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Clinical Pathology

Types and Sources of Specimens

There are a great many clinical laboratory tests, and they are performed on blood, urine, sputum, and other body fluids, and occasionally feces (see table 4.1). Tests can be performed on whole blood (to which an anticoagulant has been added to keep it from clotting), plasma (the fluid that remains when whole blood is centrifuged to remove the suspended red and white blood cells), or serum (the clear fluid that separates from whole blood that has clotted).

Many of the substances that are measured in blood can also be analyzed in urine or other body fluids, although the results will have different reference (normal) ranges. For example, glucose, a form of sugar, is not normally found in urine, but it is in blood, where it is about twice as concentrated as it is in cerebrospinal fluid (the fluid that surrounds the brain and spinal cord).

Besides blood, urine, sputum, and cerebrospinal fluid, other body fluids commonly examined in clinical laboratories are bronchial or pleural washings (fluids from the lungs and bronchial tubes), gastric or stomach aspirations, serous (or peritoneal) fluids from the abdominal cavity, and joint fluids. The various methods for obtaining these various body fluids are described below.

Blood. Blood is most commonly drawn via venipuncture or finger sticks.

Venipuncture. Blood is usually drawn from a vein on the inside of the elbow. If your doctor orders this venipuncture procedure, the nurse or technician will first wrap a tourniquet (usually a rubber hose) around your arm above your elbow to compress the blood vessels and limit the flow of blood in the veins that would normally return to the heart. You will then be asked to make a fist, which will make your vein stand out more prominently. The skin on the inside of your elbow will be cleaned with a swab or piece of cotton dampened with alcohol, and a sterile needle inserted into your vein. A coupling device attached to the needle allows blood to be drawn automatically by vacuum pressure into rubber-stoppered tubes. When a tube is filled, it can be removed and additional ones attached, depending on the amount of blood needed.

The needle is then withdrawn from the vein, and the tourniquet removed if it hasn't been removed earlier. (Needles are always disposed of after one use so that there is no chance of spreading infection.) The entire procedure generally takes less than five minutes. You will be told to apply pressure to the puncture site with a piece of cotton for a few minutes. A small bandage may be placed over the site; this bandage can be removed in less than an hour. You should refrain from using your arm to carry heavy loads or do strenuous chores for about half an hour.

If for any reason blood cannot be drawn from an arm vein, the one inside your wrist or on the back of your hand can be used instead. For hospitalized patients, blood at times is obtained from the intravenous tubing used to deliver fluids directly into a patient's vein. Some tests are done on blood drawn from an artery instead of a vein, but these are rare. Because of the increased risk of bleeding, however, arterial blood is drawn by a doctor.

Preparation for blood drawing is minimal. You may be instructed to refrain from eating or drinking anything except water for about eight hours before blood is drawn. These so-called fasting specimens guard against interference from the elements in food or liquids that may cause inaccurate test results. Blood glucose and triglycerides (a constituent of fats) are examples of tests that should ordinarily be done on fasting specimens. For many, if not most, tests, however, nonfasting (random) specimens are fine.

The amount of blood that will be drawn depends on the total amount needed for a particular test, as well as the amount needed in each tube to mix with an anticoagulant or preservative to achieve the desired effect. While one or more tubes of whole blood may be drawn, usually only a fraction of it is needed, but that fraction may come from the whole blood, plasma, or serum. To put this in perspective, your body contains about 100 ounces, or 3 quarts, of circulating blood. A typical tube contains only about 1/3 of an ounce. A drop of blood, serum, or plasma is often enough to do one test, and sometimes many, on an automated instrument. This drop is equal to about 2/1000 of an ounce�a trivial amount compared to the total amount available in your body.

Finger sticks. If an even smaller amount of blood is needed (to check for anemia if you are planning to donate blood, for example) or if your veins are too small or too fragile for a venipuncture, blood can be obtained by sticking a finger with a small, sharp blade. This is frequently done in children. An earlobe or a heel (especially in newborns or infants) can also be used.

