Red Blood Cells (Erythrocytes)
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Red Blood Cells (Erythrocytes). Er ythrocytes (RBC). Structure Biconcave disc shape Includes Hemoglobin Lipid s , ATP, carbonic anhydrase Function O 2 and CO 2 transport. Er ythrocytes (RBC). Most abundant type of blood cells 4- 6 million /mm 3 anemi a ; number of RBC below normal

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Er ythrocytes rbc
Erythrocytes (RBC)

  • Structure

    • Biconcave disc shape

  • Includes

    • Hemoglobin

    • Lipids, ATP, carbonic anhydrase

  • Function

    • O2 and CO2 transport

Erythrocytes (RBC)

  • Most abundant type of blood cells

    • 4-6million/mm3

    • anemia; number of RBC below normal

    • polycythemia (erythrocytosis); number of RBC above normal range

  • No nucleus, mitochondria and ribosom

    • No protein synthesis

    • Energy is obtained through glycolisis, but there is no glycogen storage

  • Normal diameter 7-8 , volume 78-94 3

    • normocyte - microcyte - macrocyte

Energy use and source in RBC

  • Energy is used mainly for two functions:

    • Continuation of membrane shape - active transport

    • Homeostasis of intracellular oxidation-reduction

  • Only source of energy is glycolysis

RBC Membrane

  • The same as other biological membranes

    • Cannot synthesize its own cell membrane

  • Actin and spectrin provide strength

    • Contractility in the presence of Ca+2 ions

    • Changes in viscosity

  • Na+-K+ATPaseand Ca+2ATPase activity

  • Carbohydrates on the membrane are to do with blood types (antigens)

Hemoglobin (Hb)

  • Red color protein that carries oxygen

    • 1 g Hb binds 1,3 mlO2; 14,8 g Hb binds 20 ml O2

  • Normal range of hemoglobin: 14-16 g/dl

    • In adults, about 25-30 trillion RBC, and 900 g Hb

    • Hb constitutes 1/3 of erythrocyte weight


  • 4 globin molecules:carries CO2 (role of carbonic anhydrase)

  • 4 heme molecules:carries O2

    • Iron is required for oxygen transportation

Hematopoiesis hemopoiesis
Hematopoiesis (Hemopoiesis)

  • Production of blood cells

  • Stem cells: All formed elements of blood stem from a colony of cells

    • Proerythroblast: forms erythrocytes

    • Myeloblast: forms neutrophils, eosinophils and basophils

    • Lenfoblast: forms lymphocytes

    • Monoblast: forms monocytes

    • Megakaryoblast: forms thrombocytes

What are stem cells
What are stem cells?

  • They are of many types: epidermal, intestinal, hematopoietic, etc.

  • The defining properties of a stem cell are:

    • It is not terminally differentiated.

    • It can divide without limit.

    • When it divides, the daughter cell has a “choice”:

      • Remain a stem cell, or

      • Terminally differentiate.

Potentiality of stem cells1
Potentiality of Stem Cells

“Stem cells” have varying potentials:

  • Totipotent cells.Fertilized oocyte (zygote) & progeny of the first two cell divisions. Cells able to form the embryo and the trophoblast of the placenta.

  • Pluripotent cells. After about 4 days, the blastocyst forms; embryonic stem cells obtained from the inner cell mass, which becomes the embryo, are pluripotent, able to differentiate into almost all cells of the three germ layers – but not into an embryo.

  • Multipotential cells. Found in most tissues, these cells can produce a limited range of differentiated cell lineages appropriate to their location. (Hematopoietic stem cells from the bone marrow exemplify multipotential cells.)

  • Unipotential cells. Cells capable of generating only one cell type (epidermal stem cells, adult liver stem cells).

