Pathophysiology theories

Pathophysiology theories

Pathophysiology theories

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Etiopathogenesis - The Trigger Theory

  • Infectious Trigger: Believed to be initiated by an unidentified infectious agent in genetically predisposed children.

    • Epidemiological clues: Seasonal peaks (winter/spring), self-limited course, and geographic clustering.
    • Suspected agents: Parvovirus B19, coronaviruses (HCoV-NH), bocavirus, Staphylococcus, Streptococcus.
  • Superantigen Hypothesis: The leading theory suggests bacterial toxins act as superantigens.

    • These toxins bypass normal antigen processing.
    • They directly link MHC class II on antigen-presenting cells to the T-cell receptor (TCR).
    • Result: Massive, non-specific polyclonal T-cell activation and a subsequent cytokine storm (↑ TNF-α, IL-1, IL-6), leading to systemic inflammation and vasculitis.

Superantigenic Mechanisms and Clinical Outcomes

Exam Favourite: The superantigen theory is strongly supported by the association of Kawasaki disease with strains of Staphylococcus aureus (producing TSST-1) and Streptococcus pyogenes (producing pyrogenic exotoxins).

Immunopathogenesis - Superantigen Mayhem

  • Trigger: An unknown trigger, likely infectious, is thought to introduce superantigens (SAgs) into the host.
  • Mechanism: SAgs bypass typical antigen processing.
    • They directly cross-link the MHC class II molecules on antigen-presenting cells with the Vβ-region of the T-cell receptor (TCR).
    • This leads to massive, non-specific (polyclonal) activation of T-lymphocytes.
  • Inflammatory Cascade: Activated T-cells unleash a cytokine storm.
    • Massive release of TNF-α, IL-1, IL-6, and other pro-inflammatory mediators.
    • This drives systemic inflammation, endothelial cell activation, and widespread vasculitis.

Superantigen vs. Conventional Antigen T-cell Activation

⭐ The resulting pathology is a necrotizing vasculitis of medium-sized muscular arteries, with a distinct predilection for the coronary arteries.

Vasculitic Pathology - The Artery Attack

  • A systemic, necrotizing medium-vessel vasculitis with a strong predilection for the coronary arteries.
  • Initial Stage (Weeks 1-2): Intense inflammation with neutrophils infiltrates all vessel layers (panvasculitis), causing edema.
  • Subacute Stage (Weeks 2-4): The infiltrate evolves to lymphocytes, plasma cells, and eosinophils. This phase is critical for:
    • Progressive destruction of the tunica media and internal elastic lamina.
    • This structural damage directly weakens the wall, leading to ectasia and coronary artery aneurysms (CAA).
  • Late Stage: Active inflammation subsides. Proliferation of myofibroblasts can cause progressive stenosis, thrombosis, or occlusion.

Coronary Vasculitis: Kawasaki Disease and other types

High-Yield Fact: The destruction of the internal elastic lamina is the key pathological event predisposing to aneurysm formation, making coronary artery involvement the most feared complication of Kawasaki disease.

High‑Yield Points - ⚡ Biggest Takeaways

  • KD is an acute, necrotizing vasculitis of medium-sized arteries, especially the coronary arteries.
  • The leading theory is a superantigen-mediated immune response, likely from a common infectious agent.
  • This causes widespread T-cell activation and a massive cytokine storm (TNF-α, IL-1, IL-6).
  • Another theory involves oligoclonal IgA plasma cells infiltrating tissues like the coronary arteries.
  • Genetic susceptibility is crucial, with links to HLA-B51 and ITPKC gene polymorphisms.

Practice Questions: Pathophysiology theories

Test your understanding with these related questions

A 6-year-old boy presents to his pediatrician accompanied by his mother for evaluation of a rash. The rash appeared a little over a week ago, and since that time the boy has felt tired. He is less interested in playing outside, preferring to remain indoors because his knees and stomach hurt. His past medical history is significant for an upper respiratory infection that resolved uneventfully without treatment 2 weeks ago. Temperature is 99.5°F (37.5°C), blood pressure is 115/70 mmHg, pulse is 90/min, and respirations are 18/min. Physical exam shows scattered maroon macules and papules on the lower extremities. The abdomen is diffusely tender to palpation. There is no cervical lymphadenopathy or conjunctival injection. Which of the following will most likely be found in this patient?

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Flashcards: Pathophysiology theories

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What demographic is classically affected by Kawasaki disease? _____

TAP TO REVEAL ANSWER

What demographic is classically affected by Kawasaki disease? _____

Asian children < 4 years old

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