis

Sodium (Na+) 136 - 142 mEq/litr

Increase in dehydration ,aldosteronism , coma

,Cushing's disease ,diabetes insipidus

Decrease in severe burns , vomiting ,diarrhea ,

Addison's disease ,nephritis , excessive sweating, edema

Thyroid Hormone 80 - 200 ng/dl Increase in hyperthyroidism


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T3(Triiodothyronine ) Decrease in hypothyroidism

Thyroid Hormone

T4(Thyroxine )

4 - 11microgram / dl

Increase in hyperthyroidism

Decrease in hypothyroidism

Thyroid stimulatinghormone(TSH)

0.3 - 4.0 mU/Lit

Thyroxine binding

globulin (TBG )10 -26 microgram /dl

Increase in hypothyroidism

Decrease in hyperthyroidism

Uric acid (urate)

Male4.0 - 8.5 mg/dl

Female

2.7 - 7.3 mg/dl

Increase in impaired renal function , gout,metastatic cancer , shock, starvation

Decrease in person treated with

uricosuric drugs

Bleeding time 4 - 8 mintsIncrease in Thrombocytopenia ,severe liver disease,aplastic anemia

Erythrocytesedimentation rate

( ESR )

Female Under 50 yrs


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38 - 47 %

Decrease in anemia , leukemia , cirrhosis ,

hyperthyroidism

Platelet count150000 - 400000

/cubic mm

Increase in cancer , trauma , heart disease,cirrhosis

Decrease in anemias ,allergic condition ,during

cancer chemotherapy

Prothrombin time 11 - 15 secondsIncrease in prothrombin & vitamin K deficiancy ,

liver disease , hypervitaminosis A

Red blood cell count

(RBC)

Male

4.5 - 6.5 million /cubic mm

Female

3.9 - 5.6 million /

cubic mm

Increase in polycythemia , dehydration,following hemorrhage ,

Decrease in SLE ,anemia ,Addison's disease

Reticulocyte count

(WB)0.5 - 2.0 %

Increase in hemolytic anemia metastaticcarcinoma , leukemia

Decrease in iron deficiency & perniciousanemia ,radiation therapy ,kidney disease

White blood cell count

(WBC) Total

5000 - 10000 /cubic

mm

Increase in acute infections ,trauma , malignant

disease , cardio-vascular disease

Decrease in diabetes mellitus , anemias

,following cancer chemotherapy

WBC Differential count

Neutrophils:60-70 %

Eosinophils: 2 - 4 %

Basophils: 0.5 - 1 %

Lymphocytes:20-25%

Monocytes: 3 - 8 %

Neutrophils:

Increase in acute infections

Eosinophils:

Increase in allergic reactions

Basophils:

Increase in allergic reactions

Lymphocytes:

Increase during antigen - antibody reaction


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Monocytes:Increase in chronic infections

Interpretation of Lab Test Profiles

The Analytes

Sodium

Increase in serum sodium is seen in conditions with water loss inexcess of salt loss, as in profuse sweating, severe diarrhea orvomiting, polyuria (as in diabetes mellitus or insipidus), hypergluco- or

mineralocorticoidism, and inadequate water intake. Drugs causingelevated sodium include steroids with mineralocorticoid activity,carbenoxolone, diazoxide, guanethidine, licorice, methyldopa,oxyphenbutazone, sodium bicarbonate, methoxyflurane, andreserpine.

Decrease in sodium is seen in states characterized by intake of freewater or hypotonic solutions, as may occur in fluid replacementfollowing sweating, diarrhea, vomiting, and diuretic abuse. Dilutionalhyponatremia may occur in cardiac failure, liver failure, nephroticsyndrome, malnutrition, and SIADH. There are many other causes ofhyponatremia, mostly related to corticosteroid metabolic defects orrenal tubular abnormalities. Drugs other than diuretics may causehyponatremia, including ammonium chloride, chlorpropamide,heparin, aminoglutethimide, vasopressin, cyclophosphamide, andvincristine.

