section epub:type=”chapter” role=”doc-chapter”> After studying this chapter, the student should be able to: Urine color, which is normally various shades of yellow, can range from colorless to amber to orange, red, green, blue, brown, or even black. These color variations can indicate the presence of a disease process, a metabolic abnormality, or an ingested food or drug. However, color variations can simply result from excessive physical activity or stress. It is important to note that a change in urine color is often the initial or only reason why an individual seeks medical attention. The characteristic yellow color of normal urine is principally due to the pigment urochrome.1 A product of endogenous metabolism, urochrome is a lipid-soluble pigment that is present in plasma and excreted in urine. Patients in chronic renal failure, with decreased excretion of urochrome, may exhibit a characteristic yellow pigmentation of their skin caused by deposition of urochrome in their subcutaneous fat. Because urochrome production and excretion are constant, the intensity of the color of urine provides a crude indicator of urine concentration and the hydration state of the body. A concentrated urine is dark yellow, whereas a dilute urine is pale yellow or colorless. Urochrome, similar to other lipid-soluble pigments, darkens on exposure to light.2 This characteristic darkening is often observed in urine specimens that are improperly stored. Small amounts of urobilin (an orange-brown pigment) and uroerythrin (a pink pigment) also contribute to urine color. Urobilin and uroerythrin are normal urine constituents; uroerythrin is most evident when it deposits on urate crystals, producing a precipitate often described as brick dust. The terminology used to describe urine color often differs among laboratories. Regardless of the terminology used, an established list of terms should be available and used by all personnel in the laboratory. These terms should reduce ambiguity in color interpretation and improve consistency in the reporting of urine colors.3 Terms such as straw and beer brown should be replaced with light yellow and amber. The term bloody should be avoided. Although bloody is descriptive, it is not a color; red or pink would be more appropriate. Table 5.1 lists some appropriate terms to describe the color of urine and the substances that can cause these colors. Table 5.1 aNote that numerous medications, foods, and dyes can cause changes in urine color. This list is limited and focuses on those most commonly encountered in the clinical laboratory. An abnormal urine, that is, one that reflects a pathologic process, may not have an abnormal color, whereas a normally colored urine may contain significant pathologic elements. For example, a normal yellow or colorless urine can actually contain large amounts of glucose or porphobilinogen. In contrast, a red urine, often an indicator of the presence of blood, can result from the ingestion of beets by genetically disposed individuals. Nevertheless, urine color is valuable in the preliminary assessment of a urine specimen. Many substances are capable of modifying the normal color of urine. The same substance can impart a different color to urine depending on (1) the amount of the substance present; (2) the urine pH; and (3) the structural form of the substance, which can change over time. Red blood cells provide an excellent example. In fresh acidic urine, red blood cells can be present despite a typical yellow-colored urine, or the urine color may appear pink or red. The color of the urine varies with the quantity of red blood cells present. As red blood cells disintegrate, hemoglobin is released and oxidizes to methemoglobin, which causes the urine color to become brown or even black. Alkaline urine with red blood cells present is often red-brown in color. In such specimens, disintegration of cellular components is enhanced by the alkaline pH, and hemoglobin oxidation is promoted. When glomerular or tubular damage of nephrons occurs, blood enters the urinary tract and the hemoglobin becomes oxidized before it collects in the bladder. In this case the urine appears brownish rather than the typical red color that is associated with the presence of blood. A fresh brown urine can indicate the presence of blood, hemoglobin, or myoglobin. Distinguishing among these substances is difficult, particularly between hemoglobin and myoglobin, because all three produce a positive chemical test for blood. Red blood cells are confirmed by microscopic examination, whereas the discrimination between hemoglobin and myoglobin requires additional urine chemical testing and possibly an evaluation of the blood plasma. Chapter 6 provides further discussion on the differentiation of hemoglobin and myoglobin in urine. Bilirubin is another substance that can contribute to urine color. It is a byproduct of hemoglobin catabolism and has a characteristic yellow color. When present in sufficient amounts in urine or plasma, bilirubin imparts a distinctive amber coloration. However, upon standing or improper storage, bilirubin oxidizes to biliverdin, causing the urine to take on a greenish