For a finger stick, the nurse or technician will wash your skin with alcohol and then make a quick prick with the blade designed to obtain blood from capillaries�hair-sized vessels that connect the smallest of veins to the smallest of arteries. He or she will then gently squeeze your finger to produce drops of blood that are gathered into micropipettes (tiny glass or plastic straws) or very tiny tubes. Because capillaries are so small, they usually produce only enough blood for a few tests, and the blood flow quickly ceases. There are no precautions to take after the test; you may not even need a bandage.

Urine. Urine for analysis can be obtained in several different ways. The most common method is a random (also called a "spot" specimen that is used for the standard chemical and microscopic urinalysis. It simply requires you to urinate into a cup, jar, bottle, or tube. The container must be thoroughly clean and dry, but it needn't be sterile. If the specimen is not directly examined, or sent within a few hours to a laboratory, it should be refrigerated.

A clean catch specimen requires that you thoroughly clean your external genital area with a mild soap and water and then dry off the area before urinating into a clean, dry container. This is because skin naturally contains bacteria that could obscure bacteria from your urinary tract or falsely indicate an infection. Your doctor will commonly ask for a clean catch specimen if a kidney or bladder infection is suspected.

If a sterile urine specimen is needed to identify a specific bacterium, a doctor or nurse will obtain it by catheterization. While you are lying down, a catheter�a thin, flexible tube�is inserted into the outer opening of your urethra, the tube through which urine from your bladder leaves your body. Urine is then drained into a sterile specimen container. This technique is often used for patients who cannot urinate voluntarily. If that is the case, the catheter may be left in place.

Sometimes your doctor may request a timed test, which measures the quantity of a substance excreted in the urine over a period of time�typically 24 hours, but occasionally two, six, or 12 hours. For a 24-hour urine test, you begin by voiding and discarding the first specimen. This is because the substance being measured has to be estimated over an exact period of time. Including the first specimen, which has been building up in your bladder over an unspecified amount of time, will throw off the measurement of the substance (such as a hormone) being tested. After discarding the first specimen, you collect the rest of the urine you void over the specified time period in a clean plastic jug, which may contain a preservative (for specific instructions, see chapter 12. In the laboratory, the total volume of urine is measured and an aliquot, or sample of the total volume, is used for the analysis.

Sputum and Other Specimens. Sputum (phlegm) is the product of a deep cough and can be collected directly into a clean, widemouthed plastic or glass specimen container. Sometimes you may be asked to cough directly into a Petri dish. This round, shallow glass or plastic dish with a cover contains a gel-like substance, or medium, in which bacteria will grow.

Other body fluids (cerebrospinal, pleural, abdominal, or joint) are obtained by aspiration. After a local anesthetic is injected or applied to your skin, a fine needle is injected into the appropriate body cavity or joint, and a small amount of fluid is aspirated (withdrawn). The fluid can then be examined for its microscopic cells or chemical constituents, or cultured for infectious agents.

Feces specimens need to be collected directly into a clean, dry cardboard or plastic container.

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Table 4.1
Common Clinical Laboratory Tests Clinical laboratories are typically divided into several specialty laboratories, which may include hematology, clinical chemistry, immunology and serology, microbiology, and the blood bank. The tests described in this table are arranged according to the laboratory in which they are usually performed (indicated in boldface).
Hematology: This laboratory examines the formed or cellular elements of blood, which include red blood cells, white blood cells, and platelets (cells necessary for clotting); the amounts of clotting factors; and the types and amounts of hemoglobin, the red pigment in red blood cells. Such disorders as anemias, hemophilia and other blood-clotting disorders, and leukemias are first diagnosed and then monitored in this laboratory. Organizationally, the urinalysis laboratory is often grouped with hematology. Urine is examined both chemically and microscopically.

