Biophysical

ADIPONECTIN

Adiponectin is a hormone produced by fat cells that regulates the metabolism of lipids and glucose. Low levels of this hormone are found in people who are obese or who are at increased risk of heart attack. Adiponectin is produced and secreted exclusively by adipocytes, which regulate the metabolism of lipids and glucose. This hormone influences the body’s response to insulin and has anti-inflammatory effects on vascular endothelial cells. High blood levels are associated with a reduced risk of heart attack.

ALANINE AMINOTRANSFERASE(ALT, ALSO CALLED SGPT)

Alanine aminotransferase (ALT) is an enzyme found predominantly in liver and heart cells. Its level may be abnormally high in conditions that cause liver damage or after a heart attack. Blood levels of alanine aminotransferase (ALT) are normally low; however, liver damage (for example, due to viral hepatitis) releases ALT into the bloodstream, causing levels to rise. The ALT test is often done to determine liver function in conjunction with other tests, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), and bilirubin. Serum ALT levels are also increased after myocardial infarction or as a result of some medications. ALT is also called serum glutamic pyruvic transaminase (SGPT).

ALBUMIN

Albumin is a protein manufactured by the liver and found in abundance in the bloodstream. Its level can be abnormal in a variety of diseases and malnutrition conditions. Albumin is the most abundant protein in plasma and transports many small molecules, including bilirubin, calcium, progesterone, and certain drugs. It is also of prime importance in maintaining the oncotic pressure of the blood, since its concentration in blood is much greater than it is in extracellular fluid. Because albumin is synthesized by the liver, decreased serum albumin may result from liver disease. It can also result from kidney disease, which allows albumin to escape into the urine, or be caused by malnutrition or a low-protein diet.

ALBUMIN/GLOBULIN RATIO

The ratio of albumin to globulin in the blood may be abnormal in certain blood and immune system conditions as well as some liver and kidney diseases. A low albumin/globulin ratio may be due to overproduction of gamma globulin (as seen in monoclonal/polyclonal gammopathy, multiple myeloma or autoimmune diseases) or low levels of albumin (due to low production, as in cirrhosis, or excessive loss, as in nephrotic syndrome or protein-losing enteropathy). A high ratio suggests disorders involving low gamma-globulin production, such as agammaglobulinemia.

ALKALINE PHOSPHATASE(ALP)

Alkaline phosphatase (ALP) is an enzyme found in many tissues, including liver, bile duct, placenta, and bone. Its level may be elevated in conditions that damage or disrupt the liver, bile ducts, or bone. Because damaged or diseased tissue releases enzymes into the blood, serum ALP levels can be abnormal in many conditions, including bone disease and liver disease. Serum ALP is also increased in some normal circumstances (for example, during normal bone growth or bone fracture) or in response to a variety of drugs.

ALPHA-1-ANTITRYPSIN(A1AT)

Alpha-1-antitrypsin (A1AT) is a protein made in the liver that protects the lungs so they can work normally. Alpha-1-antitrypsin is the major protease (trypsin, chymotrypsin, elastase) inhibitor in human serum. An inherited deficiency is associated with liver and lung disease. Low levels can also be found in neonatal respiratory distress syndrome and severe protein-losing disorders. In some adults, alpha-1-antitrypsin deficiency is complicated by cirrhosis, liver cancer, rheumatoid arthritis, and pancreatitis. Increased levels may be associated with inflammation.

ALPHA-2-MACROGLOBULIN(A2M)

Alpha-2-macroglobulin (A2M) is a major blood protein that may be abnormal in certain liver, kidney, and pancreas conditions. Alpha-2-macroglobulin (A2M) function ranges from ion transport to inhibition of proteinases. Elevated levels are seen in conditions such as cirrhosis, nephrotic syndrome, severe burns, and diabetes. Decreased levels are seen in pancreatitis, fibrinolysis, and liver disease. A rare A2M deletion polymorphism has been linked to an increased risk of Alzheimer’s disease, although the mechanism is unknown.

ALPHA-FETOPROTEIN(AFP)

Alpha-fetoprotein (AFP) is a fetal protein that is detected in the mother’s blood during pregnancy. Although not diagnostic of any specific disease, it can be used as a tumor marker when found in non-pregnant adults. Its concentration peaks in the fetal bloodstream at 2-3 g/l around 12-14 weeks of gestation and then falls. Fetal malformations such as neural tube defects elevate maternal serum levels. Normal values in adult males and non-pregnant females are very low (< 40 micrograms/liter). Among cancer patients, elevated levels are seen most frequently in adults with germ cell tumors or hepatocellular carcinoma but also occur in gastric, testicular, colon, biliary, pancreatic, and lung cancers.

AMYLASE

Amylase is a digestive enzyme produced in the salivary glands and pancreas. Its levels may be elevated if the pancreas is inflamed or damaged. Amylase is involved in the digestion of glycogen and starch. Pancreatic disease or inflammation can cause amylase to escape into the blood. Drugs that can increase amylase levels include asparaginase, aspirin, cholinergic agents, corticosteroids, indomethacin, loop and thiazide diuretics, methyldopa, opiates (such as codeine and morphine), oral contraceptives, and pentazocine.

ANDROSTENEDIONE

Androstenedione is a natural steroid hormone that is modified within the body to produce the male sex hormone testosterone and the female sex hormone estrogen. Taken orally, androstenedione will increase blood levels of testosterone. Levels of this hormone may be abnormal in certain glandular conditions. Androstenedione is a 19-carbon steroid hormone and is a direct precursor to the androgen testosterone and the estrogens estrone and estradiol. Some androstenedione is secreted into the plasma and may be converted to testosterone in peripheral tissues. Androstenedione production is governed by the adrenocorticotropic hormone (ACTH).

