Page 148 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

138 ELECTROLYTE DISORDERS

permeability coefficient of the glomerulus (K f ); acute because the urinary concentrating defect can occur with-
tubular necrosis from the ischemic and toxic effects of out structural renal lesions. This condition is commonly
hypercalcemia; and CRF caused by nephron loss, misdiagnosed as primary renal failure when it is actually
nephrocalcinosis, tubulointerstitial inflammation, and prerenal failure caused by dehydration and a renal
interstitial fibrosis. concentrating defect early in the course of hypercalcemia.
Decreased urinary concentrating ability and polyuria Intrarenal causes of azotemia during hypercalcemia
are early functional effects of hypercalcemia in dogs. can be functional or structural. Hypercalcemia can induce
The concentrating defect is often out of proportion to renal vasoconstriction, resulting in decreased renal blood
the observed reduction in glomerular filtration rate flow (RBF) and GFR. In an acute model of hypercalce-
(GFR) and increase in serum creatinine or blood urea mia, reduced RBF and GFR were observed consistently
nitrogen (BUN) concentration. Urine specific gravity in conscious dogs when serum tCa concentration
is consistently less than 1.030 in dogs and was less than exceeded 20 mg/dL, but only one half of the dogs had
1.020 in more than 90% of hypercalcemic dogs in one significant reductions in GFR and RBF when serum cal-
study. 314 Urinary concentration may be well preserved cium concentration was 15 to 20 mg/dL. Little effect on
in some cats with hypercalcemia that do not have RBF and GFR was observed when serum calcium concen-
CRF. Defective urinary concentrating ability results from tration was less than 15 mg/dL. These findings are in con-
a combination of reduced tubular reabsorption of trast to those in studies of anesthetized dogs, which
sodium and impaired action of antidiuretic hormone demonstratedmuchmoresevere functionalchangesduring
on tubular cells of the collecting duct. This results in a hypercalcemia. 335 Impaired renal autoregulation related to
form of nephrogenic diabetes insipidus characterized the effects of hypercalcemia may result in azotemia at early
by hyposthenuria if the diluting segment of the nephron stages of dehydration because GFR would otherwise be
(medullary thick ascending limb of Henle’s loop) is maintained by afferent arteriolar vasodilatation.
unaffected. These effects are caused by intrinsic Acute intrinsic renal failure (AIRF) occasionally
responses of the kidneys to hypercalcemia. Some of these develops as a consequence of hypercalcemia, but chronic
effects are mediated by calcium-sensing receptors on the intrinsic renal failure is more common. Sustained renal
renal epithelial cells, 79 whereas others may be related to vasoconstriction related to hypercalcemia may result in
effects of hypercalcemia on aquaporin expression, cell ischemic tubular injury, promoting the development of
trafficking, and delivery to apical membranes of the both AIRF and chronic intrinsic renal failure and
collecting tubules. 163,459,597 Additional direct effects potentiating the direct toxic effects of calcium on tubular
of hypercalcemia on the kidneys include reduced tubular cells. The toxic effects of ionized hypercalcemia are
calcium reabsorption and antagonism of the actions of enhanced by high concentrations of PTH in animals with
PTH. These responses by the kidneys facilitate calcium CRF because excess PTH increases calcium entry into
excretion and help to ameliorate the clinical effects of cells. 403 The ascending limb of Henle’s loop and distal
hypercalcemia. Renal medullary blood flow is increased convoluted tubule show the earliest structural lesions,
in dogs with experimental hypercalcemia 86 and can but lesions in the collecting system are ultimately the
result in medullary washout as another mechanism most pronounced. Thickening and mineralization of
contributing to hyposthenuria. Isosthenuria develops if tubular basement membranes are most apparent in the
the diluting segments have been structurally altered by proximal tubule. Tubular atrophy, mononuclear cell infil-
long-standing hypercalcemia. Polydipsia occurs as com- tration, and interstitial fibrosis occur in the chronic
pensation for obligatory polyuria, but there is evidence stages. Degenerative and necrotic tubules also are
that polydipsia can be caused by direct stimulation of observed. Granular and tubular cell casts contribute to
the thirst center by hypercalcemia. 115 Mineralization of intrarenal obstruction and azotemia. 314
renal tubules, basement membranes, or the interstitium; Calcium-oxalate urolithiasis occasionally occurs in
tubular degeneration; and interstitial fibrosis are struc- animals with long-standing hypercalcemia and has been
tural changes that may occur in the kidneys secondary described in dogs and cats with primary hyperparathy-
to hypercalcemia and can contribute to impaired urinary roidism. Nephrocalcinosis and linear mineralization
concentrating ability. along the renal diverticula are nonspecific findings discov-
Dehydration is common owing to increased fluid losses ered by radiography or ultrasonography in some dogs
fromvomitingandpolyuria.Substantialcontractionofthe with long-standing hypercalcemia. Increased renal
ECF volume results in a reduction in GFR severe enough echogenicity and the medullary rim sign have been
to increase BUN and serum creatinine concentrations and described during renal ultrasonography in dogs with
to cause prerenal azotemia. The clinical axiom that dilute hypercalcemia. 28,53 These changes can occur in other
urine in association with azotemia is caused by intrinsic normocalcemic conditions and in forms of dystrophic
renallesionsmaynotbetrueinanimalswithhypercalcemia mineralization.