Blood and Hematopoiesis Review

Fundamental Characteristics and Functions of Blood

• Definition: Blood is classified as a specialized form of liquid connective tissue.

• Primary Functional Systems:

  • Transportation System:

    • Oxygen and Nutrients: Delivery of $O_2$ and vital nutrients to all peripheral cells.

    • Waste Products: Removal of metabolic waste products from cells for excretion.

    • Hormonal Transport: Moving hormones from endocrine glands to their respective target organs.

    • White Blood Cells (WBCs): Transporting leukocytes from the bone marrow to the specific tissues where they are needed for defense.

    • Platelets: Delivery to sites of vascular damage to facilitate repair.

  • Regulatory System:

    • Body Temperature: Maintenance of thermal homeostasis throughout the body.

    • Tissue Fluid Content: Managing levels to avoid dehydration or edema.

    • Hemoconcentration vs. Hemodilution: Regulating the ratio of cellular elements to fluid volume.

    • Acid-Base Balance: Crucial for maintaining the physiological $pH$ of blood, which is approximately $7.4$.

  • Defense System:

    • Phagocytosis: The active engulfing and destruction of pathogens by specific white blood cells.

    • Clotting Process: Preventing excessive blood loss through the cascade that forms stable thrombi.

Blood Composition: Fluid and Cellular Components

• Whole Blood Constituents:

  • Fluid Portion: Referred to as Plasma.

  • Cellular Portion (Formed Elements):

    • Erythrocytes: Red blood cells (RBCs).

    • Leukocytes: White blood cells (WBCs).

    • Thrombocytes: Platelets.

• K-9 (Canine) Blood Composition Analysis:

  • Body Proportions: Whole blood accounts for approximately $8\%$ of body weight; other fluids and tissues make up $92\%$.

  • Volume Split:

    • Plasma: $55\%$

    • Formed Elements: $45\%$

  • Formed Elements (Counts per $\mu\text{L}$):

    • Erythrocytes: $5.5\text{ to }8.5 \times 10^6/\mu\text{L}$.

    • Thrombocytes: $200,000\text{ to }500,000/\mu\text{L}$.

    • Leukocytes: $6,000\text{ to }17,000/\mu\text{L}$.

  • Differential WBC Count:

    • Neutrophils: $60-77\%$

    • Lymphocytes: $12-30\%$

    • Eosinophils: $2-10\%$

    • Monocytes: $3-10\%$

    • Basophils: Rare.

  • Plasma Composition:

    • Water: $91.5\%$

    • Proteins: $7\%$

      • Albumin: $44\%$

      • Globulins: $42\%$

      • Fibrinogen: $4\%$

    • Other Solutes: $1.5\%$

      • Includes carbohydrates, lipids, vitamins, hormones, and inorganic salts.

Plasma vs. Serum

• Plasma:

  • Represents the liquid portion of whole blood.

  • Comprises $45-78\%$ of total blood volume depending on species and hydration.

  • Composed of approximately $90\%$ water and $10\%$ dissolved constituents (proteins, nutrients, gases).

  • Contains Fibrinogen (clotting protein).

  • Obtained when an anticoagulant is used to prevent the blood from clotting.

• Serum:

  • Represents the liquid portion of blood remaining after clotting has occurred.

  • Lacks clotting elements because Fibrinogen is converted into insoluble Fibrin during the clot formation.

  • Description: Whole blood liquid minus cells and clotting elements.

• Physical Appearance of Plasma:

  • Typically translucent.

  • Displays varying degrees of yellow coloration dependent on hydration status and the concentration of bilirubin (a hemoglobin breakdown product).

Hematopoiesis: The Production of Blood Cells

• Definition: The continuous process of producing all blood cells. Specific terms include:

  • Erythropoiesis: Production of erythrocytes.

  • Leukopoiesis: Production of leukocytes.

  • Thrombopoiesis: Production of thrombocytes.

• Anatomical Locations of Hematopoiesis:

  • Prenatal/Newborn: Occurs in the liver, spleen, thymus (specifically T-cell maturation), and red bone marrow. In young, growing animals, red bone marrow is found in nearly all bones due to high demand.

  • Adults: Primarily limited to red bone marrow found in the ends of long bones and in flat bones. The remaining marrow space is converted to inactive yellow bone marrow (fatty).

  • Stress/Demand: In times of high demand, the liver and spleen can resume hematopoietic activities.

• The Hematopoietic Pathway:

  • Pluripotent Hematopoietic Stem Cell (PPSC): Also known as a hemocytoblast, this is the common ancestor to all blood cells.

  • Cytokines: Chemical messengers that initiate the differentiation of PPSCs into specific lineages. This process is irreversible.

  • Myeloid Lineage:

    • Erythroblasts $\rightarrow$ Erythrocytes.

    • Myeloblasts $\rightarrow$ Granulocytic leukocytes (Neutrophils, Eosinophils, Basophils) and Monocytes/Macrophages.

    • Megakaryoblasts $\rightarrow$ Megakaryocytes $\rightarrow$ Platelets.

