Course Title: PHS 213 – HUMAN PHYSIOLOGY I

TOPIC: RED BLOOD CELL (RBC)

OUTLINE

 Introduction
 Morphological features of RBC
 RBC count
 Erythrocyte Sedimentation Rate (ESR)
 Structural adaptation of RBC
 Functions of RBC
 Production of RBC (Erythropoiesis)
 Regulation of RBC production
 Haemoglobin and transport of Oxygen
 Destruction of Senile RBC
 Clinical Correlates
Introduction

Recap
 Composition of Blood:
 1. Cellular components - RBC (Erythrocytes), WBC (Leucocytes),
Plateletes (Thrombocytes)
2. Plasma- water (98%), ions, plasma proteins (albumin, globulin,
fibrinogen)
 Functions of blood
 Packed Cell Volume (PCV)/ Hematocrit value
Morphological features of RBC

 Biconcave disc and non-nucleated

 Diameter = 7-8 µm, thickness = 2.1 µm, Surface

area= 130 µm2, Volume= 80-100 fL (femtolitres, 10-
15
L)

 Each RBC contains approximately 30 pg (picogram

10-12) of Hb
 RBC Count

 Male: 4.3 – 5.3 x 10 12 / L (130 – 150g Hb)

 Female: 3.8 – 4.8 x 10 12 / L (110 – 140g Hb)

 Newborn: 7 – 8 x 10 12 / L
Erythrocyte Sedimentation Rate (ESR)

 The rate at which the erythrocytes settle down.

 Importance: Indirect way to diagnose certain chronic inflammatory diseases such as:
tuberculosis and arthritis

 Factors influencing ESR

 RBC size and count
 Plasma proteins
 pH of blood plasma
 Lipidemia
 Factors that can accelerate ESR
Physiological factors: Gravidity, menstruation
Pathological factors: tumor, liver diseases

 Values: Male = 2 - 5 mm/h

Female = 3 -8 mm/h (less RBC, more fibrinogen)
Structural adaptation of RBC

 The shape of RBC has three important adaptations:

• Diapedesis: Flexibility; ability to squeeze through narrow capillaries without

disrupting its cell membrane

• Faster rate of gas exchange in and out of the of the cell due to the greater surface area and
shorter distance to the central region (when compared to a sphere of same volume)

• Reduces wall tension as the cell swells after taking up CO 2 from the tissue
 Functions of RBC

 O2 and CO2 transport

 Buffer by regulating ECF pH

 Blood group determination

 Production of RBC

 The production of RBC is called erythropoiesis.

 It is produced in the bone marrow under the control of erythropoietin; a hormone majorly synthesize in the
peritubular capillaries of the kidney in response to local hypoxia

 In fetus, erythropoietin is majorly synthesize by the liver

 The production takes approximately 7 days

 Lifespan of RBC is approximately 120 days and is removed from the circulation by macrophages in the bone
marrow, liver or spleen
Genesis of RBC
Regulation of Erythropoiesis
Haemoglobin and transport of oxygen

 Haemoglobin (Hb) is the constituent of the red blood cell that combines with oxygen.

 Consists of two parts; The haem and the globin.

 Haem is a complex of a porphyrin ring and iron in the ferrous (Fe2+) state.

 Iron is an essential part of haemoglobin and its deficiency due to dietary inadequacy or loss
through chronic haemorrhage leads to anaemia

 The haem is conjugated with globin, a polypeptide consisting of four subunits

 The amount of oxygen the blood carries is described as the oxygen content of blood

 Vast majority of oxygen is carried bound to haemoglobin and a very small amount is dissolved in the plasma.
The total amount of oxygen carried by blood can be obtained by adding these two amounts

 Under physiological condition, the haemoglobin is almost fully saturated with oxygen as blood leaves the
lungs, and each gram of Hb contains 1.39ml of oxygen
 
 However, by the time it reaches the systemic circulation this amount has fallen slightly due to the addition of a
small volume of venous blood from the pulmonary and coronary circulations

 Therefore in the arterial circulation, one gram of Hb is around 98% saturated and contains 1.34ml of oxygen
 The amount of oxygen dissolved in the blood is proportional to the partial pressure.
 
 At 37 degrees Celcius (body temperature), 0.23ml oxygen dissolves in each litre of blood per
kPa. Therefore the O2 content of blood can be calculated from the equation below:

O2 content of blood (L) = (Hb x 1.34 x SaO2) + (0.23 x PaO2)

= (150 x 1.34 x 98%) + (0.23 x 13)

≈ 20.3 ml/L
 Oxygen combines reversibly with the ferrous ion in the haemoglobin molecule to form
oxyhaemoglobin. Hb + O2 ↔ HbO2

 In the lungs, where the partial pressure of oxygen is high, the forward reaction oxygenating
haemoglobin is favoured

 Hb + O2  HbO2

 In the tissues where the partial pressure of oxygen is low the reverse reaction reducing
haemoglobin is favoured.

