Changes

==Adrenal Glands==

==Adrenal Glands==

The adrenal glands are paired bodies lying cranial to the kidneys within the retroperitoneal space. The glands consist of two layers; the cortex and medulla.

The '''adrenal cortex''' is red to light brown in colour and is comprised of three zones. From the outer to inner, the layers are;  

The adrenal cortex is red - light brown in colour and is comprised of three zones. These zones all produce hormones derived from cholesterol which is abundant in the cells. From outer to inner the layers are zona glomerulosa, zona fasciculata and zona reticularis. The adrenal cortex represents 80-90% of the adrenal gland.

1. zona glomerulosa

The adrenal medulla is primarily involved in the production of catecholamines; epinephrine and norepinephrine. In fetal life the adrenal medulla plays a role in the autonomic nervous system. The medulla acts as a sympathetic ganglion with the postganglionic cells lacking axons. Through sympathetic preganglionic fiber stimulation the medullary cells secrete catecholamines. The adrenal medulla represents only 10-20% of the adrenal gland.

 

 

These zones all produce hormones derived from cholesterol, which is abundant in the cells. The '''adrenal cortex''' represents 80-90% of the adrenal gland. The '''adrenal medulla''' is primarily involved in the production of catecholamines; epinephrine and norepinephrine. In fetal life, the adrenal medulla plays a role in the autonomic nervous system. The medulla acts as a sympathetic ganglion with the postganglionic cells lacking axons. Through sympathetic preganglionic fiber stimulation, the medullary cells secrete catecholamines. The adrenal medulla represents only 10-20% of the adrenal gland.

[[Image:Adrenal Gland Schematic..jpg|700px|small>'''Schematic Diagram of the Adrenal Gland</small>|frameless]]

[[Image:Adrenal Gland Schematic..jpg|700px|small>'''Schematic Diagram of the Adrenal Gland</small>|frameless]]

==Embryological Origin==

==Embryological Origin==

The fetal cortex develops in the centre with the permanent cortex surrounding it. By 4 months of age the adrenal gland is fully developed.

The adrenal glands develop from two separate embryological tissues; the '''neural crest ectoderm''' and the '''intermediate mesoderm'''. The medulla originates from neural crest cells migrating from sympathetic ganglion. Mesodermal cells then surround the medulla. The adrenal cortex develops from the intermediate mesoderm. The fetal cortex develops in the centre, with the permanent cortex surrounding it. By 4 months of age the adrenal gland is fully developed.

==Anatomy==

==Anatomy==

Even though the adrenal glands gain their name through their relationship with the kidney they are in fact more closely related to the major vessels. They are closely connected to the aorta and caudal vena cava.

Even though the adrenal glands gain their name through their relationship with the kidney, they are in fact more closely related to the major vessels, including the aorta and the caudal vena cava.  

 

 

They are elongated and are often asymmetrical being moulded around the neighbouring vessels. Their size varies greatly and generally those of juveniles are larger than adults, and those of lactating or pregnant animals are larger than reproductively inactive animals. A medium-sized dog's adrenals will on average measure 2.5x1x0.5cm.

The oxygenated supply is from various branches of the following neighbouring trunks; aorta, renal artery, lumbar artery, phrenicoabdominal artery and the cranial mesenteric arteries. After perfusion of the gland, the blood pools in a central vein and then exits the gland through the hilus. This then joins up with the caudal vena cava or one of it's tributaries.

The zona glomerulosa is narrow and the cells are in a whorled pattern. The zona fasiculata is wide and the cells lie in columns. The zona reticularis is more randomly organised.

The function of the cortex is to produce '''adrenocorticoid hormones'''. The three zones each make a specific type of hormone:

The oxygenated supply is from various branches of the following neighbouring trunks; aorta, renal artery, lumbar artery, phrenicoabdominal artery and the cranial mesenteric arteries.

The Zona Fasciculata secretes '''glucocorticoids''',

After perfusion of the gland the blood pools in a central vein and then exit the gland through the hilus. This then joins up with the caudal vena cava or one of it's tributaries.

The Zona Reticularis secretes sex steroids or '''androgens'''.

1) The P450scc enzyme converts cholesterol to pregnenolone by the removal of a side chain. This is regulated by ACTH and is the rate determining step of adrenocorticoid hormone production. This occurs in the mitochondria.

