URINARY SYSTEM: HEMATOLOGY AND SERUM ELECTROLYTES
S.P. DiBartola, DVM
D.J. Chew, DVM
LEARNING OBJECTIVES
1. Understand how urinary tract diseases can affect the results obtained on a
complete blood count.
2. Understand how urinary tract diseases can affect the electrolyte results obtained
on a biochemical profile.
3. Gain confidence in interpreting complete blood counts and biochemical profiles.
Many disease processes (including diseases of the urinary system) alter the results
of commonly performed laboratory tests such as the complete blood count and
biochemical profile. The purpose of these notes is to acquaint you with abnormalities
in these commonly performed laboratory tests that may be observed in patients with
diseases of the urinary system. None of the abnormalities discussed here are
pathognomonic for urinary system disease.
I. Complete Blood Count
A. Red Blood Cells
1. Anemia initially may be masked by the effect of dehydration
(hemoconcentration). Thus, the hematocrit in a dehydrated patient with
chronic renal failure may be normal and anemia will become evident only
after fluid therapy. It is important to monitor the hematocrit serially in patients
with renal failure to detect anemia.
2. Dehydration also will increase the plasma protein concentration and it will
decrease after fluid therapy.
3. Anemia occurs in 25-50% of dogs and cats with chronic renal failure. The
anemia of chronic renal failure is a nonregenerative (normochromic
normocytic) anemia that results principally from impaired production of
erythropoietin by the kidneys and lack of its trophic effect on the bone
marrow (see notes on Chronic Renal Failure for more details).
4. Anemia usually is not present intially in patients with acute renal failure but
may develop with blood loss (e.g., gastrointestinal hemorrhage) and repeated
blood sampling.
5. Rarely, blood loss from longstanding hemorrhage into the urinary tract can
lead to regenerative anemia in patients with otherwise normal renal function
(e.g. idiopathic renal hematuria, renal telangiectasia in Pembroke Welsh Corgi
dogs).
6. Rarely, polycythemia may occur in animals with renal tumors as a result of
either chronic renal hypoxia or erythropoietin production by a renal tumor. An
increase in hematocrit due to intravascular dehydration (see above) is called
relative polycythemia. See notes on Urinary Tract Neoplasia for more details.
B. White Blood Cells
1. Chronic renal failure often is associated with mild mature neutrophilia and
mild to moderately severe lymphopenia. The lymphopenia may reflect the
stress (glucocorticoid effect) of chronic disease.
2. Leukocytosis due to neutrophila with the presence of increased numbers of
immature or "band" neutrophils (i.e., a "left shift") may be observed in
inflammatory conditions of any body system. For example, leukocytosis with
a "left shift" may be observed in acute pyelonephritis. Unfortunately, the
leukocytosis may resolve with chronicity, making chronic pyelonephritis
difficult to diagnose.
C. Platelets
1. Platelet numbers usually are normal in patients with urinary tract disease.
2. A platelet function defect may develop in uremic patients despite normal
numbers of circulating platelets. See notes on Chronic Renal Failure for more
details.
II. Serum Electrolytes
The kidneys are responsible for regulating the composition of extracellular fluid and
consequently play an important role in regulation of serum electrolyte concentrations
and acid base balance. Also, diseases of the urinary system may result in alterations
of serum electrolytes and acid base balance. The serum concentration of an
electrolyte does not necessarily reflect the total body store of the electrolyte in
question. This discussion is meant to provide a brief, general overview. For more
information on serum electrolytes (Chapters 3 through 8) and blood gases (Chapters 9
through 12), consult SP DiBartola: Fluid Therapy in Small Animal Practice, edition 2,
WB Saunders Co., Philadelphia, 2000.
A. Sodium
Species
Dog
Cat
Horse
Cattle
Normal values
145 (140-155) mEq/L
156 (149-162) mEq/L
139 (132-146) mEq/L
142 (132-152) mEq/L
1. The serum sodium concentration is an indication of the amount of sodium
relative to the amount of water in the extracellular fluid and provides no direct
information about total body sodium content. Patients with hyponatremia or
hypernatremia may have decreased, normal, or increased total body sodium
content.
2. An increased serum sodium concentration (hypernatremia) implies
hyperosmolality whereas a decreased serum sodium concentration
(hyponatremia) usually, but not always, implies hypoosmolality.
