Page 306 - Concise Pathology for Exam Preparation ( PDFDrive )

12 Haematology 291

Fate of Haemoglobin Iron (Flowchart 12.2)

Aged or senescent RBCs

Phagocytosis by reticuloendothelial system

Breakdown of haemoglobin

Release of iron into circulation

Binding of released iron to ‘Transferrin’ (β-globulin)

Reutilization of iron by marrow erythroblasts for haemoglobin synthesis
FLOWCHART 12.2. Fate of Haemoglobin Iron.

1. Released iron is also converted into:
• Storage or available iron
• Nonavailable iron
2. A small proportion of storage iron is released into the plasma.
3. A small proportion is lost in urine, sweat, faeces or blood.

Iron Absorption (Flowchart 12.3)

Iron released from food as ferric or ferrous forms

Ascorbic acid Tannins, phosphorus and
increases absorption phytic acid reduce absorption

Ferrous form is absorbed in duodenum and upper jejunum
(as ferric ions polymerize and become less soluble with increase in the duodenal pH)
FLOWCHART 12.3. Mechanism of Iron absorption.
Proximal intestine is the site of choice because it has the ideal pH (redox potential for iron
absorption) and the key proteins responsible for iron absorption are maximally expressed
in this part. A ferric reductase enzyme duodenal cytochrome b (dcytb) reductase, ex-
pressed on the enterocyte brush border, reduces ferric to ferrous form to make it a sub-
strate for transport by Divalent Metal Transporter (DMT) 1.
Mucosal uptake of haem and nonhaem iron occurs through two distinct pathways:
1. Nonhaem iron: Enters the apical and basolateral portions of villus enterocytes by the action
of transporter protein DMT1. Inside the cell, most of the iron is stored as mucosal ferritin
and not absorbed. These ferritin-containing cells are later exfoliated from the mucosal sur-
face into the intestine at the end of their 3–4-day lifespan. The remaining iron is transported
to plasma by ferroportin (IREG-1 transporter) and hephaestin (an iron oxidase).
2. Haem iron: Mechanism not well understood but it is thought that haem enters the
mucosal surface unchanged to release iron within the cells by the action of the enzyme
haem oxygenase. Iron from this source follows the same pathway as nonhaem iron
except that a small portion of the haem iron passes into the plasma intact to bind to
hemopexin, a haem-binding protein.
Storage and Transport of Iron

• Iron is stored in bone marrow, liver, spleen and skeletal muscle as ferritin and haemosiderin.
• Ferritin has a spherical outer shell of protein called apoferritin and an inner core of
trivalent iron.
• Haemosiderin is more stable, therefore less readily mobilized to haemoglobin formation.

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