1) The P450scc enzyme converts cholesterol to pregnenolone by the removal of a side chain. This is regulated by ACTH and is the rate determining step of adrenocorticoid hormone production. This occurs in the mitochondria.

2) Hydroxylation reactions occur in the mitochondria and endoplasmic reticulum converting pregnenolone into specific hormones. The location within the cortex determines the hormones produced.

2) Hydroxylation reactions occur in the mitochondria and endoplasmic reticulum converting pregnenolone into specific hormones. The location within the cortex determines the hormones produced.

===='''Mineralocorticoids'''====

===='''Mineralocorticoids'''====

These hormones regulate the metabolism of inorganic ions, such sodium, potassium and chloride. Several hormones are produced but the most important is '''aldosterone'''.

These hormones regulate the metabolism of inorganic ions, such sodium, potassium and chloride. Several hormones are produced but the most important is '''aldosterone'''. Aldosterone is formed in the zona glomerulosa by the conversion of pregnenolone to cortisol and then to corticosterone, before finally becoming aldosterone. It circulates by binding to albumin and cortisol-binding globulin. It's plasma half-life is 20 minutes. It is eventually inactivated in the liver, where it binds to glucuronic acid and is excreted in bile and urine.

It is formed in the zona glomerulosa by the conversion of pregnenolone to cortisol and then to corticosterone before finally becoming aldosterone. It circulates by binding to albumin and cortisol-binding globulin. It's plasma half-life is 20 minutes. It is eventually inactivated in the liver, where it binds to glucuronic acid and is excreted in bile and urine.

 

'''Regulation and action''' - It's main regulators of synthesis and secretion are; '''Renin''' and extracellular concentrations of potassium ions. Its main action is upon renal regulation and electrolyte and fluid balance. These are fully explained within the '''[[Renin Angiotensin Aldosterone System|renin-angiotensin]] and [[Aldosterone|aldosterone system]] pages.

It's main regulators of synthesis and secretion are; '''Renin''' and extracellular concentrations of potassium ions. Its main action is upon renal regulation and electrolyte and fluid balance. These are fully explained within the '''[[Renin Angiotensin Aldosterone System|renin-angiotensin]] and [[Aldosterone|aldosterone system]] pages.

===='''Glucocorticoids'''====

===='''Glucocorticoids'''====

'''Regulation of Synthesis and Secretion'''

'''Regulation of Synthesis and Secretion'''

This is regulated by the hypothalamus-pituitary adrenal axis as follows:

This is regulated by the hypothalamus-pituitary adrenal axis as follows:

[[Image:ACTH axis.jpg|right|thumb|205px|<small><center>'''Schematic Diagram of the Hypothalamic Pituitary Adrenal Axis, Copyright John Tulloch</center></small>]]

[[Image:ACTH axis.jpg|right|thumb|205px|<small><center>'''Schematic Diagram of the Hypothalamic Pituitary Adrenal Axis, Copyright John Tulloch</center></small>]]

* An environmental or internal stimuli (such as stress or light regulating the circadian rhythm) causes the hypothalamus to release ACTH-releasing hormone ('''ACTH-RH''').

An environmental, or internal stimuli (such as stress or light regulating the circadian rhythm) causes the hypothalamus to release ACTH-releasing hormone ('''ACTH-RH'''). ACTH-RH flows to the pituitary gland, stimulating the production of adrenocorticotrophic hormone ('''ACTH'''). ACTH binds to receptors on the cells of the adrenal cortex, thus activating adenyl cyclase. This leads to increased cAMP levels, and the mobilization of more cholesterol and so the production of more cortisol. This is the rate limiting step and is determined by the P-450-enzyme. Cortisol then has a negative feedback effect on ACTH-RH and ACTH secretion.

* ACTH-RH flows to the pituitary gland stimulating the production of adrenocorticotrophic hormone ('''ACTH''').

* ACTH binds to receptors on cells of the adrenal cortex. Thus activating adenyl cyclase.

* This leads to increased cAMP levels and the mobilization of more cholesterol and so the production of more cortisol. This is the rate limiting step and is determined by the P-450-enzyme.

* Cortisol then has a negative feedback effect on ACTH-RH and ACTH secretion.