  • Lymphoid Lineage:

    • Lymphocytes: Differentiate into B-lymphocytes, T-lymphocytes, and Natural Killer (NK) cells.

Erythrocytes: Red Blood Cells (RBCs)

• Physical Characteristics:

  • Mature Mammalian RBC: A non-nucleated, biconcave disc designed for maximum gas exchange. It stains red due to hemoglobin.

  • Composition: Approximately $65\%$ water and $35\%$ solids. Hemoglobin makes up $95\%$ of those solids.

  • Immature RBC: May still contain a nucleus before being released or shortly after.

• Species-Specific Morphology:

  • Canine: Largest RBCs (approx. $7\,\mu\text{m}$ diameter) with a distinct central pallor.

  • Size Order (Descending): Feline, horse, cow, sheep, and goat.

  • Avian, Reptiles, Fish: RBCs are oval and nucleated.

  • Camelids: RBCs are oval and non-nucleated.

  • Deer: Specific trait where RBCs can appear sickle-shaped.

• Benefits of the Biconcave Disc Shape:

  • Provides more membrane surface area for $\text{O}_2$ and $\text{CO}_2$ diffusion.

  • Creates a shorter diffusion distance to the center of the cell.

  • Allows the cell membrane to be deformable, enabling it to swell or move through narrow capillaries without rupturing.

• Erythrocyte Lifecycle:

  • Formation: Stimulated by Erythropoietin (EPO), a cytokine produced by the kidneys in response to hypoxia. EPO binds to receptors on erythroid precursors in the bone marrow.

  • Lifespan Examples:

    • Dogs: $110$ days.

    • Cats: $68$ days.

    • Humans: $120$ days.

    • Horses: $150$ days.

    • Cattle: $160$ days.

    • Mice: $20$ days.

  • Senescence: The natural process of cell aging.

  • Destruction:

    • Extravascular Hemolysis ($90\%$): Occurs outside blood vessels via macrophages. Iron is recycled to bone marrow; Heme is converted to bilirubin; amino acids from globin return to the liver.

    • Intravascular Hemolysis: RBC destruction occurring directly within the blood vessels.

Leukocytes: White Blood Cells (WBCs)

• Classification Criteria:

  • Granulocytes (contain granules): Neutrophils, Eosinophils, Basophils.

  • Agranulocytes (lack granules): Monocytes, Lymphocytes.

  • Nuclear Shape: Polymorphonuclear (multilobed), Mononuclear (single rounded), or Pleomorphic (varying shapes).

• Granulocytes Detail:

  • Neutrophils:

    • Staining: Colorless or faint violet granules.

    • Segmented (Mature): $3-5$ nuclear lobes. Predominant WBC in dogs.

    • Banded (Immature): Horseshoe-shaped nucleus; presence in blood indicates significant inflammation.

    • Function: First responders in acute inflammation ($5$-day lifespan in blood); utilize chemotaxis and phagocytosis.

  • Heterophils: Functional equivalents to neutrophils found in birds, reptiles, some fish, rabbits, and guinea pigs. They have rod-shaped, red-staining granules.

  • Eosinophils:

    • Staining: Deep pink/orange granules (pick up acidic eosin stain).

    • Function: Combat parasitic infections, modulate allergic responses, and respond to viral infections.

    • Species Variance: Cats have small rod-shaped granules; Horses have very large, intense round/oval granules; Dogs have round granules varying in size.

  • Basophils:

    • Staining: Blue-black/purple granules (basic stain).

    • Function: Least common WBC. Contain Histamine (vasodilator) and Heparin (anticoagulant). Associated with hematologic malignancies if elevated.

• Agranulocytes Detail:

  • Monocytes:

    • Size: Largest WBC ($17-25\,\mu\text{m}$).

    • Morphology: Blue-gray cytoplasm with "ground-glass" appearance; kidney-shaped nucleus.

    • Function: Differentiate into Macrophages when they enter tissues; provide powerful phagocytosis.

  • Lymphocytes:

    • Size: Smallest WBC ($7-9\,\mu\text{m}$). Predominant in ruminants and pigs.

    • Types:

      • T-cells: Cellular immunity (antigen recognition, virus-infected cells).

      • B-cells: Antibody production (bacteria and toxins).

      • NK cells: Natural killer cells for tumor and virus-infected cells.

Thrombocytes: Platelets

• Morphology: Small ($2-3\,\mu\text{m}$), irregular pieces of cytoplasm containing purple granules. They lack a nucleus.

• Formation: Driven by Thrombopoiesis. They are fragments of the cytoplasm of Megakaryocytes, giant multinucleated cells that remain in the bone marrow.

• Functions:

  • Hemostasis: Essential for stopping hemorrhage via the formation of a platelet plug.

  • Coagulation: Works with fibrinogen to form a stable thrombus.

  • Wound Repair: Release peptide growth factors to initiate the repair and regeneration of connective tissue and blood vessels.

• Disposition: They circulate in peripheral blood until removed by macrophages.