Hypocalcemia – clinical syndrome caused by low serum [Ca⁺⁺]

• Calcium Compartments
• Total Serum Calcium
• Bound to proteins – 40%
• Bound to organic and inorganic ions – 15%
• Free ionized Ca⁺⁺ – 45%
• Only the free, ionized Ca⁺⁺ is physiologically active and maintained by homeostatic mechanisms
• e.g., alkalosis increases binding of free Ca⁺⁺ to albumin resulting in ß free ionized Ca⁺⁺ without a change in total Ca⁺⁺
• Defense Against Hypocalcemia involves Ý PTH (Ý [Ca⁺⁺], but PO₄^2- may decrease)
• recall that PTH Ý bone resorption, Ý activity of renal activation of vitamin D, and Ý Ca⁺⁺ reabsorption/ß PO₄^2- reabsorption in nephron

• Acute
• Neuromuscular "Tetany" – Ý neuromuscular excitability; muscle cramps; spontaneous carpopedal spasm; laryngeal stridor, convulsions
• Chvostek's Sign – facial twitch on tapping the facial nerve
• Trousseau's Sign – carpopedal spasm when nerves in the upper arm compressed with blood pressure cuff
• also tingling in hands, feet and around mouth
• What causes this? – voltage-dependent Ca⁺⁺ channels become more active when ß in Ca⁺⁺ causes depolarization
• Elevated CSF pressure with papilledema – ß activity of pumps that pump sodium out of the CSF space
• Psychiatric Effects – irritability, anxiety, agitation, depression, mental dullness, paranoia, psychosis
• Cardiac Effects -delayed repolarization (slower generation of intracellular Ca⁺⁺ to open K⁺ channels), arrhythmias
• CHF is resistant to treatment with digoxin, since Ca⁺⁺ is required for excitation-contraction coupling
• Chronic
• Ophthalmologic Effects – premature cataract formation Þ ß activity of pumps that pump sodium out of lens
• Mental Retardation – if hypocalcemia is present in early childhood
• Dental Effects (in children) – defective enamel and root formation; dental hypoplasia, failure of adult teeth to erupt
• Basal Ganglion Calcifications with or without Movement Disorder – in long-standing, untreated hypoparathyroidism

• (1) Diminished ability to mobilize Ca⁺⁺ from bone
• Hypoparathyroidism – ß PTH Secretion – associated with ß PTH, ß Ca⁺⁺, and Ý PO₃^2-
• from surgical removal of gland, autoimmune disorders, or deficiency of Mg⁺⁺ (required for PTH synthesis)
• Pseudohypoparathyroidism – ß tissue responsiveness to PTH – associated with ß PTH, ß Ca⁺⁺, and Ý PO₃^2-
• from defective generation of cAMP in renal tubular cells in response to PTH
• type Ia – ß activity of G_S; type Ib – probably receptor abnormality; type II – problem downstream of cAMP
• Albright’s Hereditary Osteodystrophy – clinical findings associated with with pseudohypoparathyroidism type Ia only
• obesity; short, round face; mental retardation, shortening of metacarpal and metatarsal bones
• abnormal G_S can produce Albright’s without ß tissue response to PTH- "Pseudo-pseudohypoparathyroidism"
• Treatment – oral Ca⁺⁺ and large doses of Vit D
• (2) Diminished Absorption of Ca⁺⁺ from the Gut (ß Vit D Action)
• ß in Ca⁺⁺ leads to Ý PTH (Secondary Hyperparathyroidism) – may normalize Ca⁺⁺, but at expense of bone resorption
• leads to hypophosphatemia due to ß renal reabsorption and ß intestinal absorption of PO₄^2-
• ß in Vit D causes osteomalacia (ß bone mineralization)
• Etiology of ß Vit D Action
• (a) ß Vit D Production – nutritional, malabsorption, ß sun exposure, liver failure, renal-1-hydroxylase deficiency
• (b) Deficient 1,25 (OH)₂ Vit D Action – receptor deficiency, defective receptor, post-receptor defect
• (3) Increased Loss of Ca⁺⁺ from Blood into Bone and Soft Tissue
• Loss into Bone – usually from osteoblastic bone metastases
• Loss into Soft Tissues – several possible causes:
• (a) Hyperphosphatemia – sudden influx of PO₄^2- causes deposition of calcium phosphate in soft tissue
• (b) Acute Pancreatitis – release of digestive enzymes Þ fat necrosis Þ reservoir for calcium phosphate deposits