Harr: Urinalysis and Body Fluids

Which statement regarding renal function is true?
A. Glomeruli are far more permeable to H2O and
salt than other capillaries
B. The collecting tubule reabsorbs sodium and
secretes potassium in response to antidiuretic
hormone (ADH)
C. The collecting tubule is permeable to H2O only
in the presence of aldosterone
D. The thick ascending limb is highly permeable to
H2O and urea

A The formation of plasma ultrafiltrate depends upon high hydrostatic pressure and permeability of the glomeruli. Aldosterone is released when afferent arterial pressure falls, and ADH is released when plasma osmolality becomes too high. The collecting tubule reabsorbs sodium and secretes potassium in response to aldosterone, and is permeable to H2O only in the presence of ADH. The thick ascending limb is permeable to salt, but not to H2O or urea.

Which statement regarding normal salt and H2O
handling by the nephron is correct?
A. The ascending limb of the tubule is highly
permeable to salt but not H2O
B. The stimulus for ADH release is low arterial
pressure in the afferent arteriole
C. The descending limb of the tubule is impermeable
to urea but highly permeable to salt
D. Renin is released in response to high plasma
osmolality

A The tubules are able to concentrate the filtrate
because the descending limb is highly permeable to H2O and urea but not to salt, and the ascending limb is permeable to salt. Salt leaving the ascending limb creates a hypertonic interstitium that forces H2O from the descending limb. Renin is released in response to low hydrostatic pressure in the afferent arteriole,
which stimulates the juxtaglomerular cells. ADH is
released by the posterior pituitary in response to
high plasma osmolality.

Which statement concerning renal tubular
function is true?
A. In salt deprivation, the kidneys will conserve
sodium at the expense of potassium
B. Potassium is not excreted when serum
concentration is below 3.5 mmol/L
C. No substance can be excreted into urine at a rate
that exceeds the glomerular filtration rate
D. When tubular function is lost, the specific
gravity of urine will be below 1.005

A Sodium is a threshold substance, meaning that no sodium will be excreted in the urine until the renal threshold (a plasma sodium concentration of
approximately 120 mmol/L) is exceeded. Potassium is not a threshold substance and will be secreted by the tubules even when plasma potassium levels are low. Patients on diuretics or who have hypovolemia become hypokalemic for this reason. Some substances (e.g., penicillin) can be excreted at a rate exceeding glomerular filtration because the tubules secrete them. The tubules are responsible for concentrating the filtrate in conditions of water deprivation and diluting it in conditions of water excess. When tubular function is lost, salt and water equilibrate by passive diffusion and the specific gravity of the urine becomes the same as the plasma, approximately 1.010.

Which of the following is inappropriate when
collecting urine for routine bacteriologic culture?
A. The container must be sterile
B. The midstream void technique must be used
C. The collected sample must be plated within
2 hours unless refrigerated
D. The sample may be held at 2°C-8°C for up
to 48 hours prior to plating

D Urine specimens should be plated and incubated within 2 hours of collection (some labs use a 1-hour time limit), and within 24 hours if the sample is refrigerated at 2°C-8°C immediately following collection. No additives are permitted when urine is collected for culture.

Which statement about sample collection for
routine urinalysis is true?
A. Preservative tablets should be used for collecting
random urine specimens
B. Containers may be washed and reused if rinsed
in deionized H2O
C. Samples may be stored at room temperature for
up to 2 hours
D. First morning voided samples are not acceptable
when renal disease is suspected

C The first morning voided sample is the most sensitive for screening purposes because formed elements are concentrated, but random samples are satisfactory because glomerular bleeding,
albuminuria, and cast formation may occur at any
time. Preservative tablets should be avoided because they may cause chemical interference with some dry reagent strip and turbidimetric protein tests. Changes in glucose, bilirubin, and urobilinogen can occur within 30 minutes of collection. Therefore, samples should be refrigerated if not tested within 2 hours.

Which urine color is correlated correctly with the
pigment-producing substance?
A. Smoky red urine with homogentisic acid
B. Dark amber urine with myoglobin
C. Deep yellow urine and yellow foam with
bilirubin
D. Red-brown urine with biliverdin

C Homogentisic acid causes dark brown or
black-colored urine. Myoglobin causes a red to
red-brown color in urine, and biliverdin causes a
green or yellow-green color. In addition to
metabolic diseases and renal disease, abnormal
color can be caused by drugs (e.g., Gantrisin), dyes excreted by the kidneys (e.g., PSP), and natural or artificial food coloring (e.g., beets).

Which of the following substances will cause urine
to produce red fluorescence when examined with
an ultraviolet lamp (360 nm)?
A. Myoglobin
B. Porphobilinogen (PBG)
C. Urobilin
D. Coproporphyrin

D Myoglobin causes a positive test for blood but
does not cause urine to fluoresce. PBG causes urine to become dark (orange to orange-brown) on standing but does not fluoresce. Uroporphyrin
and coproporphyrin produce red or orange-red
fluorescence. Unlike hemoglobin, porphyrins lack
peroxidase activity. Urobilin is an oxidation product of urobilinogen. It turns the urine orange to orange-brown but does not produce fluorescence.

Which of the following conditions is associated
with normal urine color but produces red
fluorescence when urine is examined with an
ultraviolet (Wood's) lamp?
A. Acute intermittent porphyria
B. Lead poisoning
C. Erythropoietic porphyria
D. Porphyria cutanea tarda

B Lead poisoning blocks the synthesis of heme, causing accumulation of PBG and coproporphyrin III in urine. However, uroporphyrin levels are not sufficiently elevated to cause red pigmentation of the urine. There is sufficient coproporphyrin to cause a positive test for fluorescence. Acute intermittent porphyria produces increased urinary delta-aminolevulinic acid (Δ-ALA), and PBG. The PBG turns the urine orange to orange-brown upon standing. Erythropoietic porphyria and porphyria cutanea tarda produce large amounts of uroporphyrin, causing the urine to be red or port wine colored.

Which statement regarding porphyria is accurate?
A. Porphyria is exclusively inherited
B. All types cause an increase in urinary porphyrins
C. All types are associated with anemia
D. Serum, urine, and fecal tests may be needed for
diagnosis

D Porphyria may be inherited as a result of an enzyme defect in heme synthesis or may be acquired as a result of lead poisoning, liver failure, or drug toxicity. The inherited porphyrias consist of eight subgroups based on which enzyme is deficient. They are divided clinically into three groups: neuropsychiatric, cutaneous, or mixed. The neurological porphyrias are not associated with anemia, but erythropoietic
porphyria, a type of cutaneous porphyria, is. In
general, neurological porphyrias are associated with increases in porphobilinogen and Δ-aminolevulinic acid, while cutaneous porphyrias are associated with increased urinary porphyrins. No one sample type can be used to identify all subgroups and sometimes all three are needed.

Which is the most common form of porphyria?
A. Erythropoietic porphyria
B. Acute intermittent porphyria
C. Variegate porphyria
D. Porphyria cutanea tarda

D Porphyria is a rare condition, although most of the inherited forms are autosomal dominant. Porphyria cutanea tarda results from a deficiency of uroporphyrinogen decarboxylase, and hence, the carboxylated forms of uroporphyrin accumulate in plasma and spill into the urine. The enzyme in hepatocytes is susceptible to drugs, alcohol, and hepatitis that trigger the disease. The disease usually appears in middle-aged adults, the majority of whom have hepatitis C infection. The uroporphyrins are highly fluorescent and may cause port-wine colored urine. Affected persons present with skin blisters and skin burns if exposed to sunlight.

Which of the following methods is the least
sensitive and specific for measuring PBG in urine?
A. Watson-Schwartz test
B. LC-MS
C. Ion exchange chromatography-Ehrlich's reaction
D. Isotope dilution-MS

A The Watson-Schwartz test is a qualitative screening test for PBG and is based upon the principle that dietary indole compounds and urobilinogen can be separated from PBG by extraction. PBG is extracted in n-butanol, while urobilinogen and dietary indoles are extracted into chloroform. However, the sensitivity and specificity of the test are poor in comparison to
chromatographic and mass spectroscopic methods that better separate PBG from interfering substances. PBG is elevated in neurological porphyrias, the most common of which is acute intermittent porphyria.

