Blood Lectures

Lecture 2- Red Blood Cells (Erythrocytes)

Taye J. Lasisi, BDS, MSc, FMCDS, FWACS

08/03/2017
 Objectives
• To state the normal red blood cells indices.
• Outline the structure of hemoglobin and its
role in O2 transport.
• Discuss the production and destruction of
RBC.
• Describe ABO and Rh blood groups and their
determination.
• Mention clinical relevance
 Erythrocytes
• RBCs are biconcave discs.
• Flexible, Elastic.
• Shape provides increased
surface area for  efficiency for
diffusion of O2 & CO2
• 7-8 m diameter (>9m –
macrocytes, <6m- microcytes)
• 2.2m at edge & 1m at centre.
• Lack nuclei & mitochondria
• 4.5-5 million/mm3(females)
5million/mm3 (males)
 Properties
• Function - Transport oxygen to other cells of
the body.

• Life cycle – 100- 120 days

• Plasma membrane is composed of 50-60%

protein and 35-40% lipids, flexible and bears
antigens.
 Red Cell Production
• A process called erythropoiesis

• Begins in the embryonic yolk sac, continued in

the liver, spleen and lymph nodes in the
maturing fetus.

• The process is restricted to the bone marrow by

the end of pregnancy and after birth.

• All circulating blood cells are derived from

pluripotential hemopoietic stem cells.
 Red Cell Production

• PSC divide and develop into erythroid stem cells

(committed stem cells) to form RBC.

• Further division and maturation with synthesis of

hemoglobin to form normoblast.

• Nuclear material is extruded and the endoplasmic

reticulum is resorbed to form reticulocyte.

• The reticulocyte matures to become erythrocytes

Erythropoiesis
Erythropoiesis Mechanism
•Proliferation

• Differentiation

• Maturation

• Release

• Functional RBC

• Senile RBC 8
Erythropoiesis
9
 Formation of Hemoglobin
• Begins when the RBC is in the proerythroblast
stage and continues into the reticulocyte stage.

• The heme molecule combines with a polypeptide

chain called a globin to form a subunit of
hemoglobin called a hemoglobin chain. 

• Four hemoglobin chains bind together loosely to

form the entire hemoglobin molecule.
 Factors Needed for Formation of RBC

• Amino acids (globin formation)

• Iron (heme formation)

• Vitamin B12 (DNA maturation)

• Folic acid (vitamin B9) (DNA maturation)

• Vitamin B2 and B6 (co factors in DNA synthesis and

maturation)
 Regulation of Erythropoiesis
• The total mass of RBCs in the blood is regulated
within very narrow limits.

• Any condition that causes the quantity of O2

transported in the tissues to decrease, ordinarily
increases the rate of RBC production.

• Erythropoietin: principal factor that stimulates

RBC production.
Factors that Regulate Erythropoiesis

•State of bone marrow

•Micro-environment
•Stem cells
•Nutrients
•Hypoxia
•Erythropoietin

13
Regulation of Erythropoiesis
14
 ABO Blood Group

– 4 blood types: A, B, AB, O

– Types are identified by antigens located on the
RBC surface.
• Antigens – protein substances that can
stimulate the body to make antibodies.
• Antibody – proteins made by the body in
response to stimulation by an antigen –
• Antigen-antibody reaction causes clumping or
agglutination in the case of RBCs.
 ABO blood group
• Typing and cross-matching – process by which
blood type is identified and donor blood is
tested for possible transfusion.
• Transfusion:
– Type O is a “universal donor”, i.e. can give blood to
anyone.
– Type AB is the “universal recipient”, i.e. can
receive blood from anyone.
 Clinical Relevance: Transfusion Reactions
• People with Type A blood make
antibodies to Type B RBCs, but
not to Type A
• Type B blood has antibodies to
Type A RBCs but not to Type B
• Type AB blood doesn’t have
antibodies to A or B
• Type O has antibodies to both
Type A & B
• If different blood types are
mixed, antibodies will cause
mixture to agglutinate

Fig 13.5
13-16
 Transfusion Reactions
• If blood types don't match, recipient’s
antibodies agglutinate donor’s RBCs
• Type O is “universal donor” because lacks A &
B antigens
– Recipient’s antibodies won’t agglutinate
donor’s Type O RBCs (which lack antigens)
• Type AB is “universal recipient” because
doesn’t make anti-A or anti-B antibodies
– Won’t agglutinate donor’s RBCs

13-17
 Rhesus Blood Group
• Rh factor – Another antigen which may be present
(Rh +) or absent (Rh -) on RBCs.

– Rh negative (-) do not have natural antibodies to the Rh

antigen.

– The first time they receive blood that is Rh positive (+),

antibodies form but not a problem.

