Laboratory Tests and Values

Abbreviations

Recommended units for clinical laboratory data are provided in Box 40-1. The Joint Commission’s official “do not use” list of abbreviations is listed in Table 40-1. The list was originally created in 2004 by The Joint Commission as part of the requirements for meeting National Patient Safety Goal (NPSG) requirement 2B, which required a standardized list of abbreviations, acronyms, and symbols that are not to be used throughout the organization.

APACHE

The acute physiology and chronic health evaluation (APACHE), a system for prognosis development for critically ill patients, has been developed using a number of lab and other values. Based on data entered regarding admission diagnosis, age, health history, and the physiologic measurements taken during the first 24 hours, a predicted death rate is calculated. Length of stay in the intensive care unit (ICU) can also be predicted.

Measurements include body temperature, mean arterial pressure, heart rate, respiratory rate, partial pressure of arterial pressure, hematocrit, white blood cell (WBC) count, arterial pH, Glasgow coma scale, and serum bicarbonate, potassium, and creatinine.^70,88 Newer variables (use of mechanical ventilation and thrombolytic therapy) and adjustment to the equations used for predictions have been used to generate the latest version (APACHE IV).⁸⁹

Purpose

Laboratory tests may be used by the physician for screening (searching for an occult disease process in an otherwise healthy person), diagnosis (identifying the cause of symptoms), or monitoring (following the progress of a disease).⁶³ A single test may be used differently in different people, depending on the need for information. For example, a glucose test may be used diagnostically or as a monitoring test.

Screening tests may be used on populations in an effort to find individuals at risk for certain diseases (e.g., those with high cholesterol who could benefit from treatment before disease manifestations become evident). Screening is also done for genetic or metabolic diseases to find individuals before disease occurs. State laws generally require routine screening in newborns for a number of disorders, notably phenylketonuria, sickle cell disease, and hypothyroidism.

Certain lab tests are very sensitive and specific for certain pathologic conditions, whereas others may only provide one piece of evidence suggesting a health problem without actually providing a certain diagnosis. For the therapist, laboratory values assist in deciding whether therapy can be provided at that time, should be scaled back, or should be more aggressive.¹⁷

Some lab values are clear contraindications for receiving therapy, whereas others are suggestive that therapy provided should be less physiologically demanding. The therapist must work with other members of the health care team to determine what aspects of therapy should be held until physiologic improvement, what should be modified, and what should be done in place of the prescribed treatment plan.³¹ For example, an individual who is short of breath with blood gas values that indicate no physiologic reserve for increasing metabolic demand should not undergo therapy that involves activity; other aspects may be addressed such as positioning, pressure relief, and educating caregivers. Note also that different physicians or facilities may adopt criteria for holding therapy that vary from those suggested in the text.

Limitations of Lab Testing

Although lab tests are generally reliable, a number of issues must be addressed. First, samples used for lab analysis may be contaminated, mishandled, or mislabeled, and testing materials and techniques may be flawed. Values obtained by tests reflect the status of the person at the time the sample is obtained.

The condition of the individual may fluctuate so that a sample taken at a given time does not reflect the person’s current condition, resulting in a false positive or false negative result. Results may be influenced by medications or drugs; sex; age; weight; physiologic changes, such as pregnancy; and fluid status. The range of values for a given test in a healthy person is known as the reference range or expected value, formerly known as the normal range. The reference range depends on the methods used for the test and must be compared against the reference range specific to that laboratory.

Reference ranges may vary among different laboratories; this variability is even more obvious in the values reported as reference ranges among various laboratory textbooks. The reference values or “normal” ranges provided are not meant to be memorized and applied as a standard to every case. The reference ranges provided in this chapter give the therapist a general idea of the values expected for each test, but interpretation of specific individual values must be done using the laboratory reference values (usually provided on most laboratory reports) not these figures.

Each laboratory will include a means of assessing the results—sometimes by placing L for low or H for high after a test result or by providing the range of reference lab values for the tests performed. Certain tests may have limited predictive value. The positive predictive value of a test depends on the prevalence of the disease in a population. The less prevalent the disease, the less accurate laboratory results may be.

A test may fail to produce a result that would indicate an abnormal condition that truly exists (false negative) or the results may falsely indicate that an abnormal condition exists (false positive). Statistically, as the number of tests performed on a single individual increase, the possibility of an incorrect conclusion also increases, whether the person is sick or not.⁴⁵ This phenomenon is purely related to chance because a significant margin of error arises from the arbitrary setting of limits for normal or reference values. Laboratory tests are frequently “rechecked” in order to ensure a higher degree of diagnostic accuracy.

