Week 1: The Formed Elements of Blood

Overview of Formed Elements of Blood

• Blood contains three major formed elements:
  • Erythrocytes (Red Blood Cells, RBCs)
  • Leukocytes (White Blood Cells, WBCs)
  • Platelets (Thrombocytes)
• Plasma proteins mentioned:
  • Globulins
  • Albumin
  • Fibrinogen (inactive precursor of fibrin)
• Key processes & terms
  • Hematopoiesis / Hemopoiesis – formation of all blood cells in red bone marrow
  • Hemostasis – cessation of bleeding via vascular spasm, platelet plug, and coagulation
  • Hemolysis – rupture/destruction of erythrocytes

Erythrocytes (Red Blood Cells)

Structure & Composition

• Most numerous formed element; normal count 4.2\text{–}6.2\times10^{6}\,\text{RBCs}/\mu L
• Biconcave disc; diameter \approx 7.5\,\mu m
• Lose nucleus & mitochondria during maturation → rely on anaerobic fermentation so they deliver but do not consume O₂
• Cytoplasm ~33\% hemoglobin; each cell ≈ 2.8\times10^{8} Hb molecules

Functions

• Transport gases:
  • O₂ from lungs → tissues
  • CO₂ from tissues → lungs

Hemoglobin (Hb)

• Each Hb molecule = 4 globin chains (2 α, 2 β) + 4 heme groups
• Central Fe²⁺ atom of each heme binds 1 O₂ → 4 \text{ O}_2/\text{Hb}
• Color change: oxyhemoglobin (bright red) vs. deoxyhemoglobin (dark)
• Clinical measures
  • Hematocrit = packed RBC volume (%); higher in males (up to 52\%) than females

Erythrocyte Life Cycle & Homeostasis

• Average lifespan: 120 days
• Production = Erythropoiesis
  • Stimulated by Erythropoietin (EPO) from kidneys (minor from liver)
  • Requires iron, folic acid, vitamin B₁₂, amino acids
  • Negative-feedback: hypoxemia → kidneys ↑EPO → ↑RBCs
• Destruction
  • Old/fragile RBCs trapped in spleen ("erythrocyte graveyard") & liver → phagocytized by macrophages
  • Hemoglobin recycling
  • Globin → amino acids
  • Heme → Fe²⁺ salvaged (via transferrin) + pigment path:
    • Heme → biliverdin (green) → bilirubin (yellow-green) → released into plasma (bound to albumin) → liver → bile → intestine → urobilinogen (brown feces)

Erythrocyte Disorders

• Excess | Polycythemia

  • Primary (cancer of erythropoietic line) → hematocrit up to 80\%
  • Secondary (due to hypoxia: smoking, high altitude, dehydration, etc.)
  • Dangers: ↑blood volume, viscosity, pressure → stroke, heart failure

• Deficiency | Anemias

  1. Inadequate erythropoiesis / Hb synthesis
  • Pernicious (↓B₁₂ due to lack of intrinsic factor)
  • Iron-deficiency
  • Thalassemia (defective globin synthesis)
  • Aplastic (failure of red marrow)
  1. Hemorrhagic (blood loss)
  2. Hemolytic (RBC destruction)
  • Sickle-cell (recessive Hb defect; sickling at low O₂, protective vs. malaria)

Blood Typing

ABO System

• Antigens (agglutinogens) on RBC membrane: A or B
• Antibodies (agglutinins) in plasma are opposite to self antigens
  • Type A → anti-B; Type B → anti-A; Type AB → none; Type O → anti-A & anti-B
• Agglutination = antibody-mediated clumping

Rh (D) Factor

• D antigen present → Rh⁺; absent → Rh⁻
• Anti-D antibodies form only in Rh⁻ individuals after exposure to Rh⁺ blood

Hemolytic Disease of the Newborn (Erythroblastosis Fetalis)

• Scenario: Rh⁻ mother, Rh⁺ fetus
  • 1st pregnancy → maternal sensitization (anti-D formation)
  • 2nd Rh⁺ fetus → maternal anti-D crosses placenta → fetal agglutination / hemolysis → anemia
• Prevention: Inject RhoGAM (Rh immune globulin) at 28–32 weeks gestation to bind fetal Rh antigens

Transfusion Principles

• Recipient antibodies react with donor antigens → dangerous agglutination/hemolysis
• Universal donor = Type O (no antigens)
• Universal recipient = Type AB (no antibodies)
• Lab typing: mix blood with anti-A, anti-B, anti-D sera; observe agglutination

Leukocytes (White Blood Cells)

General Features

• Least numerous formed element; normal range 5{,}000\text{–}10{,}000\,/\mu L
• Retain organelles; lack hemoglobin
• Provide immunologic protection; exit bloodstream via diapedesis to tissues

Categories & Types

1. Granulocytes (visible granules)

   • Neutrophils 60\text{–}70\%
     • 3–5 lobed nucleus; lilac granules
     • Aggressive phagocytes of bacteria; release antimicrobial chemicals
   • Eosinophils 2\text{–}4\%
     • Bi-lobed nucleus; red-orange granules
     • Secrete enzymes vs. parasitic worms; modulate allergens & inflammation
   • Basophils <0.5\% (rarest)
     • Dark violet granules mask nucleus
     • Release histamine (vasodilator), heparin (anticoagulant), serotonin (chemotactic for other WBCs)

