1- Iron deficiency anemia 2- Anemia of Chronic disorders 3- Sideroblastic Anemia 4- Thalassemia 5- Lead poisoning 6- Iron overload

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1- Iron deficiency anemia2- Anemia of Chronic
disorders3- Sideroblastic Anemia4-
Thalassemia5- Lead poisoning 6- Iron overload
Chapter 3Hypochromic Anemia
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RBC Disorders
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Iron deficiency anemia

• Iron deficiency is the most common cause of
  anemia in every country of the world.
• It is the most important cause of a microcytic
  hypochromic anemia, in which the two red cell
  indices MCV (mean corpuscular volume) and MCH
  (mean corpuscular hemoglobin) are reduced and the
  blood film shows small (microcytic) and pale
  (hypochromic) red cells.
• This appearance is caused by a defect in
  hemoglobin synthesis

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Iron

• Iron is one of the most common elements in the
  Earth's crust, yet iron deficiency is the most
  common cause of anemia, affecting about 500
  million people worldwide. This is because the
  body has a limited ability to absorb iron and
  excess loss of iron as a result of hemorrhage is
  frequent.

Body Iron distribution and transport

• The transport and storage of iron is largely
  mediated by three proteins transferrin, the
  transferrin receptor 1 (TfR1) and ferritin.
• Transferrin can contain up to two atoms of iron.
  It delivers iron to tissues that have transferrin
  receptors, especially erythroblasts in the bone
  marrow which incorporate the iron into
  hemoglobin, the transferrin is then reutilized.
• At the end of their life, red cells are broken
  down in the macrophages of the reticuloendothelial
  system (RES) and the iron is released from
  hemoglobin, enters the plasma and provides most
  of the iron on transferrin. Only a small
  proportion of plasma transferrin iron comes from
  dietary iron, absorbed through the duodenum and
  jejunum.
• Some iron is stored in the macrophages as
  ferritin and hemosiderin
• The levels of ferritin and TfRl are linked to
  iron status so that iron overload causes a rise
  in tissue ferritin and a fall in TfRl, whereas in
  iron deficiency ferritin is low and TfRl
  increased.
• When plasma iron is raised and transferrin is
  saturated the amount of iron transferred to
  parenchymal cells (e,g, those of the liver,
  endocrine organs, pancreas and heart) is
  increased and this is the basis of the
  pathological changes associated with iron loading
  conditions

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Dietary Iron

• Iron is present in food as ferric hydroxides,
  ferric protein 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,

Iron transport

• 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, exposed on
  the apical membrane of the duodenal enterocyte.
  Haem is then digested to release iron.
• Inorganic iron absorption is favored by factors
  such as acid and reducing agents that keep iron
  in the gut lumen in the Fe2 rather than the Fe3
  state

Iron requirements

• The amount of iron required each day to
  compensate for losses from the body and for
  growth varies with age and sex it is highest in
  pregnancy, adolescent and menstruating females

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Hemoglobin-Iron cycle

• Rate Hgb synthesis depends on availability of
  iron
• 80 of body iron complexed to Heme in Hgb
• 20 stored in bone marrow, liver, spleen, and
  other organs
• Dietary Iron absorbed in the small intestine,
  especially duodenum
• Absorbed iron enters circulation and combines
  with a beta globulin (apotransferrin) to form
  transferrin

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Clinical feature Iron Deficiency anemia

• When iron deficiency is developing the
  reticuloendothelial stores (haemosiderin and
  ferritin) become completely depleted before
  anaemia occurs.
• As the condition develops the patient may develop
  the general symptoms and signs of anaemia and
  also show
• - A painless glossitis
• - Angular stomatitis
• - Brittle, ridged or spoon nails (koilonychia)
• - Dysphagia as a result of pharyngeal webs
• Pregnant women
• Increased risk of preterm delivery In the first
  two trimesters of pregnancy
• Three fold increased risk for delivering a
  low-birth weight baby

