NAME GGT (Gamma glutamyltransf erase)

ROLE
The purpose of this blood serum chemistry test is to provide information about hepatobiliary diseases, to assess liver function, and to detect alcohol ingestion. Another purpose is to distinguish between skeletal disease and hepatic disease when serum alkaline phosphatase is elevated.

NORMAL
Normal results in females under age 45, range from 5 to 27 U/L; in females over age 45 and in males, levels range from 6 to 37 U/L.

DIFF
A normal GGT level suggests such elevation stems from skeletal disease. Serum GGT values vary with the assay method used (colorimetric or kinetic). The sharpest increases in GGT levels indicate obstructive jaundice and hepatic metastasis. Elevations may indicate any acute hepatic disease, acute pancreatitis, renal disease, alcohol ingestion, postoperative status, and prostatic metastasis. This test is nonspecific, providing little data about the type of hepatic disease. GGT is particularly sensitive to the effects of alcohol in the liver, and levels may be elevated after moderate alcohol intake and in chronic alcoholism, even without clinical evidence of hepatic injury. These RBC indices are useful in the differential diagnosis of types of anemia. Anemias are classified on the basis of cell size (MCV) and cell color (MCHC). MCV less than lower limit of normal: microcytic MCV within normal range: normocytic MCV greater than upper limit of normal: macrocytic MCHC less than lower limit of normal: hypochromic MCHC with normal range: normochromic MCHC greater than upper limit of normal: hyperchromic Anemias have been classified as follows: normocytic/normochromic (NC/NC) anemia: acute blood loss aplastic anemia (for example, due to chloramphenicol toxicity) prosthetic heart valves sepsis tumor microcytic/hypochromic anemia: iron deficiency lead poisoning thalassemia microcytic/normochromic anemia: erythropoietin deficiency secondary to renal failure macrocytic/normochromic anemia: chemotherapy folate deficiency vitamin B12 deficiency

MCV (mean corpuscular volume)

MCV = Hct/Hgb Normal values: MCV: 80 to 95 femtoliter MCH: 27 to 31 picograms/ce ll MCHC: 32 to 36 grams/decilit er

Uric Acid

4.1 to 8.8 mg/dl

Greater-than-normal levels of uric acid (hyperuricemia) may indicate:

acidosis

gout

leukemia nephrolithi asis polycythe mia vera purinerich diet

alcoholi hypoparathyro sm idism diabetes lead poisoning mellitus renal toxemia of failure pregnancy severe exercise

Lower-than-normal levels of uric acid may indicate:

Fanconi's syndrome low purine diet

Wilson's disease

SIADH

Additional conditions under which the test may be performed: chronic gouty arthritis injury of the kidney and ureter

Cholesterol

140 to 310 mg/dl optimal values: 140220 mg/dl Note: mg/dl = milligrams per deciliter Normal values: 10 to 190 mg/dl Note: mg/dl = milligrams per deciliter Intracellular Normal Range: enzyme involved Laboratoryin amino acid and specific U/L carbohydrate metabolism. Present in large concentrations in liver, kidney; smaller amounts in skeletal muscle and heart. Released with tissue damage.

atherosclerosis biliary cirrhosis familial hyperlipidemias highcholesterol diet hypothyroidism myocardial infarction nephrotic syndrome uncontrolled diabetes

Triglycerides

Alanine Aminotransferase (ALT, SGPT, GPT)

cirrhosis familial hyperlipoproteinemia (rare) hypothyroidism low protein in diet and high carbohydrates poorly controlled diabetes nephrotic syndrome pancreatitis Increased in: Acute viral hepatitis (ALT>AST), biliary tract obstruction (cholangitis, choledocholithiasis), alcoholic hepatitis and cirrhosis (AST>ALT), liver abscess, metastatic or primary liver cancer; right heart failure, ischemia or hypoxia, injury to liver ("shock liver"), extensive trauma. Drugs causing cholestasis and other hepatotoxic drugs. Additional: ALT screening of donor blood used in blood banks to exclude

Albumin

non-A, non-B hepatitis. Major component Normal Range: increased in: Dehydration, shock, of plasma proteins, 3.4-4.7 g/dL hemoconcentration. influenced by nutritional state, Decreased in: Decreased hepatic hepatic function, synthesis (chronic liver disease, renal function, malnutrition, malabsorption, various diseases. malignancy, congenital analbuminemia [rare]). Increased losses (nephrotic syndrome, burns, trauma, hemorrhage with fluid replacement, fistulae, enteropathy, acute or chronic glomerulonephritis). Hemodilution (pregnancy, CHF). Drugs (eg, estrogens). Additional: Serum albumin gives an indication of severity in chronic liver disease. Useful in nutritional assessment if no impairment in production or increased loss. Alkaline Normal Range: increased in: Obstructive hepatobiliary phosphatases are Method and disease, hepatotoxic drugs, bone found in liver, age disease (physiologic bone growth, bone, intestine, dependent Paget's disease, osteomalacia, placenta. osteogenic sarcoma, bone metastases), hyperparathyroidism, rickets. Benign familial hyperphosphatasemia, pregnancy (3rd trimester), GI disease (perforated ulcer or infarct). Decreased in: Hypophosphatasia. Additional: Normal in osteoporosis. Alkaline phosphatase isoenzyme separation by electrophoresis or differential heat inactivation is unreliable. Use g-glutamyl transpeptidase (GGT), which increases in hepatobiliary disease, to infer origin of increased alkaline phosphatase (ie, liver or bone). Heterogeneous Normal Range: Elevated in: 1/3-3/4 of patients over antibodies to < 1:20 age 65 (usually in low titers), systemic nuclear antigens lupus erythematosus (98%), drug(DNA and RNA, induced lupus (100%), Sj?gren's (80%), histone and rheumatoid arthritis (30-50%), nonhistone scleroderma (60%), mixed connective proteins). tissue disease (100%), Felty's Antinuclear syndrome, mononucleosis, hepatic or antibody is biliary cirrhosis, hepatitis, leukemia, measured in myasthenia gravis, dermatomyositis, patient's serum by polymyositis, chronic renal failure. layering serum over human Additional: A negative ANA test does epithelial cells and not completely rule out SLE, but detecting the alternative diagnoses should be

Alkaline Phosphatase

ANA (Antinuclear Antibodies)

antibody with fluoresceinconjugated polyvalent antihuman immunoglobulin.

