Urine Studies



Urine Studies






OVERVIEW OF URINE STUDIES


Urine Formation

Urine is continuously formed by the kidneys. It is actually an ultrafiltrate of plasma from which glucose, amino acids, water, and other substances essential to body metabolism have been reabsorbed. The physiologic process by which approximately 170,000 mL of filtered plasma is converted to the average daily urine output of 1200 mL is complex.

Urine formation takes place in the kidneys, two fist-sized organs located outside the peritoneal cavity on each side of the spine, at about the level of the last thoracic and first two lumbar vertebrae. The kidneys, together with the skin and the respiratory system, are the chief excretory organs of the body. Each kidney is a highly discriminatory organ that maintains the internal environment of the body by selective secretion or reabsorption of various substances according to specific body needs.

The main functional unit of the kidney is the nephron. There are about 1 to 1.5 million nephrons per kidney, each composed of two main parts: a glomerulus, which is essentially a filtering system, and a tubule through which the filtered liquid passes. Each glomerulus consists of a capillary network surrounded by a membrane called Bowman’s capsule, which continues on to form the beginning of the renal tubule. The kidney’s ability to clear waste products selectively from the blood while maintaining the essential water and electrolyte balances in the body is controlled in the nephron by renal blood flow, glomerular filtration, and tubular reabsorption and secretion.

Blood is supplied to the kidney by the renal artery and enters the nephron through the afferent arteriole. It flows through the glomerulus and into the efferent arteriole. The varying size of these arterioles creates the hydrostatic pressure difference necessary for glomerular filtration and serves to maintain glomerular capillary pressure and consistent renal blood flow within the glomerulus. (The smaller size of the efferent arteriole produces an increase in the glomerular capillary pressure, which aids in urine formation.)

As the filtrate passes along the tubule, more solutes are added by excretion from the capillary blood and secretions from the tubular epithelial cells. Essential solutes and water pass back into the blood through the mechanism of tubular reabsorption. Finally, urine concentration and dilution occur in the renal medulla. The kidney has the remarkable ability to dilute or concentrate urine, according to the needs of the individual, and to regulate sodium excretion. Blood chemistry, blood pressure, fluid balance, and nutrient intake, together with the general state of health, are key elements in this entire metabolic process.


Urine Constituents

In general, urine consists of urea and other organic and inorganic chemicals dissolved in water. Considerable variations in the concentrations of these substances can occur as a result of the influence of factors such as dietary intake, physical activity, body metabolism, endocrine function, and
even body position. Urea, a metabolic waste product produced in the liver from the breakdown of protein and amino acids, accounts for almost half of the total dissolved solids in urine. Other organic substances include primarily creatinine and uric acid. The major inorganic solid dissolved in urine is chloride, followed by sodium and potassium. Small or trace amounts of many additional inorganic chemicals are also present in urine. The concentrations of these inorganic compounds are greatly influenced by dietary intake, making it difficult to establish normal levels. Other substances found in urine include hormones, vitamins, and medications. Although they are not a part of the original plasma filtrate, the urine may also contain formed elements such as cells, casts, crystals, mucus, and bacteria. Increased amounts of these formed elements are often indicative of disease.


Types of Urine Specimens

During the course of 24 hours, the composition and concentration of urine changes continuously. Urine concentration varies according to water intake and pretest activities. To obtain a specimen that is truly representative of a patient’s metabolic state, it is often necessary to regulate certain aspects of specimen collection, such as time of collection, length of collection period, patient’s dietary and medicinal intake, and method of collection. It is important to instruct patients when special collection procedures must be followed. See Appendix A: Standard Precautions for Prevention and Control of Infection and Appendix B: Guidelines for Specimen Transport and Storage for additional guidelines.


URINE TESTING

Urinalysis (UA) is one of the most frequently ordered tests. The results of UA are used to diagnose, treat, and provide follow-up for a variety of conditions, especially urinary tract infections (UTIs). In general, UA is obtained for symptoms of irritation, burning, pain, change in frequency of urination, or change in appearance of the urine.

UA is an essential procedure for patients undergoing hospital admission or physical examination. It is a useful indicator of a healthy or diseased state and has remained an integral part of the patient examination. Two unique characteristics of urine specimens can account for this continued popularity:



  • Urine is a readily available and easily collected specimen.


  • Urine contains information about many of the body’s major metabolic functions, and this information can be obtained by simple laboratory tests.

These characteristics fit in well with the current trends toward preventive medicine and lower medical costs. By offering an inexpensive way to test large numbers of people, not only for renal disease but also for the asymptomatic beginnings of conditions such as diabetes mellitus and liver disease, the UA can be a valuable metabolic screening procedure.

Should it be necessary to determine whether a particular fluid is actually urine, the specimen can be tested for its urea and creatinine content. Inasmuch as both of these substances are present in much higher concentrations in urine than in other body fluids, the demonstration of a high urea and creatinine content can identify a fluid as urine (Chart 3.1).


Laboratory Testing for Routine Urinalysis

First, the physical characteristics of the urine are noted and recorded. Second, a series of chemical tests is run. A chemically impregnated dipstick can be used for many of these tests. Standardized results can be obtained by processing the urine-touched dipstick through special automated instruments. Third, the urine sediment is examined under the microscope to identify its components.




Dipstick Testing

Although laboratory facilities allow for a wide range of urine tests, some types of tablet, tape, and dipstick tests are available for UA outside the laboratory setting. They can be used and read directly by patients and clinicians.

