Page 207 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Phosphorus: Hypophosphatemia and Hyperphosphatemia 197

the jejunum and ileum. Intestinal alkaline phosphatases point beyond the last portion of the proximal tubule
may facilitate absorption by freeing inorganic phosphate accessible by micropuncture) that is sensitive to PTH
for transport. Optimal phosphate transport occurs in an and unaffected by saline volume expansion.
2
alkaline environment, and HPO 4 is the main ionic The effects of calcitriol on renal phosphate transport
species transported. Decreased intestinal phosphate are difficult to separate from the effects of calcitriol on
absorption may occur with vitamin D deficiency and in PTH secretion and on phosphate transport in other
malabsorptive states. organs (e.g., intestine, bone). Growth hormone increases
There is no evidence of a direct effect of parathyroid proximal renal tubular phosphate reabsorption, which
hormone (PTH) on intestinal phosphate absorption, partially accounts for the increased serum phosphorus
and observed effects are probably mediated by the role concentrations found in immature animals. Insulin and
of PTH in conversion of 25-hydroxycholecalciferol to thyroxine also increase proximal tubular reabsorption of
calcitriol. High dietary ratios of calcium to phosphorus phosphate, whereas calcitonin and atrial natriuretic pep-
(>3 to 4) may suppress intestinal phosphate absorption, tide inhibit proximal tubular phosphate reabsorption.
presumably through binding of phosphate by calcium High doses of adrenocorticotropic hormone (ACTH)
and formation of poorly absorbed calcium phosphate or glucocorticoids increase renal phosphate excretion
complexes. During phosphate deprivation, the kidneys and may decrease serum phosphorus concentration.
dramatically reduce phosphate excretion to negligible The effects of acid-base balance on proximal tubular
amounts in fewer than 3 days. Obligatory gastrointestinal transport of phosphate are complex. 115 Acute metabolic
loss continues for at least 3 weeks, but there is a diminu- acidosis does not affect renal tubular reabsorption of
tion in the amount lost. 99 This gastrointestinal loss may phosphate, but chronic metabolic acidosis results in
cause a cumulative negative phosphorus balance during decreased proximal tubular transport, an effect possibly
phosphate deprivation. mediated by glucocorticoids. Respiratory acidosis
decreases and respiratory alkalosis increases proximal
RENAL HANDLING tubular reabsorption of phosphate. Volume expansion
increases urinary phosphate excretion and causes natri-
The kidneys adjust tubular reabsorption of filtered uresis because phosphate is cotransported with sodium
phosphate to maintain zero balance. Normally, 80% to in the proximal tubule.
90% of the filtered phosphate load is reabsorbed by the Recently, additional factors that impact renal handling
renal tubules, and renal dysfunction is the most common of inorganic phosphorus have been identified.
cause of hyperphosphatemia beside that found in young Phosphatonins are circulating substances that increase
dogs. 31,160 renal loss of phosphorus. More than one has been
Phosphate crosses the luminal membranes of the identified. To date, they include fibroblast growth
proximal renal tubular cells by brush border sodium- factor-23 (FGF-23), secreted frizzled-related protein
phosphate cotransporters. The main transport protein (sFRP-4), fibroblast growth factor-7 (FGF-7), and
in the proximal tubules (type IIa sodium-phosphate matrix extracellular phosphoglycoprotein (MEPE). 149
cotransporter) translocates three sodium ions and one These substances decrease sodium phosphate transporters
divalent phosphate ion across the luminal membrane in proximal convoluted tubules, whereas FGF-23 and
and thus promotes luminal electronegativity. 168 Luminal sFRP-4 are believed to also decrease formation of 1–25
entry is the rate-limiting step and the target for physio- dihydroxycholecalciferol. FGF-23 is increased in people
logic and pathophysiologic mechanisms that alter phos- with chronic renal failure, but the exact cause is unknown.
phate reabsorption. 115 High dietary intake of Intestinal phosphatonins (factors released from the
phosphorus decreases proximal tubular reabsorption, intestines due to increased intraluminal phosphate con-
whereas low dietary intake can result in nearly 100% prox- centration) have also been suggested to exist. Although
imal tubular reabsorption of phosphate. These dietary believed to be important in some pathologic conditions,
effects occur independently of changes in the plasma their impact in normal phosphorus homeostasis is
concentrations of phosphaturic hormones. PTH is the currently uncertain.
most important regulator of renal phosphate transport,
and it decreases the tubular transport maximum for phos- HYPOPHOSPHATEMIA
phate reabsorption (T maxPi ) in the proximal tubule where
most phosphate reabsorption occurs. Apparently, no
reabsorption occurs in the thin ascending limb or thick CLINICAL EFFECTS OF
ascending limb of Henle’s loop, and the presence of a HYPOPHOSPHATEMIA
reabsorptive mechanism in the distal convoluted tubule Hypophosphatemia can occur even when total body
is uncertain. Phosphate reabsorption is inhibited in the phosphorus is normal. Nonetheless, severe hypophos-
early proximal tubule by volume expansion with saline, phatemia can have many detrimental effects. The most
but there may be a more distal reabsorptive site (at some severe cellular damage seems to occur when there is