Autonomic Nervous System: Anatomy and Pathophysiology

Neurochemistry and the Adrenal Medulla

A critical component of the sympathetic response is the release of chemical messengers known as catecholamines. The primary catecholamines are epinephrine (adrenaline) and norepinephrine (noradrenaline).

The anatomy of this response involves a unique structure called the adrenal medulla. While most autonomic pathways involve a synapse between a preganglionic and a postganglionic neuron, the adrenal medulla receives direct innervation from preganglionic sympathetic fibers. In this sense, the adrenal medulla functions as a specialized sympathetic ganglion. Instead of releasing neurotransmitters into a local synapse, the adrenal medulla secretes epinephrine and norepinephrine directly into the bloodstream, allowing for a systemic, widespread sympathetic effect.

An interesting anatomical exception to the rule of neurotransmitters is found in the sweat glands; although they receive postganglionic sympathetic fibers, they secrete acetylcholine (ACh) rather than norepinephrine.

Pathophysiology: Dysautonomia and Pheochromocytoma

When the delicate balance of the autonomic nervous system is disrupted, several clinical conditions can arise.

Dysautonomia

Dysautonomia refers to a broad category of disorders characterized by a malfunction in the autonomic nervous system. Patients with dysautonomia often exhibit a combination of both sympathetic and parasympathetic dysfunction. These conditions can be acute or chronic, and may originate in either the central or peripheral nervous systems.

The etiologies (causes) of dysautonomia are diverse and include:

• Autoimmunity and paraneoplastic disorders
• Toxins
• Diabetes
• Guillain-Barré syndrome
• Parkinson’s disease
• Spinal cord disorders (e.g., multiple sclerosis or trauma)

Pheochromocytoma

A more specific and severe pathology involving the autonomic system is pheochromocytoma. This is a tumor of the adrenal medulla that results in the uncontrolled release of catecholamines (epinephrine and norepinephrine).

Because these tumors cause excessive sympathetic activity, the clinical presentation is often dramatic. Uncontrolled catecholamine release can lead to life-threatening complications, including:

• Malignant hypertension (extremely high blood pressure)
• Cerebrovascular accidents (stroke)
• Myocardial infarction (heart attack)

Statistics show that approximately 10% of pheochromocytoma cases are inherited in an autosomal dominant (AD) pattern, and about 10% of cases are malignant.

Diagnosis and Treatment

To diagnose a pheochromocytoma, clinicians look for elevated levels of catecholamines in the patient's plasma or in a 24-hour urine collection. A key diagnostic indicator is that these catecholamine levels will not be suppressed by the administration of clonidine. Once diagnosed, the primary treatment is the surgical resection of the tumor, supplemented by pharmacological management to control hypertension.