Potassium

Increase in serum potassium is seen in states characterized byexcess destruction of cells, with redistribution of K+ from the intra- tothe extracellular compartment, as in massive hemolysis, crushinjuries, hyperkinetic activity, and malignant hyperpyrexia. Decreasedrenal K+ excretion is seen in acute renal failure, some cases ofchronic renal failure, Addison's disease, and other sodium-depleted


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states. Hyperkalemia due to pure excess of K+ intake is usuallyiatrogenic.

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/herarm with the tourniquet in place prior to venipuncture. Hemolysis andmarked thrombocytosis may cause false elevations of serum K+ aswell. Failure to promptly separate serum from cells in a clot tube is anotorious source of falsely elevated potassium.

Decrease in serum potassium is seen usually in states characterizedby excess K+ loss, such as in vomiting, diarrhea, villous adenoma ofthe 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 familialperiodic paralysis. Drugs causing hypokalemia include amphotericin,carbenicillin, carbenoxolone, corticosteroids, diuretics, licorice,salicylates, and ticarcillin.

Chloride

Increase in serum chloride is seen in dehydration, renal tubularacidosis, acute renal failure, diabetes insipidus, prolonged diarrhea,salicylate toxicity, respiratory alkalosis, hypothalamic lesions, andadrenocortical hyperfunction. Drugs causing increased chlorideinclude acetazolamide, androgens, corticosteroids, cholestyramine,diazoxide, estrogens, guanethidine, methyldopa, oxyphenbutazone,phenylbutazone, thiazides, and triamterene. Bromides in serum willnot be distinguished from chloride in routine testing, so intoxicationmay show spuriously increased chloride [see also "Anion gap,"below].

Decrease in serum chloride is seen in excessive sweating, prolongedvomiting, salt-losing nephropathy, adrenocortical defficiency, variousacid base disturbances, conditions characterized by expansion ofextracellular fluid volume, acute intermittent porphyria, SIADH, etc.


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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 inserum bicarbonate (HCO3

-) concentration rather than dissolved CO2gas, or PCO 2 (which accounts for only a small fraction of the total).Increased serum bicarbonate is seen in compensated respiratoryacidosis and in metabolic alkalosis. Diuretics (thiazides, ethacrynicacid, furosemide, mercurials), corticosteroids (in long term use), andlaxatives (when abused) may cause increased bicarbonate.

Decrease in blood CO2 is seen in metabolic acidosis and

compensated respiratory alkalosis. Substances causing metabolicacidosis include ammonium chloride, acetazolamide, ethylene glycol,methanol, paraldehyde, and phenformin. Salicylate poisoning ischaracterized by early respiratory alkalosis followed by metabolicacidosis with attendant decreased bicarbonate.

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

collected in this manner.

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

Anion gap

Increased serum anion gap reflects the presence of unmeasuredanions, as in uremia (phosphate, sulfate), diabetic ketoacidosis

(acetoacetate, beta-hydroxybutyrate), shock, exercise-inducedphysiologic anaerobic glycolysis, fructose and phenforminadministration (lactate), and poisoning by methanol (formate),ethylene glycol (oxalate), paraldehyde, and salicylates. Therapy withdiuretics, penicillin, and carbenicillin may also elevate the anion gap.


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Decreased serum anion gap is seen in dilutional states andhyperviscosity syndromes associated with paraproteinemias.Because bromide is not distinguished from chloride in somemethodologies, bromide intoxication may appear to produce adecreased anion gap.

Glucose

Hyperglycemia can be diagnosed only in relation to time elapsed aftermeals and after ruling out spurious influences (especially drugs,including caffeine, corticosteroids, estrogens, indomethacin, oralcontraceptives, lithium, phenytoin, furosemide, thiazides, thyroxine,and many more). Previously, the diagnosis of diabetes mellitus wasmade by demonstrating a fasting blood glucose >140 mg/dL

(7.8mmol/L) and/or 2-hour postprandial glucose >200 mg/dL (11.1mmol/L) on more than one occasion. In 1997, theAmerican DiabetesAssociationrevised these diagnostic criteria. Thenew criteriaare asfollows:

Symptoms of diabetes plus a casual plasma glucose of200 mg/dL [11.1 mmol/L] or greater.