A brown or black pigment in urine can be
caused by:
A. Gantrisin (Pyridium)
B. Phenolsulfonphthalein
C. Rifampin
D. Melanin

D Excretion of melanin in malignant melanoma and
homogentisic acid in alkaptonuria cause the urine
to turn black on standing. Other substances that
may cause brown or black-colored urine are
methemoglobin, PBG, porphobilin, and urobilin.
Gantrisin, PSP dye, and rifampin are three examples of drugs that cause a red or orange-red color in urine.

Urine that is dark red or port wine in color may be
caused by:
A. Lead poisoning
B. Porphyria cutanea tarda
C. Alkaptonuria
D. Hemolytic anemia

B Porphyria cutanea tarda and erythropoietic porphyria produce sufficient uroporphyrins to cause dark red urine. Acute intermittent porphyria produces large amounts of PBG, which may be oxidized to porphobilin, turning the urine orange to orange-brown.

Which of the following tests is affected least by
standing or improperly stored urine?
A. Glucose
B. Protein
C. pH
D. Bilirubin

B Standing urine may become alkaline due to loss of volatile acids and ammonia production. Bilirubin
glucuronides may become hydrolyzed to unconjugated bilirubin or oxidized to biliverdin,
resulting in a false-negative dry reagent strip test.
Glucose can be consumed by glycolysis or oxidation by cells.

Which type of urine sample is needed for a
D-xylose absorption test on an adult patient?
A. 24-hour urine sample collected with 20 mL
of 6 N HCl
B. 2-hour timed postprandial urine preserved with
boric acid
C. 5-hour timed urine kept under refrigeration
D. Random urine preserved with formalin

C The D-xylose absorption test is used to distinguish pancreatic insufficiency from intestinal malabsorption. The test requires a blood sample taken 2 hours after oral administration of 25 g of D-xylose, and a 5-hour timed urine sample. D-xylose is absorbed without the aid of pancreatic enzymes, and is not metabolized
by the liver. Therefore, deficient absorption (denoted by a plasma level < 25 mg/dL and urine excretion of < 4g/5hours) points to malabsorption syndrome. Tests requiring a 24-hour urine sample include catecholamines, vanillylmandelic acid (VMA), metanephrines, cortisol, and estriol.

Which of the following is inappropriate
when collecting a 24-hour urine sample for
catecholamines?
A. Urine in the bladder is voided and discarded at
the start of the test
B. At 24 hours, any urine in the bladder is voided
and added to the collection
C. All urine should be collected in a single container
that is kept refrigerated
D. Ten mL of 1N sodium hydroxide should be
added to the container before collection

D When collecting a 24-hour urine sample, the bladder must be emptied of urine at the start of the test and discarded. The bladder must be emptied at the conclusion of the test and the urine added to the collection. In order to prevent degradation of catecholamines VMA, metanephrines, and cortisol, the urine must be refrigerated during storage and kept at 2°C-8°C until analysis or frozen. If the pH of the specimen exceeds 3.0, degradation of catecholamines can occur. Preservation of the urine with acid is no longer required for VMA, metanephrines and cortisol.

Urine production of less than 400 mL/day is:
A. Consistent with normal renal function and
H2O balance
B. Termed isosthenuria
C. Defined as oliguria
D. Associated with diabetes mellitus

C Normal daily urine excretion is usually
600-1,600 mL/day. Isosthenuria refers to urine
of constant specific gravity (SG) of 1.010, which
is the SG of the glomerular filtrate. Glycosuria
causes retention of H2O within the tubule,
resulting in dehydration and polyuria rather
than oliguria.

Which of the following contributes to SG, but
not to osmolality?
A. Protein
B. Salt
C. Urea
D. Glucose

A All substances that dissolve in the urine contribute to osmotic pressure or osmolality. This includes nonionized solutes such as urea, uric acid, and glucose as well as salts, but not colloids such as protein and lipids.

Urine with an SG consistently between 1.002
and 1.003 indicates:
A. Acute glomerulonephritis
B. Renal tubular failure
C. Diabetes insipidus
D. Addison's disease

C In severe renal diseases, the tubules fail to
concentrate the filtrate. Salt and H2O equilibrate by diffusion, causing an SG of about 1.010. If the SG of urine is below that of plasma, free H2O is lost. This results from failure to produce ADH (inherited diabetes insipidus) or from failure of the tubules to respond to ADH (nephrogenic diabetes insipidus, which can be caused by drugs, polycystic kidney disease, and hypercalcemia).

In which of the following conditions is the urine
SG likely to be below 1.025?
A. Diabetes mellitus
B. Drug overdose
C. Chronic renal failure
D. Prerenal failure

C Glucose and drug metabolites increase the SG of urine. In prerenal failure, the tubules are undamaged. Ineffective arterial pressure stimulates aldosterone release. This increases sodium reabsorption, which stimulates ADH release. Water and salt are retained, and the urine:plasma osmolar ratio (U:P) exceeds 2:1.
Chronic renal failure is associated with nocturia,
polyuria, and low SG caused by scarring of the
collecting tubules.

Which statement regarding methods for
measuring SG is true?
A. To correct a urinometer, subtract 0.001 per each
3°C below 15.5°C
B. Colorimetric SG tests are falsely elevated when a
large quantity of glucose is present
C. Colorimetric SG readings are falsely elevated
when pH is alkaline
D. Refractometry should be performed before the
urine is centrifuged

A The density of urine increases at low temperature, causing less fluid to be displaced by the urinometer. This causes the specific gravity to be falsely elevated unless corrected for the difference between the urine temperature and the calibration temperature (15.5°C). Cells and undissolved solutes refract light and will cause a falsely high specific gravity reading by refractometry if urine is not centrifuged. Colorimetric specific gravity tests are less sensitive to nonionized compounds such as urea and glucose, and are negatively biased when large quantities of nonelectrolytes are present. Colorimetric specific gravity readings are determined by a pH change on the test pad and are approximately 0.005 lower when pH is 6.5 or higher.

What is the principle of the colorimetric reagent
strip determination of SG in urine?
A. Ionic strength alters the pKa of a polyelectrolyte
B. Sodium and other cations are chelated by a
ligand that changes color
C. Anions displace a pH indicator from a mordant,
making it water soluble
D. Ionized solutes catalyze oxidation of an azo dye

A A polyelectrolyte with malic acid residues will ionize in proportion to the ionic strength of urine. This causes the pH indicator, bromthymol blue, to react as if it were in a more acidic solution. The indicator will be blue at low SG and green at higher SG.

Which statement regarding urine pH is true?
A. High-protein diets promote an alkaline urine pH
B. pH tends to decrease as urine is stored
C. Contamination should be suspected if urine pH
is less than 4.5
D. Bacteriuria is most often associated with a low
urine pH

C Bacteriuria is usually associated with an alkaline pH caused by the production of ammonia from urea. Extended storage may result in loss of volatile acids, causing increased pH. A high-protein diet promotes excretion of inorganic acids. The tubular maximum for H+ secretion occurs when urine pH reaches 4.5, the lowest urinary pH that the kidneys can produce.

In renal tubular acidosis, the pH of urine is:
A. Consistently acid
B. Consistently alkaline
C. Neutral
D. Variable, depending upon diet

B Renal tubular acidosis results from a defect in the renal tubular reabsorption of bicarbonate. Hydrogen ions are not secreted when bicarbonate ions are not reabsorbed. Wasting of sodium bicarbonate (NaHCO3) and potassium bicarbonate (KHCO3) results in alkaline urine and hypokalemia in association with acidosis.

The normal daily urine output for an adult is
approximately:
A. 0.2-0.5 L
B. 0.6-1.6 L
C. 2.7-3.0 L
D. 3.2-3.5 L

B Under conditions of normal fluid intake, the reference range for urine volume is 0.6-1.6 L per day. Urine output will vary widely with fluid intake. In cases of fluid deprivation, almost all filtrate will be reabsorbed, resulting in daily excretion as low as 500 mL. When fluid intake is excessive, up to 2.0 L of urine may be voided. Urine output beyond these extremes is considered abnormal.

The SG of the filtrate in Bowman's space is
approximately:
A. 1.000-1.002
B. 1.004-1.006
C. 1.008-1.010
D. 1.012-1.014

C The SG of the filtrate in Bowman's space approximates the SG of the plasma because sodium, chloride, glucose, urea, and other main solutes are completely filtered by the glomeruli. This corresponds to an osmolality of approximately 280 mOsm/kg.

