Applied Pathophysiology: Inflammation Overview

Applied Pathophysiology: Inflammation and Tissue Repair

• All disease processes cause injury, and healing requires an effective inflammatory response.
• Two main types of inflammation exist:
  • Acute inflammation: the body's expected response to injury.
  • Chronic inflammation: an altered inflammatory response due to persistent injury.

Lines of Defense

• First line: Physical barrier provided by skin and mucous membranes (chemically coated with mucus).
• Second line: Non-specific inflammatory response, identical regardless of the cause.
• Third line: Specific immune response, dependent on the invader.

Inflammation

• "Inflammare" means "set on fire." It describes the reaction of vascularized tissues to injury.
• Inflammatory conditions are named by adding "-itis" to the affected body part (e.g., appendicitis, pericarditis, neuritis).

Acute Inflammation

• Triggered by tissue injury (any form of damage).
• Three goals:
  • Increase blood flow to the injury site (vascular response).
  • Increase healing cells at the site (cellular response).
  • Remove injured tissue, preparing for tissue repair.

Vascular Response

• Facilitated by chemical mediators (inflammatory mediators).
• The process involves initial vasoconstriction, followed by vasodilation and increased capillary permeability.
• The goal is to increase blood flow to the injured area, which contains phagocytic cells (like macrophages) and other components for healing. The increased flow also helps dilute harmful substances.

Capillaries

• Capillaries exchange oxygen, nutrients, and waste products between blood and tissues.
• Blood flow through capillaries is regulated by pre-capillary sphincters.

Fluid Movement in Capillaries

•  Net filtration pressure (NFP) determines fluid movement.
• Hydrostatic pressure (HP) "pushes" fluid out of capillaries.
• Osmotic pressure (OP) "pulls" fluid into capillaries.
• Normal capillaries have balanced forces between them

Exudates

• Vary based on fluid type, plasma protein content, and cell presence.
• Types include:
  • Serous: watery fluid, low protein.
  • Hemorrhagic: severe tissue injury, RBC leakage.
  • Fibrinous: large fibrinogen amounts.
  • Membraneous/Pseudomembraneous: forms on mucous membranes.
  • Purulent/Suppurative: contains pus, degraded white blood cells, proteins, and tissue debris

Inflammatory Mediators

• Cell-derived: proteins generated within cells, including white blood cells, platelets, and endothelial cells.
• Plasma-derived: plasma proteins, including the complement system, kinin system, and clotting system, continuously circulate.

Inflammatory Mediators within Plasma

• Three major interrelated systems regulate inflammatory mediators: Complement, Clotting, and Kinin.

Initial Steps in Inflammatory Response

• Tissue injury triggers the following:
  • Blood vessel vasodilation
  • Increased vascular permeability
  • Activation of the clotting cascade
  • Continued release of vasoactive inflammatory mediators

Cellular Response

• After vessel dilation, cells are needed for healing.
• Three essential steps:
  • Chemotaxis: migrating cells to the injury site.
  • Cellular adherence: cells bind to the site.
  • Cellular migration: cells move across between endothelial cells (diapedesis)

Phagocytosis

• Inflammatory cells release more inflammatory mediators to attract neutrophils.
• Neutrophils then aggressively destroy/phagocytize causative agents.
• Healthy tissue damage can occur.

Summary

• Tissue injury triggers the production and release of inflammatory mediators like histamine, leukotrienes, and prostaglandins.
• These mediators cause vasodilation and increased capillary permeability.
• Chemotaxis, adherence, migration and phagocytosis follow.
• Manifestations include redness, heat, swelling, pain, and loss of function.

Manifestations of Inflammation

• Local manifestations: redness, heat, swelling, pain, loss of function.
• Systemic manifestations: fever, weight loss, fatigue, headache, lethargy.
• Lymphadenitis: lymph node inflammation.

Laboratory Diagnosis

• Non-specific tests like CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) identify inflammation.
• These tests do not pinpoint the source.

Resolution of Acute Inflammation

• The inflammatory response is typically self-limiting.
• The offending agent is removed and feedback systems are regulated by plasma protein systems.
• Inflammatory mediators are deactivated.
• Chronic inflammation follows if the acute response isn't resolved.

Treatment of Inflammation

• Goals minimize damage to surrounding healthy tissues.
• Initial treatments include:
  • Reducing blood flow
  • Decreasing swelling
  • Blocking chemical mediators
  • Decreasing pain

Non-pharmacologic Treatment (RICE)

• Rest
• Ice
• Compression
• Elevation

Pharmacologic Treatment

• Medications block inflammatory mediators, reducing swelling and pain. Examples include NSAIDs and corticosteroids.