calcium homeostasis and viamin D

CALCIUM , ITS REGULATION AND VITAMIN D

1. CALCIUM and ITS
REGULATION
Dr Anu Chandran

2. CALCIUMCALCIUM
2% of body weight
99% in bones
1% in body fluids
Plasma (Extracellular fluid)
9 to 11 mg/dl
Cell (Intracellular fluid)
10
-5
– 10
-4
mmol/l

3. Distribution of Calcium in Body 
99% in bone 1% in blood and body fluids
Blood Calcium (10mg/dl)
Non diffusible 35 %
Albumin bound
80 %
Globulin bound
20 %
Diffusible 65 %
Ionized 80 % Complexed 20 %
Bicarbonate
Citrate
Phosphate
Total body calcium- 1kg

4. ROLE OF CALCIUMROLE OF CALCIUM
•Excitability of cell membranes
•Neuromuscular transmission and
muscle contraction
•Releasing of transmitters from
synapses
•“Second messenger”
•Stimulates secretory activity of
exocrine glands and releasing of
hormones
•Contractility of myocardium
•Blood coagulation

5. Calcium Absorption
•Primarily in duodenum
–20-30% 
•Adaptive changes 
                         low dietary calcium
                        growth (150 mg/d)
                         pregnancy (100 mg/d) 
                         lactation (300 mg/d) 
•Decreased by
–Oxalic  Acid,  phytates,  dietary  fiber, 
magnesium and phosphorus, tannins
Increased by    
–Acidic conditions in the intestine, 
–vit D, 
–estrogen,
–lactose

6. DIETARY CALCIUM INTAKE
1 ml ~ 1mg
1 pot ~ 150 mg
~ 35 mg/slice
1 Bowl ~ 80 mg
1 oz ~ 200 mg
Infants up to 1 yr 525
Children 1- 3 yrs 350
Children 2-6 yrs 450
Children 7-10 yrs 550
Adolescent boys 11-18 yrs 1000
Adolescent girls 11-18 yrs 800
Adults 19 above 700

7. Hormonal Regulators
•Calcitonin (CT)
•Parathormone (PTH)
•1,25 Vitamin D3

8. Calcitonin (CT)
Secreted from the C cells
in the thyroid
32 aa
t₁⁄₂ 10 minutes
MOA
Direct inhibition of
osteoclasts
Promotes deposition of
Ca++ into bone
Lowers Ca++ in blood
CT

9. Preparation
•Synthetic salmon calcitonin
•SC / IM / nasal spray
•I IU = 4mg of standard calcitonin

10. Parathormone (PTH)
•84 aa
•t₁⁄₂ 2 to 5 minutes

13. Preparation
•Recombinant PTH – TERIPARATIDE
•SC
•20 IU/ day
•12 to 18 months
•Increase bone density

14. Vitamin D
Sources
- 90% synthesised in skin via UVB light
exposure (D3)
Cholecalciferol
- 10% from food – Ergocalciferol (D2)

15. Cholesterol precursor 7-dehydrocholesterol
UV
Vitamin D3
25 Vitamin D3
1,25 Vitamin D3
Low plasma Ca++ increase kidney enzymes
calcitriol

16. Sources & Metabolism of Vitamin Sources & Metabolism of Vitamin
DD
Solar UVB (280-310nm)
Endogenous
Vitamin D
3
Dietary source
Vitamin D
2
& D
3
Oily fish, eggs,
fortified foods e.g:
 Infant formulas
 Cereals
LiverLiver
25-Hydroxyvitamin D
(major circulating metabolite)
1,25-Dihydroxyvitamin D
KidneyKidney
1α hydroxylase
(CYP27B1)
(7-dehydoxycholesterol)(7-dehydoxycholesterol)
DBP
25-hydroxylase
(CYP2R1)
24-hydroxylase
(CYP24A1)
DBP
24,25-hydroxyvitamin D
Calcitroic acid

17. VDR
+1
Gene
Transcription
RNA Polymerase II
CYTOPLASM
NUCLEUS
VITAMIN D (V) RECEPTOR (VDR)
ACTIVATION OF A VDR RESPONSIVE GENE
Hormone Regulated GeneVDRE
V
VDR
RXR
RXRVDR
V
V
V

18. Roles of 1,25-Dihydroxyvitamin D
Stimulates GI calcium and phosphate
absorption
Promotes renal calcium and
phosphate re-absorption
Calcium homeostasis: together with
PTH it mobilises calcium from
skeletal stores
Mineralisation Mineralisation of the growth plate & of the growth plate &
osteoidosteoid

19. Why do people become vitamin D deficient?
Lack of UVB sunlight exposure
(Residence in Northern or
Southern Latitudes)
Sunscreen with SPF 15+ blocks
99% vitamin D synthesis
Atmospheric Pollution
Pigmented skin
Low dietary Calcium
Impaired absorption
Impaired hydroxylation

20. Prevalence & potential significance of vitamin D
deficiency in Asian Indians
Department of Endocrinology & Metabolism,
All India Institute of Medical Sciences
New Delhi, India
VDD has been reported in all age
groups
 review is made various other
disorders