ANTI-NUCLEAR ANTIBODY(ANA)

Anti-nuclear antibodies (ANA) are antibodies that can bind to certain structures within the nucleus of our cells. Normally, there are no ANAs in the blood, but they may be detected in a variety of autoimmune diseases and arthritis conditions or even in some people who don’t have any specific disease. ANAs are gamma-globulins helpful in the evaluation of systemic lupus erythematosus (SLE) and drug-induced lupus, but levels may also be positive in cases of scleroderma, Sjögren’s syndrome, Raynaud’s disease, juvenile chronic arthritis, rheumatoid arthritis, antiphospholipid antibody syndrome, autoimmune hepatitis, type 1 diabetes mellitus, and many other autoimmune and non- rheumatological conditions associated with tissue damage. Due to the many potential causes of a positive result, additional testing is often needed.

ANTI-SACCHAROMYCES CEREVISIAE ANTIBODY(ASCA)

Anti-Saccharomyces cerevisiae (ASCA) testing may be useful in the evaluation of suspected inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. Anti-Saccharomyces cerevisiae mannan antibodies have been proposed as a new serological marker associated with Crohn’s disease. However, their clinical value is still unclear.

APOLIPOPROTEIN AI(Apo AI)

An apolipoprotein is the protein constituent of a lipoprotein, a large molecule that transports triglycerides and cholesterol through the blood. Apolipoprotein AI (Apo AI) is found in high-density lipoprotein (HDL) particles, which transport the cholesterol known as “good cholesterol.” Apo AI is instrumental in promoting the transfer of cholesterol into the liver, where it is metabolized and then excreted from the body via the intestines. Very low levels of Apo AI may be associated with a higher risk of coronary heart disease. Apo AI serves to prevent the accumulation of cholesterol-loaded macrophages, which deposit on arterial walls as foam cells (a prominent early feature of atherosclerotic lesion formation). Its primary function is to activate lecithin-cholesterol acyltransferase (LCAT) within the HDL complex, which catalyzes the esterification of cholesterol. This results in a more soluble cholesterol-HDL complex, increasing the cholesterol transport capacity of the HDL particle for subsequent removal by the liver. Apo AI is therefore a convenient marker for assessing the cholesterol-clearing capacity of the blood, and studies have clearly indicated that it is a better discriminator of angiographically documented coronary artery disease than is HDL cholesterol.

APOLIPOPROTEIN CIII(Apo CIII)

An apolipoprotein is the protein constituent of a lipoprotein, a large molecule that transports triglycerides and cholesterol through the blood. Apolipoprotein CIII (Apo CIII) is made in the liver and is found in very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particles. Very low levels of Apo CIII may be associated with a higher risk of coronary heart disease. Synthesized predominantly in the liver and to a lesser degree in the intestine, Apo CIII is found in VLDL, HDL, and chylomicron remnants, and elevated levels are associated with both primary and secondary hypertriglyceridemia. It is a cofactor for sphingomyelinase, an inhibitor of lipoprotein lipase (LPL), and may activate lecithin-cholesterol acyltransferase (LCAT). Apo CIII has been recognized as an emerging risk marker that may play a role in more effective coronary artery disease (CAD) risk assessment.

APOLIPOPROTEIN H(Apo H)

An apolipoprotein is the protein constituent of a lipoprotein, a large molecule that transports triglycerides and cholesterol through the blood. Apolipoprotein H (Apo H) is a lipoprotein made primarily by the placenta. Levels of this protein may be abnormal when miscarriages occur. The human Apo H molecule, also known as beta-2-glycoprotein 1, is expressed by placental trophoblast cells at high levels. Although its normal physiological role is not known, it appears to act as a cofactor for the binding of phospholipid autoantibodies to trophoblasts, a process involved in the pathogenesis of recurrent miscarriage (antiphospholipid syndrome). Genetic variation in apolipoprotein H affects the occurrence of antiphospholipid antibodies and apolipoprotein H concentrations in systemic lupus erythematosus.

ASPARTATE AMINOTRANSFERASE(AST, ALSO CALLED SGOT)

Aspartate aminotransferase (AST, also called SGOT) is an enzyme found in liver, muscle, and heart tissues. Diseases that affect liver cells cause them to release AST, and AST levels are also increased after a heart attack. However, mild to moderate elevations of AST are not uncommon in otherwise healthy individuals. In viral hepatitis and other forms of liver disease associated with hepatic necrosis, levels of serum AST and ALT (alanine aminotransferase) are elevated even before clinical signs and symptoms appear. Although 20- to 50-fold elevations are more frequently encountered, both enzymes may reach values as high as 100 times the upper limit of normal (ULN). Serum AST levels also increase after myocardial infarction. Pulmonary emboli can raise AST levels to 2 to 3 times the ULN, and slight to moderate elevations (2 to 5 times the ULN) are seen in acute pancreatitis, crushed muscle injuries, gangrene, and hemolytic disease.

ASPARTATE AMINOTRANSFERASE ANTIGEN(AST Ag, ALSO CALLED SGOT ANTIGEN)

Aspartate aminotransferase antigen (AST Ag, also called SGOT antigen) is an enzyme present in liver and muscle cells. Its levels are elevated in conditions affecting the heart and liver, such as viral hepatitis, hepatic congestion, myocarditis, and myocardial infarction.

B-TYPE NATRIURETIC PEPTIDE(BNP)

B-type natriuretic peptide (BNP) is found only in the ventricles of the heart. Elevation may indicate congestive heart failure. There is strong correlation between the degree of decompensation of congestive heart failure and the level of B-type natriuretic peptide. In addition, it has been very helpful in the differential diagnosis of the patient presenting with dyspnea. Recent studies suggest that B-type natriuretic peptide may have important prognostic significance in patients presenting with an acute coronary syndrome.

