Blood II – White Blood Cells and Platelets Detailed Study Notes

White Blood Cells (Leukocytes)

• Contain true nuclei unlike erythrocytes, enabling protein synthesis and sophisticated signaling.
• PRIMARY FUNCTION ➔ protection/defense of the organism.
  • Destroy infectious pathogens (bacteria, viruses, fungi, protozoa).
  • Eliminate abnormal self-cells (e.g., pre-cancerous or cancerous cells).
  • Certain sub-classes act as professional phagocytes, engulfing and degrading:
  • Dead or damaged host cells and tissues.
  • Foreign particles and cell debris.
• Circulate in the blood for markedly shorter periods than RBCs (hours → days vs. (\sim) 120\text{ d} for RBCs).
• Capable of:
  • Leaving the bloodstream (diapedesis) when signaled by chemotactic gradients.
  • Amoeboid motility within interstitial spaces.
  • Chemotaxis: attraction toward specific chemical stimuli (e.g., bacterial N-formyl-methionine, complement fragments).

Relative Abundance of Leukocyte Classes

• Classic mnemonic: “Never Let Monkeys Eat Bananas.”
• Ranked from most to least common in peripheral blood:
  • Neutrophils 50–70\%
  • Lymphocytes 20–30\%
  • Monocytes 2–8\%
  • Eosinophils 2–4\%
  • Basophils <1\%

Granulocytes (Polymorphonuclear Cells)

• Defined by abundant membrane-bound cytoplasmic granules; multilobed nuclei.
• Overall leukocyte count per microliter (mean ± range): 4360\;(1800–9950).
• Sub-types:

Neutrophils

• Count: 4150\;(1800–7300)\;\mu L^{-1}.
• Lobed nucleus increases with cell age; pale-lilac, fine granules.
• Core functions:
  • Professional phagocytes; first responders to bacterial invasion.
  • Release cytotoxic granules (defensins, lysozyme, reactive oxygen species).
• Clinical tie-in: Neutrophilia is a hallmark of acute bacterial infection; neutropenia predisposes to sepsis.
• Life span: minutes → days (short because of high oxidative burst activity).

Eosinophils

• Count: 165\;(0–700)\;\mu L^{-1}.
• Bi-lobed nucleus; bright red-orange granules rich in major basic protein.
• Key roles:
  • Combat multi-cellular parasites (helminths).
  • Moderate allergic reactions; degrade antibody-antigen complexes.
  • Release antihistamines, limiting basophil-mediated inflammation.
• Increase (eosinophilia) seen in parasitic infections, asthma, atopic allergies.

Basophils

• Rarest leukocyte: 44\;(0–150)\;\mu L^{-1}.
• Dense, dark-purple granules often obscure a bi-lobed nucleus.
• Functions:
  • Promote inflammation—granules contain histamine, heparin, leukotrienes.
  • Functionally analogous to tissue mast cells.
• Clinical pearl: Basophilia may signal chronic myelogenous leukemia (CML).
• Life span: unknown; presumed hours → days.

Agranulocytes (Mononuclear Cells)

• Lack large visible granules under light microscopy; nuclei are round or indented.
• Combined mean count: 2640\;(1700–4950)\;\mu L^{-1}.

Lymphocytes

• Count: 2185\;(1500–4000)\;\mu L^{-1}.
• Appearance: large, spherical nucleus; thin rim of cytoplasm.
• Central to adaptive immunity:
  • T lymphocytes → cell-mediated immunity.
  • T_C (cytotoxic) destroy virus-infected / malignant cells.
  • T_H (helper) coordinate entire immune response; activate B, T, and innate cells.
  • T_{reg} (regulatory) dampen autoimmunity.
  • B lymphocytes → humoral immunity.
  • Differentiate into plasma cells secreting antigen-specific antibodies.
  • Natural Killer (NK) cells → innate-like surveillance; nonspecific cytotoxicity vs. transformed cells.
• Notable properties: clonal expansion, memory formation (years → lifetime), secondary lymphoid organs (lymph nodes, spleen) act as training grounds.

Monocytes

• Count: 455\;(200–950)\;\mu L^{-1}.
• Largest circulating leukocyte; horseshoe-shaped nucleus.
• Exit blood → tissues → differentiate into macrophages or dendritic cells.
• Functions:
  • Highly effective phagocytes; engulf senescent RBCs, pathogens.
  • Antigen-presenting cells (APCs): display peptide–MHC complexes to T cells.
  • Secrete cytokines orchestrating inflammation and tissue repair.
• Clinical context: chronic inflammation (e.g., tuberculosis) marked by monocytosis.