A patient with partially compensated respiratory
alkalosis would have a urine pH of:
A. 4.5-5.5
B. 5.5-6.5
C. 6.5-7.5
D. 7.5-8.5

D Urine pH is determined by diet, acid-base balance, water balance, and renal function. In partially compensated respiratory alkalosis, the kidneys reabsorb less bicarbonate, which results in lower net acid excretion. The loss of bicarbonate helps to compensate for alkalosis and causes urine pH to be alkaline.

Which of the following is most likely to cause a
false-positive dry reagent strip test for urinary
protein?
A. Urine of high SG
B. Highly buffered alkaline urine
C. Bence-Jones protein
D. Salicylates

B In addition to highly buffered alkaline urine, a
false-positive dry reagent test may be caused by
quaternary ammonium compounds, which increase
urine pH. Because the dry reagent strip tests are
insensitive to globulins, a false negative is likely in
the case of Bence-Jones proteinuria. Positive
interference by drugs is uncommon for dry reagent strip protein tests but is common for turbidimetric tests. High urinary SG will suppress the color reaction of the strip protein tests.

When testing for urinary protein with
sulfosalicylic acid (SSA), which condition
may produce a false-positive result?
A. Highly buffered alkaline urine
B. The presence of x-ray contrast media
C. Increased urinary SG
D. The presence of red blood cells (RBCs)

B Turbidimetric assays are used to test urine suspected of giving a false-positive dry reagent strip test for albumin because the urine is highly alkaline (pH ≥ 8.0) or contains pigmentation that interferes with reading the protein test pad. In addition, SSA tests are used when screening urine for an increased concentration of globulins because dry reagent strip tests are far less
sensitive to globulins. Sulfosalicylic acid is less specific but more sensitive for albuminuria than dry reagent strip tests. Iodinated dyes, penicillin, salicylate, and tolbutamide may result in false positives. Trace turbidity is difficult to determine when urine is cloudy due to bacteriuria, mucus, or crystals. Alkaline urine may titrate SSA, reducing its sensitivity.

A discrepancy between the urine SG determined
by measuring refractive index and urine osmolality
would be most likely to occur:
A. After catheterization of the urinary tract
B. In diabetes mellitus
C. After an intravenous pyelogram (IVP)
D. In uremia

C The IVP dye contains iodine and is highly refractile. This increases the refractive index of urine, causing falsely high measurement of solute concentration. The refractive index is affected by the size and shape of solutes and undissolved solids such as protein. Osmolality is the most specific measure of total solute concentration because it is affected only by the number of dissolved solutes.

Which of the following is likely to result in a
false-negative dry reagent strip test for
proteinuria?
A. Penicillin
B. Aspirin
C. Amorphous phosphates
D. Bence-Jones protein

D Dry reagent strip tests using tetrabromophenol blue or tetrachlorophenol tetrabromosulfophthalein are poorly sensitive to globulins and may not detect immunoglobulin light chains. Turbidimetric methods such as 3% SSA will often detect Bence-Jones protein but may give a false-positive reaction with penicillin,
tolbutamide, salicylates, and x-ray contrast dyes
containing iodine. Amorphous phosphates may
precipitate in refrigerated urine, making interpretation of turbidimetric tests difficult.

Daily loss of protein in urine normally does not
exceed:
A. 30 mg
B. 50 mg
C. 100 mg
D. 150 mg

D Small amounts of albumin and other low molecular weight proteins such as amylase, β-microglobulins, and immunoglobulin fragments are excreted in the urine. Proteinuria does not normally exceed 30 mg/dL or 150 mg/day. The detection limit of the SSA test to albumin is approximately 1.5-2.0 mg/dL, and for dry
reagent strip tests is approximately 15 mg/dL.
Therefore, trace positives by either method may
occur in the absence of renal disease.

Which of the following is least likely to cause a
false-positive result with turbidimetric protein
tests?
A. Tolbutamide
B. X-ray contrast media
C. Penicillin or sulfa antibiotics
D. Ascorbic acid

D Ascorbic acid may reduce diazo salts used in the bilirubin and nitrite tests, and react with hydrogen peroxide in peroxidase reactions. Therefore, persons taking megadoses of ascorbic acid (vitamin C) may show negative interference with tests for glucose, blood, bilirubin, and nitrite. Ascorbate does not cause either a false-negative or positive reaction for protein.

Which statement best describes the clinical utility
of tests for microalbuminuria?
A. Testing may detect early renal involvement in
diabetes mellitus
B. Microalbuminuria refers to a specific subfraction
of albumin found only in persons with diabetic
nephropathy
C. A positive test result indicates the presence of
orthostatic albuminuria
D. Testing should be part of the routine urinalysis

A The microalbumin test is an assay for measuring urinary albumin concentration that has an increased sensitivity (detection limit below 15 mg/dL), and is recommended for persons who are at risk for chronic renal disease, especially persons with diabetes mellitus. In diabetes, an early sign of renal involvement is an increased rate of albumin excretion in the range of 20-200 μg/mL or in excess of 30 mg albumin per gram creatinine. Results in this range are significant in the at-risk population even though the dry reagent strip test for protein may be negative. Consequently, dry reagent strip tests for
microalbuminuria are too sensitive for use in routine urinalysis, but are useful in screening persons with diabetes and hypertension for increased urinary albumin excretion.

Dry reagent strip tests for microalbuminuria that
compare albumin to creatinine determine the
creatinine concentration based upon which
principle?
A. Formation of a Cu+2-creatinine complex
B. Enzymatic assay using sarcosine oxidase and
peroxidase
C. Reaction of creatinine with alkaline sodium
picrate
D. Change in pH as creatinine is converted to
creatine

A The dry reagent strip test for creatinine contains
anhydrous buffered CuIISO4, alcoholic
tetramethylbenzidine, and diisopropyl benzene
dihydroperoxide. In the presence of creatinine, a
copper-creatinine complex forms. This catalyzes the oxidation of a benzidine derivative by an alcoholic peroxide, forming a blue color on the test pad. Color intensity is proportional to creatinine concentration. Negative interference occurs from ascorbate and EDTA (which chelates the copper). Positive interference occurs from hemoglobin and some drugs (e.g., nitrofurantoin antibiotics). The microalbumin concentration is determined by the protein error of indicator effect using a dye with increased sensitivity, bis-tetrabromosulfonephthalein.

Which of the following conditions is least likely
to be detected by dry reagent strip tests for
proteinuria?
A. Orthostatic albuminuria
B. Chronic renal failure
C. Pyelonephritis
D. Renal tubular proteinuria

D The detection limit (sensitivity) of dry reagent strip protein tests is approximately 15 mg/dL albumin and is sufficient to detect urinary albumin levels found in orthostatic albuminuria and renal diseases, with the exception of tubular proteinuria. Renal tubular proteinuria results from failure of damaged tubules to reabsorb β-microglobulin. Dry reagent strip tests for
proteinuria are poorly sensitive to globulins and do not detect small quantities of hemoglobin, myoglobin, or microglobulins. Protein electrophoresis is used to detect β2-microglobulinuria.

The normal renal threshold for glucose is:
A. 70-85 mg/dL
B. 100-115 mg/dL
C. 130-145 mg/dL
D. 165-180 mg/dL

D The renal threshold is the concentration of a substance (e.g., glucose) in blood that must be exceeded before it can be detected in the urine. Threshold substances require a carrier to transport them from the tubular lumen to the vasa recta. When the carrier becomes saturated, the tubular maximum is reached, causing the substance to be excreted in the urine.

In which of the following conditions is glycosuria
most likely?
A. Addison's disease
B. Hypothyroidism
C. Pregnancy
D. Hypopituitarism

C In addition to diabetes mellitus, glycosuria may occur in other endocrine diseases, pregnancy, in response to drugs that affect glucose tolerance or renal threshold, and several other conditions, especially those involving the liver or central nervous system (CNS). Cushing's disease and hyperthyroidism cause impaired glucose tolerance and hyperglycemia. Increased estrogens produced in pregnancy lower the renal threshold for glucose and may impair glucose tolerance. Hyperpituitarism causes hyperglycemia mediated by increased release of growth hormone.

In addition to ascorbate, the glucose oxidase
reaction may be inhibited by which substance?
A. Acetoacetic acid (AAA)
B. ε-Aminocaproic acid
C. Creatinine
D. Azopyridium

A AAA and salicylates may inhibit the glucose oxidase reaction by the same mechanism as ascorbate. These reducing agents compete with the chromogen for hydrogen peroxide. Low SG may increase and high SG decrease the color reaction for glucose in urine.

