Readings: Tilley 212 - 213, 248 - 251, 260 - 261,
322 - 325, 326 - 327, 330 - 333
In animals with renal disease, the Complete Blood Count
(CBC) is generally nonspecific. Chronic renal failure may lead to
a nonregenerative anemia, due to decreased production of erythropoietin,
and inflammation occurring in the kidneys may lead to a neutrophilia
with a left shift and other changes associated with the inflammatory
leukocyte profile.
A complete urinalysis should be performed, including
urine chemistries, because changes frequently occur in the urine before
they are seen in the blood. A modified abrupt water deprivation
test should be performed to determine if diabetes insipidus is present.
Clinical chemistries are relatively insensitive due to
compensatory hypertrophy, and should always be performed concurrently
with a urinalysis. The primary chemistries used to assess renal
function are nonprotein nitrogens and electrolytes.
Nonprotein nitrogens (NPNs) are waste products
resulting from protein metabolism. They are normally present in
small amounts in serum. The most commonly assessed NPNs are blood
urea nitrogen (BUN) and creatinine. Azotemia is a laboratory finding of
increased NPNs. It most frequently occurs in chronic renal failure
and / or cardiovascular disease. Uremia is a multisystemic
toxic syndrome due to renal disease and azotemia. Signs of uremia
include lethargy, anorexia, depression, vomiting and diarrhea, polyuria
and polydipsia and uremic breath.
Blood Urea Nitrogen
Blood Urea Nitrogen (BUN) is used as a routine
screening test and when renal disease is suspected. BUN is formed
during the catabolism of proteins, is processed in the liver and is the
primary protein excretory product. Most BUN is excreted via the
kidneys, although a small amount is loss through the skin and
gastrointestinal tract. Some urea nitrogen is reabsorbed by the
kidney for recycling in the body.
The specimen varies with the test, although serum is
preferred. Fasting is recommended and moderate hemolysis will not
invalidate the test. The reference range for
BUN in dogs and cats is 10 - 30 mg/dl. Testing for
BUN is unreliable in early renal disease due to compensatory
hypertrophy. Although dipsticks are available (Azostix®),
analysis in an automated chemistry machine is much more accurate and
precise.
Increased BUN may
occur due to many reasons. Prerenal azotemia can
result from a cardiovascular disorder that decreases blood flow through
the glomerulus, a high protein diet, fever (which increases protein
catabolism) and dehydration. Renal azotemia is a sign of
acute or chronic renal failure, glomerular nephritis, or tubular
necrosis. Postrenal azotemia results from urinary
obstruction. Decreased BUN is uncommon, but may
result from protein malnutrition, cirrhosis of the liver and polyuria /
polydipsia.
Creatinine
Creatinine is a
nonprotein nitrogen that is generally evaluated concurrently with BUN.
Creatine is formed from amino acids in the liver and provides
energy storage in the muscles as phosphocreatine. It is degraded
to creatinine as energy is used. Excretion is primarily via the
kidneys and no reabsorption occurs.
The preferred specimen for creatinine testing is serum
or plasma, and the test is invalidated by both moderate hemolysis and
lipemia.
The reference range for creatinine
in the dog and cat is 1 - 2 mg/dl.
Increased creatinine is primarily renal in
origin, although prerenal factors such as dehydration and cardiovascular
disease and postrenal obstruction may also cause an increase. Diet
does NOT affect creatinine levels. Compensatory hypertrophy makes
testing unreliable during the early stages of renal disease.
Body Fluids
Body fluids are the water and solutes found within and
around the cells. The primary method of water regulation is
osmosis. Two hormones also have a role in the active transport of
water.
Anti-diuretic hormone acts on the distal
convoluted and collecting tubules in the kidneys to make them more
permeable to water, resulting in water conservation.
Aldosterone, produced by the adrenal gland, moves
solutes such as sodium and potassium. Water follows the solutes
via osmosis.
Hydration can be evaluated by physical assessment (skin
turgor, capillary refill time, etc.) and by laboratory tests, especially
total solids of blood and urine specific gravity.
Electrolytes
Electrolytes should always be included in any assessment
of renal function, because of the kidneys' role in retaining
electrolytes or excreting them when present in excess.
Electrolytes have many important roles, including pH regulation, fluid
balance (via osmosis), muscle function and nerve impulse transmission.
They are measured in milliequivalents (the weight in milligrams that
combine with 1 mg of hydrogen ion).
Electrolytes should be evaluated when an animal exhibits signs of systemic
disease, including vomiting and diarrhea, polyuria and polydipsia,
lethargy, anorexia and depression, and other behavioral changes.
Sodium should also be evaluated in animals with
edema and seizures. It has an important role in osmosis and fluid
balance, pH regulation (the kidneys exchange sodium for hydrogen) and
muscle and nerve function. It is regulated by the kidney, where
aldosterone activates the sodium/potassium pump in the tubules,
conserving sodium.
Serum is the preferred specimen and hemolysis does not
invalidate the test. The reference range for the dog and cat is
140 - 155 mEq/L.
Hypernatremia is primarily seen in dehydrated
animals. Hyponatremia occurs in animals with vomiting and
diarrhea, renal wasting associated with chronic renal failure and
diabetes mellitus.
Potassium is associated with vomiting and
diarrhea, dysuria and cardiac arrhythmias and bradycardia. Because
potassium is important in muscle and nerve function, animals with
inadequate potassium may be weak and collapse. It is regulated by
aldosterone in the kidneys, and insulin and epinephrine move potassium
into cells, decreasing blood levels.
Plasma is preferred for testing, because platelets
release potassium as they form a plug, but serum can be used. Even
moderate hemolysis can invalidate potassium tests, because of the high
level of potassium in the erythrocytes.