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Causes of Iron Deficiency anemia
1- Chronic blood loss, especially uterine or from
the gastrointestinal tract, is the dominant cause
2- Increased demands during infancy,
adolescence, pregnancy, lactation and in
menstruating women account for the high risk of
anemia. Newborn infants have a store of iron
derived the breakdown of excess red cells 3- In
pregnancy increased iron is needed for an
increased maternal red cell mass of approximately
35, transfer of 300 mg of iron to the fetus and
because of blood loss at delivery. Although iron
absorption is also increased, iron therapy is
often needed if the hemoglobin (Hb) falls below
10 g/dL or the mean cell volume (MCV) is below 82
fL in the third trimester 4- Growth 5-
Erythropoietin therapy 6- Malabsorption 7- poor
diet
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Laboratory Diagnosis Iron Deficiency anemia
1- Red cell indices and blood film Even before
anemia occurs, the red cell indices fall and they
fall progressively as the anemia becomes more
severe. The blood film shows hypochromic
microcytic cells with occasional target cells and
pencil-shaped poikilocytes. The reticulocyte
count is low in relation to the degree of anemia.
A dimorphic blood film is also seen in patients
with iron deficiency anemia who have received
recent iron therapy and produced a population of
new haemoglobinized normal-sized red cells and
when the patient has been transfused. The
platelet count is often moderately raised in iron
deficiency, particularly when haemorrhage is
continuing.
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Laboratory Diagnosis Iron Deficiency anemia
2- Bone marrow iron In iron deficiency anemia
there is a complete absence of iron from stores
(macrophages) and from developing erythroblasts.
The erythroblasts are small and have a ragged
cytoplasm.
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Laboratory Diagnosis Iron Deficiency anemia
3- Serum Iron and total Iron binding
capacity Iron binding Capacity (IPC) The iron
in the serum is bound to transferrin protein. In
normal person this protein is loaded with iron
(serum iron) to about one third of its binding
capacity. The quantity of iron that can be
additionally picked up by transferrin is called
free iron binding capacity of serum. The total
quantity of iron contained in iron saturated
serum is called the total iron binding capacity
TIPC So Free iron binding capacity serum Free
iron level Total iron binding capacity
4- Serum transferrin receptor Transferrin
receptor is shed from cells into plasma. The
level of serum transferrin receptor (sTfR) is
increased in iron deficiency anemia but not in
the anemia of chronic disease or thalassaemia
trait. The level is also raised if the overall
level of erythropoiesis is increased.
5- Serum ferritin A small fraction of body
ferritin circulates in the serum, the
concentration being related to tissue,
particularly reticuloendothelial, iron stores.
The normal range in men is higher than in women
(Fig. 3.11). In iron deficiency anaemia the serum
ferritin is very low while a raised serum
ferritin indicates iron overload or excess
release of ferritin from damaged tissues
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Treatment of Iron deficiency

• The underlying cause is treated as far as
  possible. In addition, iron is given to correct
  the anaemia and replenish iron stores.
• Oral iron
• The best preparation is ferrous sulphate which is
  cheap, contains 67 mg of iron in each 200 mg
  tablet and is best given on an empty stomach in
  doses spaced by at least 6 h. If side-effects
  occur (e.g. nausea, abdominal pain, constipation
  or diarrhoea), these can be reduced by giving
  iron with food or by using a preparation of lower
  iron content (e.g. ferrous gluconate which
  contains less iron (37 mg) per 300 mg tablet).
• Oral iron therapy should be given for long enough
  both to correct the anaemia and to replenish body
  iron stores, which usually means for at least 6
  months. The hemoglobin should rise at the rate of
  approximately 2 g/dL every 3 weeks.

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Anemia of chronic disorders

• One of the most common anemias occurs in patients
  with a variety of chronic inflammatory and
  malignant diseases. The characteristic features
  are
• 1- Normochromic, normocytic or mildly
  hypochromic (MCV rarely lt75 fL) indices and red
  cell morphology.
• 2- Mild and non-progressive anaemia (hemoglobin
  rarely lt9.0 g/dL). The severity being related to
  the severity of the disease.
• 3- Both the serum iron and TIBC are reduced sTfR
  levels are normal.
• 4- The serum ferritin is normal or raised.
• 5- Bone marrow storage (reticuloendothelial) iron
  is normal but erythroblast iron is reduced.
• The pathogenesis of this anaemia appears to be
  related to
• 1- Decreased release of iron from macrophages to
  plasma
• 2- Reduced red cell lifespan
• 3- An inadequate erythropoietin response to
  anaemia caused by the effects of cytokines such
  as IL-1 and tumor necrosis factor (TNF) on
  erythropoiesis.
• The anaemia is corrected by successful treatment
  of the underlying disease and does not respond to
  iron therapy

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Sideroblastic anemia

• This is a refractory anaemia with hypochromic
  cells in the. peripheral blood and increased
  marrow iron it is defined by the presence of
  many pathological ring sideroblasts in the bone
  marrow

• Sideroblastic anaemia is classified into
  different types (and the common link is a defect
  in haem synthesis.
• In the hereditary forms the anaemia is usually
  characterized by a markedly hypochromic and
  microcytic blood picture.
• The much more common primary acquired form is one
  subtype of myelodysplasia. It is also termed
  'refractory anaemia with ring sideroblasts'.

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Lead Poisoning

• Lead inhibits both haem and globin synthesis at a
  number of points. In addition it interferes with
  the breakdown of RNA by inhibiting the enzyme
  pyrimidine 5' 'nucleotidase, causing accumulation
  of denatured RNA in red cells, the RNA giving an
  appearance called basophilic stippling
• The anaemia may be hypochromic or predominantly
  hemolytic, and the bone marrow may show ring
  sideroblasts. Free erythrocyte protoporphyrin is
  raised

• Iron overload
• There is no physiological mechanism for
  eliminating excess iron from the body and so iron
  absorption is normally carefully regulated to
  avoid accumulation.
• Iron overload can occur in disorders associated
  with excessive absorption or chronic blood
  transfusion.
• Excessive iron deposition in tissues can cause
  serious damage to organs, particularly the heart,
  liver and endocrine organs
• Heamochromatosis it is autosomal recessive
  condition which characterized by increase
  absorption of iron from gastrointestinal tract

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