,SECTION I GENERAL DISCIPLINES IN VETERINARY MEDICINE
Clinical Pathology:
Clinical Chemistry
1
CH A P TE R
Patricia A. Schenck
2. Better method than endogenous creatinine
EVALUATION OF RENAL FUNCTION
clearance and approximate inulin clearance
I. Blood urea nitrogen (BUN) in dogs
A. Decreased glomerular filtration rate (GFR) results C. Single-injection methods for estimation of GFR
in increased BUN 1. Post-iohexol clearance
B. Affected by urea production in the liver and the a. Give iohexol IV, and collect plasma at
rate of excretion by the kidney 2, 3, and 4 hours postiohexol
C. Increased dietary protein and gastrointestinal b. Plasma clearance is calculated using the area
(GI) bleeding both increase BUN under the plasma concentration vs. time curve
II. Creatinine 2. Inulin clearance is considered the gold stan-
A. An elevation indicates that less than 25% of the dard for measurement of GFR, but inulin is
original functioning renal mass remains not easily measured and is not available at
B. A normal serum creatinine concentration does commercial laboratories
not exclude the possibility of renal disease V. Urine osmolality
C. Young animals have lower serum creatinine A. There is usually a linear relationship between
concentrations than do older animals urine osmolality and specific gravity
D. Cachexia often causes lower serum creatinine B. Urine osmolality depends on the number of
concentrations osmotically active particles present in urine
III. Serum phosphorus concentration C. If urine contains a large amount of larger-molecular-
A. An increase in serum phosphorus is not seen until weight solutes such as glucose, mannitol, or radio-
more than 85% of nephrons are nonfunctional in graphic contrast agents, the urinary specific gravity
chronic renal diseases will be disproportionately high compared with the
B. Tubular reabsorption of phosphorus is regulated osmolality
by parathyroid hormone. Renal secondary hyper- VI. Fractional excretion of electrolytes
parathyroidism tends to keep the serum phos- A. Sodium
phorus concentration within normal limits by 1. Useful in the differentiation of prerenal and
excreting more phosphorus into the urine until primary renal azotemia
renal disease is advanced 2. In animals with prerenal azotemia and volume
C. Serum phosphorus concentrations can be much depletion, there should be sodium conservation
higher in immature animals because of bone with a very low fractional excretion of sodium
growth 3. In animals with primary renal disease, the frac-
IV. Renal clearance (estimation of GFR) tional excretion of sodium should be higher
A. Endogenous creatinine clearance determination than normal
1. Collect all urine for 12 or 24 hours (record B. Potassium
volume), and determine serum and urine 1. May be useful in the evaluation of chronic renal
creatinine concentrations failure patients with hypokalemia to determine
2. Performed when renal disease is suspected but whether the kidneys are contributing to the
both BUN and serum creatinine concentrations hypokalemia
are normal 2. Varies considerably depending on diet
B. Exogenous creatinine clearance C. Phosphorus
1. Creatinine is administered subcutaneously 1. May be useful during treatment of chronic
or intravenously (IV); then urine is collected renal failure to determine whether dietary or
via catheterization three times at 20-minute drug therapy is effective with a reduction in
intervals fractional excretion of phosphorus
1
drj
,2 SECTION I GENERAL DISCIPLINES IN VETERINARY MEDICINE
2. Does not offer any advantage in diagnosis of acidosis, respiratory acidosis, or paradoxical
chronic renal failure aciduria in metabolic alkalosis with potas-
VII. Urinary enzymes sium and chloride depletion
A. -glutamyltransferase (GGT) is a membrane- d. Causes of alkaline urine include plant-based
bound enzyme specific for renal tubular damage diets, urine that has been allowed to
B. N-acetyl--D-glucosaminidase (NAG) stand open to air at room temperature,
1. Lysosomal enzyme produced by many tissues postprandial alkaline tide, urinary tract
but not filtered normally infection (UTI) by urease-positive organ-
2. Increases in urinary NAG are specific for renal isms, contamination of sample with bacte-
tubular damage ria during or after collection, administra-
VIII. Urinalysis tion of alkalinizing agents, metabolic
A. Physical properties alkalosis, respiratory alkalosis, stress in-
1. Color duction of respiratory alkalosis (cats), and
a. Normally colorless to deep amber in color distal renal tubular acidosis
(if very concentrated). Deep amber color 2. Protein
may also be due to bile pigments a. Trace to 1 protein is normal in urine with
b. Red or reddish brown color is due to intact high USG