OR

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

OR

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

At least one of the above criteria must be met on more than oneoccasion, and the third method (2-hour plasma glucose after oralglucose challenge) is not recommended for routine clinical use. The

criteria apply to anyage group. This means that the classic oralglucose tolerance test is now obsolete, since it is not necessary forthe 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 ofgestation, is done by measuring plasma glucose 1 hour after a 50-
http://www.diabetes.org/http://www.diabetes.org/http://www.diabetes.org/http://www.diabetes.org/http://www.diabetes.org/DiabetesCare/Supplement198/S5.htmhttp://www.diabetes.org/DiabetesCare/Supplement198/S5.htmhttp://www.diabetes.org/DiabetesCare/Supplement198/S5.htmhttp://www.diabetes.org/DiabetesCare/Supplement198/S5.htmhttp://www.diabetes.org/http://www.diabetes.org/


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gram oral glucose challenge. If the plasma glucose is 140 mg/dL orgreater, then the diagnostic test is performed. This consists ofmeasuring plasma glucose after a 100-gram oral challenge. Thediagnostic 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 (isletcell tumor, adrenal and gastric carcinoma, fibrosarcoma, hepatoma),

severe liver disease, poisonings (arsenic, CCl4, chloroform,cinchophen, phosphorous, alcohol, salicylates, phenformin, andantihistamines), adrenocortical insufficiency, hypothroidism, andfunctional disorders (postgastrectomy, gastroenterostomy, autonomicnervous system disorders). Failure to promptly separate serum fromcells in a blood collection tube causes falsely depressed glucoselevels. If delay in transporting a blood glucose to the lab isanticipated, the specimen should be collected in a fluoride-containingtube (gray-top in the US, yellow in the UK).

In the past, the 5-hour oral glucose tolerance test was used todiagnose reactive (postprandial) hypoglycemia, but this has fallen outof favor. Currently, the diagnosis is made by demonstrating a lowplasma glucose (


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

Creatinine

Increase in serum creatinine is seen any renal functional impairment.

Because of its insensitivity in detecting early renal failure, thecreatinine clearance is significantly reduced before any rise in serumcreatinine occurs. The renal impairment may be due to intrinsic renallesions, decreased perfusion of the kidney, or obstruction of the lowerurinary tract.

Nephrotoxic drugs and other chemicals include:

antimony arsenic bismuth cadmium

copper gold iron leadlithium 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 glycolacetazolamide aminocaproic acid aminosalicylate boric acid

cyclophosphamide cisplatin dextran (LMW) furosemide

mannitol methoxyflurane mithramycin penicillamine

pentamide phenindione quinine thiazides

carbontetrachloride

Deranged metabolic processes may cause increases in serum creatinine,

as in acromegaly and hyperthyroidism, but dietary protein intake does notinfluence the serum level (as opposed to the situation with BUN). Somesubstances interfere with the colorimetric system used to measurecreatinine, including acetoacetate, ascorbic acid, levodopa, methyldopa,glucose and fructose. Decrease in serum creatinine is seen in pregnancyand in conditions characterized by muscle wasting.


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BUN:creatinine ratio

BUN:creatinine ratio is usually >20:1 in prerenal and postrenalazotemia, and


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Hypercalcemia is seen in malignant neoplasms (with or without boneinvolvement), primary and tertiary hyperparathyroidism, sarcoidosis,vitamin D intoxication, milk-alkali syndrome, Paget's disease of bone(with immobilization), thyrotoxicosis, acromegaly, and diuretic phaseof 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 spuriouslyincrease total calcium. Drugs producing hypercalcemia includealkaline antacids, DES, diuretics (chronic administration), estrogens(incl. oral contraceptives), and progesterone.

Hypocalcemia must be interpreted in relation to serum albuminconcentration (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 fromlaboratory to laboratory). True decrease in the physiologically activeionized form of Ca++ occurs in many situations, includinghypoparathyroidism, vitamin D deficiency, chronic renal failure,magnesium deficiency, prolonged anticonvulsant therapy, acutepancreatitis, massive transfusion, alcoholism, etc. Drugs producinghypocalcemia include most diuretics, estrogens, fluorides, glucose,insulin, excessive laxatives, magnesium salts, methicillin, andphosphates.