BASOPHIL COUNT

A basophil is a type of white blood cell that is involved in the body’s response to infections and allergic stimuli. Basophil levels may be elevated in conditions involving inflammation and allergic reactions. Basophils are granular leukocytes with an irregularly shaped, pale-staining nucleus that is partially constricted into two lobes. Their cytoplasm contains coarse, bluish-black granules that contain histamines, heparin, and serotonin, which are released on appropriate stimulation. An increased serum level of basophils is often seen in myxedema, hypothyroid conditions, ulcerative colitis, certain types of anemia, and in response to parasitic infections and allergic stimuli. An alteration in bone marrow function, such as leukemia or Hodgkin’s disease, may also cause an increase in basophil numbers, while corticosteroid drugs, allergic reactions, and acute infections may cause already-low basophil numbers to decrease.

BASOPHIL PERCENTAGE

The percentage of basophils (a type of white blood cell involved in the body’s response to infections and allergic stimuli) out of all the white blood cells is helpful in diagnosing certain diseases. Basophils are granular leukocytes with an irregularly shaped, pale-staining nucleus that is partially constricted into two lobes. Their cytoplasm contains coarse, bluish-black granules that contain histamines, heparin, and serotonin, which are released on appropriate stimulation. An increased serum level of basophils is often seen in myxedema, hypothyroid conditions, ulcerative colitis, certain types of anemia, and in response to parasitic infections and allergic stimuli. An alteration in bone marrow function, such as leukemia or Hodgkin’s disease, may also cause an increase in basophil numbers, while corticosteroid drugs, allergic reactions, and acute infections may cause already-low basophil numbers to decrease.

BETA-2-GLYCOPROTEIN ANTIBODY(B2GP Ab)

Antibodies to beta-2-glycoprotein (B2GP Ab) are found in conditions such as antiphospholipid syndrome, a clotting disorder which can cause recurrent miscarriage. Beta-2-glyocoprotein antibodies are also associated with an increased risk of venous and arterial thrombosis and thrombocytopenia. Unlike cardiolipin autoantibodies, which can be transiently found after infectious disease, beta-2-glycoprotein antibodies are found only in patients with autoimmune diseases.

BETA-2-MICROGLOBULIN(B2M)

Beta-2-microglobulin (B2M) is a protein found on the surface of most cells. Its levels may be especially elevated in kidney failure, inflammation, and certain cancers. B2M is found on the surfaces of all nucleated cells and is shed into the blood, particularly by tumor cells and lymphocytes. Due to its small size, it passes through the kidney’s glomerular membrane, but normally less than 1% is excreted due to reabsorption in the proximal tubules. Therefore, high plasma levels occur in renal failure, inflammation, and neoplasms, especially those associated with B-lymphocytes, and the plasma level is particularly useful in monitoring kidney transplant recipients. Beta-2-microglobulin concentrations are sometimes increased in cerebrospinal fluid (relative to serum) in acute lymphoblastic leukemia (ALL), lymphoma, and lymphoproliferative diseases.

BILIRUBIN, TOTAL

Bilirubin is a yellow breakdown product of hemoglobin, the oxygen-carrying molecule in red blood cells (RBCs). Bilirubin levels may be elevated in patients with liver disease or a blocked bile duct. Bilirubin is produced by catabolism of the heme molecule from erythrocytes. Approximately 85% come from senescent RBCs that are destroyed in the liver, spleen, and bone marrow, while the remainder comes from RBC precursors destroyed in the bone marrow and the catabolism of other heme-containing proteins, such as myoglobin, cytochromes, and peroxidases. In the hepatocytes, bilirubin is rapidly conjugated with glucuronic acid to produce bilirubin monoglucuronide (10%) and diglucuronide (90%), which are then excreted into bile. The total bilirubin value includes both conjugated and unconjugated bilirubin, whereas bilirubin fractionation distinguishes between the levels of each. High unconjugated bilirubin levels are most commonly seen in newborns due to premature breakdown of erythrocytes and ineffective erythropoiesis, although Crigler-Najjar syndrome and Gilbert’s syndrome also produce unconjugated bilirubinemia through the inability to conjugate bilirubin at the normal rate. Conjugated bilirubin levels increase to abnormal values when any portion of the biliary tree becomes blocked or abnormally permeable, retarding the passage of bilirubin and other bile components.

BLOOD UREA NITROGEN(BUN)

Blood urea nitrogen (BUN) is a test that measures the amount of urea nitrogen in the blood. Urea is the major breakdown product of bodily protein and contains nitrogen. Urea and other nitrogen-rich waste products are normally eliminated from the bloodstream by the kidneys, so an increased BUN level may indicate impaired renal (kidney) function. However, many factors besides renal disease can cause BUN alterations. An elevated BUN level may also be caused by congestive heart failure as a result of poor renal perfusion, dehydration, shock, hemorrhage into the gastrointestinal tract, acute myocardial infarction, stress, or excessive protein intake or protein catabolism. A decreased level may be seen in liver failure, malnutrition, anabolic steroid use, or impaired nutrient absorption. In patients with liver disease, the BUN level may be low even if the kidneys are normal.

BLOOD UREA NITROGEN/CREATININE RATIO

Unlike urea, blood creatinine is relatively insensitive to body hydration and the presence of blood or meat in the intestinal tract; therefore, the blood urea nitrogen (BUN)-to-creatinine ratio may help to distinguish impaired kidney function due to dehydration from other kinds of kidney damage. The ratio of BUN:creatinine is normally 10:1 but can increase to 20:1 or even higher with dehydration. An increased BUN:creatinine ratio may also be due to certain types of kidney disease, breakdown of blood in the intestinal tract, increased dietary protein, or any clinical circumstance resulting in reduced blood flow to the kidneys (such as heart failure or renal artery disease). The BUN:creatinine ratio is decreased in other renal conditions, liver disease, malnutrition, and sickle cell anemia.

BORDETELLA PERTUSSIS ANTIBODY(B. PERTUSSIS Ab)

Bordetella pertussis antibody is evidence of recent infection with, exposure to, or vaccination with Bordetella pertussis, the bacterium causing whooping cough.