Rbc formation erythropoiesis
RBC Formation (Erythropoiesis)

  • In the adult, all blood cell formation (including erythropoiesis) occurs in the red bone marrow

  • All blood cells develop from stem cells called hemocytoblasts

Red Blood Cells




Myeloid Stem Cell


Lymphoid Stem Cell


Erythropoiesis production of rbc
Erythropoiesis (production of RBC) hematopoietic stem cell (P-HSC)

Weeks 16-20

Week 2

Week 6


Week 8

Myeloid phase


Hepatic phase

Mesoblastic phase

Myeloid phase

Prenatal Life

Postnatal Life

P hematopoietic stem cell (P-HSC)renatal period-1

  • Mesoblastic phase

  • It starts in the vitellus sac at the second week

    • These are erythrocytes with nuclei

  • Embriyonic hemoglobins:

    • Hb Gower I, Gower II and Portland 1

P hematopoietic stem cell (P-HSC)renatal period-2

  • Hepatic phase

  • Liver takes part starting from the week 6

  • Spleen is involved starting from the week 8

  • Fetal hemoglobin:

    • HbF (2 and 2 )

P hematopoietic stem cell (P-HSC)renatal period-3

  • myeloid phase

  • Starts between the weeks 16 and 20 in the bone marrow

    • All bones

    • Hemopoiesis

  • HbA (2 and 2 ): mature hemoglobin

P hematopoietic stem cell (P-HSC)ostnatal Period

  • Only in the bone marrow(myeloid)

    • All bones contribute up to the age of 5

    • Later, erythropoiesis regresses from the distal to the proxymale

    • vertebra, sternum, costa, cranium and femur

    • Red bone marrow turns into yellow marrow (reversible)

      • Lipid infiltration

Sites of hemopoiesis in postnatal life hematopoietic stem cell (P-HSC)

E hematopoietic stem cell (P-HSC)rythropoiesis

  • BFU-E and CFU-E cells

    • Response to different levels of EPO

  • proerythroblast

  • basophil erythroblast

  • Polychromatophil erythroblast

  • Orthochromatophil erythroblast

  • Reticulocyte

  • Erythrocytes

Genesis of Red Blood Cells hematopoietic stem cell (P-HSC)

Regulation of Erythropoiesis hematopoietic stem cell (P-HSC)

  • Primary stimulus is hypoxia

  • Tissue oxygenation

    • Blood flow

    • Blood hemoglobin levels

    • Oxygen saturation of hemoglobin

    • Affinity of hemoglobin to oxygen

E hematopoietic stem cell (P-HSC)rythropoietin (EPO)

  • Fetus and newborn

    • 85% Liver

      • hepatocyte, Kupffer cells, endothelial cells

    • 15% kidney

      • Endothelial cells, glomerulus, JGH, proxymal tubule

  • Adult

    • 85% kidney

    • 15% liver and other tissues

      • glomus caroticum, macrophages

Regulation of Erythropoiesis hematopoietic stem cell (P-HSC)

E rythropoiesis
E hematopoietic stem cell (P-HSC)rythropoiesis

  • Erythropoietin: a hormone that stimulates erythropoiesis

    • It stimulates both differentiation and maturation

Maturation of red blood cells – Vit B hematopoietic stem cell (P-HSC)12 and Folic acid

  • Both vitamins are necessary for DNA synthesis

  • Deficiency of either of these vitamins causes maturation failure in the process of erythropoiesis

  • Pernicious anemia – Megaloblastic anemia

  • Vit B12 absorption and storage

  • Intrinsic factor: released from parietal cells in the stomach

  • Complex of Vit B12 + intrinsic factor cannot be digested by the enzymes in the stomach

  • Lack of intrinsic factor causes serious absorption abnormalities of Vit B12

Deformability of Erythrocytes hematopoietic stem cell (P-HSC)

H hematopoietic stem cell (P-HSC)emoglobin (Hb)

  • Normal range of hemoglobin: 14-16 g/dl

    • Men: 16 g/dl = 21 ml O2 /dl blood

    • Women: 14 g/dl = 19 ml O2 /dl blood

Formation of hemoglobin
Formation of Hemoglobin hematopoietic stem cell (P-HSC)

  • 2 succinyl-CoA + 2 glycine = pyrrole

  • 4 pyrrole protoporphyrin IX

  • protoporphyrin IX + Fe++ Heme

  • Heme + globin hemoglobin chain (alpha or beta)

  • 2 alpha + 2 beta chains Hemoglobin A

Hemoglobi n
Hemoglobi hematopoietic stem cell (P-HSC)n

  • Hemoglobin synthesis begins in the proerythroblasts and continues until reticulocytes

  • It consists of iron containing heme and globin

  • Hemoglobin A contains 2a ve 2b chain

  • There are different types of these chains (a, b, d ve g)

  • Hb molecule binds to oxygen loosely and reversibly

Hemoglobin a
Hemoglobin hematopoietic stem cell (P-HSC) A

  • 4 globin molecules:carries CO2 (role of carbonic anhydrase)

  • 4 hem molecules:carries O2

    • Iron is required for oxygen transportation

Lifecycle of an rbc
Lifecycle of an RBC hematopoietic stem cell (P-HSC)

  • RBCs are subjected to incredible mechanical stress.