Iron

Serum iron may be increased in hemolytic, megaloblastic, andaplastic anemias, and in hemochromatosis, acute leukemia, leadpoisoning, pyridoxine deficiency, thalassemia, excessive iron therapy,and after repeated transfusions. Drugs causing increased serum ironinclude chloramphenicol, cisplatin, estrogens (including oralcontraceptives), ethanol, iron dextran, and methotrexate.

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

Alkaline phosphatase (ALP)

Increased serum alkaline phosphatase is seen in states of increasedosteoblastic activity (hyperparathyroidism, osteomalacia, primary and


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metastatic neoplasms), hepatobiliary diseases characterized by somedegree of intra- or extrahepatic cholestasis, and in sepsis, chronicinflammatory bowel disease, and thyrotoxicosis. Isoenzymedetermination may help determine the organ/tissue responsible for analkaline phosphatase elevation.

Decreased serum alkaline phosphatase may not be clinicallysignificant. However, decreased serum levels have been observed inhypothyroidism, scurvy, kwashiokor, achrondroplastic dwarfism,deposition of radioactive materials in bone, and in the rare geneticcondition hypophosphatasia.

There are probably more variations in the way in which alkalinephosphatase is assayed than any other enzyme. Therefore, the

reporting units vary from place to place. The reference range for theassaying laboratory must be carefully studied when interpreting anyindividual result.

Lactate dehydrogenase (LD or "LDH")

Increase of LD activity in serum may occur in any injury that causesloss of cell cytoplasm. More specific information can be obtained byLD isoenzyme studies. Also, elevation of serum LD is observed dueto in vivo effects of anesthetic agents, clofibrate, dicumarol, ethanol,

fluorides, imipramine, methotrexate, mithramycin, narcoticanalgesics, nitrofurantoin, propoxyphene, quinidine, andsulfonamides.

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 (particularlytemperature) vary among labs. The reference range for the assayinglaboratory 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).

ALT (SGPT)


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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 whichcause intrahepatic or extrahepatic obstruction of bile ducts, includingparenchymatous liver diseases with a major cholestatic component(e.g., cholestatic hepatitis). Lesser elevations of gamma-GT are seenin other liver diseases, and in infectious mononucleosis,hyperthyroidism, myotonic dystrophy, and after renal allograft. Drugscausing hepatocellular damage and cholestasis may also causegamma-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 acommon culprit.

Decreased gamma-GT is not clinically significant.

Bilirubin

Serum total bilirubin is increased in hepatocellular damage (infectioushepatitis, alcoholic and other toxic hepatopathy, neoplasms), intra-and extrahepatic biliary tract obstruction, intravascular and

extravascular hemolysis, physiologic neonatal jaundice, Crigler-Najjarsyndrome, Gilbert's disease, Dubin-Johnson syndrome, and fructoseintolerance.

Drugs known to cause cholestasis include the following:

aminosalicylic androgens azathioprine benzodiazepines


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acid

carbamazepine carbarsone chlorpropamide propoxyphene

estrogens penicillin gold Na thiomalate imipramine

meprobamate methimazole nicotinic acid progestins

penicillin phenothiazinesoralcontraceptives

sulfonamides sulfoneserythromycinestolate

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 incholestasis and late in the course of chronic liver disease. Indirect(unconjugated) bilirubin tends to predominate in hemolysis andGilbert'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 involume contraction, venous stasis, or in hypergammaglobulinemia.


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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 naturalcondition. Relative increase may occur in hemoconcentration.

Absolute increase may occur artificially by infusion of hyperoncoticalbumin suspensions.

Decreased serum albumin is seen in states of decreased synthesis(malnutrition, malabsorption, liver disease, and other chronicdiseases), 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 thealbumin/globulin ratio) in states characterized by chronic inflammationand in B-lymphocyte neoplasms, like myeloma and Waldenstrm'smacroglobulinemia. More relevant information concerning increasedglobulin may be obtained by serum protein electrophoresis.

Decreased globulin may be seen in congenital or acquiredhypogammaglobulinemic states. Serum and urine proteinelectrophoresis may help to better define the clinical problem.

T3 uptake

This test measures the amount of thyroxine-binding globulin (TBG) inthe patient's serum. When TBG is increased, T3 uptake is decreased,and vice versa. T3 Uptake does notmeasure the level of T3 or T4 inserum.

