Reversible vs Irreversible Ischemic Cell Injury

Ischemia

Severity (blood flow loss) 70%

Cell resilience (mitochondrial reserve) 50%

Simulation speed 1.0×

Tissue State

ISCHEMIA — pump failing

Mean ATP level

100%

Mean cell volume

100%

Irreversibly injured

Elapsed time

0.0 s

How it works

Every cell here tracks a simplified ATP budget. Ischemia cuts oxygen delivery, so oxidative phosphorylation collapses and ATP decays; reperfusion restores it:

dATP/dt = -k_isch·(1-r) + k_regen·r·(1-ATP)
k_isch  = severity / resilience   (per cell, resilience has small random spread)
r       = 1 while reperfusing, else 0

The Na⁺/K⁺-ATPase pump needs ATP to keep sodium (and the water that follows it osmotically) out of the cell. Pump activity is modeled as a cooperative function of ATP, and cell volume grows when the pump can't keep up:

Pump activity P = ATP²
dV/dt = α·(1-P) - β·P·(V-1),  V clamped to [1, 1.6]

This is reversible cell injury — cloudy swelling — as long as it is corrected in time. But each cell also integrates an injury clock while ATP stays below a critical threshold. Once that clock exceeds the cell's mitochondrial reserve, the mitochondrial permeability transition pore opens, ATP synthesis becomes permanently impossible, and the cell is marked irreversibly injured — it will proceed to necrosis and rupture no matter what reperfusion does afterward.

Severity — how completely blood flow (and therefore oxygen) is cut off; higher severity drains ATP faster.
Resilience — the tissue's mitochondrial/glycolytic reserve; higher resilience slows ATP loss and raises the injury-clock threshold before the point of no return.
Start Reperfusion — restores blood flow. Cells still above the point of no return recover fully (classic reversible injury); cells that already crossed it cannot be saved and continue toward necrosis — the simulator's version of "no-reflow" / reperfusion not helping a dead cell.

Clinical relevance: this is the same principle behind the treatment-window urgency in stroke thrombolysis and cardiac reperfusion therapy — tissue salvage is only possible before the point of no return is crossed.

Healthy (high ATP) Reversibly injured (swollen) Irreversible / necrotic

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