Page 60 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

50 ELECTROLYTE DISORDERS

the granular cells of the juxtaglomerular apparatus REGULATION OF WATER BALANCE
through a b 1 -adrenergic effect. The angiotensin II ulti- The osmolality of ECF and serum sodium concentration
mately produced also stimulates proximal tubular sodium
are regulated by adjusting water balance. Osmoreceptors
reabsorption. The direct effects of catecholamines on
in the hypothalamus constitute the afferent limb (sensors)
proximal tubular sodium reabsorption are important
for regulation of water balance. Vasopressin (antidiuretic
because they offset the tendency of the increase in
hormone) release is stimulated when the osmoreceptors
systemic arterial pressure to cause pressure natriuresis
shrink in response to plasma hyperosmolality and is
(see the Pressure Natriuresis section).
inhibited when they swell in response to plasma hypo-
osmolality. Vasopressin (water output) and thirst (water
Angiotensin II input) constitute the efferent limb (effectors) for the
Decreased perfusion pressure in the afferent arterioles regulation of water balance (see Table 3-1).
increases renin release from the granular cells of the Vasopressin (Antidiuretic Hormone)
juxtaglomerular apparatus and initiates the cascade of
events leading to production of angiotensin II. Angioten- Vasopressin (antidiuretic hormone [ADH]) is a nine-
sin II-induced vasoconstriction causes efferent more than amino acid peptide synthesized in neurons of the supra-
afferent arteriolar constriction, which results in an optic and paraventricular nuclei in the hypothalamus
increase in filtration fraction and changes in peritubular (Fig. 3-4). It travels down the axons of these neurons
capillary Starling forces (decreased hydrostatic pressure and is released into the circulation at the level of the
and increased oncotic pressure) that facilitate neurohypophysis.
proximal tubular reabsorption of sodium and water (see Vasopressin increases the reabsorption of water in the
Fig. 3-3). Angiotensin II also directly stimulates the collecting ducts of the kidneys and increases the perme-
1
þ
Na -H þ antiporter in the proximal tubules, which ability of the medullary collecting ducts to urea. Vaso-
facilitates sodium reabsorption and stimulates secretion pressin attaches to V 2 receptors on the basolateral
of aldosterone from the adrenal gland. membranes of the principal cells of the cortical and med-
ullary collecting ducts. The hormone-receptor complex
Atrial Natriuretic Peptide activates a guanine nucleotide regulatory protein (G s ),
resulting in replacement of guanosine diphosphate
Atrial natriuretic peptide is one member of a family of
(GDP) with guanosine triphosphate (GTP) and stimula-
natriuretic proteins that also includes brain natriuretic
tion of adenyl cyclase in the cell membrane. Formation of
peptide (which ironically predominates in the cardiac
cyclic adenosine monophosphate (cAMP) results in acti-
ventricles) and C-type natriuretic peptide in the central vation of protein kinase A, which in turn phosphorylates a
nervous system. 97 Atrial natriuretic peptide is synthesized
specific serine residue on subunits of the tetrameric
and stored in atrial myocytes until it is released in response aquaporin 2 (AQP2) proteins found in membranes of
to atrial distention caused by volume expansion. It has a subapical vesicles in the cytoplasm of the principal cells.
number of effects that facilitate renal excretion of sodium.
Phosphorylation results in trafficking and insertion of
Atrial natriuretic peptide causes dilation of the afferent
AQP2 water channels into the luminal membranes of
arterioles and constriction of the efferent arterioles, lead- 121,164
the principal cells. When vasopressin is absent or
ing to a primary increase in the GFR. It relaxes mesangial
in low concentration, AQP2 channels are removed from
cells, resulting in an increase in the glomerular surface
the luminal membrane by endocytosis. Aquaporin 3
area available for filtration. Atrial natriuretic peptide also
(AQP3) and 4 (AQP4) channels are found in the
inhibits sodium reabsorption in the cortical and inner
basolateral membranes of the principals cells and repre-
medullary collecting ducts and inhibits renin secretion,
sent exit pathways for water that enters the cells via the
thereby decreasing production of angiotensin II and lim-
luminal AQP2 channels. The AQP3 channel is found in
iting the effects of angiotensin II on proximal tubular the cortical and outer medullary collecting ducts, whereas
sodium reabsorption. Finally, it inhibits aldosterone AQP4 is located primarily in the inner medullary
secretion by adrenal zona glomerulosa.
collecting ducts. In the absence of vasopressin, urine
osmolality can be decreased to as low as 50 mOsm/kg
Pressure Natriuresis
by continued reabsorption of sodium without water as
Renal sodium excretion and water excretion are markedly tubular fluid passes down the collecting ducts. The V 1A
increased when renal arterial pressure increases even receptors are located in vascular smooth muscle and cause
slightly without a change in the GFR. The mechanism vasoconstriction when AVP binds to them. V 1B receptors
for pressure natriuresis appears to be entirely intrarenal are found primarily in the hypothalamus where AVP
and does not require neural or endocrine input (i.e., it binding leads to increased secretion of corticotropin.
occurs in the isolated denervated kidney). The effectors The effect of vasopressin on urea reabsorption may be
of sodium balance are summarized in Table 3-3. important in the pathogenesis of medullary washout of