Adrenal Glands Flashcards
What are the two layers of the adrenal gland and what hormones do they produce?
Adrenal cortex - corticosteroids
adrenal medulla - catecholamines
Where are the adrenal glands located?
Above each kidney
What are the three layers of the adrenal cortex and what hormone do they secrete?
Zona glomerulosa - mineralocorticoids
zona fasciculata - glucocorticoids
zona reticularis - adrenal androgens
What are examples of each of the hormones secreted by the layers of adrenal cortex and what is function of each?
mineralocorticoids regulate mineral balance e.g. aldosterone
glucocorticoids regulate blood glucose e.g. cortisol
adrenal androgens responsible for masculisation e.g. catecholamines
What proteins are used to transport each hormone secreted by adrenal cortex?
cortisol primarily corticosteroid binding globulins
aldosterone primarily albumin
androgens primarily albumin
What are all corticosteroids derived from?
steroid hormones so cholesterol
What is the rate limiting step in synthesis of steroid hormones from cholesterol
- Conversion of cholesterol to pregnenolone using ACTH (adrenocorticotrophic hormone) enzyme
What enzyme is essential in aldosterone synthesis?
Ang II activates aldosterone synthase which is needed in aldosterone synthesis
Where would you usually find adrenal steroid hormone receptors and what effect do they cause?
usually intracellular, readily diffuse across membrane
have genomic effect (receptor complex binds to hormone response element)
Where would you usually find catecholamine hormone receptors and what effect would they cause?
Extracellular (G-protein linked)
use cAMP as 2nd messenger and activate kinase which brings about response in target cell
How is hormone release from adrenal medulla regulated and what hormones are released?
- Electrical signal from spinal cord travels through pre-ganglionic neurone to chromaffin cells in adrenal medulla where cell body of post-ganglionic present but not axon
- chemical messenger secreted directly into circulation
- usually adrenaline but can secrete noradrenaline
What are the triggers for cortisol secretion?
Physical stress - trauma or injury e.g. surgery or exercise
Emotional stress - stressful live events e.g. tests
Chemical stress - hypoglycaemia
Extreme temperature changes
In what way is cortisol secretion triggered?
- Stress stimuli causes hypothalamic neurones to release CRH (corticotrophin hormone)
- CRH stimulates corticotropes on anterior pituitary to release ACTH
- ACTH travels in blood to adrenal cortex where triggers zone fasciculata to increase cortisol secretion
What are the negative feedback loops to stop cortisol secretion?
Long: ACTH and CRH secretion switched off by cortisol
short: ACTH switches off CRH
Why would you expect different cortisol readings throughout the day?
Cortisol follows diurnal rhythm
ACTH and cortisol highest just before you wake up and follow until reach lowest at night
What protein carries cortisol?
transcortin
How are cortisol levels tested for?
- test urine or saliva over 24h period
- free (unbound) cortisol will appear in high levels in urine or saliva if excess cortisol as transcortin saturated
What are the actions of glucocorticoids?
1) muscle - net loss of amino acids so can be converted to glucose
2) Liver - amino acids and glycerol converted to glucose (gluconeogenesis) + when high glucose converted to glycogen (glycogenesis)
3) Fat - lipolysis breakdown of fat into free fatty acids
4) immune system repressed
What are the roles of cortisol in adaption to stress?
1) Promotes rapid supply of glucose to tissues
2) needs to be present for other hormones to work optimally
Which hormones require cortisol to work?
1) Insulin counter-regulatory hormones = glucagon, adrenaline and growth hormone
2) expression of adrenergic and angiotensin II receptors in CV system
What are the effects of the regulatory hormones on glucose metabolism?
glucagon inc: glycogenolysis and gluconeogenesis dec: glycogen storage
Adrenaline inc: glycogenolysis and gluconeogenesis dec: glucose oxidation, glycogen storage and muscle/adipose glucose uptake
Growth Hormone inc: gluconeogenesis dec: muscle/adipose glucose uptake, glycogen storage and glucose oxidation
What are the effects of Insulin on glucose metabolism?
decrease gluconeogenesis and glycogenolysis
increase glycogen storage, glucose oxidation and muscle/adipose tissue glucose uptake
What are the effects of cortisol on glucose metabolism?
increase gluconeogenesis and glycogen storage
decrease muscle/adipose tissue uptake of glucose and oxidation of glucose
What are the causes of glucocorticoid excess (Cushing syndrome)?
