Composition and Function of Blood and Haematopoiesis

General Composition of Blood

  • Blood is viewed as a complex mixture consisting of liquid plasma and various formed elements (cells).
  • Total Blood Volume Breakdown:
    • Plasma: Compiles approximately 55%55\% of the total blood volume.
    • Cells (Formed Elements): Compiles approximately 45%45\% of the total blood volume.
  • Haematocrit: This term refers specifically to the percentage of blood volume that is occupied by red blood cells (typically reflective of the 45%45\% cell volume mentioned above).

Detailed Composition of Plasma

Plasma is the liquid component of blood, described as a solution of various substances within water. It consists of interstitial fluid plus specific plasma proteins.

  • Water: The major component of plasma, making up approximately 91%91\% of its weight.
  • Proteins (7%7\% by weight):
    • Albumins and Globulins: These are critical for maintaining osmotic pressure in the circulatory system. They also act as buffers to maintain pH and serve as transport vehicles for various substances.
    • Fibrinogen: A protein essential for the blood clotting cascade.
    • Antibodies: Involved in the immune response.
    • Others: Includes enzymes, enzyme precursors, and enzyme cofactors.
  • Other Solutes (2%2\% by weight):
    • Electrolytes: Various ions required for cellular function.
    • Nutrients: Glucose, amino acids, and lipids.
    • Waste Products: Metabolic by-products like urea and creatinine.
    • Gases: Dissolved O2O_2 and CO2CO_2.
    • Regulatory Substances: Hormones and vitamins.

Erythrocytes (Red Blood Cells)

  • Abundance: Erythrocytes are the most abundant cell type in the blood, with a concentration of approximately 5×1065 \times 10^6 per mlml (55 million per mlml).
  • Function: Their primary role is the facilitation of gas transport throughout the body.
  • Structural Characteristics:
    • Shape: They possess a biconcave shape maintained by a complex cytoskeleton, which increases surface area for gas exchange.
    • Organelles: Mature erythrocytes lack a nucleus and mitochondria to maximize space for hemoglobin and prevent the cell from consuming the oxygen it transports.
    • Osmotic Sensitivity: The shape of the erythrocyte is altered by changes in the osmotic pressure of the surrounding plasma.
  • Haemoglobin (Hb):
    • Concentration in blood: 140–160 g/l140–160\,g/l.
    • Each single Red Blood Cell (RBC) contains approximately 280280 million copies of Hb.
    • Molecular Structure: Hb consists of four polypeptide chains. The most common adult form includes two alpha (α\alpha) and two beta (β\beta) chains.
    • Each subunit (chain) contains a haem group, and each haem group contains one iron (FeFe) atom.

Leukocytes (White Blood Cells)

  • Abundance: Leukocytes constitutes less than 1%1\% of total blood volume. The normal concentration is 4,000−11,0004,000 - 11,000 per mlml.
  • General Features: Unlike RBCs, leukocytes are nucleated and are primarily involved in the body's immune response. They travel to sites of infection via chemotaxis (movement toward chemical stimuli) mediated by chemokines.
  • Normal Differential White Blood Cell Count:
    • Neutrophils (50−70%50-70\%): Specialized in phagocytizing pathogens; contain granules; size 12−15 μm12-15\,\mu m.
    • Lymphocytes (25−35%25-35\%): Active in specific immunity; size 8−10 μm8-10\,\mu m.
    • Monocytes (4−6%4-6\%): Become large phagocytes; size 16−20 μm16-20\,\mu m.
    • Eosinophils (1−3%1-3\%): Active in allergic reactions and combating worm infections; contain granules; size 12−15 μm12-15\,\mu m.
    • Basophils (0.4−1%0.4-1\%): Release histamine to mediate inflammatory responses; contain granules; size 9−10 μm9-10\,\mu m.

Thrombocytes (Platelets)

  • Abundance: Normal range is 150,000−450,000150,000 - 450,000 per mlml.
  • Structure: They are not whole cells but rather fragments of cytoplasm. They lack a nucleus but contain cytoplasmic granules.
  • Origin: They are released from very large cells in the bone marrow called megakaryocytes.
  • Function: Their primary role is in blood clotting and maintaining hemostasis.

