Acute Inflammation Overview

Acute Inflammation

• Definition: A protective response eliminating cell injury causes and removing damaged products/cells. Two main functions: stopping the attack and repairing the damage.
• Triggers: Infection (bacterial, fungal, toxin), injury/foreign bodies/trauma, immunological reactions (autoimmune conditions), chemical agents, and radiation.
• Stages:
  • Recognition of danger: Tissue-resident immune cells (mast cells, macrophages) detect injury via PRRs (like Toll-like receptors), recognizing pathogen factors (PAMPs) and stressed cells (DNA, heat shock proteins). They release histamine, nitric oxide (NO), and other chemicals.
  • Vasodilation and increased vascular permeability: Histamine and NO mediate vasodilation (increased blood vessel diameter), leading to stasis (slow blood flow aiding leukocyte movement), erythema (redness), and warmth. Increased permeability allows protein-rich exudate into tissues, causing edema (swelling). This delivers immune cells and mediators and clotting factors.
  • Chemotaxis: Recruitment of immune cells. WBC migration involves rolling, adhesion, and transmigration across the endothelium. Neutrophils arrive first (6-24 hours post-injury), followed by monocytes (macrophages), lymphocytes, and sometimes eosinophils (24-48 hours).
  • Systemic Response: Pyrexia (fever) and pain.

Acute Inflammation Mediators

• Preformed mediators (Mast cell degranulation): Histamine (vasodilation, bronchoconstriction, intestinal cramps/diarrhea), cytokines (TNF-α, IL-1, IL-6), chemokines (for neutrophils and eosinophils), and enzymes (tryptase, chymase, cathepsin – connective tissue changes, tissue breakdown).
• Secondary mediators (synthesized upon Mast cell activation): Eicosanoids (leukotrienes, prostaglandins, thromboxanes – increased permeability, platelet aggregation, bronchoconstriction) and Th2 cytokines (IL-4, IL-5, IL-13, GM-CSF).

Cardinal Signs of Inflammation

• Redness (Rubor): Increased blood flow.
• Heat (Calor): Increased blood flow.
• Swelling (Tumor): Exudation of fluid.
• Pain (Dolor): Release of chemical mediators, stretching of nerves by exudates.
• Loss of Function (Functio Laesa): Pain and tissue disruption.

Types of Exudates

• Serous: Cell-free plasma.
• Fibrinous: Increased fibrinogen for wound repair.
• Mucinous: Thick, clear gel-like mucous.
• Purulent: Thick, colored pus (WBCs).
• Sanguineous: Fresh bleeding.
• Mixed: Combinations (e.g., serosanguineous, mucopurulent).

Outcomes of Acute Inflammation

• Resolution: Damaging agent removed, damage repaired, full function restored.
• Abscess Formation: Walled-off pus collection (neutrophils, necrotic tissue).
• Fibrosis (Scar) Formation: Excessive connective tissue, hard, non-functional tissue.
• Chronic Inflammation: May follow acute inflammation or be a separate process.

Systemic Inflammation

• Signs: Pyrexia (fever), tachycardia (increased heart rate), rigors (chills), diaphoresis (sweating), leukocytosis (increased WBC count), lethargy, confusion, hypoxia. Caused by local inflammation mediators/toxins entering systemic circulation.
• Spectrum:
  • Systemic Inflammatory Response Syndrome (SIRS): Caused by infection or trauma, includes all signs of systemic inflammation.
  • Sepsis: Body's response to severe infection.
  • Septic Shock: Most severe sepsis; bacteria/infectious agents in blood, end-organ damage, hypotension, often fatal.

Chronic Inflammation

• Characteristics: Sustained response to injurious stimuli, long duration (days to years), involves lymphocytes (B and T cells) and macrophages.
• Causes: Persistent infection (viral or bacterial), autoimmune dysfunction, chronic diseases.
• Mediators: Proteases, cytokines (TNF, IL-1, interferon-γ), NO, eicosanoids, angiogenesis factors (PDGF, FGF, TGF-β).
• Granuloma Formation: Accumulation of mononuclear WBCs (macrophages, lymphocytes), epithelioid cells, and multinucleated giant cells in damaged tissue, associated with mycobacterial or fungal infections and chronic injury from foreign agents (e.g., silica).

Acute vs. Chronic Inflammation

• Acute: Immediate protection, rapid onset (minutes), exudates and neutrophil migration, triggered by infection, immunological responses, trauma, or foreign bodies.
• Chronic: Sustained response, long duration (days to years), involves lymphocytes and macrophages, caused by persistent infection, autoimmune dysfunction, or chronic diseases.