Test What It Shows/What It's Used For
Complete blood count (CBC) (includes white blood cell count, red blood cell count, hematocrit, red blood cell morphology and indices) and differential (the proportion of the various types of white blood cells in the blood) Identifies anemias, some cancers such as leukemias and lymphomas; evaluates blood loss and response to infection. Sometimes only a part of the CBC is performed (eg, white blood cell count or hematocrit). Often used as a general screening test before surgery or as a part of a routine medical checkup.
Platelet count, fibrinogen Evaluates, diagnoses, and monitors bleeding and coagulation (clotting) disorders.
Prothrombin time (PT), partial thromboplastin time (PTT), and specific clotting factor assays Monitors anticoagulation therapy (PT, PTT); evaluates bleeding and coagulation disorders such as hemophilia.
Reticulocyte count Assesses red blood cell production.
Routine urinalysis (includes color; pH; specific gravity; turbidity; chemical analysis for occult blood, protein, ketones, and glucose; and microscopic examination of sediment for red blood cells, white blood cells, bacteria, crystals, and casts) Indicates kidney and bladder infections and other diseases, certain metabolic and systemic diseases, dehydration, and urinary tract bleeding.

Clinical chemistry: This laboratory is concerned primarily with measuring the amounts or concentrations of various chemical constituents of blood, and less often with simply identifying their presence. The scope of clinical chemistry is very broad, and many different tests can be done to assess various substances found in blood or urine. The major ones are listed below.
Enzymes: Levels of enzyme activity in blood help determine which organs are damaged or diseased and to what extent. When organs or tissues are damaged, enzymes leak out into the blood. The following are examples of enzymes produced by various organs:

Test What It Shows/What It's Used For
Heart
Creatine kinase (CK) Early marker for acute myocardial infarction (heart attack). Also present in skeletal muscle. CK-NB is a form of CK that is mostly found in the heart muscle and provides more specific information about heart damage.
Lactate dehydrogenase (LDH) Later marker for acute myocardial infarction. Present in all organs and also released into blood in disorders of liver, kidneys, red blood cells, and muscle. Isoenzymes, or forms of the enzyme that are specific for different organs, can help pinpoint the source of LDH elevations.
Liver
Alanine aminotransferase (AAT, SGOT) and aspartate aminotransferase (AST, SGPT) Elevated in many types of liver disorders including hepatitis. May also be abnormal with damage to several other organs or tissues.
Alkaline phosphatase Elevated in obstructive liver disease, in which excretion of bile by the liver is impaired. The causes include gallstones, tumors, and some forms and stages of hepatitis. Also elevated in bone disease, including Paget's disease, vitamin D deficiency (rickets), hyperparathyroidism, and cancer that has metastasized to the bone. Because their bones are growing, healthy children have higher values than adults.
Pancreas
Amylase and lipase Elevated in inflammation of the pancreas (pancreatitis), and less often in cancer of the pancreas.

Hormones: Hormone levels in the blood are used to evaluate the function of various endocrine glands and can indicate hyper- (over) and hypo- (under) activity.

Test What It Shows/What It's Used For
Cortisol Adrenal gland function.
Catecholamines Adrenal gland: elevated with uncommon tumor of adrenal gland that can cause hypertension.
Thyroxine (T4), TSH, T4 indices Thyroid gland function.
ACTH, FSH, LH, GH (growth hormone), TSH Pituitary gland function; directly relates to function of adrenal glands, sex glands, and thyroid gland.
Parathormone Parathyroid gland function.

Lipids and lipoproteins: These help evaluate risk of coronary heart disease. They are also sometimes used as markers of liver disease and nutritional status.

Test What It Shows/What It's Used For
Cholesterol General but not absolute marker of coronary heart disease risk.
High- and low-density lipoprotein cholesterol (HDL and LDL) Breakdown of cholesterol that provides better estimate of risk than does total cholesterol alone.
Triglycerides With cholesterol, used to evaluate coronary heart disease risk.

Proteins: These reflect metabolic and nutritional status in a wide variety of disorders, and overproduction in some cancers.