Similar in appearance to pieces of blotter paper on a plastic strip, dipsticks actually function as miniature laboratories. Chemically impregnated reagent strips provide quick determinations of pH, protein, glucose, ketones (acetone or acetoacetic acid), bilirubin, hemoglobin (blood), nitrite, leukocyte esterase, urobilinogen, and specific gravity. The dipstick is impregnated with chemicals that react with specific substances in the urine to produce color-coded visual results. The depth of color produced relates to the concentration of the substance in the urine. Color controls are provided against which the actual color produced by the urine sample can be compared. The reaction times of the impregnated chemicals are standardized for each category of dipstick; it is vital that color changes be matched to the control chart at the correct elapsed time after each stick is dipped into the urine specimen. Instructions that accompany each type of dipstick outline the procedure. When more than one type of test is incorporated on a single stick (e.g., pH, protein, and glucose), the chemical reagents for each test are separated by a water-impermeable barrier made of plastic so that results do not become altered (Table 3.1). Figure 3.1 is an example of a form used to record dipstick testing results. In addition to dipsticks,
reagent strips, tablets, and treated slides for special determinations such as bacteria, phenylketonuria (PKU), mucopolysaccharides, salicylate, and cystinuria are available for urine analysis.








TABLE 3.1 Urine Testing by Dipstick/Reagent Strip






























































Possible Reaction Interference


Measurement


False-Positive


False-Negative


Correlations With Other Tests


pH


None


Runover from the protein pad may lower


Nitrite


Leukocytes


Microscopic examination


Protein


Highly alkaline urine, ammonium compounds (antiseptics), detergents


High salt concentration


Blood


Nitrite


Leukocytes


Microscopic examination


Glucose


Peroxide, oxidizing detergents


Ascorbic acid, 5-HIAA, homogentisic acid, aspirin, levodopa, ketones, high specific gravity with low pH


Ketones


Ketones


Levodopa, phenylketones


None


Glucose


Blood


Oxidizing agents, vegetable and bacterial peroxidases


Ascorbic acid, nitrite, protein, pH <5.0, high specific gravity, captopril


Protein


Microscopic examination


Bilirubin


Lodine, pigmented urine, indican


Ascorbic acid, nitrite


Urobilinogen


Urobilinogen


Ehrlich-reactive compounds (Multistix), medication color


Nitrite, formalin


Bilirubin


Nitrite


Pigmented urine on automated readers


Ascorbic acid, high specific gravity


Protein


Leukocytes


Microscopic examination


Leukocytes


Oxidizing detergents


Glucose, protein, high specific gravity, oxalic acid, gentamycin, tetracycline, cephalexin, cephalothin


Protein


Nitrite


Microscopic examination


Specific gravity


Protein


Alkaline urine


None


NOTE Tablets are becoming obsolete but are still used for certain tests, such as glucose and reducing agents.



Interfering Factors



  • If the dipstick is kept in the urine sample too long, the impregnated chemicals in the strip might be dissolved and could produce inaccurate readings and values.


  • If the reagent chemicals on the impregnated pad become mixed, the readings will be inaccurate. To avoid this, blot off excess urine after withdrawing the dipstick from the sample.




COLLECTION OF URINE SPECIMENS

Standard UA specimens can be collected any time, whereas first morning, fasting, and timed specimens require collection at specific times of day. Patient preparation and education needs vary according to the type of specimen required (Table 3.2) and the patient’s ability to cooperate with specimen collection. Clear instructions and assessment of the patient’s understanding of the process are key to a successful outcome. Assess the patient’s usual urinating patterns and encourage fluid intake (unless contraindicated). Provide verbal and written directions for self-collection of specimens. Assess for presence of interfering factors: Failure to follow collection instructions, inadequate fluid intake, certain medications, and patient use of illegal drugs may affect test results. Certain foods, or any type of food consumption in some instances, may also affect test results.


Single, Random Urine Specimen

This is the most commonly requested specimen. Because the composition of urine changes over the course of the day, the time of day when the specimen is collected may influence the findings. The first voided morning specimen is particularly valuable because it is usually more concentrated and therefore more likely to reveal abnormalities as well as the presence of formed substances. It is also relatively free of dietary influences and of changes caused by physical activity because the specimen is collected after a period of fasting and rest.



Interfering Factors



  • Feces, discharges, vaginal secretions, and menstrual blood will contaminate the urine specimen. A clean voided specimen must be obtained.


  • If the specimen is not refrigerated within 1 hour of collection, the following changes in composition may occur:



    • Increased pH from the breakdown of urea to ammonia by urease-producing bacteria


    • Decreased glucose from glycolysis and bacterial utilization


    • Decreased ketones because of volatilization




    • Decreased bilirubin from exposure to light


    • Decreased urobilinogen as a result of its oxidation to urobilin


    • Increased nitrite from bacterial reduction of nitrate


    • Increased bacteria from bacterial reproduction


    • Increased turbidity caused by bacterial growth and possible precipitation of amorphous material


    • Disintegration of red blood cells (RBCs) and casts, particularly in dilute alkaline urine


    • Changes in color caused by oxidation or reduction of metabolites








TABLE 3.2 Collection of Urine Specimens*











































































Type of Specimen


Characteristics


First Morning Specimen


Most concentrated


Free of dietary influences


Bladder-incubated


Formed elements may disintegrate if pH is high and/or specific gravity is low


Best for nitrate, protein, pregnancy tests; microscopic examination; routine screening


Random Specimen


Most convenient


Most common


Collected any time


Good for chemical screening, routine screening, microscopic examination


Clean-Catch (Midstream)


Used for random collection and bacterial culture


Minimizes bacterial counts


Second (Double-Voided) Specimen


The first morning specimen is discarded; the second specimen is collected and tested


Diabetic monitoring


Reflects blood glucose/usually fasting; less concentrated urine


Formed elements remain intact


Accurately reflects components


Postprandial


Used for glucose determination, diabetic monitoring


Collected 2 hours after a meal


Timed


Requires collection at certain time


Total specimen must be collected


Timed 2-Hour Volume


Used for urobilinogen determination


All urine saved for 2-hour period


Timed 24-Hour Volume


Necessary for accurate quantitative results


All urine saved for 24-hour period


Chemical testing


Catheter Specimen


Clamp catheter 15-30 minutes before collection


Bacterial culture


Cleanse sample port with alcohol


Insert needle into sample port; after aspirating sample, transfer to specimen container


ALERT: Unclamp catheter


Suprapubic Aspiration


Sterile bladder urine


Bacterial culture cytology


*Place urine specimens in a biohazard bag.



