Role of Calcium in Pregnancy
Calcium Stats
• Atomic number: 20
• Atomic symbol: Ca
• Atomic weight: 40.08
• Electron configuration: [Ar]4s2
• Atomic ra...
The Importance of Calcium
• Aids in building strong bones and
teeth
• Prevention of osteoporosis
• Essential in the clotti...
Skeletal roles of calcium
• Provides structural integrity of skeleton



Calcium is the substrate for bone mineralisatio...
Calcium homeostasis
storage
bone

kidney
calcium deposition

calcium resorption

Blood
Ca++

1000 g Ca++
stored in bone

i...
Calcium cycling in bone tissue
• Bone formation
– Osteoblasts
• Synthesize a collagen matrix that holds
Calcium Phospate i...
Hormonal Regulators
• Calcitonin (CT)
• Parathormone (PTH)
• 1,25 Vitamin D3
Calcitonin (CT)
• Secreted from the C cells in
the thyroid
• Lowers Ca++ in blood
• Promotes deposition of Ca++
into bone ...
Parathormone (PTH)
• Increases Ca++ in blood
• Increases Ca++ resorption from the bone
– Stimulates osteoclasts
– Increase...
Hormonal Regulators
• Calcitonin (CT)
– Lowers Ca++ in the blood
– Inhibits osteoclasts

• Parathormone (PTH)
– Increases ...
Calcium homeostasis
kidney
bone

1,25 Vit. D3 (+)
Parathormone (+)
Calcitonin (-)
resorption

Blood
Ca++

deposition
Ca++
...
Regulation
Activation of vitamin D3
- Cholecalciferol formed
in the skin by sun
- Converted in liver
(feedback effect)
- 1...
Calcium homeostasis
Relationship between calcium intake and calcium absorption /excretion
Calcium dietary intake
700 – 100...
Regulation of serum calcium homeostasis

Clin J Am Soc Nephrol 5: S23–S30, 2010
Contrasting Calcium Homeostasis in
Pregnancy & Lactation

Endocr Rev 18:832–872.
Calcium Demands in Pregnancy
BONE
Ca intake

BLOOD

KIDNEY

Numerous hormones are
involved in calcium homeostasis:
1, 25-d...
Meeting Fetal Calcium Demands
? BONE DENSITY

Ca intake

BLOOD
FETUS
1,25(OH)2D
ESTROGEN
PROLACTIN

Urine Ca
Maternal Changes in Bone During
Pregnancy
Findings in healthy populations:
Maternal Findings

No. of Longitudinal Studies
...
% Calcium Absorption

Calcium Absorption during
Pregnancy

Prepregnant

1st

2nd

Trimester

3rd
Role of Calcium in Pregnancy
• Calcium decreases risk of hypertension, pre-eclampsia,
low birth weight, and chronic hypert...
Role of Calcium Pregnancy: Implications
on Neonates
• Involved in mineralization of bones and teeth, energy and
cell produ...
Calcium Supplementation in Pregnancy
• Association between reduction in pregnancy induced
hypertension (PIH) and calcium s...
Calcium Supplementation in Pregnancy…
• Meta analysis of randomized controlled trials regarding– Mothers: hypertension +/-...
Results
• Mothers:
– Hypertension+/-proteinuria:
• Less hypertension: RR 0.81 (0.74–0.89).
• Less pre-eclampsia: RR 0.70 (...
Calcium Deficiency: Impact on
the Neonate
Specific Causes of Nutritional Calcium
Deficiency in children
• Early weaning( breast milk and formula are excellent sourc...
Clinical Manifestation of Calcium Deficiency
in Children
• Classical sign & symptoms of rickets
• Presentation may occur d...
Calcium RDA Across Various Age-groups
Group
Adult

Calcium RDA (mg/d)
Men

600

Women

600

Pregnancy

1200

Lactation
Pos...
Which Calcium Supplement?
•
•
•
•
•
•
•
•
•

Calcium phosphate (25% Ca)
Calcium carbonate (40% Ca)
Calcium lactate (13% Ca...
AAA Cal
Active absorbable algal calcium:
• Treated seaweed Cystophyllum fusiforme added HAI
(heated algal ingredient).
• C...
Benefits of AAA cal Women Health
•

