Sympathoadrenal system

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Schematic illustration of the structure of the sympathoadrenal system. Beginning in the sympathetic nervous system, an external stimulus affects the adrenal medulla and causes a release of catecholamines. Sympathoadrenal System.jpg
Schematic illustration of the structure of the sympathoadrenal system. Beginning in the sympathetic nervous system, an external stimulus affects the adrenal medulla and causes a release of catecholamines.

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 stimuli. [1] 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 adrenomedullary cells 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. [1] 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 pheochromocytoma (a tumor on the adrenal medulla) can affect the body's ability to maintain a homeostatic state. In these cases, curative agents such as adrenergic agonists and antagonists are used to modify epinephrine and norepinephrine levels released by the adrenal medulla. [2]

Contents

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 cord. [3] Electrical impulses carried by the sympathetic 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 a 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, triglyceride and glucose levels. These sympathoadrenal functions show the combined responses of the central nervous system on a multitude of external stimuli.[ citation needed ]

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 effects 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 effect of hormones.[ citation needed ]

Stress

Schematic illustration of the sympathoadrenal response to stress. Response to stress.jpg
Schematic illustration of the sympathoadrenal response to stress.

In 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. This is done through the activation by the corticotropin-releasing factor (CRF), also known as the corticotropin-releasing hormone (CRH). [4] Increased activity of the adrenal nerves is done through the receptors for the corticotropin-releasing factor within the ganglia within the sympathetic nervous system. [4] Corticotropin-releasing factors travel to the pituitary gland, 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. [4]

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 catecholamines like epinephrine and norepinephrine. [5] Concomitantly, adrenocortical cells secrete corticosteroids. These hormones (i.e., catecholamines and corticosteroids) affect a variety of organs like 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. Glucocorticoids also are in effect during times of stress for the sympathoadrenal system, but provide an inhibitory function for the protection of the body from its own immune system. The glucocorticoids work to inhibit reactions produced from the immune system during times of stress that could cause damage within the body. [4] Glucocorticoids work to inhibit the uptake of catecholamines, like norepinephrine and epinephrine, by the nerves. [4] 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. [4]

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. Hypertension, or high blood pressure, has a multitude of possible causes, one of which being the elevated levels of ACTH. [6] Hypertension also causes an increase in catecholamine release during experiments of stress-induced situations. [7] While hypertension and Cushing's syndrome are not correlational, roughly 80% of individuals diagnosed with Cushing's syndrome also have hypertension. [6] Both Cushing's syndrome, termed Cushing's disease in this case, and hypertension involve the excess production and release of adrenocorticotropic hormone. [6] Hypertension can also be caused by the overproduction of molecules released from the sympathoadrenal system besides ACTH, such as mineralocorticoids and glucocorticoids. [8] 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. [8]

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. [9] In some cases, 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. [9]

Exercise and Metabolism

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. Trained individuals become accustomed to utilizing less oxygen such as when performing anaerobic exercises so that their body will eventually feel the stress on their body over a longer period of time. Along with an increase in epinephrine and norepinephrine, increased sympathoadrenal activity results in an increase in glycogen hydrolysis which ultimately increases glucose release needed for energy. [10]

Metabolism, or the processes within living cells or organisms to maintain life, is affected by the sympathoadrenal system, especially glucose and fat metabolism. Glucose, a necessary source of energy for cells, can undergo an increase in production due to elevated secretion of epinephrine in the body. The mechanism lies in epinephrine being secreted by the adrenal medulla and activating glycogenolysis (the breakdown of glycogen into glucose, or promoting gluconeogenesis (glucose formation). While epinephrine has a greater effect in glucose production, norepinephrine can also increase glucose levels but at high concentrations. It has even been found that norepinephrine may play a role in enhancing the uptake of glucose in skeletal muscle and adipose tissues. As for fat metabolism, the catecholamines (epinephrine and norepinephrine) help stimulate lipolysis (the breakdown of fat) resulting in an increase in energy and a decrease in fat. [11] This explains the need for exercise to help increase the body's metabolism.[ citation needed ]

Diseases

Hypoglycemia

This is a representation of the kidneys in the human body. The left kidney depicted is healthy with normal functioning. The right kidney depicted has a tumor (shown inside the red circle). This disease is called pheochromocytoma and causes an increased level of adrenaline to be released into the circulatory system. Tumor on the Kidney.png
This is a representation of the kidneys in the human body. The left kidney depicted is healthy with normal functioning. The right kidney depicted has a tumor (shown inside the red circle). This disease is called pheochromocytoma and causes an increased level of adrenaline to be released into the circulatory system.