red blood cells (RBCs), hemoglobin, or b. Dipstick methods are more sensitive to
myoglobin albumin than globulins
c. Dark brown to black is most likely due c. False positives occur in very alkaline urine or
to the conversion of hemoglobin to in urine contaminated with benzylalkonium
methemoglobin chloride
d. Yellow-brown to yellow-green is due to d. Renal proteinuria may result from increased
bilirubin glomerular filtration of protein, failure of
e. Green color may be due to Pseudomonas tubular reabsorption of protein, tubular
infection or to oxidation of bilirubin to secretion of protein, protein leakage from
biliverdin damaged tubular cells, or renal parenchy-
2. Appearance mal inflammation
a. Urine is normally clear in dogs but may be e. Persistent moderate or heavy proteinuria
cloudy in about 20% in the absence of urine sediment abnormali-
b. Cloudy urine usually contains increased ties suggests glomerular disease
cells, crystals, mucus, or casts f. Active sediment with mild to moderate
c. Horse urine is typically cloudy because of proteinuria suggests inflammatory renal
mucus disease or lower urinary tract disease
d. Rabbit urine is white and opaque because 3. Glucose
of the high concentration of calcium a. Normally not present in dog and cat urine
carbonate b. Glucose appears in urine if plasma glucose
3. Odor exceeds approximately 180 mg/dL in the
a. The normal odor of urine is due to volatile dog and 300 mg/dL in the cat
fatty acids c. Causes of glucosuria include diabetes melli-
b. An ammonia odor is due to release of tus (most common), stress or excitement
ammonia by urease-producing bacteria (especially in cats), chronically sick cats in
4. Urine specific gravity (USG) is the weight of the absence of hyperglycemia, renal tubular
urine compared to that of distilled water disease, administration of glucose-containing
a. USG estimated by dipstrip is NOT accurate. fluids, and severe urethral obstruction in
USG should be estimated by refractometry. some cats
Make sure the refractometer is temperature 4. Ketones
compensated and has different scales for a. Not normally present in dog and cat urine
different species b. Inadequate consumption of carbohydrates
b. First-morning urine samples typically have or impaired utilization of carbohydrates can
the highest urinary concentration lead to ketone production
c. Dogs or cats with any detectable dehydration c. Causes of ketonuria include diabetic keto-
should elaborate maximally concentrated acidosis (most common), starvation or
urine (USG 1.040) prolonged fasting, glycogen storage dis-
B. Chemical examination ease, low carbohydrate-high fat diet, and
1. pH persistent hypoglycemia (decreased insulin
a. Measurement by pH meter is superior to induces ketone formation)
dipstrip methods 5. Bilirubin
b. Urine pH varies with diet and acid-base a. Only conjugated bilirubin appears in the
balance. Urine pH is usually acidic in urine. A small amount of bilirubin may
carnivores and alkaline in herbivores normally be seen in concentrated urine
c. Causes of acidic urine include meat diets, samples from normal male dogs. It is not
administration of acidifying agents, metabolic normally found in cat urine
drj
, CHAPTER 1 Clinical Pathology: Clinical Chemistry 3
b. Bilirubin is derived from the breakdown of (3) Clumps or “rafts” are most common
heme by the reticuloendothelial system in neoplasia but may occur with
c. Bilirubin may appear in the urine prior to inflammation
the observation of hyperbilirubinemia c. Renal epithelial cells
d. Causes of bilirubinuria include hemolysis, (1) Small epithelial cells from the renal
liver disease, extrahepatic biliary obstruc- tubules or pelvis
tion, fever, and starvation (2) Appearance in urine is never normal
6. Blood and is observed in patients with isch-
a. Positive earlier than the observation of emic, nephrotoxic, or degenerative
hematuria renal disease
b. Dipstick tests do not differentiate from 5. Casts are cylindrical molds of the renal tubules
intact RBCs or hemoglobin composed of aggregated protein or cells
c. Causes of hemoglobinuria from hemolysis a. Hyaline
include transfusion reaction, immune (1) Pure protein precipitates of Tamm-
mediated hemolytic anemia, disseminated Horsfall mucoprotein
intravascular coagulopathy (DIC), splenic (2) Dissolve rapidly in dilute or alkaline
torsion, severe hypophosphatemia, heat urine
stroke, zinc toxicity, and phosphofructoki- (3) Have the least pathologic significance
nase or pyruvate kinase deficiency and may form transiently with fever,
C. Urinary sediment exercise, or passive congestion to the
1. Sediment preparation kidney
a. Perform on fresh urine samples b. Cellular casts
b. Centrifuge 5 to 10 mL of urine at 1000 to (1) White cell casts suggest pyelonephritis
