erythropoiesis and regulation of rbc formation

8/3/2019 Erythropoiesis and Regulation of Rbc Formation

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Dr. Eeman At-Taras

Dr. Mohammed Suliman


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Anemia = low hematocrit

Polycythemia = high hematocrit

Hemopoiesis (hematopoiesis) =

process by which formed elements of blood develop.


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Describe the functional importance oferythrocytes

List different tissue in which red blood cellproduction occurs

Describe the process of erythropoiesis

State the role of erythropoietin in red bloodcell production

List factors that enhance RBC maturation


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Red blood cells (RBCs)

Biconcave disc

4.8 million RBC/ul blood(females)

5.4 million RBC/ul blood(males)

2 million new mature RBCsmust enter the circulationper second to make up forloss


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Functions: Transport of hemoglobin Carrying O2 from lungs to tissues

Carbonic anhydrase CO2 + H2O H2CO3 Elimination of CO2

Buffering in the blood Hemoglobin serves as an acid-base buffer


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33% of RBC weight isdue to hemoglobin

Each RBC hasapprox. 280 millionhemoglobinmolecules

Hemoglobin bindsand releases nitricoxide (vasodilator)

23% of CO2 istransported byhemoglobin

Lack of nucleus,allows for morespace for oxygentransport

RBCs generate ATPanaerobically (nomitochondria)


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Pluripotenthematopoietic stemcells all cells inthe circulating

blood are derivedfrom it

Colony-formingunit-erythrocyte

(CFU-E) committedstem cell thatproduceserythrocytes


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Starts in bonemarrow Proerythroblast

Rate oferythropoiesis isdetermined by

reticulocytecounts Normally 0.5 1.5.%

of total RBCs


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Proerythroblast = first cell identified as belonging to thered blood cell line

Basophil erythroblasts = first generation cells resultingfrom divisions of proerythroblastic cells Little hemoglobin produced

Polychromatophil and orthochromatic erythroblasts =hemoglobin concentration increases; nucleus condenses

Reticulocyte = nucleus remnant extruded from cell andendoplasmic reticulum reabsorbed; cells pass from bonemarrow to blood capillaries (diapedesis)

Mature erythrocyte = remaining basophilic material ofreticulocyte disappears


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Growth inducers (e.g. interleukin-3)

Promote growth and reproduction of all different

types of committed stem cells or of specific

types of cells

Differentiation inducers

Enhances the differentiation of a specific cell

type

Formation of growth and differentiation

inducers occurs outside of the bone marrow


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Glycoprotein (molec. Wt = 34,000)

Produced by the kidneys in response to

hypoxia

Approx. 90% of all erythropoietin

Some (approx. 10%) produced in the liver

Stimulates red blood cell production

Stimulates production of proerythroblasts from

stem cells

Promotes the rapid development of

proerythroblasts


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http://kidney.niddk.nih.gov/kudiseases/pubs/anemia/images/Anemia-Kidney.jpg

Erythropoietin (EPO)


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Hypoxia = cellular oxygen deficiency

Lower oxygen content at high altitudes

Anemia

Lack of iron

Lack of certain amino acids

Lack of vitamin B12


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Early embryonic life:

primitive RBCs are

produced in the yolk sac

Second trimester: RBC

production in the liver,

some in the spleen and

lymph nodes

Late gestation and after

birth: RBC production in

bone marrow

Bone marrow

Red bone marrow = highly vascularized

Yellow bone marrow = mostly fat cells


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Until age 5: bonemarrow of allbones produces

RBCs

After age 20: longbone marrow

produces veryfew RBCs RBC production by

membranous bonemarrow


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Nutritional status

Vitamin B12 Stimulate formation of thymidine triphosphate (building block of

DNA)

Needed for maturation of RBCs

Maturation failure (due to formation of premature, fragilemacrocytes)

Prenicious anemia Atrophic gastric mucosa

y Poor absorption of vitamin B12

Folic acid Normally in green vegetables, some fruits and liver

Destroyed during cooking

Lack = maturation failure


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Iron

Increases the oxygen-carrying capacity of

hemoglobin in red blood cells

Absorbed from the intestinal tract by the aid ofapotransferrin


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RBCs have a typical life span of 120 days

With age, the plasma membrane becomes

fragile and ruptures

Ruptured RBC are phagocytosed in the spleen

and liver

Break down products are recycled


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Guyton and Hall, 11th edition. Chapter 32

Tortora and Derrickson, 11th edition. Chapter

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erythropoiesis and regulation of rbc formation

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