Pathophysiology of Chronic Inflammation

Chronic Inflammation

• Develops in 3 ways: on top of acute inflammation, repeated bouts of acute inflammation, or starts as chronic (e.g., T.B.)
• Causes: persistent acute inflammation, infection by certain pathogens (e.g., T.B. bacilli), continuous exposure to irritant, impaction of foreign materials, autoimmune diseases, and diseases of unknown cause (e.g., inflammatory bowel disease)

Types of Chronic Inflammation

• Chronic nonspecific inflammation: no characteristic histopathological appearance
• Chronic specific inflammation: characteristic histopathological pattern (granulomatous inflammation)

Granulomatous Inflammation (Granuloma)

• Definition: focal accumulation of macrophages (epithelioid cells) with lymphocytes, plasma cells, multinucleated giant cells, and fibroblasts
• Types of granuloma:
  • Infective granuloma: bacterial (e.g., T.B., leprosy), parasitic (e.g., bilharziasis, toxoplasma), and fungal (e.g., histoplasmosis)
  • Non-infective granuloma: silicosis, asbestosis
  • Foreign body granuloma: around foreign bodies (e.g., piece of wood, suture material)
• Fate: heals by fibrosis with scar formation

Acute vs. Chronic Inflammation

• Onset: acute (sudden), chronic (gradual)
• Duration: acute (short), chronic (long)
• Irritant: acute (severe), chronic (mild)
• Local reactions:
  • Acute: thin-walled congested capillaries, diffuse infiltration by acute inflammatory cells, fibrin threads, and coagulated fluid exudates
  • Chronic: thick-walled blood vessels, perivascular infiltration by chronic inflammatory cells, and background of necrosis and progressive fibrosis
• Systemic reactions: acute (marked), chronic (mild)

Repair

• Definition: replacement of damaged tissue by living tissue
• Types:
  • Regeneration: replacement of destroyed tissue by the same cells (e.g., repair of bone fracture)
  • Repair by fibrosis: replacement of destroyed tissue by granulation tissue which matures to fibrosis

Types of Cells

• Labile cells: continuous proliferation to replace aging cells (e.g., stratified squamous epithelium of skin, columnar epithelium of GIT)
• Stable cells: proliferate when needed (e.g., parenchymatous cells, mesenchymal cells)
• Permanent cells: cannot proliferate at all (e.g., muscle cells, nerve cells)

Granulation Tissue

• Definition: red, granular, soft, painless, and bleeds easily
• Formation: in the gap of healing wounds, consisting of fibroblasts, collagen, newly formed blood vessels, and scattered macrophages and inflammatory cells
• Fate: excess collagen deposition, obliteration of capillaries, and scar formation

Wound Healing

• Healing by primary intention: clean surgical wounds, minimal tissue destruction, minimal bleeding, no bacterial infection, and good apposition of wound edges
• Healing by secondary intention: gaping wounds, marked tissue destruction, bleeding, infection, and poor apposition of wound edges

Healing by Primary Intention

• Initial hemorrhage: blood clot fills wound cavity
• Inflammation (24 hours): PNL's infiltrate blood clot
• Epithelial changes (48 hours): epithelial cells from wound edges proliferate
• Early granulation tissue (3rd day): macrophages replace PNL's, stimulate ingrowth of fibroblasts and angioblasts, and form collagen type III