Disorders of Red Blood Cells

Professor Myat ThandarDepartment of PhysiologyUniversity of Medicine 1Disorders of Red Blood Cells1Functions of RBCsO2 transport (Hb in the RBCs)CO2 transportAcid-base balance2Functional Importance of the Biconcave Shape of RBCsLarger surface area for O2 diffusionThinness of cell membrane enables O2 to diffuse easilyFlexibility of membrane facilitates the transport function

3Network of Fibrous Proteins of RBCsSpectrin and AnkyrinImparts elasticity and stability to membrane and allows RBCs to deform easily

4Haemoglobin A natural pigment, reddish when oxygenated4 polypeptide chains (a globin portion and a heme unit)

5Haemoglobin F in Fetus Higher affinity for O2 than adult HbHbF is replaced within 6 months of birth with HbA

6Haemoglobin SynthesisAvailability of iron for heme synthesisAmount of iron: 2 g in women and 6 g in men

Clinically, decreased ferritin levelsusually indicate the need for prescription of iron supplements.7

8Red Cell ProductionUntil 5, almost all bones; After 20, membranous bonesApproximately 1% of total RBC is generated from bone marrow each dayReticulocyte count serves as an index of erythropoietic activity of bone marrow

9Hematopoietic 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, SCFErythropoietinGM-CSFStages of Erythropoiesis10Red Cell Production

11Red Cell MaturationReduction in the cell sizeIncrease in the amount of haemoglobinDisappearance of nucleus, andChange in staining characteristics of cytoplasm: basophilic to eosinophilic. This is partly due to a fall in content of RNA.

12Erythropoietin

13Human ErythropoietinProduced 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

14Destruction of Red Blood Cells

15Excretion of Bilirubins

Excess bilirubin elimination leads tobilirubin gallstones

If red cell destruction and bilirubinproduction is excessive, yellow discoloration of the skin, jaundice, occurs due to accumulationof unconjugated bilirubin16Haemoglobin binding protein Haptoglobin in the plasmaOther plasma proteins albumin also binds to HbExtensive destruction of RBCs (haemolytic transfusion reactions), binding capacity is exceededHaemoglobinaemia and haemoglobinuria resultsHaemoglobinuria

17Red Cell Metabolism

2,3-DPG decreases affinity of Hb for O2, facilitating the release of O2 at tissue levelsIncreased 2,3-DPG occurs in chronic hypoxia such as chronic lung diseases, anemia and residence at high altitude

18Inhibition of Oxygen Haemoglobin BindingCertain chemicals : nitrates and sulfatesHb reacts with nitrite to form methaemoglobin

G6PD deficiency predisposes to oxidative denaturation of hemoglobinwith resultant red cell injury and lysis (oxidative stress generated by infection or exposure to certain drugs)

19Laboratory TestsUsing automated blood cell counters: red cell content and indicesRed cell indices are used to differentiate type of anemias by size or color of red cellsHaemoglobinHematocritMean 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)20Laboratory TestsMean cell haemoglobinA stained blood smear: information about size, color and shape of red cells and the presence of immature or abnormal cellsIf blood smear is abnormal, bone marrow examination may be indicatedBone marrow aspiration from posterior iliac crest or the sternum21Red cell count and Haemoglobin severity of anemiaRed cell characteristics

Sizenormocytic, microcytic or macrocyticColornormochromic, hypochromicShapethe cause of anemia22AnemiaValues of hemoglobin, hematocrit or RBC counts which are more than 2 standard deviations below the meanHGB