1 ROUTINE PHYSICAL AND BIOCHEMICAL URINE TESTS

Question 1

Which statement regarding renal function is true?
A. Glomeruli are far more permeable to H2O and salt compared with 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 and urea

Answer 1

A. Glomeruli are far more permeable to H2O and salt compared with other capillaries

The formation of plasma ultrafiltrate depends on 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.

Question 2

Which statement regarding normal salt and H2O handling by the nephron is correct?
A. The thick 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

Answer 2

A. The thick ascending limb of the tubule is highly permeable to salt but not H2O

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 thick 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.

Question 3

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 less than 3.5 mmol/L
C. No substance can be excreted into urine at a rate that exceeds the glomerular filtration rate (GFR)
D. When tubular function is lost, the specific gravity (SG) of urine will be below 1.005

Answer 3

A. In salt deprivation, the kidneys will conserve sodium at the expense of potassium

Sodium is a threshold substance; that is, no sodium will be excreted in 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 SG of urine becomes the same as that of plasma, approximately 1.010.

Question 4

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 to 8°C for up to 48 hours prior to plating

Answer 4

D. The sample may be held at 2°C to 8°C for up to 48 hours prior to plating

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

Question 5

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. A midday sample is preferred when renal disease is suspected

Answer 5

C. Samples may be stored at room temperature for up to 2 hours

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.

Question 6

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

Answer 6

C. Deep yellow urine and yellow foam with bilirubin

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, dyes excreted by the kidneys, and natural or artificial food coloring.

Question 7

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

Answer 7

D. Coproporphyrin

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.

Question 8

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

Answer 8

B. Lead poisoning

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 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 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.

Question 9

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

Answer 9

D. Serum, urine, and fecal tests may be needed for diagnosis

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 PBG and Δ-aminolevulinic acid (porphyrin precursors), whereas 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.

Question 10

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

Answer 10

D. Porphyria cutanea tarda

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 urine. The enzyme in hepatocytes is susceptible to drugs, alcohol, and hepatitis, which 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 they have been exposed to sunlight.

Question 11

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 reaction
D. Isotope dilution–MS

Answer 11

A. Watson-Schwartz test

The Watson-Schwartz test is a qualitative screening test for PBG and is based on the principle that dietary indole compounds and urobilinogen can be separated from PBG by extraction. PBG is extracted in n-butanol, whereas urobilinogen and dietary indoles are extracted into chloroform. However, the sensitivity and specificity of the test are poor in comparison with 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.

Question 12

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

Answer 12

D. Melanin

Excretion of melanin in malignant melanoma and homogentisic acid in alkaptonuria cause 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 red or orange-red urine.

Question 13

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

Answer 13

B. Porphyria cutanea tarda

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.

Question 14

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

Answer 14

B. Protein

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

Question 15

Which one of the following characteristics would be a reason for performing a microscopic examination of urinary sediment?
A. High volume
B. Color intensity
C. Turbidity
D. Specimen from a Foley catheter

Answer 15

C. Turbidity

Urine microscopy reflex testing is used by laboratories that do not perform automated microscopic urinalysis because of the low likelihood of significant findings when the microscopic analysis is performed on samples with normal physical characteristics and biochemical results. Urine samples with abnormal color and clarity are usually included in the criteria for reflex testing because either may be associated with abnormal cells or crystals.

Question 16

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

Answer 16

C. All urine should be collected in a single container that is kept refrigerated

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. To prevent degradation of the catecholamines, vanillylmandelic acid (VMA), metanephrines, and cortisol, urine must be refrigerated during storage and kept at 2°C to 8°C until analysis or frozen. If the pH of the specimen exceeds 3.0, degradation of catecholamines can occur. Preservation of urine with acid is no longer required for VMA, metanephrines, and cortisol.

Question 17

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

Answer 17

C. Defined as oliguria

Normal daily urine excretion is usually 600 to 1,600 mL/day. Isosthenuria refers to urine of constant 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.

Question 18

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

Answer 18

A. Protein

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.

Question 19

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

Answer 19

C. Diabetes insipidus

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).

Question 20

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

Answer 20

C. Chronic renal failure

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 (U:P) ratio exceeds 2:1. Chronic renal failure is associated with nocturia, polyuria, and low SG caused by scarring of the collecting
tubules.

