Wk 29 Flashcards
What hormones are released from the adrenal cortex?
What hormones are released from the adrenal medulla?
Cortex= Glucocorticoids (cortisol, corticosterone)
Medulla= Adrenalin and noreadrenalin
What are the 3 layers of the adrenal cortex and what hormones does each layer secrete?
Outermost layer= Zona glomerulosa (Mineralocorticoids- mainly aldosterone)
Middle= Zona fasculata (Glucocorticoids- mainly cortisol)
Inner cortex= Zona reticularis (Androgens)
What hormone does the hypothalamus release that goes to the anterior pituitary to stimulate the next hormone (related to glucocorticoid release from adrenal cortex)?
What hormone does the anterior pituitary release?
Hypothalamus releases: Corticotropin-releasing hormone (CRH)
Anterior pituitary then releases: Adrenocorticotropic hormone (ACTH)
CRH released by hypothalamus in response to what?
Stressors
Where does the synthesis of cortisol occur in the adrenal cortex?
What is cortisol made from?
Zona fasciculata
Cholesterol
How does Adrenocorticotrophic releasing hormone stimulate the adrenal gland to produce steroid hormones?
It promotes the uptake and release (from storage) of cholesterol so steroids can be synthesised
What is the major carrier of cholesterol to peripheral tissues?
LDL
Corticotrophin Releasing Hormone is released as pulsatile secretions so this stimulates Adrenocorticotrophic Hormone to also be released in pulsations…
Which time of the day has the highest pulsations?
Late night/ early morning
Is cortisol lipid or water soluble?
Lipid sol
What are the carrier proteins that transport cortisol in the blood? 2
Cortisol binding globulin or transcortin (albumin does a lil bit)
Secretion of cortisol is mainly controlled by ACTH, but secretion is also promoted by what 3 things?
Vasopressin/ ADH (increases BP)
Nitric Oxide
Some cytokines
Does cortisol promote or inhibit the release of CRH and ACTH?
Inhibits (Neg feedback loop)
What is Cushing’s Disease and does it increase or decrease ACTH and cortisol?
It is a tumor in the pituitary gland that makes ACTH so there is high cortisol and because there is neg feedback, this lowers the really high levels of ACTH so ACTH levels can be high or normal
What is Cushing’s syndrome caused by? 2 options
Adrenal tumour or Ectopic ACTH
Adrenal tumour= Lots of cortisol being produced which has neg feedback on ACTH so low ACTH (same action with steroid drugs)
Ectopic ACTH= lots of ACTH and lots of cortisol
What is Adrenal Insufficiency? 2 options
It can be either Addison’s Disease or Hypopituitarism
Addison’s disease= adrenal damage so high levels of ACTH but still low levels of cortisol
Hypopituitarism= Pituitary gland isn’t secreting ACTH properly so low ACTH and therefore low cortisol
What is an anabolic effect of cortisol? (on the liver)
What are 2 catabolic effects of cortisol? (on muscle and adipose tissue)
Anabolic on Liver: Gluconeogenesis (making blood glucose from AA and glycerol etc)
Catabolic on muscle: Protein breakdown
Catabolic on adipose: lipolysis
Is cortisol slow or fast acting? Why?
Slow because effects on transcription and translation
What is the main action of cortisol?
It is a glucocorticoid so main action is on glucose metabolism: anti-insulin effect so releases stored glucose into blood (enhances action of glucagon)
How does cortisol stimulate the urea cycle in the liver?
By gluconeogenesis in the liver
As AA are converted to glucose, lots of nitrogen is generated which needs to be cleared so urea cycle enzymes are recruited and the nitrogen enters the cycle and is converted to urea which is excreted by kidneys
How does cortisol affect the muscles?
It stimulates protein catabolism to release AAs for gluconeogenesis in the liver
Excess cortisol (Cushing’s) promotes fat in which locations and promotes lipolysis in which locations?
Promotes fat storage in visceral locations and fat breakdown in peripheral locations
What is the most common reason for giving people cortisol in medications?
What is a consequence of too much cortisol medication?
It has potent anti-inflammatory and immunosuppressive effects
In large quantities, cortisol depresses immune function
Although cortisol is the body’s primary stress hormone so it increases our energy to deal with stress and also increases cognitive performance and decreases inflammation, prolonged exposure to excess glucocorticoids may have adverse metabolic consequences, such as _________________ and ________________
The development of insulin resistance and Type 2 diabetes
Impact of elevated cortisol…
How does it promote or worsen diabetes?
What does dyslipidaemia lead to?
(also muscle wasting and osteoporosis, mood swings and memory impairments)
Why do people with Cushing’s have slowed wound healing?
It promotes hyperglycaemia
Visceral obesity
Slow wound healing because the immune system is suppressed
What triggers the release of Aldosterone from the Zona Glomerulosa in the adrenal gland?
What triggers the release of catecholamines from the adrenal medulla?
Circulating Angiotensin 2 and high plasma K+ and low plasma Na
Direct action of sympathetic nervous system
Does Aldosterone act on the cell surface or in the nucleus of the renal tubular cells?
What receptor does it bind to?
What does this activate?