BRAIN-DERIVED NEUROTROPHIC FACTOR(BDNF)

Brain-derived neurotrophic factor (BDNF) is a protein found in the central nervous system, which is important to the survival of existing brain cells and the growth of new brain cells. BDNF levels may be abnormally low in certain nervous system conditions such as depression and Alzheimer’s disease. Neurotrophins are soluble polypeptide growth factors widely recognized for their roles in the mammalian nervous system. BDNF is a central nervous system protein that helps to support existing neurons and encourage neural and synaptic growth. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system and usually die soon after birth, suggesting that BDNF plays an important role in normal development. Exposure to stress and the stress hormone corticosterone decreases the expression of BDNF in rats and leads to eventual atrophy of the hippocampus if exposure is persistent. Similar atrophy has been shown to take place in humans suffering from long-term depression, while physical activity has been reported to increase BDNF expression in the brain and spinal cord. Various studies have shown possible links between low BDNF levels and other affective disorders.

C-PEPTIDE

C-peptide (also called insulin C-peptide) is a subunit of the hormone insulin. C-peptide is measured in newly diagnosed diabetes patients to determine how much insulin is being produced in the body. Insulin is formed by the cleavage of C-peptide from proinsulin, and C-peptide is released from the pancreas in equimolar concentrations with insulin. However, it has no known biologic activity. C-peptide is measured to evaluate residual beta cell function in patients with insulin-treated diabetes mellitus in order to distinguish endogenous from exogenous insulin sources. In transient diabetes mellitus, the return of C-peptide concentrations to within the normal range provides evidence of remission.

C-REACTIVE PROTEIN(CRP)

C-reactive protein (CRP) is a protein produced in the liver, whose levels rise dramatically in the presence of inflammation or infection. Although not a telltale diagnostic sign of any one condition, CRP may be measured to check for rheumatoid arthritis or to measure a patient’s response to treatment. As a marker of inflammation, CRP has also been established as an important predictor of cardiovascular risk. As an acute phase reactant, CRP can be used as a general screening aid for inflammatory diseases, infections, and neoplasms. In addition, CRP in large concentrations (>5 mg/dL) predicts progression of erosions in rheumatoid arthritis. Elevated serum CRP is characteristic of bacterial, but not viral, meningitis or meningoencephalitis. Elevated CRP levels are also associated with an increased risk of myocardial infarction in patients with stable and unstable angina and predict the risk of first myocardial infarction and ischemic stroke in apparently healthy individuals.

CALCITONIN

Calcitonin is a hormone secreted by the thyroid. It helps to regulate calcium and phosphate levels in the bloodstream and promotes bone formation. Calcitonin levels may be significantly elevated in thyroid cancer. Calcitonin is secreted by the parafollicular C-cells of the thyroid. Its primary physiological effect is to lower serum calcium and phosphate levels. Elevated levels of calcitonin (>100 pg/ml) may be encountered in a variety of pathological conditions, including leukemias and myeloproliferative disorders. The test is most often used to detect and confirm medullary carcinoma of the thyroid gland, and calcitonin may be detectable in blood even when the tumor is clinically occult. It is also used as a serum tumor marker for small cell (oat cell) lung carcinoma.

CALCIUM(Ca)

Calcium (Ca) is an element found in the body that is an important component of bone. It is also important in normal cell function, muscle contraction, heart action, nervous system maintenance, and blood clotting. The parathyroid glands regulate serum calcium concentrations and bone metabolism. In turn, serum calcium concentrations regulate parathyroid hormone (PTH) secretion via negative feedback. Hypercalcemia may be caused by hyperparathyroidism, multiple myeloma, or excessive vitamin D intake, while hypocalcemia may result from hypoparathyroidism, low vitamin D intake, pregnancy, osteomalacia, and certain renal diseases.

CAMPYLOBACTER JEJUNI ANTIBODY(C. JEJUNI Ab)

Campylobacter jejuni is a bacterium that causes infectious diarrhea. The antibody against C. jejuni indicates recent infection with or prior exposure to these bacteria. C. jejuni infection causes cramping, diarrhea, abdominal pain, and fever within 2 to 5 days after exposure to the organism. It is one of the most common bacterial causes of diarrhea. Most cases come from handling or ingesting raw or undercooked poultry.

CANCER ANTIGEN 15-3(BR-MA)

BR-MA, also called cancer antigen 15-3 (CA-15-3), is a tumor marker most useful as an indicator of the effects of treatment in women diagnosed with breast cancer, especially advanced breast cancer. Other conditions that may also raise BR-MA levels include lung cancer, ovarian cancer, prostate cancer, benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, hepatitis, pregnancy, and lactation. BR-MA measures a circulating adenocarcinoma-associated antigen belonging to a family of high molecular- weight glycoproteins normally present in human milk fat globule membranes. Although elevated levels are present in only a small percentage of patients with localized disease, two-thirds of cases with metastasis will have significantly elevated levels. BR-MA levels may also be elevated in patients with cirrhosis, sarcoidosis, tuberculosis, systemic lupus erythematosus, and malignancies of the pancreas, colon, and liver.

CANCER ANTIGEN 19-9(CA 19-9)

Cancer antigen 19-9 (CA 19-9) is a cancer marker whose levels may be elevated in cancers of the digestive tract (colorectal, pancreatic, stomach, and bile duct cancers), particularly cancer of the pancreas. Higher levels of CA 19-9 tend to be associated with more advanced disease, but several noncancerous conditions may also elevate CA 19-9 levels, including gallstones, pancreatitis, and cirrhosis of the liver. CA 19-9 is a derivative of the Leab blood group antigen present on normal mesenteric epithelium and thus is not expressed in Lewis-negative individuals (about 7% of the U.S. population). One use of CA 19-9 is in predicting the operability of carcinoma of the pancreas. It is also expressed in most patients with carcinomas of the liver, biliary tract, stomach, and colon. The specificity of CA 19-9 is limited by its expression in patients with pancreatitis and inflammatory gastrointestinal diseases. CA 19-9 and carcinoembryonic antigen (CEA) may be used together to help differentiate benign disease from pancreatic carcinoma, since elevations of both are suggestive of neoplasia.