Hematopoiesis – Formation of Blood Elements

• Definition: continuous production of RBCs, WBCs, and platelets.
• Post-natal site: red bone marrow (vertebrae, pelvis, sternum, ribs).
• Hierarchical lineage tree:
  • Multipotent Hematopoietic Stem Cell (HSC) a.k.a. hemocytoblast.
  • Self-renewal: some daughter cells remain stem cells.

Myeloid Lineage

• HSC → Common Myeloid Progenitor (CMP) → gives rise to:
  • Proerythroblast → Reticulocyte → \color{red}{\text{Erythrocyte}}.
  • Megakaryoblast → Megakaryocyte → shed cytoplasmic fragments → \text{Platelets}.
  • Myeloblast → granulocytes (neutrophil, eosinophil, basophil).
  • Monoblast → monocyte/macrophage.

Lymphoid Lineage

• HSC → Common Lymphoid Progenitor (CLP) →
  • Lymphoblast → B cell, T cell, NK cell.
• T lymphocytes migrate to the thymus for maturation (positive & negative selection).

Platelets (Thrombocytes)

• Cytoplasmic fragments of megakaryocytes; diameter (\sim) 2–4\,\text{\mu m}.
• Lack nuclei but contain mitochondria, glycogen, and alpha/dense granules.
• Concentration: 150–400\times10^{3}\;\mu L^{-1} (reference from standard hematology).
• Primary roles in hemostasis:
  1. Release pro-clotting chemicals upon activation (ADP, thromboxane A$_2$, serotonin, Ca$^{2+}$).
  2. Form a temporary platelet plug that seals minor endothelial tears.
  3. Facilitate clot retraction via actin–myosin–like contractions.
• Clinical correlation: thrombocytopenia (<100\times10^{3}/\mu L) → bleeding risk; thrombocytosis → thrombosis.

Hemostasis – Multistep Prevention of Blood Loss

1. Vascular Phase

• Immediate reflexive vasoconstriction of damaged vessel.
• Endothelial cells:
  • Contract, exposing basement membrane & collagen.
  • Secrete endothelin, prostaglandins, tissue factor.
  • Become sticky, aiding platelet adherence.

2. Platelet Phase

• Platelet Adhesion: bind exposed collagen via von Willebrand factor (vWF).
• Activation → shape change (spiky projections), degranulation.
• Aggregation → positive feedback recruiting additional platelets; forms a platelet plug.
• Secreted mediators include ADP, thromboxane A$_2$, platelet-activating factor (PAF), Ca$^{2+}$.

3. Coagulation Phase

• Conversion of liquid blood → gel-like clot (fibrin mesh).
• Requires \ge 11 plasma proteins (clotting factors, mostly synthesized in liver) plus Ca$^{2+}.
• Vitamin K is essential for (\gamma)-carboxylation of factors II, VII, IX, X.
• Pathways:
  • Extrinsic Pathway – initiated by tissue factor (factor III) from damaged endothelium.
  • Intrinsic Pathway – triggered by contact activation (collagen, glass); involves platelet phospholipids.
  • Common Pathway – convergence at factor X → prothrombinase → converts prothrombin (II) → thrombin (IIa) → fibrinogen (I) → fibrin (Ia) → stabilized by factor XIII.
• Feedback regulation:
  • Antithrombin III, Protein C/S system, & heparin (released by basophils/mast cells) inhibit over-clotting.

4. Fibrinolysis

• Gradual clot removal to restore vessel patency.
• Key components:
  • Plasminogen (inactive) incorporated into clot during formation.
  • Tissue plasminogen activator (tPA) → converts plasminogen → plasmin.
  • Plasmin digests fibrin mesh → fibrin degradation products (FDPs).
• Pharmacologic parallel: recombinant tPA used to lyse thrombi in ischemic stroke.

Ethical / Clinical / Real-World Implications

• Understanding WBC differentials guides antibiotic stewardship, oncology diagnostics, and allergy management.
• Hemostasis knowledge underpins safe surgical practice, anticoagulant therapy (warfarin blocks vitamin K cycle, heparin potentiates antithrombin), and thrombolytic interventions.
• Platelet donation & storage logistics depend on recognizing their short shelf-life ((\sim) 5–7\text{ d}$$) and temperature requirements.
• Vaccination leverages lymphocyte memory, a principle derived from adaptive immune characteristics reviewed above.