considered. Pattern of staining of ANA may give some clues to diagnoses, but since the pattern also changes with serum dilution, it is not routinely reported. Only the rim (peripheral) pattern is highly specific (for SLE). Not useful as a screening test. Should be used only when there is clinical evidence of a connective tissue disease Normal Range: none present

ANCA (antineutrophil cytoplasmic antibodies), P-ANCA (perinuclear) C-ANCA (cytoplasmic)

Anti-Cardiolipin (Anti-Phospholipid)

Anti-DNA

Tests are on the blood serum. CANCA is most seen in Wegener's granulomatosus. C-ANCA suggests a systemic vasculitis disease, and is rarely seen in patients with lupus. P-ANCA is most seen in necrotizing, crescentic glomerulonephritis and polyarteritis nodosa. P-ANCA is found in some lupus patients. Anticardiolipin antibodies are a subset of a group of antibodies which react with negatively charged phospholipids. Antibodies to cardiolipin have been associated with an incresased incidence of vascular thrombosis, thrombocytopenia and recurrent fetal loss in patients with SLE. IgG or IgM antibodies directed against host double-stranded DNA.

Normal Range for anti-IgG: 0 20 GPL Normal Range for anti-IgM: 0 - 10 MPL.

increased in: SLE, some connective tissue diseases, and in Antiphospholipid Syndrome. Additional: Patients with acute and chronic infections (including syphilis, HIV, Lyme disease) may also have increased anti-cardiolipin antibodies

Normal Range: increased in: Systemic lupus < 1:10 titer erythematosus (60-70%, specificity 95%). Anti-ds-DNA antibody is not found in drug-induced lupus. Additional: High titers are seen only in SLE. Titers of anti-ds-DNA correlate well with disease activity and with occurrence of glomerulonephritis.

Antinerythrocyte antibodies (anti-

The direct Coombs Normal Range: test measures the none present presence of

RBC) also known as Coombs test

Antineurofilament antibodies

Anti-Cardiolipin (Anti-Phospholipid)

Antinerythrocyte antibodies (antiRBC) also known as Coombs test

antibodies that are bound to the surface of circulating RBCs. Indirect Coombs measures *free* anti-RBC antibodies. The sensitivity of this test is in question-but it remains the standard for detection of autoimmune anemia. Limited studies have been done with this test. Antibodies against neurofilaments in blood serum. 60% of diffuse NP lupus patients have shown this antibody. MPLAnticardiolipin antibodies are a subset of a group of antibodies which react with negatively charged phospholipids. Antibodies to cardiolipin have been associated with an incresased incidence of vascular thrombosis, thrombocytopenia and recurrent fetal loss in patients with SLE. The direct Coombs test measures the presence of antibodies that are bound to the surface of circulating RBCs. Indirect Coombs measures *free* anti-RBC antibodies. The sensitivity of this test is in question-but it remains the standard for detection of

Normal Range: non present

Normal Range for anti-IgG: 0 20 GPL Normal Range for anti-IgM: 0 - 10

increased in: SLE, some connective tissue diseases, and in Antiphospholipid Syndrome. Additional: Patients with acute and chronic infections (including syphilis, HIV, Lyme disease) may also have increased anti-cardiolipin antibodies.

Normal Range: none present

Antineurofilament antibodies

Antineuronal antibodies

Anti-ribosomal P

Anti-Ro/SS-A

autoimmune anemia. presentLimited studies have been done with this test. Antibodies against neurofilaments in blood serum. 60% of diffuse NP lupus patients have shown this antibody. Most specifically, this is IgG neuronreactive antibody radioimmunoassay performed on the cerebrospinal fluid. In the general lupus population, 75% with neuropsyciatric (NP) lupus are detected, as compared to 10% without NP lupus-*false positive*. Highest titers are found in patients with diffuse NP lupus (seizures, organic brain syndrome)--90%. 40% of focal NP are positive (stroke, cranial neuropathy, transverse myelitis). Antibodies to ribosomal P protein from blood serum. 80 - 90% positive in NP lupus that manifests with psychosis or depression. Autoantibody against acidic nuclear ribonucleoproteins that is found in patients with some connective tissue diseases, especially Sjogren's syndrome.

Normal Range: non

Normal Range: non present

Normal Range: Negative

Normal Range: Positive in: Primary Sjogren's Negative syndrome (70%), SLE (40%), rheumatoid arthritis (10%). Additional: Anti-La/SS-B is another antibody against acidic ribonucleoproteins that is less sensitive for Sjogren's (50-60%) and SLE (1015%). Patients with antibodies to SS-A may have a negative ANA test.

Aspartate Aminotransferase (AST, SGOT, GOT)

U/LIntracellular Normal Range: enzyme involved Laboratoryin amino acid and specific carbohydrate metabolism. Present in large concentrations in liver, skeletal muscle, brain, red cells, and heart. Released into the bloodstream when tissue is damaged.

increased in: Acute viral hepatitis (ALT>AST), biliary tract obstruction (cholangitis, choledocholithiasis), mononucleosis, alcoholic hepatitis and cirrhosis (AST>ALT), liver abscess, metastatic or primary liver cancer, myocardial infarction, myopathies, muscular dystrophy, dermatomyositis, rhabdomyolysis, ischemic injury to liver ("shock liver") or hypoxia. Hepatotoxic drugs (eg, isoniazid).

Bilirubin

Blood Urea Nitrogen (BUN)