2. Agranulocytes (no visible granules)

   • Monocytes 3\text{–}8\%
     • Largest WBC; kidney-/horseshoe-shaped nucleus
     • Leave blood → macrophages; phagocytize debris; act as antigen-presenting cells (APCs)
   • Lymphocytes 25\text{–}35\%
     • Large round nucleus, thin rim cytoplasm
     • T cells (mature in thymus): direct attack on infected/malignant cells
     • B cells (mature in marrow): → plasma cells → antibodies
     • Provide long-term immunity

Mnemonic: "Never Let My Engine Blow" → Neutrophils 60 | Lymphocytes 30 | Monocytes 8 | Eosinophils 3 | Basophils 0

Leukocyte Homeostasis

• Leukopoiesis from hematopoietic stem cells in marrow
• Lifespans
  • Granulocytes: circulate ≈48\text{ h} → tissues few days
  • Monocytes: blood 10\text{–}20\,h → macrophages (years)
  • Lymphocytes: continuously recirculate; memory cells can live for decades
• Dead neutrophils = major component of pus

Leukocyte Disorders

• Leukopenia (<5{,}000/\mu L): heavy-metal poisoning, radiation, viral infections, immunosuppressants
• Leukocytosis (>10{,}000/\mu L): infection, allergy, dehydration, stress
• Leukemia (cancer of hemopoietic tissues)
  • Myeloid (granulocytes) vs. Lymphoid (lymphocytes)
  • Acute (rapid, fatal months) vs. Chronic (slow, insidious)

Platelets (Thrombocytes)

Structure & Production

• Cytoplasmic fragments of mega-karyocytes
• Lifespan <7 days; count 150\text{–}400\times10^{3}/\mu L
• Thrombopoiesis regulated by Thrombopoietin (liver, kidneys)
  • Hematopoietic stem cell → megakaryocyte in marrow → cytoplasmic extensions → platelet fragments enter blood

Functions

• Secrete vasoconstrictors (e.g., serotonin) → reduce blood loss
• Form temporary platelet plug at injury
• Release chemo-attractants for leukocytes
• Secrete growth factors (PDGF) → stimulate fibroblasts & smooth muscle for repair

Hemostasis (3 Steps)

1. Vascular Spasm
   • Immediate vasoconstriction of damaged vessel (smooth muscle + serotonin)
2. Platelet Plug Formation
   • Endothelium coated with prostacyclin (platelet repellent); injury exposes collagen → platelets adhere & extend pseudopods
   • Positive feedback: degranulation releases ADP, serotonin, thromboxane A₂ → recruit more platelets
3. Coagulation (Clotting)
   • Goal: convert soluble fibrinogen → insoluble fibrin mesh
   • Requires >30 clotting factors (procoagulants) mainly from liver; identified by Roman numerals (e.g., VIII, IX)
   • Two pathways
     • Extrinsic: initiated by tissue factor (Factor III) from damaged tissue
     • Intrinsic: initiated by factors within blood (e.g., platelet Factor XII)
   • Both converge on Factor X activation

Common Pathway (with Ca^{2+})

(\text{Extrinsic or Intrinsic}) \rightarrow \text{Factor }X \xrightarrow{+\text{III},\,Ca^{2+}} \text{Prothrombin Activator} \rightarrow \text{Prothrombin} \,(II) \rightarrow \text{Thrombin} \rightarrow \text{Fibrinogen} \rightarrow \text{Fibrin}

Clot Removal & Prevention

• Fibrinolysis
  • Kallikrein converts plasminogen → plasmin (dissolves fibrin)
• Natural anticoagulant controls
  • Platelet repulsion by smooth endothelium/prostacyclin
  • Dilution of thrombin by flowing blood
  • Anticoagulants: Heparin (basophils/mast cells) blocks thrombin; Antithrombin (liver) deactivates thrombin

Coagulation Disorders

• Hemophilia (sex-linked recessive; mainly males)
  • A: lack Factor VIII (≈80\%)
  • B: lack Factor IX (≈15\%)
  • C: lack Factor XI (≈5\%)
• Thrombosis: clot (thrombus) in unbroken vessel; if dislodged → embolus (risk of MI, stroke, PE)
• Hematoma: clotted blood mass in tissues (bruise)

Integrative & Clinical Connections

• Erythroblastosis fetalis illustrates antigen–antibody reactions across placenta; prophylaxis with RhoGAM protects future pregnancies
• Sickle-cell trait confers partial protection vs. malaria ⇒ example of balanced polymorphism
• Basophil secretion (histamine + heparin) integrates inflammation with coagulation control
• Hemoglobin recycling links spleen function, liver metabolism (bilirubin → bile), and GI excretion (urobilinogen)

Quick Reference / Mnemonics

• WBC order (decreasing %) – Never Let My Engine Blow
• Coagulation common path – "X marks the spot for prothrombin activator"
• Anemia categories – Production, Loss, Destruction
• Polycythemia dangers – "3 V’s": Volume, Viscosity, (blood) Velocity/pressure