Sodium

Sodium is a critical determinant of fluid volume in the body. Under normal circumstances, increases in the amount of sodium in the body lead to retention of water and a loss of sodium leads to loss of water in the body. Changes in plasma sodium concentration indicate a loss of homeostasis. Sodium concentration may be altered by excessive infusion or ingestion of water or excessive production of antidiuretic hormone. Sodium concentration may increase when excessive water is lost from the body such as in profuse sweating or decreased antidiuretic hormone (ADH) production (diabetes insipidus). Increased fluid volume increases blood pressure and may increase cell volume. Neurons are especially vulnerable to cell swelling, leading to neurologic dysfunction, possibly progressing to coma or death.

Potassium

Potassium is particularly important for function of excitable cells (e.g., nerve, muscles, and heart). The heart muscle is most susceptible to potassium disturbances, and arrhythmias and cardiac arrest can result from hypokalemia or hyperkalemia. Abnormal values in either direction can lead to cardiac rhythm disturbance and muscle weakness or irritability. Potassium measurements provide useful information about renal and adrenal disorders and about water and acid-base imbalances. Potassium acts as a part of the body’s buffer system regulated by its excretion through the urine.

Chloride

Chloride levels tend to change along with changes in sodium and water (H₂O). Bicarbonate ion (HCO₃⁻) is a critical component of acid-base balance. HCO₃⁻ acts as a buffer, preventing changes in plasma pH. Low HCO₃⁻ occurs in conditions that produce metabolic acidosis such as diabetic ketoacidosis. Respiratory compensation for metabolic acidosis results in loss of carbon dioxide (CO₂) from the plasma, which in turn reduces the amount of HCO₃⁻ from the plasma.

Bicarbonate works as buffer as a result of the equilibrium reaction of CO₂ + H₂O yielding H₂CO₃, which in turn is in equilibrium with HCO₃⁻ + hydrogen (H⁺). Exhaling CO₂ is the equivalent of losing an equal number of H⁺. Conversely, slowing ventilation allows CO₂ and thereby H⁺ to accumulate in the blood and lower pH. The renal system also contributes to pH regulation by altering the amount of H⁺ that passes in the urine and by synthesizing HCO₃⁻.

Renal compensation is slower to correct pH, requiring several days, as opposed to the more rapid respiratory response. The ability to regulate pH can be compromised by either respiratory or renal disease. Hypoventilation allows carbon dioxide and thereby acid to accumulate. Renal disease decreases the ability of the kidney to selectively alter fluid concentration, usually resulting in acidosis. Table 40-3 provides lab values that indicate whether acidosis or alkalosis is metabolic or respiratory and whether it is compensated. Further discussion of acid-base balance in disease may be found in Chapter 5.

Magnesium

Magnesium, like calcium, is involved in regulation of excitable cells but is not part of the BMP and is ordered separately. Low magnesium also results in arrhythmias, weakness, muscle spasms, and numbness. Magnesium (see Table 40-2) may be reduced in diabetes; with the use of diuretics; as a result of chronic vomiting or diarrhea; and may be increased by renal failure, hyperparathyroidism, or hypothyroidism.

Blood Glucose

In addition to the BMP, blood glucose may be measured under particular conditions to diagnose a suspected alteration in glucose homeostasis. Reference values for glucose testing are shown in Table 40-4. Fasting blood sugar (FBS), as the name implies, is done after fasting (at least 8 hours). Not eating overnight should allow blood sugar to fall to normal, whereas a random measurement may be elevated by eating close to the time of the test.

Another test is the 2-hour postprandial blood sugar (PPBS); 2 hours should be sufficient time for blood glucose to return to normal following eating. Another test, the oral glucose tolerance test (OGTT) involves con- sumption of a fixed amount of glucose and measurement of blood glucose at fixed intervals afterward to determine how quickly blood sugar can be brought back to normal. A person with a normal response will have a modest elevation in blood glucose after 1 hour and a return to normal by 2 hours. Blood glucose in an individual with either a lack of insulin or lack of insulin response will remain elevated after more than 2 hours.

A test for long-term glycemic control (ability to maintain a steady blood sugar concentration) is glycosylated hemoglobin (HbA_1C). The amount of glycosylated hemoglobin measured in the red blood cells (RBCs) depends on the amount of glucose available in the bloodstream over the 120-day lifespan of the RBC, thereby reflecting the average blood sugar level for the 100-to 120-day period before the test.