The reference range for potassium in the dog is 4.5 -
5.5 mEq/L and for the cat is 4.0 - 4.5 mEq/L.
Hyperkalemia can
produce life threatening cardiac arrhythmias. It results from
cellular injury, acute renal failure, urinary obstruction or rupture and
hypoadrenocorticism. Hypokalemia is associated with vomiting and diarrhea and with renal wasting in
chronic renal failure, especially in cats.
Chloride has important roles in osmosis and water
balance, and takes the form of hydrochloric acid in the stomach.
It passively follows sodium, so it is indirectly controlled by
aldosterone.
Serum or heparinized plasma can be used and mild
hemolysis does not invalidate the test. The reference range in the
dog is 105 - 115 mEq/L and in the cat is 117 - 123 mEq/L.
Hyperchloremia occurs with dehydration, diarrhea,
diabetes insipidus and diabetes mellitus. Hypochloremia is
associated with vomiting and hypoadrenocorticism.
Acid-Base Balance (a subset of electrolytes)
The acidity or alkalinity of the body is based on the
concentration of hydrogen ions in body fluids. Organic acids are
produced by all cells during metabolism. Some acids are volatile,
formed as carbon dioxide combines with water forming carbonic acid (CO2
+ H2O → H2CO3)
and are regulated by respiration. Nonvolatile acids exit the body
via the kidneys or are buffered by chemical systems in the body.
The body must maintain a
narrow pH for enzymatic and metabolic reactions to occur. The pH
should be between 7.35 - 7.45. A pH less than 6.8 or more than 7.8
results in death. Body pH is maintained by three mechanisms-
-
Buffer systems are the
first response, and neutralize acid. Buffers include the
carbonic acid-bicarbonate system, the phosphate system, hemoglobin and
proteins. The buffer system has limited capacity and is easily
overwhelmed.
-
Respiration is the second
response, although it is not able to completely compensate for changes
in pH.
-
The third is renal
excretion. This is the body's long term response to changes in
pH, and it works the slowest of the three systems.
The carbonic
acid-bicarbonate buffer is system is one of the most important in the
body and is capable of causing rapid readjustments to maintain
homeostasis. It interacts with the respiratory and renal systems:
CO2
+ H2O ßà H2CO3
ßà H+ + HCO3-
The respiratory system affects volatile organic acids.
Increasing respirations eliminates volatile acids (i.e. CO2
), but not able to completely normalize the pH.
The kidneys are the ultimate regulators of body pH, but
they're slow. They selectively absorb and secrete hydrogen ions,
but it takes 12 - 24 hours for the kidneys to begin to respond and days
to peak.
Bicarbonate (HCO3-) should
be evaluated in animals with vomiting and diarrhea, dehydration and
renal failure. It is a buffer than transforms toxic CO2
into HCO3-. Arterial blood should be used
and lithium heparinized plasma collected for the test.
The reference range for bicarbonate in the dog is 18 -
24 mEq/L and for the cat is 17 - 21 mEq/L.
Disturbances of acid-base balance fall into four
categories. Most animals compensate for the disturbance, and
actual lab results often show a blend of more than one disorder.
Metabolic acidosis is the most common small
animal acid-base disorder. The bicarbonate value is <17 mEq/L in
the dog or 16 mEq/L in cats and the pH is less than 7.35. The
animal has deficient bicarbonate due to loss from diarrhea or renal
failure or excess acid from ketoacidotic diabetes mellitus or ethylene
glycol toxicity. The signs reflect the underlying cause, and
animals with metabolic acidosis exhibit central nervous system (CNS)
depression manifested as disorientation or a coma. Respirations
increase as the animal attempts to decrease the acidosis by breathing
out carbon dioxide.
Respiratory acidosis occurs when there is excess
carbonic acid due to impaired respirations from pneumonia, chronic
obstructive pulmonary disease (COPD) or gas anesthesia.
Respirations decrease, causing the imbalance, and CNS
depression occurs.
Metabolic alkalosis occurs when there is a loss
of hydrogen ions by vomiting. Respirations decrease as the animal
attempts to preserve carbon dioxide (but can't go low enough to resolve
the problem). CNS stimulation (tetany) occurs.
Respiratory alkalosis occurs when there is
insufficient carbonic acid. This is most frequently seen when a
frightened animal or one in pain hyperventilates. Deep and rapid
respirations along CNS stimulation, leading to tetany and convulsions,
occurs.
The anion gap is a mathematical calculation used
to determine the cause of metabolic acidosis. It is calculated
with the formula:
(Na+ + K+) – (Cl-
+ HCO3-) = anion gap (in mEq / L)
A normochloremic acidosis, for example, is seen in
animals with ketoacidotic diabetes mellitus, ethylene glycol toxicity or
uremic acidosis. A hyperchloremia acidosis is associated with
severe diarrhea.
Blood Gas Analysis is used to evaluate
respiratory function and acid-base status and is routinely used to
monitor patients with respiratory disease, acid-base disturbances such
as renal disease or diabetes mellitus, critically ill animals and
anesthetized animals.
Specimens include whole blood with heparin
anticoagulant, venous blood for all parameters except oxygen or arterial
blood, which can be used to test for all substances. The specimen
must be handled carefully to ensure that it does not contact air, which
can change the level of blood gases. Tests should be run
immediately.
Blood gas analytes include:
-
Blood pH (which usually varies in the direction of the
primary acid-base disorder).
-
PaO2 (partial pressure of oxygen, which evaluates oxygenation
of blood and helps determine if the patient needs oxygen)
-
PaCO2 (partial pressure of carbon dioxide, which evaluates
ventilation)
-
Bicarbonate (which evaluates the acid-base balance of
blood)