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Basics ⬇

Basics

Definition

Low total and ionized serum calcium concentration

Pathophysiology

  • Of the total circulating serum calcium, 40–50% is protein-bound, 40–50% is ionized, and 10% is complexed with other substances. Protein-bound and complexed calcium are unavailable for use by tissues. Only ionized calcium is available to tissues and is responsible for clinical problems (hypo- and hypercalcemia). Routine measurement of ionized calcium is difficult; many biochemical profiles record only total serum calcium, but some blood analyzers can measure ionized calcium. Mechanisms of hypocalcemia include: Low concentrations of binding proteins-hypoalbuminemia
    • Reduced intestinal absorption-deficient vitamin D (renal disease, severe intestinal disease, rickets, chronic glucocorticoid treatment)
    • Reduced renal and bone resorption-hypoparathyroidism
    • Inadequate dietary intake
    • Excessive loss-lactation (eclampsia)
    • Sequestration-saponification (acute pancreatitis)
    • Binding/complexing with administered, ingested, or endogenous chemicals-phosphate-containing enemas, citrate toxicosis (multiple citrate-containing anticoagulant transfusions), ethylene glycol toxicosis, oxalate toxicosis, low calcium/high phosphorus diet (nutritional secondary hyperparathyroidism), acute tumor lysis syndrome (hyperphosphatemia from cancer therapy-induced rapid destruction of tumor cells)
    • Impaired synthesis or refractoriness to PTH-hypomagnesemia
    • Target organ calcitriol (vitamin D) resistance (vitamin D-dependent rickets type 2)
    • Multifactorial-ionized hypocalcemia in the critically patient

Systems Affected

  • Cardiovascular-ECG changes and bradycardia
  • Gastrointestinal-anorexia and vomiting (especially cats)
  • Nervous/Neuromuscular-seizures, tetany, ataxia, and weakness
  • Ophthalmic-posterior lenticular cataracts
  • Respiratory-panting

Signalment

Species

Dog and cat

Breed Predilections

Varies depending on the underlying cause

Mean Age and Range

Varies depending on the underlying cause

Predominant Sex

Varies depending on the underlying cause

Signs

General Comments

Signs of the underlying disease may be seen without clinical signs of hypocalcemia, because the latter do not occur until total serum calcium falls below 6.7 mg/dL.

Historical Findings

  • Seizures
  • Muscle trembling, twitching, or fasciculations
  • Ataxia or stiff gait
  • Weakness
  • Panting
  • Facial rubbing
  • Vomiting
  • Anorexia

Physical Examination Findings

  • Ataxia, stiff gait, weakness, muscle fasciculation, trembling, twitching.
  • Fever.
  • Posterior lenticular cataracts in patients with primary hypoparathyroidism.

Causes

Non-pathologic Hypocalcemia

  • Laboratory error-repeat serum calcium determinations to confirm true hypocalcemia, especially if significant hypocalcemia despite absence of clinical signs.
  • Hypoalbuminemia-most common cause; accounts for more than 50% of patients; reduction of protein-bound calcium without affecting ionized calcium; not associated with clinical signs.
  • Alkalosis-causes a reduction in both ionized and total measured calcium; not associated with clinical signs unless in cases of borderline low serum ionized calcium concentrations.

Pathologic Hypocalcemia

  • Primary hypoparathyroidism.
  • Hypoparathyroidism secondary to bilateral thyroidectomy (or other corrective hyperthyroid therapies, such as ultrasound-guided thyroid gland ethanol injection or thyroid gland radiofrequency heat ablation) and parathyroid damage.
  • Hypoparathyroidism secondary to ultrasound-guided parathyroid gland radiofrequency heat ablation (for hyperparathyroidism/parathyroid masses) and parathyroid damage.
  • Renal failure-acute or chronic.
  • Ethylene glycol toxicosis.
  • Oxalate toxicosis (lily, philodendron, etc.).
  • Acute pancreatitis.
  • Puerperal tetany-eclampsia.
  • Phosphate-containing enemas.
  • Nutritional secondary hyperparathyroidism.
  • Puerperal tetany (eclampsia).
  • Hypomagnesemia.
  • Intestinal malabsorption.
  • Citrate toxicosis-multiple blood transfusions or improper citrate-blood ratio.
  • Post-hyperparathyroid correction due to prolonged negative feedback–induced hypofunction of normal parathyroid glands.
  • Rickets – rare in dogs and cats (hypovitaminosis D, decreased plasma calcitriol) or vitamin D–dependent rickets type 2 (target organ calcitriol receptor resistance).
  • Acute tumor lysis syndrome.
  • Ionized hypocalcemia in the critically ill patient. Multifactorial: parathyroid dysfunction; cytokine suppression of parathyroid function; vitamin D deficiency; hypomagnesemia; calcium chelation; accumulation of calcium in soft tissues, body fluids, and cells.

