Acute Inflammation: Vascular Events

Introduction & Cardinal Signs - Red Carpet Rollout

• Acute inflammation: Rapid defense; delivers leukocytes & plasma proteins to injury.
• Hallmarks: Vascular changes (the "red carpet") causing visible signs.
• Cardinal Signs (Celsus & Virchow):
  • Rubor (Redness): Vasodilation (e.g., histamine).
  • Tumor (Swelling): ↑ Vascular permeability, fluid exudation.
  • Calor (Heat): ↑ Blood flow.
  • Dolor (Pain): Mediators (bradykinin, $PGE_2$), tissue tension.
  • Functio laesa (Loss of function): Result of other signs. 📌 Mnemonic: PRISH (Pain, Redness, Immobility, Swelling, Heat).

⭐ Celsus described the first four signs (rubor, tumor, calor, dolor); Virchow added the fifth, Functio laesa.

Vasodilation - Pipes Wide Open

• Initial, brief vasoconstriction (neurogenic; endothelin).
• Followed by sustained vasodilation:
  • Primarily affects arterioles; later opens new capillary beds.
  • Key Mediators:
    • Histamine & Serotonin (early; from mast cells, platelets).
    • Nitric Oxide (NO) (from endothelium via eNOS).
    • Bradykinin.
    • Prostaglandins (PGI₂, PGE₂, PGD₂).
• Mechanism: Relaxation of vascular smooth muscle.
• Results:
  • ↑ Blood flow (active hyperemia) to the affected area.
  • Causes cardinal signs: Rubor (redness) & Calor (heat).

⭐ Histamine is a principal mediator of the immediate transient phase of increased vascular permeability and vasodilation, released mainly from mast cells, basophils, and platelets in response to various stimuli.

Increased Vascular Permeability - Leaky Vessels Ahoy!

Key to acute inflammation, allowing plasma proteins & leukocytes to exit vessels. Leads to exudate & edema.

• Mechanisms:
  • Endothelial Cell Contraction (Most Common):
    • Mediators: Histamine, bradykinin, leukotrienes (C4, D4, E4), Substance P.
    • Rapid, short-lived (15-30 min).
    • Mainly affects venules.
    • Forms intercellular gaps.
  • Endothelial Injury:
    • Direct: Burns, toxins, trauma.
    • Leukocyte-mediated: During adhesion/emigration.
    • Rapid or delayed onset; prolonged duration.
    • Affects arterioles, capillaries, venules.
  • Transcytosis:
    • ↑ Vesicular transport across cytoplasm.
    • Mediator: Vascular Endothelial Growth Factor (VEGF).
    • Mainly venules.
  • Leakage from New Blood Vessels:
    • During repair (angiogenesis); immature vessels are leaky.

⭐ Exam Favourite: The most common mechanism of increased vascular permeability is endothelial cell contraction, primarily mediated by histamine, leading to transient leakage in venules.

Stasis & Exudation - Slowing & Spilling

• Stasis: Marked slowing of blood circulation in microvasculature.
  • Mechanism: ↑ vascular permeability → loss of protein-rich fluid from plasma → ↑ blood viscosity & concentration of RBCs.
  • Result: Small vessels become packed with slow-moving RBCs.
• Exudation: Escape of fluid, proteins, and blood cells from the vascular system into interstitial tissue or body cavities.
  • Exudate: Inflammatory extravascular fluid with high protein content (specific gravity > 1.020), cellular debris. Often contains fibrinogen (→ fibrin).
  • Significance: Implies significant alteration in small vessel permeability.
  • Contrast: Transudate is low protein fluid (specific gravity < 1.012), an ultrafiltrate of plasma, due to hydrostatic imbalance, not permeability change.

⭐ Accumulation of protein-rich exudate leads to swelling (tumor), a cardinal sign of acute inflammation.

Edema Formation - Puffing Up

• Fluid accumulation in interstitial tissue, causing swelling (tumor).
• Pathophysiology: Altered Starling forces.
  • ↑ Hydrostatic pressure (capillary): Due to arteriolar dilation & ↑ blood flow.
  • ↓ Colloid osmotic pressure (plasma): Due to protein leakage (albumin) from ↑ vascular permeability.
  • Net result: ↑ Outward movement of fluid from capillaries into interstitium.

⭐ Inflammatory edema is typically an exudate: protein-rich (specific gravity >1.020, protein >2.5-3 g/dL) with inflammatory cells.

High‑Yield Points - ⚡ Biggest Takeaways

• Vasodilation (mediated by histamine, NO) causes rubor (redness) and calor (heat).
• Increased vascular permeability (driven by histamine, leukotrienes) leads to protein-rich exudate and edema (tumor).
• Endothelial cell contraction in post-capillary venules is the main mechanism for early, transient leakage.
• Stasis of blood flow, due to fluid loss, concentrates red blood cells, facilitating leukocyte margination.
• Exudate (SG > 1.020, protein > 2.5 g/dL) indicates inflammation, unlike transudate.
• The Triple Response of Lewis (flush, flare, wheal) demonstrates key histamine-mediated vascular events in skin.