Integrating homeostasis, rheostasis and allostasis: A hierarchical model of physiological regulation and disease

Homeostasis remains a central principle of physiology, describing how biological systems maintain critical variables within viable ranges through feedback regulation. However, physiological stability does not require constancy, as illustrated by circadian rhythms, fever, inflammatory responses and anticipatory adaptations to stress and expected demand. This narrative review integrates homeostasis, rheostasis and allostasis within a hierarchical model of physiological regulation. In this framework, homeostasis provides local correction of deviations, rheostasis modifies defended ranges according to time and physiological state and allostasis anticipates future demands through coordinated neural, endocrine, autonomic, metabolic and immune responses. Health is conceptualised as flexible coordination among these regulatory levels, whereas disease may emerge when regulation becomes insufficient, mistimed, persistently activated or uncoupled across biological scales. The model is represented using illustrative dynamic equations and examined in relation to evidence from chronobiology, neuroendocrinology, immunology and systems physiology. It suggests that complex disorders may be better characterised through temporal trajectories, variability, phase, recovery and inter-system coupling than through isolated average measurements alone. This framework generates testable hypotheses for physiological research and may inform future research on approaches combining correction of peripheral dysfunction, restoration of biological timing and reduction of sustained allostatic load.