Calcium homeostasis is regulated by calcitonin, parathyroid hormone, and vitamin D. Calcium is primarily stored in bones and is present in small amounts in extracellular fluid. The majority of calcium in blood is ionized and plays important roles in cell excitability, muscle contraction, and hormone secretion. Dietary calcium absorption occurs mainly in the duodenum and is regulated by hormones and vitamin D. Hypocalcemia and hypercalcemia can result from disorders of the parathyroid gland, kidneys, bone, or vitamin D metabolism and cause neuromuscular and cardiac symptoms. Treatment involves addressing the underlying cause and correcting calcium levels.
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 m
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
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
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
MineralisationMineralisation 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
21.
22. Low Calcium & Vitamin D StatusLow Calcium & Vitamin D Status
Vitamin D Dietary 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
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
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
CALCITONIN (CT)
-Secreted from the C-cells in the thyroid gland
-Lowers Ca++ in blood
-Promotes deposition of Ca++ into bone
-actually inhibits bone resorption in osteoclasts (ask them what osteoclasts do)
-control of secretion:
-increased plasma Ca++ stimulates C-cells to synthesize and release CT
-Ca++ receptor on the cell membrane (draw on board!!)
-when Ca++ binds the extracellular domain, activates Gs protein—Adenylate Cyc--increasing Camp
-CT action needed
-after meals, to prevent post-prandial hypercalcemia
-gastrin (secreted in response to food in the stomach) also stimulates CT secretion
-CT also important during pregnancy and lactation, to protect mother from Ca++ demands of fetus
PARATHORMONE (PTH)
-secreted from cells of the parathyroid glands (chief cells)
-increases Ca++ in the blood
-remove the gland, plama Ca++ levels plummet, tetanic convulsions and death result
-increases Ca++ resorption from the bone (how could it do that?)
-stimulates the osteoclasts
-increases the number of osteoclasts
-increases Ca++ resorption from the pre-urine filtrate in the nephron (draw this!)
-Control of secretion:
-low extracellular Ca++ causes PTH release
-Similar Ca++ receptor as found with CT (how does this work?)
-except, when bound by Ca++, activates Gi protein, inhibiting cAMP levels, which decreases PTH secretion
-PTH action needed for fine control of plasma Ca++ levels
Calcitriol is 1,25(OH)2 Vit D
1,25 Vitamin D3
-made in the liver, the skin, the liver, and the kidney
Liver: cholesterol precursor transformed to 7-dehydrocholesterol
Skin: UV transforms 7-dehydrocholesterol to Vit D3
Liver: Enzyme transforms Vit D3 to 25-OH-Vit D3
Kidney: Enzyme transforms 25-Vit D3 to 1,25 Vit D3
-lack of melanin pigment in Northen Europeans was thought to account for the lower light level: let more UV across the skin to ensure high enough levels of Vit. D3
-increases Ca++ uptake from the gut
-made from cholesterol…….acts like a steroid…..what kind of receptors? How would they act? (they increase transcription and translation of Ca++ transport proteins in the epithelial cells of the gut)
-minor roll: also acts to stimulate osteoclasts, (which would do what?) increasing Ca++ resorption from the bone
-control of secretion:
-low Ca++ levels causes increase of PTH, which increases enzymes in the kidney (more enzyme, more 1,25 Vit. D3)
Covering but also lack of sun UVB in UK anyway! (esp winter to spring)
Define osteoblasts (builders) and osteoclasts (resorbers) again
Calcitonin
Parathormone
Vit D3
Other hormonal regulators of Ca++ homeostasis: Estrogens
-stimulate osteoblast activity , limits osteoclast activity, and enhance PTH secretion
-although there is a lot of disagreement on what estrogens do exactly in bone
-estrogens changes the set point of PTH cells in the parathyroid so a greater reduction of Ca++ is needed to increase PTH secretion (so E2 decreases Ca++ loss from bones)
Clinical aspects:
-(there are not many clinical problems with Ca++, because it rapidly leads to death)
-Osteoporosis: decalcification and loss of bone matrix from the skeleton
-maximum bone mass is achieved in women at age 35
-in the 30 years after menopause, women lose 30-50% of their bone mass
-more common in women than men, may be because women have smaller bone calcium reserves
-treatment:
-estrogen replacement
-increased Ca++ in the diet (slow down Ca++ turnover from bone)
-exercise (especially weight bearing activities)
stimulates bone deposition
raquet arm of tennis players is 35% more dense than other arm