Figure 3.

Tipping Points and Cascading Systems Failure. If there is control failure at one component level of the schematic illustrated in Figure 2 due to the feed-forward loop of inflammation à damage à inflammation, the “tipping” of that system past a point of no return can lead to an override of control mechanisms at the higher level, leading to a cascading effect that culminates in systemic dysfunction (Red Arrows). Importantly, spillover to the next component not only affects that component, but also affects the prior one, propagating the feed-forward behavior of inflammation back across components and compartments (Blue Arrows). Note that these components can be defined by scale of organization, but also by the spatial containment inherent to an organ’s anatomical structure and relationship to other organ systems.