Blood Composition of blood - PowerPoint Presentation

Slide1

Blood

Composition of blood

Cells & Plasma

Cells 1. RBC :

Erythroid

2. WBC : Myeloid

Neutrophils

Basophils

Eosinophils

:Lymphoid cells

Lymphocytes

: Macrophage system

Monocytes

3. Platelets

Hemopoiesis

Committed stem cells

Hemopoiesis

Pleuripotent

hemopoietic

stem cell differentiate into Committed stem cells maturing in a particular cell eg Colony forming unit (CFU)erythrocyte will mature into an erythrocyte . GM-CFU into granulocytes & Monocyte.

Growth promoters like Interleukin-3 induce growth of all the cells in bone marrow.

Differentiation factors like GM –CSF stimulates the differentiation of

monocytes

and except

basophil

all the granulocytes.

Lymphocytes are differentiate & mature in Thymus (T cell) /

bursal

equivalent(B cell)

eg

liver in mid fetal life & bone marrow in late fetal life & after birth.

Erythropoiesis

Areas

: yolk sac: primitive embryo

Liver :mid gestation

Spleen & LN also contributeBone marrow : After birth & adultStages of

erythropoiesis

Pleuripotent

& Committed cells ( CFU- E)

Proerythoblast: First identifiable cell of series derived from CFU-E & it give rise basophilic erythroblast (early normoblast) with little Hb. Next generation cell Polychromatophilic erythroblast ( intermidiate normoblast)has Hb saturation of 34% & this gives Orthochromatic erythroblast (Late Normoblast) & subsequently Reticulocyte (Golgi body & mitochondrion turns into reticulum) which disappears within 1-2 days. 1-2 % of circulating RBC are actually reticulocytes.

Early

normoblast

Intermediate

normoblast

Late

Normoblast

Red Blood Corpuscle (RBC)

RBC : biconcave disk ,7.5

μ

M diameter 2.5

μM thick at periphery , contains 29 pg

Hb

. 5.4 million/

μ

L (male) 4.8 (Female)in number

Characteristics of RBC Variable CalculatnMale Female

Hematocrit

47%

42%

RBC Count

5.4

m/

μ

L

4.8 m/μLHemoglobin16 G%14 G%Mean Corpuscular Volume (MCV)Hct x10 RBC count87 fL 87 fLMean Corpuscular Hemoglobin MCHHb x10RBCcount29 pG29 pGMean corp Hb Conc MCHC Hbx100Hct 34%34%

Role of erythropoietin, B12 & Folate in

Erythropoiesis

Hypoxia causes increase in erythropoietin production from kidney, erythropoietin in turn enhances RBC production

Formation of Erythropoietin. (EP) 90%

erythropoietin in kidney 10% in liver. In the kidneys the erythropoietin is formed in tubular epithelial cells.

Ep

stimulates

hemopoietic

stem cell to proliferate into

proerythroblast. Vitamin B12 and folic acid are essential for the synthesis of thymidine triphosphate, & DNA ,hence, deficiency cause failure of nuclear maturation & cell division. The erythroblastic cells of bone marrow, fail to proliferate rapidly, produce macrocytes, with weak cell membrane & oval in shape cells.

Features of Iron, B12 & folate deficiency

anemias

Pathology

Hemoglobin

RBC Count

MCV

MCH

MCHC

Iron deficiencyMale< 13.6Female < 12.0 LessMale <4.3Female 3.5 Less < 75 μ Lreduced < 25 pGreduced

< 27 reduced

B12 & folic acid deficiencyLess

Less > 110

Normal/ reducedNormal

Bone marrow

Normoblast

Megaloblast

Classification of Anemia according to Underlying Cause

Blood Loss

Acute: trauma

Chronic: lesions of gastrointestinal tract, gynecologic disturbances

Defect in RBC Increased Destruction (Hemolytic Anemias

)

(A) Intrinsic (

intracorpuscular

) abnormalities

(a)Hereditary membrane abnormalities Membrane skeleton proteins: spherocytosis, elliptocytosis (b) Hereditory Enzyme deficiencies Glycolytic enzymes: pyruvate kinase, hexokinase,Enzymes of hexose monophosphate shunt: glucose-6-phosphate dehydrogenase, glutathione synthetase.

