U01.04.011 Inflammation

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Learning Objective

Describe the purpose, mechanisms, cardinal signs, and systemic manifestations of inflammation, and recognize how inflammatory responses can become harmful.

Definition & Purpose

Inflammation is a protective response designed to:

  • Eliminate the initial cause of cell injury (eg, microbes, toxins)
  • Remove necrotic cells and damaged tissues
  • Initiate tissue repair

Inflammation is broadly divided into acute and chronic inflammation.

USMLE Pearl: Although protective, inflammation can be harmful if:

  • Excessive (eg, septic shock)
  • Prolonged (eg, chronic infections such as tuberculosis)
  • Inappropriate (eg, autoimmune diseases like SLE)

Cardinal Signs of Inflammation (with Mechanisms)

Rubor & Calor (Redness and Warmth)

  • Mechanism: Vasodilation due to relaxation of arteriolar smooth muscle → ↑ blood flow
  • Mediators: Histamine, prostaglandins, bradykinin, nitric oxide (NO)

Tumor (Swelling)

  • Mechanism: Increased vascular permeability → leakage of protein-rich fluid (exudate) from postcapillary venules into the interstitial space
  • Leads to ↑ interstitial oncotic pressure
  • Mediators: Leukotrienes (C4, D4, E4), histamine, serotonin, bradykinin
  • Caused by endothelial cell contraction or disruption (eg, tissue injury)

Dolor (Pain)

  • Mechanism: Sensitization of sensory nerve endings
  • Mediators: Bradykinin, prostaglandin E2 (PGE2), histamine

Functio Laesa (Loss of Function)

  • Mechanism: Impaired tissue function due to pain, swelling, and structural damage
  • Example: Inability to make a fist due to hand cellulitis

Systemic Manifestations of Acute Inflammation

(Acute-Phase Reaction)

Fever

  • Mechanism: Pyrogens (eg, LPS) stimulate macrophages to release IL-1 and TNF
  • These cytokines increase COX activity in perivascular cells of the anterior hypothalamus
  • → ↑ PGE2 → ↑ hypothalamic temperature set point

Leukocytosis

  • Mechanism: ↑ white blood cell count
  • Predominant cell type depends on the inciting agent:
    • Bacterial infections → neutrophils
    • Viral infections → lymphocytes

Increased Acute-Phase Reactants

  • Produced by: Liver
  • Key inducer: IL-6
  • Examples: C-reactive protein (CRP), fibrinogen, serum amyloid A

High-Yield USMLE Step 1 Summary

  • Redness & warmth: vasodilation
  • Swelling: increased vascular permeability (exudate)
  • Pain: Bradykinin & PGE2
  • Fever: IL-1, TNF → PGE2
  • Acute-phase proteins: IL-6–mediated liver synthesis

Activity

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