Nucleus
MR receptor
Activates expression of several genes that leads to Na channel at the luminal membrane (to reabsorb Na from urine into cell) and a Na/K ATPase at the basement membrane (to reabsorb Na from cell into blood and K from blood into cell to go into urine)
How long does aldosterone action usually take?
Slow- about 30 mins
What are the effects of aldosterone?
Increases Na (and hence water) reabsorption in kidneys (and excretion of K)
Stimulates ADH which triggers thirst and further promotes water reabsorption in kidneys
Blood pressure increased (too much can lead to hypertension)
Adrenergic alpha 1 receptors leads to what?
Adrenergic beta 2 receptors leads to what?
(Beta 1 increase HR and heart contractility)
Alpha 1= constriction of smooth muscles (peripheral arteries)
Beta 2= relaxation of smooth muscles (bronchioles and coronary arteries)
Adrenergic Receptors…
Where are alpha 1 receptors?
Where are alpha 2 receptors?
Where are Beta 1 receptors?
Where are Beta 2 receptors?
Beta 3 somewhere else
Alpha 1= blood vessels, GIT, skin
Alpha 2= CNS
Beta 1= Heart (increase contractility and HR)
Beta 2= Coronary vessels (dilate), lungs, smooth muscles of GIT
What 2 things cause the release of CRH from the hypothalamus (to stimulate ACTH and then cortisol?)
Circadian rhythms and stress
What are the 4 causes of Cushing syndrome?
Pituitary adenoma (Cushing disease)
ATCH secreting tumour
Tumour of adrenal cortex (secreting cortisol)
Long term use of corticosteroids (asthma)
What is the cause of Addison’s Disease?
An auto-immune destruction of the zona fasiculata of the adrenal cortex so there is inadequate production of cortisol
Signs and symptoms of Addison’s disease? (5)
Fatigue and weakness (due to inability to release glucose into blood- especially during stress)
Low BP
Hypoglycaemia
Darkening of skin (elevated pituitary MSH)
What is the most common cause of excess catecholamine secretion?
A Pheochromocytoma of the adrenal medulla (a secretory tumour that releases excessive amounts of adrenalin and NA)
What are the symptoms of excess sympathetic activation?
High BP
Heart palpitations
Anxiety and panic attacks
What is the usual treatment of excess catecholamine secretion?
Adrealectomy
Clinical uses of corticosteroids? (2)
Replace mineralcorticoids
Replace glucocorticoids (like in Addison’s Disease where there isn’t enough cortisol)
What is the fun thing about hydrocortisone and cortisone?
They have equal mineralocorticoid and glucocorticoid effects
What is the benefit of combining glucocorticoids with cytotoxic drugs in brain cancer?
Reduces cerebral oedema
What are the different ways glucocorticoids can be used for anti-inflammatory/ immunosuppresive effects?
Asthma
Topical (skin, eye, ear, nose) for eczema and allergic conjunctivitis/ rhinitis)
Hypersensitivity states (severe allergic reactions)
Autoimmune diseases
To prevent graft vs host disease after organ or bone marrow transplant
What are the adverse effects of exogenous glucocorticoids?
The 3 main ones and then 5 extras
Immune Suppression
Cushing’s syndrome
Adrenal Insuficiency
Osteoperosis Osteonecrosis Growth retardation Metabolic dysfunction Fluid retention/ hypertention
How does the use of exogenous glucocorticoids lead to osteoperosis?
Because there is inhibition of gonadal steroid hormones so osteoclasts are stimulated and osteoblasts are inhibited
ALSO decreased GIT absorption of Ca so rise in PTH and bone resorption
How do exogenous glucocorticoids lead to fluid retention/ hypertention?
At higher doses, glucocorticoids act on mineralocorticoid receptors and stimulate the effects of aldosterone so there is an increase in Na and water reabsorption and increase in K and H+ excretion in urine
What is the main thing in the immune function that glucocorticoids suppress?
Prostaglandins
How do glucocorticoids lead to peptic ulcers?
They block prostaglandins which are needed for the protection of stomach mucosa
What adverse effects do glucocorticoids have on the CNS?
What effect do they have on the eyes?
What do they do to the HPA (Hypothalamus Pituitary Adrenal) axis?
CNS- euphoria, depression and psychosis
Cataracts and glaucoma (vision loss due to optic nerve damage)
Generalised suppression of HPA axis
What happens to the HPA axis after long term use of glucocorticoids?
What does sudden withdrawal lead to?
Which options of administration do these effects occur from?
There is decreased production of ACTH and impaired cortisol and androgen production which leads to adrenal gland atrophy
Acute adrenal insufficiency
Oral, inhaled, intranasal and topical administration
What symptoms occur with sudden withdrawal of glucocorticoids (symptoms of acute adrenal insufficiency)?
GI symps (nausea, vom, abso pain) Dehydration Hypotention Fever Lethargy and malaise Hyponatraemia and hyperkalaemia
How long does it take for full adrenal function to recover?
8 weeks but may take much longer after prolonged high dose treatment
Do glucocorticoids lead to a psychological dependence?
No, there is no reward pathway that is stimulated with their use so there is no psychological dependence, just physiological dependence
The route of administration can limit systemic exposure to glucocorticoids.
What are 3 examples of this?
Inhalation to target lungs for asthma
Topical to target skin for eczema
Intranasal to target nose for rhinitis
