Hematopoiesis and Blood Components

Hematopoiesis

  • Definition: The production of blood cells.
  • Location:
    • Small Children: Occurs in distal long bones and the axial skeleton (almost all bone marrow is hematopoietic).
    • Adults: Occurs primarily in the axial skeleton. Distal long bones lose hematopoietic activity.

Medullary vs. Extramedullary Hematopoiesis

  • Medullary Hematopoiesis: Occurs inside the bone marrow.
  • Extramedullary Hematopoiesis: Occurs outside the bone marrow.

Hematopoiesis Locations Through Development

  • Zygote: Hematopoiesis first occurs in the yolk sac.
  • Fetal Development: As organs develop, hematopoiesis occurs in the liver and spleen.
  • Late Fetal Stage: Bone marrow takes over as bones develop, and liver and spleen activity decreases.
  • At Birth: Ideally, all hematopoiesis is medullary.

Bone Marrow Aspirates

  • Children: Typically taken from the tibia due to thin skin and ease of access.
  • Adults: Usually taken from the iliac crest (hips).

Erythrocytes (Red Blood Cells)

  • Average Diameter: 7-8 micrometers (μm\mu m).
  • Normal Red Blood Cell Description: Normocytic, normochromic.

Red Blood Cell Size

  • Microcytic: Less than 6 μm\mu m in diameter.
  • Macrocytic: Greater than 9 μm\mu m in diameter.

Central Pallor

  • Indication: Reflects the amount of hemoglobin inside the cell.
  • Hypochromia: Larger area of central pallor indicates less hemoglobin.
  • Hyperchromia: Smaller or no area of central pallor indicates more hemoglobin.

Spherocytes

  • Cells with no area of central pallor.
  • Have increased osmotic fragility and can lyse more rapidly.
  • Typically microcytic-Hyperchromic

Blood Volume

  • Females: 4-5 liters.
  • Males: 5-6 liters.
  • Note: Blood volume depends on body size.

Blood Components

  • Plasma: 55% of blood volume.
  • Formed Elements: 45% of blood volume.
    • Red Blood Cells: 44% of formed elements.
    • Buffy Coat: 1% of formed elements, containing white blood cells and platelets.

Erythropoietin (EPO)

  • Definition: A hormone produced in the kidneys that regulates oxygen-carrying capacity.
  • Function: Released in response to decreased oxygen-carrying capacity.
  • Mechanism: Stimulates the bone marrow to produce erythrocytes.

Thrombopoietin

  • Released from the liver to stimulate thrombocyte (platelet) production.

Pluripotent Stem Cells

  • Definition: Stem cells in hematopoietic tissue that can differentiate into any type of blood cell.
  • Location: Hematopoietic tissue.
  • Key Feature: Self-replication.
  • Clinical Significance: Lack of self-replication can lead to anemias like aplastic anemia.

Hemoglobin Components

  • Heme (iron within a protoporphyrin ring).
  • Globin chains.
  • Note: A decrease in the synthesis of any of these components leads to decreased hemoglobin production.

Red Blood Cell Metabolic Pathways

  • Emden-Meyerhof Pathway (Glycolytic Pathway): Responsible for ATP production (approximately 2 ATP).
    • Physiological Importance: Allows for anaerobic energy production, preventing the red blood cell from consuming the oxygen it transports.
  • Methemoglobin Reductase Pathway: Maintains iron in a reduced state to prevent methemoglobin formation.
  • Luebering-Rapoport Pathway: Production of 2,3-DPG.
  • Phosphogluconate Pathway: Reduces oxidative stress.

Hemoglobin Types

  • Hemoglobin A (Normal Adult Hemoglobin): Contains two alpha and two beta globin chains.
  • Hemoglobin F (Fetal Hemoglobin): Contains two alpha and two gamma globin chains.
    • Has a higher affinity for oxygen, facilitating oxygen extraction from maternal blood.

2,3-DPG

  • Function: Modulates hemoglobin's affinity for oxygen.
    • Presence: Decreases oxygen affinity, placing hemoglobin in a tense state, and releasing oxygen to tissues (deoxyhemoglobin).
    • Absence: Increases oxygen affinity, placing hemoglobin in a relaxed state (oxyhemoglobin), and reducing oxygen delivery to tissues.

Spherocytes (Revisited)

  • Microcytic, hyperchromic cells with increased osmotic fragility.
  • Cells lyse easily due to their already swollen state.