Long-Term, Timed Urine Specimen (2-Hour, 24-Hour)

Some diseases or conditions require a second morning specimen or a 2-hour or 24-hour urine specimen to evaluate kidney function accurately (see Table 3.2). Substances excreted by the kidney are not excreted at the same rate or in the same amounts during different periods of the day and night; therefore, a random urine specimen might not give an accurate picture of the processes taking place over a 24-hour period. For measurement of total urine protein, creatinine, electrolytes, and so forth, more accurate information is obtained from a long-term specimen. All urine voided in a 24-hour period is collected into a suitable receptacle; depending on the intended test, a preservative is added, the collection is kept refrigerated, or both (Table 3.3).



Special Considerations



  • In a health care facility, responsibility for the collection of urine specimens should be specifically assigned.


  • When instructing a patient about 24-hour urine collections, make certain the patient understands that the bladder must be emptied just before the 24-hour collection starts and that this preliminary specimen must be discarded; then, all urine voided until the ending time is saved.


  • Do not predate and pretime requisitions for serial collections. It is difficult for some patients to void at specific times. Instead, mark the actual times of collection on containers.


  • Documentation of the exact times at which the specimens are obtained is crucial to many urine tests.


  • Instruct the patient to urinate as near to the end of the collection period as possible.







  • When a preservative is added to the collection container (e.g., HCl preservative in 24-hour urine collection for vanillylmandelic acid [VMA]), the patient must take precautions against spilling the contents and receiving an acid burn. Instructions regarding spillage need to be provided before the test begins.


  • The preservative used is determined by the urine substance to be tested for. The laboratory usually provides the container and the proper preservative when the test is ordered. If in doubt, verify this with the laboratory personnel.








TABLE 3.3 24-Hour Collection: Standards for Timed Urine Specimen Collection























































































































































































































































































Test Element and Purpose


Preservative


Specimen Handling and Storage


Acid mucopolysaccharides (inherited enzyme deficiency in infants with mental retardation or failure to thrive)


20 mL toluene (add at start of collection)


Refrigerate during collection; include patient’s age


Aldosterone (cause of hypertension)


1 g boric acid per 100 mL urine


Refrigerate


Amino acids, quantitative (aminoaciduria, screen for inborn errors of metabolism and genetic abnormalities)


None


Refrigerate during collection


Aminolevulinic acid (porphyria and lead poisoning)


25 mL of 50% acetic acid; for children <5 y, use 15 mL of 50% acetic acid


Refrigerate or ice; protect from light


Amylase (differentiates acute pancreatitis from other abdominal diseases)


None


Refrigerate during collection


Arsenic (arsenic poisoning—occupational exposure)


20 mL of 6N HNO3 in a metal-free container


Refrigerate during collection


Cadmium (toxic levels, including occupational exposure)


20 mL of 6N HNO3 in a metal-free container


Refrigerate during collection


Calcium, quantitative Sulkowitch (hypercalciuria as in hyperparathyroidism, hyperthyroidism, vitamin D toxicity, Paget’s disease, osteolytic diseases, and renal tubular acidosis)


30 mL of 6N HCl


Refrigerate during collection


Catecholamine fractions, urinary free catecholamines (measure adrenomedullary function to diagnose pheochromocytoma)


25 mL of 50% acetic acid; for children <5 y, use 15 mL of 50% acetic acid


Refrigerate or freeze, pH 1-3


Chloride (electrolyte imbalance, dehydration, metabolic alkalosis)


None


Refrigerate during collection


Chromium (toxic levels, including occupational exposure)


20 mL of 6N HNO3 in a metal-free container


Refrigerate


Citrate/citric acid (renal disease)


10 g boric acid


Refrigerate


Copper (Wilson’s disease)


20 mL of 6N HNO3 in a metal-free container


Refrigerate during collection


Cortisol, free (hydrocortisone levels in adrenal hormone function)


30 mL of 6N HCl


Refrigerate during collection


Creatinine (to evaluate disorders of kidney function)


None


Refrigerate during collection


Creatinine clearance (measures kidney function, primarily glomerular filtration)


None


Refrigerate during collection


Cyclic adenosine monophosphate


None


Refrigerate during collection; freeze a portion after collection


Cystine, quantitative (to diagnose cystinuria, inherited disease characterized by bladder calculi)


20 mL of toluene


Refrigerate during collection, pH 2-3; if not acidified—freeze


Δ-Aminolevulinic acid (porphyria and lead poisoning)


30 mL of 33% glacial acetic acid


Protect from light; refrigerate during collection


Electrolytes, sodium, potassium (electrolyte imbalance)


None, or 1.0 g boric acid


Refrigerate


Estriol, estradiol (menstrual and fertility problems, male feminization characteristics, estrogen-producing tumors, and pregnancy)


1.0 g boric acid


Refrigerate during collection


Estrogens, total, nonpregnancy or third trimester (estrogen levels for menstrual and fertility problems, pregnancy and estrogen-producing tumors)


1.0 g boric acid


Refrigerate during collection


Follicle-stimulating/luteinizing hormone (gonadotropic hormones, FSH and LH to determine cause of gonadal deficiency)


1.0 g boric acid or none


Store frozen


Glucose (glucosuria to screen, confirm, or monitor diabetes mellitus, rapid intestinal absorption)


1.0 g boric acid or NaF


Store in dark bottle


Histamine (chronic myelogenous leukemia, carcinoids, polycythemia vera)


None


Refrigerate; freeze portion after collection


Homogentisic acid


None


Freeze portion after collection


Homovanillic acid (to diagnose neuroblastoma, pheochromocytoma, ganglioblastoma)


15 mL of 50% acetic acid <5 y, 25 mL of 50% acetic acid >5 y, to maintain pH 2.0-4.0


Refrigerate during collection


17-Hydroxycorticosteroids (adrenal function by measuring urine excretion of steroids to diagnose endocrine disturbances of the adrenal androgens, Cushing’s, Addison’s, and so forth)