3. Hypernatremia develops when water intake has been inadequate, when fluid
losses have been hypotonic to extracellular fluid, or when an excessive
amount of sodium has been ingested or administered parenterally. Causes of
hypernatremia include:
a. Pure water loss
i. Lack of intake
ii. Excessive water loss in urine (e.g., diabetes insipidus)
b. Hypotonic fluid loss
i. Gastrointestinal loss (e.g., vomiting, diarrhea)
ii. Third space loss (e.g., peritonitis, pancreatitis)
iii. Renal loss (e.g., osmotic diuresis in diabetes mellitus, polyuric renal
failure, postobstructive diuresis)
c. Gain of impermeant solute
i. Salt poisoning
ii. Hypertonic fluid administration
4. Hyponatremia develops when the patient is unable to excrete ingested water
or when urinary and other fluid losses have a combined osmolality greater
than that of ingested or parenterally administered fluids. In most instances,
hyponatremia is accompanied by hypoosmolality. Total body sodium content
and extracellular fluid volume in patients with hyponatremia may be increased
(hypervolemia), normal (normovolemia), or decreased (hypovolemia):
a. Hyponatremia with hypervolemia
i. severe liver disease
ii. congestive heart failure
iii. nephrotic syndrome
b. Hyponatremia with normovolemia
i. psychogenic polydispia
ii. administration of drugs with antidiuretic effects
iii. administration of hypotonic fluids
c. Hyponatremia with hypovolemia (MOST common situation)
i. gastrointestinal losses (e.g., vomiting, diarrhea)
ii. third space losses (e.g., pancreatitis, peritonitis, uroabdomen, pleural
effusion)
iii. hypoadrenocorticism
iv. diuretic administration
B. Chloride
Species
Dog
Cat
Horse
Cattle
Normal values
110 (105-115) mEq/L
120 (115-125) mEq/L
104 (99-109) mEq/L
104 (97-111) mEq/L
1. Chloride is the most abundant anion in extracellular fluid, and Cl- and HCO3are the only important resorbable anions in renal tubular fluid. An alteration in
the normal relationship between these ions underlies the pathophysiology of
acid base disturbances such as hyperchloremic (normal anion gap) metabolic
acidosis and hypochloremic metabolic alkalosis (refer to Fluid Therapy notes
for more details).
2. Causes of hypochloremia
a. Vomiting of stomach contents in dogs and cats or sequestration of fluid in
the stomach (e.g., abomasal torsion in cattle)
b. Overzealous use of diuretics (e.g., furosemide, thiazides)
c. Compensation for chronic respiratory acidosis
3. Causes of hyperchloremia
a. Excessive loss of sodium relative to chloride (as compared to extracellular
fluid composition) (e.g., diarrhea)
b. Excessive gain of chloride relative to sodium (as compared to extracellular
fluid composition) (e.g., NH4Cl, KCl, 0.9% NaCl, hypertonic saline, salt
poisoning)
c. Excessive chloride retention by the kidneys (e.g., renal tubular acidosis,
acetazolamide, spironolactone, compensation for chronic respiratory
alkalosis)
C. Potassium
Species
Dog
Cat
Horse
Cattle
Normal values
4.5 (3.5-5.5) mEq/L
4.5 (3.5-5.5) mEq/L
3.8 (2.6-5.0) mEq/L
4.8 (3.9-5.8) mEq/L
1. Hypokalemia arises from decreased intake, translocation of potassium from
extracellular to intracellular fluid, and excessive loss of potassium by either
the gastrointestinal or urinary routes.
a. Decreased intake of potassium alone is unlikely to cause hypokalemia but,
it may be a contributing factor.
b. Translocation
i. Alkalemia
ii. Insulin and glucose-containing fluids
c. Increased loss
i. Gastrointestinal (e.g., vomiting of stomach contents, diarrhea)
ii. Urinary (e.g., chronic renal failure, renal tubular acidosis,
postobstructive diuresis, mineralocorticoid excess, diuretics).
2. Hyperkalemia is uncommon if renal excretion of potassium is normal. Causes
of hyperkalemia include:
a. Increased intake is unlikely to cause hyperkalemia if renal function is
normal unless potassium intake is iatrogenic (e.g., infusion of potassiumcontaining fluids at an excessively rapid rate)
b. Translocation
i. Acute mineral acidosis (e.g., HCl, NH4Cl)
ii. Insulin deficiency (e.g., diabetic ketoacidosis)
c. Decreased urinary excretion
i.
ii.
iii.
iv.
v.