Test What It Shows/What It's Used For
Albumin Reduced in some forms of liver and kidney disease, and in malnutrition.
Globulins Elevated in some chronic infectious and inflammatory illnesses and some blood cancers. This test includes globulins or antibodies produced by the body in response to infections and allergens. Abnormal globulins can be detected in multiple myeloma and related disorders. Protein electrophoresis fractionates serum proteins into various classes, which allows for more specific diagnoses.

Electrolytes: These tests help to identify and evaluate such metabolic disorders as acidosis, alkalosis, malnutrition, dehydration, and various bone, kidney, and endocrine gland disorders. Results of these tests are nonspecific, and can be abnormal in a variety of disorders too numerous to include here (although a few are listed in table 4.2). Electrolytes are also affected by megadoses of vitamins and minerals, and by such drugs as diuretics and antacids.
Marked abnormalities in electrolytes can have important, and sometimes urgent, medical consequences and therefore require rapid intervention and treatment. In seriously ill, hospitalized patients, these tests may need to be monitored frequently, so that any abnormalities can be quickly corrected.
Electrolytes, which may vary individually or in concert with each other, are often measured in a group. The term usually refers to sodium, potassium, chloride, and bicarbonate (some labs report CO2 instead), but may also include calcium, phosphorus, and magnesium.
Blood glucose (blood sugar): The glucose tolerance test is used to assess the handling of glucose by the body. In one form of diabetes (Type 1), it reflects insulin release by the pancreas. In the other (Type 2), it reflects insulin sensitivity of various body tissues, such as liver and muscle. It is also used to assess low blood glucose, although less frequently.

Test What It Shows/What It's Used For
Glucose, fasting Diagnoses and monitors diabetes mellitus, evaluates and diagnoses other disorders of carbohydrate metabolism, and diagnoses hypoglycemia (low blood sugar).
Glucose tolerance test Follow-up test that allows more specific diagnosis of diabetes mellitus after finding elevated fasting blood glucose levels.

Other metabolic products:

Test What It Shows/What It's Used For
BUN (blood urea nitrogen) and creatinine Measures these metabolic waste products eliminated by the kidneys. Elevated when kidney filtration function is impaired and in dehydration.
Uric acid Measures these metabolic waste products derived from proteins. Elevated in gout, in some forms of kidney disease, and with excessive tissue destruction.

Vitamins and trace elements: Vitamin and trace element (mineral) levels can indicate deficiencies that can be responsible for anemias and nervous system and metabolic disorders, as well as excess due to industrial or environmental exposure, which can result in symptoms and signs of toxicity or poisoning. (For testing for substance abuse, see chapter 29.

Test What It Shows/What It's Used For
Folic acid Evaluates anemia.
Vitamin B12 Evaluates anemia and neurological symptoms.
Other vitamins (thiamine, C) Only very rarely measured to evaluate various unexplained symptoms consistent with vitamin deficiency.
Lead Unexplained anemia and/or neurological symptoms. Screening of infants and young children for environmental exposure.
Mercury, arsenic Unexplained neurological symptoms; suspicion of poisoning.

Immunology and serology: This laboratory is involved with identifying antibodies (proteins produced in the body in response to an antigen, which can be an infectious agent, virus, toxin, or other foreign substance) or in the diagnosis of autoimmune diseases (antibodies against the body's own tissues) and immunodeficiency states (indicative of an underactive immune system).

Test What It Shows/What It's Used For
Antibodies to infectious agents Exposure to various infectious agents.
Antinuclear antibodies, complement, autoantibodies Autoimmune diseases, especially systemic lupus erythematosus.
Antistreptolysin O titer Streptococcal infection, acute rheumatic fever, acute glomerulonephritis, and other streptococcal enzymes.
Heterophil agglutinins and monospot test Infectious mononucleosis.
Human leukocyte antigen (HLA) Correlation with disease syndromes, paternity exclusion testing, and transplantation donor and recipient matching (tissue typing).
Immunoglobulins Immunodeficiency states and certain malignancies, especially multiple myeloma.
Rheumatoid factor Arthritis classification and diagnosis of rheumatoid arthritis.
VDRL (Venereal Disease Research Laboratory) Syphilis; if positive, must be confirmed with a more specific test.

