Group+5

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 * //Learning Outcomes//**
 * //Locate the Adrenal Glands and differentiate between the Adrenal Medulla and the Adrenal Cortex//
 * //Describe the relationship between the Adrenal Glands and the Nervous System//
 * //List and discuss the hormones that the Adrenal Glands produce and their effects on the body//
 * //Explain why synthetic Adrenaline is often added to local anaesthetics used in dentistry//




 * __1. Introduction to the Adrenal Glands__ **

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Adrenal Glands are the bodies main protection against acute and chronic stress. The glands are yellow, pyramid-shaped and sit on the superior surface of the kidneys in the thoracic abdomen (Griffen & Ojeda, 2000). Part of the endocrine system the adrenal glands release hormones as a response to stressors. Adrenal glands are covered by a connective tissue, which is then covered by a layer of fat for protection and insulation. In general they weigh approximately 5 grams, measure 30 mm wide, 50 mm long and about 10 mm thick. These sizes change as secretory demands increase or decrease.The glands are comprised of two parts; the adrenal cortex, which releases steroid hormones, protects against immediate stress or injury and the adrenal medulla, which releases catecholamines which instigate the mobilization of glucose and fatty acids and prepare body organs for action during acute stress. Thus the relationship of the glands with the nervous system is that of a responsive nature to stimulants (in this case strssors) which are transmitted from the neurons to the brain and then back to the adrenal glands, stimulating the release of specific hormones to assist the body in coping with the stressor. ======

__The Adrenal Cortex:__
The adrenal cortex is the site in which corticosteroid hormones are synthesized from cholesterol. The three main steroid hormones secreted by the adrenal cortex are; The cortical cells which secrete these hormones are divided into three distinct zones; the superficial //zona glomerulosa// which secretes mineralocorticoids, the //zona fasciculata// which releases glucocorticoids, and the inner most functional zone, the //zona reticularis// whcih secretes gonadocorticoids.
 * mineralocorticoids, these help control and regulate water, mineral and electrolyte concentrations in the body, for example, aldesterone, a hormone that helps control the body's sodium levels.
 * glucocorticoids, these are essentially metabolic hormones such as cortisol which is the main glucocorticoid secreted, it increases blood pressure and blood sugar levels and reduces immune responses,
 * gonadocorticoids, sexy hormones such as testosterone

The secretion of these various hormones is regulated by neuroendocrine hormones that are secreted fromt eh hypothalamus and the pituitary gland. The medulla contrastingly is directly innervated and it is the nerve impulses that directly stimulate the secretion of hte medulla's hormones.

__The Medulla:__ The Adrenal Medulla secretes catechloamines, epinephrine or norepinephrine (also called adrenaline or noradrenalin). These hormones cause an immediate short term response to stress known as the "fight or flight" response. The effects of epinephrine include; increased heart rate, increased blood sugar levels, decreased immune response, bronchiol dialation, increased blood flow to the skeletal muscles and heart. Norepinephrine has a greater influence on blood pressure and peripheral vasoconstriction which allows blood flow to the skeletal muscles and heart to be increased.

As mentioned before some nerve fibres synapse with the medullary cells in the adrenal glands. These preganglionic fibres directly stimulate the medulla to secrete norepinephrine and epinephrine into the blood stream.



Table 1. The Adrenal Hormones - adapted from Marieb


 * __3. Adrenal glands and the Nervous System __**
 * The adrenal glands are **part of the peripheral nervous system. The peripheral nervous system can be divided into conscious and unconscious activity. The conscious activity is controlled by the somatic (voluntary) nervous system and unconscious activities, such as actions of the heart, are controlled by the autonomic (involuntary) nervous system.



The autonomic nervous system is divided into two subsystems: · Parasympathetic nervous system · Sympathetic nervous system These subsystems have opposite effects. The autonomic nervous system is firstly stimulated by the preganglionic neurons located in the CNS. These neurons run to a ganglion in the body and synapse with postganglionic neurons which run to the effector organ (cardiac muscle, smooth muscle, or a gland).  Neurons in the parasympathetic NS secrete a neurotransmitter called acetylcholine at the synapses. This decreases overall physical activity so the parasympathetic NS is associated with rest. Neurons in the sympathetic NS secrete a neurotransmitter called noradrenaline (norepinephrine) at the synapses. This increases overall physical activity and causes a flight or fight response.

