Physicochemical Abnormalities

Abnormal Color

Refer to Chapter 33.

Abnormal Specific Gravity

Problem Definition and Identification. USG is an estimate of the concentration of solutes in the urine and is used to evaluate the ability of the kidneys to appropriately concentrate urine. While many urine dipsticks contain a “specific gravity” reagent pad, these are not reliably accurate and should not be interpreted. Specific gravity must be determined by using a refractometer. If there are large amounts of high-molecular-weight substances such as glucose or protein in the urine, the USG will overestimate the solute concentration of the urine and thus the renal concentrating ability. The effect of glucose on the USG is fairly small. The USG rises by approximately 0.004 per 1,000 mg/dL of glucose.

TABLE 56-2. Terminology

Finally, it is imperative to remember that any given USG may be normal depending on the hydration status of the animal in order to maintain normal water balance. USG must always be interpreted in light of the animal’s hydration status, other findings (e.g., presence of azotemia), and recent therapy that might affect renal concentrating ability.

Pathophysiology. Initially, urine is an ultrafiltrate of plasma and, if it is unmodified by the kidneys, it will have a specific gravity similar to the plasma ultrafiltrate (~1.008–1.012). Normal flow of urine through the loop of Henle combined with the countercurrent exchange mechanism of the renal vasculature sets up a concentration gradient of various solutes (primarily urea, sodium, and chloride) in the medulla of the kidney so that it is extremely hypertonic compared to plasma. The ascending loop of Henle is impermeable to water, but sodium and chloride are actively removed from the tubules so that the urine exiting the loop of Henle is hypotonic (USG <1.005).

The urine is then modified as it passes back through the renal medulla in the collecting ducts. The tubular cells of the collecting ducts are permeable to water only in the presence of antidiuretic hormone (ADH). If the animal is overhydrated, ADH is not produced and the urine passes through the collecting ducts unmodified (very dilute), thus eliminating excess free water from the body. If the animal is dehydrated, osmoreceptors in the hypothalamus detect the increase in plasma osmolality and stimulate ADH release from the pituitary. In the presence of the ADH, the cells of the collecting duct are permeable to water and, as the urine in the collecting duct passes through the hypertonic medulla, water is reabsorbed by equilibrating with the hypertonic renal medulla. Thus, water is removed from the urine, which then becomes more concentrated.

Normal concentrating ability can be lost if there is renal disease that causes loss of sufficient functioning nephrons or disruption of normal renal architecture to prevent the development of the normal medullary concentration gradient. Even in the lack of intrinsic renal disease, concentrating ability can also be lost by conditions that result in the medullary gradient being “washed out” (i.e., prolonged severe polyuria and renal sodium loss in Addison’s disease) or conditions that limit the responsiveness of tubular cells to ADH (i.e., hypercalcemia and corticosteroid excess). Also, rapid flow of urine through the medulla in states of polyuria limits the time available for normal equilibration with the medullary gradient and thus will reduce the final concentration of the urine.

Categories of USG and Their Interpretation

USG >1.030 (Dog)/1.040 (Cat). In a dehydrated, nonazotemic animal, this would indicate an appropriate physiologic response to conserve body water. In an azotemic animal, urine concentrated to this extent typically indicates adequate remaining renal function to clear waste products and thus suggests a prerenal cause for the azotemia. However, experimental studies have shown that cats with surgically induced, azotemic renal failure may retain concentrating ability of this magnitude, so renal disease cannot be confidently ruled out in this species on the basis of a single USG. In any azotemic animal, the resolution (or lack thereof) of the azotemia to rehydration and fluid dieresis should help clarify the nature of the azotemia.

USG = 1.013−1.029 (Dog)/1.039 (Cat). This is the range that many random free-catch urine samples are in and, in normal animals, would reflect the level that is needed to maintain hydration. These animals would be able to concentrate their urine further if an appropriate stimulus (i.e., dehydration) were present.

