Download Iron absorption and transport - Wk 1-2

Iron absorption and transport
Wk 12 LO’s
1. Outline the absorption, plasma transport and tissue storage of iron
Absorption
 complex and poorly understood
 primary site for absorption is the duodenum (although some may occur in the stomach,
ileum and colon)
 2 distinct pathways:
1. Haem Iron
- approximately 25% of the haem iron derived from haemoglobin, myoglobin and
other animal proteins is absorbed
- gastric acid releases haem from its apoproteins
- haem is absorbed directly into the mucosal cells
- inside the mucosal cells, haem is enzymatically degraded to release iron
2. Non-haem iron
- only 1-2% absorbed by complex and poorly understood mechanisms
A possible Method of Inorganic (non-haem) Iron Absorption
 in the acid pH of the stomach, luminal mucins bind iron
 keep iron soluble and available for absorption in the more alkaline pH of the duodenum
 iron binds to integrin-like molecule at the surface of duodenal cells that somehow facilitates
its passage across the cell membrane (possibly by an iron transporter)
 a cytosolic protein called mobilferrin accepts iron within the cell and delivers it to ferritin or
transferrin
Plasma Transport
 iron is transported in the plasma by iron-binding glycoprotein called transferrin
 transferrin is synthesised in the liver
 in the normal individual transferrin is about 33% saturated with iron
 plasma tranferrin delivers iron to cells, including erythroid precursors for Hb synthesis
 immature RBCs have high affinity receptors for transferrin
Storage
 Total quantity of iron in the body averages 4-5g, 65% of which is in the form of
haemoglobin, 4% myoglobin
 iron is stored in the form of ferritin (15-30%) or haemosiderin
ferritin
 is a protein-iron complex that is found in all tissues but especially in the liver, spleen, bone
marrow and skeletal muscles
 Liver – most ferritin stored in the parenchymal cells (from plasma transferrin)
 Spleen and bone marrow – mostly in mononuclear phagocytic cells (from breakdown of
RBCs)
haemosiderin
 in lysosomes - protein shells of ferritin are degraded and iron is aggregated into
haemosiderin granules
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after absorption, haem and non-haem iron enter a common pool in the mucosal cell
a fraction is transferred to plasma transferrin and most is deposited to ferritin, to be
transferred more slowly to transferrin, or to be lost in sloughing off of mucosal cells
the extent to which iron follows these different pathways is dependent on the body’s iron
requirements
2. Explain why iron deficiency is common by reference to the rate limiting steps for
iron absorption
An iron deficiency may result from:
a) dietary insufficiency
b) impaired absorption
c) increased requirement
d) chronic blood loss
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the bioavailability of iron is as important as the overall content with haem iron (from red
meat) being much easier to absorb than inorganic iron
inorganic iron absorption is also influenced by other dietary contents – ascorbic acid
(vitamin C), citric acid, amino acids and sugars in the diet enhance uptake while tannates
(in tea), carbonates, oxalates and phosphates inhibit its absorption
the complex nature of iron absorption means that we need to ingest 10-20mg daily, yet
only absorb around 1mg of that
Factors that influence uptake of iron from the diet:
– Dietary iron content
– Gastric acidity
 proteases free the iron (Fe3+ attached to proteins)
 HCl solubilises the iron (Fe3+→Fe2+)
– Reducing substances
 Dietary Vit C ↑ the ferrous (Fe2+) fraction and so ↑ uptake
– Alcohol increases uptake
– Pancreatic bicarbonate
 aids formation of ferric hydroxide which is poorly absorbed
3. Outline the means of gain and loss of iron from the body
Gain
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Loss
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about 5-10mg (men) and 7-20mg (women) daily dietary intake (only10-15% absorbed)
 the amount of iron absorbed depends on and is regulated by, the body’s need for
iron
about 20mg of iron is recycled daily:
 RBCs engulfed by macrophages of the reticulo-endothelial system at the end of
their lifespan
 some of the iron released is incorporated into new haemoglobin molecules and
some enters the blood stream and is transported by transferrin to iron stores
(ferritin and haemosiderin)
there is no physiological mechanism for iron excretion
when body reserves of iron are adequate, very little is released into the portal blood and
iron stored as ferritin is lost from the body as the mucosal cells of the digestive tract slough
off
1-2 mg iron is lost by an adult male individual as follows:
– Skin: cell loss: 0.3 mg
– Gut: cell loss (gut mucosa) 0.7 mg
blood loss (2-3 ml) 1.0–1.5 mg
– Urine: cell loss: 0.1 mg
In females, an additional 20-30 mg iron is lost each month due to menstruation
Pregnancy and lactation also increase the iron losses.
4. Briefly describe the clinical features of iron overload
Haemochromatosis is a condition in which the amount of total body iron is increased. Excess iron
is deposited in and causes damage to several organs, including the liver.
Clinical features of haemochromatosis:
– Liver damage (cirrhosis), 10-20% develop hepatic cancer
– Pancreatic dysfunction: diabetes mellitus
– Heart: Cardiac failure
– Adrenal cortex: Addison's Disease
– Leaden-grey skin pigmentation due to excess melanin production especially in exposed
parts, axillae, groin and genetalia
– impotence, lack of libido and testicular atrophy
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These features only manifest themselves after long-term accumulation of iron and are
therefore usually only seen in middle-age.
More common in men than in women as women have some protection against iron
accumulation (possibly due to menstruation)