Hydropic swelling is an early indicator of cell injury. It results from na+-k+ pump dysfunction at the cell membrane. Intracellular accumulations of abnormal endogenous or exogenous particles indicate a disorder of cellular metabolism. Damage from accumulation of abnormal intracellular protein is limited by chaperone proteins that attempt to refold the protein into its correct shape and by the ubiquitin- proteosome system that digests targeted proteins into fragments. Adaptive cellular responses indicate cellular stress caused by altered functional demand or chronic sublethal injury. Hypertrophy and hyperplasia generally result from increased functional demand. Atrophy results from decreased functional demand or chronic ischemia. Necrosis occurs when the injury is too severe or prolonged to allow adaptation and is usually a consequence of disrupted blood supply. Local and systemic indicators of cell death include pain, elevated serum enzyme levels, inflammation (fever, elevated wbc count, malaise), and loss of function.