calcium homeostasis ppt physiology endocrinology

1. CALCIUM HOMEOSTASIS

2. PHYSIOLOGICAL EFFECTS OF CALCIUM
• Normal Value – 9.4mg/dl
• Contraction of skeletal Muscles
• Contraction of cardiac muscles
• Contraction of Smooth Muscles
• Hemostasis & Blood Clotting
• Transmission of nerve impulses
• Second Messenger

4. Calcium in the Plasma & Interstitial Fluid
• Plasma proteins – Non diffusible – 41%
• Anionic Substances – Diffusible - 9%
• Ionized – Diffusible – 50%

6. Phosphate
• 85% - Bones
• 14-15% - Cells
• Less than 1% - ECF

7. Inorganic Phosphates in ECF
• HPO4
- & H2PO4
-
• 3- 4 mg/dl in adults
• 4-5 mg/dl in children
• pH of ECF – highly ACIDIC
Increase in H2PO4
-
Decrease in HPO4
-

9. Sites of Calcium Storage
• Bones – 99%
• Organic Matrix – 30%
90 -95% - Collagen Fibres
Tensile strength
5-10% - Ground Substance
ECF, Proteoglycans
Control deposition of calcium salts
• Salts – 70%
Hydroxyapatite Ca10 (PO4)6(OH)2
Compressional strength

10. Mechanism of Bone Calcification
• OSTEOBLASTS  Collagen Monomers  Collagen
fibers  OSTEOID
• Ca salts Precipitate on surface of collagen fibers
• Entrapped quiscent osteoblasts in osteoid –
OSTEOCYTES

11. • Hydroxyapatite does not precipitate in ECF
despite supersaturation of Ca & P ions 
• PYROPHOSPHATE

12. Calcium Exchange Between Bone and
ECF
• BONE - exchangeable calcium - in equilibrium
with the calcium ions in the extracellular fluids
• 0.4 to 1 % - total bone calcium.
• calcium deposited in bones - readily
mobilizable salt such as CaHPO4

13. • Deposition of Bone by the Osteoblasts
• Absorption of Bone—Function of Osteoclasts
• Large , Phagocytic, Multinucleated
• Derivatives of MONOCYTES

14. PTH receptors on OSTEOBLAST
OSTEOPROTEGERIN LIGAND (OPGL)
PRE – OSTEOCLAST  MATURE OSTEOCLAST
Villus like projections – Ruffled Border
Proteolytic Enzymes ACIDs– Citric Acid, Lactic Acid
Dissolve Organic Matrix Dissolution of Bone Salts

16. • Stromal cells in the bone marrow, osteoblasts, &
T lymphocytes –
• Receptor activator for nuclear factor kappa beta
ligand (RANKL) on their surface.
• come in contact with appropriate monocytes
expressing RANK (ie, the RANKL receptor)
• Differentiation of monocytes into osteoclasts

17. osteoprotegerin (OPG),
• Osteoblasts
• osteoclastogenesis inhibitory factor (OCIF)
• “decoy” receptor
• Inhibits bone resorption.
• OPG  binding to OPGL  preventing OPGL
from interacting with its receptor inhibiting
differentiation of preosteoclasts into mature
osteoclasts that resorb bone

18. BONE REMODELLING
• Bone deposition & Absorption are normally in
equilibrium
• Bone adjusts its strength in proportion to degree
of bone stress
• Rate of Bone Deposition & Reabsorption
Children – Rapid – Little brittleness
Old age – Slow – very brittle – easily fractured

20. Parathyroid Hormone (PTH)
• Parathyroid Glands
• Four
• Behind Thyroid Gland
• 6mm X 3mm X 2 mm
• Chief cell –
PTH
• Oxyphil Cells
Modified Chief cells – No PTH Secretion

21. • 84 Amino Acids
• PTH is encoded by a gene on chromosome 11
• M.W – 9500
• half-life of PTH - approximately 10 min
• cAMP mediates the effect of PTH

23. PTH
• Increase Calcium & Phosphate Absorption from
BONE
• Increases Ca reabsorption & decreases phosphate
reabsorption – renal tubules
• Decrease excretion of Calcium & Increases
Phosphate Excretion by kidneys
• Synthesis of active form of vitamin D

24. PTH effect on BONE
• RAPID PHASE
OSTEOLYSIS
• SLOW PHASE
Proliferation of Osteoclasts
Increased Osteoclastic reabsorption of BONE

25. parathyroid hormone related
protein (PTHrP)
• produced by many different tissues
• 140 amino acid
• encoded by a gene on human chromosome12
• PTHrP and PTH bind to the hPTH/PTHrP
receptor
• PTHrP  paracrine factor - acting close to
where it is produced.