1) hypothalamic tumour
2) anterior pituitary tumour
3) adrenal tumour
4) Ectopic tumour usually lungs
5) Iatrogenic Cushing syndrome
What is Cushing disease?
Cushing syndrome when caused by anterior pituitary tumour
What do primary and secondary hyper secretion mean?
Primary: adrenal cortex tumour so excessive cortisol secretion
Secondary: hypothalamic or anterior pituitary tumour so excessive CRH or ACTH release causing excessive cortisol release
What are the common symptoms of Cushing Syndrome?
- Abnormal fat deposition: fat in face and abdomen very thin elsewhere
- round face and red cheeks due to warmth
- warm
- Stretch marks (abdominal striae)
- easy bruising (due to thinning of blood vessels)
- easy to get infections as immune system suppressed
What effects does Cushing syndrome have on metabolism?
Carbohydrate:
Hyperglycaemia
hypertension as cortisol bids to aldosterone receptors
Protein:
causing protein shortage, striae, easy bruising and thinning of skin
Why can you sometimes get osteoporosis when taking glucocorticoids?
impacts calcium metabolism:
- reduces calcium uptake form GI
- increases reabsorption of calcium from bone
- increases excretion of calcium
What is the Cushing mnemonic?
C - Central obesity, Collagen fiber weakness and comedones (acne)
U - Urinary free cortisol and glucose increase
S - Striae and surpassed immunity
H - hypercortisolism, hyperglycaemia, hypertension and hypercholesterolamia
I - iatrogenic (causes)
N - noniatrogenic (causes)
G - glucose intolerance and growth retardations
What does the RAAS system regulate?
Blood pressure using blood volume and systemic vascular resistance
What are the two main stimuli of RAAS?
1) increased potassium concentration in ECF which directly stimulates aldosterone secretion
2) Ang II which directly stimulates adrenal cortex to secrete aldosterone
What stimulates Ang II secretion?
1) dehydration
2) sodium deficiency
3) dec in blood volume (e.g. in haemorrhage)
Why does decrease in blood volume increase Ang II secretion?
- Decrease in Blood volume decreases BP which decreases renal plasma flow and in response juxtaglomerular cells of kidneys produce renin
- Renin converts Angiotensinogen in liver to Angiotensin I
- Angiotensin converting enzyme located in blood capillaries in lungs converts Ang I to Ang II
How does aldosterone decrease BP?
- Aldosterone works in kidneys to increase sodium and water reabsorption and in return get increased secretion of potassium and hydrogen ions
- When sodium reabsorbed, water reabsorbed as well which increases blood volume and so blood pressure
What does aldosterone do in the cell of distal nephron?
- Receptor mainly in cytoplasm of cell
- Causes genomic effects increasing protein production and so increases ion channels (in particular sodium channels) to:
1) increase sodium into blood
2) increase potassium excretion
3) increase Blood volume
What can be taken as a replacement for aldosterone?
fludrocortisone
What can be taken as a replacement for Cortisol?
hydrocortisone
In what three ways can aldosterone deficiency be fatal?
1) increased loss of sodium and water means dehydration and hypotension which can cause circulatory shock
2) renal retention of potassium = hyperkalaemia and so cardiac excitability and ventricular fibrillation
3) renal retention of hydrogen and cause metabolic acidosis
What is primary hyper and hypo - aldosteronism?
Hyper - also called Conns syndrome, caused by adrenal tumour
Hypo - caused by adrenal insufficiency (usually enzymes needed to manufacture aldosterone)
What is secondary hyper and hypo - aldosteronism?
Hyper - caused by overactivity of RAAS system usually secondary to other problems
Hypo - caused by renal insufficiency e.g. CKD so not enough renin
What does Conns syndrome cause?
- Hypertension
- hypokalaemia
- hypervolemia
- metabolic alkalosis
Pathology of primary hyperaldosteronism?
- tumour secretes aldosterone
- aldosterone increases sodium retention and increases ECF
- increases BP
- plasma volume expansion decreases renin
- increase potassium loss and hydrogen loss
What is Addisons disease?
