Page 481 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Fluid, Electrolyte, and Acid-Base Disturbances in Liver Disease 469

These hemodynamic maladjustments are mediated by respectively. Conivaptan has been shown to correct
the renin-angiotensin-aldosterone system (RAAS) and hyponatremia in euvolemic or hypervolemic patients. 9
SNS in response to underfilling of the systemic arterial
circulation and decreased renal perfusion. 25,86 Abnormal Increased Basal Cortisol and ACTH Concentrations
intrarenal accumulation of angiotensin II occurs early in Increased basal cortisol and adrenocorticotropic hor-
the disease process, even before activation of the mone (ACTH) concentrations complicate hepatic insuf-
RAAS. 125 Renal sodium conservation may be related in ficiency associated with acquired portosystemic
part to enhanced sensitivity to aldosterone. shunting in dogs, but normal adrenal response to low-
dose dexamethasone suppression is maintained. 180 High
Effect of Portosystemic Shunting on Sodium basal cortisol concentrations also were found in dogs with
and Water Retention congenital PSVA, and concentrations normalized after
Portosystemic shunting also may affect sodium and water successful shunt ligation. 203 In another report, baseline
retention, and surgically created portosystemic shunts in cortisol concentrations in dogs with congenital PSVA
experimental dogs have been used to study the effects of and in healthy dogs undergoing ovariohysterectomy were
diverted hepatoportal perfusion on sodium and water similar. Response to ACTH did not correlate with post-
balance. Ten weeks after end-to-side portocaval shunt operative hypoglycemia or prolonged anesthetic recov-
formation, plasma volume, systemic blood pressure, ery, which was previously thought to be due to
and central venous pressures were maintained, and no inadequate adrenal respose. 105 Dogs with PSVA also have
changes in GFR, plasma renin activity, or aldosterone high free-water flux and an abnormally high GFR that
concentrations were identified. 124 Some dogs maintained normalize after shunt ligation. 65 It is unknown if this
normal sodium balance after ingestion of 150 mEq/day response relates to abnormal cortisol concentration or
of sodium, but others developed ascites. 124 These hemodynamic adjustments. Other potential causes for
findings indicate that in some situations portosystemic hypercortisolemia in dogs with congenital PSVA include
shunting alone can impair ability to adapt to increased decreased hepatic synthesis of cortisol binding proteins,
sodium loads. This finding may explain the tendency to decreased hepatic clearance of cortisol, peripheral resis-
form ascites in some dogs with PSVA (especially those tance to cortisol, or stress associated with chronic
with ductus venosus) and hypoalbuminemia or after nonadrenal illness. 105
administration of sodium-rich crystalloids.
Altered Steroid Hormone Metabolism
Specific Mechanisms of Water and Altered steroid hormone metabolism also may contribute
Electrolyte Disturbances in Cirrhosis to sodium retention in cirrhosis. Abnormally increased
and Portosystemic Shunting serum bile salt concentrations may inhibit 11b-
Nonosmotic Vasopressin Stimulation hydroxysteroid dehydrogenase-2 (11b-HSD-2), the
Nonosmotic stimulation of AVP is a central factor enzyme that interconverts endogenous and exogenous
mediating water retention in cirrhosis. 90 Acute changes biologically active 11b-hydroxysteroids and their inactive
in portal venous pressure in cirrhotic dogs initiate AVP- 11-ketosteroid counterparts. 11b-HSD-2 selectively
mediated antidiuresis. Both systemic and splanchnic arte- modulates access of aldosterone to mineralocorticoid
rial vasodilatation can stimulate nonosmotic AVP release receptors and normally is located in mineralocorticoid-
and activate other antidiuretic and vasopressor responsive tissues (including the distal nephron).
systems. 86,90 Early in cirrhosis (“compensated cirrho- Absence or inhibition of 11b-HSD-2 can mimic mineral-
sis”), transient neurohormonal responses increase plasma ocorticoid excess by allowing inappropriate access of 11b-
volume and temporarily suppress baroreceptor signaling. hydroxyglucocorticoids to mineralocorticoid
4,114,171
As the disease progresses, arterial vasodilatation worsens, receptors. The up-regulation of the vasopressin-
and neurohormonal responses are no longer able to com- regulated water channel aquaporin-2 (AQP2) and
pensate. At this point, vasoconstrictor systems become increased targeting of AQP2 to luminal membranes likely
continuously stimulated and promote the sodium and to contribute to the increased water reabsorption and uri-
water retention that causes edema and ascites. The nary concentration in hepatic cirrhosis. 114
response is exaggerated by abnormal retention of AVP
as a result of impaired metabolism. Normally, the kidney Abnormal Aldosterone Release and Responsiveness
and liver metabolize AVP, but decreased AVP clearance in to Aldosterone
hepatic disease correlates with disease severity. 200 High (or inappropriately normal) aldosterone
Conivaptan, a nonpeptide, dual V1a/V2 AVP receptor concentrations precede and accompany pathologic
antagonist has shown promising results in both sodium retention in humans and animals with cirrhosis.
animals 240 and humans. 9 It binds competitively and Experimentally, hepatic venous congestion and acute por-
reversibly with high affinity to the V1a and V2 receptors tal hypertension stimulate aldosterone secretion. 23 The
that mediate vasoconstriction and water permeability, importance of aldosterone in sodium and water retention