hue. Bilirubin is also susceptible to photo-oxidation by artificial light or sunlight; therefore, specimens must be stored properly to avoid degradation of this component. This photosensitivity is temperature dependent; optimal specimen stability is obtained by storing the specimens at low temperatures in the dark. Some substances are colorless and normally do not contribute to urine color. However, upon standing or improper storage, they convert to colored compounds. Urobilinogen, a normal constituent in urine, is colorless, whereas its oxidation product urobilin is orange-brown. Porphobilinogen, a colorless and chemically similar (tetrapyrroles) substance, is a solute found in the urine of patients with abnormal porphyrin metabolism (heme synthesis). Porphobilin, the oxidation product of porphobilinogen, can impart a pink color to urine. As a result, urine that contains these substances can change color over time; this may alert the laboratorian to its presence and the need for additional testing. However, these color changes are often subtle and take hours to develop. A multitude of urine colors results from ingested substances, and often the colors have no clinical significance. Highly pigmented foods such as fresh beets, breath fresheners containing chlorophyll, candy dyes, and vitamins A and B can impart distinctive colors to urine. Included in this group of ingested substances are numerous medications, some of which are used specifically to treat urinary tract infection. Other medications are present because they are eliminated from the body in the urine. Table 5.2 lists commonly encountered drugs and the colors they impart to the urine. It is worth noting that phenazopyridine, a urinary analgesic used in the treatment of urinary tract infections and often encountered in the clinical laboratory, imparts a distinctive yellow-orange coloration (similar to orange soda pop) with a thick consistency to the urine. This drug-produced color frequently interferes with the color interpretation of chemical reagent strip tests; alternative chemical testing methods (e.g., tablet tests, chemistry tests) must be used with these urine specimens. Table 5.2 From Ben-Ezra J, McPherson RA: Basic examination of urine. In McPherson RA, Pincus MR, editors: Clinical diagnosis and management by laboratory methods, ed 22, Philadelphia, 2011, Saunders. Pathologic conditions can be indicated by the presence of certain analytes and components that color the urine. Substances such as melanin, homogentisic acid, indican, porphyrins, hemoglobin, and myoglobin or components such as red blood cells provide evidence of a pathologic process. In each case, urine suspected of containing these components requires additional chemical testing and investigation. Many of these substances are discussed individually along with the metabolic diseases that produce them in Chapters 6 and 8. However, contaminants—substances not produced in the urinary tract—can also color the urine; these include fecal material, menstrual blood, and hemorrhoidal blood. In summary, the color of urine is actually a combination of the colors imparted by each constituent present. To evaluate urine color consistently, the criteria outlined in Box 5.1 are necessary. Without attention to these details and to the use of established terminology, consistent reporting of urine color is not possible. If a normal urine specimen is shaken or agitated sufficiently, a white foam can be forced to develop at its surface that readily dissipates on standing. The characteristics of urine foam—namely, its color, ease of formation, and the amount produced—are modified by the presence of protein and bilirubin. Moderate to large amounts of protein (albumin) in urine cause a stable white foam to be produced when the urine is poured or agitated (Fig. 5.1). Similar to egg albumin, the foam that develops is thick and long lasting. In addition, a larger volume of foam is easily produced by agitation of this urine compared with urine in which protein is not present. When bilirubin is present in sufficient amounts, the foam if present will be characteristically yellow (see Fig. 5.1). This coloration may be noticed when the urine is being processed and the physical characteristics recorded. Although not definitive, this distinctive yellow coloration of the foam provides preliminary evidence for the presence of bilirubin. Most substances that intensify or change the color of urine do not alter the color or characteristics of the urine foam. In other words, despite significant changes in urine color, the foam, if forced to form by agitation, remains white and readily dissipates. Foam characteristics noted in the physical examination are not reported in a routine urinalysis; instead, they serve as preliminary and supportive evidence for the presence of bilirubin and abnormal amounts of protein in the urine. These suspected substances must be detected and confirmed during the chemical examination before either substance is reported. Clarity, along with color, describes the overall visual appearance of a urine specimen. It is assessed at the same time as urine color and refers to the transparency of the specimen. Often called turbidity, clarity describes the cloudiness of the urine caused by suspended particulate matter that scatters light. The criteria outlined in Box 5.1 for assessing urine color also apply when evaluating urine clarity. An established list of descriptive terms for clarity used by all laboratory personnel ensures consistency in reporting and eliminates ambiguity. Table 5.3 defines common clarity terminology and provides a list of substances that produce these characteristics. Table 5.3