1.0 g boric acid


Refrigerate, pH 5-7; freeze portion after collection


5-Hydroxyindoleacetic acid, serotonin (carcinoid tumors)


15 mL of 50% acetic acid <5 y, 25 mL of 50% acetic acid >5 y, to maintain pH 2.0-4.0


Refrigerate during collection; freeze portion after collection


Hydroxyproline, free (measures the free hydroxyproline [less than 10% normally]; rapid growth and increased collagen turnover)


10 mL 6N HCl per liter of urine, maintain pH <3


Refrigerate during collection; store frozen


Hydroxyproline, total 24-hour collection (bone collagen reabsorption and the degree of bone destruction from bone tumors)


10 mL 6N HCl per liter of urine, maintain pH <3


Refrigerate during collection; use gelatin-free and low-collagen diet


Immunofixation electrophoresis (measures immune status and competence by identifying monoclonal and particle protein band immunoglobulins)


None


Refrigerate


κ and λ chains quantitative, also in serum (monoclonal gammopathies, myeloma tumor burden)


None


Refrigerate


17-Ketogenic steroids (Porter-Silber and Cushing’s syndrome, adrenogenital syndrome)


1.0 g boric acid


Do not refrigerate


17-Ketosteroid, fractions (adrenal and gonadal abnormalities)


1.0 g boric acid


Do not refrigerate


Lead (lead poisoning and chelation therapy)


20 mL of 6N HNO3 in a metal-free container


Refrigerate


Lipase (acute pancreatitis and to differentiate pancreatitis from other abdominal disorders)


None


Refrigerate


Lysozyme, muramidase (to differentiate acute myelogenous or monocytic leukemia from acute lymphatic leukemia)


None


Refrigerate


Magnesium (magnesium metabolism, electrolyte status, and nephrolithiasis)


20 mL of 6N HCl in a metal-free container


Refrigerate


Manganese (toxicity, parenteral nutrition)


None


Refrigerate during collection


Mercury (toxicity, industrial and dental overexposure; inorganic mercury)


20 mL of 6N HNO3 in a metal-free container


Refrigerate; pH 2 with nitric acid


Metanephrine, total (assays of catecholamines and vanillylmandelic acid; frequently to diagnose pheochromocytoma)


30 mL of 6N HCl


pH 1-3


Metanephrine, fractions (to diagnose and monitor pheochromocytoma and ganglioneuroblastoma)


30 mL of 6N HCl, final pH <3


Refrigerate; no caffeine before or during testing


Metanephrine, total (pheochromocytoma, children with neuroblastoma, ganglioneuroma)


25 mL of 50% acetic acid; for children <5 y, use 15 mL of 50% acetic acid, or 30 mL of 6N HCl


Refrigerate; no caffeine before or during testing


MHPG (3-methoxy-4- hydroxyphenylglycol) (to classify bipolar manic depression for drug therapy)


None


Refrigerate, ship frozen


Microalbumin, 24-hour (diabetic nephropathy)


None


Refrigerate


Osmolality, 24-hour (diabetes insipidus, primary polydipsia)


None


Refrigerate


Oxalate (nephrolithiasis and inflammatory bowel diseases)


20 mL of 6N HCl


Refrigerate, pH 2-3


Phosphorous, 24-hour (renal losses; hyperparathyroidism and hypoparathyroidism)


Acid-washed, detergent-free container


Refrigerate during collection; acidify after collection


Porphobilinogens


None


Refrigerate during collection; freeze a portion; protect from light


Porphyrins, quantitative (to diagnose porphyrias and lead poisoning)


5 g sodium carbonate (do not use sodium bicarbonate)


Refrigerate; protect specimen from light


Porphyrins (to diagnose porphyrias and lead poisoning)


None (preservative is added on receipt in laboratory)


Refrigerate; protect specimen from light


Potassium, 24-hour (electrolyte imbalance, renal and adrenal disorders)


None


Refrigerate during collection


Pregnanediol, 24-hour (measures ovarian and placental function)


Boric acid


Refrigerate during collection


Pregnanetriol (adrenogenital syndrome)


25 mL of 50% acetic acid; for children <5 y, use 15 mL of 50% acetic acid


Refrigerate during collection; pH 4-4.5 after receipt in laboratory


Protein electrophoresis, 24-hour


None


Refrigerate


Protein, total (proteinuria, differential diagnosis of renal disease)


None


Refrigerate during collection


Selenium (nutritional deficiency, industrial exposure)


None


Refrigerate; transport entire specimen to laboratory


Sodium, 24-hour (electrolyte imbalance, acute renal failure, oliguria and hyponatremia, sodium excreted for diagnosis of renal and adrenal imbalances)


None


Refrigerate during collection


Substance abuse screen (specific drugs and alcohol involved in substance abuse)


None


Refrigerate or freeze


Thallium (thallium toxicity, occupational exposure)


None


Refrigerate


Thiocyanate (short-term nitroprusside therapy, cyanide poisoning)


None


Refrigerate during collection


Total protein (renal disease)


None


Refrigerate during collection


Urea nitrogen, 24-hour (kidney function, hyperalimentation)


10 g boric acid


Refrigerate


Uric acid, 24-hour (uric acid metabolism in gout and renal calculus formation)


None


Refrigerate during collection


Urobilinogen (liver function and liver cell damage)


5 g sodium carbonate and 100 mL petroleum ether (do not use sodium bicarbonate)


Refrigerate during collection; protect specimen from light; check with laboratory


Vanillylmandelic acid, quantitative (adrenomedullary pheochromocytoma, hypertension)


15 mL of 50% acetic acid <5 y, 25 mL of 50% acetic acid >5 y


Refrigerate, pH 1-3; protect from light


Zinc (industrial exposure, toxicity, nutritional, acrodermatitis enteropathica)


20 mL 6N HNO3 in a metal-free container


Refrigerate



Interfering Factors



  • Failure of patient or attending personnel to follow the procedure is the most common source of error.



    • The patient should be given both verbal and written instructions. If the patient is unable to comprehend these directions, a significant other should be instructed in the process.