Hypoglycemia, or low blood glucose, causes cardiovascular physiological effects as a result of the sympathoadrenal system. These physiological changes include an increased heart rate, increased heart contractility, and decreased peripheral arterial resistance. Together, the effects 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 decreases blood pressure and increases the heart's workload. [12] Symptoms of hypoglycemia related to the symapthoadrenal system include anxiety, tremors, irregular heartbeat, sweating, hunger, and paresthesia. Hypothermia and neurological deficits can also occur. Permanent brain damage is uncommon but have been seen in some who suffer from hypoglycemia. 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, which can have serious consequences. [13]

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. [14] 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. [13] 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. [15]

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 the adrenal medulla in tissue. Symptoms include headaches, sweating, palpitations, hypertension, hypoglycemia, anxiety, weight loss, fever, nausea, and cardiovascular complications. Pheochromocytoma can be treated through blocking the effects of the secreted catecholamines. Ideally, removal of the tumor is the preferred treatment and should be done in a timely manner for the best prognosis. On average, there is a delay of three years between initial symptoms and diagnosis because the tumors are hard to find. Diagnosis is also difficult because the symptoms are highly variable and very common in other diseases. If pheochromocytoma remains untreated, it may lead to fatal consequences especially to the cardiovascular system. [16]

Related Research Articles

<span class="mw-page-title-main">Adrenal gland</span> Endocrine gland

The adrenal glands are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which produces steroid hormones and an inner medulla. The adrenal cortex itself is divided into three main zones: the zona glomerulosa, the zona fasciculata and the zona reticularis.

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Catecholamine</span> Class of chemical compounds

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

<span class="mw-page-title-main">Sympathetic nervous system</span> Part of the autonomic nervous system which stimulates fight-or-flight responses

The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

<span class="mw-page-title-main">Cortisol</span> Human natural glucocorticoid hormone

Cortisol is a steroid hormone, in the glucocorticoid class of hormones and a stress hormone. When used as a medication, it is known as hydrocortisone.

<span class="mw-page-title-main">Fight-or-flight response</span> Physiological reaction to a perceived threat or harmful event

The fight-or-flight or the fight-flight-freeze-or-fawn is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first described by Walter Bradford Cannon. His theory states that animals react to threats with a general discharge of the sympathetic nervous system, preparing the animal for fighting or fleeing. More specifically, the adrenal medulla produces a hormonal cascade that results in the secretion of catecholamines, especially norepinephrine and epinephrine. The hormones estrogen, testosterone, and cortisol, as well as the neurotransmitters dopamine and serotonin, also affect how organisms react to stress. The hormone osteocalcin might also play a part.

<span class="mw-page-title-main">Adrenal medulla</span> Central part of the adrenal gland

The adrenal medulla is the inner part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecholamines, including epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine, in response to stimulation by sympathetic preganglionic neurons.

<span class="mw-page-title-main">Chromaffin cell</span> Neuroendocrine cells found in adrenal medulla in mammals

Chromaffin cells, also called pheochromocytes, are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monitoring carbon dioxide and oxygen concentrations in the body, maintenance of respiration and the regulation of blood pressure. They are in close proximity to pre-synaptic sympathetic ganglia of the sympathetic nervous system, with which they communicate, and structurally they are similar to post-synaptic sympathetic neurons. In order to activate chromaffin cells, the splanchnic nerve of the sympathetic nervous system releases acetylcholine, which then binds to nicotinic acetylcholine receptors on the adrenal medulla. This causes the release of catecholamines. The chromaffin cells release catecholamines: ~80% of adrenaline (epinephrine) and ~20% of noradrenaline (norepinephrine) into systemic circulation for systemic effects on multiple organs, and can also send paracrine signals. Hence they are called neuroendocrine cells.

<span class="mw-page-title-main">Baroreflex</span> Homeostatic mechanism in the body

The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure at nearly constant levels. The baroreflex provides a rapid negative feedback loop in which an elevated blood pressure causes the heart rate to decrease. Decreased blood pressure decreases baroreflex activation and causes heart rate to increase and to restore blood pressure levels. Their function is to sense pressure changes by responding to change in the tension of the arterial wall The baroreflex can begin to act in less than the duration of a cardiac cycle and thus baroreflex adjustments are key factors in dealing with postural hypotension, the tendency for blood pressure to decrease on standing due to gravity.

<span class="mw-page-title-main">Endocrine gland</span> Glands of the endocrine system that secrete hormones to blood

Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testicles, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.

Acute stress reaction and acute stress disorder (ASD) is a psychological response to a terrifying, traumatic or surprising experience. Combat stress reaction (CSR) is a similar response to the trauma of war. The reactions may include but are not limited to intrusive or dissociative symptoms, and reactivity symptoms such as avoidance or arousal. It may be exhibited for days or weeks after the traumatic event. If the condition is not correctly addressed, it may develop into post-traumatic stress disorder (PTSD).

Secondary hypertension is a type of hypertension which by definition is caused by an identifiable underlying primary cause. It is much less common than the other type, called essential hypertension, affecting only 5-10% of hypertensive patients. It has many different causes including endocrine diseases, kidney diseases, and tumors. It also can be a side effect of many medications.