Meets extra demands of Calcium especially in Pregnancy &
Lactation

•

Absorption is i...
Summary
•

Calcium is an important mineral with numerous health benefits with a
major role in bone development

•

Calcium...
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Role of calcium in pregnancy

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  • Think of it this way:
    Calcium is ingested through the gut (get more Ca++ into system)
    Calcium is secreted out of the body through the urine and the feces
    Calcium is stored in the bones
    To understand how calcium regulation occurs at the bone, we need to understand how bones work…
  • Two processes: bone formation and bone resorption, going on continuously
    Calcium phospate crystals called ‘hydroxyapatite’
    surface of crystals can exchange Ca++ and phosphate ions with extracellular fluid
    Write on board:
    -osteoblasts: builds bone (takes up Ca++ into bone)
    -osteoclasts: breaks down bone (removes Ca++ from bone)
    Now that we understand how calcium cycling happens at the bone, we can go back to the overall picture
  • 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
  • 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
  • Regulation of serum calcium homeostasis. Serum calcium homeostasis is regulated by a rapid negative feedback hormonal pathway involving the concentration of ionized calcium in serum (Ca, green arrows) and the secretion of parathyroid hormone (PTH, blue arrows) from the parathyroid.
    A fall in serum calcium (2 Ca) inactivates the calcium receptor in the parathyroid cell (CaR; green circle) and increases PTH secretion
    (1 PTH), which restores serum calcium (1 Ca) by activating the parathyroid receptor (PTHR; blue circles) in bone, to increase
    calcium resorption, and in kidney, to increase tubular calcium reabsorption.
    In kidney, the increased PTH secretion augments its calcium-restorative effect by increasing secretion of 1,25-dihydroxyvitamin D (1,25D; red arrows), which, acting on the vitamin D receptor (VDR, red circles) in gut, increases active calcium absorption and increases calcium resorption in
    bone.
  • Figure 1 Schematic illustration contrasting calcium homeostasis in human pregnancy and lactation compared with normal. The thickness of arrows indicates a relative increase or decrease with respect to the normal and nonpregnant state. Although not shown, the serum (total) calcium is decreased during pregnancy, whereas the ionized calcium remains normal during both pregnancy and lactation. (Adapted with permission from The Endocrine Society © 1997: Kovacs CS, Kronenberg HM 1997 Maternal-fetal calcium and bone metabolism during pregnancy, puerperium and lactation. Endocr Rev 18:832–872.(24))
  • Foods abundant in calcium include: dairy products, dark green vegetables, nuts, grains and beans.
  • Transcript of "Role of calcium in pregnancy"

