Professor Myat Thandar Department of Physiology University of
Medicine 1 Disorders of Red Blood Cells 1
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Functions of RBCs O 2 transport (Hb in the RBCs) CO 2 transport
Acid-base balance 2
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Functional Importance of the Biconcave Shape of RBCs Larger
surface area for O 2 diffusion Thinness of cell membrane enables O
2 to diffuse easily Flexibility of membrane facilitates the
transport function 3
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Network of Fibrous Proteins of RBCs Spectrin and Ankyrin
Imparts elasticity and stability to membrane and allows RBCs to
deform easily 4
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Haemoglobin A natural pigment, reddish when oxygenated 4
polypeptide chains (a globin portion and a heme unit) 5
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Haemoglobin F in Fetus Higher affinity for O 2 than adult Hb
HbF is replaced within 6 months of birth with HbA 6
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Haemoglobin Synthesis Availability of iron for heme synthesis
Amount of iron: 2 g in women and 6 g in men Clinically, decreased
ferritin levels usually indicate the need for prescription of iron
supplements. 7
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Red Cell Production Until 5, almost all bones; After 20,
membranous bones Approximately 1% of total RBC is generated from
bone marrow each day Reticulocyte count serves as an index of
erythropoietic activity of bone marrow 9
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Hematopoietic stem cell (HSCs) Unipotent committed stem cell
Proerythroblast (15-20 mm) Early normoblast (12-16 mm) Intermediate
normoblast (10-14 mm) Haemoglobinization begins Late normoblast
(10-14 mm) Haemoglobinization ++ Nuclear disintegration
Reticulocyte (7-8 mm) -Haemoglobinization ++ Nucleus remains only
as strands of reticular element Erythrocyte (7.5 mm) IL-1, IL-6,
IL-3 (interleukins) GM-CSF, G-CSF, SCF ErythropoietinGM-CSF Stages
of Erythropoiesis 10
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Red Cell Production 11
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Red Cell Maturation Reduction in the cell size Increase in the
amount of haemoglobin Disappearance of nucleus, and Change in
staining characteristics of cytoplasm: basophilic to eosinophilic.
This is partly due to a fall in content of RNA. 12
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Erythropoietin 13
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Human Erythropoietin Produced by recombinant DNA technology
Used for anaemia induced by chemotherapy in cancer patients, and
HIV infected persons treated with zidovudine In severe anaemia,
retic count may be as much as 30% (normal about 1%); numerous
erythroblasts may appear in the blood 14
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Destruction of Red Blood Cells 15
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Excretion of Bilirubins Excess bilirubin elimination leads to
bilirubin gallstones If red cell destruction and bilirubin
production is excessive, yellow discoloration of the skin,
jaundice, occurs due to accumulation of unconjugated bilirubin
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Haemoglobin binding protein Haptoglobin in the plasma Other
plasma proteins albumin also binds to Hb Extensive destruction of
RBCs (haemolytic transfusion reactions), binding capacity is
exceeded Haemoglobinaemia and haemoglobinuria results
Haemoglobinuria 17
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Red Cell Metabolism 2,3-DPG decreases affinity of Hb for O 2,
facilitating the release of O 2 at tissue levels Increased 2,3-DPG
occurs in chronic hypoxia such as chronic lung diseases, anemia and
residence at high altitude 18
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Inhibition of Oxygen Haemoglobin Binding Certain chemicals :
nitrates and sulfates Hb reacts with nitrite to form methaemoglobin
G6PD deficiency predisposes to oxidative denaturation of hemoglobin
with resultant red cell injury and lysis (oxidative stress
generated by infection or exposure to certain drugs) 19
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Laboratory Tests Using automated blood cell counters: red cell
content and indices Red cell indices are used to differentiate type
of anemias by size or color of red cells Haemoglobin Hematocrit
Mean corpuscular volume (MCV falls in microcytic and rises in
macrocytic anemia) Mean corpuscular haemoglobin concentration
(normochromic or normal MCHC; hypochromic or decreased color or
decreased MCHC) 20
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Laboratory Tests Mean cell haemoglobin A stained blood smear:
information about size, color and shape of red cells and the
presence of immature or abnormal cells If blood smear is abnormal,
bone marrow examination may be indicated Bone marrow aspiration
from posterior iliac crest or the sternum 21
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Red cell count and Haemoglobin severity of anemia Red cell
characteristics Sizenormocytic, microcytic or macrocytic
Colornormochromic, hypochromic Shapethe cause of anemia 22
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Anemia Values of hemoglobin, hematocrit or RBC counts which are
more than 2 standard deviations below the mean HGB
Megaloblastic Anemia Impaired DNA synthesis Enlarged red cells
(MCV >100 fL) Develop slowly Vitamin B 12 and folic acid
deficiency 54
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Vitamin B 12 Deficiency Anemia: B 12 Absorption 55
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Pernicious Anemia Atrophic gastritis Autoimmune destruction of
gastric mucosa Gastrectomy, ileal resection, inflammation or
neoplasms in terminal ileum, malabsorption syndrome MCV elevated;
MCHC is normal 56
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Vitamin B 12 Containing Food Normal body stores of 1000 to 5000
g provide the daily requirement of 1 g for a number of years.
Therefore, deficiency develops slowly 57
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Diagnosis of B 12 Deficiency The Shilling test 24 hour urinary
excretion of radiolabelled vitamin B 12 administered orally
Detection of parietal cell and intrinsic factor antibodies Lifelong
intramuscular or high oral doses of vitamin B 12 is required
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Folic Acid 60
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Folic Acid Deficiency Total body stores amount to 2000 to 5000
g and 50 g is required in the daily diet. A dietary deficiency may
result in anaemia in a few months Pregnancy increases the need for
folic acid 5 to 10 fold 61
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Aplastic Anemia Reduction of all 3 hemopoietic cell lines Onset
may be insidious but may be abrupt and severe 62
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Therapy in Aplastic Anemia 64
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Therapy in Aplastic Anemia Immunosuppressive therapy with
lymphocyte immune globulin Avoid offending agents Antibiotics for
infection Red cell transfusion to correct anaemia Platelets and
corticosteroid therapy to minimize bleeding 65
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Chronic Disease Anemia Occur as a complication of chronic
infections, inflammation, cancer and chronic kidney diseases Short
red cell life span; deficient red cell production; a blunted
response to erythropoietin, and low serum iron Mild anemia
normocytic and normochromic with low reticulocyte counts In chronic
renal diseases, uremic toxins and retained nitrogen interfere with
actions of erythropoietin; hemolysis and blood loss associated with
hemodialysis and bleeding tendencies also contribute to anemia
66
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Therapy in Chronic Disease Anemia Short-term erythropoietin
therapy Iron supplementation Blood transfusions In future iron
chelating agents and cytokines to stimulate erythropoietin
production 67