Urethral obstruction
Ruptured bladder
Anuric or oliguric renal failure
Hypoadrenocorticism
Drugs (e.g., angiotensin-converting enzyme inhibitors, potassiumsparing diuretics)
D. Total CO2 or HCO3Species
Dog
Cat
Horse
Cattle
Normal values
21 (17-24) mEq/L
20 (17-24) mEq/L
27 (24-30) mEq/L
25 (20-30) mEq/L
1. The total CO2 content is a measure of all potential sources of CO2 in plasma
or serum.
a. When the sample is handled anaerobically, this includes HCO3- ions,
dissolved CO2, carbamino CO2 bound to amino groups in hemoglobin,
H2CO3, and CO3-2 ions. The total amount of carbamino CO2, H2CO3, and
CO3-2 present is negligible, and total CO2 usually is defined as HCO3- +
dissolved CO2 or HCO3- + 0.03 x pCO2, where 0.03 is the solubility
coefficient for CO2 in plasma.
b. If the sample is handled aerobically, dissolved CO2 is released to the
atmosphere and the total CO2 measurement is essentially equal to the
concentration of HCO3- in the sample. Thus, in routine clinical practice the
total CO2 determination often is considered synonymous with [HCO3-].
c. Determination of total CO2 does not allow differentiation of metabolic and
respiratory acid base disorders.
d. A high total CO2 indicates either metabolic alkalosis or respiratory
acidosis.
e. A low total CO2 indicates either metabolic acidosis or respiratory
alkalosis.
f. Evaluation of the clinical setting is necessary to make a judgement about
which acid base disturbance is most likely. If there is doubt, blood gas
analysis is required for proper management.
g. Chronic renal failure is accompanied by a mild to moderate wellcompensated metabolic acidosis due to decreased renal excretion of fixed
acid (see notes on Renal Regulation of Acid Base Balance).
h. In acute renal failure, metabolic acidosis may be much more severe
because there has been insufficient time for renal compensatory responses
to develop.
E. Calcium
Species
Dog
Cat
Horse
Cattle
Normal values
10.1 (9.0-11.3) mg/dL
9.2 (8.0-10.5) mg/dL
12.4 (11.2-13.6) mg/dL
11.0 (9.7-12.4) mg/dL
1. Total serum calcium concentration is composed of three components:
a. Ionized calcium: This free calcium is the biologically active component
and represents approximately 50% of the total serum calcium
concentration.
b. Complexed calcium: This calcium is bound to organic and inorganic
anions in plasma and represents approximately 10% of the total serum
calcium concentration.
c. Protein-bound calcium: This calcium is bound mainly to albumin and
represents approximately 40% of the total serum calcium concentration.
2. The serum calcium concentration reported on routine biochemistry profiles is
the total serum calcium concentration.
3. Hypercalcemia may be caused by dehydration, various malignancies (e.g.,
lymphosarcoma, perirectal apocrine gland adenocarcinoma),
hypoadrenocorticism, acute or chronic renal failure, hypervitaminosis D
(including cholecalciferol-containing rodenticides), primary
hyperparathyroidism, and some skeletal lesions.
4. Hypocalcemia may be caused by hypoalbuminemia (the most common cause),
acute or chronic renal failure, ethylene glycol intoxication, eclampsia, acute
pancreatitis, and primary hypoparathyroidism.
5. Approximately 5-10% of dogs with chronic renal failure develop
hypercalcemia. Hypercalcemia may pose a threat to renal function because it
can further damage the kidney by causing renal vasoconstriction and renal
interstitial mineralization. Possible mechanisms of hypercalcemia in renal
failure include:
a.
b.
c.
d.
e.
f.
Reduced urinary excretion of calcium due to low GFR
Decreased renal degradation of PTH
Hypercitricemia and increased complexed calcium
Autonomous parathyroid gland secretion of PTH
Increased PTH set point for calcium
Increased intestinal sensitivity to low concentrations of calcitriol
6. In some hypercalcemic patients with renal failure it can be difficult to
determine which came first -- the renal failure or hypercalcemia. Careful
consideration of historical, physical, laboratory, and radiographic findings
usually will allow the clinician to decide.
7. Serum ionized calcium concentration is normal or low when measured in dogs
with chronic renal failure that have increased total serum calcium
concentrations.
8. Hypercalcemia develops in nephrectomized ponies and in some horses with
naturally-occurring renal disease. The mechanism is unknown but may be
related to the observation that horses normally absorb large amounts of
calcium from their gastrointestinal tract and rely upon renal excretion of much
of this calcium. Large amounts of calcium carbonate crystals normally are
present in equine urine.