    • If required, the proper preservative must be used.


  • Instruct the patient to use toilet paper after transferring the urine to the 24-hour collection container. Toilet paper placed in the specimen decreases the actual amount of urine available and contaminates the specimen.


  • The presence of feces contaminates the specimen. Patients should void first and transfer the urine to the collection receptacle before defecating.


  • If heavy menstrual flow or other discharges or secretions are present, the test may have to be postponed, or an indwelling catheter may need to be inserted to keep the specimen free of contamination. In some cases, thorough cleansing of the perineal or urethral area before voiding may be sufficient. If in doubt, communicate with laboratory personnel and the patient’s physician.



ROUTINE URINALYSIS (UA) AND RELATED TESTS

The process of UA determines the following properties of urine: color, odor, turbidity, specific gravity, pH, glucose, ketones, blood, protein, bilirubin, urobilinogen, nitrite, leukocyte esterase, and other abnormal constituents revealed by microscopic examination of the urine sediment. A 10-mL urine specimen is usually sufficient for conducting these tests (Table 3.4).








TABLE 3.4 Normal Values in Urinalysis





























General Characteristics and Measurements


Chemical Determinations


Microscopic Examination of Sediment


Color: pale yellow to amber


Glucose: negative


Casts negative: occasional hyaline casts


Appearance: clear to slightly hazy


Ketones: negative


Red blood cells: negative or rare


Specific gravity: 1.005-1.025 with a normal fluid intake


Blood: negative


Crystals: negative (none)


pH: 4.5-8.0; average person has a pH of about 5-6


Protein: negative


White blood cells: negative or rare


Volume: 600-2,500 mL/24 h; average 1200 mL/24 h


Bilirubin: negative Urobilinogen: 0.5-4.0 mg/d Nitrite for bacteria: negative Leukocyte esterase: negative


Epithelial cells: few; hyaline casts 0-1/lpf


lpf, lower-power field.








FIGURE 3.2. Sample reports of routine urinalysis and culture sensitivity.

(Recently, urine tests have been developed to detect prostate and breast cancer biomarkers.) See sample reports of routine urinalysis and culture sensitivity at the end of this section (Fig. 3.2).


Urine Volume

Urine volume measurements are part of the assessment for fluid balance and kidney function. The normal volume of urine voided by the average adult in a 24-hour period ranges from 600 to 2500 mL; the typical amount is about 1200 mL. The amount voided over any period is directly related to the individual’s fluid intake, the temperature and climate, and the amount of perspiration that occurs. Children void smaller quantities than adults, but the total volume voided is greater in proportion to their body size.







FIGURE 3.2. Continued

The volume of urine produced at night is < 700 mL, making the day-to-night ratio approximately 2:1 to 4:1.

Urine volume depends on the amount of water excreted by the kidneys. Water is a major body constituent; therefore, the amount excreted is usually determined by the body’s state of hydration. Factors that influence urine volume include fluid intake, fluid loss from nonrenal sources, variations in the secretion of antidiuretic hormone (ADH), and the necessity to excrete increased amount of solutes such as glucose or salts. Polyuria is marked increase of urine production. Oliguria is decreased urinary output. The extreme form of this process is anuria, a total lack of urine production.


Reference Values


Normal

Children: 500-1400 mL/24 hours or 500-1400 mL/day Adults: 800-2500 mL/24 hours or 800-2500 mL/day




Interfering Factors



  • Polyuria



    • Intravenous glucose or saline


    • Pharmacologic agents such as thiazides and other diuretics


    • Coffee, alcohol, tea, caffeine


  • Oliguria



    • Water deprivation, dehydration


    • Excessive salt intake



Urine Specific Gravity (SG)

Specific gravity (SG) is a measurement of the kidneys’ ability to concentrate urine. The test compares the density of urine against the density of distilled water, which has an SG of 1.000. Because urine is a solution of minerals, salts, and compounds dissolved in water, the SG is a measure of the density of the dissolved chemicals in the specimen. As a measurement of specimen density, SG is influenced by both the number of particles present and the size of the particles. Osmolality is a more exact measurement and may be needed in certain circumstances.

The range of urine SG depends on the state of hydration and varies with urine volume and the load of solids to be excreted under standardized conditions; when fluid intake is restricted or increased, SG measures the concentrating and diluting functions of the kidney. Loss of these functions is an indication of renal dysfunction.


Reference Values


Normal

Normal hydration and volume: 1.005-1.030 (usually between 1.010 and 1.025)

Concentrated urine: ≥ 1.025

Dilute urine: 1.001-1.010

Infant <2 years old: 1.001-1.006

NOTE Specific gravity should be corrected for protein (increases SG 0.001 per 0.4 g/dL) and glucose (increases SG 0.004 per 10 g/L).





Interfering Factors



  • Radiopaque x-ray contrast media, minerals, and dextran may cause falsely high SG readings on the refractometer. The reagent dipstick method is not affected by high-molecular-weight substances. SG > 1.040 suggests radiopaque contrast material is in the urine.


  • Temperature of urine specimens affects SG; cold specimens produce falsely high values using the hydrometer.


  • Highly buffered alkaline urine may also cause low readings (with dipsticks only).


  • Elevated readings may occur in the presence of moderate amounts of protein (100-750 mg/dL) or with patients receiving intravenous albumin.


  • Detergent residue (on specimen containers) can produce elevated SG results.


  • Diuretics and antibiotics cause high readings.


  • See Appendix E for drugs that affect test outcomes.


Intervention


Pretest Patient Care



  • Explain the purpose and procedure for urine collection.


  • Follow guidelines in Chapter 1 for safe, effective, informed pretest care.


Posttest Patient Care



  • Interpret test outcomes, counsel, and monitor appropriately for conditions associated with altered SG.


  • Follow Chapter 1 guidelines for safe, effective, informed posttest care.