26. • marked effect on the growth & development
of cartilage in utero.
• inhibits excitotoxic damage to developing
neurons.
• Ca 2+ transport in the placenta.
• In the absence of PTHrP, teeth cannot erupt.

28. Vitamin D
• Nuclear Receptors
• Hormonal effect of Vitamin D
Calbindin
Intestinal Calcium Absorption
• Increases Phosphate Absorption by intestines
• Decreases Renal Calcium & Phosphate Excretion
• Increases Bone Absorption

31. CALCITONIN
• Parafollicular cells / C cells in Thyroid Gland
• Remanants of Ultimobrachial gland
• 32 AA M.W - 3400
• Decreases Plasma Ca Concentration
• Decreases Absorptive activity of Osteoclast
• Decreases Formation of new Osteoclasts

32. • Weak effect on Plasma Ca Concentration
• PTH overrides the Calcitonin effect

34. • ECF Ca – 6mg/dl
• Neuronal Membrane Permeability for Sodium
increases Initiation of action Potentials
Excitable Nervous System
• TETANY
Carpopedal Spasm
Laryngismus Stridulus

36. • Trousseau’s Sign
Circulation to forearm is occluded
with the cuff of BP apparatus – Carpal Spasm
• Chvostek’s Sign
Tapping skin over facial nerve in front of
EAR – Facial muscle twitching ( Upper Lip)
• ERB’s Sign:
Hyperexcitability of Motor Nerves

37. • More than 12mg/dl
• Sluggish Reflex activities
• Muscle weakness
• Lack of appetite
• Depressed contractility of muscle walls – Constipation
• Abdominal pain

38. HYPOPARATHYROIDISM
• Hypocalcemia ( 6-7mg/dl)
• TETANY
• Laryngeal Muscles – Most sensitive to tetanic spasm
• TREATMENT:
PTH
Vitamin D - 1,00,000 units /day + 1 -2g of Calcium

39. Pseudohypoparathyroidism
• Hereditary disorder
• Target tissues are unresponsive to PTH
• Signs & Symptoms of hypoparathyroidism
• PTH is normal or even elevated
• Reduction of the activity of Gs

40. PRIMARY HYPERPARATHYROIDISM
• Tumor of Parathyroid gland
• Women
• Osteoclastic activity >>> Osteoblastic activity
• Osteitis Fibrosa Cystica –
Large punched out cystic areas filled with osteoclast

41. Parathyroid Poisoning & Metastatic Calcification
• > 17mg/dl
• CaHPO4 crystal deposition in
Alveoli of lungs
Tubules of Kidney
Thyroid gland
Walls of arteries ( Arteriosclerosis)

42. Kidney Stones
• crystals of calcium phosphate precipitate in the
kidney – Calcium Phosphate Stones
• formation of renal calculi is greater in alkaline
urine than in acid urine
• Acidotic diets & acid drugs – treatment of calculi

43. Secondary Hyperparathyroidism
• High levels of PTH – Compensation of Hypocalcemia
• Vitamin D deficiency
• Chronic Renal Disease

44. Rickets—Vitamin D Deficiency
• Children
• Vitamin D deficiency – Decrease Ca & Phosphate
• Increases PTH  Osteoclastic absorption of
BONE weakens BONE
• Treatment:
• Vitamin D
• Calcium

45. OSTEOMALACIA – Adult Rickets
• Inadequate Mineralization of BONE
• Steatorrhoea ( failure to absorb fat) 
Vitamin D ( fat soluble )  passesd in feces
• RENAL RICKETS :
• Prolonged Kidney damage  decreased
formation of Vitamin D  Osteomalacia

49. Vitamin D Resistant Rickets
• Congenital reduced absorption of Phosphate in
Renal Tubules Congenital Hypophosphatemia
• Treatment:
Phosphate instead of Ca & Vitamin D

50. OSTEOPOROSIS
• Decreased Bone Matrix
• OLD age
• Osteoblastic Activity reduced  Decreased
Bone Deposition

51. CAUSES of OSTEOPOROSIS
• Lack of Physical Stress – Inactivity
• Malnutrition – Reduced Protein Matrix formation
• Lack of Vitamin C
• Postmenopausal Lack of Oestrogen –
Oestrogen decreases number & activity of osteoclast
• OLD AGE – Protein anabolic functions decrease
• CUSHINGS SYNDROME- Glucocorticoids decrease
osteoblastic activity
• Hyperparathyroidism