The Adrenal Gland COPY Flashcards
where are the adrenal glands?
Adrenal glands are situated on the superior pole of the kidney in the retroperitoneal space, each weighing ~4g in adults
Similar to the pituitary, the adrenal gland is composed of two quite separate endocrine glands rolled into one structure
what are the 2 seperate parts called?
adnreal medulla (~25%)
adrenal cortex (~75%)
what is the adrenal medulla? and what does it secrete?
a modified sympathetic ganglion (neuroendocrine gland)
Secretes catecholamines from the postganglionic cell, mainly epinephrine (adrenaline) but also norepinephrine and dopamine
amine hormones
what is the adrenal cortex and what does it secrete?
a true endocrine gland and secretes 3 classes of steroid hormones, the first 2 of which are of particular importance:
- Mineralocorticoids e.g. aldosterone: involved in the regulation of Na+ and K+
- Glucocorticoids e.g. cortisol: involved in maintaining plasma glucose
- Sex steroids e.g. testosterone
Aldosterone and cortisol are essential for survival
What is an example of a mineralocorticoid and its function?
Mineralocorticoids e.g. aldosterone: involved in the regulation of Na+ and K+
What is an example of a glucocorticoid and its function?
Glucocorticoids e.g. cortisol: involved in maintaining plasma glucose
Cortex surrounds the _______ and is arranged in _ concentric zones, producing different hormones
medulla
3
Zona glomerulosa =
aldosterone
Zona fasciculata =
glucocorticoids
Zona reticularis =
sex hormones
how does the synthetic pathway in the adrenal cortex work in order to produce different hormones?
All steroid hormones are derived from cholesterol, but different enzymes are found in different adrenal zones, resulting in different end products e.g. enzymes needed to make aldosterone are found only in the zona glomerulosa
Progesterone can be changed into sex steroids, aldosterone and cortisol
Different layers contain different enzymes localising different steroid hormones being localised to the layers
what is the most important enzyme in the synthetic pathway in the adrenal cortex?
what are some defects in 21-hydroxylase?
Defects in 21-hydroxylase is a common cause of congenital adrenal hyperplasia resulting in deficiency of aldosterone and cortisol and associated disruption of salt and glucose balance
Androgen biosynthesis is unaffected so accumulating steroid precursors are channelled into excessive adrenal androgen production
Babies born deficient in glucocorticoids and mineralocorticoids
Babies turn this excess cholesterol into more sex steroids
Babies born with ambiguous genitalia
Struggle to maintain blood glucose balance as loos of glucocorticoids
what is the hypothalamic-pituitary-adrenal pathway?
Also short-loop feedback by ACTH on CRH
A deficit in 21-hydroxylase results in adrenal hyperplasia. Why???
Levels of cortisol decrease resulting in negative feedback loop removing the break on the hypothalamus and anterior pituitary resulting in them giving more production of hormones and they are tropic hormones so cause growth so end up getting hyperplasia of the adrenal cortex
- Lack of 21-hydroxylase inhibits synthesis of cortisol
- This removes the negative feedback on ACTH and CRH release
- Increased ACTH secretion is responsible for enlargement of adrenal glands
- Negative feedback of ACTH on CRH synthesis remains
- Babies become very ill within a few days of birth
Cortisol is a ____________ hormone
glucocorticoid
influences glucose metabolism
~95% of plasma cortisol is…………….
bound to a carrier protein, cortisol binding globulin (CBG)
works with glucagon to increase BG
where are cortisol receptors? and what does binding to the receptor cause?
All nucleated cells have cytoplasmic glucocorticoid receptors
The hormone receptor complex migrates to the nucleus, binding to DNA via a hormone-response element to alter gene expression, transcription and translation
when is cortisol released throughout the day?
Plasma levels of cortisol show a very characteristic pattern
There is a marked circadian rhythm, preceded by a similar pattern of release of ACTH. Cortisol “burst” persists longer than ACTH burst because half-life is much longer
Peak is ~ 6-9am, nadir (lowest level) is ~ midnight.
Other fluctuations during the day are due to effects of other stimuli which are related to stress
Cortisol tends to peak early in the morning which is opposite to GH
Between 6 and 8 in the morning is highest
ACTH drives cortisol release so see the peaks following each other
Cortisol is around longer than ATCH as it is a peptide hormone and cortisol are steroid hormones so have a longer half life
Cortisol is your stress hormone – getting up is physiologically stressful on the body as need to get energy and mobilise glucose energy stores and the cardiovascular system has to work hard, increase cognitive and skeletal muscle load
is cortisol essential for life?
Yes
Removal of the adrenal glands in animals results in death in a few weeks
what happens when adrenal glands are removed?
Loss of cortisol means animals cannot deal with stress, particularly in terms of maintaining blood glucose levels. Cortisol as a glucocorticoid is crucial in helping to protect the brain from hypoglycaemia. It has a permissive action on glucagon, which is vitals as glucagon alone is inadequate in responding to a hypoglycaemic challenge
Removal of adrenal glands also renders animals incapable of maintaining their extracellular fluid volume, an effect mediated by aldosterone (see later)
What are the actions of cortisol on glucose metabolism (glucocorticoid actions)?
- Gluconeogenesis: Cortisol stimulates formation of gluconeogenic enzymes in the liver thus enhancing gluconeogenesis and glucose production. This is aided by cortisol’s action on muscle:
- Proteolysis: cortisol stimulates the breakdown of muscle protein to provide gluconeogenic substrates for the liver
- Lipolysis: similarly, cortisol stimulates lipolysis in adipose tissue which increases [FFA] plasma creating an alternative fuel supply that allows [BG] to be protected while also creating a substrate (glycerol) for gluconeogenesis
- Decreases insulin sensitivity of muscles and adipose tissue
In all these glucose counter-regulatory effects, cortisol is acting to oppose insulin, not surprisingly therefore excess cortisol is diabetogenic
is cortisol anabolic or catabolic?
catabolic
what are some Additional Actions of Cortisol (non- glucocorticoid)?
