Lecture 21 + 22: Adrenal Glands Flashcards
what tissues make up the adrenal gland
adrenal cortex (outer) adrenal medulla (inner)
what category of hormones does each tissue of the adrenal gland produce
cortex - corticosteroids
medulla - catecholamines
name the three Zona that make up the cortex and the type of hormones they secrete
- glomerulosa (outer) = mineralocorticoids
- fasciculata (middle) = glucocorticoids
- reticularis (inner) = adrenal androgens
why do the three Zona of the adrenal cortex secrete different types of hormones
each zone possesses different enzymes involved in the manufacture of these hormones
what are all corticosteroids formed from
cholesterol
what hormone stimulates the conversion of cholesterol to pregnenolone
ACTH (adrenocorticotrophic hormone)
what is the rate limiting step in synthesis of steroid hormones
conversion of cholesterol to pregnenolone
what peptide hormone is necessary for synthesis of aldosterone
Angiotensin 2 - activates aldosterone synthase enzyme
where are most steroid hormone receptors found
inside cell within cytoplasm and within nucleus
what type of effects do steroid hormones have when binding to receptors inside cell
genomic effects - either activate or inhibit transcriptase in DNA
what makes the adrenal medulla different from the normal sympathetic nervous pathway
- normal SNS –> preganglionic neuron extending from spinal cord and terminating on postganglionic neuron which then goes on to innervate organs and tissues
- adrenal medulla –> no axon accompanying postganglionic cell body so ganglionic cell bodies within adrenal medulla release chemical transmitter directly into circulation upon appropriate stimulation
what is the principal output of the adrenal medulla
adrenaline/epinephrine
also secretes some noradrenaline/norepinephrine
where are most receptors for catecholamines found and why
on cell surface membrane because catecholamines are hydrophilic
what effect do catecholamines have on the cell they bind to
non-genomic effect –> cause alterations in proteins; enzymes or ion channels –> leads to target cell response
what is the principal stimulus for cortisol secretion
stress e.g. physical, emotional, chemical
outline the process by which cortisol is released
- stress acts on hypothalamus
- CRH (corticotropin releasing hormone) released
- stimulates corticotrophins in ant. pit. to secrete ACTH
- ACTH stimulates zona fasciculata to secrete cortisol
what is the second stimulus for cortisol secretion
diurnal rhythm for cortisol secretion
when are ACTH levels at their lowest
at night when sleeping appx 1-3am
when are peak ACTH levels
in the morning when you wake up appx 7-9am
what time would you measure Cortisol levels if suspecting excess cortisol
at night between 12-3am –> if levels are high (when should be low) the excess is likely
when is the pulsatile secretion of cortisol also inversed
in patients who might work night shifts –> awake sleep cycle is inversed
name a binding protein for cortisol in the blood
transcortin
describe the binding of cortisol and transcortin in the blood in normal cortisol levels
- most cortisol in blood (85%) bound to transcortin
- transcortin almost fully saturated
- free cortisol levels are low
describe the binding of cortisol and transcortin in the blood in high cortisol levels
- transcortin quickly saturated
- greatly increased free cortisol
- urinary free cortisol (UFC) high
what could high UFC indicate
adrenal disorder
outline the actions of glucocorticoids
- mainly catabolic reactions
muscle
- -> breakdown prot. to a.a. (a.a. then converted to gluc. in liver)
- -> i.e. net loss of a.a. so favours -ve nitrogen balance
liver
- -> gluconeogenesis of a.a.
