Page 143 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Calcium: Hypercalcemia and Hypocalcemia 133

Caution should be exercised in the interpretation of In 1633 canine serum samples, the use of an adjustment
tCa measurements performed on small serum or plasma formula to predict iCa status showed a higher diagnostic
volumes. When submitted volume is inadequate, dilution disagreement than did serum tCa measurement alone. 519
with water or saline is often performed. In an in-house Diagnostic disagreement was 37% between tCa adjusted
commercial laboratory study, when samples were diluted to total protein and iCa measurement and 38% between
1:3, serum tCa concentrations were nearly 3 mg/dL tCa adjusted to albumin and iCa measurement. In 490
lower than when analyzed in undiluted samples (Antech dogs with CRF, diagnostic disagreement between
newsletter May 1999). adjusted tCa and iCa measurement increased to 53%,
indicating the poor performance of the adjustment
Normal Values formulas in the prediction of iCa status. In all dogs, hyper-
The range for serum tCa concentration in normal dogs calcemia and normocalcemia were overestimated, and
and cats is wide and varies among laboratories (see hypocalcemiawasunderestimatedwheneitheradjustment
Table 6-1). Each laboratory should establish normal formula was used. In dogs with CRF, however, hypercal-
values. Variability may result from differences in age, diet, cemia was overestimated, and normocalcemia and hypo-
duration of fasting before sampling, and time of sam- calcemia were underestimated. Because of the high
pling, in addition to differences in analytical methods. degree of diagnostic disagreement between adjusted tCa
Normal serum tCa concentrations in mature dogs and and iCa measurement, the use of adjustment formulas to
cats are approximately 10.0 and 9.0 mg/dL, respectively. predict iCa status cannot be recommended.
No difference in serum tCa concentration has been
ascribed to breed or sex in normal dogs and cats, but IONIZED CALCIUM
115,240
an effect of aging has been observed in the dog. Ionized calcium is the biologically active form of calcium,
Dogs younger than 3 months of age have slightly higher and its homeostasis is important for many physiologic
mean serum calcium concentrations (approximately functions. 478 Calcium ion regulates its own homeostasis
11.0 mg/dL) than those of dogs older than 1 year directly by binding to cell membrane receptors specific
(approximately 10.0 mg/dL), probably because of nor- for iCa. 79 The cell membrane calcium receptors are pres-
mal bone growth. In a small percentage of normal young ent in parathyroid chief cells and C cells of the thyroid
dogs, serum tCa concentrations may be greater than gland, in which iCa regulates PTH and calcitonin secre-
12.0 mg/dL and as high as 15.0 mg/dL. 417 Dietary cal- tion, respectively. Calcium receptors are also present on
cium, phosphorus, and vitamin D supplementation renal tubular cells, and iCa directly regulates its own
should be evaluated in dogs with serum tCa tubular reabsorption rate. Therefore, serum iCa concen-
concentrations greater than 12.0 mg/dL. tration is controlled by interacting feedback loops that
involve iCa, phosphate, PTH, calcitriol, and calcitonin.
Adjusted Total Calcium These mechanisms help maintain serum iCa concentra-
It has been reported that serum tCa concentrations tion in a narrow range.
should be “corrected” or “adjusted” relative to the total For accurate assessment of calcium status, iCa must be
serum protein or albumin concentration to improve diag- measured directly. Ionized calcium measurement has
nostic interpretation. 184,376 Such correction seemed log- been shown to be superior to serum tCa measurements
ical because binding of serum calcium to protein is in many conditions, especially in hyperparathyroidism,
substantial, and 80% to 90% of the calcium bound to renal disease, hypoproteinemia and hyperproteinemia,
proteins is bound to albumin. The correlation between acid-base disturbances, and critical illnesses. 218,519,638
serum tCa and serum albumin or total protein Changes in the magnitude of serum protein concentra-
concentrations was moderate, and adjustment formulas tion, individual protein binding capacity and affinity,
were developed for use in dogs older than 1 year. These serum pH, and complexed calcium all interact to deter-
adjustment formulas were not recommended for use in mine the iCa concentration, independent of the tCa con-
cats because there was no linear relationship between centration. Fasting serum samples collected at the same
serum tCa and serum albumin and total protein time in the morning are advised.
concentrations in this species. 189
It has been assumed that serum tCa concentrations Analytical Methods
that correct into the normal range are associated with Use of automated equipment with a calcium ion-selective
normal serum iCa concentration. Likewise, samples with electrode allows easy and accurate measurement of iCa in
values that fail to correct into the normal range are pre- blood, plasma, or serum. 64 Newly developed electrodes
sumed to have abnormal serum iCa concentrations. minimize interference by other ions (e.g., magnesium,
However, these formulas were developed without verifi- lithium, and potassium), protein, or hemolysis. 220 Never-
cation by serum iCa measurements. Correction of serum theless, differences among analyzers exist, and it is
tCa concentration for albumin did not improve the cor- recommended that reference ranges be established for
relation between serum tCa and iCa concentrations. 385 each analyzer. 265