CANCER ANTIGEN 125(CA 125)

This test may be used to follow women who have already been diagnosed with ovarian cancer and is a good indicator of whether a patient is responding to treatment and whether she remains in remission after treatment. Cancer antigen 125 (CA 125) is a glycoprotein found in increased amounts on the cell surfaces of many ovarian epithelial malignancies. Elevated CA 125 levels are associated with serous, endometrioid, and clear cell carcinomas of the ovary. More than 80% of non-mucinous, epithelial ovarian carcinomas, as well as many uterine tumors, express elevated levels of CA 125. However, conditions such as endometriosis, normal pregnancy, pelvic inflammatory disease, uterine fibroids, hepatitis, pancreatitis, and cirrhosis may also contribute to elevated serum CA 125 levels. Breast, lung, and gastrointestinal tract cancers may also be associated with an elevation of this tumor marker.

CARBON DIOXIDE(CO2)

Carbon dioxide (CO2) is a gas that dissolves in water to make carbonic acid, which means that measurement of carbon dioxide levels in the blood can help to indicate the blood’s acidity. Measurement of CO2 content is part of an electrolyte panel to screen for an electrolyte or acid-base imbalance. Higher than normal carbon dioxide levels may reflect excessive loss of acid (as with recurrent vomiting or continuous gastric drainage) or acid-base disorders (such as primary aldosteronism or Cushing syndrome). Lower than normal levels are common in acidosis (as in diabetic ketoacidosis, kidney disease, and severe diarrhea) or respiratory alkalosis.

CARCINOEMBRYONIC ANTIGEN(CEA)

Carcinoembryonic antigen (CEA) is a protein normally found in fetal gut tissue. Its levels may be increased in the presence of various cancers, particularly colon and rectal cancer, but also breast, lung, pancreatic, thyroid, and genitourinary cancers. Benign conditions, including smoking, infection, inflammatory bowel disease, and liver disease, can also raise CEA levels. Carcinoembryonic antigen levels are used to monitor patients with various malignancies, evaluate response to therapy, and potentially indicate recurrence and prognosis. CEA has broad tumor specificity; elevated levels are seen in cancers of the colon, rectum, stomach, breast, lung, pancreas, thyroid, and genitourinary system. Higher levels also may indicate a greater likelihood of metastasis. Levels usually fall following successful treatment and remain stable; rising levels in these patients may indicate recurrence.

CENTROMERE PROTEIN B ANTIBODY(CENP-B Ab)

Antibodies to centromere protein B are found in a variety of autoimmune conditions and arthritis diseases. Centromere antibodies demonstrate a specific anti-nuclear antibody assay pattern, which is present in 80% to 90% of individuals with CREST variant scleroderma, 30% of Raynaud’s syndrome patients, 12% of patients with mixed connective-tissue disease, diffuse scleroderma, interstitial pulmonary fibrosis, or primary biliary cirrhosis, and a smaller percentage of patients with systemic lupus erythematosus and rheumatoid arthritis.

CHLAMYDIA PNEUMONIAE ANTIBODY(C. PNEAUMONIAE Ab)

Chlamydia pneumoniae is a bacterium that causes pneumonia, bronchitis, sinusitis and pharyngitis in both adults and children. Chronic low-level infection may injure blood vessels and has been seen in patients who have suffered a heart attack or heart disease. The presence of this antibody indicates recent infection with or exposure to C. pneumoniae. In addition to causing pneumonia and other upper and lower respiratory ailments, chronic infection with C. pneumoniae can initiate and perpetuate vascular endothelial damage and has recently been implicated in atherogenesis, asthma, otitis media, multiple sclerosis, and age-related macular degeneration. Studies have demonstrated a consistent association between elevated C. pneumoniae antibody titers and myocardial infarction or chronic heart disease.

CHLAMYDIA TRACHOMATIS ANTIBODY(C. TRACHOMATIS Ab)

Chlamydia trachomatis is a bacterium that is transmitted by sexual contact and commonly causes infections of the female reproductive tract. This antibody indicates recent infection with or exposure to C. trachomatis. It is one of the most common sexually transmitted organisms in the U.S. today, with more than 3 million people infected each year. It is asymptomatic in 80% of women and 50% of men but may result in cervicitis or pelvic inflammatory disease in females, urethritis or epididymitis in males, and conjunctivitis or pneumonia in neonates.

CHLORIDE(Cl)

Chloride (Cl) is an electrolyte that is important in water distribution and general cell function. Its levels may be abnormal in a variety of metabolic and kidney conditions. Chloride is significantly involved in the maintenance of water distribution, osmotic pressure, blood pH, kidney function, and acid-base balance. Hypochloremia is observed with burns, Cushing’s syndrome, heart failure, salt-losing nephritis, metabolic alkalosis, chronic compensated respiratory acidosis, and diabetic ketoacidosis. In Addison’s disease, chloride levels are usually maintained close to normal except in an Addisonian crisis, when chloride as well as sodium levels may drop significantly. Hyperchloremia occurs with dehydration, renal tubular acidosis, acute renal failure, metabolic acidosis associated with prolonged diarrhea and loss of sodium bicarbonate, diabetes insipidus, adrenocortical hyperfunction, hyperparathyroidism, salicylate intoxication, and respiratory alkalosis. Urinary excretion of chloride decreases when losses by other routes are increased.

CHOLESTEROL

Cholesterol is a lipid that is found in our diet as well as manufactured by the liver. It is an important component in a variety of hormones. Significant elevation in cholesterol levels is a risk factor for coronary heart disease. Although a portion of the body’s cholesterol is derived from dietary intake, most is synthesized by the liver and other tissues. A single total cholesterol value more than 20% below the suggested age- and sex-adjusted upper reference limits virtually eliminates a diagnosis of hyperlipoproteinemia. Total cholesterol, HDL-cholesterol, and LDL-cholesterol levels are highly useful in the determination of risk for coronary artery disease and stroke. Standardized by reference methods provided by the CDC, laboratory reference intervals reflect “ideal” or “healthy” levels for reduced risk with values relatively comparable from laboratory to laboratory.

