Inflammation Overview and Classification

Inflammation

• Inflammation is a complex host response to eliminate foreign invaders
• It's a protective response involving host cells, blood vessels, and proteins
• The goal is to eliminate the initial cause of injury, necrotic cells, and initiate tissue repair
• Harmful agents are diluted, destroyed, or neutralized

Classification of Inflammation

• Acute inflammation
  • Rapid onset, short duration (minutes to days)
  • Characterized by fluid and protein exudation, and neutrophilic leukocyte accumulation
• Chronic inflammation
  • More insidious, longer duration (days to years)
  • Influx of lymphocytes, macrophages, and associated vascular proliferation and fibrosis (scarring)

Induction of Inflammation

• Induced by chemical mediators produced by host cells in response to harmful stimuli
• Resident cells (macrophages, dendritic cells, mast cells) sense infection or injury
• Cytokines and other mediators induce and regulate the inflammatory response

Cardinal Signs of Inflammation

• External manifestations are heat, redness, swelling, pain, and loss of function

Steps of the Inflammatory Response (Five Rs)

• Recognition of the injurious agent
• Recruitment of leukocytes
• Removal of the agent
• Regulation (control) of the response
• Resolution (repair)

Vascular Changes in Inflammation

• Increased blood flow (vasodilation) and increased vascular permeability
• Initial transient vasoconstriction, followed by vasodilation
• Increased vessel permeability allows plasma proteins to leave the circulation
• Fluid leakage leads to edema

Cellular Events (Leukocyte Recruitment and Activation)

• Leukocytes are delivered to the site of injury and activated for function
• Leukocytes ingest harmful agents, kill microbes, and eliminate necrotic tissue
• However, leukocyte products can damage normal tissues
• Host defense mechanisms include checks and balances

Leukocyte Recruitment

• Leukocytes circulate rapidly in blood, but in inflammation, they adhere, then migrate to the site of injury
• Margination, rolling, adhesion, transmigration, and migration constitute the sequence of events

Leukocyte Activation

• Once leukocytes are recruited, stimuli like microbes, necrotic products, activate them
• Leukocytes use receptors to sense harmful stimuli, inducing a series of responses (leukocyte activation)

Phagocytosis

• Three steps:
  • Recognition and attachment of the particle (microbes, dead cells) to the leukocyte
  • Engulfment, forming a phagocytic vacuole for the ingested particle
  • Killing and degradation of the ingested particle through introduction of microbicidal substances within lysosomes

Outcomes of Acute Inflammation

• Resolution: Regeneration and repair (tissue regeneration and function restoration)
• Chronic inflammation: follows if the offending agent is not removed and tissues cannot regenerate; possible scarring
• Scarring: inflammation in non-regenerating tissues leads to fibrosis where connective tissue fills the injury site

Morphologic Patterns of Acute Inflammation

• Serous inflammation: outpouring of watery, protein-poor fluid (e.g., blister)
• Fibrinous inflammation: severe injuries with large molecules (like fibrinogen), exudates
• Suppurative (purulent) inflammation/abscess: pus formation (neutrophils, necrotic cells, edema), focal collections of pus
• Ulcers: local defects in tissue surfaces resulting from necrosis, inflammatory tissue destruction