Microbiology: This laboratory is responsible for the diagnosis of infections by isolating and identifying infectious agents in blood, urine, sputum, feces, cerebrospinal fluid, and other body fluids, and for testing for their sensitivity to various antibiotics used to treat these infections. Bacteria, viruses, parasites, and fungi are identified by using such techniques as staining, microscopic examination, and chemical, immunological, and genetic tests.

Test What It Shows/What It's Used For
Acid-fast stain Identifies bacteria that cause tuberculosis and monitors therapy.
Blood culture Septicemia or "blood poisoning" (bacterial infection of the blood).
Gram stain Identifies disease-causing microorganisms including fungi in body fluids and wounds.
Microscopic stool examination for ova and parasites Identifies disease-causing parasites such as amoebae, pinworms, hookworms, etc.
Sputum culture Identifies disease-causing organisms of the lower respiratory tract; evaluation of pneumonia and bronchitis.
Routine culture and sensitivity (of many body fluids or sites and wounds) Isolates and identifies disease-causing organisms; tests for effective antibiotic therapy.
Cell culture Identifies disease-causing viruses.

Blood bank: This area is responsible for the selection and preparation of appropriate, compatible blood components (red blood cells, platelets, and plasma) that are safe for transfusion into patients. Blood products are also tested to be sure they are free from infectious diseases such as HIV and hepatitis viruses B and C. This laboratory also evaluates transfusion reactions by diagnosing their cause, determining whether or not it is safe to proceed with a transfusion, and selecting further components that are safe for transfusing. The blood bank may have a donor service to draw units of blood for general use and for autologous transfusions (for elective-surgery patients who wish to donate their own blood before surgery so that it will be available to them if they need it).

Test What It Shows/What It's Used For
ABO group and Rh type, or type and cross match Establishes blood group (A, B, AB, or O) and Rh type (positive or negative) to ensure compatibility of transfused blood between donor and recipient.
Antibody screening Ensures that blood is safe for transfusion.
Direct Coombs' Tests for antibodies on surface of red blood cells in autoimmune hemolytic anemias, transfusion reactions, and erythroblastosis fetalis (newborn hemolytic disease).

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Laboratory Profiles

When you go for a routine checkup or for evaluation of a specific symptom, your doctor will often order a set list of tests called a laboratory, chemical, or biochemical profile. This standard series of tests is done on a single blood or urine specimen. The reasoning behind this is that screening tests occasionally lead to an unsuspected finding, and with modern automated instruments, as many as 30 common tests can often be done for the same cost as four or five tests ordered separately. Although laboratories differ, the most common component tests are among those described in the laboratory sections of this chapter (for a typical group of tests, see table 4.2).

The value of laboratory profiles is somewhat controversial, however, since such broad screening tests rarely lead to the diagnosis of unsuspected illnesses. Moreover, they can result in abnormal findings in the absence of disease, possibly leading to unnecessary workups. The trend among doctors now is to be very selective and to order tests based only on specific patient complaints. In fact, since March 1996, Medicare policy has been to cover only specific blood tests considered medically necessary based on symptoms, family history, or risk profiles for a specific disease. Although many private health insurers continue to pay for laboratory profiles, such organizations as the American College of Physicians (ACP) recommend that they not be done on healthy patients without specific risk factors.

A more effective variation of the general profile concept is an organ profile. This is ordered when a patient has symptoms that suggest a disease of a specific organ or organ system. Common examples would be a liver profile, a lipid profile, or a thyroid profile. In these instances, the tests comprising the profile, when considered in the context of one another, provide a much more complete picture of the condition of an organ or organ system than any single test by itself. In a sense, a complete blood count (CBC), which includes a hematocrit, red and white blood cell counts, a hemoglobin measurement, and a white blood cell differential, can be considered a hematology profile. Similarly, profiles can be customized according to a clinical problem.