COLLAGEN TYPE 1 ANTIBODY

Collagen autoantibodies have been observed in a variety of autoimmune diseases, including mixed connective tissue disease, systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis (RA), and vasculitis. Collagen type 1 antibodies are found in about 85% of SLE patients, as well as in adult and juvenile RA and relapsing polychondritis.

COLLAGEN TYPE 2 ANTIBODY

Collagen autoantibodies have been observed in a variety of autoimmune diseases, including mixed connective tissue disease, systemic lupus erythematosus, progressive systemic sclerosis, rheumatoid arthritis (RA), and vasculitis. Collagen type 2 antibodies are present in the serum of about 70% of RA patients and 40% to 50% of relapsing polychondritis patients. Autoimmunity to type 2 collagen may be instrumental in the pathogenesis of RA.

COLLAGEN TYPE 4 ANTIBODY

Collagen autoantibodies have been observed in a variety of autoimmune diseases, including mixed connective tissue disease, systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, and vasculitis. Collagen type 4 antibodies occur in Goodpasture’s syndrome, scleroderma, SLE, progressive systemic sclerosis, polyarteritis nodosa, primary Raynaud’s phenomenon, and vasculitides, among other conditions.

COLLAGEN TYPE 6 ANTIBODY

Collagen autoantibodies have been observed in a variety of autoimmune diseases, including mixed connective tissue disease, systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, and vasculitis. Antibodies against collagen type 6 are present in a number of chronic diseases including diabetes mellitus, rheumatoid arthritis, and alcoholism.

COMPLEMENT 3(C3)

Complement 3 (C3) levels may be low in a variety of autoimmune diseases and other conditions. Quantitation of C3 is used to detect individuals with hereditary C3 deficiency or those with diseases in which complement is consumed at an increased rate. These include systemic lupus erythematosus, chronic active hepatitis, infective endocarditis, certain fungal and parasitic infections, septicemia, shock, and glomerulonephritis. Low C3 levels may also be seen in patients with burns, malignant hypertension, and disseminated intravascular coagulation. Elevated C3 levels may occur in cancer and ulcerative colitis.

COMPLEMENT FACTOR C1Q ANTIBODY(C1Q ANTIBODY)

Complement factor C1q is a protein involved in the immune system. Antibodies to C1q may be present in certain autoimmune diseases and arthritis conditions. C1q is a component of the C1 molecular complex, and C1q antibody levels are useful in the detection of circulating immune complexes (CICs). CICs are formed by the interaction of antibodies with specific antigens and are normally cleared rapidly by the reticuloendothelial system. However, in some cases, CICs are deposited in tissues with associated inflammatory- mediated damage. Elevated CIC levels have been detected in a variety of autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis), certain cases of glomerulonephritis, infectious diseases (e.g., Lyme disease, chronic HBV infection, HIV infection, endocarditis), and some malignancies.

CORTISOL

Cortisol is an important steroid hormone that regulates numerous body systems, including the response to infection and inflammation, blood sugar levels, and bone metabolism. Cortisol levels are often measured to evaluate the function of the pituitary and adrenal glands. Cortisol (hydrocortisone) is primarily produced in the adrenal gland. It stimulates conversion of proteins to carbohydrates, raises blood glucose levels, and promotes glycogen storage in the liver. Cortisol levels may be elevated in patients with adrenal tumors and Cushing’s syndrome. Lower than normal levels may indicate Addison’s disease or hypopituitarism.

CREATINE

Creatinine is a protein waste product generated by muscle metabolism and eliminated by the kidneys. Creatinine is a useful indicator of kidney function, and its levels are significantly elevated when kidney function is impaired. Because creatinine is released at a constant rate (depending on muscle mass), its serum level is a good indicator of glomerular filtration rate and renal function. Daily excretion of creatinine can be increased by 10% to 30% as a result of dietary intake. Elevated levels may indicate diabetic nephropathy, preeclampsia or eclampsia, glomerulonephritis, or rhabdomyolysis. Lower than normal levels may indicate late stage muscular dystrophy or myasthenia gravis.

CREATINE KINASE MB(CK-MB)

Creatine kinase MB (CK-MB) is a protein derived from heart muscle. Levels of this protein are significantly elevated when the heart muscle is damaged, as occurs during a heart attack. Damaged cardiac tissue releases CK-MB from 2 to 8 hours following acute myocardial infarction (AMI). CK-MB values peak at 9 to 30 hours after infarction and return to baseline within 48 to 72 hours. They are also useful in monitoring reperfusion during thrombolytic therapy after AMI. Rhabdomyolysis and other causes of skeletal muscle injury can also increase CK-MB levels.

CREATINE KINASE, TOTAL(CK TOTAL)

Creatine kinase (CK) is an enzyme found in skeletal muscle, heart muscle, and brain tissue. Its levels are significantly elevated when skeletal or heart muscles are damaged. Its measurement is often used to diagnose a heart attack or evaluate an episode of chest pain. Also called CPK, CK is an enzyme catalyzing the reversible transfer of phosphate from phosphocreatine to ADP, forming creatine and ATP, which is of importance in muscle contraction. CK levels are elevated after myocardial infarction and in the presence of neuromuscular disease or muscle damage caused by drugs, trauma, or immobility.

CYTOCHROME P450 ANTIBODY

This antibody against one of the cytochrome P450 enzymes (a family of enzymes involved in the metabolism of foreign compounds) is sometimes present in patients with type II autoimmune hepatitis and other liver diseases. Cytochrome P450 enzymes catalyze various oxidative reactions in the human liver, intestine, kidney, lung, and central nervous system. They are involved in the metabolism of many endogenous and exogenous substrates, including drugs, toxins, hormones, and natural plant products. Antibodies against a particular cytochrome P450 isoenzyme, called anti-LKM (liver kidney microsome), have been identified in patients with autoimmune hepatitis type II and in a small number of patients with chronic hepatitis C.

