Calcium Homeostasis

Ihab Samy
Lecturer of Surgical Oncology
National Cancer Institute
Cairo University
2010
 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
 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
 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

 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
 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.
 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.
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Second level
● Third level
● Fourth level
Calcium ● Fifth level

regulates
PTH
secretion
 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.

 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
 Calcium Homeostasis
Parathyroid “C” Cells

PTH Calcitonin

Inhibit
Inhibit

Bone Bone
Kidney Kidney
e

S ti
lat

Intestine
mu
mu

la t
Sti

e
[Ca++] [Ca++]
In plasma In plasma
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Second level
Maximum
● Third level
● Fourth level
secretion of PTH ● Fifth level
occurs at plasma
Ca2+ below 3.5
mg/dL.

At Ca2+ above 5.5

mg/dL, PTH
secretion is
maximally
inhibited.
 Hypercalcemia

Symptoms and Signs

Only 20 % people with hypercalcemia exhibit

signs and symptoms

“Calcium Stones, fragile bones, abdominal

groans, psychic moans and fatigue overtones”
 Etiologies of Hypercalcemia

Increased GI Absorption Decreased Bone Mineralization

Milk-alkali syndrome
Elevated PTH
Elevated calcitriol
Vitamin D excess Aluminum toxicity
Excessive dietary intake
Granuomatous diseases
Decreased Urinary Excretion
Elevated PTH
Hypophosphatemia Thiazide diuretics
Elevated calcitriol
Increased Loss From Bone Elevated PTH
Increased net bone resorption
Elevated PTH
Hyperparathyroidism
Malignancy
Osteolytic metastases
PTHrP secreting tumor
Increased bone turnover
Paget’s disease of bone
Hyperthyroidism
 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
 Etiologies of Hypocalcemia
Decreased GI Absorption Increased Urinary Excretion
Poor dietary intake of calcium Low PTH
Impaired absorption of calcium
s/p thyroidectomy
Vitamin D deficiency
s/p I131 treatment
Poor dietary intake of vitamin D
Autoimmune hypoparathyroidism
Malabsorption syndromes
PTH resistance
Decreased conversion of vit. D to calcitriol
Vitamin D deficiency / low 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
 Hypocalcemia

PTH Resistance
Pseudohypoparathyroidism
● Congenital defect

● Absent metacarpal, short stature, round face, mental disability

● Target organ unresponsiveness to PTH

● Serum PTH levels high

Thank You