Blood Components & Hemostasis – Lecture Review

Red Blood Cells (Erythrocytes)

• Lifespan

  • Average life expectancy ≈ 120 \text{ days} (≈ 4 months).
  • Destruction mainly occurs in spleen & liver by macrophages (“red-blood-cell graveyards”).
  • Daily turnover: \dfrac{2 \times 10^5 \text{ RBC}}{\text{sec}} are removed & replaced.
  • Clinical notes
  • Shortened lifespan → hemolytic anemias, mechanical trauma (e.g., prosthetic valves).
  • Prolonged lifespan is rare; usually indicates decreased erythropoiesis.

• Structure & Function of Hemoglobin (Hb)

  • Tetrameric protein: 2 α-chains + 2 β-chains (adult HbA).
  • Each chain carries one heme → 4 \text{ O}_2 molecules per Hb.
  • Iron in the ferrous state (Fe²⁺) binds O₂ reversibly.
  • Other roles
  • Transports \approx 20\% of CO₂ as carbamino-Hb.
  • Buffers blood pH by binding H⁺.
  • Variants: HbA₂, fetal HbF (α₂γ₂), HbS (sickle-cell).

Blood Typing & Antigens

• Definition
  • Antigen = surface glycoprotein/glycolipid capable of eliciting an immune response.
• Major Systems
  • ABO (A, B antigens) • Rh (D antigen) most clinically significant.
• Relationship
  • Blood type reflects which antigens are present on RBC membranes.
  • Plasma contains naturally occurring antibodies (isohemagglutinins) against absent ABO antigens.
  • Example: Type A person (A antigen) possesses anti-B antibodies.
• Transfusion Reactions
  • Mismatch → agglutination, complement activation, hemolysis → acute renal failure.
  • Universal donor: O⁻ (no A, B, or Rh antigens).

Hemostasis After a Paper Cut (Restoring Blood Loss Balance)

1. Vascular Spasm
   • Immediate vasoconstriction ↓ blood flow.
   • Mediated by endothelin, myogenic reflex, pain receptors.
2. Platelet Plug Formation
   • Adhesion – platelets bind exposed collagen via von Willebrand factor (vWF).
   • Activation – shape change, degranulation (ADP, TXA₂, serotonin).
   • Aggregation – GP IIb/IIIa receptors link via fibrinogen → soft plug.
3. Coagulation (Clotting Cascade)
   • Extrinsic (tissue factor, factor VII) & Intrinsic (contact activation, factor XII) converge → activate factor X.
   • Prothrombin (II) → Thrombin (IIa).
   • Thrombin converts Fibrinogen → Fibrin → stabilizes plug.
   • Requires \text{Ca}^{2+}, vitamin K-dependent factors II, VII, IX, X.
4. Clot Retraction
   • Actomyosin in platelets contracts → serum expulsion, wound edges approximate.
5. Fibrinolysis (Clot Removal)
   • Plasmin (from plasminogen via tPA, urokinase) degrades fibrin → D-dimers.

Plasma Proteins & Their Functions

• Albumin (≈ 60\% of plasma proteins)
  • Maintains colloid osmotic pressure (oncotic pressure) ≈ 25 \text{ mmHg}.
  • Transports fatty acids, bilirubin, drugs; major blood buffer.
• Globulins (≈ 36\%)
  • α & β globulins: carrier proteins for metal ions, lipids, hormones.
  • γ globulins = immunoglobulins (antibodies) → adaptive immunity.
• Fibrinogen (≈ 4\%)
  • Soluble precursor to fibrin; essential for blood clot formation.
  • Low fibrinogen (hypofibrinogenemia) → bleeding diathesis.

White Blood Cells (Leukocytes)

• Granulocytes

  • Neutrophils (50–70 % WBC)
  • First responders; phagocytose bacteria; form pus.
  • Eosinophils (1–4 %)
  • Combat parasitic worms, modulate allergic reactions (histaminase).
  • Basophils (
  • Release histamine, heparin; analogous to mast cells in tissues.

• Agranulocytes

  • Lymphocytes (20–40 %)
  • T cells (cell-mediated immunity), B cells (plasma cells → antibodies), NK cells (tumor/virus lysis).
  • Monocytes (2–8 %)
  • Circulate 12–24 h → migrate → macrophages (Kupffer cells, microglia, osteoclasts).

• Functional Activity Timeline

  • Acute bacterial infection → ↑ neutrophils.
  • Viral infection → ↑ lymphocytes.
  • Allergies/parasitic infection → ↑ eosinophils.
  • Chronic infection (e.g., TB) → ↑ monocytes.

Cellular Migration Terms

• Chemotaxis
  • Directed movement of cells toward increasing concentration of a chemical attractant (e.g., IL-8, C5a, bacterial peptides).
  • Positive vs negative chemotaxis.
• Diapedesis (Extravasation)
  • Passage of leukocytes through intact endothelium.
  • Steps: rolling (selectins) → activation (chemokines) → adhesion (integrins) → transmigration (PECAM-1).

Quantitative & Pathological Conditions

• Leukopenia
  • WBC count < 4 \times 10^3 \/ \mu L.
  • Causes: chemotherapy, aplastic anemia, HIV, SLE.
  • Risk: opportunistic infections.
• Leukemia
  • Malignant proliferation of WBC precursors in bone marrow → ↑ immature blasts in blood.
  • Classified by speed (acute vs chronic) & cell line (myeloid vs lymphoid).
  • Symptoms: anemia, infections, bleeding, bone pain.
• Lymphoma
  • Solid tumors of lymphoid tissue.
  • Hodgkin (Reed-Sternberg cells) vs Non-Hodgkin varieties.
  • Presents with painless lymphadenopathy, B-symptoms (fever, night sweats, weight loss).

Major Functions of Blood (Summary)

• Transport
  • O₂ from lungs → tissues, CO₂ to lungs.
  • Nutrients, hormones, metabolic waste.
• Regulation
  • pH via bicarbonate buffer; body temperature distribution.
  • Fluid balance & oncotic pressure.
• Protection
  • Hemostasis prevents blood loss.
  • Immune cells + antibodies defend against pathogens.

Connections & Clinical Relevance

• Vitamin K deficiency (e.g., in newborns or warfarin therapy) ↓ factors II, VII, IX, X → prolonged bleeding.
• Rh incompatibility in pregnancy → hemolytic disease of the newborn; prevented by anti-D Ig (RhoGAM).
• Complete blood count (CBC) gives RBC, WBC, platelet counts; differential highlights shifts in leukocyte populations.
• D-dimer testing assesses fibrinolysis; elevated in DVT, PE, DIC.