Urology

The Significance of Abnormal Urine Color

Martha K. Terris, M.D.
Assistant Professor of Urology
Chief of Urology, Veterans Affairs Palo Alto Health Care System

INTRODUCTION
The normal color of urine ranges from light yellow to dark amber, depending on the concentration of solutes in the urine. Urochrome is the name of the pigment that gives urine its characteristic yellow color (1). Patients may be quite frightened at any unusual color of their urine. Other urinary complaints may accompany changes in urine color. Such symptoms include urinary urgency (having to hurry to get to the bathroom), frequent urination, burning pain with urination (known as "dysuria" which can suggest infection or tumor), or colicky pains (suggesting stones), as well as any food colorings, over-the-counter or prescription medications, or diagnostic dyes recently ingested (2,3). Also important are the circumstances surrounding noticing the color. This is easier in men since standing to urinate allows them to notice urine color as it enters the toilet bowl. The color may only appear after the urine contacts the container or the water in the toilet bowl. Sometimes the urine has to sit in the sun for hours before the color appears. Women usually notice abnormal color on tissue after wiping. It can be sometimes challenging to distinguish the source of the color from the reproductive, gastrointestinal tract, or genitourinary tract in women. A full pelvic examination and catheterized urine specimen is often necessary.

White or cloudy urine is most commonly a result of phosphaturia (2,3). This is a benign condition in which excess amorphous phosphate crystals form in urine. Adding a drop of acetic acid to the urine sample will result in immediate clearing of the urine. Phosphaturia is usually intermittent, occurring following a meal or after ingesting a large quantity of milk. White urine is sometimes due to pyuria (abundant white blood cells) in association with an infection of the urinary tract (1-4). White cloudy urine can rarely be due to chyluria (lymph fluid), resulting from a communication with between the lymphatic system and the urinary tract (3).

RED / PINK
Pink or red urine should prompt an immediate visit to your doctor. The first test is a dipstick for blood. A positive dipstick for blood implies the presence of red cells, free hemoglobin (from broken down red blood cells), or myoglobin (from broken down muscle cells), which can be double-checked by examining the urinary sediment for red cells and the serum for hemoglobinemia. In patients with normal renal function, hemoglobinuria can be distinguished from myoglobinuria by drawing a blood sample, spinning it down, and looking at the serum (4-6). Free hemoglobin produces a pink serum which will test positive with the dipstick. Myoglobin is cleared more efficiently by the kidneys, usually leaving a clear serum which tests negative with the dipstick. Contamination of the urine sample with hypochlorite bleach can cause a false positive test for hemoglobin (5).

Red blood cells in the urine may be from kidney loss (termed "glomerular" blood cells) in patients with renal disease. Red cells in the urine of these individuals will usually be misshapen and accompanied by protein in the urine.

Normal appearing red blood cells (termed "epithelial" red blood cells to identify them as cells coming from the urinary epithelium instead of the contorted "glomerular" red blood cells) may be present during a urinary tract infection, urinary stone, or urinary malignancy. Red blood cells are common in the urine after urologic procedures and occasionally following catheter placement. Complete urine testing (called "urinalysis") for the presence of bacteria and white blood cells, urine culture, cystoscopy, intravenous pyelogram, and/or other imaging studies my be necessary to clarify the source of the blood.

If the urine is red and acid but does not contain hemoglobin, myoglobin, or red blood cells, suspect an indicator dye such as phenolphthalein (the laxative in ExLax) in which case the red should disappear when the urine is alkalinized with a few drops of potassium hydroxide (6). Blackberries and beets can turn acid urine red due to the presence of anthrocyanin, while rhubarb, anthraquinone laxatives, and some diagnostic dyes will redden urine only when it is alkaline (6,7).

Eosin turns urine pink or red in natural light but fluoresces green under ultraviolet light (6). The anesthetic, propofol, has been reported to cause pink coloration of the urine, particularly in alcoholics (8). Other medications that can cause red urine are the phenytoin, phenothiazines, e.g., Compazine (6,9). Red urine can also be caused by chronic lead and mercury poisoning.

ORANGE
Orange urine may be produced by phenazopyridine (Pyridium) or ethoxazene (Serenium), both of which are used as urinary tract anesthetics to diminish dysuria (6). Pyridium also can make a dipstick test appear falsely positive for bilirubin. Rifampin, phenacetin, sulfasalazine, Vitamin C, riboflavin, and carrots will also turn urine dark yellow to orange (6,10). An opaque orange-pink urine color can result from abundant uric acid crystals which can be seen in acidic urine of patients who have undergone intestinal by-pass surgery or are receiving chemotherapy for malignancy (10).