Haematopoiesis

  • Timeline and Location:
    • Process begins in the embryo.
    • Until the age of 55, all bone marrow is active in blood cell production.
    • Throughout adult life, active marrow (red marrow) decreases, while inactive marrow (yellow marrow) increases.
    • In adults, active red marrow remains in the pelvis, spine, ribs, cranium, and the proximal ends of large bones (e.g., femur, humerus).
  • Hierarchical Stages of Haematopoiesis:
    1. Pluripotent Haemopoietic Stem Cells: Self-renewing cells that can give rise to any blood cell line.
    2. Multipotent Stem Cells: Still self-renewing, but more committed to specific lineages.
    3. Burst Forming Progenitor Cells: Limited capacity for self-renewal.
    4. Precursor Cells (Blasts): These are no longer self-renewing cells. They undergo approximately 66 cell divisions to increase numbers.
    5. Mature Cells: These are the final, non-mitotic cells that enter circulation.

Regulation by Cytokines

  • Colony Stimulating Factors (CSFs): Produced by endothelial cells (EC), marrow fibroblasts, and white blood cells. They regulate leukopoiesis (production of WBCs) by stimulating mitosis and maturation of stem cells to meet the body's needs.
  • Interleukins (ILs): Various types (e.g., IL-3, IL-7) involved in cell signaling for different lineages.
  • Stem Cell Factor (SCF): A cytokine essential for stem cell maintenance.
  • Thrombopoietin (TPO): A glycoprotein that regulates the growth and maturation of megakaryocytes into platelets.
  • Erythropoietin (EPO): A glycoprotein that regulates erythropoiesis (production of RBCs); it is released by the kidneys in response to tissue hypoxia (low oxygen levels).

Erythropoiesis Pathway

  • Progression: Multipotent stem cell →\rightarrow Large nucleated erythroblast (approx. 20 μm20\,\mu m) →\rightarrow Maturation and nucleus expulsion →\rightarrow Reticulocyte (immature RBC, approx. 7 μm7\,\mu m).
  • Exit: The reticulocyte leaves the bone marrow and enters the general circulation, where it matures into a functional erythrocyte (approx. 8 μm8\,\mu m).

Functions of Blood

  • Transport: Moves gases (O2O_2, CO2CO_2), nutrients, waste products, and hormones.
  • Homeostasis: Maintenance of body temperature through heat distribution.
  • Defense: Provides defense mechanisms via white blood cells and antibodies.

Blood Cell Pathologies

Anaemia (Red Blood Cell Disorders)

  • Sickle Cell Anaemia: Caused by abnormal Hemoglobin (HbS). HbS crystallizes when deoxygenated, causing the RBC to take a sickle shape and potentially block vessels.
  • Haemolytic Anaemia: Can be hereditary or acquired. RBCs become spherical and fragile, leading to easy rupture.
  • Iron-deficiency Anaemia: Characterized by low RBC count or low Hb content. Cells are typically microcytic (small) and hypochromic (pale).
  • Pernicious Anaemia: Typically related to Vitamin B12 deficiency.
  • Normocytic Anaemia: RBCs are normal in size but the overall count is low.
  • Polycythaemia vera: A condition of overproduction of RBCs.
  • Haemochromatosis: A condition involving iron overload in the body.

Leukocyte Disorders

  • Leukopenia: A low white blood cell count. Causes include chemotherapy, radiation, autoimmune diseases, spleen/liver diseases, viral infections, and nutrient deficiencies (vitamins/minerals).
  • Leukocytosis: A high white blood cell count. Causes include infection, allergy, systemic/inflammatory diseases (like Rheumatoid Arthritis), tissue damage (burns), physical/emotional stress, pregnancy, and certain medications.
  • Leukaemia: A type of cancer involving white blood cells. Types mentioned include:
    • Lymphocytic
    • Myelogenous
    • Erythroid