– The second exposure can produce a transfusion reaction

(hemolysis and possible kidney damage).
 Hemoglobin
• Red oxygen carrying pigment in RBC .
• Cytoplasm in each RBC contains about 280
million hemoglobin molecules.
• Hb constitutes 90-95% of dry cell mass and 30-
34% of wet cell mass.
• Molecular weight - 64,450
• Normal Hb concentration:
– 12-18 g/dL (males)
– 12-16g/dL (females).
 Hemoglobin
• Is a globular structure.
• Consists of 2 main parts.
• Haem (heme): Iron porphyrin complex.
• Globin: The 4 polypeptide chains.
• Hb is an assembly of four globular subunits.
• Each subunit is composed of a protein chain tightly
associated with a non-protein haem group.
• Each molecule of Hb contains 2 pairs of polypeptide
chains.
 Globin
• Types of polypeptide chains: α, Β, γ, δ

• ε –Embryonic

• ζ- Embryonic

• Polypeptide chains have helical structure,

folded over to give globular structure with a
deep pocket in which haem lies.
 Hemoglobin Reactions
• Combines reversibly with oxygen to form
oxyhaemoglobin (unstable).

• Combines reversibly with carbon dioxide to

form carbaminohaemoglobin (unstable).

• Combines with carbon monoxide more avidly

to form carboxyhemoglobin (very stable).
 Reaction with oxygen
• Hb combines sequentially with O2.
• Deoxygenated hemoglobin is in the T (tense)-state.
• Binding of initial molecule of oxygen causes
conformational changes.
• Oxygenated hemoglobin is in R (relaxed)-state .
· The R-state has a higher affinity for O2 than the T-
state.
Oxygen-Hemoglobin Dissociation Curve

• A sigmoid shape curve that relates the

percentage saturation of the O2 carrying power
of Hb to the PO2.

• The affinity of hemoglobin for O2 is affected by

pH, temperature, and the concentration of 2,3-
bisphosphoglycerate (2,3-BPG) in the RBCs.
Oxygen-Hemoglobin Dissociation Curve

• As the curve shifts

from A to B (right) the
affinity for O2
decreases

• Increasing
temperature, CO2 will
shift the curve to the
right
 Types of Hb
Normal Abnormal
• Embryonic: • Haemoglobinopathies:
• Gower 1- ζ2ε 2 • HbS,
• Gower 2-α 2 ε 2 • HbC
• Hb Portland- ζ 2 γ 2 • Thallasaemias- α and β
• Fetal- Hb F - α 2 γ 2 • Hb Barts -γ 4
• Adult- Hb A- α 2β 2 • Hb H. β 4
• HbA 2 - α 2δ 2
• Glycosylated Hb Aic -
 Sickle Cell Mutation
Chromosome 16   
5' 3'
Chromosome 11  G A   *
5' 3'

Normal (HbA)   Abnormal (HbS)

CCT GAG GAG   CCT GTG GAG
-Pro-Glu-Glu- A S -Pro-Val-Glu-
5 6 7 5 6 7

-O2 -O 2
+O 2 +O 2
• Repeated sickling and
unsickling damages RBC
membranes
• cells are less flexible and
block microcirculation and
hemolyse easily.
• Homozygotes SS have
severe hemolytic anaemia–
sickle cell anaemia
• Heterozygotes AS have
sickle cell trait. Dont
hemolyse
Clinical Relevance: Sickle cell disease

•  flexibility
•  fragility
•  blood viscosity
•  O2
•  sickling
• “crisis”
• Painful ischemia
17.10b
– Lack of O2
 Catabolism of Hemoglobin
• After 120 days old RBCs are removed from blood by
phagocytic cells in liver, spleen & bone marrow
• Globin is split from the heme.
• The globin is returned to the plasma protein and
amino acid pool.
• Heme iron is returned to the plasma iron pool and recycled
back into hemoglobin production
• Opening of the porphyrin ring yields biliverdin and
carbon monoxide.
• Biliverdin is converted to bilirubin
 Catabolism of Hemoglobin
• Bilirubin(not water soluble) passes into the blood &
is bound to albumin (unconjugated bilirubin).
• Unconjugated bilirubin is conjugated with
glucuronic acid (conjugated bilirubin- water
soluble) by the liver & cleared from the blood.
• Bilirubin passes into bile and gets to intestine
where it is metabolised to urobilinogen.
• Urobilinogen is converted to stecobilin in feaces.
• A small fraction is excreted in kidney and becomes
oxidised to urobilin on exposure to air.
 Clinical Relevance: Jaundice
• Jaundice is yellowish discoloration of skin and
mucous membrane due to excess bilirubin.
• Hemolytic: when there is increased destruction
of red blood cells.
• Occurs in neonates due to immature pathway for
glucuronidation causing physiological jaundice.
• Other causes: Infections , G6PD deficiency etc.
• Excess unconjugated bilirubin in circulation, can
cross blood brain barrier to cause brain damage.
Questions???
 Summary
• RBCs are important cellular component of blood
containing Hb which is the O2 carrying pigment.

• Formation of RBCs involves different stages which

requires important factors and mainly regulated by
erythropoietin.

• Abo blood group is the most commonly blood grouping

that classify individuals to blood group A, B, AB and O
based on the type of antigen present on the RBC
membrane.
 Further Reading
• Guyton and Hall Textbook of Medical
Physiology
• Ganong’s review of Medical Physiology
• Essentials of Medical Physiology by Oyebola