    1. 1. Role of Calcium in Pregnancy
    2. 2. Calcium Stats • Atomic number: 20 • Atomic symbol: Ca • Atomic weight: 40.08 • Electron configuration: [Ar]4s2 • Atomic radius: 197.3 pm • Melting point: 842 0C • Boiling point: 1484 0C • Oxidation state: 2
    3. 3. The Importance of Calcium • Aids in building strong bones and teeth • Prevention of osteoporosis • Essential in the clotting of blood • Aids nerves in sending messages • Aids in the contraction of muscles
    4. 4. Skeletal roles of calcium • Provides structural integrity of skeleton   Calcium is the substrate for bone mineralisation Skeletal mass cannot be built or maintained if calcium intake is insufficient or calcium losses are excessive • Bone is the reservoir for calcium and replenishes extracellular fluid (ECF) losses • Calcium plays a role in muscular, neural and most metabolic processes Med J Aust 2005; 182: 281-285 Calcif Tissue Int 2002; 70: 70-73. 2. Medicine Today 2005; 6: 43-50.
    5. 5. Calcium homeostasis storage bone kidney calcium deposition calcium resorption Blood Ca++ 1000 g Ca++ stored in bone intake Ca++ absorbed into blood excretion Ca++ lost in urine Calcium in the diet calcium lost in feces small intestine
    6. 6. Calcium cycling in bone tissue • Bone formation – Osteoblasts • Synthesize a collagen matrix that holds Calcium Phospate in crystallized form • Once surrounded by bone, become osteocyte • Bone resorption – Osteoclasts • Change local pH, causing Ca++ and phosphate to dissolve from crystals into extracellular fluids
    7. 7. Hormonal Regulators • Calcitonin (CT) • Parathormone (PTH) • 1,25 Vitamin D3
    8. 8. Calcitonin (CT) • Secreted from the C cells in the thyroid • Lowers Ca++ in blood • Promotes deposition of Ca++ into bone (inhibits osteoclasts) • Control of secretion from ccells: CT
    9. 9. Parathormone (PTH) • Increases Ca++ in blood • Increases Ca++ resorption from the bone – Stimulates osteoclasts – Increases number of osteoclasts • Increases Ca++ resorption from nephron • Necessary for fine control of Ca++ plasma levels
    10. 10. 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
    11. 11. Calcium homeostasis kidney bone 1,25 Vit. D3 (+) Parathormone (+) Calcitonin (-) resorption Blood Ca++ deposition Ca++ 1,25 Vit D3 PTH Ca++ Ca++ Ca++ small intestine
    12. 12. Regulation Activation of vitamin D3 - Cholecalciferol formed in the skin by sun - Converted in liver (feedback effect) - 1,25 DHCC formation in kidney - Controlled by PTH - Plasma calcium concentration inversely regulates 1,25 DHCC
    13. 13. Calcium homeostasis Relationship between calcium intake and calcium absorption /excretion Calcium dietary intake 700 – 1000 mg/d PTH - 20-35% PTH, 1,25(0H)2D 500 mg/d Plasma & ECF Calcium 9.0 – 10.5 mg/100ml GH, PO4, Sex hormones, Calcitonin PTH, 1,25(0H)2D 500 mg/d 50-250 mg/d Calcium balance (equilibrium) for post-menopausal women reached at intake of ~1000 mg/ day PTH 450 – 900 mg/d 100 – 300 mg/d FAO/WHO expert consultation on human vitamin and mineral requirements, Update March 2002; HP Kruse, Grundzüge der Osteologie, Springer Verlag 1984
    14. 14. Regulation of serum calcium homeostasis Clin J Am Soc Nephrol 5: S23–S30, 2010
    15. 15. Contrasting Calcium Homeostasis in Pregnancy & Lactation Endocr Rev 18:832–872.
    16. 16. Calcium Demands in Pregnancy BONE Ca intake BLOOD KIDNEY Numerous hormones are involved in calcium homeostasis: 1, 25-dihydroxyvitamin D (1,25-(OH)2D) Parathyroid hormone (PTH)
    17. 17. Meeting Fetal Calcium Demands ? BONE DENSITY Ca intake BLOOD FETUS 1,25(OH)2D ESTROGEN PROLACTIN Urine Ca
    18. 18. Maternal Changes in Bone During Pregnancy Findings in healthy populations: Maternal Findings No. of Longitudinal Studies Decrease in bone density 6 studies 2-4 % loss Increase in bone density 1 study No change in bone density 4 studies Difficulties with previous studies: • Final bone measurements are made up to 6 mo postpartum – a time when lactation induced bone changes have already occurred. • Small sample sizes • Few studies have measurements throughout pregnancy due to radiation exposure to DXA.
    19. 19. % Calcium Absorption Calcium Absorption during Pregnancy Prepregnant 1st 2nd Trimester 3rd
    20. 20. Role of Calcium in Pregnancy • Calcium decreases risk of hypertension, pre-eclampsia, low birth weight, and chronic hypertension in children • Recommended for high risk women with low calcium intake, if pre-eclampsia is important in the population • Calcium has other health benefits not related to pregnancy: – – – – – Maintaining bone strength Proper muscle contraction Blood clotting Cell membrane function Healthy teeth
