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The sympathoadrenal system is a physiological connection between the sympathetic nervous system and the adrenal medulla and is crucial in an organism’s physiological response to outside stimulus. When the body receives sensory information, the sympathetic nervous system sends a signal to preganglionic nerve fibers, which activate the adrenal medulla through acetylcholine. Once activated, norepinephrine and epinephrine are released directly into the blood by postganglionic nerve fibers where they act as the bodily mechanism for “fight or flight” responses. Because of this, the sympathoadrenal system plays a large role in maintaining glucose levels, sodium levels, blood pressure, and various other metabolic pathways that couple with bodily responses to the environment. During numerous diseased states, such as hypoglycemia or even stress, the body’s metabolic processes are skewed. The sympathoadrenal system works to return the body to homeostasis through the activation or inactivation of the adrenal gland. However, more severe disorders of the sympathoadrenal system such as phaeochromocytoma (a tumor on the adrenal medulla) can affect the body’s ability to maintain a homeostatic state. In such cases, curative agents such as adrenergic agonists and antagonists are used to modify epinephrine and norepinephrine levels released by the adrenal medulla.

Function
The normal function of the sympathoadrenal system is to help the body regulate responses to environmental stimuli. These stimuli travel through the sympathetic nervous system by means of preganglionic nerve fibers that emerge from the thoracic spinal chord. Since both the sympathetic nerve fibers and adrenal medulla are part of the central nervous system (CNS), electrical impulses carried by the nervous system are converted to a chemical response in the adrenal gland. Chromaffin cells contained in the adrenal medulla act as postganglionic nerve fibers that release this chemical response into the blood as circulating messenger. The sympathoadrenal system can activate and discharge chemical messengers as a single unit to activate an organism’s “fight or flight” response. This “sympathoadrenal discharge” causes an increase in heart rate, cardiac output, blood pressure, and glucose levels. These sympathoadrenal functions show the combined responses of the central nervous system on a multitude of external stimuli.

Chemical messengers:
The two main chemical messengers of the sympathoadrenal system are norepinephrine and epinephrine (also called noradrenaline and adrenaline respectively). These chemicals are created by the adrenal glands after receiving neuronal signals from the sympathetic nervous system. The different physiological affects of these chemicals depend on the particular tissue that it innervates. As part of the sympathoadrenal system, these chemicals act rapidly and dispel quickly as opposed to the longer lasting affect of hormones.

Stress
Within the brain, reception of a signal for a stressor by the hypothalamus leads to an increase in activity of the sympathoadrenal system, essentially within the nerves that send signals to the adrenal glands through the activation by the corticotropin-releasing factor (CRF), also known as the corticotropin-releasing hormone (CRH). Increased activity of the adrenal nerves is done through the receptors for the corticotropin-releasing factor within the ganglia within the sympathetic nervous system. Corticotropin-releasing factors travel to the pituitary, where they activate the release of adrenocorticotropic hormone (ACTH). The release of the adrenocorticotropic hormone is determined by the release of the corticotropin-releasing factor as the interruption of the corticotropin-releasing factor causes a weakening of the adrenocorticotropic hormone response.

Adrenocorticotropic hormones bind to ACTH receptors on the cells within the adrenal medulla and adrenal cortex, causing a signal cascade within the adrenomedullary cell, ultimately releasing the neurotransmitter acetylcholine. The neurotransmitter acetylcholine causes the excitation of the nerves that innervate the skeletal muscles along with the muscles surrounding certain bodily systems such as the cardiovascular system and respiratory system, causing an increase in force production by the skeletal muscles along with accelerated heart rate and breathing rate, respectively. Glucocorticoids also are in affect during times of stress for the sympathoadrenal system, but provide an inhibitory function for the protection. The glucocorticoids work to inhibit reactions produced from the immune system during times of stress that could cause damage within the body. Glucocorticoids work to inhibit the uptake of catecholamines, like norepinephrine and epinephrine, by the nerves. The increase in activity of synthesis of norepinephrine and epinephrine within the medulla is done from glucocorticoids through the increase in reaction rate of certain enzymes, such as: tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine-β-hydroxylase, and phenylethanolamine N-methyltransferase.

