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Describe the sites of erythropoiesis

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(RBC)

(2)

Learning Objectives

At the end of the session you must be able to :

Describe the morphology and function of RBC

Describe the sites of erythropoiesis

Describe Stages of Differentiation of Red Blood Cells

Enumerate the factors regulating

erythropoiesis

(3)

Q.1. Which dietary component is needed for the synthesis of DNA and influences the production of RBCs?

a. Calcium b. Iron

c. Vitamin A d. Folic acid e. Vitamin D

MCQ

(4)

MCQ

Q.2. 1 gm of haemoglobin can combine with?

a. 13.4 ml of oxygen

b. 1.34 ml of oxygen

c. 20 ml of oxygen

d. 2 ml of oxygen

(5)

Q.3. The hormone erythropoietin stimulates red blood cell production in the red bone marrow. Where in the body is erythropoietin produced?

a) Spleen b) Kidney c) Liver

d) Thyroid

MCQ

(6)

Red Blood Cell = Erythrocyte

Red blood cells (RBC) constitute 99 % of cellular component of blood.

Lacks a nucleus, and contains

hemoglobin—a red, iron-rich protein that binds oxygen.

Function in the transportation of oxygen to

cells and tissues and carbon dioxide from

cells and tissues to the lungs for exchange

with O2

(7)

Hematocrit?

Adult males: 42%-54%

Adult women: 38%-46%

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RBC Morphology

RBC is a flexible ,

biconcave disc like cell.

Diameter – 7.2 μm (6.9-7.4)

Thickness – 2.5 μm at

periphery & 1 μm at centre

The average volume of

the RBC is 90 – 95 μm3 .

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RBC Morphology

Cross section of capillary with red blood cells

Human red blood cells (4,000× magnification).

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RBC Morphology

Advantages of biconcave shape –

Flexible capillaries minimum diameter – 3.5 μm.

RBC a “bag” that can be deformed into almost any shape.

Greater surface area

Can withstand changes of osmotic pressure

Allow easy exchange of O2, CO2 & rapid diffusion of other substances.

Spectrin

a contractile protein

maintains shape and flexibility of RBC

(11)

Normal counts

Counts are measured as the number of red cells per cubic millimeters (mm3) of blood.

At birth – 6-7 millions/mm3

Adult males – 5-6 millions/mm3

Adult females – 4.5-5.5 millions/mm3

Persons living at high altitudes have greater numbers of RBCs

(12)

Heamoglobin conc. of RBC

The whole blood of men contains an average of 15 g of Hb / 100 ml of blood

for women, it contains an average of 14 g / 100 ml

1 gram of hemoglobin can combine with 1.34 ml of oxygen.

Therefore, in a normal man a maximum of about 20 ml of oxygen can be carried in hemoglobin in each 100 ml of blood,

In a normal woman 19 ml of oxygen can be carried.

(13)

MCV MCH

MCHC

(14)

Erythropoiesis

Erythropoiesis (from Greek 'erythro'

meaning "red" and 'poiesis' meaning "to make") is the process which produces

red blood cells (erythrocytes).

(15)

Sites of Erythropoiesis

During intrauterine life

Mesoblastic stage/Intravascular stage (3rd week to 3 months)

Yolk sac (nucleated RBC)

Hepatic stage (after 3 months)

Liver and spleen

Myeloid stage (20th week – till birth)

Bone marrow

(16)

Sites of Erythropoiesis

In children

Bone marrow of all bones (till 5 years of age)

Marrow of only long bones (till 20 years of age

In adults (after 20yrs)

Proximal portions of the humeri, femur and tibiae,

Skull

Vertebrae

Ribs

Sternum

pelvis

Membranous bones

(17)

Sites of Erythropoiesis

(18)

Stages of Erythropoiesis

The blood cells begin their lives in the bone marrow from a single type of cell called the pluripotential hematopoietic stem cell (PHSC).

Hematopoietic stem cells (HSCs) are bone marrow cells that are capable of producing all types of

blood cells.

They differentiate into one or another type of

committed stem cells (progenitor cells). These in turn form the various differentiated types of blood cells.