A positive glucose oxidase test and a negative test
for reducing sugars indicates:
A. True glycosuria
B. False-positive reagent strip test
C. False-negative reducing test caused by ascorbate
D. Galactosuria

A Glucose oxidase is specific for β-D-glucose. Therefore, a positive reaction is always considered significant unless contamination is evident. A reducing test should not be used to confirm a positive glucose oxidase test because it is not as specific or as sensitive. Reducing sugar tests are used to screen infants for inborn errors of carbohydrate metabolism such as galactosuria but are not used to screen for glycosuria.

A negative glucose oxidase test and a positive test
for reducing sugars in urine indicates:
A. True glycosuria
B. A false-negative glucose oxidase reaction
C. The presence of a nonglucose reducing sugar
such as galactose
D. A trace quantity of glucose

C Reducing tests utilize alkaline copper sulfate and heat to oxidize glucose. Other reducing substances, including several sugars and antibiotics, may react, making the test inappropriate as a screening test for glucose. A positive test for reducing sugars seen with a negative glucose oxidase test may occur in lactose, galactose, and fructosuria and other disorders of carbohydrate metabolism.

In what condition may urinary ketone tests
underestimate ketosis?
A. Acidosis
B. Hemolytic anemia
C. Renal failure
D. Excessive use of vitamin C

A Tests for urinary ketone bodies are sensitive to AAA. They react weakly with acetone and do not react with β-hydroxybutyric acid. Acidosis favors formation of β-hydroxybutyric acid and may cause a falsely low estimate of serum or urine ketones in diabetic ketoacidosis. Ketonuria has many causes other than diabetic ketoacidosis such as pregnancy, fever, protein calorie malnutrition, and dietary carbohydrate restriction. Trace ketones tend to be more clinically significant when seen in urine with a low specific
gravity.

AAA is detected in urine by reaction with:
A. Sodium nitroprusside
B. o-Toluidine
C. m-Dinitrobenzene
D. m-Dinitrophenylhydrazine

A Urinary ketones are detected using alkaline sodium nitroprusside (nitroferricyanide). Mesna and other sulfhydryl compounds may cause a false positive with dry reagent strip tests and phenylpyruvic acid (PKU) and some antibiotics with the classical tube test.

Nondiabetic ketonuria can occur in all of the
following except:
A. Pregnancy
B. Renal failure
C. Starvation
D. Lactate acidosis

B Ketonuria results from excessive oxidation of fats forming acetyl coenzyme A (CoA). In addition to diabetes mellitus, ketonuria occurs in starvation, carbohydrate restriction, alkalosis, lactate acidosis, and von Gierke disease (glycogen stores cannot be utilized). Ketonuria also occurs in pregnancy, associated with increased vomiting and cyclic fever.

Which of the following statements regarding the
classical nitroprusside reaction for ketones is true?
A. The reaction is most sensitive to acetone
B. Nitroprusside reacts with acetone, AAA, and
β-hydroxybutyric acid
C. It may be falsely positive in phenylketonuria
D. The reaction is recommended for diagnosing
ketoacidosis

C Tests for ketones are less sensitive to acetone
than AAA and do not detect β-hydroxybutyric
acid. High levels of phenylpyruvic acid (phenylketonuria) will cause a false-positive
reaction in the classical nitroprusside reaction but
do not usually interfere with the dry reagent strip
test for ketones. Serum ketones can be measured
by gas chromatography, and β-hydroxybutyric acid can be measured enzymatically. The enzymatic assay for β-hydroxybutyrate in plasma is the recommended test for diagnosing ketoacidosis since acidosis favors its formation.

Hemoglobin in urine can be differentiated from
myoglobin using:
A. 80% ammonium sulfate to precipitate
hemoglobin
B. Sodium dithionite to reduce hemoglobin
C. o-Dianisidine instead of benzidine as the color
indicator
D. The dry reagent strip blood test

A Both hemoglobin and myoglobin have peroxidase activity and cause a positive blood test. However, myoglobin is soluble in 80% w/v ammonium sulfate in urine, but hemoglobin precipitates. A positive blood reaction with supernatant after addition of ammonium sulfate and sodium hydroxide (NaOH) confirms the presence of myoglobin. The presence of RBCs indicates that hemoglobin rather than myoglobin is present; however, the absence of RBCs does not rule out hemoglobin as the cause of a
positive blood test.

Which of the following conditions is associated
with a negative blood test and an increase in urine
urobilinogen?
A. Calculi of the kidney or bladder
B. Malignancy of the kidney or urinary system
C. Crush injury
D. Extravascular hemolytic anemia

D A positive test for blood can occur from renal or lower urinary tract bleeding, ntravascular hemolytic anemia, and transfusion reaction. Extravascular hemolysis results in increased bilirubin production rather than plasma hemoglobin. This may cause increased urobilinogen in urine but not a positive blood reaction.

Which statement about the dry reagent strip blood
test is true?
A. The test is based on the reaction of hemoglobin
with peroxidase
B. Abnormal color may be absent from the urine
when the reaction is positive
C. A nonhemolyzed trace is present when there
are 1-2 RBCs per high-power field
D. Salicylates cause a false-positive reaction

B The blood reaction uses anhydrous peroxide
and tetramethylbenzidine. Hemoglobin has peroxidase activity and catalyzes the oxidation of
tetramethylbenzidine by peroxide. The reaction is
sensitive to submilligram levels of free hemoglobin, whereas visible hemolysis does not occur unless free hemoglobin exceeds 20 mg/dL. The test detects approximately 4-5 intact RBCs per high-power field as a nonhemolyzed trace. Greater than 3 RBCs/HPF is abnormal.

A moderate-positive blood test and trace protein
test are seen on the dry reagent strip, and
11-20 red blood cells per high-power field are
seen in the microscopic exam. These results are
most likely caused by which of the following?
A. Transfusion reaction
B. Myoglobinuria
C. Intravascular hemolytic anemia
D. Recent urinary tract catheterization

D The blood test detects intact RBCs, hemoglobinuria, and myoglobinuria. Causes of hemoglobinuria include intravascular hemolytic anemias, transfusion reactions, and lysis of RBCs in the filtrate or urine caused by alkaline or hypotonic conditions. Causes of hematuria
include acute and chronic glomerulonephritis,
pyelonephritis, polycystic kidney disease, renal calculi, bladder and renal cancer, and postcatheterization of the urinary tract.

Which of the following results are discrepant?
A. Small amount of blood but negative protein
B. Moderate amount of blood but no RBCs in
microscopic exam
C. Negative blood but 6-10 RBCs/high-power
field (HPF)
D. Negative blood, positive protein

C The blood test detects as little as 0.015 mg/dL free hemoglobin and 4-5 RBCs/μL. The protein test detects 15 mg/dL albumin but substantially more hemoglobin is required to give a positive test. Therefore, a small blood reaction (nonhemolyzed or moderately hemolyzed trace, trace, or small) usually occurs in the absence of a positive protein. A positive blood test often occurs in the absence of RBCs in the microscopic exam. This can result from intravascular hemolysis, myoglobinuria, or lysis of RBCs caused by alkaline or hypotonic urine. A positive test for protein and a negative blood test occurs commonly in conditions such as orthostatic albuminuria, urinary
tract infection, and diabetes mellitus. However, a
negative blood test should not occur if more than
3-4 RBCs per HPF are seen in the microscopic.
Either the blood test is falsely negative (a missed
nonhemolyzed trace) or yeast have been mistaken
for RBCs.

Which of the following statements regarding the
dry reagent strip test for bilirubin is true?
A. A positive test is seen in prehepatic, hepatic,
and posthepatic jaundice
B. The test detects only conjugated bilirubin
C. Standing urine may become falsely positive due
to bacterial contamination
D. High levels of ascorbate will cause positive
interference

B Only the conjugated form of bilirubin is excreted into the urine. Urinary bilirubin is positive in necrotic and obstructive jaundice but not in prehepatic jaundice, which results in a high level of serum unconjugated bilirubin. The highest levels of urinary bilirubin occur in obstructive jaundice, which causes decreased urinary urobilinogen. Very few drugs have been
reported to interfere with urine bilirubin tests, which are based upon formation of azobilirubin by reaction with a diazonium salt. Positive interference by rifampin and chlorpromazine have been reported. Urine must be fresh because sunlight destroys bilirubin. Bacteria may cause hydrolysis of glucuronides, forming unconjugated bilirubin, which does not react with the diazonium reagent. Ascorbate inhibits the reaction by reducing the diazo reagent.

