Common diagnostic tests used in Hepatitis
Alanine aminotransferase (ALT, SGPT, GPT), serum
Normal Range: Laboratory-specific U/L
SI Units: 5kat/L
Blood tube color: Marbled
Cost: $9
Physiologic Basis:
* Intracellular enzyme involved in amino acid and carbohydrate
metabolism. Present in large concentrations in liver, kidney;
smaller amounts in skeletal muscle and heart. Released with tissue
damage.
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.
Comments:
* ALT screening of donor blood used in blood banks to exclude
non-A, non-B hepatitis.
Aspartate aminotransferase (AST, SGOT, GOT), serum
Normal Range: Laboratory-specific U/L
SI Units: 5kat/L
Blood tube color: Marbled
Cost: $9
Physiologic Basis:
* Intracellular enzyme involved in amino acid and 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).
Decreased in:
Comments:
* Test not indicated for diagnosis of myocardial infarction.
Gamma-glutamyl transpeptidase (GGT), serum
Normal Range: Laboratory-specific U/L
SI Units: 5kat/L
Blood tube color: Marbled
Cost: $9
Physiologic Basis:
* GGT is an enzyme present in liver, kidney, and pancreas. * It
transfers C-terminal glutamic acid from a peptide to other peptides
of L-amino acids.
* It is induced by alcohol intake and is an extremely sensitive
indicator of liver disease, particularly alcoholic liver
disease.
Increased in: Liver disease: acute viral or toxic hepatitis,
chronic or subacute hepatitis, cirrhosis, biliary tract obstruction
(intrahepatic or extrahepatic), primary or metastatic liver
neoplasm, alcoholic hepatitis, mononucleosis. Drugs (by enzyme
induction): phenytoin, barbiturates, alcohol.
Comments:
* 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.
Bilirubin (T Bili), serum
Normal Range: 0.1-1.2 Direct (conjugated to glucuronide)
bilirubin, 0.1-0.4 mg/dL (< 7 5mol/L); Indirect (unconjugated)
bilirubin, 0.2-0.7 mg/dL (< 12 5mol/L) mg/dL
SI Range: 2-21 5mol/L
Blood tube color: Marbled
Cost: $22
Physiologic Basis:
* Bilirubin, a product of hemoglobin metabolism, is conjugated in
the liver to the mono- and diglucuronides and excreted in bile.
Some conjugated bilirubin is bound to serum albumin, so-called D
(delta) bilirubin.
* Elevated serum bilirubin occurs in liver disease, biliary
obstruction, or hemolysis.
Increased in: Acute or chronic hepatitis, cirrhosis, biliary
tract obstruction, toxic hepatitis, congenital liver enzyme
abnormalities (Dubin-Johnson, Rotor's, Gilbert's, Crigler-Najjar
syndromes), fasting, hemolytic disorders. Hepatotoxic drugs.
Comments:
* Assay of total bilirubin includes conjugated (direct) and
unconjugated (indirect) bilirubin plus delta bilirubin (conjugated
bilirubin bound to albumin).
* It is usually clinically unnecessary to fractionate total
bilirubin. The fractionation is unreliable by the diazo reaction
and may underestimate unconjugated bilirubin. 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.
Iron (Fe3+), serum
Normal Range: 50-175 5g/dL
SI Range: 9-31 5mol/L
Blood tube color: Marbled
Specfics of collection: Avoid hemolysis.
Cost: $9
Physiologic Basis:
* 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.
Increased in: Hemochromatosis, hemosiderosis (eg, multiple
transfusions, excess iron administration), hemolytic anemia,
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.
Comments:
* Used in evaluation of iron deficiency (see TIBC and
Ferritin).
Iron binding capacity, total (TIBC), serum
Normal Range: 250-460 5g/dL
SI Range: 45-82 5mol/L
Blood tube color: Marbled
Cost: $34
Physiologic Basis:
* 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 16P60% of its capacity to bind iron, ie, % saturation of iron
binding capacity is 16P60%.
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.
Comments:
* 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.
Cholesterol, serum
Normal Range: Desirable < 200 Borderline 200-239 High risk
> 240 mg/dL
SI Range: Desirable < 5.2 Borderline 5.2-6.1 High risk > 6.2
mmol/L
Blood tube color: Marbled
Specfics of collection: Fasting preferred.
Cost: $9
Physiologic Basis:
* Cholesterol level is determined by lipid metabolism, which is in
turn influenced by heredity, diet, and liver, kidney, thyroid, and
other endocrine organ functions.
* Total cholesterol (TC) = LDLC + HDLC + TG/5 (valid only if
triglyceride [TG] < 400).