If an animal is dehydrated or azotemic and produces urine in this range, it suggests a partial lack of concentrating ability due to either an intrinsic renal disease or a nonrenal factor interfering with concentrating ability (e.g., glucocorticoid excess, hypercalcemia, diuretic administration, and Addison’s disease). Renal failure is often caused by slowly progressive loss of renal function and thus a slow progressive loss of concentrating ability. Animals whose maximal concentrating ability is in this range have maintained more functional renal mass than those in the fixed range (isosthenuric range) but have inadequate nephrons to fully concentrate the urine.

USG = 1.008−1.012. Urine in this range is of the same concentration as that of the ultrafiltrate of plasma which is initially produced by the glomerulus, and is termed isosthenuria. It strongly suggests a defect in renal concentrating ability (unless the animal is on IV fluids or is consuming excessive water voluntarily). If such an animal is azotemic or dehydrated, it confirms a concentrating defect and is likely the result of end-stage renal failure. Nonrenal factors listed previously could result in isosthenuric urine.

USG <1.007. Urine with USG <1.007 is more dilute than the glomerular filtrate, and is termed hyposthenuria. It does indicate that some renal function exists because diluting the urine is an active process of the kidneys. Hyposthenuric urine is normal in an animal that is overhydrated and needs to clear free water. Animals consistently producing urine in this range typically have either primary polydipsia, diabetes insipidus (central or nephrogenic), or hyperadrenocorticism. These can be differentiated through the cautious use of water deprivation testing, ADH administration, or other specific endocrine tests (see Chapter 5).

Abnormal pH

Problem Definition and Identification. Most urine dipsticks include a pH reagent pad that will measure the pH of the urine to the nearest 0.5 pH units. This is only an estimate of pH and not as accurate as a pH meter, but it is sufficient for clinical use. However, given the imprecision and the fact that units are reported only in 0.5 increments, overinterpretation should be avoided.

The pH of a urine sample will increase if the urine is not examined soon after collection. Carbon dioxide in the sample is volatile and diffuses out. Carbon dioxide acts as an acid since it is in equilibrium with carbonic acid. In addition, discolored urine can interfere with interpretation of changes in the color pad.

Pathophysiology. In health, pH of the urine is most dependent on diet; diets high in animal protein produce acidic urine pH, while primarily vegetable diets result in alkaline urine pH. Most dogs and cats have neutral to acidic urine pH.

Urine pH can be affected by the acid–base status of the animal. pH will change in acid–base abnormalities due to renal attempts to correct the systemic pH. Acidotic animals should have acidic urine as the kidneys excrete excess H+ ions to normalize blood pH. Similarly, alkalotic animals should have urine with a higher pH.

Urinary tract infections (UTIs) with urease-positive bacteria (which convert urea to ammonia) may result in an increased urine pH.

Diagnostic Plan. If an atypical urine pH is encountered (typically alkaline in dogs and cats), the diet of the animal and the possibility of UTI with urease-producing bacteria should be considered. Subsequently, the systemic acid–base status of the animal should be considered.

Most often, urine pH is evaluated to monitor effectiveness of therapeutic attempts to alter the pH (using dietary changes or supplements) in order to eliminate or prevent recurrence of urolithiasis.

Proteinuria

Problem Definition and Identification. Protein is normally present in very low quantities in the urine (at or below the limit of sensitivity of the routine urine dipstick pads). Trace to 1+ results may be normal in animals with concentrated urine.

Numerous factors related to the methodology of protein detection used on the reagent strips as well as physiologic factors are important for interpretation of proteinuria.

The protein pad on a urine dipstick reads from trace (equivalent to 5–20 mg/dL) to 4+ (equivalent to >1,000 mg/dL). The protein pad is associated with the most error in reading because the color changes are minor. In addition, this test is influenced by the pH of the urine. In alkaline urine, the strips may read falsely elevated protein levels. Also, dipstick protein pads are more sensitive to albumin than they are to globulins.

Because of these issues, positive protein readings should be rechecked by a separate method. One common test used in laboratories is the sulfosalicylic acid test that evaluates the turbidity of the urine following precipitation of proteins in the urine by the addition of an acidic reagent. Urine proteins may also be measured by chemical methods, which are much more precise and accurate. The chemical tests are also called “quantitative urine protein” because they give an exact numerical concentration of urine protein rather than semiquantitative (i.e., 1+, 2+, etc.) results. These are used to determine the urine protein/creatinine ratio.

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