Transcript Iron deficiency anemia

Red cells
Men
• Hemoglobin (g/l)
140-180
• Hematocrit (%)
40-52
• Red cell count (1012/l) 4.5-6.5
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Women
120-160
36-48
3.9-5.6
Reticulocyte count (%)
0.5-1.5
Mean cell volume (fl)
80-95
Mean corpuscular hemoglobin (pg)
27-33
Mean corpuscular hemoglobin concentration (gm/dL) 33-37
Red cells
pathological conditions:
I. decrease in the circulating red cell mass
(poss. with structural abnormalities)
very common - anaemia
II. increase in the circulating red cell mass
less common
polycythemia =erythrocytosis=polyglobuly
reactive – low levels of oxygen in the PB
(heart disease, high altitude)
neoplastic – polycythemia vera
= chronic myeloproliferative disease
Anaemia
decrease in the total circulating red cell mass
(hematocrit, hemoglobin concentration)
Classification: A. underlying mechanism
blood loss
increased destruction
decreased production
B. morphology of erythrocytes
size (micro-, macro-, normocytic)
shape (spherocytosis, stomato-,...)
color (degree of hemoglobinization:
normo- hypo-, hyperchromic)
Blood loss
•acute or chronic
•internal or external
Acute
• Hypovolemia – shock
• Anemia – normocytic normochromic
• Shift of water – hemodilution –↓ hematocrite
• Compensatory increase of red cell production
• Reticulocytes
• Chronic
• hypochromic sideropenic anemia
Iron deficiency anemia
• body iron = functional + storage;
• F - 2g, M - 6g
• 1. Lack in diet, low absorption
• 2. Increased requirement
• !!!3. Chronic blood loss!!! - GIT, GYN
The internal iron cycle
Plasma iron bound to transferrin transported to the marrow,
transferred to developing red cells, incorporated into hemoglobin.
Mature red blood cells released into the circulation, after 120 days
ingested by macrophages in RES, iron extracted
from hemoglobin, returned to the plasma.
PB: ery pale + small
BM: erythroid hyperplasia, loss of iron
alopecia, koilonychia, atrophy of tongue,
gastric mucosa
Plummer-Vinson syndrome:
siderop.an., atrophic glossitis, esophageal
webs
Hypochromic microcytic anemia
of iron deficiency
Small red cells - narrow rim of peripheral hemoglobin.
Scattered fully hemoglobinized cells - blood transfusion,
Iron deficiency anaemia
nail beds pale
nails flattened, brittle
Iron deficiency anaemia
koilonychia
nails concave, ridged, brittle
Iron deficiency anaemia
angular cheilosis
fissuring and ulceration
Iron deficiency anaemia
flattening and loss of papillae
bald , fissured tongue
Increased destruction
=lysis of red cells=hemolysis
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intravascular – rare (mechanical injury – artificial
valves or microthrombi, exogenous toxic agents,
complement fixation (transfusion of mismatched
blood)
Extravascular - more common, when red cells
considered foreign or less deformable
Hemolytic anemia
Abnormality:
 intracorpuscular or extracorpuscular
 hereditary (intra) or acquired (extra)
Hemolytic anemia
• premature destruction of red cells
• accumulation of the products of the hemoglobin
catabolism
• BM – increased erythropoiesis, extreme:
extramedullary hematopoiesis
• PB: reticulocytosis
• high bilirubin –gallstones; jaundice, blr in urine
• chronic duration: hemosiderosis
• splenomgaly
Increased destruction of ery=hemolysis
I. Intrinsic
A. hereditary
• membrane – cytoskeleton, lipid synthesis
• enzymes – deficiencies - G6PD, glutathione
synthetase, pyruvate kinase
• hemoglobin - deficient synthesis of globin,
structurally abnormal Hb
B. acquired
• membrane defect: paroxysmal nocturnal
hemoglobinuria
• II. Extrinsic
• antibodies, trauma, infection, chemical injury
Pathophysiology
of hereditary spherocytosis
Red cell membrane cytoskeleton
Alterations leading to spherocytosis and hemolysis
Mutations weakening interactions involving α-spectrin, β-spectrin, ankyrin
band 4.2, or band 3 cause the normal biconcave red cell to
lose membrane fragments and become spherical
spherocytic cells: less deformable than normal, become trapped in the
Splenic sinus
A red cell squeezing from the red pulp cordsinto the sinus lumen.
Note the degree of deformability required for red cells to pass
through the wall of the sinus.
Hereditary spherocytosis (peripheral smear)
anisocytosis and several dark-appearing spherocytes with no
central pallor. Howell-Jolly bodies (small dark nuclear remnants)
Hereditary stomatocytosis
Akanthocytosis
Hereditary elliptocytosis
Hereditary elliptocytosis
Enzyme deficiency: G6PD deficiency
effects of oxidant drug exposure (PB)
Red cells with precipitates of denatured globin (Heinz bodies)
splenic macrophages pluck out these inclusions → "bite cells"
Pathophysiology of sickle cell anemia
Sickle cell anemia (PB)
Splenic remnant in sickle cell anemia
Pathogenesis of β-thalassemia major
aggregates of unpaired
α-globin chains not
visible
Blood transfusions
correct the anemia
reduce
the stimulus for marrow
expansion,
but add to systemic iron
overload
Decreased production
disorders of proliferation and differentiation

stem cells

erythroblasts
Impaired:
 DNA synthesis – B12, folic acid
 hemoglobin synthesis
- heme
(lack of iron)
- globin

others
Vitamin
B12
absorption
Megaloblastic anaemia
Acute leukaemia
Megaloblastic anaemia pernicious
lemon-yellow appearance
pallor (anaemia)
+ jaundice (ineffective
erythropoiesis)
Pernicious anaemia (38 ys.)
premature greying, blue eyes, vitiligo
Megaloblastic anaemia
spontaneous bruising
Pernicious anaemia
spinal cord demyelination
Stomach
normal
atrophy - pern. an.
Coeliac disease - jejunum
normal villi
subtot. villous atrophy
Aplastic anemia
Markedly hypocellular marrow
contains mainly fat cells.
Raynaud phenomenon
autoimmnune haemolytic anaemia
Sideroblastic anaemia (Perl´s stain)
collars of iron granules around the nucleus
Anemia of chronic disease
*Infections
*immunologic
*neoplasms
Mechanism: defect in reutilization of iron
(transfer, cytokines]
! abundant storage iron
Anemia: normo, normo or hypo, micro
Aplastic anemia
• Failure or suppression of myeloid stem cell
• PANCYTOPENIA
• primary OR secondary - drugs , chemicals
infections
irradiation
inherited
BM: hypocellular, PB: pancytopenia,
symptoms
spleen normal
Fanconi anemia
AR,
defective DNA repair
anomalies – bones, kidney, spleen
Pure red cell aplasia
• Isolated absence of red cell precursors
acute
drug, virus
aplastic crisis
OR
insidious
thymoma
Other forms of marrow failure
• Myelophthisic an. - space occupying
lesions
(meta, TBC]
• diffuse liver disease, chronic renal failure