RBC Anemia and polycythemia pdf - Dr. Mohammed Fatih

RBC Anemia and polycythemia

Red Blood Cells (Erythrocytes):
Functions of RBC:

The major function of red blood cells, also known as

erythrocytes,

is to transport

hemoglobin,

which in turn

carries oxygen

from the

lungs to the tissues.
The red blood cells contain a large quantity of

carbonic anhydrase

an enzyme that catalyzes the reversible reaction between carbon
dioxide (CO2) and water to form carbonic acid (H2CO3),
. The rapidity of this reaction makes it possible for the water of the
blood to

transport enormous quantities of CO2

in the form of

bicarbonate ion (HCO3–) from the tissues to the lungs, where it is
reconverted  to  CO2  and  expelled  into  the  atmosphere  as  a  body
waste product.
The  hemoglobin  in  the  cells  is  an  excellent

acid-base buffer

(as is

true of most proteins), so that the red blood cells are responsible
for most of the acid-base buffering power of whole blood.

Shape and Size of Red Blood Cells:

Normal red blood cells, are

biconcave

discs having a mean

diameter of about 7.8 micrometers
The red blood cell is a “bag” that can be deformed into almost any
shape.

Concentration of Red Blood Cells in the Blood:

In normal

men

, the average number of red blood cells per cubic

millimeter is 5,200,000;
in normal

women

, it is 4,700,000.

Persons living at high altitudes have greater numbers of red blood
cells.

Quantity of Hemoglobin in the Cells:-

When the hematocrit and the quantity of hemoglobin in each

respective cell are normal, the whole blood of men contains an
average of

grams of hemoglobin per 100 milliliters of cells (dl);

for women, it contains an average of

grams per 100 milliliters

(dl).

Each gram of pure hemoglobin is capable of combining with

1.34

milliliters of oxygen.

Production of Red Blood Cells

Areas of the Body That Produce Red Blood Cells.

In the

early

weeks

of embryonic life, primitive, nucleated red blood cells are

produced in the

yolk sac

. During the

middle

trimester

of gestation,

the

liver

is the main organ for production of red blood cells, but

reasonable numbers are also produced in the

spleen

and

lymph

nodes

. Then, during the

last

month

or so of gestation and after

birth, red blood cells are produced exclusively in the

bone marrow

The bone marrow of essentially all bones produces red blood

cells until a person is

years old

. The marrow of the long bones,

except for the proximal portions of the humeri and tibiae, becomes
quite fatty and produces no more red blood cells after about age

years

. Beyond this age, most red cells continue to be produced in the

marrow of the membranous bones, such as the

vertebrae,

sternum,

ribs

and

ilia

. Even in these

bones, the marrow
becomes less
productive as age
increases.

Genesis of Blood Cells:

Pluripotential Hematopoietic Stem Cells, Growth Inducers, and

Differentiation Inducers.

The blood cells

begin

their lives in the bone marrow from a single type

of cell called the

pluripotential hematopoietic

stem cell, from which all the

cells of the circulating blood are eventually derived.

As these cells reproduce, a small portion of them

remains exactly

like

the original pluripotential cells and is retained in the bone marrow to
maintain a supply of these, although their numbers diminish with age.

The intermediate stage cells are very much like the pluripotential stem

cells, even though they have already become committed to a particular line
of cells and are called

committed stem cells.

A committed stem cell that produces erythrocytes is called a colony-forming
unit–erythrocyte, and the abbreviation

CFU-E

is used to designate this type

of stem cell. Likewise, colony-forming units that form granulocytes and
monocytes have the designation

CFU-GM

, and so. Growth and reproduction

of the different stem cells are controlled by multiple proteins called

growth

inducers

Four major growth inducers have been described, each having different
characteristics. One of these,

interleukin-3

, promotes growth and

reproduction of virtually all the different types of committed stem cells,
whereas the others induce growth of only specific types of cells.

Differentiation

inducers

. causes one type of committed stem cell to

differentiate one or more steps toward a final adult blood cell.

Formation of the growth inducers and differentiation inducers is itself

controlled

factors

outside

the bone marrow. For instance, in the case of

erythrocytes

(red

blood

cells),

exposure of the blood to low oxygen for a long

time results in growth induction, differentiation, and production of greatly
increased numbers of erythrocytes. In the case of some of the

white

blood

cells, infectious diseases cause growth, differentiation, and eventual
formation of specific types of white blood cells that are needed to combat
each infection.

