Blood ch1`9

Major Body Fluids:

1. Blood: Circulates inside blood vessels

2. Interstitial Fluid (ISF): Bathes body cells/tissues

3. Lymph: Circulates inside lymph vessels

4. Hematology: Study of blood, blood-forming tissues, and associated disorders

   • Diseases:

     • Hemolytic Disease

     • Sickle Cell Disease

Functions of Blood:

1. Transportation:

   • Gases: Oxygen (O2), Carbon Dioxide (CO2)

   • Nutrients and Hormones

   • Cells: E.g., WBC for immunity

   • Heat and Wastes: Helps in heat distribution and waste removal

2. Regulation:

   • pH Balance: Buffering to maintain [H+]

   • Body Temperature

   • Water Content: Regulates cell hydration

3. Protection:

   • Inflammation & Immunity

   • Hemostasis: Coagulation to seal cuts

Physical Characteristics of Blood:

• Viscosity: Higher than water

• Temperature: 100.4°F (38°C)

• pH: 7.35–7.45

• Blood Volume: 4-6L

  • Maintained through negative feedback mechanisms

• Weight: Blood constitutes ~8% of total body weight

Components of Blood:

• Centrifuged Blood:

  • Plasma (top) – 55%

  • Formed Elements (45%):

    • Buffy Coat (middle): WBCs and platelets

    • Red Blood Cells (bottom)

Formed Elements:

• Short-Lived: Most need constant replenishment

  • RBCs and platelets regulated via negative feedback

  • WBCs count varies based on challenges (e.g., pathogens, tissue injury)

• Hemopoiesis (Hematopoiesis):

  • Blood cell production from Pluripotent Stem Cells

  • Differentiate into various blood cells

Sites of Hemopoiesis:

• Embryo: Yolk sac

• Fetus (up to 6 months):

  • Liver

  • Spleen

  • Thymus

  • Lymph nodes

• Fetus (7-9 months):

  • Red Bone Marrow

• Birth → Adulthood:

  • Red Bone Marrow (primary site)

Red Bone Marrow:

• Highly Vascularized Connective Tissue

  • Newborns: All bone marrow is red

  • As We Age: Red marrow replaced by yellow marrow in long bones

  • Flat Bones: Predominant site for hematopoiesis (pelvis, sternum, ribs, vertebrae, scapulae)

Formation of Blood Cells:

• Pluripotent Hematopoietic Stem Cells:

  • Differentiate into Lymphoid Stem Cells (T cells, B cells, NK cells) and Myeloid Stem Cells (other blood cells)

• Growth Factors:

  • Erythropoietin (EPO): Stimulates RBC production in red bone marrow

  • Thrombopoietin: Stimulates platelet precursor production

  • Cytokines: Stimulate WBC production (colony-stimulating factors, interleukins)

Red Blood Cell (RBC) Formation:

• Process:

  1. CFU-E → Proerythroblast → Reticulocyte → RBC

  2. Reticulocytes enter the bloodstream, mature into RBCs

  3. Reticulocyte Count: 0.5–1.5% of RBCs

  4. RBC Maturation: Lose organelles (e.g., mitochondria) to become mature cells

RBC Anatomy:

• Shape: Biconcave discs (8µm diameter)

• Plasma Membrane: Strong and flexible

• No Nucleus/Organelles:

  • Can't reproduce or metabolize extensively

  • Anaerobic ATP production (don't consume O2)

• Hemoglobin:

  • Located in cytosol

  • Binds and transports O2 and CO2

  • Iron in heme binds reversibly with O2

RBC: Other Functions:

1. Oxygen Transport: Carry O2 from lungs to tissues

2. Nitric Oxide Release: In hypoxia, promotes vasodilation, improving blood flow and O2 delivery

3. Carbonic Anhydrase: Converts CO2 + H2O to carbonic acid for CO2 transport

RBC Life Cycle:

• Lifespan: ~120 days

  • Wear and tear on plasma membrane leads to rupture

• Aged RBCs: Removed by phagocytic macrophages in the spleen and liver

  • Hemoglobin Recycling:

    • Globin: Reused for protein synthesis

    • Iron: Carried by transferrin to liver, stored as ferritin, or used in RBC production

    • Heme: Converted to bilirubin, excreted via liver in bile

White Blood Cells (WBCs)

1. Characteristics:

   • Nucleated cells without hemoglobin

   • Lifespan: Usually hours to a few days

     • Can be quantified when activated

     • Normal Count: 5000–10,000 WBCs/mL

   • Leukocytosis: WBC count > 10,000 (high count)

   • Leukopenia: WBC count < 5,000 (low count)

2. Differential Count:

   • Two Principal Types (based on granule staining):

     • Granular: Neutrophils, eosinophils, basophils

     • Agranular: Lymphocytes, monocytes/macrophages, NK cells

WBC Cell Types:

1. Neutrophils (60-70% of WBCs):

   • Multi-lobed nucleus (2-5 lobes)