Routine Urinalysis—the Physical Examination
Key Terms1
Color
Color
Substance
Comments and Clinical Correlation
Colorless to pale yellow
Dilute urine
Fluid ingestion; polyuria due to diabetes mellitus or diabetes insipidus
Yellow
Normal urine
Due to the normal pigment, urochrome (as well as uroerythrin and urobilin)
Dark yellow to amber
Concentrated urine, excessive urobilin
Limited fluid intake—dehydration, strenuous exercise, first morning specimen, fever; excessive conversion of urobilinogen to urobilin with time
Bilirubin
If shaken, foam is yellow
Dark yellow-green
Biliverdin
Greenish coloration due to bilirubin that oxidized to biliverdin upon standing or improper storage
Orange
Foods
Carotene
High consumption of vegetables and fruits that contain carotene
Drugs
Phenazopyridine (Pyridium, Azo-Gantrisin)
Medication—urinary analgesic; bright color at acid pH
Warfarin (Coumadin)
Medication—anticoagulant
Rifampin
Medication—tuberculosis treatment
Bright yellow
Foods
Riboflavin
Multivitamins, B-complex vitamins
Yellow-brown
Drugs
Nitrofurantoin
Medication—antibiotic
Pink
Blood
Hemoglobin, red blood cells (RBCs)
Blood in urine from urinary tract or from contamination (e.g., menstrual bleeding)
Inherited
Porphobilin
Oxidized porphobilinogen (colorless); caused by improper handling and storage of urine specimens; associated with acute intermittent porphyria (a rare genetic disorder)
Red
Blood
RBCs
Intact RBCs observed microscopically; urine cloudy
Hemoglobin
Urine clear, if no intact RBCs present (e.g., intravascular hemolysis); hemolysis evident in plasma/serum
Foods
Beet ingestion
In acidic urine of genetically disposed individuals; alkaline urine is yellow
Drugs
Senna
Over-the-counter laxatives (e.g., Ex-Lax)
Red-purple
Inherited
Porphyrins
Excessive oxidation of colorless porphyrinogens and porphobilinogen to colored compounds (rare conditions); caused by improper handling and storage of these specimens
Brown
Myoglobin
Rhabdomyolysis—urine clear; plasma/serum normal yellow appearance
Blood
Methemoglobin
Oxidized hemoglobin
Drugs
Metronidazole (Flagyl)
Medication—treatment for trichomoniasis, Giardia, amebiasis; darkens the urine
Dark brown to black
Melanin
Oxidized melanogen (colorless); develops upon standing and associated with malignant melanoma
Inherited
Homogentisic acid
Color develops upon standing in alkaline urine; associated with alkaptonuria (a genetic metabolic disorder)
Blue or green
Infection
Dyes
Drugs
Drug
Color
Alcohol, ethyl
Pale yellow or colorless (diuresis)
Amitriptyline (Elavil)
Blue-green
Anthraquinone laxatives (senna, cascara)
Reddish, alkaline; yellow-brown, acid
Chlorzoxazone (Paraflex) (muscle relaxant)
Red
Deferoxamine mesylate (Desferal) (chelates iron)
Red
Ethoxazene (Serenium) (urinary analgesic)
Orange, red
Fluorescein sodium (given intravenously)
Yellow
Furazolidone (Furoxone) (Tricofuron) (an antibacterial, antiprotozoal nitrofuran)
Brown
Indigo carmine dye (renal function, cystoscopy)
Blue
Iron sorbitol (Jectofer) (possibly other iron compounds forming iron sulfide in urine)
Brown on standing
Levodopa (L-dopa) (for parkinsonism)
Red then brown, alkaline
Mepacrine (Atabrine) (antimalarial) (intestinal worms, Giardia)
Yellow
Methocarbamol (Robaxin) (muscle relaxant)
Green-brown
Methyldopa (Aldomet) (antihypertensive)
Darkens; if oxidizing agents present, red to brown
Methylene blue (used to delineate fistulas)
Blue, blue-green
Metronidazole (Flagyl) (for Trichomonas infection, amebiasis, Giardia)
Darkens, reddish brown
Nitrofurantoin (Furadantin) (antibacterial)
Brown-yellow
Phenazopyridine (Pyridium) (urinary analgesic), also compounded with sulfonamides (Azo-Gantrisin)
Orange-red, acid pH
Phenindione (Hedulin) (anticoagulant) (important to distinguish from hematuria)
Orange, alkaline; color disappears on acidifying
Phenol poisoning
Brown; oxidized to quinones (green)
Phenolphthalein (purgative)
Red-purple, alkaline pH
Phenolsulfonphthalein (PSP, also bromsulphthalein [BSP])
Pink-red, alkaline pH
Rifampin (Rifadin, Rimactane) (tuberculosis therapy)
Bright orange-red
Riboflavin (multivitamins)
Bright yellow
Sulfasalazine (Azulfidine) (for ulcerative colitis)
Orange-yellow, alkaline pH
Foam
Clarity
Term
Definition
Possible Causes
Clear
No (or rare) visible particles; transparent
Hazy or slightly cloudy
Visible particles present; newsprint can be read when viewed through urine tube
Clarity varies with the substance and the amount present:
Cloudy
Significant particulate matter; newsprint is blurred or difficult to read when viewed through urine tube
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Routine Urinalysis—the Physical Examination
Learning Objectives