* Since LDL cholesterol (LDLC) is the clinically important entity,
it is calculated as LDLC = TC - HDLC - TG/5, and this is valid only
if specimen is obtained fasting (in order to obtain relevant
triglyceride and HDL levels).
Increased in: Familial or polygenic hyperlipoproteinemia,
familial dysbetalipoproteinemia, familial combined hyperlipidemia,
hyperlipoproteinemia and hyperalphalipoproteinemia,
hyperlipoproteinemias secondary to hypothyroidism, uncontrolled
diabetes mellitus, nephrotic syndrome, chronic hepatitis, biliary
cirrhosis, obstructive jaundice, hypoproteinemia,
glomerulonephritis, chronic renal failure, gout, malignancy
(pancreas, prostate), pregnancy, alcoholism, glycogen storage
diseases types I, III, IV, anorexia nervosa, GH deficiency, dietary
excess. Drugs: androgens, chlorpropamide, corticosteroids, oral
contraceptives, phenytoin, progestins, thiazides, others.
Decreased in: Acute hepatitis, alcoholic cirrhosis, Gaucher's
disease, hyperthyroidism, acute infections, anemia, malnutrition,
alphalipoprotein deficiency (Tangier disease), malignancy (liver),
severe acute illness, extensive burns, COPD, rheumatoid arthritis,
mental retardation, intestinal lymphangiectasia, apolipoprotein
deficiency.
Comments:
* 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 (see Ref
1).
Triglyceride (Tg), serum
Normal Range: < 165 mg/dL
SI Range: < 1.65 g/L
Blood tube color: Marbled
Specfics of collection: Fasting specimen required.
Cost: $9
Physiologic Basis:
* Dietary fat is hydrolyzed in the small intestine, absorbed and
resynthesized by mucosal cells, and secreted into lacteals as
chylomicrons.
* Triglycerides in the chylomicrons are cleared from the blood by
tissue lipoprotein lipase
. * Endogenous triglyceride production occurs in the liver, and
triglycerides are transported in association with b-lipoproteins
(very low density lipoproteins).
Increased in: Hypothyroidism, diabetes mellitus, nephrotic
syndrome, chronic alcoholism (fatty liver), biliary tract
obstruction, stress, familial lipoprotein lipase deficiency;
familial dysbetalipoproteinemia, familial combined hyperlipidemia;
obesity, viral hepatitis, cirrhosis, pancreatitis, chronic renal
failure, gout, pregnancy, glycogen storage diseases types I, III,
VI, anorexia nervosa, dietary excess. Drugs: beta-blockers,
cholestyramine, corticosteroids, diazepam, diuretics, estrogens,
oral contraceptives.
Decreased in: Tangier disease (alpha-lipoprotein deficiency),
hypo-and abetalipoproteinemia, malnutrition, malabsorption,
parenchymal liver disease, hyperthyroidism, intestinal
lymphangiectasia. Drugs: ascorbic acid, clofibrate, nicotinic acid,
gemfibrozil.
Comments:
* If serum is clear, triglyceride is < 350 mg/dL.
* Hypertriglyceridemia in an asymptomatic person who does not have
a strong family history of coronary heart disease or a personal
history of hypercholesterolemia is not a definite risk factor for
coronary heart disease.
Lactate dehydrogenase (LDH), serum
Normal Range: Laboratory-specific
Blood tube color: Marbled
Specfics of collection: Hemolyzed specimens are unacceptable.
Cost: $9
Physiologic Basis:
* 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
following hemolysis.
Increased in: Tissue necrosis, especially in acute injury of
cardiac 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.
Decreased in: Clofibrate, fluoride (low dose).
Comments:
* LDH is elevated after myocardial infarction (2P7 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.
Fetoprotein, a- (AFP), serum
Normal Range: 0-15 ng/mL
SI Range: 0-15 5g/L
Blood tube color: Marbled
Specfics of collection: Unhemolyzed
Cost: $48
Physiologic Basis:
* Alpha-fetoprotein is a glycoprotein produced both early in fetal
life and by some tumors.
Increased in: Hepatocellular carcinoma (72%), massive hepatic
necrosis (74%), viral hepatitis (34%), chronic active hepatitis
(29%), cirrhosis (11%), regional enteritis (5%), benign gynecologic
diseases (22%), testicular carcinoma (embryonal) (70%),
teratocarcinoma (64%), teratoma (37%), ovarian carcinoma (57%),
endometrial Ca (50%), cervical Ca (53%), pancreatic Ca (23%),
gastric Ca (18%), colon Ca (5%).
Negative in: Seminoma
Comments:
* In hepatocellular Ca or germ cell tumor associated with
elevated AFP, the test may be helpful in detecting recurrence after
therapy.
