Adrenal Gland Flashcards
Describe the location and shape of adrenal glands
- 2 triangular structures placed over each kidney
What is the adrenal gland composed of
- 2 separate endocrine tissues surrounding each other
- adrenal cortex , adrenal medulla on inside
- derived embryologically from different tissues
What is the function of the adrenal cortex and adrenal medulla
- Adrenal cortex: corticosteroids
- Adrenal medulla : catecholamines
Name the zones of the adrenal Cortex , types of hormones it secretes and what each zone secrete
- zona glomerulosa : mineralcorticoids
- zona fasiculata : glucocorticoids
- zona reticularis : adrenal androgens
- cortex secretes steroid lipophilic hormones that need to be transported in blood bound to plasma proteins
What are mineralocorticoids , give example
- hormone that regulates mineral and electrolyte balance in body
- ex: aldosterone
What are glucocorticoids , give example
- hormone that regulates blood glucose level and protein & fat metabolism
- ex: cortisol
What are adrenal androgens ,
- hormones responsible for masculinization
- important in children before puberty and adult women
Why are adrenal androgens not important in terms of male physiology
- because males already have testes that produce testosterone and responsible for masculinization
What is cortisol usually bound to
- corticosteroid binding globulin and albumin
What is aldosterone usually bound to
- albumin
what is androstenedione usually bound to
- albumin
Where are mineralocorticoids formed from and what stimulates it’s secretion
- cholesterol
- conversion of cholesterol to second step of mineralocorticoid pathway is influenced by ACTH
Where are the receptors of steroid hormones located
- inside the cell
Describe the composition and function of the adrenal medulla
- modified part of SNS
- adrenal medulla has no axon accompanying postganglionic sympathetic neurons in it so it releases chemical transmitter directly into blood
- releases adrenaline and noradrenaline
Why are chemical transmitters secreted in adrenal medulla called hormones
- because they are released into the blood and not transported by axons
What stimulates cortisol secretion
- physical stress ( ex: exercise )
- emotional
- chemical ( hypoglycaemia )
- extreme temperature
- diurnal rythme for cortisol secretion
Describe regulation of glucocorticoids secretion
- stress acts on hypothalamus to release CRH , which acts on anterior pituitary to release ACTH
- ACTH travels in blood to zona faciculata to stimulate glucocorticoids secretions ( cortisol )
- cortisol acts as negative feedback for ACTH and CRH secretion
What is the diurnal rhythm for cortisol ( same as ACTH )
- low levels of ACTH at night time
- and high levels before we get up in morning
Why are random cortisol measurements not helpful
- because cortisol follows the awake sleep diurnal rhythm
- could be reversed with people who work night shifts
How is cortisol measured , what would you see with normal cortisol levels
- in urine or saliva
- 85% of cortisol will be bound to transcortin in blood
- transcortin almost fully saturated
- free cortisol levels low
What would you find with high cortisol levels (3)
- transcortin quickly saturated
- greatly increased free cortisol
- Urinary free cortisol high ( UFC)
Actions of glucocorticoids ( in the 4 areas )
- muscle : break down protein in muscle tissue to amino acids = converted to glucose
- liver : gluconeogensis & glycogenesis ( only anabolic action )
- Fat cells : free fatty acid mobilization through lipolysis
- immune system : suppressed - anti-inflammatory
Give example conditions where glucocorticoids are given
- rheumatoid arthritis : to alleviate inflammation
- helps prevent organ rejection after transplant
Cortisol’s role to adaptation to stress
- promotes supply of glucose to tissue ( muscle & fat break down )
- permissive hormone : affects counter-regulatory hormones which counter insulin ( glucagon , adrenaline , GTH ) AND cortisol is required for expression of adrenergic & angiotensin II receptors in CVS
What is a permissive hormone
- hormone that needs to be present for other hormones to work optimally
Describe cortisol’s action on the CVS
- cortisol needs to be present for expression of adrenergic and angiotensin 2 receptors
