Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

V. Physiology of Acid-Base Balance
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hydrogen loss, bicarbonate retention, or as a contraction alkalosis.
A contraction alkalosis occurs with reduction of ECF
fluid volume resulting from a loss or sequestration of sodium
and chloride containing fluid without commensurate loss of
bicarbonate ( Garella et al ., 1975 ). Excessive hydrogen ion
losses can result in a metabolic alkalosis.
a . Causes of Metabolic Alkalosis
The most common causes of increased hydrogen loss are
gastrointestinal losses of chloride-rich fluids associated with
vomiting in small animals ( Strombeck, 1979 ) or sequestration
of chloride-rich fluid in the abomasum and forestomach
of ruminants ( Gingerich and Murdick, 1975b ; McGuirk and
Butler, 1980 ). Excessive renal hydrogen loss associated with
mineralocorticoid excess, diuretic usage (particularly the loop
diuretics such as furosemide), and low chloride intake may
cause or contribute to the generation of a metabolic alkalosis
( Rose, 1984 ). Most of these disorders are also associated
with the development of significant sodium and chloride deficits
and resultant decreases in effective circulating volume.
These deficits and the responses that decreased effective circulating
volume induce are central features of the processes
that maintain and perpetuate a metabolic alkalosis. Hydrogen
loss from the ECF can also occur with hydrogen movement
into the cells in response to potassium depletion ( Irvine and
Dow, 1968 ). Excessive bicarbonate administration is an additional
potential cause of metabolic alkalosis. Most normal
animals can tolerate large doses of bicarbonate, and excesses
are rapidly eliminated by renal excretion ( Rumbaugh et al .,
1981 ). However, patients with decreases in effective circulating
blood volume or with potassium or chloride deficits may
not tolerate a bicarbonate load because renal clearance of
excess bicarbonate is likely to be impaired.
The factors that are responsible for the maintenance of
a metabolic alkalosis all impair renal bicarbonate excretion.
These factors may include decreased glomerular filtration
of bicarbonate seen in some types of renal failure.
However, the most common factor is increased renal tubular
bicarbonate resorption, which is associated with the
renal response to decreases in the effective circulating fluid
volume, potassium depletion, or chloride depletion ( Rose,
1984 ). Sodium resorption is enhanced in response to hypovolemia
to help restore normal effective circulating fluid
volume. The maintenance of electroneutrality requires that
sodium resorption in the proximal tubule must be accompanied
by a resorbable anion such as chloride, whereas
in the distal tubule, sodium resorption is associated with
the secretion of a cation, usually hydrogen or, to a lesser
extent, potassium. The only resorbable anion normally
present in appreciable quantities in the proximal tubular
fluid is chloride. In a metabolic alkalosis, plasma bicarbonate
is increased and chloride concentration is generally
decreased as the result of disproportionately high chloride
losses that result from vomiting, sequestration of gastric
fluid ( Whitlock et al ., 1975b ), diuretic usage, or heavy
sweat losses in exercising horses ( Carlson, 1975 , 1979b ).
The relative lack of the resorbable anion, chloride, in the
proximal tubule thus allows a larger amount of sodium
to reach the distal tubule where the action of aldosterone
enhances hydrogen loss into the tubular lumen in exchange
for sodium. The maintenance of effective circulating
volume is so critical that the body chooses to maintain circulating
volume by enhanced sodium resorption by whatever
means necessary, even at the expense of extracellular
pH. Renal hydrogen excretion is directly linked with bicarbonate
resorption. Thus, it is not possible to eliminate the
excess bicarbonate, and the metabolic alkalosis is maintained
( Rose, 1984 ). This mechanism is the reason for the
paradoxic acid urine seen in some patients with metabolic
alkalosis ( Gingerich and Murdick, 1975a, 1975b ; McGuirk
and Butler, 1980 ). Hypokalemia is another factor that
contributes to the maintenance of a metabolic alkalosis.
Hypokalemia is associated with an increase in intracellular
hydrogen ion concentration. Increased renal tubular cell
hydrogen ion concentration may enhance hydrogen secretion
and thus bicarbonate reabsorption by the tubular cells.
b . Compensation
Chemoreceptors in the respiratory center sense the alkalosis,
and the respiratory response to a metabolic alkalosis is
hypoventilation resulting in an increase in p CO 2 . In dogs,
the expected compensating response is an increase of p CO 2
of 0.7 mmHg for each mEq/l increase in bicarbonate.
2 . Respiratory Alkalosis
Respiratory alkalosis is associated with an increase in pH
and a decrease in p CO 2 .
a . Causes of Respiratory Alkalosis
Respiratory alkalosis is due to hyperventilation, which
may be stimulated by hypoxemia associated with pulmonary
disease, congestive heart failure, or severe anemia.
Hyperventilation may also be associated with psychogenic
disturbances or neurological disorders that stimulate the
medullary respiratory center such as salicylate intoxication
or Gram-negative sepsis. Respiratory alkalosis may
be seen in animals in pain or under psychological stress.
Hyperventilation may occur in dogs and other nonsweating
animals as they employ respiratory evaporative processes
for heat loss to prevent overheating ( Tasker, 1980 ).
b . Compensation
The initial compensating response to an acute respiratory
alkalosis is a modest decline in ECF bicarbonate concentration
as the result of cellular buffering. Subsequent renal
responses result in decreased ECF bicarbonate concentration
through reduced renal bicarbonate reabsorption. These
responses require 2 to 3 days for completion. The decline
in bicarbonate is partially offset by chloride retention in
order to retain electroneutrality. Thus, hyperchloremia