1500 rpm for 5 minutes. Stain with but may also be caused by interstitial ne-
Sedi-Stain phritis, nephrosis, or glomerulonephritis
c. Number of casts is recorded per low-power (2) Red cell casts are fragile and rarely
field, and cells are recorded per high-power found. They may be noted in acute
field glomerulonephritis, renal trauma, or
2. RBCs after violent exercise
a. Occasional RBCs are normal (3) Hemoglobin casts are casts where the
b. Excessive number of RBCs is called hema- hemoglobin color is retained in the cast
turia, but origin cannot be determined (4) Renal epithelial casts occur with severe
c. Lipid droplets are often confused with tubular injury and suggest acute tubular
RBCs, especially in cats necrosis or pyelonephritis (Figure 1-1)
d. Causes of hematuria include trauma, (5) Renal fragments are a variant of epithe-
urolithiasis, neoplasia, UTIs idiopathic lial casts where portions of the renal
feline lower urinary tract disease, chemi- tubules slough into urine. Their appear-
cally induced cystitis, systemic diseases ance suggests severe renal injury
associated with hemorrhage, renal infarct, (6) Mixed casts contain multiple cell types
nephritis, nephrosis, parasites, renal c. Granular casts (Figure 1-2)
pelvic hematoma, or genital tract (1) Represent the degeneration of cells or
contamination precipitation of filtered plasma proteins
3. White blood cells (WBCs) (2) Fatty casts are a type of granular cast
a. Occasional WBCs are normal that may be seen in nephrotic syn-
b. Excessive WBCs in urine sediment is called drome or diabetes mellitus
pyuria and indicates inflammation some-
where in the urinary tract or contamination
from the genital tract
c. Clumped WBCs are typically due to infectious
organisms
d. Causes of pyuria include urinary tract
inflammation or genital tract
contamination
4. Epithelial cells
a. Squamous epithelial cells
(1) Large, polygonal cells with small, round
nuclei
(2) Common in voided or catheterized
samples
b. Transitional epithelial cells
(1) A small number is normal Figure 1-1 Photomicrograph of an epithelial cell cast in urine. Small renal
(2) Increased in infection, irritation, or epithelial cells can be identified in this case (white arrows). (Courtesy Nancy
neoplasia Facklam; from Ettinger SJ, Feldman EC. Textbook of Veterinary Internal
Medicine, 6th ed. St Louis, 2005, Saunders.)
drj
Clinical Pathology:
Clinical Chemistry
1
CH A P TE R
Patricia A. Schenck
2. Better method than endogenous creatinine
EVALUATION OF RENAL FUNCTION
clearance and approximate inulin clearance
I. Blood urea nitrogen (BUN) in dogs
A. Decreased glomerular filtration rate (GFR) results C. Single-injection methods for estimation of GFR
in increased BUN 1. Post-iohexol clearance
B. Affected by urea production in the liver and the a. Give iohexol IV, and collect plasma at
rate of excretion by the kidney 2, 3, and 4 hours postiohexol
C. Increased dietary protein and gastrointestinal b. Plasma clearance is calculated using the area
(GI) bleeding both increase BUN under the plasma concentration vs. time curve
II. Creatinine 2. Inulin clearance is considered the gold stan-
A. An elevation indicates that less than 25% of the dard for measurement of GFR, but inulin is
original functioning renal mass remains not easily measured and is not available at
B. A normal serum creatinine concentration does commercial laboratories
not exclude the possibility of renal disease V. Urine osmolality
C. Young animals have lower serum creatinine A. There is usually a linear relationship between
concentrations than do older animals urine osmolality and specific gravity
D. Cachexia often causes lower serum creatinine B. Urine osmolality depends on the number of
concentrations osmotically active particles present in urine
III. Serum phosphorus concentration C. If urine contains a large amount of larger-molecular-
A. An increase in serum phosphorus is not seen until weight solutes such as glucose, mannitol, or radio-
more than 85% of nephrons are nonfunctional in graphic contrast agents, the urinary specific gravity
chronic renal diseases will be disproportionately high compared with the
B. Tubular reabsorption of phosphorus is regulated osmolality
by parathyroid hormone. Renal secondary hyper- VI. Fractional excretion of electrolytes
parathyroidism tends to keep the serum phos- A. Sodium
phorus concentration within normal limits by 1. Useful in the differentiation of prerenal and
excreting more phosphorus into the urine until primary renal azotemia
renal disease is advanced 2. In animals with prerenal azotemia and volume
C. Serum phosphorus concentrations can be much depletion, there should be sodium conservation
