Calcium Disorders

Chapter 56 Calcium Disorders



Todd Green, DVM, Dennis Chew, DVM, DACVIM



KEY POINTS



• Severe hypercalcemia or hypocalcemia can be lethal in dogs and cats, especially if extremes of serum calcium concentration develop rapidly.

• Disorders of hypocalcemia are encountered more commonly than are disorders of hypercalcemia.

• Hypocalcemia based on total serum calcium is often mild and less frequently requires calcium-specific management than does hypercalcemia.

• Toxicity of hypercalcemia is greatly magnified if the serum phosphorus concentration is also increased.

• No calcium-specific management is indicated when the total serum calcium is increased but the ionized calcium level is normal.

• No calcium-specific management is indicated when the total serum calcium is decreased, but the ionized calcium level is normal.

• Hypercalcemic crisis is most likely to be encountered when there is toxicity from excess vitamin D metabolites circulating in the body.

• Acute management of moderate to severe ionized hypercalcemia involves intravenous saline, furosemide, calcitonin, and glucocorticoids.

• Severe hypercalcemia may benefit from intermittent intravenous doses of bisphosphonates to decrease osteoclast function. Pamidronate is the first-choice bisphosphonate in veterinary medicine, but zoledronate is more potent and is achieving greater popularity among oncologists.

• In many instances, management of severe and symptomatic hypocalcemia involves the administration of immediate intravenous boluses of calcium salts followed by a continuous rate infusion to maintain normal serum ionized calcium levels.

• Ionized hypocalcemia occurs more frequently than predicted when only the total serum calcium is measured, especially in the critical care setting.


CALCIUM HOMEOSTASIS


Calcium is an important electrolyte that is crucial for numerous intracellular functions, extracellular functions, and skeletal bone support. Calcium is necessary for muscle contraction; ionized calcium mediates acetylcholine release during neuromuscular transmission. Calcium also stabilizes nerve cell membranes by decreasing membrane permeability to sodium. Because of the complexity of its functions, normal homeostatic control mechanisms attempt to keep serum calcium within a narrow range. When these homeostatic mechanisms are disrupted or overwhelmed, conditions of hypocalcemia and hypercalcemia can occur. Three primary forms of calcium exist in serum and plasma: ionized (free), protein bound, and complexed (calcium bound to phosphate, bicarbonate, lactate, citrate, oxalate).1 The ionized form of calcium is the biologically active form in the body and is considered the most important indicator of functional calcium levels.


Calcium regulation is a complex process involving primarily parathyroid hormone (PTH), vitamin D metabolites, and calcitonin. These calcium regulatory hormones exert most of their effects on the intestine, kidney, and bone. PTH is synthesized and secreted by the chief cells of the parathyroid gland in response to hypocalcemia or low calcitriol levels (also known as 1,25(OH)2D3, the principal active vitamin D metabolite). PTH is synthesized and secreted constantly at low rates to maintain serum ionized calcium levels within a narrow range in healthy animals. PTH secretion normally is inhibited by increased serum ionized calcium levels, as well as by increased concentration of circulating calcitriol. The principal action of PTH is to increase blood calcium levels through increased tubular reabsorption of calcium, increased osteoclastic bone resorption, and increased production of 1,25(OH)2D3.


Vitamin D and its metabolites also play a central role in calcium homeostasis. Dogs and cats, unlike humans, photosynthesize vitamin D inefficiently in their skin and therefore depend on vitamin D in their diet.2 After ingestion and uptake, vitamin D is first hydroxylated in the liver to 25(OH)D3 (calcidiol), and then it is further hydroxylated to calcitriol by the proximal tubular cells of the kidney. This final hydroxylation by the 1α-hydroxylase enzyme system to form active calcitriol is under tight regulation, and is influenced primarily by serum PTH, calcitriol, phosphorus, and calcium concentrations. Decreased levels of phosphorus, calcitriol, and calcium promote calcitriol synthesis, and increased levels of these substances all cause a decrease in calcitriol synthesis.


In terms of calcium homeostasis, calcitriol primarily acts on the intestine, bone, kidney, and parathyroid gland. In the intestine, calcitriol enhances the absorption of calcium and phosphate at the level of the enterocyte. In the bone, calcitriol promotes bone formation and mineralization by regulation of proteins produced by osteoblasts. In addition, calcitriol is also necessary for normal bone resorption because of its effect on osteoclast differentiation. In the kidney, calcitriol acts to inhibit the 1α-hydroxylase enzyme system, as well as to promote calcium and phosphorus reabsorption from the glomerular filtrate. In the parathyroid gland, calcitriol acts to inhibit the synthesis of PTH.