The A_1C test determines the fraction of hemoglobin containing bound glucose and reflects the average blood glucose concentration over a number of weeks to months, as opposed to the snapshot view provided by blood glucose monitoring. The more glucose the RBC was exposed to, the greater the HbA_1C percentage. An important advantage of this test is that the sample is not affected by short-term variations such as food intake, exercise, stress, hypoglycemic agents, or compliance. The HbA_1C measurement is now used more frequently than the 2-hour PPBS in monitoring people with diabetes.

Oral hypoglycemic agents are usually recommended when A_1C levels are greater than 7.0%. People with HbA1c concentrations less than 5% have the lowest rates of cardiovascular disease and mortality.³⁶ See Chapter 11 for further details.

Blood Urea Nitrogen and Creatinine

BUN and creatinine (see Table 40-2) are used to evaluate kidney function in individuals with kidney failure, for differential diagnosis if kidney disease is suspected, to monitor treatment of kidney disease, and to monitor kidney function while clients are using certain drugs.¹ Creatinine is a normal waste product related to creatinine phosphate, a mechanism of regenerating adenosine triphosphate (ATP) in skeletal muscle. Normally, the amount of creatinine in the blood is kept at a normal level by clearance in the kidneys. Because release of creatinine into the blood from muscle remains constant, a rise in serum creatinine usually represents a decline in the kidney’s capacity for excreting wastes.

The rise in creatinine levels is directly correlated with the amount of loss of nephron function. With aging, there is a decrease in lean body mass (muscle tissue), possibly resulting in decreasing creatinine values. However, serum creatinine may remain normal in an older person even with significant declines in creatinine clearance and renal function because of the decline in lean body mass.

Causes for elevated creatinine may include glomerulonephritis, pyelonephritis, acute tubular necrosis, obstruction by prostate disease or kidney stones, or decreased renal blood flow. Creatinine may also be elevated as a result of excessive release of creatinine caused by muscle injury.

BUN also rises with decreased renal function, caused in particular by decreased renal blood flow, as opposed to decreased glomerular filtration (creatinine). Because BUN reflects a balance of nitrogen added to the blood and excreted by the kidney, BUN may be elevated by increased protein catabolism or dietary intake of protein.

Gastrointestinal bleeding will increase BUN because of the breakdown of protein from the blood within the gastrointestinal tract. The synthesis of urea also depends on the liver. People with severe primary liver disease will have a decreased BUN. With combined liver and renal disease (as occurs in hepatorenal syndrome), the BUN can be normal, not because renal excretory function is good but rather because poor hepatic functioning resulted in decreased formation of urea.

Hepatic Function Panel

The liver is one of the first organs exposed to bacteria and toxins in the bloodstream; when the liver is not functioning well, these substances may reach the heart and lungs. This is one reason why people with liver failure are at high risk of multiorgan dysfunction syndrome (MODS; also known as multiple organ failure syndrome [MOFS]) (see Chapter 5). Since no one liver function test can pinpoint the specific liver dysfunction, physicians rely on various tests and measures in conjunction with clinical observations and other diagnostic tests (Table 40-5).

Measuring transaminases (enzymes) released into the blood from liver cells when they are damaged provides information about liver function and, in particular, the amount of inflammation in the liver. For example, ALT is an enzyme that serves as a sensitive indicator of hepa- tocellular damage; it is the primary test for detecting hepatitis.

ALP is related to the bile ducts and is increased when they are blocked and may indicate gallbladder, liver, and bile duct disease¹ but may also be elevated from increased bone turnover in chronic renal failure.⁴⁶ ALP may be elevated in diseases other than liver injury. Increased levels of this enzyme may indicate hyperparathyroidism, Paget’s disease of bone, or rheumatoid arthritis. It is also elevated in biliary obstruction or with hepatocytic carcinoma.

AST is found in the liver and also in the heart and skeletal muscles and historically had been used for differential diagnosis of chest pain. Bilirubin is measured as either total bilirubin, or direct bilirubin and indirect separately to determine the cause of elevated bilirubin. Total bilirubin can be elevated by liver disease or other causes such as bile duct occlusion and hemolytic anemia. Levels of albumin and total protein reflect the ability of the liver to synthesize proteins.¹

ALT, AST, GGT, and LDH are elevated with injury to hepatocytes. LDH may be elevated by injury to other tissues, such as myocardial infarction, or by cancer cells. Therefore elevated LDH may raise the suspicion of metastatic disease, particularly osteosarcoma.