higher in immature animals because of bone with a very low fractional excretion of sodium
growth 3. In animals with primary renal disease, the frac-
IV. Renal clearance (estimation of GFR) tional excretion of sodium should be higher
A. Endogenous creatinine clearance determination than normal
1. Collect all urine for 12 or 24 hours (record B. Potassium
volume), and determine serum and urine 1. May be useful in the evaluation of chronic renal
creatinine concentrations failure patients with hypokalemia to determine
2. Performed when renal disease is suspected but whether the kidneys are contributing to the
both BUN and serum creatinine concentrations hypokalemia
are normal 2. Varies considerably depending on diet
B. Exogenous creatinine clearance C. Phosphorus
1. Creatinine is administered subcutaneously 1. May be useful during treatment of chronic
or intravenously (IV); then urine is collected renal failure to determine whether dietary or
via catheterization three times at 20-minute drug therapy is effective with a reduction in
intervals fractional excretion of phosphorus
1
drj
,2 SECTION I GENERAL DISCIPLINES IN VETERINARY MEDICINE
2. Does not offer any advantage in diagnosis of acidosis, respiratory acidosis, or paradoxical
chronic renal failure aciduria in metabolic alkalosis with potas-
VII. Urinary enzymes sium and chloride depletion
A. -glutamyltransferase (GGT) is a membrane- d. Causes of alkaline urine include plant-based
bound enzyme specific for renal tubular damage diets, urine that has been allowed to
B. N-acetyl--D-glucosaminidase (NAG) stand open to air at room temperature,
1. Lysosomal enzyme produced by many tissues postprandial alkaline tide, urinary tract
but not filtered normally infection (UTI) by urease-positive organ-
2. Increases in urinary NAG are specific for renal isms, contamination of sample with bacte-
tubular damage ria during or after collection, administra-
VIII. Urinalysis tion of alkalinizing agents, metabolic
A. Physical properties alkalosis, respiratory alkalosis, stress in-
1. Color duction of respiratory alkalosis (cats), and
a. Normally colorless to deep amber in color distal renal tubular acidosis
(if very concentrated). Deep amber color 2. Protein
may also be due to bile pigments a. Trace to 1 protein is normal in urine with
b. Red or reddish brown color is due to intact high USG
red blood cells (RBCs), hemoglobin, or b. Dipstick methods are more sensitive to
myoglobin albumin than globulins
c. Dark brown to black is most likely due c. False positives occur in very alkaline urine or
to the conversion of hemoglobin to in urine contaminated with benzylalkonium
methemoglobin chloride
d. Yellow-brown to yellow-green is due to d. Renal proteinuria may result from increased
bilirubin glomerular filtration of protein, failure of
e. Green color may be due to Pseudomonas tubular reabsorption of protein, tubular
infection or to oxidation of bilirubin to secretion of protein, protein leakage from
biliverdin damaged tubular cells, or renal parenchy-
2. Appearance mal inflammation
a. Urine is normally clear in dogs but may be e. Persistent moderate or heavy proteinuria
cloudy in about 20% in the absence of urine sediment abnormali-
b. Cloudy urine usually contains increased ties suggests glomerular disease
cells, crystals, mucus, or casts f. Active sediment with mild to moderate
c. Horse urine is typically cloudy because of proteinuria suggests inflammatory renal
mucus disease or lower urinary tract disease
d. Rabbit urine is white and opaque because 3. Glucose
of the high concentration of calcium a. Normally not present in dog and cat urine
carbonate b. Glucose appears in urine if plasma glucose
3. Odor exceeds approximately 180 mg/dL in the
a. The normal odor of urine is due to volatile dog and 300 mg/dL in the cat
fatty acids c. Causes of glucosuria include diabetes melli-
b. An ammonia odor is due to release of tus (most common), stress or excitement
ammonia by urease-producing bacteria (especially in cats), chronically sick cats in
4. Urine specific gravity (USG) is the weight of the absence of hyperglycemia, renal tubular
urine compared to that of distilled water disease, administration of glucose-containing
a. USG estimated by dipstrip is NOT accurate. fluids, and severe urethral obstruction in
USG should be estimated by refractometry. some cats
Make sure the refractometer is temperature 4. Ketones
compensated and has different scales for a. Not normally present in dog and cat urine
different species b. Inadequate consumption of carbohydrates
b. First-morning urine samples typically have or impaired utilization of carbohydrates can
the highest urinary concentration lead to ketone production
c. Dogs or cats with any detectable dehydration c. Causes of ketonuria include diabetic keto-