Which of the following reagents is used to detect
urobilinogen in urine?
A. p-Dinitrobenzene
B. p-Aminosalicylate
C. p-Dimethylaminobenzaldehyde
D. p-Dichloroaniline

C Urobilinogen reacts with Ehrlich's aldehyde
reagent (p-dimethylaminobenzaldehyde in
HCl) to form a pink color. Dry reagent strips
use either p-dimethylaminobenzaldehyde or
4-methoxybenzene diazonium tetrafluoroborate
to detect urobilinogen. The former reagent may
react with PBG, salicylate, and sulfonamides giving
falsely high results. False-positive results may occur in the presence of Pyridium and Gantrisin, which color the urine orange-red. Formalin may cause a false-negative reaction.

Which of the following statements regarding
urinary urobilinogen is true?
A. Diurnal variation occurs with highest levels seen
in the early morning
B. High levels occurring with a positive bilirubin
test indicate obstructive jaundice
C. Dry reagent strip tests do not detect decreased
levels
D. False-positive results may occur if urine is stored
for more than 2 hours

C Urobilinogen exhibits diurnal variation, and highest levels are seen in the afternoon. A 2-hour
postprandial afternoon sample is the sample of
choice for detecting increased urine urobilinogen.
Urobilinogen is formed by bacterial reduction of
conjugated bilirubin in the bowel. In obstructive
jaundice, delivery of bilirubin into the intestine is
blocked, resulting in decreased fecal, serum, and
urine urobilinogen. However, the dry reagent strip
tests are not sensitive enough to detect abnormally low levels. Urobilinogen is rapidly oxidized to urobilin, which does not react with dry reagent strip tests.

Which of the following statements regarding the
test for nitrite in urine is true?
A. It detects more than 95% of clinically significant
bacteriuria
B. Formation of nitrite is unaffected by the
urine pH
C. The test is dependent upon an adequate dietary
nitrate content
D. A positive test differentiates bacteriuria from in
vitro bacterial contamination

C The nitrite test is dependent upon the activity of bacterial reductase, and false negatives have been reported when urine is highly acidic. Nitrite is formed by reduction of diet-derived nitrates and reacts with p-arsanilic acid or sulfanilamide to form a diazonium compound. This reacts with benzoquinoline to form a pink azo dye. False negatives also occur in the presence
of ascorbate, which reduces the diazonium product. Nitrite is positive in about 70% of clinically significant bacterial infections of the urinary tract. Sensitivity is limited by the requirements for dietary nitrate and 3-4 hour storage time in the bladder. In addition, the
causative bacteria must be able to reduce nitrate.

Which statement about the dry reagent strip test
for leukocytes is true?
A. The test detects only intact white blood
cells (WBCs)
B. The reaction is based upon the hydrolysis of
substrate by WBC esterases
C. Several antibiotics may give a false-positive
reaction
D. The test is sensitive to 2-3 WBCs per HPF

B PMNs in urine are detected by the presence
of esterases that hydrolyze an ester such as
indoxylcarbonic acid. The product reacts with a
diazonium salt to give a purple color. The test
detects esterases in urine as well as intact WBCs
but is not sensitive to less than 5-10 WBCs per HPF. Several antibiotics, high protein, and high SG
inhibit the esterase reaction. Formalin may cause a
false-positive result.

Which of the following statements about
creatinine clearance is correct?
A. Dietary restrictions are required during the
24 hours preceding the test
B. Fluid intake must be restricted to below 600 mL
in the 6 hours preceding the test
C. Creatinine clearance is mainly determined by
renal tubular function
D. Creatinine clearance is dependent upon lean
body mass

D Although some creatinine is derived from the diet, it is rapidly filtered by the glomeruli, and time variations are reduced by collection of urine for at least 4 hours. Creatinine is produced from oxidation of creatine at a constant rate of about 2% per day. It is filtered completely and not significantly reabsorbed. However, creatinine secretion by the tubules is increased when filtrate flow is slow, and patients must be given at least
600 mL of H2O at the start of the test and kept well hydrated throughout. Body size determines how much creatinine is produced, and clearance must be normalized to eliminate this variable. Due to the difficulty in collecting a valid 24-hour urine sample, the eGFR is recommended as the screening test for low GFR. Creatinine clearance should be used in situations where lean body mass may not be accurately represented by the patient's age and gender as used in the MDRD formula for eGFR.

A male patient's eGFR is 75 mL/min. This
indicates:
A. Normal glomerular filtration rate
B. The patient is uremic and will be hyperkalemic
C. Renal tubular dysfunction
D. Reduced glomerular filtration without uremia

D Normal eGFR is 90-120 mL/min. Values below the lower reference limit, but above 60 mL/min, indicate glomerular damage but not of severity sufficient to cause symptoms or uremia.

Which of the following tests is a specific measure
of glomerular filtration?
A. p-Aminohippuric acid (PAH) clearance
B. Fishberg concentration test
C. Mosenthal dilution test
D. Cystatin C

D Cystatin C is a small protease inhibitor that is
produced at a constant rate, eliminated exclusively by glomerular filtration, and is not dependent on age, sex, or nutritional status. Plasma cystatin C is increased when the glomerular filtration rate is decreased, and levels can be used to give an eGFR in a similar manner to plasma creatinine. PAH is a substance that is completely filtered by the glomerulus and also secreted by the tubules. PAH clearance has been used rarely to measure renal blood flow. The other two tests are measures of tubular function, but are used infrequently because they are associated with significant health risks. The Fishberg concentration test measures the ability to concentrate urine after deprivation of water. The Mosenthal test measures the ability to excrete free water after excessive water intake..

Which statement regarding urea is true?
A. Urea is 100% filtered by the glomeruli
B. Blood urea levels are independent of diet
C. Urea is not significantly reabsorbed by the
tubules
D. Urea excretion is a specific measure of glomerular
function

A BUN is a sensitive indicator of renal disease, but is not specific for glomerular function. BUN levels are affected by diet, hepatic function, tubular function, and filtrate flow as well as the glomerular filtration rate. Although urea is completely filtered by the glomerulus, the tubules reabsorb 30%-40% of the filtered urea, and this is why BUN concentration is higher than plasma creatinine. In prerenal failure, up to 70% of the filtered urea can be reabsorbed owing to the slow movement of filtrate through the tubules.
This causes BUN to rise much more than plasma
creatinine in this condition. A BUN:creatinine ratio
of 20:1 is highly suggestive of prerenal failure.

Given the following data, calculate the creatinine
clearance.
Serum creatinine = 1.2 mg/dL;
urine creatinine = 100 mg/dL;
urine volume = 1.4 L/day;
body surface area = 1.80 m2
A. 47 mL/min
B. 78 mL/min
C. 100 mL/min
D. 116 mL/min

B The clearance formula is U ÷ P × V × 1.73/A, where
U = urine creatinine (mg/dL), P = plasma
creatinine (mg/dL), V = urine volume (mL/min),
and 1.73 = mean body surface area (m2):
100 mg/dL ÷ 1.2 mg/dL × 1.4L/day ×
1,000 mL/L × 1 day/1,440 min ×
(1.73 m2 ÷ 1.8 m2) = 78 mL/min
Note that the creatinine clearance is low (lower
reference limit approximately 95 mL/min for males
and 85 mL/min for females), although the serum
creatinine is still within normal limits (0.5-1.2 mg/dL). The clearance test is more sensitive if done properly, since as serum creatinine goes up, the urine creatinine goes down.

Which of the following dyes are used in
Sternheimer-Malbin stain?
A. Hematoxylin and eosin
B. Crystal violet and safranin
C. Methylene blue and eosin
D. Methylene blue and safranin

B Sternheimer-Malbin stain is a supravital stain used to help differentiate renal tubular epithelium from transitional cells and PMNs. The mononuclear cells are clearly distinguished from both live and dead PMNs. Transitional cells have pale blue cytoplasm, but renal cells take up both dyes, resulting in an azurophilic appearance (orange-purple cytoplasm and dark purple nucleus).