    • Why are they unable to synthesize replacements for damaged parts?

  • After ≈120d, the RBC cell membrane ruptures, or the damage is detected by phagocytic cells and the RBC is engulfed.

  • If the RBC hemolyzes, its contained Hb will be excreted by the kidneys

A macrophage phagocytizing multiple RBCs

Life span and destruction of rbcs
Life span and destruction of RBCs hematopoietic stem cell (P-HSC)

  • Because of lack of nuclei, they cannot divide and grow

  • They have a life span of 120 days

  • Old erythrocytes are destructed in the spleen, liver and bone marrow

  • Hemoglobin is broken down to heme and globin

  • Iron part of heme is stored for re-use

  • Porphyrin part of hemoglobin is converted to bilirubin and secreted into bile

Iron – Fe hematopoietic stem cell (P-HSC)+2,+3

  • 50 in men and 35 mg/kg in women (total 4-5 gr)

    • 60-65% in hemoglobin

    • 4% myoglobin

    • 1% bound to plasma transferrin

    • The rest is in ferritin or hemosiderin

  • Amount of iron bound to transferrin 110-130 g

  • Daily need of iron lost through urine, feces and bleeding should be compensated

Transferrin - siderofilin hematopoietic stem cell (P-HSC)

  • It is a 1-globulin

  • It has two sides to bind iron (ferri)

    • One side leaves iron to the liver and the other to bone marrow for hemoglobin synthesis

  • Saturation of transferrin with iron (normally 35%)

Absorption of iron hematopoietic stem cell (P-HSC)

  • Iron is absorbed in ferro (+2) form

    • Absorption in all parts of the small intestine

  • It binds to apoferritin in the intestinal cells and stored as ferritin

  • Iron in ferritin is in the form of ferri (+3)

    • Liver is the largest storage site

    • Homeostasis is maintaned through the intestinal depot

Iron Transport and Metabolism hematopoietic stem cell (P-HSC)

Iron Overload Disease hematopoietic stem cell (P-HSC)

  • hemosiderin

  • hemochromatosis

    • Bronze diabetes

    • Cirrhosis

    • Cancer

    • Gonadal atrophy

Iron Deficiency hematopoietic stem cell (P-HSC)

  • Hepatic diseases

  • Deficiency of reducing substances in the digestive tract

    • Ca+2, ascorbic acid, lactic acid, pyruvate, glucose and sorbitol

    • Excessive Ca+2

  • Oxalate, phytate, phosphate

  • Important symptom: geophagy

Other factors hematopoietic stem cell (P-HSC)

  • Time of iron supplementation

  • Injections in cases of absorption problems

  • Overload of iron facilitates production of microorganisms

    • transferrin and lactoferrin are anti-microbial

Anemia hematopoietic stem cell (P-HSC)

  • Decrease in RBC count and/or amount of Hb

  • Reduced capacity of blood to carry O2

    • Tachycardia, tachypnea

    • Tiredness, feeling cold

  • General causes

    • Blood loss

    • Reduced erythropoiesis

    • Increased destruction of RBC

    • Inadequate of production of EPO

Classification of Anemias hematopoietic stem cell (P-HSC)

  • Hemorrhagic anemias; blood loss

  • Hemolytic anemias; hemolysis

  • Vitamin deficiency anemias (megaloblastic anemia)

  • Iron deficiency anemia

  • EPO deficiency caused anemia

  • Aplastic anemia (Fanconi anemia)

Hemolytic Anemias hematopoietic stem cell (P-HSC)

  • Intracorpuscular causes

    • hereditary spherocytosis

    • sickle cell anemia; HbS

    • thalassemia (Mediterranian anemia, cooley anemia)