- -> glycogenesis (when gluc. levels high) ANABOLIC
fat cells
–> lipolysis
immune system and inflammation
- -> suppresses - decreases no. of WBC and their motility/action
- -> reduction in inflammatory mediators
what is the only anabolic action of cortisol
glycogenesis in liver when glucose levels are high
describe cortisol’s role in adaptation to stress
- directly promotes rapid supply of glucose to tissues
- permissive hormone
describe how cortisol is a permissive hormone
- needs to be present for other hormones to work optimally
- affects other counter regulatory hormones
- required for expression of adrenergic and angiotensin 2 receptors in CVS
- –> cortisol needed to maintain normal BP
- –> cortisol important in body’s response to hypertension + hypovolaemia
what is a counter regulatory hormone
hormone whose actions oppose the action of insulin
what is Cushing’s syndrome
glucocorticoid excess / hypercorticolism
name some causes of Cushing’s syndrome
- hypothalamic tumour
- ant. pit. tumour
- adrenal tumour
- ectopic tumour
- iatrogenic Cushing’s syndrome –> exogenous glucocorticoids
what cause of Cushing’s syndrome is most likely
ant. pit. tumour 60-70% of cases –> known as Cushing’s disease (secondary level disorder)
Where is the most likely place to find an ectopic ACTh tumour in the body
in the lung
describe hormone levels in 2nd hypersecretion due to hypothalamic problem
- high CRH
- high ACTH
- high cortisol
describe hormone levels in 2nd hypersecretion due to ant. pit. problem
- low CRH
- high ACTH
- high cortisol
describe hormone levels in 1st hypersecretion due to problem in adrenal cortex
- low CRH
- low ACTH
- high cortisol
describe some of the features of Cushing’s syndrome
- deposition of fat in face and abdomen
- thin limbs
- abdominal striae
- bruising of skin
- thinning of skin and BV
- pink in face
- moon face
- dorsal cervical fat pad
outline the effects of Cushing’s syndrome on carbohydrate metabolism
- hyperglycaemia –> adrenal diabetes
- ^ in BP due to cortisol binding to mineralocorticoid receptors
outline the effects of Cushing’s syndrome on protein metabolism
- protein shortage –> muscle weakness
- striae / stretch lines
- easy bruising and thinning skin
outline side effects for patients who take exogenous glucocorticoids
- osteoporosis incl. pathological fractures
- immune suppression
- delayed healing of fracture and soft tissue injuries
how does cortisol impact calcium metabolism
- reduces uptake of calcium from GIT
- increases reabsorption of calcium from bone and excretion
outline signs and symptoms of Cushing’s syndrome using mnemonic CUSHING
C - central obesity, collagen fibre weakness, comedones
U - UFC + glucose ^
S - striae, suppressed immunity
H - hypercorticolism, hypertension, hyperglycaemia, hypercholestorolaemia
I - iatrogenic
N - noniatrogenic (neoplasms)
G - gluc. intolerance, growth retardation
to which cause of Cushing’s syndrome does ‘Cushing’s disease’ specifically refer to
pituitary adenoma
in adult patient w/ diagnosed Cushing’s disease, which treatment is preferred…
- bilateral adrenalectomy
- unilateral adrenalectomy
- resection of pituitary tumour
- pituitary tumour resection
give two important roles of RAAS
- critical regulator of blood volume and systemic vascular resistance
- important in long term regulation of BP
name two main stimuli for ^ aldosterone production
- ^ K+ conc in ECF –> directly stims adrenal cortex to produce aldosterone
- Angiotensin 2 –> directly stimulates adrenal cortex to produce aldosterone
what zone of adrenal cortex produces aldosterone
- zona glomerulosa
when is angio 2 increased
- Na+ deficiency
- dehydration
- haemorrhage (drop in blood volume –> decrease in BP –> decreases renal blood flow); juxtaglomerular cells produce renin
outline actions of aldosterone (mineralocorticoid effect)
- ^ Na+ and H2O reabsorption
- ^ K+ and H+ exertion in urine
- ^ blood volume
- BP returns to normal
describe the effects of aldosterone deficiency
- ^ loss of Na+ and H2O in urine
- -> dehydration
- -> plasma depletion
- -> hypotension
- renal retention of K+ and hyperkalaemia
- -> ^ cardiac excitability
- -> ventricular fibrillation
- renal retention of H+
- -> metabolic acidosis
describe the difference between primary and secondary hypoaldosteronism
primary = problem in adrenal gland
secondary = problem in kidney –> reduced renin production
what is Conn’s syndrome
primary hyperaldosteronism - over production of aldosterone due to problem in adrenal glands
what is the most common cause of Conn’s syndrome
adrenal adenoma (75% cases)
outline effects of Conn’s syndrome
- hypertension
- hypokalaemia (due to ^ Na+ retention)
- hypervolaemia
- metabolic alkalosis (^ H+ loss)
what is secondary hyperaldosteronism
overactivity of RAAS
main difference between primary and secondary hyperaldosteronism
primary = low renin levels secondary = high renin levels
what is Addison’s disease
primary adrenocortical insufficiency
–> destruction of both adrenal cortices