Question 21

Which statement regarding methods for measuring SG is true?
A. Refractometry is the most accurate way to determine dissolved solute concentration
B. Colorimetric SG test results are falsely elevated when a large quantity of glucose is present
C. Colorimetric SG readings are falsely low when pH is alkaline
D. Refractometry should be performed before the urine is centrifuged

Answer 21

C. Colorimetric SG readings are falsely low when pH is alkaline

Cells and undissolved solutes refract light and will cause a falsely high specific gravity reading by refractometry if urine is not centrifuged. Colorimetric SG tests are less sensitive to nonionized compounds, such as urea and glucose, and are negatively biased when large quantities of nonelectrolytes are present. Colorimetric SG readings are determined by a pH change on the test pad and are approximately 0.005 lower when pH is 6.5 or higher. Osmometry is the most accurate way to measure the concentration of dissolved solutes in urine.

Question 22

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

Answer 22

A. Ionic strength alters the pKa of a polyelectrolyte

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.

Question 23

Which statement regarding urine pH is true?
A. A high-protein diet promotes 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

Answer 23

C. Contamination should be suspected if urine pH is less than 4.5

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 hydrogen ion secretion occurs when urine pH reaches 4.5, the lowest urinary pH that the kidneys can produce.

Question 24

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

Answer 24

B. Consistently alkaline

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.

Question 25

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

Answer 25

B. 0.6 to 1.6 L

Under conditions of normal fluid intake, the reference range for urine volume is 0.6 to 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.

Question 26

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

Answer 26

C. 1.008 to 1.010

The SG of the filtrate in the Bowman space approximates the SG of 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.

Question 27

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

Answer 27

D. 7.5 to 8.5

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 compensate for alkalosis and causes urine pH to be alkaline.

Question 28

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

Answer 28

B. Highly buffered alkaline urine

In addition to highly buffered alkaline urine, a false-positive protein result on the dry reagent strip 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 result 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.

Question 29

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)

Answer 29

B. The presence of x-ray contrast media

Turbidimetric assays are used to test urine suspected of giving a false-positive result on the dry reagent strip test for albumin because the urine is highly alkaline (pH greater than or equal to 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. SSA is less specific but more sensitive for albuminuria than conventional dry reagent strip tests. Iodinated dyes, penicillin, salicylate, and tolbutamide may result in false-positive results. Trace turbidity is difficult to determine when urine is cloudy as a result of bacteriuria, mucus, or crystals. Alkaline urine may titrate SSA, reducing its sensitivity. For these reasons, the SSA test is not used routinely.

Question 30

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 intravenous pyelography (IVP)
D. In uremia

Answer 30

C. After intravenous pyelography (IVP)

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.

Question 31

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

Answer 31

D. Bence-Jones protein

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.

Question 32

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

Answer 32

D. 150 mg

Small amounts of albumin and other low molecular weight proteins, such as amylase, β-microglobulins, and immunoglobulin fragments, are excreted in 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 to 2.0 mg/dL, and for dry reagent strip tests, it is approximately 15 mg/dL. Therefore, trace positives by either method may occur in the absence of renal disease.

Question 33

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

Answer 33

D. Ascorbic acid

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.

Question 34

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

Answer 34

A. Testing may detect early renal involvement in diabetes mellitus

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 to 200 µg/mL or in excess of 30 mg albumin per gram of
creatinine. Results in this range are significant in the at-risk population, even though the dry reagent strip test for protein may yield negative results. 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.

Question 35

Dry reagent strip tests for microalbuminuria that compare albumin to creatinine determine the creatinine concentration based on 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

Answer 35

A. Formation of a Cu+2 creatinine complex

The dry reagent strip test for creatinine contains anhydrous buffered copper II sulfate (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 ethylenediaminetetraacetic acid (EDTA), which chelates the copper. Positive interference occurs from hemoglobin and some drugs (e.g., nitrofurantoin). The microalbumin concentration is determined by the protein error of indicator effect using a dye with increased sensitivity, bis-tetrabromosulfonephthalein.

Question 36

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

Answer 36

D. Renal tubular proteinuria

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 small proteins, such as β2 microglobulin. Dry reagent strip tests for proteinuria are poorly sensitive to globulins and do not detect small quantities of hemoglobin, myoglobin, or microglobulins. Electrophoresis of urine is used to detect renal tubular proteinuria.

Question 37

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

Answer 37

D. 165 to 180 mg/dL

The renal threshold is the concentration of a substance (e.g., glucose) in blood that must be exceeded before it can be detected in 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 urine.

Question 38

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

Answer 38

C. Pregnancy

In addition to diabetes mellitus, glycosuria may occur in other endocrine diseases, in pregnancy, in response to drugs that affect glucose tolerance or renal threshold, and in several other conditions, especially those involving the liver or the central nervous system (CNS). Cushing 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.

Question 39

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

Answer 39

A. Acetoacetic acid (AAA)

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.

Question 40

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

Answer 40

A. True glycosuria

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 result on the glucose oxidase test because this test 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.