Adrenal glands is a component of the autonomic nervous system. They respond to the pituitary glands which releases a hormone called adrenocorticotrophic (ACTH) into the blood which is then transported to the adrenal gland. The pituitary glands release of hormone is stimulated from the hypothalamus through the sympathetic nervous system involved in fight of flight response. The hypothalamus produces hormone cortcotropin releasing factor (CRF). The pituitary glands then produce more than two dozen steroid hormones, collectively known as cortcosteroids according to the level of corticosteroids the body needs. The hypothalamus releases CRF in response to the release of cortisol, the body’s chief fighting hormone to deal with physical or mental stress. The adrenal glands responds to stressors with the release of epinephrine and norepinephrine. These hormones bind to adrenergic receptors. Epinephrine help regulate the bodies:
 * Blood pressure
 * Heart rate
 * Sweating
 * Increase in metabolic rate

__**4. The effect of Adrenal glands on the body.**__ The Adrenal Medulla and the Adrenal Cortex operate almost as two seperate glands each releasing different hormones for different functions. The different hormones create very different and specific effects on the body.

//__The Adrenal Cortex:__

Zona Glomerulosa -// Mineralocorticoids from the zona glomerulosa control mineral and water levels within the body (Marieb, 2007). Aldosterone is the main mineralocorticoid released targeting the distal tubule of the kidney, its function is to maintain the sodium balance in extracellular fluids. It also controls the reabsorption of sodium from urine filtrate.

//Zona Fasiculata -// Glucocorticoids from the zona fasiculata are essential for the body to function as they are involved in energy metabolism and assist in resisting stress. The primary glucocorticoid is cortisol which helps keep blood sugar levels constant and maintain the blood volume level. However during times of stress (infection,physical/emotional trauma) larger amounts of this hormone is released with the effect of provoking gluconeogenesis (the formation of glucose from fats and proteins). It also stimulates the fatty acids in adipose tissue ready for use by the body to ensure that glucose is readily available for the brain. Glucocorticoids also cause a rise in blood prssure and thus circulatory efficiency. However not all effects this hormone has are good, it also has anti-inflammatory and anti-immune effects.

//Zona Reticularis -// Gonadocorticoids are secreted from the zona reticularis. These includ the sex hormones such as androgen and estrogen. These are vital when reaching puperty for growth and development of sexual characteristics however hypersecretion or excessive secretion of gonadocorticoids can lead to mascullinization. For females this can mean facial hair and excessive hair on arms, legs etc. For males the effect is of an intense sex drive.

//__The Adrenal Medulla:__//

The adrenal medulla facillitates the "fight or flight" reaction by secreting epinephring (adrenalin) and norepinephrine (noradrenaline).

//Epinephrine -// The release of epinephrine increases the heart rate and the strength of the heart contractions. This allows increased blood flow to the skeletal muscles and brain and relaxes smooth muscles. It also assists the conversion of glycogen to glucose in the liver dilation of the bronchiols, narrows bloodvessels to the skin and intestines. Chronic stress, or the over stimulation of the adrenal medulla can lead to exhaustion and lower the immune response.

//Norepinephrine -// Unline epinephrine that affects the smooth muscle, metabolic processes adn cardiac output norepinephrine has strong vasoconstrictive effects which have the consequential result of increasing the blood pressure. Norepinephrine also works as a neurotransmitter residing inthe axon terminals of nerve cells it passes on information from one nerve to the next.


 * __5. Diseases Associated with the Adrenal Glands__**

Adrenal disorders can cause adrenal glands to make too much or not enough hormones. With Cushing's syndrome, there's too much cortisol, contrastingly with Addison's disease, there is not enough. Tumors, infection and cancers can also cause disorders.


 * Cushing's syndrome** (Hypercortisolism) is caused by long-term exposure to too much cortisol. Sometimes, taking synthetic hormone medicine to treat inflammatory disease can lead to Cushing's syndrome. Cushing's syndrome is rare however symptoms include:
 * Upper body obesity
 * Thin arms and legs
 * Severe fatigueand muscle weakness
 * High blood pressure
 * High blood sugar levels
 * Easily Bruised

Often dentists are the first to discover Addison's due to the multipe brown pigments in teh mouth that can occur.
 * Addison's disease** (Adrenal insufficiency) is usually caused by a problem in the immune system it affects all ages and both sexes equally.It occurs as a result of low cortisol and even low aldosterone levels and consequently as a result of loss of function in the adrenal cortex. This can occur when the immune system imstakenly attacks its own tissues, damaging the adrenal glands. There are two main types of Addison's disease; Primary which involves direct loss of cortex function and, Secondary which is due to a dysfunction in the pituitary gland leading to a decreased production of ACTH hormone.