Additional: Test not indicated for diagnosis of myocardial infarction. Bilirubin, a product Normal Range: increased in: Acute or chronic hepatitis, of hemoglobin 0.1-1.2 Direct cirrhosis, biliary tract obstruction, toxic metabolism, is (conjugated to hepatitis, congenital liver enzyme conjugated in the glucuronide) abnormalities (Dubin-Johnson, Rotor's, liver to the mono- bilirubin, 0.1- Gilbert's, Crigler-Najjar syndromes), and diglucuronides 0.4 mg/dL (< 7 fasting, hemolytic disorders. and excreted in mol/L); Hepatotoxic drugs. bile. Some Indirect conjugated (unconjugated) Additional: Assay of total bilirubin bilirubin is bound bilirubin, 0.2- includes conjugated (direct) and to serum albumin, 0.7 mg/dL (< unconjugated (indirect) bilirubin plus so-called D (delta) 12 mol/L) delta bilirubin (conjugated bilirubin bilirubin. Elevated mg/dL bound to albumin). It is usually clinically serum bilirubin unnecessary to fractionate total occurs in liver bilirubin. The fractionation is unreliable disease, biliary by the diazo reaction and may obstruction, or underestimate unconjugated bilirubin. hemolysis. Only conjugated bilirubin appears in the urine and it is indicative of liver disease; hemolysis is associated with increased unconjugated bilirubin. Persistence of delta bilirubin in serum in resolving liver disease means that total bilirubin does not effectively indicate time course of resolution. Urea, an end Normal Range: increased in: Renal failure (acute or product of protein 8-20 mg/dL chronic), urinary tract obstruction, metabolism, is dehydration, shock, burns, CHF, excreted by the gastrointestinal bleeding. Drugs with Additional: kidney. BUN is Urease assay renal toxicity, eg, gentamicin. directly related to method protein intake and commonly Decreased in: Hepatic failure, nephrotic nitrogen used. BUN/Cr syndrome, cachexia (low-protein and metabolism and ratio (normally high-carbohydrate diets). inversely related to 12:1-20:1) the rate of decreased in excretion of urea. acute tubular Urea concentration necrosis, in glomerular advanced liver filtrate is the same disease, low as in plasma, but protein intake, its tubular following reabsorption is hemodialysis. inversely related to BUN/Cr ratio the rate of urine increased in

formation.

Aspartate Aminotransferase (AST, SGOT, GOT)

Bilirubin

Blood Urea Nitrogen (BUN)

dehydration, GI bleeding, increased catabolism. Intracellular Normal Range: increased in: Acute viral hepatitis enzyme involved Laboratory(ALT>AST), biliary tract obstruction in amino acid and specific U/L (cholangitis, choledocholithiasis), carbohydrate mononucleosis, alcoholic hepatitis and metabolism. cirrhosis (AST>ALT), liver abscess, Present in large metastatic or primary liver cancer, concentrations in myocardial infarction, myopathies, liver, skeletal muscular dystrophy, dermatomyositis, muscle, brain, red rhabdomyolysis, ischemic injury to liver cells, and heart. ("shock liver") or hypoxia. Hepatotoxic Released into the drugs (eg, isoniazid). bloodstream when tissue is Additional: Test not indicated for damaged. diagnosis of myocardial infarction. Bilirubin, a product . Normal increased in: Acute or chronic hepatitis, of hemoglobin Range: 0.1-1.2 cirrhosis, biliary tract obstruction, toxic metabolism, is Direct hepatitis, congenital liver enzyme conjugated in the (conjugated to abnormalities (Dubin-Johnson, Rotor's, liver to the mono- glucuronide) Gilbert's, Crigler-Najjar syndromes), and diglucuronides bilirubin, 0.1- fasting, hemolytic disorders. and excreted in 0.4 mg/dL (< 7 Hepatotoxic drugs. bile. Some mol/L); conjugated Indirect Additional: Assay of total bilirubin bilirubin is bound (unconjugated) includes conjugated (direct) and to serum albumin, bilirubin, 0.2- unconjugated (indirect) bilirubin plus so-called D (delta) 0.7 mg/dL (< delta bilirubin (conjugated bilirubin bilirubin. Elevated 12 mol/L) bound to albumin). It is usually clinically serum bilirubin mg/dL unnecessary to fractionate total occurs in liver bilirubin. The fractionation is unreliable disease, biliary by the diazo reaction and may obstruction, or underestimate unconjugated bilirubin. hemolysis. Only conjugated bilirubin appears in the urine and it is indicative of liver disease; hemolysis is associated with increased unconjugated bilirubin. Persistence of delta bilirubin in serum in resolving liver disease means that total bilirubin does not effectively indicate time course of resolution Urea, an end Normal Range: increased in: Renal failure (acute or product of protein 8-20 mg/dL chronic), urinary tract obstruction, metabolism, is dehydration, shock, burns, CHF, excreted by the gastrointestinal bleeding. Drugs with kidney. BUN is renal toxicity, eg, gentamicin. directly related to protein intake and Decreased in: Hepatic failure, nephrotic nitrogen syndrome, cachexia (low-protein and metabolism and high-carbohydrate diets). inversely related to the rate of Additional: Urease assay method excretion of urea. commonly used. BUN/Cr ratio Urea concentration (normally 12:1-20:1) decreased in in glomerular acute tubular necrosis, advanced liver filtrate is the same disease, low protein intake, following as in plasma, but

C3

C4

its tubular hemodialysis. BUN/Cr ratio increased reabsorption is in dehydration, GI bleeding, increased inversely related to catabolism. the rate of urine formation. The classic and Normal Range: increased in: Many inflammatory alternative 64-166 mg/dL conditions as an acute phase reactant, complement active phase of rheumatic diseases pathways (rheumatoid arthritis, SLE, etc), acute converge at the C3 viral hepatitis, myocardial infarction, step in the cancer, diabetes, pregnancy, complement sarcoidosis, amyloidosis, thyroiditis. cascade. Low levels indicate Decreased by: Decreased synthesis activation by one (protein malnutrition, congenital or both pathways. deficiency, severe liver disease), or Most diseases with increased catabolism (immune complex immune disease, membranoproliferative complexes will glomerulonephritis [75%], SLE, show decreased Sjogren's, rheumatoid arthritis, C3 levels. Test as disseminated intravascular coagulation, usually performed paroxysmal nocturnal hemoglobinuria, is an autoimmune hemolytic anemia, gramimmunoassay (by negative bacteremia) and increased radial loss (burns, gastroenteropathies). immunodiffusion or nephelometry). Additional: Complement C3 levels may be useful in following the activity of immune complex diseases. The best test to detect inherited deficiencies is CH50. Levels can confirm specific C3 defect. C4 is a component Normal Range: increased in: Various malignancies: not of the classic 15-45 mg/dL clinically useful. complement pathway. Decreased by: Decreased synthesis, Depressed levels increased catabolism (SLE, rheumatoid usually indicate arthritis, proliferative classic pathway glomerulonephritis, hereditary activation. angioedema), and increased loss (burns, protein-losing enteropathies). Congenital deficiency. Additional: Low C4 accompanies acute attacks of hereditary angioedema, and C4 is used as a first-line test for the disease. C1 esterase inhibitor levels are not indicated for the evaluation of hereditary angioedema unless C4 is low. Congenital C4 deficiency occurs with an SLE-like syndrome. Test as usually performed is an immunoassay and not a functional assay. Normal Range: increased in: Hyperparathyroidism, 8.5-10.5 mg/dL malignancies secreting PTH-like substances (especially squamous cell carcinoma of lung, renal cell carcinoma), vitamin D excess, milk-

