Blood Cells

Red blood cell

White blood cell
Platelet

Dr. Humaira
Aman
 OBJECTIVES
• At the end of the lecture, student would be
able to:
 Identify the cells found in normal blood.
 Describe erythrocytes
 Know the normal parameters of RBC
 Define normal and abnormal morphology of
RBC
 Describe the functions of each cell.
 Define Erythropoiesis
 Blood Cells
Blood cells are erythrocyte (red blood cell, RBC),
leukocyte (white blood cell, WBC) and thrombocyte
(platelet, P).
Red blood cells (erythrocytes)
• Essentially a bag of hemoglobin.
• Circular, elastic, biconcave discs without nuclei.
7.8m, thickness 1~2.5 m.
Red blood cells cont..
– Average volume 90-
95 mm3
– Average area of a red
cell is 120 µ2

– Flexible

– About 1% of RBC are

reticulocytes (about
50,000/μL)
Red blood cell count Male: 4.32-5.72 trillion cells/L
(4.32-5.72 million cells/mcL)
Female: 3.90-5.03 trillion
cells/L
(3.90-5.03 million cells/mcL)

Hemoglobin Male: 13.5-17.5 grams/dL

(135-175 grams/L)
Female: 12.0-15.5 grams/dL
(120-155 grams/L)
Variation in RBC count
• Inc. at high attitude
• Inc. during muscular exercise
• Inc. with temperature
• Inc. in obstructive lung disease
• Dec. with Inc. oxygen tension
as in mines
 • Variation in size and
shape of RBC:
 Microcytosis= dec. size &
• Normocytic= vol. of RBC
 Macrocytosis= inc. size &
Normal RBC
vol. of RBC
 Anisocytosis= irregularity in
• Normochromic= size of RBC
Normal Hb conc.  Poikilocytosis= irregularity
In RBC in shape of RBC
 Polychromasia= irregularity
in color of RBC
 Spherocytosis= spherical –
shaped RBC
 Functions of RBC

• RBC can be used for transportation of

O2 and CO2 in the blood.
• RBC can be served as pH buffer.
Life and breakage of RBC
• Life-span: 120 days, about 4 months
• Breakage: places are liver, spleen and
lymphatic node, and after breakage, Hb
released from RBC immediately combine with
plasma α2-globulin (Hb touched protein) which
is taken in by liver for iron reuse.
 Erythropoiesis: Formation
of RBC (erythrocytes)
• Early few weeks of embryo nucleated RBCs are
formed in yolk sac.
• Middle trimester mainly in liver & spleen & lymph
nodes.
• Last months RBCs are formed in bone marrow of
all bones
• Bone marrow of flat bone continue to produce
RBC into adult life
• Shaft of long bone stop to produce RBC at
puberty while epiphysis continued
Hemopoietic process and hemopoietic
stem cells,
Committed
Stem Cells
Stages of differentiation of
RBC
– Stages of RBC development
• Committed stem cell
– Proerthroblast
– basophil erythroblast
– polychromatophil
erythroblast
– orthochromatic
erythroblast
– Reticulocytes
– Mature erythrocytes
• Rapid RBC production  
reticlocytes in the
circulation
Hematopoietic growth factors

Growth Factors Function: stimulate

progenitor of the followings:
GM-CSF (granulocyte- Granulocyte-monocyte
macrophage CSF)
G-CSF (granulocyte CSF) Granulocyte

M-CSF (macrophage CSF) Monocyte

EPO (Erythropoietin) Erythrocyte

IL-1,3,6 (Interleukin-3, 1, 6) Myeloid lineage

TPO (Thrombopoietin) Platelet

 ERYTHROPOIETIN
• Protein - Produced in the kidney
• Necessary for erythroid proliferation
and differentiation
• Absence results in apoptosis
(programmed cell death) of
erythroid committed cells
• Anemia of renal failure 2° to lack of
EPO
ERYTHROPOIETIN
Regulation of Production
Tissue oxygenation and RBC
formation
ERYTHROPOIETIN
Mechanism of Action
HEMOGLOBIN

Pavla Balínová
Hemoglobin
• What is it?
– Iron- bearing protein (conjugated) which is the main component of
the RBC
– Gives the red cell its color
• Synthesis
– Majority synthesized at the polychromatophilic normoblast stage
• Regulation
– Stimulated by tissue hypoxia
– Hypoxia causes the kidneys to increase production of EPO, which
increases RBC and hemoglobin production
• Function
– Carry oxygen from the lungs to the tissues
– Remove CO2
– Buffering action, maintains blood pH as it changes from
oxyhemoglobin (carrying O2) to deoxyhemoglobin ( without O2)
Hemoglobin Reference
Ranges
• Adults
– Male 13-17 g/dl
– Female12-16 g/dl

