Page 51 - Essential Haematology

Chapter 3 Hypochromic anaemias / 37

When plasma iron is raised and transferrin is inflammation interleukin 6 (IL - 6) and other
saturated the amount of iron transferred to paren- cytokines increase hepcidin synthesis (Fig. 3.4 ).
chymal cells (e.g. those of the liver, endocrine
organs, pancreas and heart) is increased and this is
Dietary i ron
the basis of the pathological changes associated with

iron loading conditions. There may also be free iron Iron is present in food as ferric hydroxides, ferric –
in plasma which is toxic to diff erent organs. protein and haem – protein complexes. Both the iron
content and the proportion of iron absorbed diff er
from food to food; in general, meat – in particular
Hepcidin
liver – is a better source than vegetables, eggs or

Hepcidin is a 25 - amino acid polypeptide produced dairy foods. The average Western diet contains
by liver cells. It is the major hormonal regulator 10 – 15 mg iron daily from which only 5 – 10% is

of iron homeostasis (Fig. 3.4 ). It inhibits iron normally absorbed. The proportion can be increased

release from macrophages and intestinal epithelial to 20 – 30% in iron deficiency or pregnancy (Table
cells by its interaction with the transmembrane iron 3.2 ) but even in these situations most dietary iron
exporter ferroportin, accelerating degradation of remains unabsorbed.
ferroportin mRNA. Raised hepcidin levels therefore
reduce iron absorption and iron release from
Iron a bsorption
macrophages.
Organic dietary iron is partly absorbed as haem
and partly broken down in the gut to inorganic
Control of hepcidin expression
Membrane bound hemojuvelin (HJV) is a co -
receptor with bone morphogenetic protein (BMP) Table 3.2 Iron absorption.

which stimulates hepcidin expression. A complex

between HFE and transferrin receptor 2 (TfR2 ) Factors favouring Factors reducing

promotes HJV binding to BMP. The amount of absorption absorption

HFE – TfR2 complex is determined by the degree of
Haem iron Inorganic iron
iron saturation of transferrin as follows. Diferric 2 + 3 +
transferrin competes with TfR1 for binding to Ferrous form (Fe ) Ferric form (Fe )
HFE. The more diferric transferrin, the less TfR1 is Acids (HCl, vitamin C) Alkalis – antacids,

bound to HFE and more HFE is available to bind pancreatic secretions
to TfR2 with consequently increased hepcidin syn-
Solubilizing agents Precipitating agents
thesis. Low concentrations of diferric transferrin, as
(e.g. sugars, amino – phytates,
in iron deficiency, allow HFE binding to TfR1, acids) phosphates, tea

reducing the amount of HFE able to bind TfR2 and
Reduced serum Increased serum
thus reducing hepcidin secretion.
hepcidin, e.g. iron hepcidin, e.g. iron
Matriptase 2 digests membrane - bound HJV.
defi ciency excess
In iron deficiency, increased matriptase activity

therefore results in decreased hepcidin synthesis. Ineffective Decreased
Erythroblasts secrete two proteins, GDF 15 and erythropoiesis erythropoiesis
TWSG1, which suppress hepcidin secretion. In Pregnancy Infl ammation
conditions with increased numbers of early eryth-
Hereditary
roblasts in the marrow (e.g. conditions of ineff ective
haemochromatosis
erythropoiesis such as thalassaemia major), iron
absorption is increased because of suppression of Increased expression Decreased expression
hepcidin secretion by these two proteins. Hypoxia of DMT - 1 in duodenal of DMT - 1 in duodenal
enterocytes enterocytes
also suppresses hepcidin synthesis whereas in