Red Blood Cell Physiology

• The lecture focuses on the physiology of red blood cells (RBCs).
• The instructor for this course is Magdy Youssef from the department of physiology.

Learning Outcomes

• List general functions of blood and its composition.
• Identify erythrocyte count, shape, sizes, structure, and functions.
• Understanding hemoglobin (Hb) steps, formation, types, and fetal Hb combination.
• Discuss erythropoiesis stages and factors affecting its regulation.
• Explain the mechanisms of iron and vitamin B12 absorption.

General Functions of Blood

• Transport medium
• Haemostatic function
• Homeostatic function
• Defensive function

Composition of Blood

• Blood consists of cellular elements and plasma.
• Cellular elements: Represent approximately 45% of blood.
• Cellular elements include RBCs, WBCs, and platelets
• Plasma: Accounts for about 55% of blood volume (3500 ml).
• Plasma Composition: Around 90% water, 0.9% inorganic substances, and 9.1% organic substances.
• Inorganic substances: Include cations like Na+ and K+, also anions such as Cl-, HCO3, PO4, and SO4.
• Organic substances: Plasma proteins (6-8 gm%) and lipids, among others organic substances.

Erythrocytes (RBCs)

• Adult male: Approximately 5.2 million/mm³.
• Adult female: Approximately 4.7 million/mm³.
• Newborns: Higher count, ranging from 6-8 million/mm³.
• Children and elderly: Tend to have lower counts.
• Shape: Biconcave discs (2.5 μm thick and 7.8 μm in diameter).
• Average volume: 90 μm³.
• Biconcave shape advantages: Increases surface area, minimizes membrane tension during volume changes, and provides cell flexibility.
• Primary function: Transport of O2 from the lungs to tissues and CO2 from tissues to the lungs with the help of hemoglobin (Hb).
• Hemoglobin: Serves as an excellent acid-base buffer.
• RBCs: Produce blood viscosity, which contributes to peripheral resistance and maintaining arterial blood pressure (ABP).
• Cell membrane functions: Keeps Hb inside cells, provides a large surface area for gas exchange, and contains glycoproteins (antigens) used for blood group determination.

Types of Hemoglobin (Hb)

• Adult hemoglobin (Hb A): Contains two alpha and two beta polypeptide chains.
• Fetal hemoglobin (Hb F): Has a greater affinity for O2 than Hb A.
• Hb F: Composed of two alpha and two gamma chains.

Hemoglobin Content

• Adult male: 14-18 gm/dl.
• Adult female: 12-16 gm/dl.
• Newborn infant: Up to 19 gm/dl.
• Hb combines loosely and reversibly with O2 to form oxyhemoglobin.
• O2 is attached to the Fe++ in the hemoglobin.

Life Span and Fate of RBCs

• Life span: Is approximately 120 days.
• Old RBCs: Rupture, especially in the spleen.
• Released Hb from ruptured RBCs: Phagocytosed by macrophages.
• Hb breaks down into globin and heme.
• Globin: Further breaks down into amino acids.
• Heme: Breaks down into iron and biliverdin.
• Biliverdin: then converts to bilirubin.

Erythropoiesis

• The process: New RBC production.
• In the first trimester: Occurs in the yolk sac.
• In the middle trimester: Occurs in the liver, spleen, and lymph nodes.
• In the last trimester and after birth: Takes place in the red bone marrow (all bones).
• After age 20: Occurs in the red bone marrow of flat bones (skull, vertebrae, sternum, ribs, and pelvic bones) and proximal parts of long bones.

Factors Affecting Erythropoiesis

• Defective tissue oxygenation (O2 lack or hypoxia) is the primary factor stimulating RBC production.
• Low tissue O2 levels: can be due to hemorrhage, cardiac and/or lung diseases, or high altitudes, this increases erythropoiesis by releasing erythropoietin hormone.

Role of the Kidney (Erythropoietin Hormone)

• Glycoprotein: Molecular weight of 34,000.
• In adults: 90% produced by the kidneys, 10% from the liver.
• In fetal life: Erythropoietin is produced only by the liver.
• Stimulates: The production of proerythroblasts from stem cells
• Speeds up: All stages of development into erythroblasts and then into mature RBCs.
• Regulation: Stimulated by hypoxia, epinephrine, norepinephrine, prostaglandins, cobalt, androgen, adenosine.

Additional Factors Affecting Erythropoiesis:

• Healthy liver: Site of formation of the globin portion of Hb, production of 10% of erythropoietin, and storage of iron and vitamin B12.
• Hormones: Thyroid hormones, androgens, and glucocorticoids stimulate erythropoiesis.
• Proteins: Especially animal proteins that contain the essential amino acids.
• Copper and cobalt: These act as cofactors in Hb synthesis, cobalt is a part of vitamin B12 and stimulates erythropoietin secretion.
• Iron: Enters the formation of heme.
• Folic acid and vitamin B12: These are essential for the maturation of RBCs.

Iron

• Total quantity in body: 4-5 gm is the total quantity of Iron.
• Distribution: 65% in the form of hemoglobin, 4% in the form of myoglobin, 1% in cytochrome enzymes, 0.1% combined with transferrin, and 15-30% stored in the form of ferritin
• Daily Loss and Intake: Equal.
• Males: 0.6 mg.
• Females: 1.3 mg.
• Storage form in tissues: Ferritin.
• Transporing Protein: Transferrin.

Vitamin B12

• Sources: Animal foods ex: liver, meat and chicken.
• Daily requirement: 5 micrograms.
• Deficiency: Leads to Megaloblastic anemia.

Folic Acid

• Sources: Green vegetables, fruits, liver, and meat.
• Importance: Essential for maturation of RBCs.
• Deficiency: Leads to megaloblastic anemia.

Review Questions

• Which of the following is needed for erythropoiesis? Vitamin B12
• Which of the following is most probably to occur in a person living at high altitude? Increased red blood cell count
• Which of the following is the source of erythropoietin? Kidneys
• Which of the following is needed for vitamin B12 absorption? Intrinsic factor