- stop hypotension , hypovaleamia
Causes of glucocorticoids excess ( Cushing’s syndrome ) - 5 causes
- tertiary : hypothalamic tumour
- secondary : anterior pituitary tumour
- primary : adrenal tumour
- ectopic tumour ( outside of hypothalamus , pituitary , adrenal gland )
- iatrogenic Cushing’s syndrome : excessive use of exogenous glucocorticoids
What is the difference between Cushing’s syndrome and Cushing’s disease
- Cushing’s syndrome is anything that causes an excess of glucocorticoids
- Cushing’s disease is when an anterior pituitary tumour causes excess glucocorticoids
What would a patient with Cushing’s disease look like
- deposition of adipose tissue in face
- warm : pink cheeks
- deposition of fat in abdominal region & stretch marks
- very thin limbs
- bruising of skin : skin and walls of blood vessels begin to thin due to excess cortisol
- cervical fat pad : fat is mobilized to centre of body
Effects of Cushing’s syndrome on carbohydrate metabolism
- hyperglycaemia : increased blood glucose levels
- adrenal diabetes
What can cause flushed look on patient with Cushing’s syndrome
- cortisol binds with mineralocorticoids, so excess cortisol will increase blood pressure
Effects of Cushing’s syndrome on protein metabolism
- muscle weakness
- osteoporosis
- delayed healing of fractures and wounds
- cortisol reduces Ca uptake from GI tract and increases absorption of Ca from bone which is then excreted
Cushing’s syndrome Symptom mnemonic
C: central obesity . collagen fibre weakness, comedones
U : urinary free cortisol and glucose
S: striae, suppressed immunity
H : hypercortisolism, hypertension, hyperglycaemia , Hypercholesterolaemia
I: iatrogenic
N: iatrogenic
G: glucose intolerance , growth retardation
In an adult patient with diagnosed Cushing’s disease what treatment is preferred ?
a: bilateral adrenalectomy b: unilateral adrenalectomy c: resection of pituitary tumour
C: resection of pituitary tumour
What is the RAAS and what does it do
- renin angiotensin aldosterone system
- regulator of blood volume and systemic vascular resistance
- important for long term regulation of blood pressure
- composed of renin , angiotensin I and angiotensin II
What are the two stimulants of aldosterone
- increased potassium in ECF which directly stimulates adrenal cortex
- angiotensin II directly stimulates adrenal cortes
What stimulates angiotensin II
- dehydration
- sodium deficiency
- decrease in blood volume
Why is angiotensin II stimulated by decreased blood volume
- decrease BV decreases BP decreases renal blood flow
- juxtaglomerular cells in kidney release renin
- Renin converts angiotensinogen to Angiotensin I
- angiotensin I converts to angiotensin II in lung
What is the function of aldosterone
- works in kidneys to increase sodium reabsorption
- increase potassium and H + excretion in urine
- water reabsorbed with sodium which increases blood volume and blood pressure
What is the role of ACTH in aldosterone secretion
- not a big role
- angiotensin II is the stimulant not ACTH
Aldosterone deficiency consequences
- increased loss of sodium and water in urine = dehydration , plasma depletion , hypotension
- renal retention of potassium = hyperkalaemia = increase cardiac excitability = V fib
- renal retentions of H+ results in acidosis
Why is aldosterone deficiency serious
- acute aldosterone deficiency can lead to death in 2 days
What are the two forms of hypoaldosteronism and what happens each
- primary : adrenal insufficiency - problem with synthesis of enzymes needed to synthesize aldosterone
- secondary : renal sufficiency - renal failure results in no renin production
What is Conn’s syndrome
- primary hyperaldosteronism
- due to adrenal adenoma
- very rare condition
- excess secretion of aldosterone results in hypertension , hyperkalemia , hypervolemia and alkalosis
What is the difference between primary and hyperaldosteronism
- renin levels in primary are low but high in secondary due to overactivity of RAAS
What is Addison’s disease
- primary adrenocortical insufficiency
- destruction of both adrenal cortices ( usually autoimmune )
What happens if one adrenal cortex is destroyed
- other adrenal cortex will hypertrophy , hyperplasia will take place
- it will take over secretion of cortisol
