Vascular changes in inflammation

Vasodilation & Permeability - Leaky Pipes Open

• Phase 1: Vasodilation
  • Brief, transient vasoconstriction (neurogenic) followed by vasodilation.
  • Mediators: Histamine, Prostaglandins, Nitric Oxide (NO).
  • Results in ↑ blood flow (hyperemia), causing Rubor (redness) and Calor (heat).

• Phase 2: Permeability
  • Hallmark of acute inflammation, leading to protein-rich exudate & edema (Tumor).
  • Mechanisms:
    • Endothelial cell contraction (Immediate, transient): Most common; mediated by histamine, bradykinin, leukotrienes in post-capillary venules.
    • Direct endothelial injury (Immediate, sustained): Severe insults like burns or toxins.
    • Leukocyte-mediated injury: Late response.
    • Increased transcytosis: Via VEGF.

⭐ Histamine-mediated endothelial contraction is the principal mechanism of the immediate transient phase of increased vascular permeability, primarily affecting post-capillary venules.

Stasis & Leukocyte Margination - Cellular Traffic Jam

• Stasis: A direct result of ↑ vascular permeability.

  • Loss of protein-rich fluid (exudate) leads to ↑ blood viscosity and hemoconcentration (↑ RBCs).
  • This dramatically slows blood flow, especially in post-capillary venules.

• Leukocyte Margination: The hemodynamic consequence of stasis.

  • As blood flow slows, heavy leukocytes fall out of the central axial stream and move towards the vessel periphery.
  • This peripheral positioning allows neutrophils to tumble along and interact with the endothelial surface, a prerequisite for adhesion.

⭐ Pavementing: A severe manifestation of margination where the endothelial surface becomes so densely lined with leukocytes that it resembles a cobblestone pavement. It is a hallmark of florid acute inflammation.

Edema & Fluid Dynamics - The Fluid Shift

• Fluid movement across capillaries is governed by Starling forces: the balance between hydrostatic pressure (pushes fluid out) and plasma colloid oncotic pressure (pulls fluid in).
• Exudate: Inflammatory edema.
  • Caused by ↑ vascular permeability from mediators like histamine.
  • Endothelial gaps allow protein and cells to leak into the interstitium, causing a large ↑ in interstitial oncotic pressure ($\oldsymbol{\pi_i}$).
  • Characteristics: High protein (>2.9 g/dL), high specific gravity (>1.020), cellular. Appears cloudy.
• Transudate: Non-inflammatory edema.
  • Caused by altered Starling forces, not permeability changes.
  • Common causes: ↑ hydrostatic pressure (heart failure) or ↓ oncotic pressure (liver disease, nephrotic syndrome).
  • Characteristics: Low protein (<2.5 g/dL), low specific gravity (<1.012), acellular. Appears clear.

⭐ Light's Criteria are used clinically to differentiate pleural exudates from transudates, critical for diagnosing the cause of a pleural effusion. 📌 EXudate = EXiting protein & cells due to inflammation.

• Vasodilation (via histamine, NO) and increased blood flow cause redness and heat.
• Increased vascular permeability is the hallmark of acute inflammation, leading to protein-rich exudate and swelling.
• The most common mechanism is endothelial cell contraction (gaps), a rapid, reversible process mediated by histamine and bradykinin.
• Direct endothelial injury causes immediate, sustained leakage in severe injuries.
• Loss of fluid leads to stasis, concentrating RBCs and promoting leukocyte margination.