Urine Osmolality

Osmolality, a more exact measurement of urine concentration than SG, depends on the number of particles of solute in a unit of solution. More information concerning renal function can be obtained if
serum and urine osmolality tests are run at the same time. The normal ratio between urine and serum osmolality is 3:1. A high urine-to-serum ratio is seen with concentrated urine. With poor concentrating ability, the ratio is low.

Whenever a precise measurement is indicated to evaluate the concentrating and diluting ability of the kidney, this test is done. Urine osmolality during water restriction is an accurate test of decreased kidney function. It is also used to monitor the course of renal disease; to monitor fluid and electrolyte therapy; to establish the differential diagnosis of hypernatremia, hyponatremia, and polyuria; and to evaluate the renal response to ADH.


Reference Values


Normal

24-hour specimen: 300-900 mOsm/kg of H2O Random specimen: 50-1200 mOsm/kg of H2O Urine-to-serum ratio: 1:1 to 3:1




Interfering Factors



  • Intravenous sodium administration


  • Intravenous dextrose and water administration




Urine Appearance

The first observation made about a urine specimen is usually its appearance, which generally refers to the clarity of the specimen.

Cloudy urine signals a possible abnormal constituent, such as white blood cells (WBCs), red blood cells (RBCs), or bacteria. On the other hand, excretion of cloudy urine may not be abnormal because a change in urine pH can cause precipitation, within the bladder, of normal urinary components. Alkaline urine may appear cloudy because of phosphates; acid urine may appear cloudy because of urates.


Reference Values


Normal

Fresh urine is clear to slightly hazy.




Interfering Factors



  • After ingestion of food, urates, carbonates, or phosphates may produce cloudiness in normal urine on standing.


  • Semen or vaginal discharges mixed with urine are common causes of turbidity.


  • Fecal contamination causes turbidity.


  • Extraneous contamination (e.g., talcum, vaginal creams, radiographic contrast media) can cause turbidity.


  • “Greasy” cloudiness may be caused by large amounts of fat.



  • Often, normal urine develops a haze or turbidity after refrigeration or standing at room temperature because of precipitation of crystals of calcium oxalate or uric acid.


Urine Color

The yellow color of urine is caused by the presence of the pigment urochrome, a product of metabolism that under normal conditions is produced at a constant rate. The actual amount of urochrome produced depends on the body’s metabolic state, with increased amounts being produced in thyroid conditions and fasting states.

Urine specimens may vary in color from pale yellow to dark amber. Variations in the yellow color are related to the body’s state of hydration. The darker amber color may be directly related to the urine concentration or SG.


Reference Values


Normal

The normal color of urine is pale yellow to amber.

Straw-colored urine is normal and indicates a low SG, usually < 1.010. (The exception may be a patient with an elevated blood glucose concentration, whose urine is very pale yellow but has a high SG.)

Amber-colored urine is normal and indicates a high SG and a small output of urine.




Interfering Factors



  • Normal urine color darkens on standing because of the oxidation of urobilinogen to urobilin. This decomposition process starts about 30 minutes after voiding.


  • Some foods cause changes in urine color:



    • Beets turn the urine red.


    • Rhubarb can cause brown urine.


  • Many drugs alter the color of urine:



    • Cascara and senna laxatives in the presence of acid urine turn the urine reddish brown; in the presence of alkaline urine, they turn the urine red.


    • Bright-yellow color in alkaline urine may be a result of riboflavin or phenazopyridine.


    • Urine that darkens on standing may indicate antiparkinsonian agents such as levodopa (Sinemet).


    • Black urine may be caused by cascara, chloroquine, iron salts (ferrous sulfate, ferrous fumarate, ferrous gluconate), metronidazole, nitrofurantoin, quinine, or senna.


    • Blue urine may be caused by triamterene.


    • Blue-green urine may be caused by amitriptyline, methylene blue, or mitoxantrone.


    • Orange urine may be caused by heparin, phenazopyridine, rifampin, sulfasalazine, or warfarin.


    • Red-pink urine may be caused by chlorzoxazone, daunorubicin, doxorubicin, heparin, ibuprofen, methyldopa, phenytoin, rifampin, or senna.


    • Pink to brown urine may be caused by laxatives.


    • Brown urine may be caused by chloroquine, furazolidone, or primaquine.


    • Green urine may be caused by indomethacin.





Urine Odor

Normal, freshly voided urine has a faint odor owing to the presence of volatile acids. It is not generally offensive. Although not part of the routine UA, abnormal odors should be noted.


Reference Values


Normal

Fresh urine from most healthy persons has a characteristic aromatic odor.




Interfering Factors



  • Some foods, such as asparagus, produce characteristic urine odors.


  • Bacterial activity produces ammonia from the decomposition of urea, with its characteristic pungent odor.


Urine pH

The symbol pH expresses the urine as a dilute acid or base solution and measures the free hydrogen ion (H+) concentration in the urine; 7.0 is the point of neutrality on the pH scale. The lower the pH, the greater the acidity; the higher the pH, the greater the alkalinity. The pH is an indicator of the renal tubules’ ability to maintain normal hydrogen ion concentration in the plasma and extracellular fluid. The kidneys maintain normal acid-base balance primarily through reabsorption of sodium and tubular secretion of hydrogen and ammonium ions. Secretion of an acid or alkaline urine by the kidneys is one of the most important mechanisms the body has for maintaining a constant body pH.

Urine becomes increasingly acidic as the amount of sodium and excess acid retained by the body increases. Alkaline urine, usually containing bicarbonate-carbonic acid buffer, is normally excreted when there is an excess of base or alkali in the body.

The importance of urinary pH lies primarily in determining the existence of systemic acid-base disorders of metabolic or respiratory origin and in the management of urinary conditions that require the urine to be maintained at a specific pH.



Control of Urine pH

Control of urinary pH is important in the management of several diseases, including bacteriuria, renal calculi, and drug therapy in which streptomycin or methenamine mandelate is being administered.



  • Renal calculi



    • Renal stone formation partially depends on the pH of urine. Patients being treated for renal calculi are frequently given diets or medication to change the pH of the urine so that kidney stones will not form.