Risk Factors

  • Puerperal tetany (eclampsia)-small-breed bitches during first 21 days of nursing, but can rarely affect large breeds and can rarely occur preparturient. Preparturient eclampsia has also been reported in cats.
  • Post-corrective procedures for hyperthyroidism and hyperparathyroidism (parathyroid damage or prolonged negative feedback–induced hypofunction of normal parathyroid glands).

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Clinical signs of hypocalcemia-rule-out primary hypoparathyroidism, hypoparathyroidism secondary to corrective hyperthyroid and hyperparathyroid therapy and parathyroid damage, puerperal tetany (eclampsia), and intoxication leading to rapid calcium binding/complexing (e.g., phosphate-containing enemas, ethylene glycol); other causes rarely lower the serum calcium enough to cause clinical signs.
  • Polyuria and polydipsia-rule-out renal failure.
  • Neurologic signs-rule-out ethylene glycol toxicosis.
  • Vomiting and diarrhea-rule-out acute pancreatitis, intestinal malabsorption, renal failure, and ethylene glycol toxicosis.
  • Bone pain or fractures-rule-out nutritional secondary hyperparathyroidism.

Laboratory Findings

Drugs That May Alter Laboratory Results

  • Sodium bicarbonate may cause alkalosis and lower the serum calcium concentration.
  • Samples collected in EDTA tubes may have a falsely low serum calcium concentration because of calcium chelation.

Disorders That May Alter Laboratory Results

  • Lipemia can raise the serum calcium significantly.
  • Hypoalbuminemia can falsely lower the serum calcium (see causes of non-pathogenic hypocalcemia).

CBC/Biochemistry/Urinalysis

  • Low calcium.
  • Mild-to-moderate anemia possible with chronic renal failure, nutritional secondary hyperparathyroidism, or intestinal malabsorption.
  • Leukocytosis possible with acute pancreatitis.
  • Hypoalbuminemia with hypoproteinemia-induced hypocalcemia-intestinal malabsorption, protein-losing nephropathy, other causes.
  • High total CO2 with alkalosis-induced hypocalcemia.
  • High BUN and creatinine with acute and chronic kidney injury, ethylene glycol toxicosis, or oxalate toxicosis.
  • High phosphorus with acute and chronic kidney injury, ethylene glycol toxicosis, oxalate toxicosis, primary hypoparathyroidism, hypoparathyroidism secondary to hyperthyroid or hyperparathyroid corrective procedures and parathyroid damage, acute tumor lysis syndrome, or in patients receiving phosphate-containing enemas.
  • High amylase and lipase in many, but not all, patients with acute pancreatitis.
  • Isosthenuria with chronic kidney injury, moderate-to-advanced acute kidney injury, ethylene glycol toxicosis, or oxalate toxicosis.
  • Glucosuria in some patients with acute kidney injury, ethylene glycol toxicosis, or oxalate toxicosis.

Other Laboratory Tests

  • Ionized calcium-helps determine if clinical signs are due to hypocalcemia as this is the active form of calcium.
  • Ethylene glycol test-indicated in patients suspected of ingesting ethylene glycol within the previous 12–16 hours (questionable reliability).
  • Pancreatic lipase immunoreactivity-indicated in patients suspected of having acute pancreatitis.
  • PTH assay-indicated when primary hypoparathyroidism is suspected.
  • Serum magnesium concentration-hypomagnesemia is a rare cause of hypocalcemia.
  • Plasma calcitriol (vitamin D, 1,25 dihydroxycholecalciferol) concentration-indicated to screen for rickets or vitamin D-dependent rickets type 2 (rare).

Imaging

  • Radiography usually normal.
  • Possibly, small kidneys with chronic renal disease and large kidneys with acute kidney injury, hyperechoic renal parenchyma on ultrasound with ethylene glycol toxicosis, or oxalate toxicosis.
  • Possibly, osteopenia and pathologic fractures with nutritional secondary hyperparathyroidism.
  • Possibly, mild pleural effusion and decreased anterior abdominal detail from effusion with pancreatitis.

