Chagas disease, caused by the parasite Trypanosoma cruzi, affects approximately 18 million people worldwide. Complications from the disease result in about 50,000 deaths each year. The most severe forms of the disease involve enlargement of the esophagus, colon, and heart. Loss of parasympathetic control is a significant factor in the initial stages of the disease. Soon after infection, the parasympathetic neurons that innervate the heart, esophagus, and colon are destroyed, leading to arrhythmias, potential sudden death, and impaired peristalsis. In approximately 30% of infected individuals, chronic cardiomyopathy, which is the dysfunction of the heart muscle, can occur and ultimately lead to death. The exact pathogenesis of cardiomyopathy is not fully understood, but one leading theory involves autoimmunity. Antibodies against the parasite's antigens have been found to bind to the β-adrenergic and M2 acetylcholine receptors in the heart. These antibodies not only trigger autoimmune responses that destroy heart muscle but also act as agonists at these receptors, causing inappropriate responses of the cardiovascular system to changing external demands.

Autonomic function is centrally controlled through various pathways, including spinal cord and brainstem reflex pathways, as well as descending control systems originating in higher levels of the nervous system, such as the hypothalamus.

Different organs are under autonomic control. For example, the size of the pupil is determined by the dilator and constrictor muscles of the iris, which are controlled by sympathetic and parasympathetic fibers, respectively. Sympathetic innervation of the eye, through thoracic white rami and sympathetic trunk ganglia, causes pupil dilation, which occurs during emotional excitement or in response to painful stimulation. Norepinephrine acts as the neurotransmitter at the sympathetic postganglionic synapses, binding to α receptors.

In contrast, the parasympathetic nervous system has the opposite effect on pupillary size. While sympathetic stimulation leads to pupil dilation, parasympathetic stimulation causes pupil constriction. The preganglionic parasympathetic nerves responsible for innervating the pupillary constrictor are located in the Edinger-Westphal nucleus within the midbrain. These nerves travel in cranial nerve III, and damage to this nerve can result in pupil dilation, known as mydriasis.
Chagas disease istheresultofinfectionbytheparasiteTrypanosoma cruzi. About18millionpeopleareinfectedworldwide,andapproximately50,000dieeachyearasaresultofcomplicationsfromthedisease.Themostseriousformsinvolveenlargementoftheesophagus,colon,andheart.Lossofparasympatheticcontrolisasignificantcomponentoftheinitialstagesofthedisease;shortlyaftertheinitialinfection,theparasympatheticneuronsinnervatingtheheart,esophagus,andcolonaredestroyed,whichleadstoarrhythmias(andpotentiallysuddendeath)andaperistalsis.Chroniccardiomyopathy(malfunctionoftheheartmuscle)thatcanleadtodeathoccursinapproximately30%ofthoseinfected.Althoughthepathogenesisofthecardiomyopathyisnotfullyunderstood,oneleadingideainvolvesautoimmunity.Antibodiesagainsttheparasiticantigenshavebeenfoundtobindtotheβ-adrenergicandM2acetylcholinereceptorsintheheart.Theseantibodiesnotonlytriggerautoimmuneresponsesthatdestroyheartmusclebutalsoactasagonistsatthesereceptorsandcauseinappropriateresponsesofthecardiovascularsystemtochangingexternaldemands.
Central Control of Autonomic Function
The discharges of autonomic preganglionic neurons are controlled by pathways that synapse on autonomic preganglionic neurons. The pathways that influence autonomic activity include spinal cord and brainstem reflex pathways, as well as descending control systems originating at higher levels of the nervous system, such as the hypothalamus.
Examples of Autonomic Control of Particular Organs
The dilator and constrictor muscles of the iris, which are under the control of sympathetic and parasympathetic fibers, respectively, determine the size of the pupil. Activation of sympathetic innervation of the eye, via thoracic white rami and sympathetic trunk ganglia, dilates the pupil, which occurs during emotional excitement and also in response to painful stimulation. The neurotransmitter at the sympathetic postganglionic synapses is norepinephrine, and it acts at α receptors.
The parasympathetic nervous system exerts an action on pupillary size opposite that of the sympathetic nervous system. Whereas the sympathetic system elicits pupillary dilation, the parasympathetic system constricts the pupil. The preganglionic parasympathetic nerves that innervate the pupillary constrictor are in the Edinger-Westphal nucleus, which is in the midbrain, and travel in cranial nerve III, and so damage to this nerve can lead to a dilated pupil (mydriasis).