Sample "Pathophysiologic Hypothesis"

Diagram (click to enlarge)

Interpretative summary

A woman fainted in the street on her way out of her doctor’s office just after she had gotten an intramuscular injection of a non-steroidal anti-inflammatory drug (diclofenac) for her chronic back pain. The underlying process was a systemic allergic reaction to the drug resulting in anaphylactic shock (IgE-mediated, “immediate type” immune hypersensitivity reaction). Systemic release of histamine and other inflammatory mediators from activated mast cells caused peripheral smooth muscle relaxation. The resulting decreased systemic vascular resistance leads to decreased effective circulating blood volume resulting in hypotension and decreased perfusion of the central nervous system, which was likely the proximate cause of her loss of consciousness.

A complicating feature of the case is that the initial electrocardiogram on arrival at the emergency room suggested myocardial ischemia raising the possibility that the syncope was due to cardiogenic rather than anaphylactic shock. On the day following her hospitalization the patient did in fact develop chest pain, which was ultimately diagnosed as unstable angina resulting from significant coronary atherosclerosis. The coincidence of having the first symptoms of cardiac ischemia at the time of an anaphylactic reaction suggested that the allergic reaction itself caused instability of the long-standing, otherwise quiescent atherosclerotic plaque in the coronary arteries. An inflammatory reaction, triggered by mast cells within the plaque could have been responsible for this instability via histamine-mediated vasospasm (note that histamine effects on larger arteries is opposite that on microvessels) and/or plaque disruption with platelet aggregation and intermittent vascular occlusion.