Calcium

Level of ionized calcium is regulated by parathyroid hormone and

vitamin D. Serum calcium equals the sum of ionized calcium plus complexed calcium and calcium bound to proteins (mostly albumin).

alkali syndrome, multiple myeloma, Paget's disease of bone with immobilization, sarcoidosis, other granulomatous disorders, familial hypocalciuria, vitamin A intoxication, thyrotoxicosis, Addison's disease. Drugs: antacids (some), calcium salts, chronic diuretic use (eg, thiazides), lithium, others. Decreased in: Hypoparathyroidism, vitamin D deficiency, renal insufficiency, pseudohypoparathyroidism, magnesium deficiency, hyperphosphatemia, massive transfusion, hypoalbuminemia.

CH50

Chloride

Additional: Need to know serum albumin to interpret calcium level. For every decrease in albumin by 1 mg/dL, calcium should be corrected upward by 0.8 mg/dL. The quantitative Normal Range: Decreased with: >50-80% deficiency of assay of hemolytic Laboratoryprimary pathway complement complement specific U/mL components in congenital or acquired activity depends deficiency. on the ability of the primary Normal in: Deficiencies of alternative complement pathway, complement components. pathway to induce hemolysis of red Additional: This is a functional assay of cells sensitized biologic activity. Sensitivity to with optimal decreased levels of complement amounts of anticomponents depends on exactly how red cell antibodies. the test is performed. It is used to For precise detect congenital and acquired severe titrations of deficiency disorders of the primary hemolytic complement pathway. complement, the dilution of serum that will lyse 50% of the indicator red cells is determined as the CH50. This arbitrary unit depends on the conditions of the assay and is therefore laboratoryspecific. Chloride, the Normal Range: increased in: Renal failure, nephrotic principal inorganic 98-107 meq/L syndrome, renal tubular acidosis, anion of dehydration, overtreatment with saline, extracellular fluid, hyperparathyroidism, diabetes is important in insipidus, metabolic acidosis from maintaining normal diarrhea (loss of HCO3), respiratory acid-base balance alkalosis, hyperadrenocorticism. Drugs:

and normal osmolality. If chloride is lost (as HCl or NH4Cl), alkalosis ensues; if chloride is ingested or retained, acidosis ensues.

acetazolamide (hyperchloremic acidosis), androgens, hydrochlorothiazide, salicylates (intoxication).

Cholesterol

Decreased in: Vomiting, diarrhea, gastrointestinal suction, renal failure combined with salt deprivation, overtreatment with diuretics, chronic repiratory acidosis, diabetic ketoacidosis, excessive sweating, SIADH, salt-losing nephropathy, acute intermittent porphyria, water intoxication, expansion of extracellular fluid volume, adrenal insufficiency, hyperaldosteronism, metabolic alkalosis. Drugs: aldosterone, chronic laxative or bicarbonate ingestion, corticosteroids and ACTH (alkalosis), diuretics. Cholesterol level is Normal increased in: Familial or polygenic determined by lipid Range: hyperlipoproteinemia, familial metabolism, which Desirable < dysbetalipoproteinemia, familial is in turn 200 Borderline combined hyperlipidemia, influenced by 200-239 High hyperlipoproteinemia and heredity, diet, and risk > 240 hyperalphalipoproteinemia, liver, kidney, mg/dL hyperlipoproteinemias secondary to thyroid, and other hypothyroidism, uncontrolled diabetes endocrine organ mellitus, nephrotic syndrome, chronic functions. Total hepatitis, biliary cirrhosis, obstructive cholesterol (TC) = jaundice, hypoproteinemia, LDLC + HDLC + glomerulonephritis, chronic renal TG/5 (valid only if failure, gout, malignancy (pancreas, triglyceride [TG] < prostate), pregnancy, alcoholism, 400). Since LDL glycogen storage diseases types I, III, cholesterol (LDLC) IV, anorexia nervosa, GH deficiency, is the clinically dietary excess. Drugs: androgens, important entity, it chlorpropamide, corticosteroids, oral is calculated as contraceptives, phenytoin, progestins, LDLC = TC thiazides, others. HDLC - TG/5, and this is valid only if Decreased in: Acute hepatitis, alcoholic specimen is cirrhosis, Gaucher's disease, obtained fasting (in hyperthyroidism, acute infections, order to obtain anemia, malnutrition, alphalipoprotein relevant deficiency (Tangier disease), triglyceride and malignancy (liver), severe acute illness, HDL levels). extensive burns, COPD, rheumatoid arthritis, mental retardation, intestinal lymphangiectasia, apolipoprotein deficiency. Additional: It is important to treat the cause of secondary hypercholesterolemia (hypothyroidism, etc). National Cholesterol Education Program Expert Panel has published clinical recommendations for cholesterol management.

Creatinine

Differential Neutophils Lymphocytes Monocytes Eosinophils Basophils Large unstained cells

Endogenous creatinine is excreted by filtration through the glomerulus and by tubular secretion. Clinically, creatinine clearance is an acceptable measure of glomerular filtration rate but sometimes overestimates GFR. For each 50% reduction in GFR, serum creatinine approximately doubles. White blood cell differentials are now done on automated flow cytometry instruments in order to provide reproducible data. 10,000 wbcs are classified on the basis of size and peroxidase staining as neutrophils, monocytes or eosinophils (which are all peroxidase positive) and as lymphocytes and large unstained cells (which are peroxidase negative). These large unstained cells (LUC), larger than normal lymphocytes, may be atypical lymphocytes, myeloperoxidase deficient cells or peroxidase negative blasts. Basophils are identified using two angle light scattering, based on their singular

Normal Range: increased in: Acute or chronic renal 0.6-1.2 mg/dL failure; urinary tract obstruction, nephrotoxic drugs. Decreased in: Reduced muscle mass, possible drug effect. Additional: In alkaline picrate method, substances other than Cr (eg, acetoacetate, acetone, bhydroxybutyrate, a-ketoglutarate, pyruvate, glucose) may give falsely high results. Therefore, patients with diabetic ketoacidosis may have spuriously elevated Cr. Cephalosporins may spuriously increase or decrease Cr measurement. Increased bilirubin may spuriously decrease Cr.