    • Calcium phosphate, calcium carbonate, and magnesium phosphate stones develop in alkaline urine. In such instances, the urine must be kept acidic (see Diet, number 4, below).


    • Uric acid, cystine, and calcium oxalate stones precipitate in acid urines. Therefore, as part of treatment, the urine should be kept alkaline (see Diet, number 4, below).


  • Drug treatment



    • Streptomycin, neomycin, and kanamycin are effective for treating genitourinary tract infections, provided the urine is alkaline.


    • During sulfa therapy, alkaline urine should help prevent formation of sulfonamide crystals.


    • Urine should also be kept persistently alkaline in the presence of salicylate intoxication (to enhance excretion) and during blood transfusions.


  • Clinical conditions



    • The urine should be kept acidic during treatment of UTI or persistent bacteriuria and during management of urinary calculi that develop in alkaline urine.


    • An accurate measurement of urinary pH can be made only on a freshly voided specimen. If the urine must be kept for any length of time before analysis, it must be refrigerated.


    • Highly concentrated urine, such as that formed in hot, dry environments, is strongly acidic and may produce irritation.


    • During sleep, decreased pulmonary ventilation causes respiratory acidosis; as a result, urine becomes more acidic.


    • Chlorothiazide diuretic administration causes acid urine to be excreted.


    • Bacteria from a UTI or from bacterial contamination of the specimen produce alkaline urine. Urea is converted to ammonia.


  • Diet



    • A vegetarian diet that emphasizes citrus fruits and most vegetables, particularly legumes, helps keep the urine alkaline. Alkaline urine after meals is a normal response to the secretion of hydrochloric acid in gastric juice (“alkaline tide”).


    • A diet high in meat and protein keeps the urine acidic.


    • Cranberry and prune juices will maintain an acidic urine and will help reduce UTIs.


Reference Values


Normal

The pH of normal urine can vary widely, from 4.6 to 8.0.

The average pH value is about 6.0 (acidic).





Interfering Factors



  • With prolonged “standing,” the pH of a urine specimen becomes alkaline because bacteria split urea and produce ammonia. Note: A urine pH of >9.0 is indicative of prolonged standing.


  • Ammonium chloride and mandelic acid may produce acid urines.


  • Runover between the pH testing area and the highly acidic protein area on the dipsticks may cause alkaline urine to give an acidic reading.


  • Sodium bicarbonate, potassium citrate, and acetazolamide may produce alkaline urine.


  • Urine becomes alkaline after eating because of excretion of stomach acid; this is known as the “alkaline tide.”


  • The pH tends to be low following overnight fasting and high following ingestion of a meal.



Urine Blood or Hemoglobin (Hb)

The presence of free hemoglobin in the urine is referred to as hemoglobinuria. Hemoglobinuria can be related to conditions outside the urinary tract and occurs when there is such extensive or rapid destruction (intravascular hemolysis) of circulating erythrocytes that the reticuloendothelial system
cannot metabolize or store the excess free hemoglobin. The hemoglobin is then filtered through the glomerulus. Hemoglobinuria may also occur as a result of lysis of RBCs in the urinary tract.

When intact RBCs are present in the urine, the term hematuria is used. Hematuria is most closely related to disorders of the renal or genitourinary systems in which bleeding is the result of trauma or damage to these organs or systems.

This test detects RBCs, hemoglobin, and myoglobin in urine. Blood in urine is always an indicator of damage to the kidney or urinary tract.

The use of both a urine dipstick measurement and microscopic examination of urine provides a complete clinical evaluation of hemoglobinuria and hematuria. Newer forms of dipsticks contain a lysing reagent that reacts with occult blood and detects intact as well as lysed RBCs.

When urine sediment is positive for occult blood but no RBCs are seen microscopically, myoglobinuria can be suspected. Myoglobinuria is caused by excretion of myoglobin, a muscle protein, into the urine as a result of (1) traumatic muscle injury, such as may occur in automobile accidents, football injuries, or electric shock; (2) a muscle disorder, such as an arterial occlusion to a muscle or muscular dystrophy; (3) certain kinds of poisoning, such as carbon monoxide or fish poisoning; or (4) malignant hyperthermia related to administration of certain anesthetic agents. Myoglobin can be distinguished from free hemoglobin in the urine by chemical tests.


Reference Values


Normal

Negative (< 0.03 mg free Hb/dL or <10 Ercs/µL)

Hb = hemoglobin

Ercs = erythrocytes




Interfering Factors



  • Drugs causing a positive result for blood or hemoglobin include:



    • Drugs toxic to the kidneys (e.g., bacitracin, amphotericin)


    • Drugs that alter blood clotting (warfarin [Coumadin])


    • Drugs that cause hemolysis of RBCs (aspirin)


    • Drugs that may give a false-positive result (e.g., bromides, copper, iodides, oxidizing agents)


  • High doses of ascorbic acid or vitamin C may cause a false-negative result.


  • High SG or elevated protein reduces sensitivity.


  • Myoglobin produces a false-positive result.


  • Hypochlorites or bleach used to clean urine containers causes false-positive results.



  • Menstrual blood may contaminate the specimen and alter results.


  • Prostatic infections may cause false-positive results.


  • See Appendix E for a complete list of drugs that affect test outcomes.



Urine Protein (Albumin), Qualitative and 24-Hour

The presence of increased amounts of protein in the urine can be an important indicator of renal disease. It may be the first sign of a serious problem and may appear before any other clinical symptoms. However, there are other physiologic conditions (e.g., exercise, fever) that can lead to increased protein excretion in urine. Also, there are some renal disorders in which proteinuria is absent.

In a healthy renal and urinary tract system, the urine contains no protein or only trace amounts. These consist of albumin (one third of normal urine protein is albumin) and globulins from the plasma. Because albumin is filtered more readily than the globulins, it is usually abundant in pathologic conditions. Therefore, the term albuminuria is often used synonymously with proteinuria.