Addison's disease is also rare, symptoms include:
 * Weight loss
 * Muscle weakness
 * Fatigue that gets worse over time
 * Low blood pressure
 * Patchy or dark skin (can affect the mouth at an early stage with multiple flat and pigmented lesions)
 * nausea,
 * vomiting
 * hypotension


 * __6. Adrenalin in Anaesthetics__**

The sensation of pain is registered by the brain though the nervous system, more specifically through neurons (nerve cells). Nerve cells are made up of; extensions called dendrites that have sensory receptors located on their ends and are attached to a cell body from which another extension called an axon extends ending in axon terminals. Pain is initially sensed as a disturbance by the sensory receptors on the dendrites. This disturbance forms a message that is transmitted down the body of the cell through the axon to the axon terminals. From the axon terminals, neurotransmitters are released into a gap between the axon terminals and the dentrites of the following neuron called the synaptic celft, and traverse this gap to connect with specific chemoreceptors on an adjcent neuron, creating a depolarisation in the membrane of that neuron, that continues the transmission of the message. The axon is key in the continuation of this message and in ensuring the message is sent expediently and correctly. The axon is a long thing extension of the neuron with a negative intracellularcharge and a positive charge outside of the cell membrane. The message is sent down the axon in the form of an electronic impulse called the action potential. This electronic impulse is facillitated by transmembrane proteins called sodium channels that are stimulated to open by a disturbance in the cell membrane. These channels move sodium ions inside the cell creating an overall positive charge inside the membrane and a negative charge outside the cell membrane. This change in polarity stimulates potassium channels to open and releases potassium ions to the outside of the cell regulating the polarity of the cell to negatively charged intercellularly and positively charged outside the cell. This change in polarity and then regulation of polarity continues down the length of the axon to the axon terminals.

Local anaesthetics (LA) are often used to reduce the patients discomfort and levels of pain felt during difficult or cmoplex procedures. When placed near never membranes anaesthetics produce a temporary conduction blockage of neural impulses, preventing nerve impulses traveling to the central nervous system (Miller, 2000). This temporary blockage of neural transmissions is caused by anaesthetics blocking the passage of Sodium ions throught the axon's sodium ion channels. On these channels are specific receptors that particles in the LA attach to. When the sodium channels are in a closed or inactive state (not transmitting an impulse) the molecules in the LA bind to the channels arresting the channels in this closed or 'off' configuration. Thus the channel is no longer permeable to sodium ions slowing the rate of depolarization to a great extent. So much so that the action potential is no longer propogated along the nerve membrane.

Unfortunately most local anaesthetics can have a vasodilative (expanding effect) on the vessels surrounding the site of the LA which increases the rate of absorbtion after the injection (Tuckley 1994). The Vassodilation increases the liklihood of the anaesthetic quickly wearing off as the movement and the ease of penetration through blood vessel walls increases allowing the diffusion of the LA molecules and reducing the concentration of the anaesthetic in the desired area. As a result vasoconstrictors are often added to the anaesthetic to reduce the dialating effect of the anaesthetic which in turn increases the potency and the length of time the anaesthetic is active by limiting the spread of the anaesthesia to a specific desired area of tissue (Tuckley 1994). Epinephrine or nor epinephrine (adrenalin or nor adrenilin) is a vasoconstrictor. When added to LA limits systemic absorption thus prolonging the duration of the action of LA by keeping the molecules in contact with the nerve fibres(Miller, 2000). On rare occations, the epinephrine may accidently be injected into a vein instead of a muscle tissue. This can cause a very dramatic increase in heart rate. (Figure 3: Dental Anaesthetic syringe.)


 * __7. Reference List__**

Encyclopaedia Britannica 2009, //Adrenal gland//, United States, viewed 23 Semptember 2009 []

Griffin James E. & Ojeda Sergio R. (2000), Textbook of Endocrine Physiology fourth Edition, Oxford University Press, United States of America

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Marieb Elaine N, Hoehn Katja, 2007, //Human Anatomy & Physiology// seventh edition, Pearson Benjamin Cummings, San Fransisco

Martini, F 2006, //Fundamental of Anatomy & Physiology//, 8th edn, Pearson Education, United States of America

Medline Plus 2009, //Adrenal gland disorders//, United States, viewed 23 September 2009, []

Shlafer Marshal, 2004, //Pharmacology:PreTest self-assesment and review,// Eleventh edition, pg 67, McGraw-Hill Professional Publishers

Stoelting Rober K., Miller Ronald D., 2000, //Basics of Anaesthesia// 4th edition, pages 80-84, Churchill Livingstone, Philadelphia Pennsylvania

Tuckley. J.M.1994, "The Pharmacology of Local Anaesthetic Agents", //Update in Anaesthesia// Issues 4, article 7. World Anaesthesia Online, last Updated 26th of February 2008. []

University of Virginia health system, //Endocrinology; The Adrenal Glands,// Updated February 12 2004, viewed September 15th 2009 []