Lecture III

• Inflammation is a response of vascularized tissues that delivers leukocytes and molecules of host defense from the circulation to the sites of infection and cell damage
• Classic signs of inflammation:

  • Rubor (redness) and Calor (heat)
  • Tumor (swelling)
  • Dolor (pain)
  • Functio laesa (loss of function)
• Release of vasoactive mediators by immune cells and endothelium leads to arteriolar smooth muscle relaxation, vasodilation, and increased blood flow
• Release of mediators from immune cells and endothelium or damage to endothelium leads to separation of endothelial junctions, increased vascular permeability, and leakage of protein-rich fluid from postcapillary venules into the interstitial tissue (exudate)
• Stimulation of free nerve endings by certain mediators and H+ leads to pain
• Leukocyte recruitment to sites of inflammation involves neutrophils and macrophages, with neutrophil extravasation occurring in 5 steps: Margination, Rolling, Adhesion, Diapedesis, and Migration
• Margination is the distribution of leukocytes peripherally along the endothelial surface, facilitated by rouleaux formation and dilation of post-capillary venules
• Rolling is a transient weak interaction of leukocytes with endothelial cells mediated by adhesion molecules (selectins)
• Leukocyte adhesion is the firm binding of leukocytes to endothelium prior to migrating out of the vasculature, mediated by integrins
• Diapedesis is the transmigration of leukocytes across endothelial barriers, facilitated by the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1)
• Migration is the process by which leukocytes travel through the interstitium to the site of inflammation, mediated by chemotaxis
• Neutrophil extracellular traps (NETs) are extracellular fibrillar networks that concentrate antimicrobial substances at sites of infection and trap microbes
• Morphologic patterns of acute inflammation include dilation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue
• Possible outcomes of acute inflammation:

  • Persistent acute inflammation
  • Resolution with regeneration
  • Resolution with scarring
  • Abscess formation
  • Chronic inflammation
• Fibrinous inflammation involves the development of a fibrinous exudate when vascular leaks are large or there is a local procoagulant stimulus, leading to the deposition of fibrin in the extracellular space
• Purulent (suppurative) inflammation is characterized by the production of pus, consisting of neutrophils, necrotic cell debris, and edema fluid, with abscesses being localized collections of pus