Disturbances of Serum Calcium

FIGURE 5-18

FIGURE 5-17

Physiologic response to hypocalcemia. Hypocalcemia stimulates both parathyroid hormone (PTH) release and PTH synthesis. Both hypocalcemia and PTH increase the activity of the 1-a-hydroxylase enzyme in the proximal tubular (PT) cells of the nephron, which increases the synthesis of 1,25-dihy-droxy-vitamin D3 (1,25(OH)2D3). PTH increases bone resorption by osteoclasts. PTH and 1,25(OH)2D3 stimulate Ca reabsorption in the distal convoluted tubule (DCT). 1,25(OH)2D3 increases the fractional absorption of dietary Ca by the gastrointestinal (GI) tract. All these mechanisms aid in returning the serum Ca to normal levels [1].

CAUSES OF HYPOCALCEMIA

FIGURE 5-18

Causes of hypocalcemia (decrease in ionized plasma calcium).

Lack of parathyroid hormone (PTH)

Increased calcium complexation

After thyroidectomy or parathyroidectomy

"Bone hunger" after parathyroidectomy

Hereditary (congenital) hypoparathyroidism

Rhabdomyolysis

Pseudohypoparathyroidism (lack of

Acute pancreatitis

effective PTH)

Tumor lysis syndrome

Hypomagnesemia (blocks PTH secretion)

(hyperphosphatemia)

Lack of Vitamin D

Malignancy (increased osteoblastic activity)

Dietary deficiency or

malabsorption (osteomalacia)

Inadequate sunlight

Defective metabolism

Anticonvulsant therapy

Liver disease

Renal disease

Vitamin D-resistant rickets

Distillation

FIGURE 5-19

Physiologic response to hypercalcemia. Hypercalcemia directly inhibits both parathyroid hormone (PTH) release and synthesis. The decrease in PTH and hypercalcemia decrease the activity of the 1-a-hydroxylase enzyme located in the proximal tubular (PT) cells of the nephron, which in turn, decreases the synthesis of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3). Hypercalcemia stimulates the C cells in the thyroid gland to increase synthesis of calci-tonin (CT). Bone resorption by osteoclasts is blocked by the increased CT and decreased PTH. Decreased levels of PTH and 1,25(OH)2D3 inhibit Ca reabsorption in the distal convoluted tubules (DCT) of the nephrons and overwhelm the effects of CT, which augment Ca reabsorption in the medullary thick ascending limb leading to an increase in renal Ca excretion. The decrease in 1,25(OH)2D3 decreases gastrointestinal (GI) tract absorption of dietary Ca. All of these effects tend to return serum Ca to normal levels [1].

FIGURE 5-20

CAUSES OF HYPERCALCEMIA Causes of hypercalcemia (increase in ionized plasma calcium).

CAUSES OF HYPERCALCEMIA Causes of hypercalcemia (increase in ionized plasma calcium).

Excess parathyroid hormone (PTH) production

Increased intestinal absorption of calcium

Primary hyperparathyroidism

Vitamin D intoxication

"Tertiary" hyperparathyroidism*

Milk-alkali syndrome*

Excess 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3)

Decreased renal excretion of calcium

Vitamin D intoxication

Familial hypocalciuric hypercalcemia

Sarcoidosis and granulomatous diseases

Thiazides

Severe hypophosphatemia

Impaired bone formation and incorporation of

Neoplastic production of 1,25(OH^D3 (lymphoma)

calcium

Increased bone resorption

Aluminum intoxication*

Metastatic (osteolytic) tumors (eg, breast, colon, prostate)

Adynamic ("low-turnover") bone disease*

Humoral hypercalcemia

Corticosteroids

PTH-related protein (eg, squamous cell lung, renal

cell cancer)

Osteoclastic activating factor (myeloma)

1,25 (OH)2D3 (lymphoma)

Prostaglandins

Hyperthyroidism

Immobilization

Paget disease

Vitamin A intoxication

*Occurs in renal failure.

*Occurs in renal failure.

AVAILABLE THERAPY FOR HYPERCALCEMIA*

Therapy available for the treatment of hypercalcemia.

Agent

Mechanism of action

Saline and loop diuretics

Increase renal excretion of calcium

Corticosteroids

Block 1,25-dihydroxy-vitamin D3

synthesis and bone resorption

Ketoconazole

Blocks P450 system, decreases

1, 25-dihydroxy-vitamin D3

Oral or intravenous phosphate

Complexes calcium

Calcitonin

Inhibits bone resorption

Mithramycin

Inhibits bone resorption

Bisphosphonates

Inhibit bone resorption

*Always identify and treat the primary cause of hypercalcemia.

*Always identify and treat the primary cause of hypercalcemia.

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