Ischemia-reperfusion injury

Ischemia-reperfusion injury

Ischemia-reperfusion injury

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IRI: The Basics - Comeback Kid's Curse

Ischemia-Reperfusion Injury Mechanism

Paradoxical exacerbation of cell injury after restoring blood flow to ischemic tissue. The very act of reperfusion triggers a cascade of damage, driven by several key mechanisms.

  • Core Mechanisms: 📌 RICM of Injury
    • Reactive Oxygen Species (ROS): Sudden O₂ influx fuels a burst of ROS from mitochondria & neutrophils.
    • Inflammation: Complement activation (C5a) and cytokines recruit neutrophils, which release proteases and more ROS.
    • Ca²⁺ Overload: Ischemic pump failure leads to ↑ intracellular Ca²⁺; reperfusion worsens this, activating damaging enzymes.
    • Mitochondrial Dysfunction: Ca²⁺ and ROS trigger the opening of the Mitochondrial Permeability Transition Pore (MPTP), leading to apoptosis.

⭐ Reperfusion can cause microvascular injury and endothelial swelling, leading to impaired blood flow in small vessels-the "no-reflow" phenomenon-despite restoration of circulation in larger arteries.

IRI: Damage Deep-Dive - The Oxygen Paradox

Ischemia-reperfusion injury mechanism

Re-introducing O₂ to ischemic tissues paradoxically worsens injury. Key drivers:

  • Reactive Oxygen Species (ROS) Burst:

    • Incomplete reduction of O₂ by damaged mitochondria generates superoxide ($O_2^•−$).
    • Inflammatory cells (neutrophils) produce ROS via NADPH oxidase.
    • Leads to lipid peroxidation → membrane damage.
  • Inflammation Amplification:

    • Reperfusion recruits neutrophils.
    • Release of proteases & elastases damages endothelium and parenchyma.
    • Cytokine release (TNF, Interleukins) fuels the inflammatory fire.
  • Complement Activation:

    • Ischemia promotes deposition of IgM antibodies on endothelial cells.
    • Reperfusion activates complement pathway → C5a (chemoattractant) & MAC (cell lysis).

High-Yield: A major source of damage in IRI is the respiratory burst from recruited neutrophils, which use the enzyme NADPH oxidase to generate a flood of superoxide radicals upon reperfusion.

IRI: Clinical Picture - Tissues Tell The Tale

  • Heart: Post-angioplasty, watch for reperfusion arrhythmias, myocardial stunning (prolonged dysfunction despite restored flow), and microvascular injury. Key histologic finding: contraction band necrosis.
  • Brain: Following thrombolysis for stroke, can lead to hemorrhagic transformation and cerebral edema.
  • Kidney: Ischemic acute tubular necrosis (ATN) can worsen despite re-established perfusion.
  • Lungs & Gut: Reperfusion can trigger acute respiratory distress syndrome (ARDS) or increase gut permeability, risking sepsis.

Contraction band necrosis is a classic histologic sign of cardiac IRI. Massive Ca²⁺ influx upon reperfusion causes myocyte hypercontraction, creating distinct eosinophilic bands.

Myocardial contraction band necrosis after reperfusion

High‑Yield Points - ⚡ Biggest Takeaways

  • Ischemia-reperfusion injury is a paradoxical increase in cell damage after restoring blood flow.
  • Primarily driven by a surge in reactive oxygen species (ROS) from reperfused tissues and leukocytes.
  • Mitochondrial permeability transition is a critical event, causing mitochondrial dysfunction and cell death.
  • Features an intense inflammatory response, with neutrophil infiltration worsening the damage.
  • Complement activation contributes to inflammation and direct cell injury.
  • Clinically key in thrombolysis, angioplasty, and organ transplantation.

Practice Questions: Ischemia-reperfusion injury

Test your understanding with these related questions

An 82-year-old woman is brought to the emergency department after losing consciousness at her nursing home. She had been watching TV for several hours and while getting up to use the bathroom, she fell and was unconscious for several seconds. She felt dizzy shortly before the fall. She does not have a headache or any other pain. She has a history of hypertension, intermittent atrial fibrillation, and stable angina pectoris. Current medications include warfarin, aspirin, hydrochlorothiazide, and a nitroglycerin spray as needed. Her temperature is 36.7°C (98.1°F), pulse is 100/min and regular, and blood pressure is 102/56 mm Hg. Physical exam shows a dry tongue. A fold of skin that is pinched on the back of her hand unfolds after 2 seconds. Cardiopulmonary examination shows no abnormalities. Further evaluation of this patient is most likely to show which of the following findings?

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Flashcards: Ischemia-reperfusion injury

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Hyperplastic arteriolosclerosis may lead to _____ necrosis of the vessel wall with hemorrhage

TAP TO REVEAL ANSWER

Hyperplastic arteriolosclerosis may lead to _____ necrosis of the vessel wall with hemorrhage

fibrinoid

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