Testing Technology

Automation and computerization have increased dramatically in clinical pathology laboratories, allowing lab staff to keep up with the high volume and array of tests now available. Conversion from manual to automated procedures means that tests can be done rapidly, in large batches, with very small or "micro" amounts of specimens, and by fewer staff. The computer-calculated results are highly accurate because the potential for human error that can occur with each step of multiple-step processes has been eliminated.

Many clinical chemistry tests are routinely processed on large instruments called multichannel analyzers, by only one or two technicians, generating up to 20 different test results per minute on a single patient's blood specimen. Various instruments allow for about 80% of tests in clinical chemistry to be highly automated. The remaining 20% of technically complex and highly specialized tests that are less automated or performed manually can consume more than half of laboratory staff time.

Automation has not only enhanced speed and accuracy, but has also allowed computerized reporting of test data. Often different analyzers from different laboratories can be linked, enabling laboratories to produce a single report of a patient's tests from all laboratories. For hospital patients these reports can be generated daily, or even more frequently, and can show data from previous days for purposes of comparison or creating comprehensive records. Results from the laboratory can even be displayed directly on terminals in patient care units.

Clinical laboratories use all of the technologies described below in analyzing test data.

Immunoassays. This group of laboratory techniques is used to identify such diverse substances as infectious diseases, hormones, vitamins, drugs, cardiac enzymes, and antigens (proteins) associated with cancer. These techniques are exquisitely sensitive and, in some instances, capable of measuring less than a billionth of a gram of a biological substance.

Immunoassay technology is based on the antigen-antibody response, that is, the ability of the body to develop antibodies (proteins made by the immune system) to protect against antigens (proteins on the surface of invaders such as bacteria, viruses, or allergens). Since there is a specific antibody for each specific antigen, it is possible to test for one using the other. That is, if one is placed in close proximity to the other, such as happens when a small amount of a known antigen is placed in a test tube that is then filled with blood that contains an antibody for it, they will bind together and can be identified by using a special marker.

Immunoassay testing relies on tagging antibodies or antigens with different markers such as radioisotopes, enzymes, or fluorescent chemicals, in order to make the substance tested for visible. For example, in radioimmunoassay (RIA), the antigens are tagged with a radioisotope; in some nonisotopic immunoassay, with a special dye that shows up as glowing particles under a fluorescent microscope. In enzyme-linked immunosorbent assay (ELISA)�an increasingly popular technique used in such diverse circumstances as testing for allergies and antibodies to the HIV virus�the antibodies are tagged with enzymes.

There are many types of immunoassays. In addition to RIA and ELISA, the most common ones include enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay, and enzyme immunoassay.

Spectrophotometry. This technique measures the intensity of color formed when the substance being tested for reacts with added chemical reagents. It is the basis for most automated tests performed on multichannel analyzers. Applications vary from highly automated tests to simple procedures for blood sugar testing that can be performed at home.

Electrophoresis. This technique is based on the differences in movement of electrically charged particles under the influence of an electrical current. The size, shape, and electrical charge of the particles will affect the direction, distance, and rate of movement and can be used to distinguish between two substances, such as different proteins. There are several variations on this technique, including the following:

Serum protein electrophoresis. Separates serum proteins, which is useful in diagnosing and monitoring multiple myeloma and related disorders, evaluating and monitoring chronic inflammatory conditions, and evaluating and managing kidney disease, liver disease, and nutritional status.

Immunoelectrophoresis. Proteins are separated in an electrical field and further identified by reaction with specific antibodies. This is most often used for diagnosing and classifying multiple myeloma, and also for diagnosing some immunodeficiency states.

Hemoglobin electrophoresis. Separates the various types of hemoglobin (red pigment in red blood cells). Used in diagnosing sickle-cell anemia, thalassemia, and related congenital blood disorders.

Chromatography. A technique for separating substances on the basis of their molecular size, or physical or chemical properties, which is used to measure drugs, some proteins, and hormones, among other substances. Variations of this technique are based on the medium in which the chromatography is performed. These include high-performance liquid chromatography (HPLC), thin-layer chromatography (TLC), and gas-liquid chromatography (GLC).

