An injurious agent may act at some site other than the tissue in question to produce an abnormality in the immediate environment of the cell or cause accumulation of some toxic substance, which in turn causes cell damage. Representative causes of indirect injury include accumulation of toxic products in kidney and liver failure or a change in extracellular pH, electrolyte concentrations, or core body temperature. These indirect injuries may result in cell damage in many different tissues throughout the body, eg, structural and functional abnormalities in the brain in liver failure (hepatic encephalopathy).