Normal Range: A left shift usually suggests infection (rarely leukemia). The reproducibility of 1.8-6.8 K/mL 100 cell manual differentials is notoriously poor, because of statistical 0.9-2.9 K/mL error in counting and observer 0.1-0.6 K/mL variation, however, review of blood 0-0.4 K/mL smears is useful to visually identify rare abnormal cells, blasts, nucleated rbcs, 0-0.1 K/mL morphologic abnormalities e.g., 0-0.2 K/mL hypersegmentation, toxic granulation, sickle cells, target cells, spherocytes, basophilic stippling, and to look for rouleau (stacking of red cells due to increased globulins) and clumped platelets. White blood cell differential is unlikely to be abnormal with a normal wbc count or to be changed if the total wbc count is unchanged. Increased neutrophils: suggests infection (bacterial or early viral, rarely leukemia), acute stress, acute and chronic inflammations, tumor, drugs, DKA. Decreased neutrophils: suggests aplastic anemia, drug-induced neutropenia (e.g., chloramphenicol, phenothiazine, antithyroid drugs, sulphonamide), folate or B12 deficiency, Chediak-Higashi syndrome, malignant lymphoproliferative disease, physiologic in children up to 4 years. Increased lymphocytes: viral infection (especially, infectious mononucleosis, pertussis), thyrotoxicosis, adrenal insufficiency disease (ALL, CLL),

resistance to lysis. There will also be an indication of more immature neutrophils (commonly called a left shift) based on the ratio of mono/polymorpho nuclear white cells (lobularity index).

chronic infection, drug and allergic reactions, autoimmune disease. Decreased lymphocytes: immune deficiency syndrome. Comments: Increased monocytes: inflammation, infection, malignancy, TB, myeloproliferative disorders. Decreased monocytes: depleted in overwhelming bacterial infection. Increased eosinophils: allergic states, drug sensitivity reaction, skin disorders, tissue invasion by parasites, periarteritis nodosa, hypersensitivity response to malignancy (e.g. Hodgkin's disease), pulmonary infiltrative disease, disseminated eosinophilic hypersensitivity disease. Decreased eosinophils: acute and chronic inflammation, stress, drugs: steroids.

Erythrocyte Sedimentation Rate (Sed Rate, ESR)

Gamma-Glutamyl Transpeptidase (GGT)

Increased basophils: hypersensitivity reactions, drugs, myeloproliferative disorders (CML, polycythemia vera), myelofibrosis. Erythrocytes in Normal Range: increased in: Infections (osteomyelitis, plasma usually Male: < 10 pelvic inflammatory disease [75%]), settle slowly. Female: < 15 inflammatory disease (temporal However, if they arteritis, polymyalgia rheumatica, aggregate for any rheumatic fever), malignant neoplasms, reason (usually paraproteinemias, anemia, pregnancy, because of plasma chronic renal failure, GI disease proteins called (ulcerative colitis, regional ileitis). acute phase reactants, eg, Decreased in: Polycythemia, sickle cell fibrinogen), they anemia, spherocytosis, anisocytosis, settle rapidly. hypofibrinogenemia, Sedimentation of hypogammaglobulinemia, congestive RBCs occurs heart failure, microcytosis, drugs (high because of their dose corticosteroids). Low value of no greater density diagnostic significance. than plasma. ESR measures the Additional: There is a good correlation distance in mm between ESR and C-reactive protein, that erythrocytes but ESR is less expensive. Test is fall during 1 hour. useful and indicated only for diagnosis and monitoring of temporal arteritis and polymyalgia rheumatica. The test is not sensitive or specific for other conditions. ESR is higher in women and older persons. U/LGGT is an Normal Range: increased in: Liver disease: acute viral enzyme present in Laboratoryor toxic hepatitis, chronic or subacute liver, kidney, and specific hepatitis, cirrhosis, biliary tract pancreas. It obstruction (intrahepatic or transfers Cextrahepatic), primary or metastatic

Glucose

terminal glutamic acid from a peptide to other peptides of Lamino acids. It is induced by alcohol intake and is an extremely sensitive indicator of liver disease, particularly alcoholic liver disease. Normally, the . Normal glucose Range: 60-115 concentration in mg/dL extracellular fluid is closely regulated so that a source of energy is readily available to tissues and no glucose is excreted in the urine

liver neoplasm, alcoholic hepatitis, mononucleosis. Drugs (by enzyme induction): phenytoin, barbiturates, alcohol. Additional: Useful in follow up of alcoholics undergoing treatment. Test sensitive to modest alcohol intake. Test positive in 90% of patients with liver disease. Used to confirm hepatic origin of elevated serum alkaline phosphatase. increased in: Diabetes mellitus, Cushing's syndrome (10-15%), chronic pancreatitis (30%) Drugs: corticosteroids, phenytoin, estrogen, thiazides Decreased in: Pancreatic islet B cell disease with increased insulin, insulinoma, adrenocortical insufficiency, hypopituitarism, diffuse liver disease, malignancy (adrenocortical, stomach, fibrosarcoma), infant of diabetic mother, enzyme deficiency diseases (galactosemia, etc). Drugs: insulin, ethanol, propranolol, sulfonylureas, tolbutamide, other hypoglycemic agents.

Hematocrit

The hematocrit represents the percentage of whole blood volume made up by erythrocytes. Laboratory instruments calculate the Hct from the erythrocyte count and the MCV, ie, Hct = RBC x MCV.

