IRON DEFICIENCY ANAEMIA

DR MRS STELLA KANU

BMLS MBBS MSc
 OUTLINE
 INTRODUCTION/DEFINITION
 IRON DISTRIBUTION & TRANSPORT
 DIETARY IRON
 IRON ABSORPTION
 PATHOPHYSIOLOGY
 CAUSES OF IRON DEFICIENCY
 CLINICAL SIGNS AND DIAGNOSIS
 TREATMENT
 DEFINITION
“Anaemia is decreased haemoglobin
concentration, PCV or red cell mass, for
age, sex and environment resulting in
defective tissue oxygenation”
Most commonly encountered problem in haematology
More common in women, children & elderly
Not a disease but an expression of underlying disease
conditions
Normal adult red cell value
Iron deficiency is the end result of iron loss in
excess of iron absorption.
• There are three stages of iron deficiency:
• The iron stores are reduced but are still
sufficient for erythropoiesis.
• The iron stores are depleted; then
erythropoiesis is reduced.
• Manifest iron deficiency anemia has
developed (erythropoiesis reduced;
hemoglobin has reduced to less than normal).
On a worldwide basis, iron deficiency is among the most frequent
causes of
anemia. Persons with an increased iron demand, such as pregnant or
menstruating
women, or children in the stages of growth and development, are the
first to
develop an iron deficiency anemia. It is the
most important cause of a microcytic hypochromic
anaemia, in which the two red cell indices MCV
(mean corpuscular volume) and MCH (mean
corpuscular haemoglobin) are reduced and the
blood film shows small (microcytic) and pale
(hypochromic) red cells. . Children fed with cow’s milk often develop
an iron deficiency because of the low iron content of this milk. In
adults, iron
deficiency is most often due to blood loss from the gastrointestinal or
urogenital tract
 IRON DISTRIBUTION AND TRANSPORT
Only a small amount of iron is gotten from dietary iron absorbed through
the duodenum and jejunum.
The transport and storage of iron is mediated by 3 proteins .
 Transferrin
 The transferrin Receptor-1
 Ferritin.
Transferrin delivers iron to tissues that have transferrin Receptors especially
erythroblasts in the bone marrow which incorporate the iron into
hemoglobin. At the end of th life span of red blood cells, they are broken
down in the macrophages ,the iron is released from the hemoglobin ,enters
plasma ad provides most of the iron on transferrin .
 IRON DISTRIBUTION
Some iron is stored in the macrophages as ferritin and
hemosiderin.
Ferritin is a water soluble protein-iron complex which
hemosiderin is an insoluble protein iron complex.
Ferritin contains up to 20% of its weight as iron while
hemosiderin contains 37% iron by weight .
Ferritin is not visible by light microscopy while hemosiderin is
visible in macrophages and other cells by light microscopy
after straining my Perl's`(Prussian blue) reaction.
Iron in ferritin and hemosiderin is in the ferric form, vitamin c
being involved. A copper-containing enzyme , caeruloplasmin,
catalyses oxidation of the iron to the ferric form for binding to
plasma transferrin.
Dietary iron
Iron is present in food as ferric hydroxides, ferricprotein
and haem-protein complexes. Both the iron
content and the proportion of iron absorbed differ
from food to food; in general, meat-in particular liver
-is a better source than vegetables, eggs or dairy
foods, The average Western diet contains 10-15 mg
iron daily from which only 5-10% is normally
absorbed, The proportion can be increased to
20-30% in iron deficiency or pregnancy
 Iron absorption
• Factors reducing absorption
• Inorganic iron
• Ferric form (Fe3+)
• Alkalis-antacids, pancreatic
secretions
• Precipitating agents-phytates,
phosphates
• Iron excess
• Decreased erythropoiesis
• Infection
• Tea
• Decreased expression of DMT-1
and ferroportin
• in duodenal enterocytes
• Increased hepcidin.
• Factors favouring absorption
• Haem iron
• Ferrous form (Fe2+)
• Acids (HCl, vitamin C)
• Solubilizing agents (e.g. sugars,
amino acids)
• Iron deficiency
• Ineffective erythropoiesis
• Pregnancy
• Hereditary haemoc1uomatosis
• Increased expression of DMT-1
and ferroportin
• . in duodenal enterocytes
Iron absorption
Organic dietary iron is partly absorbed as haem
and partly broken down in the gut to inorganic iron.
Absorption occurs through the duodenum. Haem
is absorbed through a specific receptor, HCP-I,
exposed on the apical membrane of the duodenal enterocytes.Haem is then digested to
release iron. Inorganic iron absorption is favoured by and reduced by the above factors on
the table.
When a negative iron balance occurs, iron resorption first increases from the normal value
of 5–10% to a maximum of 20%. If the iron stores are completely
exhausted, as can be recognized by a decrease of the serum iron and ferritin and
an increase in transferrin, then the erythropoiesis becomes defective. Abnormally
small, poorly hemoglobinized (hypochromic) red blood cells are synthesized.
After a few weeks, the total hemoglobin concentration decreases (manifest
iron deficiency anemia). If the iron deficiency is more severe, the synthesis of
other iron-dependent proteins (e.g., cytochromes, myoglobin, flavoproteins) is
also impaired.
Pathophysiology
The normal body iron content is 3–5 g. This quantity is contained in hemoglobin,
myoglobin, iron stores, and in the reticuloendothelial system (RES); a small amount is contained
in serum as ferritin. Iron absorption and iron loss are
normally kept constant during adult life. The daily iron demand is 1.3 mg for men
and 1.8 mg for women (during the years of menstruation). Adolescents and
pregnant women need more iron. Generally, the Western diet contains sufficient
iron to compensate for the daily iron losses. Iron resorption takes place mainly
in the duodenum and, to some extent, in the jejunum. The mucosal cells regulate
intestinal iron absorption. Iron is either directly absorbed and transferred into the
circulating blood or stored in the mucosal cells as ferritin. If serum iron is low,
iron uptake from the gastrointestinal tract is rapid; if serum iron is elevated or
normal, more iron is retained in the mucosal cells. The iron transport from blood
to different sites of iron utilization or storage is then performed by transferrin, a
specialized transport protein of the β-globulin fraction of human serum. One
molecule of transferrin can bind two iron atoms. Normally, about 30% of the total
iron-binding capacity is saturated with iron. In the next step, the transferring iron
complex is bound to transferrin receptors on the surface of erythroblasts and
other cells. Nonutilized iron is then either transported to different storage tissues
and accumulated as ferritin or hemosiderin, or excreted via the kidneys. The total
iron storage pool is about 800 mg in men and 400 mg in women
 CAUSES OF IRON DEFICIENCY