Red Blood Cells

RBC count (or a simpler means of assessing the capacity of the blood to carry oxygen such as hemoglobin [Hgb] concentration or hematocrit [HCT]) correlate with a person’s endurance and orthostatic tolerance. A relative decrease in the capacity of blood to carry oxygen is termed anemia. Several additional tests may be required to determine the cause of anemia, including intrinsic factor, vitamin B12, and folic acid, which are necessary for erythropoiesis. Mean cell volume, mean cell Hgb, red cell distribution width (variation in RBC size), presence of immature cells (reticulocytes), and ferritin may be necessary to diagnose the cause of anemia.

Ferritin is an intracellular store of iron. Its value declines in anemia caused by chronic iron deficiency and severe protein depletion (e.g., burns or malnutrition). Elevation of ferritin is also used as an indicator of states of chronic iron excess such as hemochromatosis.¹

Men with essential hypertension may have a high prevalence of increased iron stores and metabolic abnormalities that are part of the insulin-resistance–associated hepatic iron overload syndrome (IRHIO).⁶⁰ In general, individuals with elevated ferritin are at increased risk for insulin-resistance syndrome.^21,86 A major limitation to the test for ferritin levels is the fact that ferritin can be elevated in conditions that do not reflect iron stores such as acute inflammatory diseases, infections, and metastatic malignancies.

White Blood Cells

WBC count can be provided as a total, a count of individual types of leukocytes, or subtypes of leukocytes. WBCs may either increase or decrease in disease. In general, an increase suggests infection or other inflammatory response. WBC count may decrease as a result of bone marrow disease or chemotherapy for cancer or to prevent transplant rejection.

The primary therapy implications are related to the presence of infection with elevated leukocyte count (leukocytosis) or risk of patients/clients becoming infected with a low WBC count (leukopenia). In particular, neutropenia is a risk factor for nosocomial infection. Facility policy may require supply of individual equipment, air filtration systems, gowning, gloving, and facemasks.⁸⁴

Platelets

Platelet count is decreased by excessive bleeding, coagulation disorders, autoimmune disorders, or histocompatibility problems caused by transfusion of incompatible platelets. Indications for platelet count include unexplained bruising and long coagulation time.

Platelet count is decreased in bone marrow diseases, such as aplastic anemia, leukemia, multiple myeloma, and other cancer in the bone marrow. In addition, chronic bleeding, autoimmune disease, and factors that suppress cell production by the bone marrow (e.g., cancer or other chemotherapies) may be causes of a low platelet count (thrombocytopenia).⁸⁰

Tests of RBCs

Symptoms of anemia may be present in spite of normal RBC count, or the cause of anemia may need to be identified. Therefore more specific testing of RBCs may be needed. These include tests of RBC size, shape, maturity, and the type and concentration of hemoglobin inside them.

White Blood Cell Tests

Various disease states are characterized by their effects on specific types of WBCs. The elevation or depression of one type may be useful in diagnosis. A CBC can only demonstrate a normal level, a decreased level (leukocytopenia), or an elevated level (leukocytosis). Both the absolute numbers and the numbers of white cells relative to each other can be useful in diagnosis. An analysis of the relative numbers of different types of white cells is known as a white cell differential or diff.

Tests of Coagulation

Several tests are related to coagulability. Historically prothrombin time (PT) and activated partial thromboplastin time (aPTT) have been used to determine coagulability either diagnostically or to monitor anticoagulant therapy of heparin and warfarin. These medications are used for many conditions including atrial fibrillation; prevention of acute myocardial infarction in people with peripheral arterial disease; prevention of stroke, recurrent MI, or death in people who have had an MI; valvular heart disease (native and prosthetic); and venous thromboembolism (prevention or treatment).²⁷

The international normalized ratio (INR) was developed to provide results that would not vary between laboratories. Individuals receiving anticoagulation therapy because of coronary artery disease, cerebrovascular disease, atrial fibrillation, history of deep venous thrombosis (DVT), and other reasons are anticoagulated to an INR of 2 to 3.²⁴

As INR increases, however, the risk of bleeding with minor trauma increases and excessive bleeding may occur during surgery, as well as spontaneous bleeding. Within the past few years, low-molecular-weight heparins (LMWHs) have been developed. In spite of the greater cost, use of LMWHs has increased because of the more rapid onset of anticoagulation, lower risk of platelet-dependent thrombus formation,⁴¹ and less prolongation of bleeding time indices.^23,48

Although INR has been an effective test for anticoagulation produced by heparin and warfarin, aPTT is used to monitor the effectiveness of LMWH. Therapeutic INR takes days to reach and is related more to extrinsic coagulation pathway, whereas LMWH can reduce coagulability much more rapidly as measured by aPTT, which is a better measure of intrinsic coagulation pathway.