22. Low Calcium & Vitamin D StatusLow Calcium & Vitamin D Status
Vitamin DDietary Ca
 Low Ca intake leads to secondary hyperparathyroidism &
raised serum
1,25(OH)2D concentration
 Raised serum 1,25(OH)2D concentration degrades 25OHD
to inactive
24,25-dihydroxyvitamin D, thereby depleting body stores of
vitamin D
Clements et al. Nature 1987;325:62–5

23. Current vitamin D intake
recommendations
Age Current Recommended
Daily Intake
Under 50 200 IU
50-70 400 IU
Over 71 600 IU

24. T h e E n d o c r i n e
S o c i e t y ’ s
Clinical Guidelines

25. Key clinical
recommendation
SEVERE
In patients with severe vitamin D deficiency,
50,000 IU of vitamin D should be given daily
for 8 weeks, followed by weekly doses of
50,000 IU.
After repletion of body stores, 800 IU of
vitamin D daily or 50,000 IU of vitamin D once
or twice monthly is adequate maintenance
therapy

26. Lack of adequate sunlight or chronic sunscreen use
–Ultraviolet lamp or increased sun exposure
–Whole body exposure to a minimal erythemal
dose of sunlight is equal to 10,000 to 75,000 IU of
oral vitamin D
•Fat malabsorption
–25-hydroxyvitamin D, 20 to 30 mcg per day
•Cirrhosis, nephrotic syndrome, renal failure, chronic
corticosteroids, anticonvulsants
–1,25-dihydroxyvitamin D, 0.15 to 0.5 mcg daily

27. Calcium homeostasis
Blood
Ca++
small intestine
kidney
Ca++
Ca++
Ca++
bone
1,25 Vit. D3 (+)
1,25 Vit D3
deposition
Calcitonin (-)
Ca++
PTH
Parathormone (+)
resorption

28. Disorders of calcium
homeostasis
•Hypercalcemia
•Hypocalcemia

29. Etiologies of Hypercalcemia
Increased GI
Absorption
Elevated calcitriol
Excessive dietary intake
Increased Loss
From Bone
Decreased Urinary
Excretion
Thiazide diuretics
Elevated calcitriol
Elevated PTH

Hyperparathyroidism
Malignancy
Metastasis
Pagets disease
hyperthyroidism

30. Clinical Features of Hypercalcemia
Acute Chronic
Gastro-
intestinal
Anorexia, nausea,
vomiting
Dyspepsia, constipation,
pancreatitis
Renal Polyuria, polydipsia Nephrolithiasis,
nephrocalcinosis
Neuro-
muscular
Depression, confusion,
stupor, coma
Proximal muscle weakness,
atrophy of type II muscle
fibers, hyperreflexia, gait
disturbance
Cardiac Bradycardia, first degree
atrio-ventricular block,
↓QTc interval on ECG
Hypertension, digitalis
sensitivity

31. Management of Hypercalcemia
•Depending upon the Symptoms and signs of acute
hypercalcemia and serum calcium > 12 mg/dL -
series of urgent measures are instituted which
include
• Hydration
–Loop diuretics
–Bisphosphonates
–Calcitonin
–Glucocorticoids
–Calcimimetics ( CINACALCET) – BLOCK PTH
–Gallium

32. Bisphosphonates
•Pyrophosphate analogs
MOA
•Concentrate at the site of active remodeling
•Incorporate into bone matrix
•Induce apoptosis in the osteoclast

33. Examples
•Medronate
•Clodronate
•Etidronate
•Tiludronate
•Pamidronate
•Alendronate
•Ibandronate
•Risedronate
•zoledronate

34. Etiologies of
Hypocalcemia
Decreased GI Absorption Decreased Bone Resorption/
Increased Mineralization
Hypoparathyroidism
Pseudohypoparathyroid
ism
Vitamin D deficiency /
low calcitriol
Osteoblastic
metastases
• Poor dietary intake of
calcium
• Impaired absorption of
calcium
•Vitamin D deficiency
•Malabsorption syndromes
•Liver failue
•Renal failure
•Low PTH

35. Clinical Presentation of
Hypocalcemia
–Tetany
–Paresthesias
,
–Muscle
cramps
–Seizures
–Fatigue,Anxi
ety
–Polymyositis
–Laryngeal
bronchial
spasms

36. Treatment of Hypocalcemia
–Calcium gluconate –
contains 90 mg of elemental calcium per 10 mL
ampule
–1 to 2 ampules diluted in 50 to 100 mL of 5%
dextrose is infused over 10 minutes.
–oral calcium initiated

37. Hormonal Regulators
•Calcitonin (CT)
–Lowers Ca++ in the blood
–Inhibits osteoclasts
•Parathormone (PTH)
–Increases Ca++ in the blood
–Stimulates osteoclasts
•1,25 Vitamin D3
–Increases Ca++ in the blood
–Increase Ca++ uptake from the gut
–Stimulates osteoclasts

38. Thank you