Although minor when compared with the effects of PTH and the vitamin D metabolites, calcitonin also plays a role in calcium homeostasis. It is produced in the thyroid gland in response to increased concentration of calcium following a calcium-rich meal and also during hypercalcemia. Calcitonin acts on the bone to inhibit osteoclastic bone resorption activity.



CALCIUM MEASUREMENT



Sample Handling Techniques


When sampling patients for calcium measurements, the patient should fast before collection if possible. Both serum and heparinized plasma samples can be used. When plasma samples are used, certain anticoagulants such as oxalate, citrate, and ethylenediaminetetraacetic acid should not be used, because they can dramatically lower calcium levels when measured in the laboratory. When measuring ionized calcium, serum is preferred over whole or heparinized blood. In addition, anaerobic samples are preferred for ionized calcium measurement, because pH can alter the concentration. In aerobic conditions, carbon dioxide can be lost, thus raising the pH in the sample. An alkalotic pH may increase the binding of calcium to protein and therefore artificially decrease the amount of ionized calcium in the sample. Aerobic samples can be used with reasonable diagnostic accuracy for ionized calcium measurement when sent to a referral laboratory, but species-specific correction formulas are needed that correct the sample pH to 7.40. Hand-held point-of-care analyzers consistently report ionized calcium values that are less than those from bench machines; this error increases with the magnitude of the calcium being measured.3



Ionized Versus Total Calcium


The calcium status of most animals usually is obtained first via measurement of total calcium. However, this parameter frequently does not reflect the ionized calcium concentration of the diseased patient,4 especially in critically ill animals. Therefore, for accurate assessment of patient calcium status, measurement of ionized calcium is recommended. So-called correction formulas that are used to predict ionized calcium status from total serum calcium are quite inaccurate.4



HYPERCALCEMIA


Hypercalcemia can be caused by numerous disease processes (Box 56-1) and may exert toxic systemic effects in multiple organs when ionized hypercalcemia is present.



Box 56-1 Differential Diagnoses for Hypercalcemia


Modified from DiBartola SP: Fluid, electrolyte, and acid-base disorders in small animal practice, ed 3, St Louis, 2006, Saunders.DMSO, Dimethyl sulfoxide.



Nonpathologic



Postprandial

Juvenile, growing animal

Laboratory error

Lipemia


Transient or Inconsequential



Hemoconcentration

Hyperproteinemia

Hypoadrenocorticism


Pathologic or Persistent/Consequential



Parathyroid Dependent




Primary hyperparathyroidism

• Adenoma

• Adenocarcinoma

• Hyperplasia

• Overdose recombinant PTH


Parathyroid Independent




Malignancy

Humoral hypercalcemia of malignancy
• Lymphosarcoma

• Anal sac apocrine gland adenocarcinoma

• Carcinoma (thyroid, prostate, mammary, etc.)

• Thymoma

Hematologic malignancies (bone marrow osteolysis, local osteolytic disease)
• Lymphosarcoma

• Multiple myeloma

• Leukemia

• Myeloproliferative disorders

Bone neoplasia (primary or metastatic)

Idiopathic hypercalcemia (cats)

Chronic renal failure

Calcinosis cutis—during recovery, especially after DMSO

Hypervitaminosis D
• Iatrogenic

• Plants (calcitriol glycosides)

• Rodenticide (cholecalciferol)

• Antipsoriasis creams (calcipotriene or calcipotriol)

Granulomatous disease (calcitriol synthesis)
• Fungal

• Injection site reaction

Acute renal failure

Skeletal lesions
• Osteomyelitis

• Hypertrophic osteodystrophy

• Disuse osteoporosis

• Bone infarction

Excessive oral calcium
• Calcium-containing intestinal phosphate binders

Related posts:

  1. Deteriorating Mental Status
  2. Hyperthermia and Fever
  3. Ventilator-Associated Lung Injury
  4. Allergic Airway Disease in Dogs and Cats and Feline Bronchopulmonary Disease

Stay updated, free articles. Join our Telegram channel
Tags:
Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Calcium Disorders

Full access? Get Clinical Tree
Get Clinical Tree app for offline access