Question 41

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

Answer 41

C. The presence of a nonglucose reducing sugar, such as galactose

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 result for reducing sugars seen with a negative glucose oxidase test result may occur in lactose, galactose, and fructosuria and other disorders of carbohydrate metabolism. Such tests should always be confirmed with chromatography to identify the specific sugar and with assay of the specific enzyme involved.

Question 42

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

Answer 42

A. Acidosis

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 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 SG.

Question 43

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

Answer 43

A. Sodium nitroprusside

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

Question 44

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

Answer 44

B. Renal failure

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.

Question 45

Which of the following statements regarding the classic 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

Answer 45

C. It may be falsely positive in phenylketonuria

Tests for ketones are less sensitive to acetone than to AAA and do not detect βhydroxybutyric acid. High levels of phenylpyruvic acid (phenylketonuria) will cause a false-positive reaction in the classic 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.

Question 46

Hemoglobin in urine can be differentiated from myoglobin by 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

Answer 46

A. 80% ammonium sulfate to precipitate hemoglobin

Both hemoglobin and myoglobin have peroxidase activity and cause a positive blood test result. However, myoglobin is soluble in 80% weight per volume (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 the presence of hemoglobin as the cause of a positive blood test result.

Question 47

Which of the following conditions is associated with a negative blood test result 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

Answer 47

D. Extravascular hemolytic anemia

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

Question 48

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 to 2 RBCs per high-power field (RBCs/HPF)
D. Salicylates cause a false-positive reaction

Answer 48

B. Abnormal color may be absent from the urine when the reaction is positive

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/HPF as a nonhemolyzed trace. Greater than 3 RBCs/HPF is abnormal.

Question 49

A moderately positive result on the blood test and trace protein test are seen on the dry reagent strip, and 11 to 20 RBCs/HPF are seen in the microscopic examination. 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

Answer 49

D. Recent urinary tract catheterization

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 cancers, and catheterization of the urinary tract.

Question 50

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 examination
C. Negative blood, but 6 to 10 RBCs/HPF
D. Negative blood, but positive protein

Answer 50

C. Negative blood, but 6 to 10 RBCs/HPF

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

Question 51

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

Answer 51

B. The test detects only conjugated bilirubin

Only the conjugated form of bilirubin is excreted into 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 on the 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.

Question 52

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

Answer 52

C. p-Dimethylaminobenzaldehyde

Urobilinogen reacts with the Ehrlich aldehyde reagent (p-dimethylaminobenzaldehyde in hydrochloric acid [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 urine orange-red. Formalin may cause a false-negative reaction.

Question 53

Which of the following statements regarding urinary urobilinogen is true?
A. Diurnal variation occurs, and the highest levels are seen in the early morning
B. High levels accompanied by a positive bilirubin test result 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

Answer 53

C. Dry reagent strip tests do not detect decreased levels

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.

Question 54

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 on adequate dietary nitrate content
D. A positive test differentiates bacteriuria from in vitro bacterial contamination

Answer 54

C. The test is dependent on adequate dietary nitrate content

The nitrite test is dependent on the activity of bacterial reductase, and false-negative results 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-negative results 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- to 4-hour storage time in the bladder. In addition, the causative bacteria must be able to reduce nitrate.

Question 55

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 on the hydrolysis of substrate by WBC esterases
C. Several antibiotics may give a false-positive reaction
D. The test is sensitive to 2 to 3 WBCs/HPF

Answer 55

B. The reaction is based on the hydrolysis of substrate by WBC esterases

Polymorphonuclear cells (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 to 10 WBCs/HPF. Several antibiotics, high protein, and high SG inhibit the esterase reaction. Formalin may cause a false-positive result.

Question 56

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 on lean body mass

Answer 56

D. Creatinine clearance is dependent on lean body mass

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 24 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. Because of the difficulty in collecting a valid 24-hour urine sample, the estimated glomerular filtration rate (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 Modification of Diet in Renal Disease Study (MDRD) formula for eGFR.

Question 57

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

Answer 57

D. Reduced glomerular filtration without uremia

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

Question 58

Which of the following substances can be used to calculate eGFR?
A. p-Aminohippuric acid (PAH)
B. Glycine
C. Cysteine
D. Cystatin C

Answer 58

D. Cystatin C

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, gender, or nutritional status. Plasma cystatin C is increased when the GFR 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. Amino acids
are partially reabsorbed by the tubules and are not present in blood at a constant rate.

Question 59

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

Answer 59

A. Urea is 100% filtered by the glomeruli

Blood urea nitrogen (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 GFR. Although urea is completely filtered by the glomerulus, the tubules reabsorb 30% to 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 as a result of 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.

Question 60

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

Answer 60

B. 78 mL/min

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 because as serum creatinine goes up, urine creatinine goes down.