The mucosal block theory proposes that iron absorption is regulated at the level of intestinal mucosal cells. It occurs in four steps: 1) soluble iron salts in the intestine are absorbed, 2) gastroferrin transports iron to the duodenum, 3) iron enters mucosal cells as Fe2+, and 4) most absorbed iron is exported into plasma by transport proteins, while some is stored in the cells. Regulation of iron absorption occurs when the mucosal cells detect sufficient iron has been absorbed and block further uptake, preventing excess iron absorption.
2. Introduction
• Normally , the loss of iron from the body of a men is
limited to 1 mg/day.
• Menstruating woman lose iron with menstrual blood .
• Around 10-20 mg of fe is taken in the diet and only
about 10% is absorbed .
• The greatest need of iron is during infancy and
adolescence .
• The only mechanism by which total body stores of iron
is regulated is at the level of absorption .
• Garnick proposed a mucosal block theory for iron
absorption .
3. Mucosal block theory :-
• Step 1 :-
• Soluble inorganic salts of iron are easily absorbed from
small intestine .
• HCL present in gastric juice liberates free fe3+ from non-
heam proteins.
• Vitamin C and glutathione in diet reduce fe3+ to fe2+ ,
• Which is less polymerizable and more soluble form of
iron .
• Vitamin C and amino acid can form iron –ascorbate and
iron – amino acid chelates which are readily absorbed .
• Heam is absorbed as such.
4. Step 2:-
• Gastroferrin , a glycoprotein in gastric juice is
believed to bind iron and facilitates its uptake in
duodenum and jejunum .
Step 3:-
• The absorption of iron from intestinal lumen into
mucosal cells takes place as fe2+.
5. Step 4 :-
• Events in intestinal mucosal cells (
enterocyte /mucosal cell).
• Enterocyte in the proximal duodenum are
responsible for absorption of iron .
• Incoming iron in the fe3+ state is reduced to
fe2+ by an enzyme “ferrireductase” present
on the surface of enterocytes , it is helped
by “vitamin C” present in the foods .
6. • This protein is not specific for iron as it can
transport a wide rang of divalent cations.
• Once it is inside , it can either be stored as “feritin”
or it can be transferred across the basolateral
membrane into the plasma where it is called
bound to “transferrin” .
• Passage of fe2+ across the basolateral membrane
is carried out by another protein called iron
regulatory protein 1 (IREG1) .
• The transfer of iron (fe2+) from the apical surfaces
of enterocytes into their interiors is performed by a
proton –coupled divalent metal transporter (DMT1)
7. •Most of fe2+ required to be absorbed is transferred
to plasma by a fe2+ transporter ( FP) .
# Fe2+ in the enterocytes also came from “heam” by
the action of “heam oxidase” enzyme on heam .
# IREG1 may interact with the copper containing
protein called “hephaestin” ,a protein similar to
caeruloplasmin .hephaestin is thought to have a
“ferroxidase” activity which is important in the
release of iron from cell as fe3+, the form in which,
it is transported in the plasma by transferrin.
8.
9.
10. Overall regulation :-
• Iron absorption is complex and not well
understood mechanistically .
•It is exerted at the level of the enterocyte
where further absorption of iron is blocked if
sufficient amount taken up ,for body need , -
so called dietary regulation exerted by
“mucosal block” (Garnick Hypothesis).
11.
12.
13. Iron requirements :-
• Varies according to age ,sex, weight , and
state of health.
• Adult male –(10mg/day.)
• Adult female –(20 mg/day.)
• Pregnant woman –(10 mg/day.)
• Lactating woman –(25-30 mg/day).
• Children -10-15 mg/day.
14. Factors :-
1. Source of iron has marked effect on absorption.
a. Heam iron by animal product ,Hb, myoglobin (absorbs
20-30%)
b. Non heam iron –plant ,heam iron,(absorbs 1-15%).
2. Absorption of non heam iron influenced by:-
• compotion of diet- vit.c, glutathione, meat ,fish
,poultry . Inhibitor –phytates ,tea,oxalate,coffee,
• pH of the intestinal milieu –> “HCL(gastric juice)
librates fe3+from non heam iron-will serve as increase
solubility of dietary non heam iron” ,high alk. pH-
causes precipitation .
• State of health .healthy adult absorbs fe -5-10%( 1-2
mg) , iron deficient –adult absorbs 10-20% ( 3-6 mg ) .
15. # Diminished absorption of gut due
to :-
• Achlorhydria ,
• Achyla gastrica,
• Resection of gut,
• Several Gastrectomitomies,
• IDA,
• Desquamation –less ferritin.
• Parasitic/bacterial/fungal infection,
• Malignancies ,
• RA (rheumatoid arthritis) ,
• PUD (PEPTIC ULCER DISEASES) ,