Additional: Diagnosis of diabetes mellitus is consistent with a fasting plasma glucose >140 mg/dL on more than one occasion. Hypoglycemia is defined as glucose <50 mg/dL in men and <40 mg/dL in women. Normal Range: increased in: Hemoconcentration (as in Male: 39-49 dehydration, burns, vomiting), Female: 35-45 polycythemia, extreme physical Ageexercise. dependent Decreased in: Anemia: macrocytic (liver disease, hypothyroidism, vitamin B12 deficiency, folate deficiency), normocytic anemia (early iron deficiency, anemia of chronic disease, hemolytic anemia, acute hemorrhage) and microcytic anemia (iron deficiency, thalassemia). Additional: Conversion from hemoglobin to hematocrit is roughly Hgb x3 = Hct. Hematocrit reported by clinical laboratories is not a spun hematocrit. The spun hematocrit may be spuriously high if the centrifuge is not calibrated, if the specimen is not

Hemoglobin

spun to constant volume, or if there is "trapped plasma." Hemoglobin is the Normal Hemoglobin is increased in: major protein of Hemoconcentration (as in dehydration, Range: erythrocytes and Male: 13.6burns, vomiting), polycythemia, transports oxygen 17.5 extreme physical exercise, heavy from the lungs to Female: 12.0- smoking (due to presence of peripheral tissues. 15.5 nonfunctional carboxyhemoglobin). It is measured by spectrophotometry Hemoglobin is decreased in: Anemia: on automated macrocytic (liver disease, instruments after hypothyroidism, vitamin B12 deficiency, hemolysis of red folate deficiency), normocytic anemia cells and (early iron deficiency, anemia of conversion of all chronic disease, hemolytic anemia, hemoglobin to acute hemorrhage) and microcytic cyanmethemoglobi anemia (iron deficiency, thalassemia). n. Additional: Hypertriglyceridemia and very high WBC counts can cause false elevations of Hgb. IgG makes up Normal Range: increased in: IgG: Polyclonal: about 85% of total IgA: 78-367 Autoimmune diseases (eg, SLE, RA), serum mg/dL IgG: sarcoidosis, chronic liver diseases, immunoglobulins 583-1761 some parasitic diseases, chronic or and predominates mg/dL IgM: 52- recurrent infections. Monoclonal: late in immune 335 mg/dL Multiple myeloma (IgG type), responses. It is the lymphomas or other malignancies. IgM: only Polyclonal: Isolated infections such as immunoglobulin to viral hepatitis, infectious cross the placenta. mononucleosis, early response to IgM antibody bacterial or parasitic infection. predominates Monoclonal: Waldenstrom's early in immune macroglobulinemia, lymphoma. IgA: responses. Polyclonal: Chronic liver disease, Secretory IgA chronic infections (especially of the GI plays an important and respiratory tracts). Monoclonal: role in host Multiple myeloma (IgA). defense mechanisms by Decreased in: IgG: Immunosuppressive blocking transport therapy, genetic (severe combined of microbes across immunodeficiency, Wiskott-Aldrich mucosal surfaces. syndrome, common variable immunodeficiency). IgM: Immunosuppresive therapy. IgA: Inherited IgA deficiency (ataxia telangiectasia, combined immunodeficiency disorders). Additional: IgG deficiency is associated with recurrent and occasionally severe pyogenic infections. Most common form of multiple myeloma is the IgG type. Normal Range: increased in: Hemochromatosis, 50-175 g/dL hemosiderosis (eg, multiple transfusions, excess iron administration), hemolytic anemia,

Immunoglobulins (IG)

Iron

Plasma iron concentration is determined by absorption from

intestine; storage in intestine, liver, spleen, bone marrow; rate of breakdown or loss of hemoglobin; rate of synthesis of new hemoglobin.

pernicious anemia, aplastic or hypoplastic anemia, viral hepatitis, lead poisoning, thalassemia. Drugs: dextran, estrogens, ethanol, oral contraceptives. Decreased in: Iron deficiency, nephrotic syndrome, chronic renal failure, many infections, active hematopoiesis, remission of pernicious anemia, hypothyroidism, malignancy (carcinoma), postoperative state, kwashiorkor, drugs. Additional: Used in evaluation of iron deficiency (see TIBC and Ferritin). increased in: Iron deficiency anemia, late pregnancy, infancy, hepatitis. Drugs: oral contraceptives. Decreased in: Hypoproteinemic states (eg, nephrotic syndrome, starvation, malnutrition, cancer), chronic inflammatory disorders, chronic disease, chronic liver disease. Additional: Increased % transferrin saturation with iron: in iron overload (iron poisoning, hemolytic anemia, sideroblastic anemia, thalassemia, hemochromatosis, pyridoxine deficiency, aplastic anemias). Decreased % transferrin saturation with iron: in iron deficiency (usually saturation <16%). Transferrin levels can also be used to assess nutritional status.

Iron Binding Capacity

Lactate Dehydrogenase (LDH)

Iron is transported in plasma complexed to the metal-binding globulin, transferrin, which is synthesized in the liver. Total iron binding capacity is calculated from transferrin levels measured immunologically. Each molecule of transferrin has two iron-binding sites, so its iron binding capacity is 1.47 mg/g. Normally, transferrin carries an amount of iron representing about 16?60% of its capacity to bind iron, ie, % saturation of iron binding capacity is 16-60%. LDH is an enzyme that catalyzes the interconversion of lactate and pyruvate in the presence of NAD/NADH. It is widely distributed in body cells and fluids and since its RBC/plasma ratio is high, it is spuriously elevated in plasma/serum

Normal Range: 250460 g/dL

Normal Range: increased in: Tissue necrosis, Laboratoryespecially in acute injury of cardiac specific muscle, RBCs, kidney, skeletal muscle, liver, lung, skin. Commonly elevated in various carcinomas and in Pneumocystis carinii and B cell lymphoma in AIDS. Marked elevations occur in hemolytic anemias, vitamin B12 deficiency anemia, folate deficiency anemia, polycythemia vera, acute (but not chronic) hepatitis, cirrhosis, obstructive jaundice, renal disease, musculoskeletal disease, CHF. Drugs causing hepatotoxicity or hemolysis.

following hemolysis.

Decreased in: Clofibrate, fluoride (low dose).

Magnesium

Additional: LDH is elevated after myocardial infarction (2-7 days), in liver congestion (eg, in CHF) and in Pneumocystis carinii pneumonitis. LDH is not a useful liver function test and it is not specific enough for the diagnosis of hemolytic or megaloblastic anemias. Its main diagnostic use is in myocardial infarction in which the CKMB elevation has passed. With the availability of specific LD1 measurements, the total LD level may no longer be useful. Magnesium is Normal Range: increased in: Dehydration, tissue primarily an 1.8-3 mg/dL trauma, renal failure; intracellular cation hypoadrenocorticism; hypothyroidism. (second most Drugs: aspirin (prolonged use), lithium, abundant, 60% magnesium salts, progesterone, found in bone). In triamterene, vitamin D (renal failure). extracellular fluid, it influences Decreased in: Chronic diarrhea, enteric neuromuscular fistula, starvation, chronic alcoholism, response and chronic liver disease, total parenteral irritability. A nutrition with inadequate replacement, magnesium deficit hypoparathyroidism (especially postmay exist with little parathyroid surgery), high-dose vitamin or no change D and calcium therapy, acute apparent in serum pancreatitis, delirium tremens, chronic level. glomerulonephritis, hyperaldosteronism, diabetic ketoacidosis, SIADH, pregnancy. Drugs: albuterol, amphotericin B, calcium salts, cisplatin, citrates (blood transfusion), cyclosporine, diuretics, ethacrynic acid. Additional: Mg2+ concentration is determinated by intestinal absorption, renal excretion, and exchange with bone and with intracellular fluid. Normal Range: increased in: Macrocytosis. 26-34 pg Decreased in: Microcytosis (iron deficiency, thalassemia). Hypochromia (lead poisoning, sideroblastic anemia, anemia of chronic disease).