Mass Spectrometry. In combination with chromatographic techniques described above, this technology makes possible very specific identification and measurement of substances on the basis of their physical structure. It is widely used in screening for illicit drug use, to provide definitive confirmation when an initial immunoassay screen is positive.

Atomic Absorption and Flame Emission Spectrometry. When a solution is converted to the gaseous state in a hot flame, dissolved metals, depending on the conditions, will either emit or absorb light at a wavelength that is characteristic of that element. A type of spectrophotometer measures the amount of light emitted or absorbed. Many trace metals can be measured by these techniques, including the amount of lead in the blood, a measurement of great importance in pediatrics.

Specific Ion Electrode. The potential, or voltage, of specially designed electrodes is altered when exposed to certain elements (ions) in the blood that are critical for normal metabolic functioning. The current generated by the electrode is a measure of the amount of the substance present. This technology is used in many multichannel automated analyzers, as well as smaller instruments that are devoted to urgent laboratory services. Critically important tests that employ specific ion electrodes include those used to measure levels of the electrolytes sodium, potassium, bicarbonate, and calcium.

Automatic Blood Cell Counters. Used in the hematology laboratory for automated counting and typing of blood cells (CBC). These are commonly used for evaluating and monitoring anemia, infection, bleeding, leukemias, and cancer chemotherapy, for screening before surgery, and for general health screening.

Flow Cytometry and Molecular Diagnostics. Two relatively new techniques that are used in both anatomical pathology and clinical pathology laboratories. (For more information, see the discussion of new diagnostic technologies below.)

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Table 4.2
Common Blood Profile Tests and What They Most Often Mean Test Increase May Mean Decrease May Mean
Albumin N/A. Malnutrition; liver or kidney failure; gastrointestinal malabsorption.
Alkaline phosphatase Liver disease; biliary tract disease; some bone diseases. Rare congenital disease.
Bilirubin Liver disease; hemolytic anemia. N/A.
BUN (blood urea nitrogen) Kidney failure; dehydration, blood in gastrointestinal tract. Liver failure.
Calcium Parathyroid gland hyperfunction; thyroid gland hyperfunction, certain cancers; various bone diseases, Vitamin D intoxication. Kidney failure, parathyroid gland hypofunction; malnutrition; Gl malabsorption; Vitamin D deficiency.
Chloride Acid-base imbalance resulting from gastrointestinal, adrenal, and renal disease. Gastrointestinal loss; some kidney disease; adrenal gland hyperfunction, acid-base imbalance.
CO2 Acid-base imbalance from a variety of causes including respiratory failure and vomiting. Acid-base imbalance from a variety of causes including kidney disease, diabetic acidosis, and diarrhea.
Creatinine Kidney failure; dehydration. N/A.
Glucose Diabetes mellitus; adrenal gland hyperfunction; intravenous glucose fluids. Excess insulin, liver failure, adrenal gland hypofunction, starvation.
Phosphorus Kidney failure; parathyroid gland hypofunction. Parathyroid hyperfunction; malnutrition; Gl malabsorption; vitamin D deficiency.
Potassium Kidney failure; adrenal gland hypofunction; acid-base imbalance. Diuretic therapy; diarrhea; vomiting; adrenal gland hyperfunction; acid-base imbalance.
SGOT (AST) Liver disease or damage; heart injury; muscle injury. N/A.
SGPT (ALT) Liver disease. N/A.
Sodium Dehydration; adrenal gland hyperfunction; some kidney disease; diabetes insipidus. Kidney failure; adrenal gland hypofunction; gastrointestinal loss; diuretics; overhydration; kidney, liver, and heart failure.
Total protein Multiple myeloma; chronic infection or inflammation. Malnutrition; liver or kidney failure; gastrointestinal malabsorption.
Uric acid Gout; kidney failure; some blood malignancies; tissue destruction. Some uncommon congenital diseases.