Diagnostic Procedures

ECG changes include prolongation of the ST and QT segments; sinus bradycardia and wide T waves or T wave alternans in some patients.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Inpatient treatment for clinical hypocalcemia.
  • Emergency treatment is usually only needed with primary hypoparathyroidism, hypoparathyroidism secondary to hyperthyroid or hyperparathyroid corrective procedures and parathyroid damage, puerperal tetany (eclampsia), recent phosphate-containing enema administration, citrate toxicosis (rare), and ethylene glycol toxicosis.
  • Longt-term and short-term treatments are usually needed only to treat primary hypoparathyroidism and puerperal tetany (eclampsia), respectively.
  • Puerperal tetany (eclampsia)-remove puppies from bitch and hand-nurse until weaned.

Diet

Diet change recommended for nutritional secondary hyperparathyroidism (to a balanced diet) and renal failure (see Renal Failure, Chronic).

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Emergency Treatment

  • Calcium gluconate 10% solution-5–15 mg/kg (0.5–1.5 mL/kg) give IV slowly to effect over a 10-minute period; monitor heart rate and stop temporarily if bradycardia occurs; if ECG monitoring is possible, QT interval shortening is an indication to temporarily stop administration.
  • Calcium chloride 10% solution-also effective; extremely caustic if administered extravascularly, and three times more potent than calcium gluconate; the mg/kg dosage is the same as for calcium gluconate (5–15 mg/kg), but only one-third the volume is needed (0.15–0.5 mL/kg).

Short-Term Treatment Immediately After Correction of Tetany for Hypoparathyroidism

  • With calcium gluconate 10% solution, relapse of clinical signs after emergency treatment can be prevented by use of constant-rate IV infusion of 60–90 mg/kg/day (6.5–9.75 mL/kg/day) added to fluids that do not contain bicarbonate. This follow-up treatment is rarely necessary for postparturient eclampsia.
  • Subcutaneous calcium gluconate 10% diluted 2–4 times with saline can be administered 3 or 4 times daily for initial control of tetany (reported to be safe in most patients but there have been reports of marked inflammatory calcinosis cutis associated with the subcutaneous treatment option).

Long-Term Treatment

See Hypoparathyroidism.

Contraindications

Avoid bicarbonate as alkalinization may further decrease serum calcium levels.

Possible Interactions

  • Calcium salts may precipitate if added to solutions containing bicarbonate, lactate, acetate, or phosphates.
  • See Hypoparathyroidism.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • For patients requiring long-term hypocalcemia therapy, serum calcium should be assessed 4–7 days following initial treatment, then (if normocalcemic) monthly for the first 6 months, then every 2–4 months.
  • Goal is to maintain serum calcium concentration between 8 and 10 mg/dL.

Expected Course and Prognosis

  • Varies depending on the underlying cause.
  • Recurrence of hypocalcemia following calcium administration is common; monitoring is advised.

Miscellaneous ⬆

Miscellaneous

Pregnancy/Fertility/Breeding

  • Hypocalcemia can lead to weakness and dystocia.
  • Puerperal tetany (eclampsia) usually is seen in small-breed bitches during the first 21 days of nursing a litter.

Abbreviations

  • Ca = calcium
  • ECG = electrocardiogram
  • EDTA = ethylene diamine tetraacetic acid
  • PTH = parathyroid hormone

Suggested Reading

Drobatz K, Casey KK. Eclampsia in dogs: 31 cases (1995–1998). J Am Vet Med Assoc 2000, 217: 216–219.

Feldman EC, Nelson RW. Hypocalcemia and primary hypoparathyroidism. In: Feldman EC, Nelson RW, eds., Canine and Feline Endocrinology and Reproduction, 3rd ed. St. Louis: Saunders, 2004, pp. 716–742.

Schaer M, Ginn PE, Fox LE, et al. Severe calcinosis cutis associated with treatment of hypoparathyroidism in a dog. J.Am Anim Hosp Assoc 2001, 37:364–369.

Waters CB, Scott-Moncrieff JCR. Hypocalcemia in cats. Compend Contin Educ Pract Vet 1992, 14:497–507.

Author Michael Schaer

Consulting Editor Deborah S. Greco

Acknowledgment The author and editors acknowledge the prior contribution of Mitchell A. Crystal.

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