Physiology - GI - DIGESTION AND ABSORPTION - Iron

  1. The majority of iron in the body is stored as _______. Excess iron is deposited primarily in ________. The body maintains rigid control over iron absorption and loss through mechanisms not well understood.
    • hemoglobin in red blood cells
    • the liver, spleen and bone marrow
  2. Identify the dietary source of heme iron. Describe the mechanisms mediating its transport from lumen to blood. Discuss the function of heme oxygenase (oxidase), iron binding protein (mobilferrin), ferritin, and transferrin.
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  3. Identify the dietary sources of non-heme iron. Discuss the molecular model for its absorption from lumen to blood. List the storage sites.
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  4. Discuss factors that affect iron bioavailability. Describe the mechanism for regulation of iron absorption and the function of iron regulatory protein (IREG). Define hemochromatosis. Discuss the causes symptoms of iron overload.
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  5. Absorption Sites
    • primarily duodenum
    • secondary jejunum
  6. Ingested Forms
    • 1) Non-Heme Iron - vegetables and iron pills
    • - present as insoluble iron salts or as free ion
    • - absorption pH dependent
    • 2) Heme Iron – hemoglobin and myoglobin of red meats
    • - 50% of dietary intake
  7. Non-Heme Iron
    • 1) Fe3+ (ferric form) - most prevalent
    • - poorly soluble and poorly absorbed
    • - insoluble complexes pH > 3 - duodenum
    • - insoluble dietary complexes - phosphate, cereals and tannins in tea
    • - gastric acidity – promotes solubility with mucins

    • 2) Fe2+ (ferrous form) - salt in vitamin pills - readily soluble pH > 8
    • - also formed by reducing Fe+3 to Fe+2 by
    •     - brush border ferric reductases
    •     - vitamin C
    •     - reducing agents in bile
  8. Apical Iron Transport
    • - non heme iron - absorbed primarily - duodenum
    •     - carrier protein - transferrin - secreted into lumen
    •         - binds 2 ion
  9. Nonheme Iron - Apical Transport Receptor
    • 1) Transferrin receptor (Tf) - duodenum and upper jejunum
    • - binds 2 ions Fe+2 - internalized - endocytosis
    • - Fe comes out of the vesicle
    • - Tf and receptor- recycle across apical membrane
    • - Tf - dissociates from receptor
    • - re-enters duodenum - binds more Fe+2

    • 2) DCT-1 (Divalent Cation Transporter-1) – duodenum and upper jejunum
    • - cotransport of Fe+2 with H
    • - lumenal acidity - important
    • - also transports toxic divalent ions (Cd+2, Pb+2)
  10. Basolateral Transport - when body needs Fe
    - 2 pathways

    • - mobilferrin - transports Fe to basolateral membrane - 2-3 hours
    •     - IREG-1 (Iron Responsible Group) - basolateral transporter
    •     - specialized basolateral membrane receptor
    •     - associated with hephastin = oxidase required for extrusion

    • - extruded iron - diffuses through interstitial space - enters capillaries
    •     - 2 molecules Fe bind to plasma transferrin (β-globulin -synthesized by liver)
    •          - transported to storage pool in liver and elsewhere
    •          - storage cells also have receptors - bind & internalize complex
  11. Heme Iron Transport – from ______
    hemoglobin and myoglobin

    • - less affected by dietary components
    • - heme-Fe - complex soluble at neutral pH
    • - duodenal lumen - proteolytic enzymes – release heme iron group from protein-globulin complex
    •     - apical transport of complex – unclear
    • - cytosol
    •     - heme oxidase/oxygenase – releases free Fe
    •         - heme degraded
    •         - remaining receptors recycled or degraded
    •     - mobilferrin binds Fe
    •         - enters pathway previously described for nonheme iron
  12. Regulation of Iron Absorption
    • - Storage pool – about 4 grams
    • - 60-70% stored in in red cell Hgb - remainder stored - liver, spleen, bone marrow
    • - Loss - 1 mg/day
    •     - sloughing of cells
    •     - gastrointestinal secretions, sweat
  13. Rigid regulation of iron according to body needs
    - sensors unknown

    • - Mucosal Block Theory - programmed to restore lost iron
    •     - cells - receptors for transferrin-iron complex

    • - high blood levels or need for Fe decreases
    •     - Iron Regulatory Protein (IRP) in cytosol binds Fe
    •         - down regulates expression of Fe transporters
    •        - absorption decreases
    •        - apoferritin synthesis increases - increases iron storage (ferritin pool)

    • - increased iron need (Fe deprivation or hemorrhage)
    •     - crypt cells express more brush border receptors
    •     - cytosolic IRP (Iron Regulatory Protein)
    •        - upregulates transporter expression - DCT-1 and IREG-1
    •           - transporters and absorption increase
    • - site of sensors unknown
  14. Iron Deficiency Anemia
    • – most prevalent nutritional deficiency
    • - 30% population anemic
    • - prevalent in females
    •     - affects 50% under age 50
    • - symptoms – fatigue, cold extrematies, shortness of breath
    •     - common to others disorders - misdiagnosis
  15. bioavailability - major determinant
    • - Fe may exist in nonabsorbable form
    •     - complexed with oxalate (spinach)

    • - may form insoluble complexes with diet
    •     - tannins in coffee and tea (antioxidant polyphenols
    •     - dairy products
    •     - brans and fiber (phytic acid)
    •     - food preservatives (EDTA) – Ca2+ chelator - read label
    •     - form insoluble salt - carbonates, hydroxides, phosphates

    - absorption enhanced by gastric acidity
  16. Hemochromatosis -
    Iron Overload
  17. Primary Hemochromatosis
    • - seldom appears before age 30
    • - congenital defect of Fe regulating system
    •     - system senses Fe defecit
    •     - cells continually signaled to absorb and store excess iron
    •         - stores excess Fe in multi-organ systems
    •         - affected transport site - unknown

    • - symptoms
    •     - cirrhosis of liver
    •     - pancreatic damage – diabetes
    •     - pituitary failure

    - treatment – regular bleeding
  18. Secondary Hemochromatosis
    • - regulating system overwhelmed with Fe
    •     - chronic red cell destruction
    •     - liver disease
    •     - chronic excessive Fe intake (rare)

    - Treatment - address medical cause
Author
akhan
ID
316021
Card Set
Physiology - GI - DIGESTION AND ABSORPTION - Iron
Description
Physiology - GI - DIGESTION AND ABSORPTION - Iron - M Stout
Updated