Iron

  • Location: Majority is bound to hemoglobin.
  • Importance: Essential for oxygen transport;
  • Iron must be in the ferrous (Fe2+Fe^{2+}) state.
  • Iron is conserved within the body, with minimal loss except through gastrointestinal shedding and menstruation.

Ferritin vs. Transferrin

  • Similarity: Both are related to iron metabolism.
  • Difference:
    • Ferritin: Storage form of iron (Fe3+).
    • Transferrin: Transport protein for iron (Fe3+), delivering iron to the bone marrow for erythropoiesis.

Iron Deficiency Anemia

  • Most common anemia worldwide, especially in menstruating females.
  • Caused by blood loss and inadequate iron replacement.

Megaloblastic Anemia

  • Caused by a decrease in vitamin B12 or folic acid, leading to impaired DNA synthesis.
  • Characterized by macroovalocytes in the peripheral blood and intramedullary hemolysis.
  • Hypersegmented neutrophils are also seen.

Relationship between Folic Acid and B12

  • B12 is required to recycle the methyl group from methyl tetrahydrofolate, enabling folate recycling for DNA synthesis.

Vitamin B12 Absorption

  • Intrinsic factor is required for B12 absorption into mucosal cells.
  • Pernicious anemia is caused by issues with intrinsic factor and is a common type of megaloblastic anemia.
  • Transcobalamin II transports B12 to the bone marrow.
  • B12 deficiency can cause neurologic manifestations like tingling in the fingers and toes.

Anemia Compensation

  • The bone marrow can increase output to compensate for anemia.
  • Compensatory mechanisms:
    • Increased erythropoietin (EPO) levels.
    • Increased reticulocytosis (elevated reticulocyte count).
    • The body can increase red blood cell output about six times the normal amount.

Hemoglobinopathies

  • Blood disorders affecting hemoglobin.

Types of Hemoglobinopathies

  • Quantitative (Thalassemias): Decreased production of one or more globin chains.
  • Qualitative: Structural or functional defects in globin chains, often due to single amino acid substitutions.

Sickle Cell Anemia

  • Type: Qualitative hemoglobinopathy.
  • Cause: Amino acid substitution of valine for glutamic acid on the beta-globin chain.
  • Sickle Cell Disease (Heterozygous): Carrier state with potentially normal life.
  • Sickle Cell Anemia (Homozygous): HbSS, significant clinical manifestations, including sickle cell crisis.

Leukocytes and Their Functions

  • Neutrophils:
    • First line of defense and most mobile cells.
    • Function through chemotaxis, opsonization, recognition, digestion, ingestion, and killing.
  • Eosinophils:
    • Response to parasitic infections and allergic reactions.
    • Contain histamine.
  • Basophils:
    • Hypersensitivity reactions, contain histamine that can cause anaphylaxis.
  • Lymphocytes: Immunologic responses (B cells, T cells, natural killer cells).
  • Monocytes: Scavengers, including red pulp macrophages (littoral cells) in the spleen, and involved in hemostasis to break down blood clots.

Leukocyte Abundance

  • Neutrophils are the most numerous leukocytes in the blood.

Leukemia

  • Definition: Cancer of the blood involving bone marrow failure.

Leukemia Types

  • Acute Leukemia:
    • Characterized by immature (blast) cells.
    • Requires immediate treatment.
    • Can affect children.
  • Chronic Leukemia:
    • Characterized by mature cells.
    • Insidious onset, often affecting adults.
    • May involve active monitoring.

Leukemia Lineage

  • Lymphocytic Leukemia: Affects B cells or T cells (lymphoid line).
  • Myeloid Leukemia: Affects other blood cells (myeloid line).

Complications of Leukemia

  • Accumulation of monoclonal cells leads to pancytopenia (decrease in other cell lines).
    • Anemia: Reduced oxygen-carrying capacity.
    • Thrombocytopenia: Easy bruising.
    • Leukopenia: Increased susceptibility to infection.

Coombs Test

  • Purpose: To rule out immune-mediated destruction of blood cells.
  • Immune cells target blood cells, leading to penias.

Lymphomas

  • Reed-Sternberg Cell:
    • Massive multinucleated cell seen in Hodgkin's lymphoma.
    • Most common form is nodular sclerosis.
  • Distinction from Leukemia: Typically present with a mass (axonal lymphoma).
  • Overlap: Small lymphocytic leukemia and small lymphocytic lymphoma are sometimes classified as the same disease.