Which of the following statements regarding
WBCs in urinary sediment is true?
A. "Glitter cells" seen in the urinary sediment are a
sign of renal disease
B. Bacteriuria in the absence of WBCs indicates
lower urinary tract infection (UTI)
C. WBCs other than PMNs are not found in
urinary sediment
D. WBC casts indicate that pyuria is of renal, rather
than lower urinary, origin

D The majority of WBCs in the urinary sediment will be PMNs. Eosinophils and mononuclear WBCs will occasionally be seen. High numbers of eosinophils often indicate an allergic drug reaction, causing inflammation in the medullary interstitium and tubules. Mononuclear cells are especially likely in patients with chronic inflammatory diseases and in renal transplant rejection, where they may account for as many as 30% of the WBCs. Glitter cells are PMNs with highly refractile granules exhibiting Brownian movement. They are seen only when urine SG is below 1.020. These cells resist staining with Sternheimer-Malbin stain and are considered to be living (fresh) WBCs. When seen in large numbers, they indicate urinary tract injury (with pseudopod extensions, they point to infection). The presence of bacteria in urine in the absence of PMNs usually results from contamination by vaginal or skin flora that multiply in vitro, especially in unrefrigerated specimens. The presence of WBC casts is always significant, and when associated with pyuria and bacteriuria, indicates renal involvement in the infection.

Which description of sediment with
Sternheimer-Malbin stain is correct?
A. Transitional epithelium: cytoplasm pale blue,
nucleus dark blue
B. Renal epithelium: cytoplasm light blue, nucleus
dark purple
C. Glitter cells: cytoplasm dark blue, nucleus dark
purple
D. Squamous epithelium: cytoplasm pink, nucleus
pale blue

A After staining with Sternheimer-Malbin stain,
transitional epithelium are readily differentiated from renal tubular cells and WBCs because their cytoplasm is pale blue. Live WBCs exclude Sternheimer-Malbin stain, while dead cells stain with a deeply blue-purple nucleus and pale orange-blue cytoplasm. Renal epithelium have an orange-purple cytoplasm and dark purple nucleus. Squamous epithelium have a blue or purple cytoplasm and an orange-purple nucleus. Red cells stain very pale pink or not at all and hyaline casts stain faintly pink.

SITUATION: A 5-mL urine specimen is submitted
for routine urinalysis and analyzed immediately.
The SG of the sample is 1.012 and the pH is 6.5.
The dry reagent strip test for blood is a large
positive (3+) and the microscopic examination
shows 11-20 RBCs per HPF. The leukocyte
esterase reaction is a small positive (1+), and the
microscopic examination shows 0-5 WBCs per
HPF. What is the most likely cause of these
results?
A. Myoglobin is present in the sample
B. Free hemoglobin is present
C. Insufficient volume is causing microscopic results
to be underestimated
D. Some WBCs have been misidentified as RBCs

C Given the SG and pH, most RBCs and WBCs will
be intact. Both the RBC and WBC counts are lower
than expected from the dry reagent strip results.
Myoglobin or free hemoglobin may account for the poor correlation between the blood reaction and the RBC count, but this does not explain the lower than expected WBC count. Microscopic reference ranges are based upon concentrating a uniform volume of sediment from 12 mL of urine. When less urine is used, falsely low results will be obtained unless corrective action is taken. The specimen should be diluted with normal saline to 12 mL, then centrifuged at 450 × g for 5 minutes. Sediment should be prepared according to the established procedure and the results multiplied by the dilution factor (in this case, 12 ÷ 5, or 2.4).

Which of the following statements regarding
epithelial cells in the urinary system is correct?
A. Caudate epithelial cells originate from the upper
urethra
B. Transitional cells originate from the upper
urethra, ureters, bladder, or renal pelvis
C. Cells from the proximal renal tubule are usually
round in shape
D. Squamous epithelium line the vagina, urethra,
and wall of the urinary bladder

B Caudate cells are transitional epithelium that have a sawtooth-shaped tail and are found in the urinary bladder and the pelvis of the kidney. Transitional epithelia line the upper two-thirds of the urethra and the ureters as well as the urinary bladder and renal pelvis. Renal tubular cells may be columnar, polyhedral, or oval, depending upon the portion of the tubule from which they originate. Cells from the proximal tubule are columnar and have a distinctive brush border. Squamous epithelia line the vagina and lower third of the urethra.

Which of the statements regarding examination
of unstained sediment is true?
A. Renal cells can be differentiated reliably from
WBCs
B. Large numbers of transitional cells are often seen
after catheterization
C. Neoplastic cells from the bladder are not found
in urinary sediment
D. RBCs are easily differentiated from nonbudding
yeast

B Renal cells and PMNs are about the same size
and can be confused in unstained sediment.
Catheterization often releases large clumps or
sheets of transitional and squamous cells. These
should be distinguished from neoplastic cells
derived from the urinary bladder. When cells
appear atypical (e.g., large cells in metaphase),
they should be referred to a pathologist for
cytological examination. Nonbudding yeast cells
are approximately the same in size and appearance as RBCs. When RBCs are seen in the absence of a positive blood test, the probability of an error in microscopy is high. The microscopic examination should be reviewed for the presence of yeast.

Which of the following statements regarding cells
found in urinary sediment is true?
A. Transitional cells resist swelling in hypotonic
urine
B. Renal tubular cells are often polyhedral and have
an eccentric round nucleus
C. Trichomonads have an oval shape with a
prominent nucleus and a single anterior
flagellum
D. Clumps of bacteria are frequently mistaken for
blood casts

B Transitional epithelial cells readily take up H2O and appear much larger than renal cells or WBCs when urine is hypotonic. Transitional cells are considered a normal component of the sediment unless present in large numbers and associated with signs of inflammation such as mucus and PMNs, or presenting features of malignant cells. In contrast, renal cells are significant when seen conclusively in the sediment. They are often teardrop, polyhedral, or elongated cells with a round eccentric nucleus. Conclusive identification requires staining. Trichomonas vaginalis displays an indistinct nucleus and two pairs of prominent anterior flagella. Amorphous urate crystals
deposited on the slide may be mistaken for granular or blood casts.

Which of the following statements regarding
RBCs in the urinary sediment is true?
A. Yeast cells will lyse in dilute acetic acid but RBCs
will not
B. RBCs are often swollen in hypertonic urine
C. RBCs of glomerular origin often appear
dysmorphic
D. Yeast cells will tumble when the cover glass is
touched but RBCs will not

C RBCs are difficult to distinguish from nonbudding yeast in unstained sediment. RBCs tumble when the cover glass is touched and will lyse when the sediment is reconstituted in normal saline containing 2% v/v acetic acid. A nonhemolyzed trace blood reaction confirms the presence of RBCs. RBCs have a granular appearance in hypertonic urine due to crenation. The RBC membrane becomes distorted when passing through the glomerulus, often appearing scalloped, serrated, or invaginated. Such cells are called dysmorphic RBCs and are associated with glomerulonephritis.

Renal tubular epithelial cells are shed into the
urine in largest numbers in which condition?
A. Malignant renal disease
B. Acute glomerulonephritis
C. Nephrotic syndrome
D. Cytomegalovirus (CMV) infection of the kidney

D Although seen in glomerulonephritis and
pyelonephritis, the largest numbers of renal tubular cells appear in urine in association with viral infections of the kidney. Renal epithelium may
show characteristic viral inclusions associated with
CMV and rubella. High numbers of renal epithelium are also found in the sediment of patients with drug-induced tubular nephrosis and some cases of heavy metal poisoning. Renal tumors do not usually shed cells into the urine.

The ova of which parasite may be found in the
urinary sediment?
A. T. vaginalis
B. Entamoeba histolytica
C. Schistosoma hematobium
D. Trichuris trichiura

C Ova of S. hematobium are most often recovered from urine because the adult trematodes colonize the blood vessels of the urinary bladder. The eggs are approximately 150 × 60 μm and are nonoperculated. They are yellowish and have a prominent terminal spine.

Oval fat bodies are often seen in:
A. Chronic glomerulonephritis
B. Nephrotic syndrome
C. Acute tubular nephrosis
D. Renal failure of any cause

B Oval fat bodies are degenerated renal tubular epithelia that have reabsorbed cholesterol from the filtrate. Although they can occur in any inflammatory disease of the tubules, they are commonly seen in the nephrotic syndrome, which is characterized by marked proteinuria and hyperlipidemia.

All of the following statements regarding urinary
casts are true except:
A. Many hyaline casts may appear in sediment after
jogging or exercise
B. An occasional granular cast may be seen in a
normal sediment
C. Casts can be seen in significant numbers even
when protein tests are negative
D. Hyaline casts will dissolve readily in alkaline urine

C Proteinuria accompanies cylindruria because protein is the principle component of casts. After strenuous exercise, hyaline casts may be present in the sediment in significant numbers but will disappear after resting for at least 24 hours.

