Lecture 2

Factors Essential for RBC Production

• Three key factors are essential for red blood cell (RBC) production:

  • Cytokines: Erythropoietin (EPO) stimulates RBC production.

  • Dietary factors: Iron (needed for hemoglobin), folic acid, and vitamin B12 are crucial.

  • Intrinsic factor: Produced by stomach cells and necessary for vitamin B12 absorption.

Regulation of RBC Production by Erythropoietin

• Erythropoietin (EPO):

  • A cytokine that stimulates RBC synthesis.

  • Secreted by the kidneys in response to decreased oxygen delivery.

  • EPO acts on bone marrow hematopoietic stem cells to increase RBC production.

• Mechanism:

  • Decrease in tissue oxygenation \rightarrow stimulates EPO release from kidneys \rightarrow stimulates hematopoietic stem cells in bone marrow \rightarrow increases RBC production \rightarrow increases oxygen-carrying capacity of blood \rightarrow increases tissue oxygenation.

• Hypoxia:

  • Low oxygen concentration in the blood.

  • Factors contributing to hypoxia: low blood volume, anemia, low hemoglobin, poor blood flow, pulmonary disease.

  • Any factor that reduces the blood's ability to carry oxygen, affects oxygen delivery to tissues, or impairs oxygen intake.

Uptake and Recirculation of Iron

• Iron:

  • Essential for RBC production.

  • Obtained from food and absorbed into the blood in the intestine.

  • Transported in blood bound to transferrin (iron transport protein).

  • Utilized in bone marrow for RBC production.

• Body iron reserve:

  • 50% from hemoglobin of dying RBCs.

  • 25% stored in other iron-containing proteins.

  • 25% stored in the liver bound to ferritin (a protein).

Recycling of Iron From Old/Damaged RBCs

• Old or damaged RBCs are taken up by macrophages in the spleen via phagocytosis.

• Process:

  • Hemoglobin \rightarrow broken down into heme and globin.

  • Heme \rightarrow broken down into iron and biliverdin.

    • Iron \rightarrow absorbed into blood for erythropoiesis or stored in spleen or liver bound to ferritin.

    • Biliverdin \rightarrow converted to bilirubin \rightarrow secreted into bile and enters the small intestine.

  • Globin \rightarrow broken down into amino acids.

Absorption of Vitamin B12

• Vitamin B12 is required for normal RBC production.

• Obtained from the diet.

• Absorption from the GI tract requires intrinsic factor (a protein), secreted by cells in the stomach wall.

• Vitamin B12 and IF form a complex to allow vitamin B12 to be absorbed.

• Pernicious Anemia:

  • Caused by a lack of vitamin B12.

Anemia

• Anemia: decreased oxygen-carrying capacity of the blood due to a deficiency of RBCs and/or hemoglobin contained in the RBCs.

• Specific factors leading to anemia:

  • Lack of iron.

  • Pernicious anemia: lack of intrinsic factor or Vitamin B12.

  • Aplastic anemia: damage of bone marrow due to radiation/drugs.

  • Chronic kidney disease (reduced level of erythropoietin, EPO).

  • Hemolytic anemia: increased breakdown due to abnormal shape of RBC or due to immune reactions during transfusion.

  • Hemorrhagic anemia: increased blood loss due to injury, bleeding ulcers or chronic menstruation.

  • Abnormal structure of hemoglobin.

Normal and Abnormal Hemoglobin

• Normal adult hemoglobin:

  • HbA (2 alpha and 2 beta chains).

• Sickle cell disease:

  • Have abnormal Hb called HbS.

  • Characteristics of disease: sickle-shaped RBC with hard, nonflexible cell membranes.

  • RBC in sickle cell disease are damaged as they pass through capillaries, leading to hemolytic anemia.

  • An autosomal recessive disease (the gene for Hb S has to be inherited from both parents).

Immunity

• Immunity: Process that helps a cell or the interior of our body defend against anything foreign- it protects our ‘self’ from our ‘non-self’

• Two types of immunity:

  • Innate (natural) immunity

  • Acquired (adaptive/specific) immunity

Innate/Natural Immunity

• Immunity we are born with

• Includes non-specific defenses in the body such as physico-chemical barriers, or physiological and chemical barriers of the body (skin, enzymes in body fluids, acid secretion in stomach, WBCs)

Acquired/Adaptive/Specific Immunity

• Acquired over time and upon exposure to foreign pathogens/cells

• Foreign object triggers the immunity to develop

• WBC important

The White Blood Cell Story

• WBC

  • Produced from pluripotent stem cells in bone marrow

  • Pluripotent cells converted to: granulocytes (neutrophils/eosinophils/basophils), monocytes or lymphocytes (B cells and T cells)

  • Lymphocytes

    • Production begins in bone marrow

    • Migrate to thymus to complete development then return to blood

    • May migrate to peripheral tissues and are returned to circulation by lymphatic system

Role of WBC’s: Two Main Types of Immunity

• Innate/Natural Immunity

  • Key Features

    • Non-specific

    • No memory

    • Fast (sec/min/h)

  • Major cells involved

    • Phagocytes (neutrophils and macrophages)

  • Major molecules involved

    • Complement system

• Acquired/Adaptive Immunity

  • Key Features

    • Specific

    • Has memory

    • Slow (days/weeks)

  • Major cells involved

    • Lymphocytes (B and T cells)

  • Major molecules involved

    • Antibodies

    • Cytotoxic molecules

Role of the Immune Systems

• Appropriate responses of the immune system: defense, remove old/damaged/abnormal cells

• Inappropriate responses of the immune system: allergies, autoimmune reactions