1. Calcium Homeostasis
Ihab Samy
Lecturer of Surgical Oncology
National Cancer Institute
Cairo University
2010

2. Facts About Calcium
Date of Discovery: 1808
Discoverer: Sir Humphrey Davy
Name Origin: From the latin word calcis
(lime)
Uses: life forms for bones and shells
Obtained From: chalk, limestone, marble.
3.5% of crust

3. Physiological importance of Calcium
 Calcium salts in bone provide structural integrity
of the skeleton
 Calcium ions in extracellular and cellular fluids is
essential to normal function of a host of
biochemical processes
 Neuoromuscular excitability
 Blood coagulation
 Hormonal secretion
 Enzymatic regulation

4. Calcium Homeostasis
 99% of body calcium is in the skeleton
 0.9 % intracellular
 0.1% extracellular
 45% bound to plasma proteins mainly albumin
 45% in ionized form (the physiologically active form)
 10% complexed with anions (citrate, sulfate, phosphate)
 Corrected calcium = (4-serum albumin) X 0.8 + measured serum
calcium

5. Calcium Regulation
 Parathormone (PTH)
 4 parathyroid glands
 Release of PTH (chief cells) in response to drop in serum calcium
 Magnesium needed to activate PTH release
 Effects on bone, kidney and indirectly on intestines
 Activates osteoclasts/osteoblasts leading to bone resorption and release
of calcium and phosphorous
 Promotes reabsorption of calcium and excretion of phosphorous in the
kidney
 Activates vitamin D

8. Calcium Regulation
 Vitamin D
 2 sources
 Skin and Diet.
 25 (OH) Vitamin D
 Storage form of Vitamin D.
 Liver.
 1,25 (OH) Vitamin D
 Active form of Vitamin D.
 Activated by PTH and hypophosphatemia through 1-alpha
hydroxylase enzyme in the kidney.

10. Calcium Regulation
 PTH secretion responds to small alterations in plasma
Ca2+ within seconds.
 A unique calcium receptor within the parathyroid chief
cell membrane senses changes in the extracellular fluid
concentration of Ca2+.
 This is a typical G-protein coupled receptor that activates
phospholipase C and inhibits adenylate cyclase 
increase in intracellular Ca2+ via generation of inositol
phosphates and decrease in cAMP which prevents
exocytosis of PTH from secretory granules.

11. Calcium
regulates
PTH
secretion

12. Calcium Regulation
• When Ca2+ falls, cAMP rises and PTH is secreted.
• 1,25-(OH)2-D inhibits PTH gene expression, providing another
level of feedback control of PTH.
• Despite close connection between Ca2+ and PO4, no direct
control of PTH is exerted by phosphate levels.

13. Calcium Homeostasis
 Calcitonin
 Little role in calcium homeostasis.
 Secreted by parafollicular C cells of thyroid.
 Neural cell origin
 Medullary Hyperplasia/Cancer
 Most sporadic case
 MEN IIA or IIB
 15 % cases

14. Parathyroid “C” Cells
PTH Calcitonin
Bone
Kidney
Intestine
Bone
Kidney
[Ca++] [Ca++]
Stimulate
Stimulate
Inhibit
Inhibit
In plasma In plasma
Calcium Homeostasis

15. Maximum
secretion of PTH
occurs at plasma
Ca2+ below 3.5
mg/dL.
At Ca2+ above 5.5
mg/dL, PTH
secretion is
maximally
inhibited.

16. Hypercalcemia
 Symptoms and Signs
 Only 20 % people with hypercalcemia exhibit
signs and symptoms
 “Calcium Stones, fragile bones, abdominal
groans, psychic moans and fatigue overtones”

18. Etiologies of Hypercalcemia
Increased GI Absorption
Milk-alkali syndrome
Elevated calcitriol
Vitamin D excess
Excessive dietary intake
Granuomatous diseases
Elevated PTH
Hypophosphatemia
Increased Loss From Bone
Increased net bone resorption
Elevated PTH
Hyperparathyroidism
Malignancy
Osteolytic metastases
PTHrP secreting tumor
Increased bone turnover
Paget’s disease of bone
Hyperthyroidism
Decreased Bone Mineralization
Elevated PTH
Aluminum toxicity
Decreased Urinary Excretion
Thiazide diuretics
Elevated calcitriol
Elevated PTH

19. Familial Hypocalciuric
Hypercalcemia
(FHH)
 Genetic, autosomal dominant
 Mimics primary hyperparathyroidism
 PTH slightly high, however inappropriate for
level of calcium
 Mutation in parathyroid calcium sensor
 Higher setpoint
 Low urinary calcium/creatinine <0.01
 No end organ damage
 No treatment required

20. Etiologies of Hypocalcemia
Decreased GI Absorption
Poor dietary intake of calcium
Impaired absorption of calcium
Vitamin D deficiency
Poor dietary intake of vitamin D
Malabsorption syndromes
Decreased conversion of vit. D to calcitriol
Liver failure
Renal failure
Low PTH
Hyperphosphatemia
Decreased Bone Resorption/Increased
Mineralization
Low PTH (aka hypoparathyroidism)
PTH resistance (aka pseudohypoparathyroidism)
Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases
Increased Urinary Excretion
Low PTH
s/p thyroidectomy
s/p I131 treatment
Autoimmune hypoparathyroidism
PTH resistance
Vitamin D deficiency / low calcitriol

21. Hypocalcemia
 PTH Resistance
 Pseudohypoparathyroidism
 Congenital defect
 Absent metacarpal, short stature, round face, mental disability
 Target organ unresponsiveness to PTH
 Serum PTH levels high

22. Thank You