• Children
– Birth 13.5-20.0 g/dl
– 6-12 years 11.5-15.5 g/dl
Structure
 Heme group
• Porphyrin ring
• Ferrous iron
 4 polypeptide
Subunits
(Globin chain)
– 2 Alpha Chains
– 2 Beta chains
Structure of hemoglobin
• each globin contains 1 heme group with a central
Fe2+ ion (ferrous ion)

Figure is found at http://faculty.etsu.edu/currie/images/hemat3.jpg

Heme structure
(cyclic tetrapyrrole)
•Heme contains:
 conjugated system of
double bonds → red
colour
 4 nitrogen (N) atoms

 1 iron cation (Fe2+)

→ bound in the middle of
tetrapyrrole skelet by
coordination covalent
bonds
methine bridge pyrrole ring
 Properties of iron in heme

• Coordination number
of iron in heme = 6

6 bonds:
• 4x pyrrole ring
(A,B,C,D)
• 1x link to a protein
• 1x link to an oxygen
Adult haemoblobin
Hb A Hb A2 Hb F

structure a22 a2d2 a22

% Normal % 96-98 % 1.5-3.2 % 0.5-0.8

Abnormal Hb
Hb S
Hb C
Hb E
Methemoglobin
Hemoglobin Synthesis
• Synthesis
– Occurs in the mitochondria of developing red
cells as they mature in the bone marrow
– Processes necessary for normal synthesis
• Adequate iron supply & delivery
• Adequate synthesis of protoporphyrins
• Adequate globin synthesis
: Heme synthesis
 Final formation of heme

• Fe2+ is incorporated into protoporphyrin IX

• reaction is catalyzed by enzyme heme synthase

Figure was assumed from http://www.porphyrin.net/mediporph/_netbiochem/synthesis/

ferrochelatase.html
Hemoglobin Synthesis
Normal Hemoglobin Function
• When fully saturated, each gram of hemoglobin
binds 1.34 ml of oxygen.
• The degree of saturation is related to the oxygen
tension (pO2), which normally ranges from 100
mm Hg in arterial blood to about 35 mm Hg in
veins.
• The relation between oxygen tension and
hemoglobin oxygen saturation is described by the
oxygen-dissociation curve of hemoglobin.
• The characteristics of this curve are related in part
to properties of hemoglobin itself and in part to
the environment within the erythrocyte, including
pH, temperature, ionic strength, and
concentration of phosphorylated compounds,
especially 2,3-diphosphoglycerate (2,3-DPG).
Oxygen transport
• The amount of O2 bound to hemoglobin
and released to tissues depends on PO2
and PCO2, but also the affinity of
hemoglobin for O2.
• Oxyhemoglobin: hemoglobin with oxygen
• Deoxyhemoglobin: hemoglobin without
oxygen
• Oxygen affinity is the ease with which
hemoglobin binds and releases oxygen.
Oxygen Affinity
• Determines the proportion of O2 released
to the tissues or loaded onto the cell at a
given oxygen pressure.
• Increases in oxygen affinity means
hemoglobin has an increased affinity for
O2, so it binds more. However, it does
not want to give it up.
• Decreases in oxygen affinity, cause O 2 to
be released.
Bohr Effect
• Alterations in blood pH, shifts
oxygen dissociation curve
• In acidic pH, the curve shifts to the
right
• Results in an enhanced capacity to
release O2 where it is needed
Hb-oxygen
dissociation curve
 The
normal position of curve
depends on

 Concentration of 2,3-DPG
 H+ ion concentration (pH)
 CO2 in red blood cells
 Structure of Hb
Oxygen Dissociation Curve
• Right-Shift
– Hgb has less attraction
for O2
– Hgb willing to release
O2 to tissue
– Examples: anemia,
acidosis
– Even though there may
be less RBC’s, they act
more efficiently to
deliver O2 to target
Oxygen Dissociation
Curve
• Left shift
– Hgb has more
attraction for O2
– Hgb less willing to
release O2 to
tissue
– Examples: ,
alkalosis
Hb-oxygen
dissociation curve
 Right shift (easy oxygen delivery)
 High 2,3-DPG
 High H+
 High CO2
 HbS

 Left shift (give up oxygen less

readily)
 Low 2,3-DPG
 HbF
Functions of
Haemoglobin
 Oxygen delivery to the tissues
 Reaction of Hb & oxygen

 Oxygenation not oxidation

 One Hb can bind to four O2 molecules
 Less than .01 sec required for oxygenation
 chain move closer when oxygenated
 When oxygenated 2,3-DPG is pushed out
 chains are pulled apart when O2 is
unloaded, permitting entry of 2,3-DPG
resulting in lower affinity of O2
Oxy &
deoxyhaemoglobin