Red Blood Cells (RBCs) Overview

• Module covering "Blood and Immune" topics for Semester 2

RBCs (Red Blood Cells) General Overview

• RBCs are circular and biconcave in shape
• Average RBC diameter is 7.2 μm, and their thickness is 2.2 μm
• RBCs lack a nucleus, ribosomes, and mitochondria, therefore technically aren't true cells
• Primarily composed of hemoglobin (Hb)
• Main function is to transport oxygen (O2) and carbon dioxide (CO2)

Biconcave Shape of RBCs

• Biconcave shape increases the surface area of RBCs
• This shape is maintained by ankyrin and spectrin proteins
• Problems with this shape is is absent in spherocytosis
• The shape results in minimal membrane tension when volume increases

Key RBC Metrics

• Normal RBC count in adult males is 5.4 million/mm3
• Normal RBC count in adult females is 4.8 million/mm3
• RBCs are circular, biconcave, and non-nucleated
• Biconcave shape increases the surface area-to-volume (S/V) ratio
• Biconcave shape enables RBCs to pass through narrow capillaries
• Average RBC size is 7.5 µm in diameter, 2 µm thick with a .90 cubic microns volume
• Hemoglobin (Hb) concentration:
  • Men: ~16 g/dl
  • Women: ~14 g/dl

Functions of RBCs

• Contributes to the maintenance of blood viscosity, which is essential for maintaining arterial blood pressure (ABP)
• Essential to carry oxygen and carbon dioxide
• Membrane keeps hemoglobin inside and prevents its escape into the plasma
• Membrane contains agglutinogens that determine blood groups
• Shape increases the surface area for gas exchange
• High degree of flexibility: they can deform into almost any shape enables passage through narrow vessels
• After deformation, they can resume their normal shape

Erythropoiesis

• Erythropoiesis is the process of origin, development, and maturation of erythrocytes
• Hemopoiesis (or hematopoiesis) is the process of origin, development, and maturation of all blood cells

Sites of Erythropoiesis

• Fetal life: Liver, spleen, and bone marrow
• After birth: Bone marrow
• After 20 years of age: Membranous bone marrow in vertebrae, sternum, ribs, ilia, and upper ends of the humerus and femur

Factors Affecting Erythropoiesis

• Erythrocyte numbers are regulated to provide sufficient tissue oxygenation
• Key factors influencing erythropoiesis include:
  • Oxygen supply to the tissues and the role of erythropoietin
  • Healthy bone marrow
  • Healthy liver
  • Hormones
  • Diet

Oxygen Supply and Erythropoietin

• Conditions that decrease O2 supply increase the production rate of erythrocytes
• Conditions leading to increased rate of production include:
  • High altitude
  • Increased oxygen demand in athletes
  • Chronic respiratory diseases (e.g. COPD)
  • Anemia
  • Prolonged heart failure

Stimulating Secretion of Erythropoietin

• Hypoxia
  • There is evidence that oxygen tension in the kidney is the major factor regulating erythropoiesis
• Alkalosis that develops during acclimatization to high altitude
• Cobalt salts and androgens
• β-adrenergic stimulants and adenosine facilitate erythropoietin secretion

Erythropoietin Overview

• Glycoprotein with 165 amino acids
• Major quantity secreted by peritubular capillaries of the kidney, and a small quantity is also secreted from the liver
• The stimulant for secretion is hypoxia

Healthy Bone Marrow

• Essential for the production of erythrocytes
• The bone marrow can be destroyed by X-rays, atomic radiation, and drugs such as chloramphenicol
• Bone marrow can also be destroyed by malignant tumors leading to aplastic anemia

Healthy Liver

• Essential for erythropoiesis
• Site of the globin portion formation for hemoglobin
• Formation of 10% of erythropoietin hormone
• Storage of iron and vitamin B12

Hormones That affect Erythropoiesis

• Erythropoietin hormone
• Androgens stimulate erythropoietin secretion
• Thyroid hormone stimulates general metabolism

Maturation Factors

• Vitamin B12, intrinsic factor, and folic acid are necessary for RBC maturation

Vitamin B12 (Cyanocobalamin)

• Necessary maturation factor for erythropoiesis
  • Also called extrinsic factor since it is primarily obtained from the diet
• Absorption from the intestine requires the presence of intrinsic factor of Castle
• Stored mostly in the liver and, in small quantities, in muscle
• When necessary, transported to the bone marrow to promote RBC maturation
• Also produced in the large intestine by intestinal flora

Action of Vitamin B12

• Essential for DNA synthesis in RBCs
• Deficiency leads to failure in cell maturation and reduction in cell division
  • The resultant cells are larger with fragile/weaker cell membranes, causing macrocytic anemia
• Deficiency causes pernicious anemia
  • Vitamin B12 can be called an antipernicious factor

Intrinsic Factor of Castle

• Produced in gastric mucosa by the parietal cells of the gastric glands
• Essential for the absorption of vitamin B12 from the intestine
• Absence leads to vitamin B12 not being absorbed from the intestine, resulting in pernicious anemia
• Deficiency occurs due to:
• Severe gastritis
• Ulcer
• Gastrectomy

Folic Acid

• Essential for maturation and required for DNA synthesis
• Absence leads to decreased DNA synthesis, causing failure of maturation
  • This leads to megaloblastic anemia

Diet and nutrition

• A proper diet is essential for erythropoiesis because it facilitates the production of erythrocytes
• Adequate Dietary measures include consuming essential factors such as:
• Proteins of high biological value.
• Minerals:
• Iron :Heme part of hemoglobin.
• Copper important for iron absorption from GIT
• Cobalt as Co-factors for formation of Hb.
• Cobalt as a part of vit. B12.
• Vitamins: Vitamin C. Vitamin B12. Folic acid.