Mnemonic

Cardinal Signs of Inflammation

A mnemonic for the five classical signs of acute inflammation.

Expansion

Rubor, calor, tumor, dolor and functio laesa

Mnemonic

The four of Celsus, with Galen’s fifth:

  • Rubor - redness, from vasodilatation
  • Calor - heat, from increased blood flow
  • Tumor - swelling, from increased vascular permeability and exudate
  • Dolor - pain, from bradykinin and prostaglandins, and pressure
  • Functio laesa - loss of function, added by Galen

“Red, hot, swollen, painful, and it does not work.”

Each maps onto a mechanism, which is why the list is more than a mnemonic: vasodilatation comes from histamine, prostaglandins and nitric oxide; permeability from histamine and bradykinin acting on venules; pain from bradykinin and prostaglandin E2, which is precisely what NSAIDs block by inhibiting cyclooxygenase.

The acute response is neutrophil driven and lasts hours to days; the chronic response is lymphocyte and macrophage driven, with tissue destruction and repair proceeding simultaneously, which is why chronic inflammation causes fibrosis.

Expansion

  • Rubor (redness): vasodilatation of arterioles, mediated by histamine, prostaglandins and nitric oxide
  • Calor (heat): increased blood flow bringing core temperature to the surface
  • Tumor (swelling): increased vascular permeability producing a protein-rich exudate
  • Dolor (pain): bradykinin and prostaglandins sensitising nerve endings, plus pressure from the swelling
  • Functio laesa (loss of function): the fifth sign, added by Virchow

The vascular sequence is: transient vasoconstriction, then vasodilatation with increased flow, then increased permeability causing stasis, then leucocyte margination and emigration.

Exudate versus transudate is the key distinction. An exudate is protein-rich with a high specific gravity and cells, resulting from increased permeability; a transudate is protein-poor, resulting from altered hydrostatic or oncotic pressure. Light’s criteria apply this distinction to pleural fluid.

Anti-inflammatory drugs act on the mediators: NSAIDs on prostaglandins, antihistamines on histamine, corticosteroids on phospholipase A2 and on gene transcription more broadly.