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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Red Blood Cells (Erythrocytes)

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Red blood cells erythrocytes

Red Blood Cells (Erythrocytes)


Er ythrocytes rbc

Erythrocytes (RBC)

  • Structure

    • Biconcave disc shape

  • Includes

    • Hemoglobin

    • Lipids, ATP, carbonic anhydrase

  • Function

    • O2 and CO2 transport


Red blood cells erythrocytes

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


Red blood cells erythrocytes

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


Red blood cells erythrocytes

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)


Red blood cells erythrocytes

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


Hemoglobin

Hemoglobin

  • 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


Embryonic stem cells

Embryonic Stem Cells

Human ESC


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 cells

Potentiality of Stem Cells


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

Monocytes

Platelets

Granulocytes

Myeloid Stem Cell

Hemocytoblast

Lymphoid Stem Cell

Lymphocytes


Formation of multiple different blood cells from pluripotent hematopoietic stem cell p hsc

Formation of multiple different blood cells from pluripotent hematopoietic stem cell (P-HSC)


Erythropoiesis production of rbc

Erythropoiesis (production of RBC)

Weeks 16-20

Week 2

Week 6

Birth

Week 8

Myeloid phase

Spleen

Hepatic phase

Mesoblastic phase

Myeloid phase

Prenatal Life

Postnatal Life


Red blood cells erythrocytes

Prenatal 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


Red blood cells erythrocytes

Prenatal 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 )


Red blood cells erythrocytes

Prenatal period-3

  • myeloid phase

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

    • All bones

    • Hemopoiesis

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


Red blood cells erythrocytes

Postnatal 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


Red blood cells erythrocytes

Sites of hemopoiesis in postnatal life


Red blood cells erythrocytes

Erythropoiesis

  • BFU-E and CFU-E cells

    • Response to different levels of EPO

  • proerythroblast

  • basophil erythroblast

  • Polychromatophil erythroblast

  • Orthochromatophil erythroblast

  • Reticulocyte

  • Erythrocytes


Red blood cells erythrocytes

Genesis of Red Blood Cells


Red blood cells erythrocytes

Regulation of Erythropoiesis

  • Primary stimulus is hypoxia

  • Tissue oxygenation

    • Blood flow

    • Blood hemoglobin levels

    • Oxygen saturation of hemoglobin

    • Affinity of hemoglobin to oxygen


Red blood cells erythrocytes

Erythropoietin (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


Red blood cells erythrocytes

Regulation of Erythropoiesis


E rythropoiesis

Erythropoiesis

  • Erythropoietin: a hormone that stimulates erythropoiesis

    • It stimulates both differentiation and maturation


Red blood cells erythrocytes

Maturation of red blood cells – Vit B12 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


Red blood cells erythrocytes

Deformability of Erythrocytes


Red blood cells erythrocytes

Hemoglobin (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

  • 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

Hemoglobin

  • 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 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

  • 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

  • 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


Red blood cells erythrocytes

Iron – Fe+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


Red blood cells erythrocytes

Transferrin - siderofilin

  • 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%)


Red blood cells erythrocytes

Absorption of iron

  • 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


Red blood cells erythrocytes

Iron Transport and Metabolism


Red blood cells erythrocytes

Iron Overload Disease

  • hemosiderin

  • hemochromatosis

    • Bronze diabetes

    • Cirrhosis

    • Cancer

    • Gonadal atrophy


Red blood cells erythrocytes

Iron Deficiency

  • 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


Red blood cells erythrocytes

Other factors

  • Time of iron supplementation

  • Injections in cases of absorption problems

  • Overload of iron facilitates production of microorganisms

    • transferrin and lactoferrin are anti-microbial


Red blood cells erythrocytes

Anemia

  • 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


Red blood cells erythrocytes

Classification of Anemias

  • Hemorrhagic anemias; blood loss

  • Hemolytic anemias; hemolysis

  • Vitamin deficiency anemias (megaloblastic anemia)

  • Iron deficiency anemia

  • EPO deficiency caused anemia

  • Aplastic anemia (Fanconi anemia)


Red blood cells erythrocytes

Hemolytic Anemias

  • 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 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 (SCA)

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


Red blood cells erythrocytes

Thalassaemia (Mediterranean Anemia)

  • 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

  • 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 DEFICIENCYFunction of G6PD


Glucose 6 phosphate dehydrogenase g6pd anemia

Glucose -6-Phosphate Dehydrogenase (G6PD) Anemia

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

Erythroblastosis 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

  • http://www.pubmedcentral.nih.gov/pagerender.fcgi?artid=1871554&pageindex=1


Red blood cells erythrocytes

Vitamin Deficiency Caused Anemia

  • folic acid

  • vitamin B12

  • vitamin B6

  • vitamin C

  • vitamin E


Red blood cells erythrocytes

Iron Deficiency Anemia

  • 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 blood cells erythrocytes

Red Bone Marrow in Aplastic Anemia

Normal Red Bone Marrow


Red blood cells erythrocytes

Polycythemia

  • 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)


Red blood cells erythrocytes

Polycythemia

  • 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?


Red blood cells erythrocytes

Secondary Polycythemia: Long term hypoxia


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