- Primary adrenocortical insufficiency
- Both adrenal cortices must be destroyed
What causes Addisons disease?
autoantibodies attach adrenal cortices or can get destruction due to haemorrhage
What is Addisonian crisis and what can happen?
rapid drop in corticoids usually due to haemorrhage
causes:
- Fatigue
- Dehydration
- vascular collapse
- renal shut down so decline in sodium and increase in potassium
What are clinical implications of Addisons disease?
Drop in glucocorticoids:
- hypoglycaemia
- reduction in fat and protein metabolism
- weight loss
- poor exercise tolerance
- poor stress tolerance
Drop in mineralocorticoids:
- less sodium and water and more potassium and hydrogen
- hypovolaemia
- decline in CO causing circulatory shock
What can cause secondary adrenocortical insufficiency?
1) pituitary/hypothalamic abnormality resting in insufficient ACTH
2) withdrawal of glucocorticoid drugs
3) failure to increase glucocorticoids during stress
Symptoms of Addisons disease?
- Hypoglycaemia
- postural hypotension
- weight loss
- GI disturbances
- Weakness
- Changes in distribution of body hair
- Bronze pigmentation of skin especially in palmar creases, nails and gums
Why is there increased bronze pigmentation?
- Adrenal failure means decrease in adrenal hormones
- increase in ACTH in response
- ACTH increase alpha-MSH
- which stimulates melanocytes
What neurotransmitter are used in the sympathetic and parasympathetic pre and post ganglionic nerves?
Sympathetic and parasympathetic pre-ganglionic = AcH released which binds to nicotinic receptors
Post-ganglionic sympathetic releases noradrenaline
parasympathetic releases AcH
What are the actions of the sympathetic nervous system?
- Dilate pupils
- inhibits salivation
- relaxes bronchi
- increase HR
- inhibits digestive activity
- stimulate glucose release from liver
- secretes adrenaline and noradrenaline from kidney
- relaxes bladder
- contracts rectum
What are the actions of the parasympathetic nervous system?
- constricts pupils
- stimulates salivation
- inhibits heart
- constricts bronchi
- stimulates digestive activity
- stimulates gallbladder
- contracts bladder
- relaxes rectum
What is the intracellular actions of catecholamines?
- receptors found on outside of cell
- G-protein linked
- cAMP secondary messenger
- non-genomic effect
How are catecholamines released from chromaffin cells?
- ACh binds to nicotinic receptor on chromaffin cell
- cell is depolarised which triggers release of adrenaline/noradrenaline via granules
How are catecholamines signalled to be released?
- hypothalamus sends an electrical signal via sympathetic nervous system
- Adrenal medulla (chromaffin cells) receive signal and secrete catecholamines
Which adrenergic receptors do noradrenaline and adrenaline have higher affinity for?
adrenaline = Beta noradrenaline = Alpha
How are catecholamines inactivated?
1) reuptake by extra-neuronal sites
2) metabolised by monoamine oxidase or catechol-O-methyltransferase
3) conjugated with glucoronide in liver
4) direct filtration into urine
Where are adrenaline or noradrenaline more effective?
adrenaline better at cardiac stimulation and increasing metabolism
noradrenaline better at constriction of blood vessels
Where would you primarily find each alpha receptor and where would you find each beta receptor?
Alpha 1 = vascular Alpha 2 = presynaptic Beta 1 = heart Beta 2 = smooth muscle Beta 3 = fat
What is the mechanism of action of adrenergic receptors?
Beta 1 and 2 increase cAMP
Alpha 2 usually inhibits cAMP
alpha one increases Inositol trisphosphate and diacylglycerol
What is the name of the catecholamine secreting tumour?
Pheochromocytoma
What are the symptoms of a catecholamine secreting tumour?
- Hypertension
- Sweating
- Headaches
- palpitations
- chest pains
- glucose intolerance
- increased metabolic rate
- anxiety
What endocrine disorders can cause hypertension?
increased catecholamines, aldosterone and cortisol
increased thyroid hormone can also cause increased systolic but not diastolic
Why will hypothalamus or anterior pituitary problems have a large impact on cortisol but not aldosterone?
Cortisol has only one way in which it can be synthesised whereas aldosterone is also synthesised though Ang II