why does Addison’s disease have to be the destruction of both adrenal cortices
if only one adrenal cortex is destroyed the other will hypertrophy and hyperplasia can take over
what usually causes Addison’s disease
autoimmune destruction of adrenal cortices
–> autoantibodies attack adrenal cortex tissue
what are some rarer causes of Addison’s disease
- haemorrhage
- TB
- malignancy
what is adrenal/addisonians crisis
acute drop in hormone secretion from adrenal cortex
outline effects of a lack of glucocorticoids
- hypoglycaemia
- reduced fat and protein metabolism
- weight loss
- poor exercise tolerance
- poor stress tolerance –> death
outline effects of a lack of mineralocorticoids
- reduced Na+, ^ K+ and H+
- hypovolaemia
- reduced CO –> circulatory collapse –> shock –> death
outline effect of lack of adrenal androgens
- no effect in males –> testosterone produced in testes
- in women can cause mood changes
what is secondary adrenocortical insufficiency
- pituitary/hypothalamic abnormality rustling in insufficient ACTH
- can have sudden withdrawal of glucocorticoid drugs
- failure to ^ glucocorticoids during stress
give some signs and symptoms of Addison’s disease
- bronze pigmentation of skin (hyperpigmentation)
- hypoglycaemia
- changes in body hair distribution
- GI disturbances
- weight loss
- weekness
- postural hypotension
give some signs/symptoms of adrenal crisis
- profound fatigue
- dehydration
- vascular collapse –> low BP
- renal shut down
- low serum Na+
- ^ serum K+
which combination of biochemical disturbances is the classical finding in a patient with untreated Addison’s disease
- hyponatraemia
- hypoglycaemia
- hyperkalaemia
in Addison’s disease where would you normally see hyperpigmentation
- areas where skin is thinner
- palmar creases
- gums
- buccal mucosa
- ridges of nails
- lips
- areola of nipples
- old scars turn darker
why do you get hyperpigmentation with Addison’s disease
- adrenal failure
- reduced adrenal hormones
- ^ ACTH
- ^ alpha MSH
- ^ melanocyte stimulation
- hyperpigmentation
what is the adrenal medulla composed of
modified post ganglionic sympathetic neurons
what is the neurotransmitter located at the preganglionic neuron for both sympathetic and parasympathetic nerves
acetylcholine
when acetylcholine from preganglionic nerves bind to nicotinic receptors on post ganglionic nerves, what is released from the post gang. (answer for both PNS and SNS)
PNS = ACh
SNS = noradrenaline
list some effects of SNS stimulation
- pupil dilation
- lower volume of thicker saliva
- activates heart ^ contractility and HR
- relaxes bronchi
- inhibits digestive activity
- stim gluc release by liver
- adrenaline and noradrenaline secretion from kidney
- relaxes bladder
- contracts rectum
compare and contrast effects of catecholamines and SNS activity
Adrenal Stim:
- generalised effects as hormones travel through blood
- exerts effects in all cells
- delay in beginning
- prolonged effects
SNS Activation:
- more localised effects due to direct innervation
- some organs/tissues have no innervation
- immediate effects
- rapid decay when activation ceases
what cells secrete catecholamines
chromaffin cells of adrenal medulla
what are catecholamines derived from
amino acid tyrosine
give examples of catecholamines
- dopamine
- noradrenaline
- adrenaline
what is the majority hormone produced in adrenal medulla
adrenaline
describe how SNS stimulation causes release of adrenaline/noradrenaline from adrenal medulla
- postganglionic nerve releases ACh
- binds to nicotinic receptors on surface of chromaffin cells
- depolarisation of chromaffin cell
- granules in cell containing adrenaline/noradrenaline fuse with plasma membrane
- exocytosis into blood
what is the trigger for release of adrenaline and noradrenaline
stress
describe metabolism of catecholamines
rapidly inactivated by:
- reuptake by extraneuronal sites
- metabolised by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)
- conjugation with glucuronide in liver (excreted in urine and bile)
- direct filtration into urine
describe the MoA of catecholamines
- receptor (G-prot linked adrenergic) mediated
- peripheral effects depend upon type and ratio of receptors in target tissues
what type of adrenergic receptor does noradrenaline have more affinity for
alpha
what type of adrenergic receptor does adrenaline have more affinity for
beta
describe the location of the different types of adrenergic receptors
- A1 = vascular
- A2 = presynaptic
- B1 = heart
- B2 = smooth muscle
- B3 = fat
which adrenergic receptor only binds to adrenaline
B2
give the effect of the different adrenergic receptors on cAMP production
A2 - decreases
B1 - ^
B2 - ^
name the disorder assc w/ adrenomedullary dysfunction
pheochromocytoma (catecholamine secreting tumour)
give some signs and symptoms of pheochromocytoma
- hypertension
- headache
- sweating
- palpitations
- chest pain
- anxiety
- gluc. intolerance
- ^ metabolic rate
in which cell type do pheochromocytomas originate
chromaffin