Which condition promotes the formation of casts
in the urine?
A. Chronic production of alkaline urine
B. Polyuria
C. Reduced filtrate formation
D. Low urine SG

C Cast formation is promoted by an acid filtrate, high solute concentration, slow movement of filtrate, and reduced filtrate formation. The appearance of a cast is dependent upon the location and time spent in the tubule, as well as the chemical and cellular composition of the filtrate.

The mucoprotein that forms the matrix of a
hyaline cast is called:
A. Bence-Jones protein
B. β-Microglobulin
C. Tamm-Horsfall protein
D. Arginine-rich glycoprotein

C Hyaline casts are composed of a mucoprotein called Tamm-Horsfall protein. In addition, casts may contain cells, immunoglobulins, light chains, cellular proteins, fat, bacteria, and crystalloids.

"Pseudocasts" are often caused by:
A. A dirty cover glass or slide
B. Bacterial contamination
C. Amorphous urates
D. Mucus in the urine

C Pseudocasts are formed by amorphous urates that may deposit in uniform cylindrical shapes as the sediment settles under the cover glass. They may be mistaken for granular or blood casts. However, they are highly refractile and lack the well-defined borders of true casts.

Which of the following statements regarding
urinary casts is correct?
A. Fine granular casts are more significant than
coarse granular casts
B. Cylindruria is always clinically significant
C. The appearance of cylindroids signals the onset
of end-stage renal disease
D. Broad casts are associated with severe renal
tubular obstruction

D There is no clinical difference between fine and coarse granular casts. Granular casts may form by degeneration of cellular casts, but some show no evidence of cellular origin. Granular casts may form from inclusion of urinary calculi, but some are of unknown etiology. Cylindruria refers to the presence of casts in the urine. Hyaline casts may be seen in small numbers in normal patients and in large numbers following strenuous exercise and long-distance running. Hyaline casts may also be increased in patients taking certain drugs such as diuretics. Broad
casts form in dilated or distal tubules and indicate
severe tubular obstruction seen in chronic renal failure. Waxy casts form when there is prolonged stasis in the tubules and signal end-stage renal failure. Cylindroids are casts with tails and have no special clinical significance.

A sediment with moderate hematuria and RBC
casts most likely results from:
A. Chronic pyelonephritis
B. Nephrotic syndrome
C. Acute glomerulonephritis
D. Lower urinary tract obstruction

C Red-cell casts indicate the renal origin of hematuria. Urinary tract obstruction may be associated with hematuria from ruptured vessels, but not casts. WBCs and WBC casts predominate in pyelonephritis. Sediment in chronic glomerulonephritis is variable, but usually exhibits moderate to severe intermittent hematuria. In addition, pyuria and cylindruria (with granular, blood, broad, waxy, and epithelial casts) are frequent. In nephrotic syndrome, the sediment may be unremarkable except for the presence of oval fat bodies and hyaline casts. In some cases, fatty, waxy, and epithelial cell casts may also be found.

Urine sediment characterized by pyuria with
bacterial and WBC casts indicates:
A. Nephrotic syndrome
B. Pyelonephritis
C. Polycystic kidney disease
D. Cystitis

B Pyelonephritis results from bacterial infection of the renal pelvis and interstitium. It is characterized by polyuria resulting from failure of the tubules to
reabsorb fluid. Obstruction of tubules and compression by WBCs may reduce glomerular
filtration as well as H2O reabsorption. The finding
of WBC casts helps to differentiate pyelonephritis
from urinary tract infection.

Which type of casts signals the presence of chronic
renal failure?
A. Blood casts
B. Fine granular casts
C. Waxy casts
D. Fatty casts

C Waxy casts form from the degeneration of cellular casts. Because the casts must remain lodged in the tubule long enough for the granular protein matrix to waxify, they are associated with chronic and end-stage renal failure. Both waxy and broad casts form in chronic renal failure when there is severe stasis, and they are associated with a poor prognosis.

SITUATION: Urinalysis of a sample from a
patient suspected of having a transfusion reaction
reveals small yellow-brown crystals in the
microscopic examination. Dry reagent strip tests
are normal with the exception of a positive blood
reaction (moderate) and trace positive protein.
The pH of the urine is 6.5. What test should be
performed to positively identify the crystals?
A. Confirmatory test for bilirubin
B. Cyanide-nitroprusside test
C. Polarizing microscopy
D. Prussian blue stain

D A positive blood test and trace protein occurring with a normal test for urobilinogen and an absence of RBCs are consistent with an intravascular transfusion reaction. Small yellow-brown granular crystals at an acid pH may be uric acid, bilirubin, or hemosiderin. Bilirubin crystals are ruled out by the negative dry reagent strip test for bilirubin. Potassium ferrocyanide is used in the Prussian blue staining reaction to detect hemosiderin deposits in urinary sediment. Hemosiderin is associated with hemochromatosis
and increased RBC destruction. Causes of urinary
hemosiderin include transfusion reaction, hemolytic anemia, and pernicious anemia.

When examining urinary sediment, which of the
following is considered an abnormal finding?
A. 0-2 RBCs per HPF
B. 0-1 hyaline casts per low-power field (LPF)
C. 0-1 renal cell casts per LPF
D. 2-5 WBCs per HPF

C Epithelial casts are rarely seen but indicate a disease process affecting the renal tubules. They are associated with diseases causing necrosis of the tubules such as hepatitis, CMV, and other viral
infections, and mercury and ethylene glycol toxicity. Even occasional cellular casts are considered clinically significant.

SITUATION: A urine sample with a pH of
6.0 produces an abundance of pink sediment
after centrifugation that appears as densely
packed yellow- to reddish-brown granules under
the microscope. The crystals are so dense that no
other formed elements can be evaluated. What is
the best course of action?
A. Request a new urine specimen
B. Suspend the sediment in prewarmed saline,
then repeat centrifugation
C. Acidify a 12-mL aliquot with three drops of
glacial acetic acid and heat to 56°C for
5 minutes before centrifuging
D. Add five drops of 1N HCl to the sediment and
examine

B Urates are yellow- or reddish-brown granules and form in acid or neutral urine. They often form following refrigeration of urine and can be dissolved by addition of warm saline or dilute NaOH. Amorphous phosphates are colorless and form in neutral or alkaline urine. They dissolve in dilute acetic acid but precipitate if heated.

How can hexagonal uric acid crystals be
distinguished from cystine crystals?
A. Cystine is insoluble in hydrochloric acid but uric
acid is soluble
B. Cystine gives a positive nitroprusside test after
reduction with sodium cyanide
C. Cystine crystals are more highly pigmented
D. Cystine crystals form at neutral or alkaline pH,
uric acid forms at neutral to acidic pH

B Flat six-sided uric acid crystals may be mistaken for cystine crystals. Both crystals form at an acid to neutral pH. Cystine crystals are colorless, while uric acid crystals are pigmented (yellow, reddish brown). Cystine transmits polarized light and is soluble in dilute HCl. Uric acid is insoluble in HCl and is less anisotropic. Cystine is reduced by NaCN forming cysteine. The -SH group of cysteine reacts with nitroprusside to form a red color.

The presence of tyrosine and leucine crystals
together in a urine sediment usually indicates:
A. Renal failure
B. Chronic liver disease
C. Hemolytic anemia
D. Hartnup disease

B Tyrosine crystals may occur in tyrosinemia, an inborn error of tyrosine metabolism caused by a deficiency of fumarylacetoacetate hydrolase,
p-hydroxyphenylpyruvic acid oxidase, or tyrosine
aminotransferase (causes of tyrosinuria). However,
when seen along with leucine crystals, the cause is
chronic liver disease, usually cirrhosis of the liver.
Tyrosine usually forms fine brown or yellow
needles, and leucine forms yellow spheres with
concentric rings.

Which of the following crystals is considered
nonpathological?
A. Hemosiderin
B. Bilirubin
C. Ammonium biurate
D. Cholesterol

C Abnormal crystals are those that result from a pathological process. Hemosiderin crystals result from intravascular RBC destruction. Bilirubin crystals are found in severe necrotic and obstructive liver diseases, and cholesterol crystals in nephrotic syndrome, diabetes mellitus, and hypercholesterolemia.

