Page 952 - Small Animal Internal Medicine, 6th Edition

924 PART VII Metabolic and Electrolyte Disorders

and change in sample pH (ionized calcium decreases as pH Clinical Features
increases). Protocols established by the clinical chemistry Although all tissues can be affected by hypercalcemia, the
VetBooks.ir laboratory for submitting blood samples for ionized calcium are the most important clinically. Secondary nephrogenic
neuromuscular, gastrointestinal, renal, and cardiac systems
determination should be followed to ensure accurate results.
diabetes insipidus, loss of the renal concentration gradient,
Handheld point-of-care analyzers typically report ionized
calcium values that are less than those reported from bench- and metastatic mineralization of the kidney cause polyuria
top machines. and polydipsia. Decreased excitability of the central and
peripheral nervous systems in conjunction with decreased
Etiology excitability of gastrointestinal smooth muscle causes leth-
Hypercalcemia is relatively common in dogs and cats. Per- argy, anorexia, vomiting, constipation, weakness, and (rarely)
sistent hypercalcemia usually results from increased calcium seizures. In rare instances, cardiac arrhythmias may develop
resorption from bone or kidney or increased calcium absorp- in animals with severe hypercalcemia (i.e., >18 mg/dL). Pro-
tion from the gastrointestinal tract. Humoral hypercalcemia longation of the PR interval and shortening of the QT inter-
of malignancy (HHM), the most common cause of hyper- val may be found on electrocardiographic readings recorded
calcemia, occurs when the tumor produces substances that in animals with milder hypercalcemia.
promote osteoclastic activity and renal calcium reabsorp- Clinical signs are often absent with mild increases in the
tion. These substances include parathyroid hormone (PTH); serum calcium concentration, and hypercalcemia is discov-
PTH–related peptide (PTHrP); 1,25-dihydroxyvitamin D; ered only after a serum biochemistry panel is performed,
cytokines, such as interleukin-1 and tumor necrosis factor; often for unrelated reasons. When clinical signs do develop,
prostaglandins; and humoral factors that stimulate renal they initially tend to be insidious in onset. The severity of
1α-hydroxylase. Tumors may also induce hypercalcemia clinical signs depends in part on the severity, rate of onset,
through local osteolytic activity after they metastasize to and duration of the hypercalcemia. Clinical signs become
bone. Less commonly, hypercalcemia develops as the result more severe as the magnitude of the hypercalcemia increases,
of impaired loss of calcium from the serum (e.g., reduced regardless of the rate of onset or duration. Clinical signs are
glomerular filtration) or reduced plasma volume (e.g., usually mild with serum calcium concentrations less than
dehydration). 14 mg/dL, are readily apparent with concentrations greater
The list of differential diagnoses for hypercalcemia in than 14 mg/dL, and become potentially life-threatening (i.e.,
dogs and cats is relatively short (see Table 47.2, p. 761). In cardiac arrhythmias) when the serum calcium concentration
the dog HHM (especially lymphoma), hypoadrenocorticism, exceeds 18 to 20 mg/dL. Clinical signs resulting from the
chronic kidney disease, hypervitaminosis D, and primary development of calcium phosphate or calcium oxalate uro-
hyperparathyroidism are the most common diagnoses. In liths may be noted.
the cat, idiopathic hypercalcemia, HHM (especially lym-
phoma and squamous cell carcinoma), and chronic kidney Diagnosis
disease are the most common diagnoses. Calcium oxalate Hypercalcemia should always be reconfirmed, preferably
urolithiasis and consumption of acidifying diets are com- from a nonlipemic blood sample obtained from the dog or cat
monly identified in cats with hypercalcemia, but their role, after a 12-hour fast, before an extensive diagnostic evaluation
if any, in causing the disorder is unknown. is undertaken. Results of CBC, serum biochemistry panel,
Hypercalcemia can develop in dogs and cats with chronic and urinalysis, in conjunction with the history and physical
kidney disease and, less commonly, acute kidney injury. The examination findings, often provide clues to the diagnosis
pathogenesis of hypercalcemia associated with chronic (see Table 47.2). Special attention should be paid to serum
kidney disease is complicated. The development of autono- electrolytes and renal parameters. Hypoadrenocorticism-
mously functioning parathyroid glands or an alteration of induced hypercalcemia typically occurs in conjunction with
the set point for PTH secretion after prolonged stimulation mineralocorticoid deficiency; hyponatremia, hyperkalemia,
of renal secondary hyperparathyroidism, decreased PTH and prerenal azotemia should be present. The serum phos-
degradation by renal tubular cells, increased PTH-mediated phorus concentration is in the lower half of the normal range
intestinal absorption of calcium, increased PTH-mediated or low with HHM and primary hyperparathyroidism (Fig.
osteoclastic bone resorption, decreased renal excretion of 53.1). If the serum phosphorus concentration is increased
calcium, and increased protein-bound or complexed frac- and renal function is normal, hypervitaminosis D and bone
tions of calcium is believed to contribute to the hypercalce- osteolysis from metastatic or primary bone neoplasia are the
mia of renal failure. Prolonged hypercalcemia, especially in primary differentials.
conjunction with concurrent high-normal to increased Determining whether kidney disease is primary or sec-
serum phosphorus concentration, can also cause nephrocal- ondary to hypercalcemia caused by another disorder when
cinosis and exacerbate kidney disease and azotemia. Deter- hyperphosphatemia and hypercalcemia coexist with azo-
mining whether the kidney disease is primary or secondary temia can be difficult. Chronic, and less commonly acute,
in a dog with hypercalcemia, hyperphosphatemia, and azo- kidney disease can cause hypercalcemia. Alternatively, dis-
temia poses an interesting diagnostic challenge (see the orders that cause persistent hypercalcemia with a concurrent
Diagnosis section). high-normal to increased serum phosphorus concentration