BLUE / GREEN
Blue or green urine may be caused by a blue dye such as methylene blue, a component in several medications (Trac Tabs, Urised, Uroblue) used to reduce symptoms of bladder inflammation or irritation (1,6). Administration of the dye, indigo carmine, turns the urine green and can last for several days if renal function is poor. While more often reported to cause pink urine, the anesthetic, propofol, has also been reported to cause green coloration of the urine (11). Amitriptyline, indomethacin, resorcinol, triamterine, cimetidine, phenergan, and several multivitamins also lend a blue-green tint to the urine (6). An inherited form of high calcium (called "familial hypercalcemia") can result in blue urine, which has lent this disease the nickname "blue diaper syndrome" (12). Another metabolic disorder, indicanuria, can cause blue urine due to tryptophan indole metabolites (12).

A blue pigment may also be produced by infection with the bacteria Pseudomonas (1,2). Dark green pigmentation, especially if associated with air (known as "pneumaturia"), urinary tract infection, and/or solid particles in the urine, can be caused by bile when there is a fistula between the urinary tract the intestines.

BROWN /BLACK
Brown or black urine (not due to myoglobin or bilirubin) may be caused by excessive L-dopa or melanin excretion as well as copper or phenol poisoning (6). Ingestion of large amounts of rhubarb, fava beans, or aloe can cause dark brownish black urine (13). Metabolites of the antihypertensive medication methyldopa (Aldomet) may turn black on contact with bleach (which is often present in toilet bowls) (6). Other medications causing brown or brown-black urine are chloraquine and primaquine, furazolidone, metronidazole, nitrofurantoin, cascara/senna laxatives, methocarbamol, and sorbitol (6). Contamination with povidone-iodine (Betadine) solution or douche can turn urine brown (14). Melanin and melanogen, found in the urine of patients with melanoma, will darken standing urine from the air-exposed surface downward (15). Alcaptonia, a rare hereditary disease, the urine will turn dark after being exposed to the air over a period of time due to the presence of homogentisic acid (16). Urinary hydroxyphenylpyruvic acid excretion due the metabolic disorder tyrosinosis will also cause urine to be brown-black in color (13). In porphyria cutanea tarda, the urine will appear reddish brown in natural light but fluoresces pink under ultraviolet light (17).

REFERENCES:
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2. Fleisher DS. Urine of abnormal color. Pediatrics. 1968 Sep;42(3):545-6.

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4. Raymond JR, Yarger WE. Abnormal urine color: differential diagnosis. South Med J. 1988 Jul;81(7):837-41.

5. Hsu RM, Baskin LB. Laboratory evaluation of discolored urine. When is it hematuria? MLO Med Lab Obs. 2000 Jul;32(7):44-52

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9. Rosenberg JW. Phenytoin and red urine. JAMA. 1983 Oct 14;250(14):1842-3.

10. Lord RC. Orange urine. Postgrad Med J. 1999 Feb;75(880):109-10.

11. Blakey SA, Hixson-Wallace JA. Clinical significance of rare and benign side effects: propofol and green urine. Pharmacotherapy. 2000 Sep;20(9):1120-2.

12. Drummond KN, Michael AF, Ulstrom RA, Good RA. The blue diaper syndrome: familial hypercalcemia with nephrocalcinosis and indicanuria. A new familial disease, with definition of the metabolic abnormality. Am J Med 1964; 37: 928Ð948.

13. Noll WW, Glass DD. Causes of dark urine. JAMA. 1980 Jun 20;243(23):2398.

14. Baker MD, Baldassano RN. Povidone iodine as a cause of factitious hematuria and abnormal urine coloration in the pediatric emergency department. Pediatr Emerg Care. 1989 Dec;5(4):240-1.

15. Jimbow K, Lee SK, King MG, Hara H, Chen H, Dakour J, Marusyk H. Melanin pigments and melanosomal proteins as differentiation markers unique to normal and neoplastic melanocytes. J Invest Dermatol. 1993 Mar;100(3):259S-268S.

16. Adonis-Koffy L, Gonzales E, Nathanson S, Spodek C, Bensman A. Alcaptonuria: a rare cause of urine discoloration. Report of a case in a newborn. Arch Pediatr. 2000 Aug;7(8):844-6.

17. Rich MW. Porphyria cutanea tarda. Don't forget to look at the urine. Postgrad Med. 1999 Apr;105(4):208-10, 213-4.

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