Hypertension and obesity
The release of adrenocorticotropic hormone is usually regulated within the sympathoadrenal system as it is tasked with maintenance of homeostasis; however, there are certain cases in which the levels of adrenocorticotropic hormones may be in excess, causing hypertension, or even Cushing’s syndrome. The high blood pressure associated with hypertension has a multitude of possible causes, one of which being the elevated levels of ACTH. Hypertension also causes an increase in catecholamine release during experiments of stress-induced situations. While hypertension and Cushing’s syndrome are not correlational, roughly 80% of individuals diagnosed with Cushing’s syndrome also have hypertension. Both Cushing’s syndrome, termed Cushing’s disease in this case, and hypertension involve the excess production and release of adrenocorticotropic hormone. Hypertension can also be caused by the overproduction of molecules released from the sympathoadrenal system besides ACTH, such as mineralocorticoids and glucocorticoids. Overproduction of these molecules causes an increase in the production and release of the catecholamines, leading the cardiovascular system to become elevated in the systolic blood pressure and the diastolic blood pressure, along with the increase in the heart rate of the individual.

Weight gain can be accomplished through the ingestion of and storage of carbohydrates and fat. Under normal conditions, adrenal hormone receptors, type I and type II, mediate the storage of carbohydrates and fats during eating. In some cases of obesity in individuals is due to the overproduction of corticoids leads to the over-activation of receptor type I and type II, causing the deposition of fat and the storage of carbohydrates, respectively; furthermore, activation of either receptor causes the individual to sustain eating.

Exercise
During exercise, the body undergoes a stress response in which more oxygen and energy is needed for physical activity. The stress induced during exercise results in an increase in the hormones, epinephrine and norepinephrine, which are known for the body’s fight or flight response. As a result, the body’s heart rate increases allowing for more blood to pump through the body system and carry oxygen needed for breathing to enhance cardiorespiratory function. In exercise trained individuals, levels of epinephrine and norepinephrine are lower compared to those who do not actively train as much. This is due to untrained individuals undergoing greater amounts of stress on their body and the greater need for oxygen and energy to perform rigorous activities. Along with an increase in epinephrine and norepinephrine, increased sympathoadrenal activity results in an increase in glycogen which ultimately increases glucose release needed for energy.

Hypoglycemia
Hypoglycemia, or low blood glucose, causes cardiovascular physiological effects as a result of the sympathoadrenal system. These effects include an increased heart rate, increased heart contractility, and decreased peripheral arterial resistance. Together, these increase peripheral blood pressure, but decrease central blood pressure. This can have larger effects on those with diabetes. Hypoglycemia may cause greater arterial wall stiffness and less elasticity, which in turn reflects blood pressure and increases the heart’s workload. Symptoms of hypoglycemia related to the symapthoadrenal system include anxiety, tremors, irregular heartbeat, sweating, hunger, and paresthesia. Hypothermia and neurological deficits can also occur while permanent brain damage is uncommon. The activation of the system is assisted by norepinephrine, acetylcholine, and epinephrine. Hypoglycemia unawareness can occur because the symapthoadrenal system response is reduced, in turn, the symptoms are reduced. Since the symptoms go unnoticed, this may lead to a dangerous cycle of hypoglycemia and an increased risk of severe hypoglycemia.

Insulin is essential in triggering the sympathoadrenal system (the release of norepinephrine and epinephrine) to respond to hypoglycemia, which then raises glucagon levels. The insulin present in the brain acts on the central nervous system by crossing the blood-brain barrier and affecting the sympathetic nervous system. Thereby, helping to initiate a response to hypoglycemia through the sympathoadrenal system. Individuals with hypoglycemia should self-monitor their blood glucose level and can take glucose in the forms of tablets or foods high in glucose. Parenteral therapy may be necessary for severe hypoglycemia. Hypoglycemia-associated autonomic failure (HAAF) can occur if left untreated. The sympathoadrenal system activity is significantly reduced because the changed glycemic threshold allows for lower glucose concentrations. Glucose cannot effectively regulate itself, decreasing epinephrine responses.

Pheochromocytoma
Pheochromocytoma are rare tumors that secrete catecholamines and affect the sympathoadrenal system. They are typically found inside the adrenal medulla, but can also be present right outside adrenal medulla in tissue. Symptoms include headaches, sweating, palpitations, Hypertension, hypoglycemia, anxiety, weight loss, fever, nausea, and cardiovascular complications. Pheochromocytoma can be treated through removal of the tumor and should be done in a timely manner. On average, there is a delay of three years between initial symptoms and diagnosis because the tumors are hard to find and the symptoms are highly variable and very common in other diseases.