Chapter 17: Blood – Structure, Function, and Hemostasis

Blood: Composition, Cellular Elements, and Hemostasis

Composition of Plasma

Plasma is the liquid matrix of blood, making up about 55% of total blood volume. It serves as a medium for transporting nutrients, hormones, and waste products throughout the body.

• Water: Comprises about 92% of plasma; acts as a solvent and helps maintain blood volume and pressure.

• Plasma Proteins: Account for about 7% of plasma. Major types include:

  • Albumins: Maintain osmotic pressure and transport substances.

  • Globulins: Involved in immune responses (immunoglobulins) and transport of lipids and metal ions.

  • Fibrinogen: Essential for blood clotting (coagulation).

• Other Solutes: About 1% of plasma; includes electrolytes (Na+, K+, Ca2+, Cl-, HCO3-), nutrients (glucose, amino acids), gases (O2, CO2), and metabolic wastes (urea, creatinine).

Example: Albumin helps maintain blood osmotic pressure, preventing excessive fluid loss from capillaries.

Cellular Elements of Blood

Blood contains three main types of formed elements, each with distinct functions and characteristics.

• Erythrocytes (Red Blood Cells, RBCs): Biconcave, anucleate cells specialized for oxygen and carbon dioxide transport via hemoglobin.

• Leukocytes (White Blood Cells, WBCs): Nucleated cells involved in immune defense. Subtypes include:

  • Granulocytes: Neutrophils, eosinophils, basophils.

  • Agranulocytes: Lymphocytes, monocytes.

• Thrombocytes (Platelets): Small, anucleate cell fragments derived from megakaryocytes; essential for blood clotting.

Example: Neutrophils are the most abundant WBCs and are first responders to infection.

Hematopoiesis: Formation of Blood Cells

Hematopoiesis is the process by which all blood cells are formed from pluripotent hematopoietic stem cells (HSCs) in the bone marrow.

• Embryo: Occurs in yolk sac, liver, spleen.

• Children: Occurs in all bones with red marrow.

• Adults: Restricted to axial skeleton (pelvis, ribs, sternum, vertebrae, proximal femur/humerus).

• Cytokines: Growth factors such as erythropoietin (EPO), thrombopoietin (TPO), and colony-stimulating factors (CSFs) regulate differentiation.

Example: EPO stimulates RBC production in response to hypoxia.

Complete Blood Count (CBC) and Blood Indices

A CBC is a routine laboratory test that quantifies the cellular components of blood and provides important diagnostic information.

• Components: RBC count, WBC count, platelet count, hemoglobin (Hb), hematocrit (Hct), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC).

• Hematocrit (Hct): Percentage of blood volume occupied by RBCs; normal adult values: males ~42-54%, females ~38-46%.

Parameter	Definition	Significance
RBC Count	Number of RBCs per microliter	Oxygen-carrying capacity
Hemoglobin (Hb)	g/dL of blood	Oxygen transport
MCV	Average RBC volume	Classifies anemia type
MCH	Average Hb per RBC	Detects hypochromia
MCHC	Average Hb concentration in RBCs	Assesses cell color

Example: Low hematocrit may indicate anemia; high values suggest polycythemia.

Red Blood Cell Structure and Hemoglobin

RBCs mature from reticulocytes, which still contain some organelles, to mature erythrocytes, which are anucleate and optimized for gas transport.

• Reticulocytes: Immature RBCs with residual RNA; mature in 1-2 days in circulation.

• Mature RBCs: Biconcave, flexible, lack nucleus and organelles.

• Hemoglobin Structure: Each molecule consists of 4 globin chains (2 alpha, 2 beta) and 4 heme groups, each binding one O2 molecule.

Hemoglobin Equation:

$\text{Hb} + 4\,\text{O}_2 \rightleftharpoons \text{Hb}(\text{O}_2)_4$

Example: Sickle cell disease results from a mutation in the beta-globin gene, altering hemoglobin structure and RBC shape.

Iron Metabolism and Hemoglobin Synthesis

Iron is essential for hemoglobin synthesis and is tightly regulated in the body.

• Absorption: Occurs in the duodenum; dietary iron is absorbed as Fe2+ or heme iron.

• Transport: Bound to transferrin in plasma.

• Storage: Stored as ferritin in the liver, spleen, and bone marrow.

• Recycling: Macrophages recycle iron from senescent RBCs.

• Excretion: Minimal; lost via sloughed mucosal cells, sweat, and menstruation.

Example: Iron deficiency impairs hemoglobin synthesis, leading to microcytic, hypochromic anemia.

Red Blood Cell Pathologies

Disorders of RBC production or survival can disrupt oxygen transport.

• Anemia: Decreased RBCs or Hb; causes include blood loss, decreased production, or increased destruction.

• Polycythemia: Increased RBC mass; may be primary (bone marrow disorder) or secondary (chronic hypoxia).

• Inherited Disorders: Spherocytosis (membrane defect), sickle cell disease (hemoglobinopathy).

Example: Sickle cell anemia causes vaso-occlusive crises and impaired oxygen delivery.

Platelets and Megakaryocytes

Platelets are small, anucleate cell fragments essential for hemostasis, derived from large bone marrow cells called megakaryocytes.

• Megakaryocytes: Large, polyploid cells in bone marrow; extend cytoplasmic processes into blood vessels to release platelets.

• Platelets: Contain granules with clotting factors, enzymes, and signaling molecules; lifespan ~7-10 days.

• Functions: Form platelet plugs, release factors for coagulation and vessel repair.

Example: Thrombocytopenia (low platelet count) increases bleeding risk.

Hemostasis and Coagulation

Hemostasis is the process that prevents blood loss after vessel injury, involving three major steps.

• Vascular Spasm: Immediate vasoconstriction to reduce blood flow.

• Platelet Plug Formation: Platelets adhere to exposed collagen, become activated, and aggregate.

• Coagulation: Cascade of enzymatic reactions leading to fibrin clot formation.

Hemostasis Steps Equation:

$\text{Vascular Spasm} \rightarrow \text{Platelet Plug} \rightarrow \text{Coagulation (Fibrin Clot)}$

Example: Platelet activation involves release of ADP and thromboxane A2, promoting further aggregation (positive feedback).

Coagulation Pathways and Fibrinolysis

Coagulation involves two initial pathways that converge to form a stable fibrin clot, followed by clot dissolution (fibrinolysis).

• Intrinsic Pathway: Triggered by contact with subendothelial collagen; involves factors XII, XI, IX, VIII.

• Extrinsic Pathway: Initiated by tissue factor (factor III) from injured cells; involves factor VII.

• Common Pathway: Both pathways activate factor X, leading to conversion of prothrombin to thrombin, which converts fibrinogen to fibrin.

• Fibrinolysis: Plasminogen is activated to plasmin by tissue plasminogen activator (tPA), which digests fibrin and dissolves the clot.

Pathway	Trigger	Key Factors
Intrinsic	Contact with collagen	XII, XI, IX, VIII
Extrinsic	Tissue factor (III)	VII
Common	Activation of X	X, V, II (prothrombin), I (fibrinogen)

Fibrinolysis Equation:

$\text{Plasminogen} \xrightarrow{\text{tPA}} \text{Plasmin}$

Example: Deficiency of factor VIII causes hemophilia A, a bleeding disorder.

Additional info: Positive feedback loops in coagulation ensure rapid clot formation but are tightly regulated to prevent excessive clotting (thrombosis).