Components of Coagulation

Specific components of coagulation may be tested on suspicion of their involvement in bleeding disorders. These include specific coagulation factors that produce hemophilia and von Willebrand’s factor.

Inhibition of Coagulation

Proteins C and S regulate the rate of blood clot formation as part of a feedback loop on thrombin production. As thrombin increases, proteins C and S are produced more rapidly and slow the coagulation cascade, thereby preventing excessive coagulation. Problems with proteins C and S can be inherited or acquired. Lack of protein C or S leads to excessive or inappropriate clotting. The exces sive clotting usually occurs in veins, increasing the risk of PE, but can also occur in arteries.

Congestive Heart Failure

Atrial natriuretic peptide (ANP) was discovered many years ago and found to provide a minor contribution to regulation of body fluid composition. As blood volume increases, stretching the atria, the amount of ANP released increases, causing the loss of sodium and water in the urine to correct excessive volume.

A similar peptide, brain natriuretic peptide (BNP), was discovered in the brain. Subsequent research showed that BNP was also found in the ventricles, but the name was retained. Testing for BNP has gained in popularity recently.

Like ANP, BNP is related to excessive blood volume. It is used for differential diagnosis of shortness of breath as BNP is elevated in congestive heart failure (CHF).^26,37 A value of greater than 100 pg/ml is considered positive for congestive heart failure. Levels of BNP rise with disease severity, so levels from 100 to 300 pg/ml generally indicate mild heart failure; 300 to 700 pg/ml indicates moderate heart failure; and levels above 700 pg/ml indicate severe heart failure.⁷⁴

Research indicates that even smaller elevations of BNP above normal are indicative of impaired cardiac pump function²⁶ and future mortality.⁸³ The BNP test can also be used to monitor disease progression in individuals with left-sided heart failure.

Risk Factors for Atherosclerotic Disease

Although lipids are important molecules involved in the storage of energy, production of steroids and bile acids, and maintenance of cell membranes, inappropriate serum levels of certain lipids are associated with atherosclerotic vascular disease. Those of particular interest include triglycerides, cholesterol, and lipoproteins. Several blood lipids are used for screening in certain populations based on age or presence of risk factors.

Cardiac Enzymes and Markers

Enzymes catalyze the chemical reactions that cells need to stay alive, but the enzymes are not destroyed in the reaction and remain in the cell. Normally, these enzymes do not leak into the bloodstream (or leak in small predictable amounts), but when a cell is stressed or damaged it releases its contents (including enzymes) into the bloodstream.

Some enzymes are present in almost all cells; others occur mainly in specific organs. The types and amounts of enzymes circulating in the bloodstream (Table 40-15) can indicate which cells (and therefore which organs) are damaged.

The laboratory tests for differential diagnosis of chest pain have changed in recent years. Carbonic anhydrase, LDH, and AST (formerly SGOT) had been used for determining whether MI had occurred and the severity of the MI. Unfortunately, these tests were not very specific and could be elevated by muscle, liver, renal, or other system injury.

Cardiovascular Pressures

A number of physiologic measurements are made in the ICU or coronary care unit to monitor cardiovascular health and response to treatment. These include central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), and pulmonary artery pressure (PAP).

CVP is measured from a catheter introduced from a peripheral vein such as the subclavian or jugular into the right atrium. CVP indicates the working pressure of the right ventricle, which can either indicate the effectiveness of the right ventricle as a pump or the fluid status of the individual. Increased CVP indicates either poor pumping function of the right ventricle or fluid overload. Dehydration, on the other hand, causes CVP to decrease.

PAWP is an indicator of the effectiveness of the left ventricle as a pump. A balloon-tipped catheter is inserted from a central vein, through the right side of the heart, and fed into the pulmonary arterial vessel. The balloon tip is forced or wedged into a small arterial vessel, and the balloon is inflated. With the balloon inflated, the catheter is exposed only to the pressure present in the fluid between the catheter tip and the left atrium. Poor pumping function of the left ventricle leads to increased pressure as determined by PAWP.

