More about RBCs

Lecture #7: More about RBCs

Erythrocyte Lifecycle

Overview of Erythrocyte Lifecycle Components

  • Erythropoiesis

  • Destruction and Recycling

  • Erythrocyte Disorders

Dietary Requirements for Erythropoiesis

Essential Nutrients for RBC Formation

  • Macromolecules and Their Monomers:

    • Iron:

    • 50% contained within hemoglobin (Hb)

    • Remaining is bound to proteins in the liver, spleen, and bone marrow

    • Free iron (Fe3+) is toxic; thus, it is stored bound to proteins.

      • Storage Proteins:

      • Ferritin and Hemosiderin: stored inside cells

      • Transferrin: present in plasma

    • Amino Acids, Lipids, and Carbohydrates: play supporting roles in erythropoiesis

  • Vitamins:

    • Vitamin B12 and Folic Acid (Vitamin B9):

    • Necessary for DNA synthesis in rapidly dividing cells

    • Note: Deficiency of either vitamin can lead to anemia.

Erythropoiesis

Definition and Contrast to Hematopoiesis

  • Hematopoiesis: Formation of blood cells.

  • Erythropoiesis: Specific formation of erythrocytes (RBCs).

  • Location: Differs from other connective tissues in that it occurs primarily in the red bone marrow.

Stages of Erythropoiesis (Key Terms)

  1. Hemocytoblast: The stem cell for all blood cells transformed into a proerythroblast.

  2. Proerythroblast: Transforms into reticulocytes within approximately 15 days.

  3. Reticulocytes:

    • Enter the bloodstream and mature into erythrocytes within 2 days.

Developmental Pathway Outline

  • Stem Cell: Hematopoietic stem cell (hemocytoblast).

  • Committed Cell: Proerythroblast.

  • Phases of Erythropoiesis:

    • Phase 1: Ribosome synthesis.

    • Phase 2: Hemoglobin accumulation.

    • Phase 3: Ejection of the nucleus transforms into the reticulocyte, eventually maturing into the erythrocyte.

Regulation of Erythropoiesis

Impact of Oxygen Levels

  • Tissue Hypoxia: Low tissue O2 levels trigger increased erythropoiesis.

  • Tissue Hyperoxia: High RBC counts lead to decreased erythropoiesis.

Balancing Factors for RBC Count

  • Hormonal controls: Erythropoietin (EPO):

    • Produced by cells surrounding capillaries in the kidney.

  • Nutritional requirements:

    • Adequate supplies of iron, amino acids, lipids, carbohydrates, and B vitamins (folic acid (B9), B12).

Hormonal Control of Erythropoiesis

Mechanism of EPO Action

  • Negative Feedback Loop:

    1. Stimulus: Hypoxia leads to decreased RBC count, hemoglobin, and O₂ availability.

    2. Kidney Response: Releases erythropoietin (EPO).

    3. Stimulation: Erythropoietin stimulates red bone marrow.

    4. Outcome: Enhanced erythropoiesis increases RBC count.

Homeostatic Control Forms

Types of Homeostatic Feedback Mechanisms

  • Negative Feedback: Works against the original stimulus (regardless of increase or decrease).

  • Positive Feedback: Amplifies the original stimulus.

  • Feedforward: Prepares for a new stimulus (e.g., digestion, thermal regulation, physical activity).

Effects of Erythropoietin (EPO)

  • Rapid maturation of committed marrow cells leads to:

    • Increased circulating reticulocyte count within 1-2 days.

  • Ethical Concern: Some athletes abuse artificial EPO, which can lead to dangerous consequences.

  • Testosterone: Enhances EPO production, leading to higher RBC counts in males.

Destruction of Erythrocytes

Life Span and Degradation Process

  • Life Span: RBCs typically last 100-120 days.

  • Characteristics: RBCs lack protein synthesis, growth, and division capability (Go phase of the cell cycle).

  • Aging Process: Old RBCs become fragile; hemoglobin begins to degenerate and are trapped in smaller circulatory vessels, particularly in the spleen and liver.

Clearance by Macrophages

  • Macrophages engulf dying RBCs primarily in the spleen and liver.

Erythrocyte Recycling & Waste Removal

Recycled Materials

  • Iron + Globin Chains: Metabolized into amino acids for reutilization.