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


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Decreased T3 uptake (increased TBG) may occur due to the effectsof 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 T

3

uptake may occur in hypothyroidism.

Thyroxine (T4)

This is a measurement of the total thyroxine in the serum, includingboth the physiologically active (free) form, and the inactive formbound to thyroxine-binding globulin (TBG). It is increased inhyperthyroidism and in euthyroid states characterized by increasedTBG (See "T3 uptake," above, and "FTI," below). Occasionally,

hyperthyroidism will not be manifested by elevation of T4 (free ortotal), but only by elevation of T3 (triiodothyronine). Therefore, ifthyrotoxicosis is clinically suspect, and T4 and FTI are normal, thetest "T3-RIA" is recommended (this is not the same test as "T3uptake," which has nothing to do with the amount of T3 in the patient'sserum).

T4 is decreased in hypothyroidism and in euthyroid statescharacterized 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 thereciprocal effects of T4 and T3 uptake to give a single figure whichcorrelates with free T4. Therefore, increased FTI is seen inhyperthyroidism, and decreased FTI is seen in hypothyroidism. Earlycases of hyperthyroidism may be expressed only by decreasedthyroid stimulation hormone (TSH) with normal FTI. Early cases ofhypothyroidism may be expressed only by increased TSH withnormal FTI. Currently, the method of choice for screening for bothhyper- and hypothyroidism is serum TSH only. Modernmethodologies ("ultrasensitive TSH") allow accurate determination ofthe very low concentrations of TSH at the phyisological cutoffbetween the normal and hyperthyroid states.


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

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

Total cholesterol has been found to correlate with total and cardiovascularmortality in the 30-50 year age group. Cardiovascular mortality increases9% for each 10 mg/dL increase in total cholesterol over the baseline valueof 180 mg/dL. Approximately 80% of the adult male population has valuesgreater than this, so the use of the median 95% of the population toestablish a normal range (as is traditional in lab medicine in general) hasno utility for this test. Excess mortality has been shown not to correlate with

cholesterol levels in the >50 years age group, probably because of thedepressive effects on cholesterol levels expressed by various chronicdiseases to which older individuals are prone.

HDL-cholesterol is "good" cholesterol, in that risk of cardiovascular diseasedecreases with increase of HDL. An HDL-cholesterol level of


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

Readers outside the US may find the following version of the table moreuseful. This uses SI units for total and HDL cholesterol:

Total cholesterol (mmol/L)3.9 4.8 5.2 5.4 5.7 5.8 6.3 6.7 7.8

------------------------------------------------------0.65 | #### 1.34 1.50 1.60 1.80 2.00 3.00 4.00 6.000.78 | #### 1.22 1.37 1.46 1.64 1.82 2.73 3.64 5.46

0.91 | #### 1.00 1.12 1.19 1.34 1.49 2.24 2.98 4.47HDL-chol 1.04 | #### 0.82 0.92 0.98 1.10 1.22 1.83 2.44 3.66(mmol/L) 1.16 | #### 0.67 0.75 0.80 0.90 1.00 1.50 2.00 3.00

1.30 | #### 0.55 0.62 0.66 0.74 0.82 1.23 1.64 2.461.42 | #### 0.45 0.50 0.54 0.60 0.67 1.01 1.34 2.011.55 | #### 0.37 0.41 0.44 0.50 0.55 0.83 1.10 1.651.68 | #### 0.30 0.34 0.36 0.41 0.45 0.68 0.90 1.35

over 1.81 | #### #### #### #### #### #### #### #### ####

Triglyceride level is risk factor independent of the cholesterol levels.

Triglycerides are important as risk factors only if they are not part of thechylomicron fraction. To make this determination in a hypertriglyceridemicpatient, it is necessary to either perform lipoprotein electrophoresis orvisually examine an overnight- refrigerated serum sample for the presenceof a chylomicron layer. The use of lipoprotein electrophoresis for routineassessment of atherosclerosis risk is probably overkill in terms of expenseto the patient.

LDL-cholesterol (the amount of cholesterol associated with low-density, orbeta, lipoprotein) is not an independently measured parameter but ismathematically derived from the parameters detailed above. Some risk-reduction programs use LDL-cholesterol as the primary target parameterfor monitoring the success of the program. The "desirable" level for LDL-cholesterol is less than 100 mg/dL.


