1. Toward a definition of “pathological process” Richard H. Scheuermann, Ph.D. Professor of Pathology Director of Biomedical Informatics U.T. Southwestern Medical Center

2. Foundational Definitions in OGMS Disorder =def. – A causally relatively isolated combination of physical components that is (a) clinically abnormal and (b) maximal, in the sense that it is not a part of some larger such combination. Disease =def. – A disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism. Pathological Process =def. – A bodily process that is a manifestation of a disorder.

3. Homeostasis We use ‘homeostasis’ to designate a disposition of the whole organism (or of some causally relatively isolated part of the organism, such as a single cell) to regulate its bodily processes in such a way as – (1) to maintain bodily qualities within a certain range or profile, and – (2) to respond successfully to departures from this range caused by internal influences or environmental influences such as poisoning. When bodily processes yield qualities outside the range of homeostasis, then the organism initiates processes designed to return the qualities to a value within this range. In some cases, homeostasis can be lost and then re-gained at a level that is clinically abnormal, for example in the case of adaptation to major injury. In other cases the organism will pass a point where it falls irreversibly outside the realm of homeostasis.

4. time state homeostatic range homeostatic set point physiological state Normal Physiological Homeostasis

5. time state infant child adult elderly

6. Dependencies Age Gender Genetic background Diet Environment Microbiome

7. Chronic Disease time state etiological event

8. Acute Disease time state etiological event disease resolution

9. Progressive Disease time state etiological event

10. Normal Adaptation time state environment change

11. Definitions time state homeostatic range homeostatic set point physiological state Homeostatic set point – the ideal state of a bodily system in a given context. Normal homeostatic range – the set of states of a bodily system considered to be clinically normal. Physiological process – a bodily process that changes the state of a bodily system such that it approaches (moves closer to) the homeostatic set point. Pathological process – a bodily process that changes the state of a bodily system away from the normal homeostatic range.