What are the causes of Addison’s disease
- usually autoimmune disorder
- can be haemorrhage , TB , malignancy
What is the acute drop of adrenocorticol hormones called
- addisonian’s crisis / acute adrenal crisis
What are the results of a lack of adrenal androgens
- changes in mood
- loss of libido
- effects females not males
What is secondary adrenocorticol insufficiency what can cause it ( 2 causes )
- abnormality in pituitary or hypothalamus that results in insufficient ACTH
- sudden withdrawal of glucocorticoid drugs or failure to increase glucocorticoids levels during stress
How does Addison’s disease present
- bronze hyperpigmentation of skin
- changes in body hair distribution
- weakness
- weight loss
- GI disturbances
- hypoglycaemia
- postural hypotension
- brown buccal pigmentation
How does addisonian’s disease present
- profound fatigue
- dehydration
- vascular collapse = decrease BP
- renal shut down
- decrease serum NA
- increase serum K
What combination of biochemical disturbances is the classical finding in a patient with untreated Addison’s disease
- Hyponatraemia , hyperkalaemia , hypoglycaemia
What causes hyperpigmentation in Addison’s disease
- adrenal failure = adrenal hormone levels decrease = reduced negative feedback = ACTH levels increase = melanocytes stimulation = increase in MSH
What neurotransmitters are located at preganglionic nerves of parasympathetic
- ACH ( acetylcholine)
What neurotransmitters are located at post ganglionic nerves of sympathetic
- noradrenaline
Compare the effects of catecholamines and SNS
- exerts effect in all cells vs some organs / tissue having no innervation
- delayed in beginning vs immediate effects
- prolonged effects vs rapid decay
- only generalized effects vs localized effects
What secretes catecholamines
- chromaffin cells in adrenaline medulla
- catecholamines derived from amino acid tyrosine
What are the 3 catecholamines
- Dopamine
- Adrenaline
- Noradrenaline
What catecholamines does the adrenal medulla produce the most
- adrenaline
What stimulates catecholamines secretion and what are the results
- ACH binding to chromaffin cell and depolarizing it
- chromaffin granules fuse with plasma membrane and exocytoze into blood
Actions of adrenaline and noradrenaline ( fight or flight )
- increase heart rate
- increase BP
- bronchioles dilation
- increase blood glucose
- decrease digestive activity
What triggers adrenaline and noradrenaline secretion and give examples
- stress
- ex: illness , exercise, hypoxia , cold
Describe the metabolism of Catecholamines
- inactivated rapidly ( many ways they can be inactivated)
- ex: reuptaked by cells, filtered into urine , metabolized by monoamine oxidase
MOA of catecholamines and their two type of receptors
- adrenergic receptor mediated
- noradrenaline binds with more affinity to alpha adrenergic receptors
- adrenaline binds with more affinity to beta adrenergic recptors
- effects depend on type and number of receptors in target tissue
Where are the alpha adrenergic receptors located
- alpha 1 : vascular
- alpha 2 : presynaptic
Where are the beta adrenergic receptors located
- beta 1 : heart
- beta 2 : smooth muscle
- beta 3 : fat
Which adrenergic receptor only binds to adrenaline
- beta 2
What has a greater physiological action in terms of cardiac stimulation
- adrenaline ( beta 1 )
What has a greater physiological action in terms of constriction of blood vessels
- noradrenaline ( alpha 1 )
What has a greater physiological action in terms of increasing metabolism
- adrenaline ( beta 3 )
Mechanism of adrenergic receptor signal transduction (for each receptor type )
- beta 1 & 2 : increases cAMP
- alpha 1 : increases IP3 by phospholipase C pathway
- alpha 2 : decrease cAMP
Describe Adrenomedullary dysfunction
- only one disorder can cause this : catecholamine secreting tumour ( pheochromocytoma )
- very rare
Symptoms of Pheochromocytoma
- hypertension
- headache
- sweating
- palpitations
- chest pain
- anxiety
- glucose intolerance
- increased metabolic rate
What endocrine disorders cause hypertension ( 4 )
- increased aldosterone , cortisol
- increased thyroid hormone results in increased SBP
- pheochromocytoma
In what cell types do pheochromocytomas originate
- chromaffin cells