PAP is also determined by a catheter inserted through a central vein, through the right side of the heart, and into the pulmonary arterial circulation. However, no balloon is inflated. The catheter is exposed to the fluctuations in pressure during the cardiac cycle as blood fills and is emptied from the pulmonary arterial vessels. Generally, one is interested in whether pulmonary hypertension exists. PAP can be measured by the same catheter used for PAWP by deflating the balloon and withdrawing the tip so it is no longer wedged. Table 40-17 lists reference values for vascular pressures.

Oxygenation of the Blood

Assessing the cardiopulmonary system’s ability to deliver oxygen may be done simply and noninvasively with pulse oximetry, which provides an estimate of the relative concentrations of saturated and unsaturated Hgb by passing different wavelengths of red light through tissue and determining the absorption at these different wavelengths.

Pulse oximetry also provides the heart rate, but the device has several limitations. Its accuracy declines when arterial blood flow becomes decreased; it does not give information about the ability to rid the body of CO₂ and regulate acid/base balance, and its accuracy is limited to about ±2%.

Cancer Screening

Cancer has overtaken heart disease as a major cause of mortality in the United States. The Human Genome Project has advanced our knowledge of genetics used to develop molecular signatures for disease diagnosis, prediction of treatment outcomes, and final prognosis.

In the last 30 years, there have been important advances in the understanding of the molecular events that underlie the development of malignancy. New techniques to analyze genetic changes and biomarkers for tumors have advanced the diagnostic and monitoring methods for cancer.

Rheumatoid Factor

Rheumatoid factor (RF), an anti-γ-globulin antibody, is elevated in rheumatoid arthritis and Sjögren’s syndrome. However, a negative test does not rule out either disease. Approximately 20% of those diagnosed with these diseases are negative for RF. A positive RF test may also occur with chronic diseases, such as SLE, endocarditis, syphilis, tuberculosis, sarcoidosis, cancer, and viral infections, and other diseases.¹

Antinuclear Antibodies

Antinuclear antibodies (ANA) are generally related to SLE. Exacerbations of SLE are related to elevations in ANA, which may occur with events such as exposure to sunlight. Human leukocyte antigen (HLA) represents the genetic contribution to the immune system. Inheritance of certain HLA proteins increases the risk of specific diseases, especially spondyloarthropathies such as ankylosing spondylitis, reactive arthropathy, Reiter’s syndrome, and psoriatic arthropathy. Not all persons with a certain HLA pattern will develop the disease, but those who do have a greater probability for its development than the general population. Other diseases and related HLA proteins are listed in Table 40-20.

Color and Appearance

The color of urine is related to a number of factors and the most important is its concentration. A pale yellow color is considered normal. Dilution of solute within increased volume of urine decreases its color, whereas reduced volume caused by dehydration increases its yellow appearance. The presence of blood with intact RBCs produces a more purple-to-red color and hemolyzed blood produces a smoky appearance.

Color may also be altered by medications, including antibiotics, some laxatives, chlorzoxazone (a muscle relaxant), and Pyridium. Pyridium is an anesthetic used for treating the burning pain of urinary tract infection that colors the urine orange. The ingestion of certain foods (e.g., rhubarb, carrots, and beets) or some vitamins and supplements can cause a change in the color of urine.

Dark brown urine may occur with liver disease or with DIC. Highly concentrated urine (e.g., decreased hydration or renal dysfunction) is also colored differently depending on the individual and may appear dark yellow, gold, or orange, often accompanied by a strong odor. Asparagus can also bring about a characteristic odor to the urine, and certain vitamin and herbal supplements can change the color (e.g., vitamin C can cause the urine to turn a bright yellow or orange).

Bleeding from the upper urinary tract (kidney and ureters) may produce dark red urine, whereas bleeding in the lower urinary tract (bladder and urethra) produces bright red urine. Occult blood, meaning hidden blood, represents a more subtle change in urine color than the red, purple, or smoky-appearing urine and is tested as part of urinalysis. Bleeding can indicate a number of disorders such as kidney stones, infection, or cancer. Frank purulence (visible pus in the urine) or a cloudy appearance is indicative of infection of the urinary tract.

Specific Gravity

Specific gravity is a test to measure the kidney’s ability to concentrate urine and depends on the state of hydration; specific gravity is an indicator of the solute present in urine. A high specific gravity indicates concentrated urine, whereas a low specific gravity indicates dilute urine. Renal dysfunction is suspected when the kidney is unable to concentrate or dilute the urine.

