THE ENDOCRINE SYSTEM, METABOLISM AND DISORDERS

Calcium, Phosphate and

Vitamin D Metabolism
Team Division of Endocrinology and Metabolism
Department of Internal Medicine,
Faculty of Medicine, Udayana University

5th April – 6th May 2019

 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
– Neuromuscular excitability
– Blood coagulation
– Hormonal secretion
– Second messenger
Distribution of Calcium
 Extracellular Calcium
• Three definable fractions of calcium in serum:
– Ionized calcium 45%
– Protein-bound calcium 45%
• 90% bound to albumin
• Remainder bound to globulins
– Calcium complexed to serum constituents 10%
• Citrate and phosphate
Daily Turnover of
Calcium
 Bone Cell Types
• Osteoblasts are the differentiated bone forming
cells and secrete bone matrix on which Ca++ and P
precipitate.
• Osteocytes, the mature bone cells are enclosed in
bone matrix.
• Osteoclasts is a large multinucleated cell derived
from monocytes whose function is to resorb bone.
Inorganic bone is composed of hydroxyapatite and
organic matrix is composed primarily of collagen.
 Parathyroid Hormone
• PTH is synthesized and secreted by the parathyroid
gland which lie posterior to the thyroid glands.
• The blood supply to the parathyroid glands is from
the thyroid arteries.
• The Chief Cells in the parathyroid gland are the
principal site of PTH synthesis.
 Synthesis of PTH
• PTH is translated as a pre-prohormone.
• Cleavage of leader and pro-sequences yield a
biologically active peptide of 84 AA.
• Cleavage of C-terminal end yields a biologically
inactive peptide.
 Regulation of PTH
• The dominant regulator of PTH is plasma Ca2+.
• Secretion of PTH is inversely related to [Ca2+].
• 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.
Cells-surface Receptors for PTH
Parathyroid Ca-sensing Receptor
PTH Mediates Bone Resorption
Serum Ca2+ Level and PTH Secretion
 Vitamin D
• Vitamin D is a lipid soluble hormone that binds to a
typical nuclear receptor, analogous to steroid
hormones.
• Vitamin D, after its activation to the hormone 1,25-
dihydroxy Vitamin D3 is a principal regulator of Ca++.
• Vitamin D increases Ca++ absorption from the
intestine by Calcium-binding protein (CaBP) and Ca++
resorption from the bone .
 Synthesis of Vitamin D
• It can be synthesized from diet (ergocalciferol/D2)
and skin (cholecalciferol/D3)
• First step, hydroxylation (by 25 hydroxylase) at C-
25 to 25-hydroxyvitamin D3 (25-OH-D3) in the liver.
• Second step, hydroxylation (by 1-α-hydoxylase) at
C-1 to 1,25-(OH)2-D3/Calsitriol in kidney.
• Phosphate inhibits 1a-hydroxylase and decreased
levels of PO4 stimulate 1a-hydroxylase activity
Calcium Uptake by Intestinal Cells
 Calcitonin
• Calcitonin acts to decrease plasma Ca++ levels.
• While PTH and vitamin D act to increase plasma
Ca++-- only calcitonin causes a decrease in plasma
Ca++.
• Calcitonin is synthesized and secreted by the
parafollicular cells (C cells) of the thyroid gland.
• Calcitonin is a physiological antagonist to PTH with
regard to Ca++ homeostasis
 Calcitonin
• The target cell for calcitonin is the osteoclast.
• Role of calcitonin in normal Ca2+ control is not
understood—may be more important in control of
bone remodeling.
• Chronic excess of calcitonin does not produce
hypocalcemia and removal of thyroid gland does
not cause hypercalcemia because PTH and Vitamin
D3 regulation dominate.
THANK YOU