Mean Corpuscular MCH calculated Hemoglobin (MCH) from measured

Mean Corpuscular Hemoglobin Concentration

values of Hb and RBC; ie, MCH = Hb/RBC. A low MCH can mean hypochromia or microcytosis or both. A high MCH is evidence of macrocytosis. MCHC describes Normal Range: how fully the 31-36 g/dL erythrocyte volume is filled with

increased in: Marked spherocytosis. Spuriously increased in autoagglutination, hemolysis (with spuriusly high Hb or low MCV or RBC),

(MCHC)

hemoglobin and is calculated from measurement of hemoglobin (Hb), mean corpuscular corpuscular volume (MCV) and red cell count (RBC); ie, MCHC = Hb/MCV x RBC.

lipemia. Cellular dehydration syndromes, xerocytosis.

Mean Corpuscular Volume (MCV)

Decreased in: Hypochromic anemia (iron deficiency, thalassemia, lead poisoning), sideroblastic anemia, anemia of chronic disease. Spuriously decreased in high WBC (with spuriously low Hgb or high MCV or RBC). Average volume of Normal Range: increased in: Liver disease, the red cell is 80-100 fL megaloblastic anemia (folate, B12 measured by deficiencies), reticulocytosis, newborn. automated Drugs: phenytoin. Spurious increase in instrument, by autoagglutination, high WBC. electrical impedance or by Decreased in: Iron deficiency, light scatter. thalassemia; decreased or normal in anemia of chronic disease. Additional: MCV can be normal in combined iron and folate deficiency. In patients with two red cell populations (macrocytic and microcytic), MCV may be normal. Patient's plasma is Normal Range: increased in: Deficiency of any activated to clot in 25-35 (range individual coagulation factor except XIII vitro by mixing it varies) Panic > and VII, nonspecific inhibitors (lupuswith phospholipid = 60 seconds like anticoagulant), specific factor and an activator inhibitors, von Willebrand's disease substance. (may also be normal), hemophilia A Screens the and B, disseminated intravascular intrinsic coagulation. Drugs: heparin, warfarin. coagulation pathway and Decreased in: Hypercoagulable states, adequacy of all DIC. coagulation factors except XIII and VII. Comments: PTT is the best test to PTT is usually monitor adequacy of heparin therapy. abnormal if level of Test not always abnormal in von any factor falls Willebrand's disease. Test may be below 30-40% of normal in chronic DIC. Very common normal. cause of prolongation is spurious presence of heparin in sample. The plasma Normal Range: increased in: Renal failure, massive concentration of 2.5-4.5 mg/dL blood transfusion, sarcoidosis, inorganic neoplasms, adrenal insufficiency, phosphate is acromegaly, hypoparathyroidism, determined by hypervitaminosis D, phosphate parathyroid gland infusions or enemas, osteolytic function, action of metastases to bone, leukemia, milkvitamin D, alkali syndrome, healing bone intestinal fractures, pseudohypoparathyroidism, absorption, renal diabetes mellitus with ketosis, function, bone malignant hyperpyrexia, cirrhosis, lactic metabolism, and acidosis, respiratory acidosis. Drugs: nutrition. eg, anabolic steroids, ergocalciferol, furosemide, hydrochlorothiazide and

Partial Thromboplastin Time

Phosphorous

others. Decreased in: Hyperparathyroidism, hypovitaminosis D (rickets, osteomalacia), malabsorption (steatorrhea); malnutrition, starvation or cachexia; GH deficiency, chronic alcoholism, severe diarrhea, vomiting, nasogastric suction, severe hypercalcemia (any cause), acute gout, osteoblastic metatases to bone, severe burns (diuretic phase), respiratory alkalosis, hyperalimentation with inadequate phosphate repletion, carbohydrate administration (intravenous), renal tubular acidosis and other renal tubular defects, diabetic ketoacidosis (during recovery), acidbase disturbances, hypokalemia, pregnancy, hypothyroidism; prolonged use of thiazides, glucose infusion, salicylates (toxicity). Drugs: eg, phosphate-binding antacids, anticonvulsants, estrogens, isoniazid, oral contraceptives. Platelets are Normal Range: increased in: Myeloproliferative released from 150-450 X 10 disorders: polycythemia vera, CML, megakaryocytes in 3/uL essential thrombocythemia, bone marrow, and myelofibrosis, after bleeding, they are important postsplenectomy, reactive for adequate thrombocytosis secondary to hemostasis. inflammatory diseases. Platelet counting is done by flow Decreased in: Decreased production: cytometer based bone marrow suppression or on size replacement, chemotherapeutic agents, discrimination other drugs, eg, ethanol. Increased using either destruction or removal: splenomegaly, electrical DIC, platelet antibodies (ITP, impedance or posttransfusion purpura, neonatal electro-optical isoimmune thrombocytopenia, drugs systems. (eg, quinidine, cephalosporins). Normal Range: Potassium is 3.5-5.0 meq/L predominantly an intracellular cation whose plasma level is regulated by renal excretion. Plasma concentration determines neuromuscular and muscular irritability. Elevated or depressed potassium

