Increased intracellular ADP stimulates the anaerobic glycolytic enzymes which results in two ATP and two lactate molecules per one glucose molecule.

ATP

• Na+/K+ ATPase pump disruption
• Na+ will diffuse to inside the cell ICF (intracellular space)
• K+ will diffuse to outside the cell ECF (extracellular space)

• The net gain of solute is accompanied by water moving from the ECF to the ICF leading to cell swelling and interstitial fluid contraction.
• This is the beginning of cytotoxic edema during which the intracellular organelles and the cellular cytoplasmic membrane are still intact.
• This stage is thought to be the initial reversible period of cytotoxic edema in which the cells are salvageable. This stage is sometimes called sick cell syndrome.
• The cells in this stage are dysfunctional, causing neuronal deficit, but are not dead.
• The cellular swelling and the contraction of the ECF compartment (interstitial fluid) leads to restriction of water Brownian motion in and out of the cell. (Restricted Diffusion State)

Normal Brownian random water motion in normal state

Normal cell	Water molecule	Swollen cell

Restricted motion of water molecules due to cellular swelling and contraction of the interstitial compartment.

Lactate

Initially the intracellular lactate increases as a result of increased anaerobic glycolysis leading to to intracellular acidosis. Later, lactate diffuses to ECF and leads to increased lactate in the interstitial fluid.

At this early stage lactate is increased, but the neurons are not irreversibly damaged, thus the neuronal marker N-Acetyl-Aspartate (NAA) is still normal.

All the above metabolic changes are thought to be a reversible stage in which the cells are still salvageable.