9. Total serum calcium concentrations are decreased in approximately 10% of
dogs with chronic renal failure. Decreased serum ionized calcium
concentration is found in 40% of dogs with chronic renal failure. Mechanisms
include:
a. "Mass Law" effect due to increased serum phosphorus concentration (i.e.,
the amounts of calcium and phosphorus that can remain in solution
together are defined by the [Ca] X [Pi] product). When this value is > 6070, soft tissue mineralization may occur.
b. Decreased production of calcitriol by the diseased kidneys results in
impaired intestinal absorption of calcium.
c. Skeletal resistance to the action of PTH in uremia.
d. Complexing of calcium with phosphate in the lumen of the intestinal tract.
10. Hypocalcemia in chronic renal failure usually is asymptomatic (i.e., tetany is
not observed) because the metabolic acidosis of renal failure leads to an
increase in the ionized component of the total serum calcium concentration.
This occurs because of a decrease in net negative charge on plasma proteins
that occurs during acidosis.
11. Hypocalcemia also may occur in acute renal failure as a result of severe
hyperphosphatemia and the "Mass Law" effect.
F. Phosphorus
SpeciesNormal values
Dog
4.2 (2.5-6.0) mg/dL
Cat
6.3 (4.5-8.1) mg/dL
Horse
4.3 (3.1-5.6) mg/dL
Cattle
6.0 (5.6-6.5) mg/dL
1. Plasma inorganic phosphorus is largely a mixture of H2PO4-1 and HPO4-2.
Since the valence and number of milliequivalents (mEq) of phosphate in
extracellular fluid are influenced by pH, it is more simple and convenient to
discuss phosphate in millimoles (mMol) or milligrams (mg) of elemental
phosphorus.
2. Serum phosphorus concentrations are reported by clinical laboratories in
terms of the amount of elemental phosphorus present and are expressed as mg
elemental phosphorus per dL serum.
3. Hypophosphatemia may be caused by translocation of phosphate from
extracellular to intracellular fluid (maldistribution), decreased renal
reabsorption of phosphate, or decreased intestinal absorption of phosphate.
4. Hyperphosphatemia may be caused by translocation of phosphate from
intracellular to extracellular fluid (maldistribution), decreased renal excretion
of phosphate, and increased intake of phosphate. Mild hyperphosphatemia is a
normal physiologic finding in young growing animals.
5. Compensatory renal secondary hyperparathyroidism maintains serum
phosphorus concentration within the normal range until > 85% of the nephron
population has become non-functional. Thus, hyperphosphatemia is not
observed in renal failure until after the onset of azotemia (loss of > 75% of the
nephron population). See notes on Chronic Renal Failure for additional
information.
6. Serum phosphorus concentration often is increased in acute renal failure with
severe reduction in glomerular filtration rate (< 15% of normal).
7. Bilateral nephrectomy in ponies leads to progressive hypophosphatemia for
unknown reasons. Hypophosphatemia also may occur in some horses with
chronic renal failure.
STUDY QUESTIONS
1. What type of anemia is expected in chronic renal failure? How would you
describe it morphologically? What causes it?
2. What effect does uremia have on the number of circulating platelets? Do these
platelets function normally?
3. Describe the leukogram in an animal with moderately severe chronic renal failure.
In an animal with acute pyelonephritis.
4. If an animal with severe anemia has a normal hematocrit at presentation, does this
mean it is not anemic? Why or why not?
5. Does a high serum sodium concentration mean there is too much sodium in the
body? If not, what does it mean?
6. Does a high serum potassium concentration mean there is too much potassium in
the body? If not, what does it mean?
7. What does total CO2 on the biochemical profile represent?
8. Can the total CO2 concentration be used to differentiate metabolic and respiratory
acid base disorders? If so, how?
9. What is the main reason hyperkalemia develops in renal failure? Is this more
common in acute or chronic renal failure?
10. What factors in renal failure predispose to hypercalcemia? To hypocalcemia?
11. What is the most common cause of hypocalcemia?
12. How is the horse different from the dog with respect to calcium and phosphorus in
renal failure?
13. Why does hyperphosphatemia eventually develop in chronic renal failure? At
what point in the progression of chronic renal failure does it develop? What
prevents it from developing sooner?
14. Of the for primary acid base disturbances, which is most likely to develop in a
uremic patient?