   • Function: Phagocytosis

2. Eosinophils (2-4% of WBCs):

   • 2 lobes connected by thick chromatin

   • Function: Associated with histamine, phagocytosis

   • Stain red

3. Basophils:

   • Release heparin, histamine, serotonin

   • Stain dark blue

4. Agranular:

   • Lymphocytes: Round, slightly indented nucleus, sky-blue cytoplasm

   • Monocytes: Kidney-shaped nucleus, blue-grey cytoplasm, foamy appearance

   • Function: Phagocytosis

Functions of WBCs:

1. Defense:

   • Combat invasion/infection

   • Promote inflammation and tissue healing

2. Mechanisms:

   • Phagocytosis (neutrophils, macrophages)

   • Antiparasitic (eosinophils)

   • Release of inflammatory mediators

   • Production of antibodies (B cells → plasma cells)

   • Cytotoxicity of target cells (CD8+ T cells, NK cells)

   • Coordination of immune response (CD4+ T helper cells)

3. Emigration:

   • WBCs can roll and exit blood vessels to reach sites of infection

Differential WBC Count:

• Purpose: Used to detect:

  • Inflammation

  • Infection

  • Parasitic infections/allergic reactions

  • Chemical/drug poisoning

  • Blood disorders (e.g., low counts)

  • Effects of chemotherapy

Platelets:

1. Platelet Production:

   • Stimulated by thrombopoietin

   • Myeloid stem cells → CFU-Meg → megakaryoblast → megakaryocyte → platelets

   • Megakaryocytes fragment into 2000-3000 pieces, each enclosed by plasma membrane

2. Platelet Anatomy:

   • No nucleus

   • Contain many vesicles with potent chemical mediators

   • Normal Count: 250,000–400,000 platelets/uL

   • Lifespan: 5-9 days

     • Aged platelets are removed by macrophages in spleen and liver

3. Platelet Function:

   • Primary Role: Blood clotting

     • Degranulation: Release of chemicals to promote clotting and aid inflammation

Hemostasis:

1. Definition: Arrest of bleeding from injured blood vessels

   • Must be rapid, localized, and carefully controlled

2. Stages of Hemostasis:

   1. Vascular Spasm: Blood vessel constriction to minimize blood loss

   2. Platelet Plug Formation: Platelets adhere and aggregate at the injury site

   3. Blood Clotting (Coagulation): Formation of a fibrin clot

Vascular Spasm:

• Mechanism: Smooth muscle contraction in vessel wall

• Triggers: Vessel damage and chemicals released by platelets and endothelial cells

• Reflexes from pain receptors may also contribute

Platelet Plug:

• Activation: Platelets adhere to exposed collagen under damaged endothelium

• Degranulation: Release of chemicals

• Aggregation: Clumping of platelets to seal injury

Coagulation:

1. Clotting Cascade:

   • Three stages:

     1. Formation of prothrombinase

     2. Conversion of prothrombin to thrombin

     3. Conversion of fibrinogen to fibrin

2. Two Pathways:

   • Extrinsic Pathway: Triggered by tissue damage and the release of Tissue Factor

   • Intrinsic Pathway: Triggered by endothelial damage (minimal)

   • Both pathways converge at the common pathway for clot formation

Hemostasis: Other Factors:

• Vitamin K: Essential for the synthesis of clotting factors (II, VII, IX, X)

• Clot Retraction: Clot tightens to pull the edges of the damaged vessel together

Fibrinolysis:

• Function: Dissolves the clot after tissue repair

• Mechanism: Plasminogen is converted into plasmin, which digests fibrin threads and inactivates clotting factors

Hemostatic Control Mechanisms:

1. Clot Localization:

   • Fibrin absorbs thrombin to prevent its spread

   • Clotting factors become diluted in the bloodstream

   • Prostacyclin inhibits platelet adhesion

2. Natural Anticoagulants:

   • Heparin

   • Antithrombin III (AT III)

   • Protein C and S

3. Thromboembolism:

   • Clots may form pathologically and obstruct blood flow

   • Embolism: Can travel to the lungs and block blood flow

Blood Groups and Blood Types:

1. Blood Group Antigens: Genetically determined on RBC surfaces

2. ABO Blood Group:

   • Antigens A and B determine blood type

   • Plasma contains antibodies (anti-A and anti-B) that react with foreign antigens

3. Rh Blood Group:

   • Rh+: RBCs have Rh antigen

   • Rh-: RBCs lack Rh antigen

4. Blood Typing:

   • Cross-matching and agglutination tests determine blood type compatibility

Hemolytic Disease of the Newborn (HDN):

• Cause: Destruction of the infant's erythrocytes by maternal antibodies (typically due to Rh incompatibility)

• Prevention: Anti-Rh gamma globulin (RhoGAM) prevents HDN by blocking the immune response

Disorders: Homeostatic Imbalances:

1. Sickle Cell Disease:

   • Abnormal hemoglobin (Hb-S) leads to RBC rupture and clotting

   • Causes anemia, fatigue, painful episodes, and delayed growth

2. Signs and Symptoms of Sickle Cell Disease:

   • Anemia

   • Shortness of breath

   • Fatigue

   • Jaundice

   • Painful episodes