Physiology - GI - DIGESTION AND ABSORPTION - Calcium

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  1. ______ is the only source of calcium. It is absorbed in the _____ primarily through _______ pathways and by ________.
    • The diet
    • intestine
    • paracellular
    • specialized transporters
  2. Describe the pathways that mediate Ca2+ transport from intestinal lumen into the interstitial space in various intestinal segments. Identify the most important pathway for each.
    • transcellular pathway:
    • mot important.
    • Ca gets in cell via CaT-1 chan
    • Ca comined with calbindin, carried around
    • via CaHATPase (primary) and Ca/Na exchanger, gets into interstitial


    • Paracellular
    • primary way
  3. Discuss the role of calbindin D, Ca2+- ATPase and Na/Ca exchange in transcellular transport. Identify all stages that are Vitamin D-dependent.
    • calbindin:
    • intracellular carrier
    • buffer intracellular [Ca]

    • CaATPase:
    • major transporter on basolateral membrane

    • Na/Ca exchanger:
    • lower affinity; important when CaATPase saturated or [Ca] too high

    • VD dependent: CaT-1, calbindin, CaATPase, tight junction permeability
    • VD independent: Ca-Na exchanger
  4. Discuss factors that affect Ca2+ bioavailability. Describe age-related diseases and symptoms of Ca2+ deficiencies
    • decrease absorption
    • oxalate: cheator
    • fiber: binds
    • caffine/phosphate:
    • fat: insoluable soap

    • increase absorption:
    • gastric acid
    • citric acid
    • ascorbic acid

    • young: teeth, soft bone, ricket
    • adult: soft bone; maternity osteoporosis
    • old: osteoporosis
  5. Dietary source of calcium _____.
    dairy products and green leafy vegetables
  6. decreasing absorption - important in low Ca diets (less than 800 mg/da)
    • - oxalate - cheater present in some nutrients
    • - dietary components
    •     - fiber - binds
    •     - fats - form insoluble soaps
    •     - phosphates (chocolate, sodas)
  7. increasing absorption
    • - gastric acidity
    • - ascorbic acid - vitamin C
    • - citric acid - (orange juice)
  8. intestinal luminal concentration
    - range
    - average
    • - 1-50 mM range
    • - 5 mM average
  9. Two absorption pathways
    • - transcellular – saturable
    • - paracellular – non saturable; primary
  10. Transcellular Pathway
    • - primary - duodenum
    • - secondary upper jejunum
    • - vitamin D regulated - steroid hormone
  11. 3 Step Transport Process
    • 1) Apical Membrane Absorption
    • - down electrochemical gradient - via Ca specific channel
    • - CaT-1 - Calcium Transporter -1
    • - 97% homology rat and human
    •     - voltage independent
    •     - predominates at low Ca2+ (< 5mM)
    •     - low transport maximum
    • 2) Cytosolic Transport
    • - calbindin D 9k (2 Ca) and D 28k (4 Ca) - apical membrane – high affinity
    • - divalent cations Pb, Ba, ... toxic - compete
    • - functions
    •     - cytosolic Ca2+ buffer - maintains low Ca - protective
    •         - uM Ca cytotoxic
    •     - cytosolic carrier - 2-4 Ca ions - increases transport
    •         - vitamin D increases carrier concentration
    • - vesicles- minor pathway
    • 3) Basolateral Membrane Transport pathways
    • a) CaATPase - high affinity – most important
    • - powerful pump – creates gradient 10,000 fold
    •     - 0.1 uM cytosol - 2-5 mM plasma
    • - H+ coupled (counter)
    • - vitamin D stimulated
    • - 50% calmodulin stimulated
    • b) Na-Ca Countertransport - low affinity
    • - important when Ca ATPase saturated or cytosolic Ca2+ increases to uM levels
    • c) vesicle - minor
  12. Importance of Vitamin D in Transcellular Transport – all stages
    • - regulates cytosolic mRNA controlling transporter expression
    • 1 CaT-1 – expression vitamin D dependent
    • - low Ca2+ - upregulates vitamin synthesis > increased CAT-1 expression
    • - increases ion absorption
    • - excess Ca2+ down regulates
    • 2 Calbindin Synthesis
    • - totally vitamin D dependent
    • - required for normal transcellular transport
    • - absence Vitamin C slows absorption > slower cytosolic diffusion
    • - increase Ca down regulates Vitamin D
    • 3. Basolateral Transport
    • - CaATPase
    • - Vitamin D increases rate and amount transported and number of transporters
    • - Na-Ca exchanger – not Vitamin D dependent
  13. Importance Vitamin D to Paracellular Ca Transport
    • – primary mechanism – throughout small intestine
    • - 3 Regulating Factors
    • 1) Luminal Ca concentration - most active when luminal Ca > 5mM – 99 % Ca paracellular
    • 2) Tight junction permeability
    • - hydrostatic forces - termed - solvent drag
    • - Ca absorption increases with faster water absorption
    • 3) - Vitamin D – important - promotes paracellular transport
    • - makes tight junctions more permeable
  14. Segment Length and Transit Time
    • - net absorption in all segments
    • - comparative absorption for a 50 mg load
    • Duodenum (2%) 2-3 mins
    • Jejunum (25%) 45 mins
    • Ileum (73%) 120 mins
    • TOTAL 168 –187 mins
    • Colon (<10%) 142 mins
    • - Absorption - depends on segment length and exposure time
    • - Major sites - jejunum and ileum
    • - colon least amount, longest time
  15. Calcium Deficiencies
    • - inadequate Ca2+ intake or supplements – seldom factors
    • 3 primary causes
    • 1) inadequate Vitamin D - most common cause
    • - insufficient sun exposure - latitude dependent - food supplements
    • 2) insufficient gastric acid - less Ca solubilization
    • - due to drugs, gastric surgery
    • 3) reduced absorptive surface (Celiac or Crohn's Disease)