should elaborate maximally concentrated acidosis (most common), starvation or
urine (USG 1.040) prolonged fasting, glycogen storage dis-
B. Chemical examination ease, low carbohydrate-high fat diet, and
1. pH persistent hypoglycemia (decreased insulin
a. Measurement by pH meter is superior to induces ketone formation)
dipstrip methods 5. Bilirubin
b. Urine pH varies with diet and acid-base a. Only conjugated bilirubin appears in the
balance. Urine pH is usually acidic in urine. A small amount of bilirubin may
carnivores and alkaline in herbivores normally be seen in concentrated urine
c. Causes of acidic urine include meat diets, samples from normal male dogs. It is not
administration of acidifying agents, metabolic normally found in cat urine
drj
, CHAPTER 1 Clinical Pathology: Clinical Chemistry 3
b. Bilirubin is derived from the breakdown of (3) Clumps or “rafts” are most common
heme by the reticuloendothelial system in neoplasia but may occur with
c. Bilirubin may appear in the urine prior to inflammation
the observation of hyperbilirubinemia c. Renal epithelial cells
d. Causes of bilirubinuria include hemolysis, (1) Small epithelial cells from the renal
liver disease, extrahepatic biliary obstruc- tubules or pelvis
tion, fever, and starvation (2) Appearance in urine is never normal
6. Blood and is observed in patients with isch-
a. Positive earlier than the observation of emic, nephrotoxic, or degenerative
hematuria renal disease
b. Dipstick tests do not differentiate from 5. Casts are cylindrical molds of the renal tubules
intact RBCs or hemoglobin composed of aggregated protein or cells
c. Causes of hemoglobinuria from hemolysis a. Hyaline
include transfusion reaction, immune (1) Pure protein precipitates of Tamm-
mediated hemolytic anemia, disseminated Horsfall mucoprotein
intravascular coagulopathy (DIC), splenic (2) Dissolve rapidly in dilute or alkaline
torsion, severe hypophosphatemia, heat urine
stroke, zinc toxicity, and phosphofructoki- (3) Have the least pathologic significance
nase or pyruvate kinase deficiency and may form transiently with fever,
C. Urinary sediment exercise, or passive congestion to the
1. Sediment preparation kidney
a. Perform on fresh urine samples b. Cellular casts
b. Centrifuge 5 to 10 mL of urine at 1000 to (1) White cell casts suggest pyelonephritis
1500 rpm for 5 minutes. Stain with but may also be caused by interstitial ne-
Sedi-Stain phritis, nephrosis, or glomerulonephritis
c. Number of casts is recorded per low-power (2) Red cell casts are fragile and rarely
field, and cells are recorded per high-power found. They may be noted in acute
field glomerulonephritis, renal trauma, or
2. RBCs after violent exercise
a. Occasional RBCs are normal (3) Hemoglobin casts are casts where the
b. Excessive number of RBCs is called hema- hemoglobin color is retained in the cast
turia, but origin cannot be determined (4) Renal epithelial casts occur with severe
c. Lipid droplets are often confused with tubular injury and suggest acute tubular
RBCs, especially in cats necrosis or pyelonephritis (Figure 1-1)
d. Causes of hematuria include trauma, (5) Renal fragments are a variant of epithe-
urolithiasis, neoplasia, UTIs idiopathic lial casts where portions of the renal
feline lower urinary tract disease, chemi- tubules slough into urine. Their appear-
cally induced cystitis, systemic diseases ance suggests severe renal injury
associated with hemorrhage, renal infarct, (6) Mixed casts contain multiple cell types
nephritis, nephrosis, parasites, renal c. Granular casts (Figure 1-2)
pelvic hematoma, or genital tract (1) Represent the degeneration of cells or
contamination precipitation of filtered plasma proteins
3. White blood cells (WBCs) (2) Fatty casts are a type of granular cast
a. Occasional WBCs are normal that may be seen in nephrotic syn-
b. Excessive WBCs in urine sediment is called drome or diabetes mellitus
pyuria and indicates inflammation some-
where in the urinary tract or contamination
from the genital tract
c. Clumped WBCs are typically due to infectious
organisms
d. Causes of pyuria include urinary tract
inflammation or genital tract
contamination
4. Epithelial cells
a. Squamous epithelial cells
(1) Large, polygonal cells with small, round
nuclei
(2) Common in voided or catheterized
samples
b. Transitional epithelial cells
(1) A small number is normal Figure 1-1 Photomicrograph of an epithelial cell cast in urine. Small renal
(2) Increased in infection, irritation, or epithelial cells can be identified in this case (white arrows). (Courtesy Nancy
neoplasia Facklam; from Ettinger SJ, Feldman EC. Textbook of Veterinary Internal
Medicine, 6th ed. St Louis, 2005, Saunders.)
drj
