CHAPTER 3.2

Inflammation

Vascular Events

Acute Inflammation

• Definition: Acute inflammation is a rapid response to injury or infection, sometimes involving the entire cardiovascular system, such as in cases of anaphylaxis and shock.

Components of Acute Inflammation

• The inflammatory response consists of four major components:
  1. Alterations in Vascular Caliber
  • Results in increased blood flow, leading to calor (heat) and rubor (redness).
  1. Structural Changes in the Microvasculature
  • Changes permit proteins and leukocytes (white blood cells) to exit the intravascular space into the extravascular space, known as tumor (swelling).
  1. Leukocyte Emigration
  • Leukocytes move from the blood vessels to accumulate at the site of injury, contributing to tumor (swelling).
  1. Physical and Chemical Activation of Nerve Endings
  • This activation is responsible for dolor (pain).

Local Manifestations of Acute Inflammation

• Major Local Manifestations: Compared to normal tissue, the major local manifestations of acute inflammation include:
  1. Vascular Dilation
  • Increases blood flow, causing erythema (redness) and warmth.
  1. Extravasation of Fluid and Proteins
  • This leads to edema (swelling).
  1. Leukocyte Emigration and Accumulation
  • Accumulation at the injury site contributes to the inflammatory response.

Vascular Changes in Acute Inflammation

• Key Changes A. Normal Fluid Exchange
  • In a normal vascular bed, two opposing forces regulate fluid movement:
    1. Hydrostatic Pressure
       • Pushes fluid out of the blood vessels.
    2. Plasma Colloid Pressure
       • Pulls fluid back into the bloodstream.
         B. Vascular Wall Changes
  • After injury, vascular walls undergo changes affecting flow, depending on the injury severity: a. Vasodilation
    • Can be preceded by transient vasoconstriction. Results in increased flow and increased hydrostatic pressure.
      b. Increased Permeability
    • Results in transudate formation and decreased intravascular plasma colloid pressure.
      C. Net Movement of Fluid
  • Results from loss of intravascular fluid leading to increased blood viscosity and stasis.

Physiological Effects of Fluid Movement During Inflammation

• Effects of Fluid Movement
  • The loss of intravascular fluid indicates:
  1. Increased Blood Viscosity
  • This causes stasis, allowing white blood cells (mostly polymorphonuclear neutrophils, PMNs) to accumulate at the endothelial surface (margination) and begin movement through the vessel wall (diapedesis).
• Fluid Movement Dynamics: Illustrates normal vs acute inflammation;
  • Normal State
    • Net flow out = hydrostatic pressure (32 mm Hg at the arterial end and 12 mm Hg at the venous end) equating to colloid osmotic pressure (25 mm Hg).
  • Acute Inflammation
    • In acute inflammation, arteriolar pressure can increase to approximately 50 mm Hg, mean capillary pressure increases due to arteriolar dilation, and venous pressure rises to about 30 mm Hg. The osmotic pressure drops to around 20 mm Hg due to protein leakage across venules.

Mechanisms of Increased Vascular Permeability

• Increased vascular permeability during inflammation can occur via several mechanisms:
  1. Formation of Venule Intra-Endothelial Gaps
  • Endothelial contraction opens gaps, facilitates rapid and transient fluid escape, localized to venules, and can be induced by cytokines and TNF.
  1. Direct Endothelial Injury
  • Necrosis and detachment affecting vessels, potentially worsened by recruited PMNs.
  1. Leukocyte Mediated Endothelial Injury
  • Caused by WBC aggregation and their release of free radicals and proteolytic enzymes.
  1. Delayed Prolonged Leakage
  • Starts 2-12 hours after injury and can last days, initiated by cytokines or other factors.
  1. Increased Transcytosis
  • Trans-endothelial channels form and are enhanced by inflammatory factors.
  1. Leakage from New Blood Vessels
  • Newly formed vessels during repair have a leaky endothelium that stabilizes with maturity.

Angiogenesis

• Vessel Maturation
  • Vessel development involves:
  1. Growth-factor Dependence
     • Loss of survival factor leads to apoptosis.
  2. Vessel Stabilization
     • Investment with mural cells and production of basement membrane.
     • Involves growth factors such as TGF-β and Angiopoietins (1 & 2).

Conclusions on Acute Inflammation

1. Alteration in Arteriolar Diameter
   • Results in increased blood flow.
2. Decreased Intravascular Volume
   • Causes stasis of flow, allowing white blood cells to marginate and emigrate.
3. Microvasculature Porosity
   • Results from:
   • Formation of venule inter-endothelial gaps.
   • Direct endothelial injury.
   • Leukocyte mediated endothelial injury.
   • Delayed prolonged leakage.
   • Increased transcytosis.
   • Leakage from new blood vessels.