Platelet Count

Potassium

concentrations interfere with muscle contraction. increased in: Massive hemolysis, severe tissue damage, rhabdomyolysi s, acidosis, dehydration, acute or chronic renal failure, Addison's disease, renal tubular acidosis type IV (hyporeninemi c hypoaldostero nism), hyperkalemic familial periodic paralysis. Drugs: potassium salts, potassiumsparing diuretics (spironolacton e, triamterene), non-steroidal antiinflammatory drugs, betablockers, ACE inhibitors. Decreased in: Low potassium intake, prolonged vomiting or diarrhea, renal tubular acidosis (types I, II), hyperaldostero nism, Cushing's syndrome, osmotic

diuresis (eg, of hyperglycemia ), alkalosis, familial periodic paralysis, diuretic therapy. Additional: Spurious K+ can occur with hemolysis of sample, delayed separation of plama from erythrocytes, prolonged fist clenching during blood drawing, tourniquet placed for prolonged periods, and very high white cell or platelet counts. The plasma Normal Range: increased in: Polyclonal or monoclonal protein 6-8 g/dL gammopathies, marked dehydration. concentration is Drugs: anabolic steroids, androgens, determined by the corticosteroids, epinephrine. nutritional state, hepatic function, Decreased in: Protein-losing renal function, and gastroenteropathies, acute burns, various disease nephrotic syndrome, severe dietary states and protein deficiency, chronic liver hydration. The disease, malabsorption syndrome, plasma protein agammaglobulinemia. concentration determines Additional: The serum total protein colloidal osmotic consists primarily of albumin and pressure. globulin. Hypoproteinemia usually means hypoalbuminemia, since albumin is the major serum protein. Globulin is calculated as total protein minus albumin. PT screens the Normal Range: increased in: Liver disease, vitamin K extrinsic pathway 11-15 seconds deficiency, intravascular coagulation, of the coagulation circulating anticoagulant, massive system. It is blood volume replacement. Drugs: performed by warfarin. adding calcium and tissue Additional: In liver disease, the PT thromboplastin to reflects the hepatic capacity for protein a sample of synthesis. PT responds rapidly to citrated, plateletaltered hepatic function because the poor plasma and serum half-lives of factors II and VII are

Protein

Prothrombin Time

Rheumatoid Factor

measuring the time required for fibrin clot formation. It is most sensitive to deficiencies in the vitamin Kdependent clotting factors II, VII, and X. It is also sensitive to deficiencies of factor V. It is insensitive to fibrinogen and not affected by heparin. It is used to monitor warfarin therapy. Heterogeneous Normal Range: autoantibodies Negative usually of the IgM (<1:16) class that react against the Fc region of human IgG.

short (hours). Routine preoperative measurement of PT is unnecessary unless there is clinical history of a bleeding disorder. Efforts to standardize and report the prothrombin time as an INR (International Normalized Ratio) depend on assigning reagents an International Sensitivity Index (ISI) so that INR = [PT patient/PT normal]ISI. However, assignment of incorrect ISI by reagent manufacturers has in fact caused a greater lack of standardization.

Positive in: Rheumatoid arthritis (7590%), Sjogren's (80-90%), scleroderma, dermatomyositis, SLE (30%), sarcoidosis, Waldenstrom's macroglobulinemia. Drugs: methyldopa, others. Low titer can be found in healthy older patients (20%). 1-4% of normals and in a variety of acute immune responses (eg, viral infections, infectious mononucleosis, and viral hepatitis), chronic infections (tuberculosis, leprosy, subacute bacterial endocarditis) and chronic active hepatitis.

Sodium

Additional: It can be useful in differentiating rheumatoid arthritis from other chronic inflammatory arthritides. However, a positive RF test is only one of several criteria needed to make the diagnosis of rheumatoid arthritis. Sodium is the Normal Range: increased in: Dehydration (excessive predominant 135-145 meq/L sweating, severe vomiting or diarrhea), extracellular polyuria (diabetes mellitus, diabetes cation. Serum insipidus), hyperaldosteronism, sodium level is inadequate water intake (coma, primarily hypothalamic disease). Drugs: steroids, determined by the licorice, oral contraceptives. volume status of the individual. Decreased in: Congestive heart failure, Hyponatremia can cirrhosis, vomiting, diarrhea, excessive be divided into sweating (with replacement of water hypovolemia, but not salt); salt-losing nephropathy, euvolemia, and adrenal insufficiency, nephrotic hypervolemia syndrome, water intoxication, SIADH. categories. Drugs: thiazides, diuretics, ACE inhibitors, chlorpropamide, carbamazepine. Additional: Spurious hyponatremia

Uric Acid

White Blood Count (WBC, Leukocyte count)

produced by severe lipemia and hyperproteinemia if sodium analysis involves a dilution step. Sodium falls about 1.6 mmol/L for each 100 mg/dL increase in blood glucose. Hyponatremia in a normovolemic patient with urine osmolality higher than plasma osmolality suggests the possibility of SIADH, myxedema, hypopituitarism, or reset osmostat. Uric acid is an end Normal Range: increased in: Renal failure, gout, product of Males: 2.4-7.4 myeloproliferative disorders (leukemia, nucleoprotein Females 1.4- lymphoma, myeloma, polycythemia metabolism and is 5.8 mg/dL vera), psoriasis; glycogen storage excreted by the disease (type I); Lesch-Nyhan kidney. An syndrome (X-linked hypoxanthineincrease in serum guanine phosphoribosyltransferase uric acid deficiency); lead nephropathy. Drugs: concentration antimetabolite and chemotherapeutic occurs with agents, diuretics, ethanol, nicotinic increased acid, salicylates (low dose). nucleoprotein synthesis or Decreased in: SIADH, xanthine oxidase catabolism (blood deficiency, low-purine diet. Fanconi's dyscrasias, syndrome, neoplastic disease (various, therapy of causing increased renal excretion), leukemia) or liver disease. Drugs: salicylates (high decreased renal dose), allopurinol (xanthine oxidase excretion (eg, with inhibitor). use of thiazide diuretics or renal Additional: Sex and age affect uric acid failure). levels. The incidence of hyperuricemia is greater in some racial groups (eg, Filipinos) than others (Whites). Measure of the Normal Range: increased in: Infection, inflammation, total number of 3.4-10 K/L hematologic malignancy, leukemias leukocytes in (AML, ALL, CML, CLL), lymphoma. whole blood. Drugs: corticosteroids. Counted on automated Decreased in: Aplastic anemia instruments using (decreased production), B12 or folate light scattering or deficiency (maturation defect), sepsis electrical (decreased survival). Drugs: impedance after phenothiazines, chloramphenicol, lysis of RBCs. aminopyrine. WBCs are distinguished from Additional: Spurious increase: with high platelets by size. number of nucleated red cells.