Page 146 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

136 ELECTROLYTE DISORDERS

versus “intact” PTH to clarify low bone turnover, renal VITAMIN D METABOLITES
osteodystrophy 406 or the dynamics of PTH secretion 507 Measurement of vitamin D metabolites is occasionally
have been attempted. 216,305 The “whole” PTH assay
helpful in diagnosing disorders of calcium homeostasis
may also be of better diagnostic value in dogs than the
(see Table 6-1). 25-Hydroxyvitamin D (calcidiol) and
“intact” PTH assay because PTH-(7-84) fragments calcitriol are the metabolites of clinical interest for detec-
may be increased in dogs as compared with humans. 168
tion of hypovitaminosis D, hypervitaminosis D, and
Whole PTH (1-84) and intact PTH (1-84 and 7-84) have
abnormalities of the renal hydroxylase system (e.g., renal
been measured in dogs, and it was observed that the
failure). The metabolites are stable during refrigeration
whole PTH/intact PTH ratio in dogs (about 36%) was
and freezing, but samples should not be exposed to light
less than in humans, and the ratio did not change during for long periods.
acute hypocalcemia. 168 In preliminary studies in cats, a The metabolites of vitamin D are chemically identical
third-generation PTH-(1-84) assay resulted in higher in all species, thus receptor-binding assays or RIAs devel-
PTH values than a second generation assay that also oped for use in humans are satisfactory for the measure-
measures the PTH-(7-84) fragment. 134 Although this 256,260
ment of the same metabolites in animals. Young
is opposite of what is found in humans, it is not unex-
growing dogs have higher calcitriol concentrations than
pected because cat and other mammalian PTH is more
mature dogs, and most mammals appear to share this
similar to human PTH in the first few amino acids than 373
attribute during rapid growth.
in the region of the tenth amino acid.
Concentrations of 25-hydroxyvitamin D are a good
PARATHYROID HORMONE-RELATED indicator of vitamin D ingestion or production in vivo
PROTEIN and can be used to diagnose hypovitaminosis D or hyper-
vitaminosis D. 107 Calcitriol assays can be used to detect
Two-site IRMA and N-terminal RIA are available for the genetic errors of vitamin D metabolism, low
measurement of human PTHrP. 49,310 These assays are concentrations of calcitriol in patients with renal failure,
useful for measuring biologically active PTHrP in the or high concentrations of calcitriol in some patients with
dog (see Cancer-Associated Hypercalcemia sec- cancer-associated hypercalcemia. 478
tion) 117,489 because of the high degree of sequence
homology of PTHrP between species, especially in the BONE BIOPSY AND BONE MARROW
N-terminal 111 amino acids. 91 An N-terminal RIA for ASPIRATION
human PTHrP did not prove useful for measuring Bonemarrowaspirationorcorebiopsyisfrequentlypartof
circulating PTHrP in a small number of horses. 490
the diagnostic evaluation of animals without an obvious
PTHrP is susceptible to degradation by serum proteases,
cause of hypercalcemia. Its greatest utility is in the discov-
and PTHrP concentrations must be measured in fresh or ery of lymphoma, myeloproliferative disease, or multiple
frozen plasma using EDTA as an anticoagulant. EDTA myeloma. Biopsy of the iliac crest is recommended for
complexes with plasma calcium, which is required for standardization, particularly when histomorphometric
function of many proteases. The addition of protease
analysis is available for the quantitative evaluation of bone
inhibitors, such as aprotinin and leupeptin, may provide formation and bone resorption. A procedure for iliac crest
further inhibition of proteolysis in plasma. 429 122,486
bone biopsy has been described. Direct biopsy of
The circulating forms of PTHrP are not completely
focal bone lesions may be diagnostic, particularly when
understood because PTHrP rapidly undergoes proteoly-
such lesions are caused by lymphoma, multiple myeloma,
sis intracellularly and extracellularly after secretion into or a metastatic bone tumor.
the blood. 429 The forms of PTHrP that are present
in vivo include intact PTHrP, an N-terminal peptide, a
combined N-terminal and midregion peptide, a HYPERCALCEMIA
90,632
midregion peptide, and a C-terminal peptide.
Fragments that have PTH-like biologic activity in vivo Hypercalcemia is an uncommon but important electro-
include N-terminal PTHrP (1-36), PTHrP (1-86), and lyte disturbance of dogs and cats. The frequency of
intact PTHrP (1-141). The two-site immunologic assays finding hypercalcemia based on evaluation of serum
measure intact PTHrP (1-141) and PTHrP (1-86) tCa in more than 10,000 canine serum samples analyzed
because antibodies bind to the N terminus and during a 6-month period at one private veterinary diag-
midregion. The N-terminal RIAs measure intact PTHrP nostic laboratory was 1.5%. 94 Of these, 28% were found
(1-141), PTHrP (1-86), and N-terminal PTHrP (1-36). to be from young growing dogs, 62% were found to be
The C-terminal PTHrP accumulates in the sera of human transient, and 18% were persistent and associated with
patients with renal failure, which suggests that C-terminal pathology.
PTHrP peptides are excreted by the kidneys, as occurs Hypercalcemia can serve as a marker of disease or can
with PTH. 89 create disease. Increases in serum iCa concentration