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A detailed statement on this subject is "Primary Prevention of CoronaryHeart Disease: Guidance From Framingham", Circulation 97:1876-1887,1998. The full text is availableonline, courtesy of theAmerican Heart

Association.

Triglycerides

Markedly increased triglycerides (>500 mg/dL) usually indicate anonfasting 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 lipoproteinelectrophoresis, but this is not usually necessary to assess a patient'srisk 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,chronic obstructive pulmonary disease, hyperthyroidism, malnutrition,and malabsorption states.

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 isusually seen in anemia of any cause with the possible exception ofthalassemia minor, where a mild or borderline anemia is seen with ahigh or borderline-high RBC. Increased RBC is seen in erythrocytoticstates, whether absolute (polycythemia vera, erythrocytosis of chronichypoxia) or relative (dehydration, stress polycthemia), and inthalassemia minor [see "Hemoglobin," below, for discussion ofanemias and erythrocytoses].

HEMOGLOBIN, HEMATOCRIT, MCV (mean corpuscular volume), MCH(mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobinconcentration)

Strictly speaking, anemia is defined as a decrease in total body red cellmass. For practical purposes, however, anemia is typically defined ashemoglobin


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MCV and MCHC (MCH is usually not helpful) into one of the followingcategories:

Microcytic/hypochromic anemia (decreased MCV, decreased MCHC)o Iron deficiency (common)o Thalassemia (common, except in people of Germanic,

Slavonic, Baltic, Native American, Han Chinese, Japanesedescent)

o Anemia of chronic disease (uncommonly microcytic)o Sideroblastic anemia (uncommon; acquired forms more often

macrocytic)o Lead poisoning (uncommon)o Hemoglobin E trait or disease (common in Thai, Khmer,

Burmese,Malay, Vietnamese, and Bengali groups)

Macrocytic/normochromic anemia (increased MCV, normal MCHC)o Folate deficiency (common)o B12 deficiency (common)o Myelodysplastic syndromes (not uncommon, especially in older

individuals)o Hypothyroidism (rare)

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

o Normoregenerative normocytic anemias (appropriatereticulocyte response)

Immunohemolytic anemia Glucose-6-phosphate dehydrogenase (G6PD) deficiency

(common) Hemoglobin S or C Hereditary spherocytosis Microangiopathic hemolytic anemia

Paroxysmal hemoglobinuriao Hyporegenerative normocytic anemias (inadequate reticulocyte

response) Anemia of chronic disease Anemia of chronic renal failure Aplastic anemia*


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*Drugs and other substances that have caused aplastic anemia include thefollowing:

amphotericin sulfonamides phenacetin trimethadionesilver chlordiazepoxide tolbutamide thiouracilcarbamazepine chloramphenicol tetracycline oxyphenbutazonearsenicals chlorpromazine pyrimethamine carbimazoleacetazolamide colchicine penicillin aspirinmephenytoin bismuth promazine quinacrinemethimazole chlorothiazide dinitrophenol ristocetinindomethacin phenytoin gold trifluoperazinecarbutamide perchlorate chlorpheniramine streptomycinphenylbutazone primidone mercury meprobamatechlorpropamide thiocyanate tripelennamine benzene

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

POLYCYTHEMIA

Polycythemia is defined as an increase in total body erythrocyte mass. Asopposed to the situation with anemias, the physician may directly measure

rbc mass using radiolabeling by 51Cr, 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 relativeerythrocytosis (as seen in stress polycythemia and dehydration). Furtherdetails of the work-up of polycythemias are beyond the scope of thismonograph.

RDW (Red cell Distribution Width)

The red cell distribution width is a numerical expression whichcorrelates with the degree of anisocytosis (variation in volume of thepopulation of red cells). Some investigators feel that it is useful indifferentiating thalassemia from iron deficiency anemia, but its use inthis regard is far from universal acceptance. The RDW may also beuseful in monitoring the results of hematinic therapy for iron-deficiency or megaloblastic anemias. As the patient's new, normally-


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sized cells are produced, the RDW initially increases, but thendecreases as the normal cell population gains the majority.