 Hb + O2  HbO2
 Thus, haemoglobin combines with oxygen in the lungs and releases it at the level of the
tissues

 Both the oxygenation and reduction of haemoglobin are extremely rapid reactions taking
less than 0.01 seconds.
 The relationship between the saturation of haemoglobin and the partial pressure of oxygen
in the blood is described by the oxygen dissociation curve.

 A right shift in the curve means that haemoglobin releases its oxygen relatively easily.
This occurs during an acidosis (decreased pH)

 A left shift in the curve means that haemoglobin accept more oxygen. This occurs during
an alkalosis (increased pH)
Oxyhaemoglobin Dissociation Curve
 The dissociation curve can be shifted to the right or left by a number of factors. The curve
is shifted to the right by:

1. Increased hydrogen ions (reduced pH)

2. Increased carbondioxide
3. Increased temperature
4. Increased DPG (2,3 diphosphoglycerate)
 DPG is formed in RBCs as a product of glycolysis. It is a highly charged ion and when it
combines with the beta chain of haemoglobin, it displaces oxygen.
 
 During exercise there is an increase in temperature, hydrogen ions, CO 2 and DPG in the
tissues, all the conditions associated with a rightward shift in the curve to help deliver
oxygen to the active muscles.
Fetal Haemoglobin (HbF)and Adult Haemoglobin (HbA)

 HbA has two alpha and two beta globin chains

 HbF is structurally different from the HbA; In HbF, the two beta chains are replaced by
two gamma chains.

 This structural difference means that fetal haemoglobin binds less avidly with DPG and,
as we know, DPG reduces the amount of oxygen that combines with haemoglobin.

 Consequently, HbF has a higher affinity for oxygen than adult haemoglobin which is
demonstrated by a leftward shift in the oxygen dissociation curve.
 This difference in haemoglobin physiology enables the fetus to extract oxygen from
maternal blood at the placenta

 Adult haemoglobin quickly replaces fetal haemoglobin after birth thus correcting the
position of the curve and allowing the baby to utilise oxygen normally.

 2.5% of adult circulating haemoglobin is HbF.

 Destruction of Senile Erythrocytes

 Reticuloendothelial cells, particularly those in spleen destroy the senile RBCs and release hemoglobin and later degrade the
hemoglobins

 The heme part of the hemoglobin is further broken down into free iron (Fe+3) and biliverdin; a green substance that is further
reduced to bilirubin (a bile pigment)

 the iron enter into the blood circulation and return to the red bone marrow to be re-used for the synthesis of new hemoglobin

 If not needed immediately for this purpose, excess iron is stored in the liver

 The iron of RBCs is actually recycled over and over again

 The globin or protein portion of the hemoglobin molecule is also catabolized by proteases into constituent amino acids to be
reused for the synthesis of new hemoglobin in the bone marrow
 The liver removes bilirubin from circulation and excretes it into bile.

 The Bile is secreted by the liver into the duodenum and passes through the small intestine
and colon.

 Bilirubin is therefore eliminated in feces, and gives feces their characteristic brown color.

 In the colon some bilirubin is changed to urobilinogen by the colon bacteria.

Destruction of Senile RBC (Adapted from Essential of Medical Physiology by K
Sembulingam)
 Clinical Correlates

 Sickle cell Anaemia

 Thalasseamia
Sickle cell Anaemia

 This is a haemoglobinopathy with autosomal recessive inheritance.

 The genetic defect leads to the substitution of valine for glutamine at position six on
globin’s beta chain, creating HbS rather than HbA

 There are a number of genotypes that make up the range of patients suffering from sickle
cell disease. The two most common are:

1 HbSS – patients who are homozygous and have sickle cell disease
2 HbSA- patients who are heterozygous and have sickle cell trait
Sickle cell Anaemia (Cont’d)

 At low partial pressures of oxygen (5-5.5kPa) deoxygenated HbS becomes insoluble

 It forms long crystals called tactoids which cause red cells to become sickle shaped and
rigid

 The distorted cell shapes and associated increased blood viscosity promote venous stasis

 This leads to local blood vessel obstruction causing ischaemia and tissue infarction. These
events are termed a sickle cell crisis
Sickle cell Anaemia (Cont’d)

 These cells have a decreased survival time of only 10-20 days

 Therefore, patients with sickle cell disease suffer from a chronic anaemia (haemolytic) and are often
jaundiced (due to conversion of haem to bilirubin).

 Patients who have sickle cell trait are also at risk of a sickle cell crisis but only at very low partial
pressures of oxygen as their erythrocytes only contain 20 to 45% HbS

 A sickledex test can confirm the presence of haemoglobin S and electrophoresis can differentiate
between trait and disease. Electrophoresis can also determine the proportion of HbA to HbS in the
blood.
Thalasseamia

 It is an inherited disease of haemoglobin production. Patients with the disorder have a

reduced or absent production of globin chains

 
 It is commonly found in people of Mediterranean origin.