Clinical signs of hypocalcemia in dogs include muscle tremors, convulsions, ataxia, and weakness. In horses, hypocalcemia is associated with synchronous diaphragmatic flutter and signs of tetany including stilted gait, muscle tremors, flared nostrils, inability to chew, recumbency, convulsions, and cardiac arrhythmias. In cows, hypocalcemia is usually manifested as weakness and recumbency. Signs of hypocalcemia develop when ionized calcium is too low for normal muscle and nerve function. Because of factors that influence ionized and protein-bound calcium fractions, the total calcium result does not necessarily correlate with ionized calcium and is not by itself always a reliable indicator of clinical hypocalcemia.

Because such a large percentage of total calcium is protein-bound, hypoalbuminemia decreases Ca, but not the ionized calcium concentration; therefore, the first step in interpreting a low Ca is to look at the albumin result. A mild hypocalcemia in the presence of hypoalbuminemia usually does not indicate a disorder of calcium metabolism. This interpretation is probably applicable for all species. For dog and man, it is said that Ca can be adjusted for albumin concentration by using the following formula:

Adjusted Ca = measured Ca - serum albumin concentration + 3.5

The equilibrium between ionized calcium and protein-bound calcium is affected by pH. Acidosis increases the ionized fraction, whereas alkalosis decreases ionized calcium; total calcium concentration is not affected by changes in pH. Therefore, an acidotic animal may show no signs of hypocalcemia yet have a Ca result low enough that signs would be expected. Conversely, an alkalotic animal may show signs of hypocalcemia yet have a Ca result that is within the reference range. The bicarbonate result and anion gap should be considered as well as the albumin result when interpreting the Ca result.

Mechanisms of hypocalcemia
  • Decreased absorption in the gastrointestinal system.
  • Increased excretion of calcium in the kidney.
  • Inhibition of osteolysis.
Causes of hypocalcemia
  • Spurious. Hypocalcemia can be due to hypoalbuminemia.
    Calcium can be measured reliably in heparinized plasma and the results are comparable to serum Ca results. However, exposure of blood to anticoagulants such as EDTA, citrate, and oxalate (the anticoagulant in the sodium fluoride tube) reduces calcium to an unmeasurable level. Since Ca < 2 mg/dl is not compatible with life, exposure to agents that chelate calcium are indicated by such a result.

  • Hypoparathyroidism. This has been reported in dogs, cats and one horse. Clinical signs include seizures, ataxia, and lens cataracts. It is characterized by hypocalcemia, normal or increased phosphate and normal magnesium. In dogs, it is usually due to lymphocytic infiltration, atrophy and fibrosis of the parathyroid gland (? immune-mediated). Low concentration of parathyroid hormone confirms primary hypoparathyroidism.

  • Nutritional secondary hyperparathyroidism. This is so-called bran disease of horses (it occurs with all grain diets or grass diets high in oxalates) but can occur in all species with excess phosphate, reduced calcium or lack of vitamin D in the diet. Ionized calcium values are low, stimulating PTH with bone resorption. Usually, parathyroid response maintains normocalcemia but at the expense of bone calcium. The usual signs in this disorder are lameness, bone pain, osteopenia (producing hyperostotic fibrous osteodystrophy - "bighead") and pathologic fractures, rather than convulsions.

  • Renal secondary hyperparathyroidism. This occurs especially in dogs, but also in cats with chronic renal failure. PTH is stimulated from low ionized calcium (due to excess phosphate), vitamin D production is impaired due to renal insufficiency, there is skeletal resistance to PTH and an altered setpoint to PTH, such that it is resistant to suppression by increased calcium. Metabolic acidosis is very common in animals with renal failure, and the acidosis tends to ameliorate signs of hypocalcemia even if total calcium is decreased.
    Acute renal tubule damage can also result in a mild hypocalcemia in horses, cattle and sheep.

  • Milk fever. This is seen in highly producing dairy cows and results in paresis. They have low calcium and phosphate. Magnesium is often normal. Eclampsia can also be seen in dogs, cats, ewes, sows, mares and goats and produces tetany in these breeds. Inability of calcium homeostatic mechanisms to compensate for loss of calcium in milk is thought to be the cause of lactation-associated hypocalcemia in dogs. The condition is seen most commonly in small breed dogs two to three weeks after whelping. Hypocalcemia associated with lactation in horses is called lactation tetany and is less common than in cows.

  • Pancreatitis. Mild hypocalcemia, usually without clinical signs referable to hypocalcemia, is fairly common in acute pancreatitis. The mechanism is unknown but postulated to be partly due to sequestration of calcium by formation of salts with fatty acids released from peripancreatic fat by the action of lipase and due to glucagon release from the inflamed pancreas stimulates calcitonin release.

  • Idiopathic hypocalcemia in foals. This is seen in young foals, from 4 days to 5 weeks old. They display tachycardia, sweating, muscle rigidity, recumbancy, seizures and opisthotonus. The prognosis is poor and many die or are euthanized. The cause is uncertain. it is thought to be similar to late neonatal hypocalcemia in human infants. The foals do not respond to calcium supplementation.

  • Hypercalcitonism: C cell tumors in dogs, horses and cattle.

  • Toxicosis: Sodium phosphate enemas, blister beetle (canthradin) toxicosis in horses, ethylene glycol toxicity (hypocalcemia is a common finding in the chemistry panel of dogs and cats poisoned with antifreeze. Precipitation of calcium by oxalate, one of the metabolites of ethylene glycol, is thought to be the mechanism. Any signs of hypocalcemia are overshadowed by those due to the primary problem.)

  • Miscellaneous causes: Sweating in horses (the chief sign in this setting is synchronous diaphragmatic flutter, which is contraction of one or both flanks coincident with the heartbeat), transport tetany, gastrointestinal disorders in horses (hypocalcemia developing secondary to gastrointestinal disorders is fairly common and in some horses, may be severe enough to require treatment with calcium-containing solutions), LDA in cattle, malignant hyperthermia, and hypomagnesemia.
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