Biocontinuum of the Pathophysiology Paradigm

Abstract

Under the various conditions of radiation therapy, the period of time from irradiation to the end of life may be characterized by continuous complications of clinical significance arising from irradiation of normal organs, alternating with clinical complication with clinically “silent” periods of the absence of such clinically significant complications. However, there is at no time a “silent” histopathologic period, i.e., absence of radiation-induced changes in the irradiated organs, although their degree of rate of progression may vary considerably. Furthermore, the addition of further stress of insult, e.g., from trauma or infection, to the organs that have sustained residual radiation damage (e.g. deterioration of the vasculature) may precipitate clinically significant complications during otherwise clinically “silent” periods. The histopathologic sequence of events after a brief radiation exposure is divided into four general phases (see Fig. 5): Casarett Hypothesis. The Biocontinuum diagram illustrates generally, with respect to clinical periods, the waxing and waning (vertically), or organ damage with time and persistence or progression of residual damage. The upper lines depict radiation damage of different degrees. The bottom line indicates the accumulation of organ damage with time of “aging”, may be additive to radiation damage in effect. The rising arrows indicate the precipitation of damage from subclinical or clinical levels to clinically significant or even lethal levels, as a result of complications such as trauma or infection or as a result of deterioration of vasculature and failure of the blood circulation. No precise values of relationships are intended for the slopes or shapes of the graph lines: Rubin Paradigm.

In memory of George Casarett.