Dilute urine has a specific gravity approaching 1.0, whereas the specific gravity caused by dehydration may reach 1.2 or greater. Specific gravity correlates with color. Urine with a specific gravity close to 1.0 will be clear, whereas specific gravity closer to 1.2 produces dark yellow urine.

When urine gives a positive result for occult blood but no RBCs are seen on a microscopic examination, myoglobinuria is suspected. Myoglobinuria is the excretion of myoglobin, a muscle protein, into the urine as a result of traumatic muscle injury (e.g., automobile accident, football injury, or electric shock), muscle disorder (e.g., muscular dystrophy, arterial occlusion to a muscle), or certain kinds of poisoning (e.g., carbon monoxide).

Glucose and Ketones

Glucose and ketones present in the urine represent alterations in glucose metabolism. Glucose present in the urine indicates saturation of the active transport mechanism for glucose from the filtered urine. Under normal circumstances, virtually all glucose that filters from the blood can be reabsorbed from the urine.

When the blood glucose level exceeds the reabsorption capacity of the renal tubules, glucose will be spilled into the urine. Failure to absorb all of the glucose indicates a very high plasma glucose concentration and most likely diabetes mellitus.

Ketones in the urine represent the failure to obtain sufficient glucose metabolism, leading to a shift of triglyceride metabolism from the Krebs cycle to the production of ketones. In healthy individuals, ketone bodies are formed in the liver and are completely metabolized so that only negligible amounts (if any) appear in the urine.

However, when glucose cannot be transferred into the cell because of an insufficiency or inefficiency of insulin, carbohydrate metabolism is altered, and fat becomes the alternate body fuel (instead of carbohydrates), producing excessive amounts of ketones. Both diabetes mellitus and starvation (including eating disorders) may be the cause of increased ketones in the urine. Table 40-21 lists reference values for urinalysis.

Gram Stain

Gram stain is used to distinguish organisms that take up the stain (gram positive) from those that do not. A number of common pathogens are gram positive, including Staphylococcus and Streptococcus species. Gramnegative organisms frequently require different antimicrobial drugs. Potassium hydroxide (KOH) is used for identifying fungal infection. Acid-fast testing is generally for determining tuberculosis infection. Acid-fast bacillus (AFB) is a term generally applied to Mycobacterium tuberculosis. Testing is done on sputum samples but may also be done with samples obtained from bronchoscopy or other tissue or fluid samples.

Cultures

Cultures are obtained to detect the presence of bacteria in the blood (e.g., bacteremia), sputum (e.g., pneumonia or tuberculosis), pleural fluid (e.g., empyema), throat (e.g., streptococci, meningococci, or gonococci), urine (e.g., urinary tract infection), skin (e.g., staphylococci, streptococci, or Pseudomonas), and wounds (e.g., staphylococci, streptococci, or Pseudomonas).

Other cultures may include stool and anal, CSF, cervical, and urethral cultures. Cultures are usually performed on the basis of clinical presentation (e.g., chills, fever, or pus). Cultures should be performed before antibiotic therapy is initiated (often the culture is taken and the antibiotic dispensed before results are known); otherwise, the antibiotic may interrupt the organism’s growth in the laboratory.

Samples of tissue or body fluids are used to determine the species or quantity of microbes present. A quantitative culture by tissue biopsy or fluid obtained by needle aspiration is best to determine the number of organisms present. Infection, delayed wound healing, and failure of skin grafts are associated with cultures numbering 100,000 or more organisms per gram. β-Hemolytic Streptococcus causes infection at a lower number per gram of tissue.⁷¹

Blood cultures are taken when systemic infection is suspected. These may be done when patients have indwelling catheters, localized infection, and other risk factors in the presence of fever, malaise, or anorexia. Skin, even in healthy individuals, is expected to have a number of organisms on its surface. In particular, species of Streptococcus, Staphylococcus, and various fungi are commonly present. In some cases, virulent strains may become present and lead to infection. Infection may take the form of a crusty, honey-colored area (impetigo), spread through follicles (folliculitis), cause abscess formation (furuncles), spread through fascial planes (carbuncles), or appear as fungal manifestations such as ringworm or athlete’s foot.

Wounds are frequently cultured for a number of reasons. Both quantitative and qualitative cultures may be taken to determine the appropriate medical treatment. Swab cultures with culturettes are still used frequently but only represent surface bacteria, which may not be the source of the infection. Biopsy of the wound or removal of fluid deep in the wound is more likely to identify the problematic microbes than a swab.