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Stages of Erythropoiesis

Committed stem cell that produces erythrocytes is called Colony-forming unit–erythrocyte, CFU-E

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PHSC Pluripotent Hemopoietic stem cell BFU-E Burst Forming Unit Erythrocyte CFU-E Colony Forming Unit Erythrocyte

PROERYTHROBLAST

BASOPHILIC ERYTHROBLAST

POLYCHROMATOPHILIC ERYTHROBLAST ORTHOCHROMATIC ERYTHROBLAST

RETICULOCYTE ERYTHROCYTE ERYTHROCYTE

E R Y T H R O P O I E S I S GM CSF erythro

IL-1,IL-6,IL-3

GM CSF erythro

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PHSC Pluripotent Hemopoietic stem cell BFU-E Burst Forming Unit Erythrocyte CFU-E Colony Forming Unit Erythrocyte

PROERYTHROBLAST EARLY NORMOBLAST

INTERMEDIATE NORMOBLAST LATE NORMOBLAST

RETICULOCYTE ERYTHROCYTE ERYTHROCYTE

E R Y T H R O P O I E S I S GM CSF erythro

IL-1,IL-6,IL-3

GM CSF erythro

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ERYTHROPOIESIS

15-20µm- basophilic cytoplasm, nucleus with nucleoli.

14-17 µm-mitosis, basophilic

cytoplasm, nucleoli disappears.

10-15µm- ’POLYCHROMASIA’

Hb appears, nucleus condenses.

7-10µm- PYKNOTIC Nucleus.

Extrusion, Hb is maximum.

7.3µm- Reticulum of basophilic material in the cytoplasm.

7.2µm- Mature red cell with Hb.

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CELLS/FEATURES SIZE CYTOPLASM NUCLEUS HAEMOGLOB IN

PROERYTHROBLAST 15‐20

μm BASOPHILIC LARGE WITH RETICULAR FORMATION

ABSENT

EARLY 12‐

16μm BASOPHILIC LARGE,NUCLEOLI

DISAPPEARED. ABSENT

INTERMEDIATE 10‐

14μm

POLYCHROM

ATIC CONDENSED APPEARS

LATE 8‐

10μm

ACIDOPHILI C

SMALL

PYKNOTIC INCREASES

RETICULOCYTE 7‐

7.5μm

RETICULUM

LIKE ABSENT INCREASES

(24)

Factors Affecting Erythropoiesis

Erythropoietin (EPO): major humoral regulator of erythropoiesis

Interleukins:

IL3, IL6 & IL1

Iron

Vitamin B12 (Cyanocobalamine) + Folic Acid + Vitamin C(Ascorbic Acid)

Intrinsic factor for absorption of B12

(25)

Erythropoietin

The principal stimulus for red blood cell is a circulating hormone called erythropoietin.

Glycoprotein MW-34000.

90% formed in endothelial cells of the

peritubular capillaries of the renal tubules.

10% formed in liver, hepatic cells & Kupffer cells.

(26)

Stimuli for production of erythropoeitin

hypoxia,

high altitude,

anemia,

chronic lung or heart diseases,

catecholamines,

prostaglandins &

androgens.

Formed in hours, RBC’s take 2-3 days to appear in peripheral blood.

Erythropoietin

(27)

Erythropoietin

erythropoietin causes the cells to pass more rapidly through the different erythroblastic stages than they normally do

The rapid production of cells continues as long as the person remains in a low O2 state or until enough RBCs have been produced to carry adequate

amounts of O2 to the tissues.

(28)
(29)

Vitamin B12, Folic Acid and Intrinsic Factor

important for final maturation of the RBCs are two vitamins, vitamin B12 and folic acid - essential for the synthesis of DNA,

Larger than normal red cells called macrocytes – irregular and oval - their fragility causes them to have a short life.

The parietal cells of the gastric glands secrete a glycoprotein called intrinsic factor, which

combines with vitamin B12 in food and makes the B12 available for absorption by the gut

(30)
(31)

Q.1. Which dietary component is needed for the synthesis of DNA and influences the production of RBCs?

a. Calcium b. Iron

c. Vitamin A d. Folic acid e. Vitamin D

MCQ

(32)

MCQ

Q.2. 1 gm of haemoglobin can combine with?

a. 13.4 ml of oxygen

b. 1.34 ml of oxygen

c. 20 ml of oxygen

d. 2 ml of oxygen

(33)

Q.3. The hormone erythropoietin stimulates red blood cell production in the red bone marrow. Where in the body is erythropoietin produced?

a) Spleen b) Kidney c) Liver

d) Thyroid

MCQ

References

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