Platelet count

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

Thrombocytopenia is divided pathophysiologically into productiondefects 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-Higashianomaly, Fanconi's syndrome, aplastic anemia (see list of drugs,above), marrow replacement, megaloblastic and severe irondeficiency anemias, uremia, etc. Consumption defects are seen inautoimmune thrombocytopenias (including ITP and systemic lupus),DIC, TTP, congenital hemangiomas, hypersplenism, followingmassive hemorrhage, and in many severe infections.

WBC (White Blood Cell) count

The WBC is really a nonparameter, since it simply represents thesum of the counts of granulocytes, lymphocytes, and monocytes perunit volume of whole blood. Automated counters do not distinguishbands from segs; however, it has been shown that if all otherhematologic parameters are within normal limits, such a distinction israrely important. Also, even in the best hands, trying to reliablydistinguish bands from segs under the microscope is fraught with

reproducibility problems. Discussion concerning a patient's bandcount probably carries no more scientific weight than a medievaltheological argument.

Granulocytes


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

Neutrophils

Neutrophilia is seen in any acute insult to the body, whetherinfectious or not. Marked neutrophilia (>25,000/L) brings up the

problem of hematologic malignancy (leukemia, myelofibrosis) versusreactive leukocytosis, including "leukemoid reactions." Laboratorywork-up of this problem may include expert review of the peripheralsmear, leukocyte alkaline phosphatase, and cytogenetic analysis ofperipheral blood or marrow granulocytes. Without cytogeneticanalysis, bone marrrow aspiration and biopsy is of limited value andwill not by itself establish the diagnosis of chronic myelocyticleukemia 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 perday smoked.

Repeated excess of "bands" in a differential count of a healthy patientshould alert the physician to the possibility of Pelger-Hut anomaly,the diagnosis of which can be established by expert review of theperipheral smear. The manual band count is so poorly reproducibleamong observers that it is widely considered a worthless test. A morereproducible hematologic criterion for acute phase reaction is thepresence in the smear of any younger forms of the neutrophilic line(metamyelocyte or younger).

Neutropenia may be paradoxically seen in certain infections,including typhoid fever, brucellosis, viral illnesses, rickettsioses, andmalaria. Other causes include aplastic anemia (see list of drugs


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above), aleukemic acute leukemias, thyroid disorders,hypopitituitarism, cirrhosis, and Chediak-Higashi syndrome.

Eosinophils

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

Eosinopenia is seen in the early phase of acute insults, such asshock, major pyogenic infections, trauma, surgery, etc. Drugs

producing eosinopenia include corticosteroids, epinephrine,methysergide, niacin, niacinamide, and procainamide.

Basophils

Basophilia, if absolute (see above) and of marked degree is a greatclue to the presence of myeloproliferative disease as opposed toleukemoid reaction. Other causes of basophilia include allergicreactions, chickenpox, ulcerative colitis, myxedema, chronichemolytic anemias, Hodgkin's disease, and status post-splenectomy.

Estrogens, antithyroid drugs, and desipramine may also increasebasophils.

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. Amature lymphocyte count >7,000/L is an individual over 50 years ofage is highly suggestive of chronic lymphocytic leukemia (CLL).Drugs increasing the lymphocyte count include aminosalicyclic acid,griseofulvin, haloperidol, levodopa, niacinamide, phenytoin, andmephenytoin.


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Lymphopenia is characteristic of AIDS. It is also seen in acuteinfections, Hodgkin's disease, systemic lupus, renal failure,carcinomatosis, and with administration of corticosteroids, lithium,mechlorethamine, methysergide, niacin, and ionizing irradiation. Of allhematopoietic cells lymphocytes are the most sensitive to whole-bodyirradiation, 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 granulomatousinflammation (TB, syphilis, brucellosis, Crohn's disease, andsarcoidosis), ulcerative colitis, systemic lupus, rheumatoid arthritis,polyarteritis nodosa, and many hematologic neoplasms. Poisoning by

carbon disulfide, phosphorus, and tetrachloroethane, as well asadministration of griseofulvin, haloperidol, and methsuximide, maycause monocytosis.

Monocytopenia is generally not a clinical problem.

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Interpretation of Lab Tests