* The test is not sensitive or specific enough to be used as a
general screening test. Screening may be justified in very high
risk populations for hepatocellular Ca.
* AFP is also used to screen pregnant women for possible fetal
neural tube defects. (There is a significant increase in maternal
serum [or amniotic fluid] when compared with that expected at a
given gestational age [15-20 weeks].)
Immunoglobulins (Ig), serum
Normal Range: IgA: 78-367 mg/dL IgG: 583-1761 mg/dL IgM: 52-335
mg/dL
Blood tube color: Marbled
Cost: $59
Physiologic Basis:
* IgG makes up about 85% of total serum immunoglobulins and
predominates late in immune responses. It is the only
immunoglobulin to cross the placenta.
* IgM antibody predominates early in immune responses.
* Secretory IgA plays an important role in host defense mechanisms
by blocking transport of microbes across mucosal surfaces.
Increased in: IgG: Polyclonal: Autoimmune diseases (eg, SLE,
RA), sarcoidosis, chronic liver diseases, some parasitic diseases,
chronic or recurrent infections. Monoclonal: Multiple myeloma (IgG
type), lymphomas or other malignancies. IgM: Polyclonal: Isolated
infections such as viral hepatitis, infectious mononucleosis, early
response to bacterial or parasitic infection. Monoclonal:
Waldenstrom's macroglobulinemia, lymphoma. IgA: Polyclonal: Chronic
liver disease, chronic infections (especially of the GI and
respiratory tracts). Monoclonal: Multiple myeloma (IgA).
Decreased in: IgG: Immunosuppressive therapy, genetic (severe
combined immunodeficiency, Wiskott-Aldrich syndrome, common
variable immunodeficiency). IgM: Immunosuppresive therapy. IgA:
Inherited IgA deficiency (ataxia telangiectasia, combined
immunodeficiency disorders).
Comments:
* IgG deficiency is associated with recurrent and occasionally
severe pyogenic infections.
* Most common form of multiple myeloma is the IgG type.
Smooth muscle antibodies, serum
Normal Range: Negative
Blood tube color: Marbled
Cost: $43
Physiologic Basis:
* Detects antibodies against smooth muscle proteins.
Positive in: Autoimmune chronic active hepatitis (40P70%,
predominantly IgG), lower titers in primary biliary cirrhosis (50%,
predominantly IgM), viral hepatitis, infectious mononucleosis,
neoplasia, cryptogenic cirrhosis (28%), <2% of normals.
Comments:
* High titers (>1:80) may be useful to distinguish autoimmune
chronic active hepatitis from other forms of hepatitis.
Antinuclear antibody (ANA), serum
Normal Range: < 1:20
Blood tube color: Marbled
Specfics of collection:
Cost: $31
Physiologic Basis:
* Heterogeneous antibodies to nuclear antigens (DNA and RNA,
histone and nonhistone proteins).
* Antinuclear antibody is measured in patient's serum by layering
serum over human epithelial cells and detecting the antibody with
fluorescein-conjugated polyvalent anti-human immunoglobulin.
Elevated in: 1/3-3/4 of patients over age 65 (usually in low
titers), systemic lupus erythematosus (98%), drug-induced lupus
(100%), Sj gren's (80%), rheumatoid arthritis (30-50%), scleroderma
(60%), mixed connective tissue disease (100%), Felty's syndrome,
mononucleosis, hepatic or biliary cirrhosis, hepatitis, leukemia,
myasthenia gravis, dermatomyositis, polymyositis, chronic renal
failure.
Comments:
* A negative ANA test does not completely rule out SLE, but
alternative diagnoses should be 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.
Antimitochondrial antibody, serum
Normal Range: Negative
Blood tube color: Marbled
Cost: $43
Physiologic Basis:
* Qualitative measure of antibodies against hepatic
mitochondria.
* Rabbit hepatocytes are incubated with serum and then (after
washing) with a fluorescein-tagged antibody to human
immunoglobulin. Hepatocytes are then viewed for presence of
cytoplasmic staining.
Increased in: Primary biliary cirrhosis (87-98%), chronic active
hepatitis (25-28%); lower titers in viral hepatitis, infectious
mononucleosis, neoplasms, cryptogenic cirrhosis (25-30%). <1% of
normals; rare in extrahepatic biliary obstruction.
Comments:
* Primarily used to distinguish primary biliary cirrhosis (antibody
present) from extrahepatic biliary obstruction (antibody
absent).
Rheumatoid factor (RF), serum
--------------------------------------------------------------------
Normal Range: Negative (<1:16) Blood tube color: Marbled Cost:
$16 Physiologic Basis: * Heterogeneous autoantibodies usually of
the IgM class that react against the Fc region of human IgG.