- Negative effect on Ca2+ balance: decrease absorption from gut, increases excretion at kidney resulting in net Ca2+ loss. Also increase bone resorption = osteoporosis
- Impairment of mood and cognition: depression and impaired cognitive function are strongly associated with hypercortisolaemia
- Permissive effects on norepinephrine: particularly in vascular smooth muscle (a-receptor effect = vasoconstrictive). Cushings Disease (hypercortisolaemia) is strongly associated with hypertension. Likewise, low levels of cortisol are associated with hypotension
- Suppression of the Immune System: Cortisol reduces the circulating lymphocyte count, reduces antibody formation and inhibits the inflammatory response. Latter effect can be useful clinically e.g. asthma/ulcerative colitis/organ transplant
what are some side effects of glucocorticoid therapy?
How is chronic glucocorticoid treatment withdrawed?
Care is required when withdrawing glucocorticoid treatment due to enhanced negative feedback effects of exogenous cortisol
Additional, therapeutic cortisol enhances the negative feedback on hypothalamus and pituitary reducing release of CRH and ACTH
Loss of trophic action of ACTH on adrenal gland cause atrophy of gland. Risk of adrenal insufficiency if withdrawal is too fast
Careful when withdrawing a patient from long term cortisol treatment, think back to this negative feedback loop
Over the treatment you have been turning down the release of the intermediate hormones
Takes time for the cortical tissue to build back up again so take them off it slowly to allows the cortex to build up to makes its own cortisol
Aldosterone is _______________
mineralocorticoid
what does aldosterone do?
acts on the distal tubule of the kidney to determine the levels of minerals reabsorbed/excreted
Aldosterone increases the reabsorption of Na+ ions and promotes the excretion of K+ ions
how is aldosteorne released?
The secretion of aldosterone by the adrenal cortex is primarily controlled by a complex reflex pathway originating in the kidney, the renin-angiotensin-aldosterone system (RAAS)
As such aldosterone will be covered in detail in the urinary lectures
what is the end effect of aldosterone release which is mainly on CVS?
- Increased aldosterone release stimulates Na+ (and H2O) retention and K+ depletion, resulting increased blood volume and increased blood pressure
- Decreased aldosterone leads to Na+ (and H2O) loss and [K+]plasma, resulting in diminished blood volume and decreased blood pressure
Aldosterone, like cortisol, is ________ ___ ____
essential for life
what is HPA?
The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus, the pituitary gland, and the adrenal glands
What are 2 main things that could go wrong with the HPA system?
hypersecretion or hyposecretion of cortisol
what are causes of hypersecretion of cortisol?
• Cushing’s syndrome/disease:
Hypersecretion is most commonly due to a tumour in:
- adrenal cortex (1o hypercortisolism = Cushing’s syndrome)
or
- pituitary gland (2o hypercortisolism = Cushing’s disease). Most common. Excess ACTH
• Iatrogenic - Too much cortisol administered therapeutically
what are causes of hyposecretion of cortisol?
- is much less common than hypersecretion
- Addison’s disease
- Hyposecretion of all adrenal steroid hormones
- Due to autoimmune destruction of adrenal cortex
what changes does cushing disease cause on the body?
fat on back of next, face and trunk
moon face = round face
thin arms and legs
Cushing’s Disease is characterised by wasting of the extremities (due to catabolic action of cortisol) but for unknown reasons fat is redistributed to the face (“moon face”) and trunk
Stress increases vulnerability to _________ via action on ___
infection
HPA
how does stress increases vulnerability to infection via action on HPA?
CRH and ACTH release is promoted by stress
Alcohol, caffeine and lack of sleep all “disinhibit” the Hypothalamo-Pituitary-Adrenal Axis (HPA). Alcohol in particular depresses the neurons involved in negative feedback further enhancing stress effect and increasing levels of CRH and ACTH
Subsequent elevation of cortisol levels effectively turn down the immune system, increasing vulnerability to infection
Cortisol is our stress hormone as it makes sure we have enough glucose in our blood in stressful situations
what is the Adrenal Medulla?
Modified sympathetic ganglion, not true endocrine tissue. Similar to posterior pituitary in having neuroendocrine role
Preganglionic sympathetic fibres terminate on specialised postganglionic cells in the adrenal medulla. These postganglionic fibres do not have axons – instead they release their neurohormones (adrenaline) directly into the blood
describe an adrenal medulla pathology?
Pheochromocytoma is a rare neuroendocrine tumour, found in adrenal medulla which results in XS catecholamines: increased HR = increased CO = very increased BP
Diabetogenic due to adrenergic effect on glucose metabolism
Responds well to surgery
what are the different sites that an endocrine pathology can happen in HPA? and are they primary, secondary or tertiary?
Pathology in hypothalamus (tertiary), anterior pituitary (secondary) or the adrenal cortex (primary)
Tertiary problems rare so not normally the hypothalamus is where the problem arises
Normally either a secondary or primary problem
wha would happen as a result of a pathology in the hypothalamus?
what would happen as a result of a pathology in the anterior pituitary?
what would happen as a result of a pathology in the adrenal cortex?
How would you determine where a endocrine pathology is in HPA?
Take blood test and measure which hormones are low and high and then you can get an idea of where the pathology may be