Normally, the glomeruli prevent passage of protein from the blood to the glomerular filtrate. Therefore, the presence of protein in the urine is the single most important indication of renal disease. If more than a trace of protein is found persistently in the urine, a quantitative 24-hour evaluation of protein excretion is necessary.


Reference Values for 24-Hour Urine


Normal

Adult male: 10-140 mg/L or 1-14 mg/dL

Adult female: 30-100 mg/L or 3-10 mg/dL

Child: <10 years old: 10-100 mg/L or 1-10 mg/dL


Reference ValuesQualitative


Normal

Negative




Collecting the Specimen for Orthostatic Proteinuria



  • The patient is instructed to void at bedtime and to discard this urine.


  • The next morning, a urine specimen is collected immediately after the patient awakens and before the patient has been in an upright position for longer than 1 minute. This may involve the use of a bedpan or urinal.


  • A second specimen is collected after the patient has been standing or walking for at least 2 hours.


  • With postural proteinuria, the first specimen contains no protein, but the second one is positive for protein.


  • The urine looks microscopically normal; no RBCs or WBCs are apparent. Orthostatic proteinuria is considered a benign condition and slowly disappears with time. Progressive renal impairment usually does not occur.



Interfering Factors for Qualitative Protein Test



  • Because of renal vasoconstriction, the presence of a functional, mild, and transitory proteinuria is associated with:



    • Strenuous exercise leading to urine protein values of up to 300 mg/24 hours


    • Severe emotional stress, seizures


    • Cold baths, exposure to very cold temperatures


  • Increased protein in urine occurs in these benign states:



    • Fever and dehydration (salt depletion)


    • Non-immunoglobulin E food allergies


    • Salicylate therapy


    • In the premenstrual period and immediately after delivery


  • False or accidental proteinuria may occur because of a mixture of pus and RBCs in the urinary tract related to infections, menstrual or vaginal discharge, mucus, or semen.


  • False-positive results can occur from incorrect use and interpretation of the color reagent strip test.



  • Alkaline, highly buffered urine can produce false-positive results on the dipstick test.


  • Very dilute urine may give a falsely low protein value.


  • Certain drugs may cause false-positive or false-negative urine protein tests (see Appendix E).


  • Radiographic contrast agents may produce false-positive results with turbidimetric measurements.



Microalbuminuria/Albumin (24-Hour Urine)

Microalbuminuria is an increase in urinary albumin that is below the detectable range of the standard protein dipstick test. It is not a different chemical form of albumin. Microalbuminuria occurs long before clinical proteinuria becomes evident.

This test allows for the routine detection of low concentrations of albumin in the urine. This test has become a standard for the screening, monitoring, and detection of deteriorating renal function in diabetic patients. Studies have shown that diabetic patients who progress to renal failure first excrete micro amounts of albumin and that, at this stage, intervening treatment can reverse the proteinuria and thus prevent progression to renal failure. This test is also used to monitor compliance with blood pressure control, glucose control, and protein restriction.


Reference Values


Normal

<30 mg/24 hours (<30 mg/day) or <20 mg/L (10-hour collection)





Interfering Factors



  • Strenuous exercise


  • Hematuria (menses)


  • High-protein diet or high salt levels



Urine β2-Microglobulin

β2-Microglobulin, an amino acid peptide component of the lymphatic human lymphocyte antibody (HLA) major histocompatibility complex, is found on the outside of the plasma membrane. It is structurally related to the immunoglobulins.

This test measures β2-microglobulin, which is nonspecifically increased in inflammatory conditions and in patients with malignancies (e.g., lymphoma, active chronic lymphatic leukemia, or multiple myeloma). It may be used to differentiate glomerular from tubular dysfunction. In glomerular disease, β2-microglobulin is increased in serum and decreased in urine, whereas in tubular disorders, it is decreased in serum and increased in urine. In aminoglycoside toxicity, β2-microglobulin levels become abnormal before creatinine levels begin to show abnormal values. Serum is also used to evaluate the prognosis of multiple myeloma.


Reference Values


Normal

Urine 24-hour specimen: <1 mg/24 hours or <1 mg/day

Blood serum specimen: <2.7 µg/mL or <2.7 mg/L




Interfering Factors



  • Acid urine—not stable, pH <6.0


  • Certain antibiotics (e.g., gentamicin, tobramycin)


  • Recent nuclear medicine scan


  • Increased synthesis in certain diseases (e.g., Crohn’s disease, hepatitis, sarcoidosis) decreases the usefulness of the blood serum test.


  • Random specimens are not recommended.



Urine Glucose (Sugar)

Glucose is present in glomerular filtrate and is reabsorbed by the proximal convoluted tubule. If the blood glucose level exceeds the reabsorption capacity of the tubules, glucose will appear in the urine. Tubular reabsorption of glucose is by active transport in response to the body’s need to maintain an adequate concentration of glucose. The blood level at which tubular reabsorption stops is termed the renal threshold, which for glucose is between 160 and 180 mg/dL (9-10 mmol/L).


Types of Glucose Tests



  • Reduction tests (Clinitest)



    • These are based on reduction of cupric ions by glucose. When the compounds are added to urine, a heat reaction takes place. This results in precipitation and a change in the color of the urine if glucose is present.


    • These tests are nonspecific for glucose because the reaction can also be caused by other reducing substances in the urine, including:



      • Creatinine, uric acid, ascorbic acid


      • Other sugars, such as galactose, lactose, fructose, pentose, and maltose


    • These tests have a lower sensitivity than enzyme tests.


  • Enzyme tests (Clinistix, Diastix, Tes-Tape)



    • These tests are based on interaction between glucose oxidase (an enzyme) and glucose. When dipped into urine, the enzyme-impregnated strip changes color according to the amount of glucose in the urine. The manufacturer’s color chart provides a basis for comparison of colors between the sample and the manufacturer’s control.


    • These tests are specific for glucose only.



Reference Values


Normal

Random specimen: Negative

24-hour specimen: 1-15 mg/dL (60-830 µmol/L) or <0.5 g/24 hours (<2.8 mmol/day)





Interfering Factors

Jun 11, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Urine Studies
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