14a: Calcium Homeostasis

Hormones that control calcium levels

Parathyroid hormone and calcitriol (active vitamin D)

Organ systems that control calcium levels

• Parathyroid glands

• Kidneys

• Bone

• Intestines

Normal number of parathyroid glands

2 per thyroid lobe → 4 total

Stimulation for PTH release

Low Ca⁺⁺ or high phosphorous

Actions of PTH

• Increases Ca⁺⁺ reabsorption in kidneys and resorption from bone

• Activates calcitriol

• Decreases phosphorous reabsorption from the kidneys

Actions of calcitriol

Increases Ca⁺⁺ and phosphorous resorption and reabsorption from bone, kidney, and intestine

Difference between PTH and calcitriol affects

Both increase Ca⁺⁺, but PTH decreases phosphorous while calcitriol increases phosphorous

Physiologic functions of Ca⁺⁺ in the body

• Enzyme cofactor

• Membrane stability

• Secondary messenger

• Nerve and neuromuscular conduction

• Muscle contraction and tone

• Bone formation

• Glycogen metabolism

Forms of Ca⁺⁺ in the blood

• Ionized/free calcium

• Protein bound (primarily albumin)

• Complexed to something non-protein

Bioactive form of Ca⁺⁺ int he blood

Ionized/free calcium

Most predominant form of Ca⁺⁺ in the blood

Ionized/free calcium

T/F: low total protein will cause clinical hypocalcemia

False

How can we accurately evaluate calcium levels in a patient with low albumin

Run an ionized Ca⁺⁺

CS of hypercalcemia

• PU/PD

• Altered muscle function → weakness

• GI signs

• Lower urinary tract signs

• Shivering

• Constipation

• AKI

Why does hypercalcemia cause PU/PD

High Ca⁺⁺ antagonizes ADH → nephrogenic diabetes insipidus → PU/PD

Why does hypercalcemia cause lower urinary tract signs

High Ca⁺⁺ results in calcium containing urinary stones

Why does hypercalcemia cause AKI

Significant high Ca⁺⁺ causes tissue mineralization, and renal tubules are most susceptible

List of the general causes of hypercalcemia

HARD IONS G or HOGS IN YARD

• Hyperparathyroidism

• Osteolytic lesions

• Granulomatous disease

• Spurious/lab error

• Idiopathic

• Neoplasia

• Y

• Addison’s

• Renal disease

• Vitamin D toxicity

What is tricky about Ca⁺⁺ and CKD/AKI

CKD/AKI may cause high or low Ca⁺⁺ in cats and dogs

MOST common causes of hypercalcemia

• Neoplasia

• Addison’s

• HyperPTH

• CKD

• Idiopathic

Common neoplasia associated with hypercalcemia

Lymphoma, especially if mediastinal

Demographic for idiopathic hypercalcemia

Cats

Most common type of hyperparathyroidism causing hypercalcemia

Primary hyperPTH: excess PTH not responding to negative feedback

Proteins secreted by tumors that increase Ca⁺⁺ levels

• PTHrP

• IL-1

• TGF

• TNF

• Etc.

How does Addison’s cause hypercalcemia

• Decreased calciuresis

• Hemoconcentration

• Increased amounts of complexed calcium

How does kidney disease cause hypercalcemia

• Decreased calciuresis

• PT hyperplasia → decreased inactivation of PTH

• Increased complexed calcium

How does granulomatous disease cause hypercalcemia

Macrophages act like renal tubular cells and activate vitamin D

Common osteolytic diseases that cause hypercalcemia

• Osteosarcoma

• Osteomyelitis

• Panosteitis

• HOD

Treatment for hypercalcemia

• Treat underlying disease

• Normal saline

• Furosemide

• Bisphosphonates

• Glucocorticoids

How does normal saline help with hypercalcemia

Promotes Ca⁺⁺ loss in the urine

How do bisphosphonates help with hypercalcemia

Paralyzes osteoclasts

What do we have to be careful of when using glucocorticoids for hypercalcemia

It can make it harder to diagnose certain diseases, chiefly lymphoma → responds well to steroids in the short term

Demographic for primary hyperPTH

Older dogs

Typical cause of primary hyperPTH

Functional benign tumor

Common CS associated with hyperPTH in dogs

• PU/OD → incontinence

• Listlessness, weakness

• Inappetence

• Lower urinary tract signs

• Etc.

Common CS associated with hyperPTH in cats

• Anorexia

• GIT signs

• PU/PD

• LUTD

• Neuro signs

Diagnostics for hyperPTH

• Hx and PE to rule out other causes

• UA

• Bloodwork

• Ultrasonography

Definitive diagnostic for hyperPTH

Paired PTH and iCa⁺⁺

UA findings consistent with hyperPTH

Dilute urine and active sediment (bacteria, stones, etc.)

Chemistry findings consistent with hyperPTH

Hypercalcemia and hypophosphatemia