1. Chronic blood loss

2. Increased demands during infancy,
adolescence pregnancy, lactation and
menstruation.
3. Malabsorption as seen in gastrectomy
gluten-induced enteropathy
4. Poor diet especially in infants &children.
Clinical Signs and Diagnosis
The symptoms of iron deficiency anemia
depend on its severity. Patients are
easily fatigued, may have dyspnea on exertion
and have pale skin and pale
mucous membranes. An atrophic glossitis,
spoon nails (koilonychia), or an
angular stomatitis develop. In very severe
cases, the patients have dysphagia
due to esophageal webs (Plummer-Vinson
syndrome). Some patients also develop
atrophic gastritis.
An early event in iron deficiency is a decrease
in serum ferritin, the major
iron storage protein. Normal serum
concentration of ferritin is 40–350 ng/mL
in men and 20–150 ng/mL in women. The
serum values reflect the body iron
stores in the reticuloendothelial system. The
next laboratory sign of iron deficiency
to develop is a decrease in the hemoglobin
concentration.
At this point the number of red blood cells can still be normal. If the iron deficiency
persists,
abnormalities of red cell morphology can be recognized (e.g., poikilocytosis,
anisocytosis, hypochromasia). The reticulocytes are generally decreased and the
red cell indices (e.g., mean corpuscular volume [MCV], mean corpuscular
hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC])
are below normal. The bone marrow morphology shows nonspecific changes.
The stainable iron, usually seen in bone marrow macrophages after staining with
Prussian blue, is decreased or absent. In iron deficiency, the transport protein
transferrin is usually increased. The serum iron concentration is generally low,
but is not a reliable indicator of the degree of iron deficiency. The transferrin
saturation (serum/total iron-binding capacity) is typically less than 10%.
A new parameter for estimating iron deficiency is the measurement of the
serum transferrin receptors. In contrast to ferritin, the levels of serum transferrin
receptors are usually not influenced by acute or chronic infections. The normal
values (as measured by ELISA) are 4–9 μg/L. In iron deficiency, the levels of
serum transferrin receptors increase proportionally to the degree of iron deficiency.
Early iron deficiency can also be diagnosed by measuring the red blood cell
protoporphyrin. The normal value is approx 30 μg/dL of red cells. In iron deficiency,
the value increases to greater than 100 μg/dL. Increased levels are also
found in lead poisoning and some sideroblastic anemias and porphyrias.
Treatment
The first step is to identify and treat the underlying cause of the iron
deficiency.
It is especially important that an underlying malignancy is not overlooked.
The standard treatment of iron deficiency is oral ferrous sulfate. One
tablet (100 mg, containing 67 mg as ferrous iron) is given before meals and
should be continued until the iron deficiency is corrected and the iron
stores are
replenished (3–4 mo in severe iron deficiency). In severe cases, two or three
tablets daily can be given. An increase
in reticulocytes should be seen 7–10 d after the iron substitution is begun if
the
iron is being adequately absorbed. A prophylactic iron treatment should he
given during
pregnancy or for premature newborns. Parenteral iron should only be given
when
oral iron is not effective or cannot be tolerated.
 Parenteral iron is preferable when
gastritis or a duodenal ulcer leads to
pronounced side effects or if a
severe malabsorption
precludes the resorption. Parenteral
iron always carries the risk of a
hypersensitivity reaction and
therefore should be given under
close medical
supervision.