Classification by underlying Mechanism

Deficiency of dietary factors/ Abnormal

Hb

Synthesis

Iron : Microcytic Hypochromic

B12 :

Macrocytic

or

Megaloblatic

anemiaFolic acid : Macrocytic or Megaloblatic anemia

Hereditary Spherocytosis

In HS primary abnormality is in supportive skeleton on IC face of RBC wall.

Spectrin

, linked to membrane at two points: through

ankyrin & band 4.2 to membrane protein band 3; & through band 4.1 to protein glycophorin. Horizontal spectrin

-

spectrin

&

spectrin

-intrinsic membrane protein interactions stabilize membrane & are responsible for shape, strength, flexibility of RBC.

Hereditary Spherocytosis

Most common pathogenic feature of HS is mutation particularly of band3,ankyrin &

spectrin

gene. In all types of HS red cell wall stability is reduced , consequently lose membrane fragments while retaining most of their volume. As a result, ratio of surface area to volume of HS cells decreases until the cells become spherical.

Disorders of Hb & RBC production

Hemoglobin

Deficient

globin

synthesis :Thalassemia syndrome Abnormal

globin

synthesis: Sickle cell anemia

RBC production

Failure of erythroblast maturation : B12 & Folate deficiencyDefect of Heme synthesis Iron deficiency The most common cause of anemia in India followed by B12 & folate deficiency

Hemoglobin

Hemoglobin is made up of 4 subunits, each have a

Heme

moiety & polypeptide chain.

HBA has one pair of α & one pair of β

globin

chain(2

α

2 β)HbA2 (2.5%) of Hb has 2α2δHbA1c glycated by glucose in diabetics if > 6.9% indicate poor control of blood sugarFetal Hb (2α2γ) has more affinity for O2 since it bind less avidly to 2,3-DPG and carries more O2 for a given pO2.

Reactions of Hemoglobin

Each of four iron atoms in hemoglobin can reversibly bind one O

2

molecule. Iron is in ferrous state, so reaction is

oxygenation, not oxidation. Because it contains 4 deoxyhemoglobin (Hb)

units,Hb

molecule represented as Hb

4

,& it actually reacts with four molecules of O

2 to form Hb4O Hb4 + O2↔ Hb4O2, Hb4O2+O2 ↔ Hb4O4 H b4O4+O2 ↔ Hb4O6 Hb4O6 +O2 ↔Hb4

O8 Deoxygenated Hb,

globin is tightly bound in tense state so low affinity for O2. Binding of one O2 loosens the binding & increase affinity for O

2, 500 times when all 4 Hb are bound with O2

Hemoglobin reactions

Methemoglobin

: Oxidizing agent & drugs convert

Hb

to methHb leading to dusky color of skin. Normally meth hemoglobin formed is converted to Hb by NADH-meth hemoglobin reductase

,. Absence of which in children cause congenital

methemoglobinemia

.

Carboxyhemoglobin

: Hemoglobin has more affinity for Carbon monoxide than for O2 which replaces O2 (CO posioning) withreduced O2 carrying capacity of Hb.

Sickle cell anemia

In

HbS

, substitution of valine

for glutamic acid at 6th position of β-chain, produces HbS.

Homozygotes

all

HbA

replaced by

HbS. Heterozygote about half is replaced. Deoxygenation, HbS molecules crystallize which distort RBC as elongated crescent or sickle. Sickling initially reversible upon reoxygenation; Later on cell wall damage occurs with each episode of sickling, & finally cells accumulate calcium, lose potassium and water, and become irreversibly sickled.

Thalassemia

Inherited disorder caused by mutations that decreases synthesis of α- or β-

globin

chains. So deficiency of hemoglobin, red cell abnormalities due to excess of other unaffected globin chain. The α chains are encoded by two α-

globin

genes, which lie in tandem on chromosome 11, while the β chains are encoded by a single β-

globin

gene located on chromosome 16. The mutations that cause

thalassemia are particularly common among Mediterranean, African, and Asian populations.