Positive in: Rheumatoid arthritis (75P90%), Sj gren's (80P90%),
scleroderma, dermatomyositis, SLE (30%), sarcoidosis, Waldenstr m's
macroglobulinemia. Drugs: methyldopa, others. Low titer can be
found in healthy older patients (20%). 1P4% 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. Comments: * 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. (cf, Antoantibodies Table, p __)
---------------------------------------------------------------------
Complement C3, plasma or serum
--------------------------------------------------------------------
Normal Range: 64-166 mg/dL SI Range: 640-1660 mg/L Blood tube
color: Lavender Cost: $32 Physiologic Basis: * The classic and
alternative complement pathways converge at the C3 step in the
complement cascade. Low levels indicate activation by one or both
pathways. * Most diseases with immune complexes will show decreased
C3 levels. * Test as usually performed is an immunoassay (by radial
immunodiffusion or nephelometry). Increased in: Many inflammatory
conditions as an acute phase reactant, active phase of rheumatic
diseases (rheumatoid arthritis, SLE, etc), acute viral
hepatitis, myocardial infarction, cancer, diabetes, pregnancy,
sarcoidosis, amyloidosis, thyroiditis. Decreased by: Decreased
synthesis (protein malnutrition, congenital deficiency, severe
liver disease), or increased catabolism (immune complex disease,
membranoproliferative glomerulonephritis [75%], SLE, Sj gren's,
rheumatoid arthritis, disseminated intravascular coagulation,
paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia,
gram-negative bacteremia) and increased loss (burns,
gastroenteropathies). Comments: * 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.
--------------------------------------------------------------------
CD4/CD8 ratio (CD4/CD8), whole blood
--------------------------------------------------------------------
Normal Range: Ratio: 0.8-2.9 CD4: 359-1725 cells/5L (29-61%) CD8:
177-1106 cells/5L (18-42%) Blood tube color: Lavender Specfics of
collection: Also request a CBC and differential if absolute count
is required. Cost: $ Physiologic Basis: * Lymphocyte identification
depends on specific cell surface antigens (clusters of
differentiation, CD) which can be detected with monoclonal
antibodies using flow cytometry. * CD4 cells are predominantly
helper-inducer cells of the immunologic system. They react with
peptide class II major histocompatibility complex antigens and
augment B cell responses and T cell lymphokine secretion. * CD8
cells can be divided into suppressor cells, which decrease B cell
responses, and cytotoxic T cells. Increased in: Rheumatoid
arthritis, type I diabetes mellitus, SLE without renal disease,
primary biliary cirrhosis, atopic dermatitis, Sezary syndrome,
psoriasis, chronic autoimmune hepatitis. Decreased in: AIDS/HIV
infection, SLE with renal disease, acute CMV infection, burns,
graft-versus-host disease, sunburn, myelodysplasia syndromes, acute
lymphocytic leukemia in remission, recovery from bone marrow
transplantation, herpes infection, infectious mononucleosis,
measles, ataxia-telangiectasia, vigorous exercise. Comments: *
Progressive decline in the number and function of CD4 lymphocytes
seems to be the most characteristic immunologic defect in AIDS. CD4
measurement is particularly useful (more useful than the CD4/CD8
ratio) in determining eligibility for therapy and in monitoring the
progress of the disease. * Absolute CD4 count depends,
analytically, on the reliability of the white blood cell
differential count, as well as on the percentage of CD4 cells
identified using the appropriate monoclonal antibody.
--------------------------------------------------------------------
Angiotensin-converting enzyme (ACE), serum
--------------------------------------------------------------------
Normal Range: Method-dependent U/L SI Units: 5kat/L Blood tube
color: Marbled Cost: $40 Physiologic Basis: * ACE is a dipeptidyl
carboxypeptidase that converts angiotensin I to the vasopressor,
angiotensin II. * ACE is normally present in the kidneys and other
peripheral tissues. In granulomatous disease, ACE levels increase,
derived from epithelioid cells within granulomas. Increased in:
Sarcoidosis (65%), hyperthyroidism, acute hepatitis, primary
biliary cirrhosis, diabetes, multiple myeloma, osteoarthritis,
amyloidosis, Gaucher's disease, pneumoconiosis, histoplasmosis,
miliary tuberculosis, drugs (dexamethasone). Decreased in: Renal
disease, obstructive pulmonary disease, hypothyrodism. Comments: *
Test is not useful as a screening test for sarcoidosis (low
sensitivity). * Specificity is compromised by positive tests in
diseases more common than sarcoidosis. * Some advocate measurement
of ACE to follow disease activity in sarcoidosis. From Detmer WM,
McPhee SJ, Nicoll D, Chou T. Pocket Guide to Diagnostic Tests.
Appleton & Lange, 1992.
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