Ischemia and hypoxia - reduced oxygen partial pressure - reduced ATP production - increased Ca2 - dysfunction of the cytochrome oxidase system (Haber-Weiss reaction becomes stronger, reactive oxygen species increase, especially H2O2 and OH* in mitochondria)

Leukotrienes and the like are produced during ischemia, causing neutrophils to gather and activate. During reperfusion, the oxygen consumption of activated neutrophils in the tissue increases significantly, producing a large amount of oxygen free radicals, that is, respiratory burst. (Oxygen free radicals can kill cells and cause further damage to tissue cells)

During ischemia, xanthine oxidase increases; during reperfusion, oxygen enters the blood, and xanthine oxidase catalyzes the production of large amounts of uric acid and H2O2.

Hypoxia-reperfusion is a stress response in which the adrenal medullary system is excited to produce a large amount of catecholamines, which are catalyzed by monoamine oxidase to form oxygen free radicals.

Destruction of cell and organelle membrane structures

Increased production of biologically active substances

Reduced ATP production

Low permeability of cell membrane to Ca2

Calcium forms a reversible complex with special ligands

The cell membrane calcium pump (Ca2-Mg2-ATPase) actively transports Ca2 outside the cell against the electrochemical gradient.

Ca2 is stored in the cytoplasm in the endoplasmic reticulum and mitochondria through calcium pumps and sodium-calcium exchange on the organelle membrane.

Transport cytosolic calcium out of the cell through sodium-calcium exchange across the cell membrane

Direct activation: During ischemia, ATP production is reduced, resulting in a decrease in sodium pump activity; during reperfusion, the sodium pump is activated to promote sodium transport outside the cell, allowing a large amount of Ca2 to be transported into the cytoplasm, and the intracellular Ca2 concentration to increase.

Indirect activation: acidosis activates sodium and hydrogen exchange proteins, increases intracellular sodium, indirectly promotes sodium and calcium exchange, and causes extracellular calcium influx.

Promote the entry of calcium in the endoplasmic reticulum into the cell, while causing the influx of extracellular calcium ions

Cell membrane damage (enhanced membrane permeability to calcium ions)

mitochondrial membrane damage

endoplasmic reticulum membrane damage

Microvascular hemorrheological changes

Increased microvascular permeability