In humans and other animals, the adrenocortical hormones are hormones produced by the adrenal cortex, the outer region of the adrenal gland. These polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to stress, and they also regulate other functions in the body. Threats to homeostasis, such as injury, chemical imbalances, infection, or psychological stress, can initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are aldosterone and cortisol. These hormones also function in regulating the conservation of water by the kidneys and glucose metabolism, respectively.

<span class="mw-page-title-main">Postganglionic nerve fibers</span> Fibers from the ganglion to the effector organ

In the autonomic nervous system, nerve fibers from the ganglion to the effector organ are called postganglionic nerve fibers.

<span class="mw-page-title-main">Phenylethanolamine N-methyltransferase</span> Mammalian protein found in Homo sapiens

Phenylethanolamine N-methyltransferase (PNMT) is an enzyme found primarily in the adrenal medulla that converts norepinephrine (noradrenaline) to epinephrine (adrenaline). It is also expressed in small groups of neurons in the human brain and in selected populations of cardiomyocytes.

<span class="mw-page-title-main">Norepinephrine</span> Catecholamine hormone and neurotransmitter

Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" is more commonly used in the United Kingdom, whereas "norepinephrine" is usually preferred in the United States. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic.

<span class="mw-page-title-main">Adrenal tumor</span> Medical condition

An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, and includes neuroblastoma, adrenocortical carcinoma and some adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but may cause significant health problems by unbalancing hormones.

<span class="mw-page-title-main">Adrenaline</span> Hormone and medication

Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions. It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output by acting on the SA node, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals, including humans, and some single-celled organisms. It has also been isolated from the plant Scoparia dulcis found in Northern Vietnam.

Non-tropic hormones are hormones that directly stimulate target cells to induce effects. This differs from the tropic hormones, which act on another endocrine gland. Non-tropic hormones are those that act directly on targeted tissues or cells, and not on other endocrine gland to stimulate release of other hormones. Many hormones act in a chain reaction. Tropic hormones usually act in the beginning of the reaction stimulating other endocrine gland to eventually release non-tropic hormones. These are the ones that act in the end of the chain reaction on other cells that are not part of other endocrine gland. The Hypothalamic-pituitary-adrenal axis is a perfect example of this chain reaction. The reaction begins in the hypothalamus with a release of corticotropin-releasing hormone/factor. This stimulates the anterior pituitary and causes it to release Adrenocorticotropic hormone to the adrenal glands. Lastly, cortisol (non-tropic) is secreted from the adrenal glands and goes into the bloodstream where it can have more widespread effects on organs and tissues. Since cortisol is what finally reaches other tissues in the body, it is a non-tropic hormone. CRH and ACTH are tropic hormones because they act on the anterior pituitary gland and adrenal glands, respectively, both of which are endocrine glands. Non-tropic hormones are thus often the last piece of a larger process and chain of hormone secretion. Both tropic and non-tropic hormones are necessary for proper endocrine function. For example, if ACTH is inhibited, cortisol can no longer be released because the chain reaction has been interrupted. Some examples of non-tropic hormones are:

Neurocardiology is the study of the neurophysiological, neurological and neuroanatomical aspects of cardiology, including especially the neurological origins of cardiac disorders. The effects of stress on the heart are studied in terms of the heart's interactions with both the peripheral nervous system and the central nervous system.

References

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  10. ↑ Ball, Derek (2015-02-01). "Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle". The Journal of Endocrinology. 224 (2): R79–95. doi: 10.1530/JOE-14-0408 . ISSN   1479-6805. PMID   25431226.
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  12. ↑ Yang, S; Park, K; Zhou, Y (2015). "The Impact of Hypoglycemia on the Cardiovascular System: Physiology and Pathophysiology". Angiology. 67 (9): 802–809. doi:10.1177/0003319715623400. PMID   26685181. S2CID   9348873.
  13. 1 2 Cryer, P.E.; Davis, S.N; Shamoon, H (2003). "Hypoglycemia in Diabetes". Diabetes Care. 26 (6): 1902–1912. doi: 10.2337/diacare.26.6.1902 . PMID   12766131.
  14. ↑ Fisher, S.J.; Brüning, J.C.; Lannon, S.; Kahn, C.R. (2005). "Insulin Signaling in the Central Nervous System Is Critical for the Normal Sympathoadrenal Response to Hypoglycemia". Diabetes. 54 (5): 1447–1451. doi: 10.2337/diabetes.54.5.1447 . PMID   15855332.
  15. ↑ Cryer, P.E. (2006). "Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes". Journal of Clinical Investigation. 116 (6): 1470–1473. doi:10.1172/JCI28735. PMC   1464914 . PMID   16741570.
  16. ↑ Lender, Lender J.; Eisenhofer, G.; Mannelli, M.; Pacak, K. (2005). "Phaeochromocytoma". The Lancet. 366 (9486): 665–675. doi:10.1016/S0140-6736(05)67139-5. PMID   16112304. S2CID   208788653.
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