    21. 21. Role of Calcium Pregnancy: Implications on Neonates • Involved in mineralization of bones and teeth, energy and cell production and electrolyte acid-base buffering. • Fetal bone and teeth calcification primarily occurs in last 2-3 months. • If calcium levels are too low, demineraliztion of mothers bones and teeth may occur. • 4 c milk daily or equivalent to supply 1200 mg calcium daily
    22. 22. Calcium Supplementation in Pregnancy • Association between reduction in pregnancy induced hypertension (PIH) and calcium supplementation. – Reduction of incidence of PIH. – Routine supplementation likely to be beneficial in women at high risk of developing PIH or have low dietary calcium intake – High calcium doses (2 g/day) not associated with adverse events. – Need adequately sized and designed trials in different settings to confirm beneficial effects. • Ca is recommended through diet in women at risk of hypertension or low calcium areas. Bucher et al 1996; Kulier et al 1998; Lopez-Jaramillo et al 1997.
    23. 23. Calcium Supplementation in Pregnancy… • Meta analysis of randomized controlled trials regarding– Mothers: hypertension +/- proteinuria, maternal death or serious morbidity, abruptio placetae, caesarean section, length of stay – Newborns: Preterm delivery, low birth weight/small for gestational age, neonatal intensive care unit admission, length of stay, still birth/death, disability, hypertension Atallah, Hofmeyr and Duley 2000.
    24. 24. Results • Mothers: – Hypertension+/-proteinuria: • Less hypertension: RR 0.81 (0.74–0.89). • Less pre-eclampsia: RR 0.70 (0.58–0.83). • Better if low calcium intake, high risk. • Newborns: – Low birth weight: RR 0.83 (0.71–0.98), best for women at highest risk. – Chronic hypertension: RR 0.59 (0.39–0.91). – No difference in preterm delivery, neonatal intensive care unit admission, stillbirth, death. Atallah, Hofmeyr and Duley 2000.
    25. 25. Calcium Deficiency: Impact on the Neonate
    26. 26. Specific Causes of Nutritional Calcium Deficiency in children • Early weaning( breast milk and formula are excellent source of calcium) • Diet with low calcium content( <200 mg/day) • Diet with high phytate, oxalate, phosphate( due to reliance on green leafy vegetables decreased absorption of dietary calcium) • Children with unconventional diet (children with milk allergy) • Transition from formula or breast milk to juice, soda, calcium poor soy milk without alternative source of dietary calcium • IV nutrition without adequate calcium • Calcium malabsorption- celiac disease, intestinal abetalipoproteinemia, small bowel resection
    27. 27. Clinical Manifestation of Calcium Deficiency in Children • Classical sign & symptoms of rickets • Presentation may occur during infancy/childhood although some cases are diagnosed at teen age • Occur later than nutritional vitamin D deficiency
    28. 28. Calcium RDA Across Various Age-groups Group Adult Calcium RDA (mg/d) Men 600 Women 600 Pregnancy 1200 Lactation Post menopausal women 800 Infants 500 Children 1 – 3 yrs 600 4 – 6 yrs 600 7 – 9 yrs 600 10 – 12 yrs 800 Boys 800 Girls 800 Boys 800 Girls 16 -18 yrs 800 Girls 13 -15 yrs Boys 800 * Nutrient Requirements & RDA in Indians. ICMR Report; National Institute & Nutrition, Hyderabad
    29. 29. Which Calcium Supplement? • • • • • • • • • Calcium phosphate (25% Ca) Calcium carbonate (40% Ca) Calcium lactate (13% Ca) Calcium chloride (27% Ca) Calcium gluconate (9% Ca) Calcium bionate (6.5% Ca) Calcium citrate Calcium citrate malate Active absorbable algal calcium (AAACa)
    30. 30. AAA Cal Active absorbable algal calcium: • Treated seaweed Cystophyllum fusiforme added HAI (heated algal ingredient). • Contains aminoacids which improve absorption at intestinal villi and provide a neutral coat for +ve ionic Ca. • Major feature: Vitamin D usually is not required for the absorption of AAA cal
    31. 31. Benefits of AAA cal Women Health • Meets extra demands of Calcium especially in Pregnancy & Lactation • Absorption is independent of gastric acid content and plasma vitamin D levels unlike CaCO3 • Offers 57% better absorption than CaCO3. • Useful for Ca supplementation in elderly patients with Ca deficiency & secondary Hyperparathyroidism due to its high absorbability from the intestine.
    32. 32. Summary • Calcium is an important mineral with numerous health benefits with a major role in bone development • Calcium deficiency has numerous implications in women from the fetal phase to the elderly post-menopausal age • The major reason for calcium deficiency in pregnant women in poor nutrition which can have detrimental effects on the bone health. • Calcium supplementation is thus imperative to ensure optimal bone as well as extra-skeletal health in a woman throughout her life especially during pregnancy & lactation.
    33. 33. Thank You

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