Stages of Differentiation of Red Blood Cells:

The first cell that can be identified as belonging to the red

blood cell series is the

proerythroblast

, once the proerythroblast has

been formed, it divides multiple times. The first-generation cells are
called

basophil

erythroblasts

because they stain with basic dyes; the

cell at this time has accumulated very little

hemoglobin

. In the

succeeding generations, the cells become filled with hemoglobin, the
nucleus

condenses

to a small size, and its final remnant is absorbed

or extruded from the cell. At the same time, the

endoplasmic

reticulum is also reabsorbed.

The cell at this stage is called a

reticulocyte

because it still contains

a small amount of basophilic material, consisting of remnants of the

Golgi

apparatus,

mitochondria

, and a few other cytoplasmic

organelles

. During this reticulocyte stage, the cells pass from the

bone marrow into the blood capillaries by diapedesis (squeezing
through the pores of the capillary membrane).

The remaining basophilic material in the reticulocyte

normally disappears within 1 to 2 days, and the cell is then a

mature

erythrocyte

. Because of the short life of the reticulocytes, their

concentration among all the red cells of the blood is normally

0.5

–

2.5

per

cent

Regulation of Red Blood Cell Production—Role of
Erythropoietin

The total mass of red blood cells in the circulatory system

is regulated within narrow limits, so that
(1) an

adequate

number of red cells is always available to provide

sufficient transport of oxygen from the lungs to the tissues,
(2) the cells do not become so numerous that they

impede

blood

flow.

Tissue

Oxygenation

Is the Most Essential Regulator of Red Blood

Cell Production.

Any condition that causes the quantity of oxygen

transported to the tissues to decrease ordinarily increases the rate of
red blood cell production. Thus, when a person becomes extremely

anemic

as a result of hemorrhage or any other condition, the bone

marrow immediately begins to produce large quantities of red blood
cells. Also, destruction of major portions of the bone marrow by any
means,  especially  by  x-ray  therapy,  causes  hyperplasia  of  the
remaining  bone  marrow,  thereby  attempting  to  supply  the  demand
for red blood cells in the body.

At very high altitudes, where the

quantity

oxygen

in the

air  is  greatly  decreased,  insufficient  oxygen  is  transported  to  the
tissues, and red cell production is greatly increased.
Various  diseases  of  the

circulation

that cause decreased blood flow

through the peripheral vessels, and particularly those that cause

failure

oxygen

absorption

by the blood as it passes through the

lungs, can also increase the rate of red cell production. This is
especially apparent in prolonged

cardiac failure

and in many

lung

diseases

, because the tissue hypoxia resulting from these conditions

increases red cell production, with a resultant increase in
hematocrit and usually total blood volume as well.

Erythropoietin Stimulates Red Cell Production, and Its Formation
Increases in Response to Hypoxia

The principal stimulus for red blood cell production in low

oxygen states is a circulating hormone called erythropoietin.
hypoxia causes a marked increase in erythropoietin production, and
the erythropoietin in turn enhances red blood cell production until
the hypoxia is relieved.

Role of the Kidneys in Formation of Erythropoietin.

In the normal person, about

90 per cent

of all

erythropoietin is  formed in  the kidneys  (tubular epithelial  cells  and
stimulated  by  oxygen  concentration  in  blood)  the  remainder  is
formed mainly in the liver.
Hypoxia  in  other  parts  of  the  body,  but  not  in  the  kidneys,
stimulates  kidney  erythropoietin  secretion,  In  particular,  both

norepinephrine

and

epinephrine

and several of the prostaglandins

stimulate erythropoietin production.
when the kidneys are destroyed by renal disease, the person
invariably becomes very anemic.

Effect of Erythropoietin in Erythrogenesis.

At hypoxia erythropoietin secretion is increased which

then

stimulate

the

production

proerythroblasts

from

hematopoietic  stem  cells  in  the  bone  marrow.  In  addition,  once  the
proerythroblasts  are  formed,  the    erythropoietin  causes  these  cells
to  pass  more  rapidly  through  the  different  erythroblastic  stages
than they normally do.

the rate of red blood cell production

can rise to perhaps 10

or more times normal.

Low oxygen
level

Anemia

Pulmonary or
cardiac diseases

Poor blood flow