Waste Products

  1. Heme: Degraded to yellow pigment bilirubin.

  2. Bilirubin Recovery:

    • Liver recovers bilirubin from blood.

    • Liver and gall bladder secrete bilirubin mixed in bile.

    • Into the small intestine, where it is further degraded to colorless urobilinogen and then to stercobilin, which gives feces its dark brown color.

    • Some urobilinogen is reabsorbed by the body and excreted by kidneys (yellow color of urine).

  3. Clinical Relevance:

    • Bilirubin and urobilinogen levels are screened in urinalysis; increased levels may indicate liver damage, internal bleeding, or excessive RBC rupture.

    • Jaundice: Accumulation of bilirubin in the skin and eyes due to RBC rupture; localized accumulation occurs with bruising.

Erythrocyte Disorders

Types of Anemia
Anemia: Blood Loss

  • Hemorrhagic Anemia:

    • Caused by rapid blood loss (e.g., from a stab wound) leading to decreased erythrocyte production.

    • Question: How long does it take to make an erythrocyte?

    • Treatment: Focus on controlling blood loss and may involve transfusions or fluid restoration.

  • Chronic Hemorrhagic Anemia:

    • Results from slight but persistent blood loss. Questions for consideration:

    • Conditions such as bleeding ulcers and excessive menstrual flow can lead to this.

    • Treatment: Identifying the source of the bleeding for targeted intervention.

Anemia: Low RBC Production

  • Iron-Deficiency Anemia:

    • Caused by hemorrhagic anemia, insufficient iron intake, or impaired iron absorption.

    • Leads to microcytic (small RBCs) and hypochromic (lack of color) RBCs.

    • Treatment: Focus on iron supplementation and diet.

  • Pernicious Anemia:

    • Caused by autoimmune destruction of cells that produce intrinsic factor needed to absorb B12; may also be due to low dietary B12 (common among vegetarians).

    • Results in poor cell division among RBC precursors.

    • Treatment: B12 injections or high doses of oral B12.

  • Aplastic Anemia:

    • Result of destruction or inhibition of bone marrow due to drugs, chemicals, radiation, or viruses.

    • All formed elements of blood are affected.

    • Treatment: May involve immunosuppressants, blood transfusions, or bone marrow transplants (both short-term and long-term solutions).

Anemia: High RBC Destruction

  • Hemolytic Anemias:

    • Characterized by premature RBC lysis. Causes include:

    • Genetic abnormalities of hemoglobin (hemoglobinopathies).

    • Incompatible blood transfusions.

    • Infections (e.g., viral or bacterial).

  • Example: Thalassemias, which involves the absence or defect of one of the globin chains.

    • Results in thin, delicate RBCs that are deficient in hemoglobin; severity varies by subtype.

  • Sickle-cell Anemia:

    • A type of thalassemia characterized by:

    • RBCs adopting a crescent shape when O2 delivery is low.

    • It is caused by a single amino acid modification in the beta chains of hemoglobin, altering a glutamic acid to valine (changing from hydrophilic to hydrophobic).

    • RBC Lifespan: Sickle cells degrade rapidly after 10-20 days (comparison to normal lifespan).

Malaria and Sickle-cell Anemia Connection

  • Epidemiology: Sickle-cell trait may enhance malaria survival as 1 million deaths occur from malaria each year, and individuals in the malarial belt often carry this mutation (including northern South America, central Africa, and southern Asia).

  • Sickle-cell Gene:

    • Two Copies: Sickle-cell anemia.

    • One Copy: Sickle-cell trait; associated with milder disease and improved chances of surviving malaria.

    • Treatment Options:

    • Hydroxyurea induces fetal hemoglobin formation, which does not sickle.

    • Various stem cell transplant strategies and gene therapy options to correct the mutation.

Polycythemia: Excess Red Blood Cells

Types of Polycythemia

  • Polycythemia Vera: Genetic disorder resulting in excess erythrocytes, leading to increased blood viscosity.

  • Secondary Polycythemia: Results from natural or artificial increases in erythropoietin production, resulting in a higher RBC count.

    • Triggers include high altitude (low O2) or blood doping (e.g., adding more RBCs or administering EPO).