    • glucose-6-phosphate dehydrogenase deficiency

    • Pyruvate kinase deficiency

    • Paroxysmal nocturnal hemoglobinuria

  • Extracorpuscular causes

    • Blood transfusion – autoantibodies

Sickle cell anemia
Sickle hematopoietic stem cell (P-HSC) Cell Anemia

  • Seen in black population

  • A mutation in the βchain of globin results in HbS

  • This hemoglobin precipitates as long crystals in RBC when it exposes to O2

  • As a result, RBC become sickle shaped and may cause blockage in small blood vessels

Sickle cell anemia sca
Sickle cell anemia hematopoietic stem cell (P-HSC) (SCA)

  • In SCA, aa valine takes the place of glutamic acid at the Hemoglobin beta polypeptide chain

Thalassaemia (Mediterranean Anemia) hematopoietic stem cell (P-HSC)

  • It is usually seen in populations in Mediterranean countries

  • One of the genes coding globin is faulty or missing

Glucose 6 phosphate dehydrogenase
Glucose 6-Phosphate Dehydrogenase hematopoietic stem cell (P-HSC)

  • Regenerates NADPH, allowing regeneration of glutathione

  • Protects against oxidative stress

  • Lack of G6PD leads to hemolysis during oxidative stress

    • Infection

    • Medications

    • Fava beans (that contain high level of oxidants)

  • Oxidative stress leads to Heinz body formation,extravascular hemolysis

G6pd deficiency function of g6pd
G6PD DEFICIENCY hematopoietic stem cell (P-HSC)Function of G6PD

Glucose 6 phosphate dehydrogenase g6pd anemia
Glucose -6-Phosphate Dehydrogenase (G6PD) Anemia hematopoietic stem cell (P-HSC)

Hereditary defect in RBC metabolism

  • Direct oxidation of hemoglobin damages RBC

  • occurs when person exposed to stressors: aspirin, sulfonamides, Vitamin K derivatives

    Manifestations: pallor, jaundice, hemoglobinuria, elevated reticulocyte count

    Diagnostics: quantitative assay of G6PD

Er yth roblastosis f e talis
Er hematopoietic stem cell (P-HSC)ythroblastosis Fetalis

  • It is a hemolytic type of anemia

  • Rh- mother, Rh+ father

  • First baby will be Rh+

  • Mixture of baby’s blood with that of mothers during labor

  • Sensitization develops in the mother against Rh+ and antibodies are formed against to Rh antigen

  • First baby is healthy

  • During the second pregnancy, the antibodies formed against Rh are transported to the baby through placenta and attack fetus’ RBC

  • This condition is known as erythroblastosis fetalis (hemolytic disease of new born)

  • Baby is anemic and hypoxic.

  • Exchange transfusion of compatible blood to the baby

  • If not treated, it may cause brain damage and death


Vitamin Deficiency Caused Anemia hematopoietic stem cell (P-HSC)

  • folic acid

  • vitamin B12

  • vitamin B6

  • vitamin C

  • vitamin E

Iron Deficiency Anemia hematopoietic stem cell (P-HSC)

  • How does iron deficiency affect O2 transport?

  • It could develop secondary to hemorrahegia

  • Iron deficiency may also present as a result of low iron intake or absorption problems in the GI tract

Red Bone Marrow in Aplastic Anemia hematopoietic stem cell (P-HSC)

Normal Red Bone Marrow

Polycythemia hematopoietic stem cell (P-HSC)

  • Total number of erythrocytes is more than the normal range

  • Polycythemia vera (erythremia):

    • Cancer of red bone marrow

    • RBC count 7-8 million/mm3

    • Hematocrit value 60-70 %

  • Secondary polycythemia: long term hypoxia

    • Cardiac failure

    • Pulmonary diseases

    • High altitude (physiological)

    • Sportive activity (physiological)

Polycythemia hematopoietic stem cell (P-HSC)

  • Causes an increase in blood pressure

  • Less blood supply to the tissues

  • Decreased blood flow as a result of increased viscosity

  • Color of the skin with polycythemia vera looks bluish (cyanotic) – subpapillary plexus

  • For treatment, blood whould be diluted with an isotonic solution (serum physiologic)

► Some athletes try to induce physiological polycythemia?

Why and How?

Secondary Polycythemia: hematopoietic stem cell (P-HSC)Long term hypoxia