CYTOMEGALOVIRUS ANTIBODY(CMV Ab)

Cytomegalovirus (CMV) is a common virus that may cause mononucleosis in healthy individuals or more severe disease in immunosuppressed persons. The presence of CMV antibody indicates recent infection or exposure. CMV infections in humans are widespread: 60% to 90% of adults have had CMV infection. Infection of healthy children and adults usually results in asymptomatic disease but can cause hepatitis or mononucleosis. If acquired in utero or at birth, CMV infection is usually asymptomatic, but in 10% of infants, it causes congenital abnormalities, including growth retardation, jaundice, hepatosplenomegaly, pneumonitis, and prematurity. CMV is a major cause of morbidity and mortality in immunosuppressed patients, who may develop pulmonary, gastrointestinal, or nervous system involvement.

DIHYDROEPIANDROSTERONE SULFATE(DHEA-S)

Dihydroepiandrosterone sulfate (DHEA-S) is a male hormone that is manufactured in the adrenal glands of both men and women. Its levels are abnormal in various glandular conditions. DHEA-S is a weak androgen secreted primarily by the zona reticularis of the adrenal cortex. Secretion is controlled by ACTH and other pituitary factors. Physiologically, DHEA-S has many roles, including the development of pubic and axillary hair, the development and maintenance of immunocompetence, and as a possible tumor marker. Serum levels of DHEA-S are 1,000 times greater than those of DHEA. Clinical indications for DHEA-S testing include hirsutism and amenorrhea (the most common sign of increased adrenal androgen production by women); polycystic ovarian syndrome (DHEA-S levels greater than 700-800 μg/dL in women are suggestive of a hormone-secreting adrenal tumor); and Cushing’s syndrome caused by an adrenal carcinoma (DHEA-S is usually not elevated if Cushing’s syndrome is caused by a benign adrenal tumor).

DIPHTHERIA TOXIN ANTIBODY

Diphtheria is an infectious disease caused by the toxin-producing bacterium Corynebacterium diphtheria. Presence of the antibody against Corynebacterium diphtheria indicates recent infection with, exposure to, or vaccination against diphtheria. Diphtheria is usually transmitted by contact with respiratory droplets from infected persons or asymptomatic carriers. It can also be transmitted by handling used tissues or using a glass or utensil used by an infected person. The incubation period is 2 to 5 days.

DOUBLE-STRANDED DNA ANTIBODY(dsDNA Ab)

Antibodies against the double-stranded DNA (dsDNA) in our own cells occur in various autoimmune and arthritis conditions. These antibodies are present in about 60% of patients with systemic lupus erythematosus, particularly those with associated nephritis, but are insufficient for diagnosing that condition. The dsDNA antibodies are also present in smaller fractions of patients with other rheumatic disorders, chronic active hepatitis, infectious mononucleosis, and biliary cirrhosis. There have been some reports of de novo development of dsDNA antibodies in patients with rheumatoid arthritis treated with infliximab (Remicade).

ENDOTHELIN 1(ET-1)

Endothelins are proteins that can powerfully constrict blood vessels. Their levels may be elevated in hypertension, chest pain (angina), and heart attack. Endothelins are also found in the central nervous system, and their levels may be elevated in conditions involving nervous system injury. Endothelins are extremely potent vasoconstrictors. Endothelin-1 is the most abundant and best characterized of three isoforms (ET-1, ET-2, and ET-3). In addition to vasoconstriction, endothelins affect neuronal excitability. Elevated plasma concentrations of endothelins have been observed in pulmonary hypertension, unstable angina, Prinzmetal’s angina, myocardial infarction, chronic heart failure, acute renal failure after renal ischemia, Raynaud’s disease, and Crohn’s disease.

EOSINOPHIL COUNT

This test measures the number of eosinophils in the blood. Eosinophils are a type of white blood cell whose levels are most commonly elevated in patients with allergies and parasitic infections. Eosinophils normally make up about 2.7% of the white blood cell count, but during eosinophilic leukocytosis, their numbers can increase by 5% to 90% (10% to 20% are most common). Eosinophils are active in allergic diseases (including asthma), parasitic infections, and other disorders, including eczema, leukemia, and autoimmune diseases. Medications that may cause an increase in eosinophils include amphetamines (appetite suppressants), tranquilizers, bulk-type laxatives containing psyllium, and certain antibiotics. Low numbers of eosinophils may be associated with alcohol intoxication or excessive production of adrenocorticosteroids.

EOSINOPHIL PERCENTAGE

This test measures the percentage of white blood cells that are eosinophils. Eosinophils are a type of white blood cell whose levels are most commonly elevated in patients with allergies and parasitic infections. The eosinophil percentage assesses the number of eosinophils in relation to other white blood cells.

EOTAXIN

Eotaxin is a protein produced by certain cells. Elevated levels of eotaxin may indicate allergic reaction or inflammation. Eotaxin is a chemokine characterized by its high chemotactic selectivity for eosinophils. It is produced by epithelial cells, endothelial cells, and eosinophils, and its expression is enhanced in allergic inflammation.

EPIDERMAL GROWTH FACTOR(EGF)

Epidermal growth factor (EGF) is a protein that stimulates cell growth (both normal and cancerous) and maturation. It is important in wound healing, but significant elevation of the levels of this protein may indicate cancer. Epidermal growth factor is a small mitogenic protein that is thought to be involved in normal cell growth, oncogenesis, and wound healing. The EGF receptor has been implicated in the development and progression of a number of human solid tumors including those of the lung, breast, prostate, colon, ovary, head, and neck.