Cerebrospinal Fluid

This fluid surrounds the brain and spinal cord and exists in cavities within the brain called ventricles and within the central canal of the spinal cord. CSF is typically collected by a lumbar puncture. At this site distal to the end of the spinal cord, a needle can be introduced without risk of injuring the spinal cord.

Both the composition and pressure of CSF may be analyzed. Infections (meningitis) may be determined by both presence of bacteria and by alterations in the normal composition of CSF. Pressure within the CSF space may be altered through blockage of the normal flow and reabsorption mechanisms of the brain, which may alter cerebral function or even cause death.

The presence of immunoglobulins (Ig) may be indicative of other disorders, especially the presence of IgG with multiple sclerosis. Other indications for lumbar puncture are included in Box 40-2.

Synovial Fluid Analysis

Arthrocentesis, the surgical puncture of a joint cavity for aspiration (withdrawal) of fluid, is performed by inserting a sterile needle into the joint space. Although the knee is the most commonly aspirated joint, arthrocentesis can be done on any major joint (e.g., shoulder, hip, elbow, wrist, ankle). This test is performed for many different reasons, such as to establish the presence of infection, crystal-induced arthritis, synovitis, or neoplasms.

Fluid may be aspirated from joints to determine the cause of joint effusion, or simply to relieve pressure caused by effusion due to acute trauma. Joint aspiration also offers the potential benefit of removing WBCs, a source of destructive enzymes, from the joint. Joint effusions may increase intraarticular pressure impairing synovial capillary perfusion. Removing synovial fluid via arthrocentesis could potentially improve the delivery of nutrients to cartilage and surrounding tissues.

Once the fluid sample is obtained, it is examined microscopically and chemically. Classification of synovial fluid is described in Table 40-23. Normal joint fluid is clear, colorless or straw-colored, and viscous because of hyaluronic acid in the absence of inflammation. A small amount of blood may be caused by needle trauma; true hemarthrosis gives the fluid a homogeneous pink or red appearance. Viscosity is reduced in people with inflammatory arthritis, and the synovial fluid tends to drip like water; fluid of high viscosity forms a string several inches long.

The mucin clot test correlates with the viscosity and is performed by adding acetic acid to joint fluid. Cell counts are also performed, including a WBC count (normal joint fluid contains fewer than 200/mm³) and neutrophils (PMNs). The concentration of WBCs determines cloudiness.

Although a low WBC count usually indicates a noninflammatory condition, a higher count does not exclude traumatic effusion. Synovial fluid WBC counts may approach 100,000/μl immediately after joint surgery. Normal synovial fluid contains 25% or fewer neutrophils. A very high percentage of PMNs (>75%) is found in most people with acute bacterial infectious arthritis (see Table 40-23).

Fluid containing 70% or more of PMNs may indicate an inflammatory process even if the total WBC count is low. The presence of crystals, which is usually associated with an inflammatory process, can be determined by examining the synovial fluid under polarized light. This test is used to differentiate between gout and pseudogout and sometimes other crystal-induced arthropathies. Finding characteristic crystals does not rule out concomitant infection.

Pleural and Pericardial Fluid Analysis

Accumulations of fluid around the lungs and heart may result from inflammatory diseases, neoplastic disease, infection, or altered lymphatic drainage. Either of these compartments may be affected in isolation or both may be affected, particularly in systemic inflammatory diseases such as amyloidosis, sarcoidosis, rheumatoid arthritis, or SLE. Accumulation of fluid in the pleural space may reduce the inflation of the lungs during inspiration or increase the work of breathing, and in severe cases, cause respiratory failure.

The pericardial space may be filled with inflammatory fluid or blood. Pericarditis may produce audible changes (friction rub) and electrocardiographic changes and other symptoms. Filling of the pericardium with blood, however, is a potentially life-threatening condition called hemopericardium.

When the right side of the heart cannot fill sufficiently to maintain cardiac output, the condition is known as cardiac tamponade resulting in acute heart failure. Fluid can be drawn from either the pleural (pleurocentesis) or pericardial spaces (pericardiocentesis) with a needle for either analysis or to relieve pressure within these spaces.

Peritoneal fluid may accumulate for a large number of reasons, including hepatic failure. Fluid drawn from the peritoneum will be analyzed for infectious agents, cancer cells, electrolytes, and other fluid components to investigate the reason for ascites, the term used to describe peritoneal fluid accumulation. Withdrawal of fluid from the peritoneum is paracentesis.

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