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Test Results and Interpretation

Test results from clinical pathology laboratories are usually represented as numbers, or occasionally, as positive or negative, meaning that the substance or disorder being tested for is or is not present. The numerical values are usually expressed as the amount of a substance present in a given quantity of body fluid. For example, the amount of phosphorus is given in milligrams per deciliter (100 mL) of blood (mg/dL).

For most numerical values, there is a range of what is considered normal. These so-called reference ranges can vary with such factors as sex and age. For example, the normal concentration of serum alkaline phosphatase, a bone enzyme, may be up to three times greater in growing children than in adults. Reference ranges can also vary according to the population being considered. For example, hospitalized patients may have a range of results that differs from that of healthy outpatients.

Although reference ranges are often relatively wide, any given individual may have a narrower range of what is normal. Thus, you may have a test result that falls within the normal range for the general population and still have a disorder. There is no way to perfectly estimate ranges because, in general, only 95% of a population is statistically described by a reference range. Thus, it is also possible for the remaining 5% to fall outside a reference range and still be healthy.

Finally, reference ranges can vary from laboratory to laboratory, depending on the technology used to analyze test results. For these reasons, reference ranges are not given in this book.

Specificity and Sensitivity. The most reliable tests are those that are both sensitive and specific, and thereby minimize the incidence of false-positive and false-negative results. "Sensitivity" refers to the ability of a test to correctly identify individuals who have a given disease or disorder. "Specificity" refers to the ability of a test to correctly exclude individuals who do not have a given disease or disorder.

A false-positive result indicates a disease in a patient who in fact does not have the disease, and these must be minimized to achieve high specificity. A false-negative result indicates that there is no disease in a patient who does have the disease, and these must be minimized to achieve high sensitivity.

An ideal test that is 100% sensitive and specific would detect everyone with a given disease but no one without it. Few, if any, tests achieve this, although many come close. Yet even with the most specific and sensitive tests, misapplication can cause difficulties. For example, even a highly specific test used in a segment of the population that is known to have very few cases of a disease (defined as a low prevalence) can have a high likelihood of yielding a false-positive result in healthy individuals. An illustration of this would be the PSA test for prostate cancer performed on males less than 40 years old: many of the positive results will be false.

Tests are only a piece of the diagnostic process; your doctor's judgment is critical. Presented with clinical laboratory results, your doctor must interpret the information in the context of your history and physical examination, as well as other diagnostic tests. If your test results are negative but your doctor suspects (based on your symptoms and complaints and the physical exam) that you have a specific disease, he or she may elect not to rule it out but to repeat the test or order a different test for the same disorder. The results of several tests taken together can provide a better evaluation of a disorder than a single test alone.

Alternatively, if you have an abnormal test result but no signs or symptoms of a particular condition, your doctor may suspect a false-positive result, which might be caused by elements in your diet or a medication you're taking, or simply because you're one of a small percentage of the population that falls outside the reference range. Finally, if your tests were ordered for monitoring purposes, your doctor may consider changes in results to be more important than any absolute value.

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DID YOU KNOW?

Blood-drawing tubes are color-coded by stopper, indicating the type of anticoagulant or preservative they contain. For example:

"Red tops" contain no anticoagulant; thus they allow the blood to clot so that serum can be drawn off.
"Lavender tops" have an anticoagulant to prevent the blood from clotting.
"Gray tops" contain a preservative that prevents the breakdown of glucose, a blood sugar.

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PATIENT TIP

Medications can interfere with some tests. Always advise your doctor of any drugs you are taking. Sometimes a medication must be stopped before a test is performed, but usually notification is all that is necessary.

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DID YOU KNOW?

The development of immunoassay technology was considered so significant that its inventors were awarded a Nobel Prize. This technology has become so ubiquitous that it is done manually in specialized laboratories, on automated instruments, in doctors' offices, and in some instances, even at home, as is the case with over-the-counter pregnancy tests.

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PATIENT TIPS