EPITHELIAL NEUTROPHIL ACTIVATING PEPTIDE 78(ENA 78)

Epithelial neutrophil activating peptide 78 (ENA 78) is a protein found in abundance in the synovial fluid and blood of patients with rheumatoid arthritis. ENA 78 levels may also be elevated in patients with non-small cell lung cancer. The epithelial neutrophil activating peptide 78 is a potent chemoattractant and activator of neutrophil function and is produced by many non-hematopoietic cell types. ENA 78 is also expressed by epithelial cells in patients with Crohn’s disease, ulcerative colitis, acute appendicitis, and allergic airway inflammation.

EPSTEIN-BARR NUCLEAR ANTIGEN ANTIBODY(EBNA)

The presence of antibodies against Epstein-Barr virus (EBV) may indicate recent infection with or exposure to this virus. Primary EBV infection is shown by rising IgG-VCA (viral capsid antigen) antibody levels and the appearance of antibody to early antigen (EA). If both IgG-VCA and EBNA antibodies are present, past infection is indicated. Using the standard immunofluorescent test, EBNA antibodies are not seen in the acute phase but slowly appear 2 to 4 months after infection and persist for life. However, some EBNA enzyme immunoassays can detect antibody within a few weeks of infection.

EPSTEIN-BARR VIRAL CAPSID ANTIGEN ANTIBODY(VCA)

The presence of antibodies against Epstein-Barr virus may indicate recent infection with or exposure to this virus. Primary EBV infection is indicated if IgM antibody to the viral capsid antigen (VCA) is present and antibody to EBV nuclear antigen (EBNA) is absent. If VCA antibodies are not detected, the patient is susceptible to EBV infection. If antibodies to both VCA and EBNA are present, then past infection (from 4 to 6 months to years earlier) is indicated.

EPSTEIN-BARR VIRUS EARLY ANTIGEN ANTIBODY(EA)

Epstein-Barr virus (EBV) is a common cause of colds. When infection with EBV occurs during adolescence or young adulthood, it causes infectious mononucleosis 35% to 50% of the time. The presence of antibodies against EBV indicates recent infection or exposure. Infections due to Epstein-Barr virus (EBV) are very prevalent in most populations. Primary infection in young children is often asymptomatic or accompanied by nonspecific, minor illness. In adolescents or young adults, primary infection manifests 35% to 50% of the time as infectious mononucleosis, which is usually self-limiting and characterized by fever, sore throat, myalgias, lymphadenopathy, and hepatosplenomegaly. EBV has also been associated with a variety of disorders in persons with AIDS; post-transplant patients may develop EBV lymphoproliferative syndrome. As with other herpes viruses, EBV establishes a lifelong dormant infection in the immune system. Late events in a very few carriers of this virus include Burkitt’s lymphoma and nasopharyngeal carcinoma. Eighty percent of patients with active EBV infection produce antibody to early antigen (EA). In the presence of antibodies to Epstein-Barr nuclear antigen, antibodies to EA suggest reactivation. However, a positive EA test does not automatically indicate that a patient’s current medical condition is caused by EBV. Many healthy people with no symptoms have antibodies to EA for years after their initial EBV infection. Reactivation is often subclinical.

ERYTHROPOIETIN(EPO)

Erythropoietin (EPO) is a protein hormone produced in the kidneys that promotes the production of red blood cells in the bone marrow. Elevated levels of EPO may be seen in patients with most kinds of anemia, while low levels are seen in chronic renal failure as well as other chronic conditions. Renal production of EPO is regulated by changes in oxygen availability; under conditions of hypoxia, the level of EPO in the circulation increases, leading to increased production of RBCs. Primary polycythemias, such as polycythemia vera, are caused by EPO-independent growth of erythrocyte progenitors from abnormal stem cells, and low-to-normal EPO levels are found in the serum of affected patients. Various secondary polycythemias are associated with the production of higher than normal levels of EPO. The overproduction of EPO may be an adaptive response associated with conditions that produce tissue hypoxia, such as living at high altitude, chronic obstructive pulmonary disease, cyanotic heart disease, sleep apnea, high-affinity hemoglobinopathy, smoking, or localized renal hypoxia. In other instances, excessive EPO levels are the result of production by neoplastic cells. Deficient levels of EPO are found in conjunction with certain anemias, including anemia of renal failure and end-stage renal disease, anemias of chronic disorders, chronic infections, autoimmune diseases, rheumatoid arthritis, AIDS, malignancies, anemia of prematurity, anemia of hypothyroidism, and anemia of malnutrition.

ESTRADIOL

Estradiol is the most potent natural estrogen (the major female hormone). Estradiol is responsible for growth of the uterus, fallopian tubes, and vagina; breast development; maturation of the external genitals; deposition of body fat in a female distribution; and ending linear growth during adolescence. Estradiol also stimulates the proliferation of the uterine lining in the first half of the menstrual cycle. Estradiol levels are used to assess fertility, amenorrhea (lack of menstruation), and precocious puberty in girls. Estradiol (estradiol-17, E2) is the most potent natural estrogen and circulates in plasma predominantly in a protein-bound form. In non-pregnant women, E2 is produced mainly by the ovaries. In men, the testes and androgen precursors are the principal source. E2 determinations have proved of value in a variety of contexts, including the investigation of precocious puberty in girls and gynecomastia in men. Principal uses have been in the evaluation of amenorrhea and in the monitoring of ovulation induction.

ESTRIOL, UNCONJUGATED

One of the three major naturally occurring estrogens, estriol is a hormone that is produced almost exclusively during pregnancy (by the placenta). Estriol measurement is used to establish fetal status and placental function during pregnancy and may be useful as an early indicator of Down syndrome. Maternal serum unconjugated estriol levels increase rapidly following the first trimester. Estriol circulating in maternal blood has a short half-life of 20 to 30 minutes, and variations in the production of estriol by the feto-placental unit are reflected rapidly in maternal serum; thus maternal estriol levels usually fall dramatically immediately before intrauterine fetal death. Although low estriol levels may be seen in a variety of fetal problems, measurement has been most useful in diabetic mothers, post-date gestation, and intrauterine growth retardation. Estriol measurements in the second trimester may also be used as an indicator of Down syndrome.