'''Action'''

'''Action'''

These are essential hormones and have multiple effects around the body.

 

* Cortisol has a '''permissive action'''. I.e. without cortisol certain chemical reactions within cells are unable to occur, for example the production of epinephrine and glucagon.

These are essential hormones and have multiple effects around the body. Cortisol has a '''permissive action''', i.e. without cortisol certain chemical reactions within cells are unable to occur, for example the production of epinephrine and glucagon. Cortisol is a '''stress hormone''', in times of stress it is released and enhances the effect of norepinephrine on blood pressure. It is also essential for the day to day maintenance of normal blood pressure and will also stimulate gluconeogenesis and inhibit certain tissues utilization of glucose. Cortisol stimulates the degradation of fats and proteins and inhibits DNA synthesis in some tissues. This along with degradation of protein, results in a '''growth-inhibiting effect''' in times of stress. It can also  have '''anti-inflammatory''' effects. It inhibits the formation of prostaglandins and cytokines and reduces the ability of white blood cells being transported to an injured area. It helps keep in check inflammatory processes that could potentially cause tissue damage. Cortisol is also '''immunosuppressive''', by reducing the lymphocyte numbers in circulation and reducing antibody production.

* Cortisol is a '''stress hormone'''. In times of stress it is released and enhances the effect of norepinephrine on blood pressure. It is also essential for the day to day maintenance of normal blood pressure. It will also stimulate gluconeogenesis and inhibit certain tissues utilization of glucose.

* It stimulates degradation of fats and proteins.

* It inhibits DNA synthesis in some tissues. This along with degradation of protein results in a '''growth-inhibiting effect''' in times of stress.

* It can have '''anti-inflammatory''' effects. It inhibits the formation of prostaglandins and cytokines and reduces the ability of white blood cells being transported to an injured area. It helps keep in check inflammatory processes that could potentially cause tissue damage.

* It is also '''immunosuppressive''' by reducing the lymphocyte numbers in circulation and reducing antibody production.

===='''Androgens'''====

===='''Androgens'''====

These hormones function as male sex hormones. The most important of these is '''testosterone'''. This is produced by the conversion of pregnenolone to dehydroepiandrosterone, then to androstenedione and finally to testosterone. This occurs in the zona reticularis. They bind in the blood to sex hormone-binding globulin (SHBG) and albumin. Most adrenal androgens have little physiological action untill they are coverted to testosterone.

These hormones function as male sex hormones. The most important of these is '''testosterone'''. This is produced by the conversion of pregnenolone to dehydroepiandrosterone, then to androstenedione and finally to testosterone. This occurs in the zona reticularis. They bind in the blood to sex hormone-binding globulin (SHBG) and albumin. Most adrenal androgens have little physiological action until they are coverted to testosterone. They have little importance within the male, however, in women adrenal androgens, which are converted to oestrogen in adipose tissue, is the most important source of oestrogen after the menopause.

They have little importance within the male. In women adrenal androgens, which are converted to oestrogen in adipose tissue, is the most important source of oestrogen after the menopause.

==='''Adrenal Medulla'''===

==='''Adrenal Medulla'''===

The adrenal medulla converts the amino acid to '''catecholamines'''. This group of hormones contain '''epinephrine''' and '''norepinephrine'''. All of the bodie's circulating epinephrine is produced by the adrenal medulla, where as norepinephrine comes from both the medulla and postganglionic sympathetic neurons.

 

The adrenal medulla converts the amino acid to '''catecholamines'''. This group of hormones contains '''epinephrine''' and '''norepinephrine'''. All of the bodies circulating epinephrine is produced by the adrenal medulla, where as norepinephrine comes from both the medulla and postganglionic sympathetic neurons.

'''Synthesis, secretion and metabolism'''

'''Synthesis, secretion and metabolism'''

'''Adrenergic Receptors'''

'''Adrenergic Receptors'''

The catecholamines bind to two types of receptor proteins in cell membranes to elicit a response; these are alpha and beta receptors. The following is a table of where the receptors are located in the body and their effects when stimulated.  

The catecholamines bind to two types of receptor proteins in cell membranes to elicit a response; these are alpha and beta receptors. The following is a table of where the receptors are located in the body and their effects when stimulated.