    • Supplement Suggestions - highly variable - vary from 500 - 1500 mg/da
    • - spread large doses over day
    • - over 400 mg/day not optimally absorbed at single dose
    • - above 500 mg - increased rigidity of vascular epithelium
    • - avoid single mega doses - blood pressure spikes and potential heart attach
  16. Clinical Manifestations
    – life stage dependent
    - early years
    - adult
    - elderly
    • – teeth
    • - soft bones – rickets

    • - osteomalacia – soft bones
    • - pregnancy - fetal demands may cause maternal osteoporosis

    • - Ca absorption declines about 70 years
    • - less solar activation - insufficient synthesis
    • - less responsive to Vitamin D
    • - osteoporosis
  17. osteoporosis
    • - delayed in men relative to women
    • - peri and post menopausal females - reduced estrogen production
    •     - reduced expression CaT-1
    •     - lower levels calbindin
    •     - fewer intracellular Vitamin D receptors
    • - treatment
    •     - high Ca alone - not prevent ostoporosis
    •     - hormone replacement therapy (HRT) controversial
    •         - bisphosphonates - side effect - necrosis of jaw
  18. Vitamin D Supplements
    • plasma levels
    • - Normal 32 – 100 ng.ml
    • - Insufficient 21 – 29 ng/ml -
    • - Deficient < 20 ng/ml
    • - 32 ng/ml - lower limit for Vitamin D adequacy
    • - high incidence fracture below level

    • spread dose over day
    • - pill range - 200 - 400 IU
    • - 400 mg per dose - best absorbed
    • - high supplement doses > 1000 mg
    •     - controversial effects on arteries
    • - approach - set dosage, measure and monitor plasma levels
  19. Benefits - Vitamin D supplement Protect Against
    • - osteoporosis, cancer (breast, prostate, intestine)
    • - autoimmune arthritis and depression
    • - Type-1 diabetes, obesity, hypertension

Card Set Information

Author:
akhan
ID:
316005
Filename:
Physiology - GI - DIGESTION AND ABSORPTION - Calcium
Updated:
2016-02-17 07:14:20
Tags:
physiology GI
Folders:
physiology
Description:
Physiology - GI - DIGESTION AND ABSORPTION - Calcium - M Stout
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