At which pH are ammonium biurate crystals
usually found in urine?
A. Acid urine only
B. Acid or neutral urine
C. Neutral or alkaline urine
D. Alkaline urine only

D Ammonium biurate is often called a "thornapple" crystal because it forms a dark brown spiny sphere. Calcium carbonate is another common crystal that is seen only in alkaline urine. Sodium urate and uric acid form in acid or neutral urine.

Which of the following crystals is seen commonly
in alkaline and neutral urine?
A. Calcium oxalate
B. Uric acid
C. Magnesium ammonium phosphate
D. Cholesterol

C Magnesium ammonium phosphate, also called triple phosphate, may be present in neutral or alkaline urine. Most commonly, triple phosphate crystals are six-sided plates that resemble a coffin lid. Crystals containing phosphates do not occur in acid urine.

Which crystal appears in urine as a long, thin
hexagonal plate, and is linked to ingestion of large
amounts of benzoic acid?
A. Cystine
B. Hippuric acid
C. Oxalic acid
D. Uric acid

B Hippuric acid forms long, colorless, flat six-sided plates. It results from the metabolism of benzoic acid and resembles the "coffin lid" appearance of triple phosphate. It may occur normally as a result of ingestion of vegetables preserved with benzoic acid.

Small yellow needles are seen in the sediment
of a urine sample with a pH of 6.0. Which of
the following crystals can be ruled out?
A. Sulfa crystals
B. Bilirubin crystals
C. Uric acid crystals
D. Cholesterol crystals

D Cholesterol crystals are colorless rectangular plates that often have a notched corner and appear stacked in a stair-step arrangement. Cholesterol crystals are highly anisotropic and can be positively identified using a polarizing microscope. Bilirubin, sulfa, or uric acid crystals may occur as small yellow or yellow-brown needles or rods in neutral or acid urine. Bilirubin crystals should be suspected when the dry reagent strip test for bilirubin is positive and cells in the sediment are dark yellow (bile stained). Sulfa crystals are soluble in acetone, concentrated
HCl, and NaOH. They can be confirmed by the
lignin test in which one drop of sediment and one
drop of 10% HCl react with newsprint to produce a
yellow-orange color.

Oval fat bodies are derived from:
A. Renal tubular epithelium
B. Transitional epithelium
C. Degenerated WBCs
D. Mucoprotein matrix

A Oval fat bodies form from degenerated renal epithelial cells that have reabsorbed cholesterol from the filtrate. They stain with Oil Red O or Sudan III. The fat globules within the cells give a Maltese cross effect when examined under polarized light.

Oval fat bodies are often associated with:
A. Lipoid nephrosis
B. Acute glomerulonephritis
C. Aminoaciduria
D. Pyelonephritis

A The term lipoid nephrosis is a synonym for idiopathic (primary) nephrotic syndrome. Like other forms of nephrotic syndrome, it is associated with gross proteinuria, edema, and hyperlipidemia; however, the idiopathic form is also associated with hematuria. It is common in children, and often associated with mutations that affect podocyte structure.

Urine of constant SG ranging from 1.008 to 1.010
most likely indicates:
A. Addison's disease
B. Renal tubular failure
C. Prerenal failure
D. Diabetes insipidus

B The SG of the filtrate in Bowman's space is
approximately 1.010. Urine produced consistently
with a SG of 1.010 has the same osmolality of the
plasma and results from failure of the tubules to
modify the filtrate.

Which of the following characterizes prerenal
failure, and helps to differentiate it from acute
renal failure caused by renal disease?
A. BUN:creatinine ratio of 20:1 or higher
B. Urine:plasma osmolal ratio less than 2:1
C. Excess loss of sodium in the urine
D. Dehydration

A Prerenal failure is caused by deficient renal blood flow. The tubules are undamaged and will reabsorb more BUN than normal because filtrate flow is slow. Under the influence of aldosterone, they reabsorb sodium and concentrate the urine. The BUN:creatinine ratio and U:P osmolal ratio are very high and sodium output low. In renal disease, the BUN:creatinine ratio is 10 or less, the U:P osmolal ratio approaches 1.0, and the daily sodium excretion is high.

Which of the following conditions characterizes
chronic glomerulonephritis and helps to
differentiate it from acute glomerulonephritis?
A. Hematuria
B. Polyuria
C. Hypertension
D. Azotemia

B Acute glomerulonephritis results in severe compression of the glomerular vessels. This reduces filtration, causing a progression from oliguria to anuria. In contrast, polyuria is associated with chronic glomerulonephritis,
which causes scarring of the collecting tubules. Both acute and chronic glomerulonephritis cause low urine osmolality, azotemia, acidosis, hypertension, proteinuria, and hematuria.

Which of the following conditions is seen in acute
renal failure and helps to differentiate it from
prerenal failure?
A. Hyperkalemia and uremia
B. Oliguria and edema
C. Low creatinine clearance
D. Abnormal urinary sediment

D Reduced glomerular filtration as evidenced by low creatinine clearance characterizes both prerenal and acute renal failure. This results in retention of fluid, causing edema, reduced urine volume, hypertension, uremia, and hyperkalemia in both prerenal and acute renal failure. The kidneys are not damaged in prerenal failure and, therefore, the microscopic examination is usually normal.

Which of the following conditions characterizes
acute renal failure and helps to differentiate it from
chronic renal failure?
A. Hyperkalemia
B. Hematuria
C. Cylindruria
D. Proteinuria

A In acute renal failure, reduced glomerular filtration coupled with decreased tubular secretion results in hyperkalemia. In chronic renal failure, scarring of the collecting tubules prevents salt and H2O reabsorption. This can result in normal or low serum potassium despite reduced glomerular filtration. The sediment in chronic renal failure is characterized by intermittent heavy hematuria and proteinuria.

The serum concentration of which analyte is likely
to be decreased in untreated cases of acute renal
failure?
A. Hydrogen ions
B. Inorganic phosphorus
C. Calcium
D. Uric acid

C Decreased glomerular filtration in renal failure results in high serum creatinine, BUN, and uric acid. Failure of the tubules results in retention of hydrogen ions and phosphates, causing acidosis and an increased anion gap. The tubules fail to respond to parathyroid hormone, resulting in excessive loss of calcium in urine. Serum sodium is usually normal or slightly increased, while hyperkalemia is a constant finding in acute renal failure.

Which of the following conditions is associated
with the greatest proteinuria?
A. Acute glomerulonephritis
B. Chronic glomerulonephritis
C. Nephrotic syndrome
D. Acute pyelonephritis

C Although all four conditions are associated with proteinuria, it is greatest in the nephrotic syndrome. Urinary albumin loss is typically in excess of 4 g/day or 3 mg per mg creatinine, causing dry reagent strip protein tests to give 3+ to 4+ reactions. In contrast to glomerulonephritis and pyelonephritis, the urinary sediment in nephrotic syndrome in adults is not usually characterized by either hematuria or pyuria.
Various casts, lipid laden renal epithelial cells, and
oval fat bodies are usually found.

Which of the following conditions is often a cause
of glomerulonephritis?
A. Hypertension
B. Cytomegalovirus infection
C. Systemic lupus erythematosus
D. Heavy metal poisoning

C Autoimmune diseases, diabetes mellitus, and
nephrotoxic drugs are common causes of acute
glomerulonephritis. Autoimmune damage may result from the deposition of antigen-antibody complexes and complement-mediated damage such as occurs in poststreptococcal glomerulonephritis, or from the production of autoantibodies that attack the basement
membrane as in Goodpasture's syndrome. Acute
glomerulonephritis is often classified by the pattern of injury rather than the cause. For example, insulin deficiency produces sclerotic vascular damage to the glomeruli, often resulting in crescentic glomerulonephritis. Group A strep and SLE result in immunologically mediated damage to the glomeruli usually causing membranous or membranoproliferative
glomerulonephritis. Cytomegalovirus infections and heavy metal poisoning cause damage to the tubules, resulting in nephrosis.

Acute pyelonephritis is commonly caused by:
A. Bacterial infection of medullary interstitium
B. Circulatory failure
C. Renal calculi
D. Antigen-antibody reactions within the glomeruli

A Acute pyelonephritis is caused by infection of the medullary interstitium, usually by coliforms that enter from the lower urinary tract. Escherichia coli is the most commonly implicated bacterium. Since it is focused in the medulla, the disease involves mainly the tubules. As opposed to acute glomerulonephritis, pyelonephritis is not associated with reduced creatinine clearance, azotemia, or oliguria. Reabsorption of salt and water are blocked, resulting in hyperkalemia, acidosis, and polyuria.