Adrenal Glands Flashcards
describe the layers of the adrenal glands from superficial to deep.
- capsule
- zona glomerulosa
- zona fasciculata
- zona reticularis
- medulla
- central vein
describe the anatomy of left adrenal gland
sits on top of the left kidney and below the spleen, has extensive blood supply from artery branch from aorta. The left adrenal vein drains into the left RENAL VEIN.
describe the anatomy of the right adrenal gland
sits on top of the right kidney, below the liver. again adrenal arteries (~57) from the aorta. Right adrenal vein dries straight into inferior vena cava.
what does the zone fasciculata look like?
looks stripy
where do the hormones produced from the adrenals leave?
the central vein
what does the adrenal medulla produce?
CHROMAFFIN Cells produce catecholamines:
- Adrenaline/epinephrine (80%)
- Noradrenaline (20%)
- Dopamine (small amounts)
what does the adrenal cortex produce?
Corticosteroids:
- Mineralocorticoids
- Glucocorticoids
- Small amount of Sex Steroids
what does the zona glomerulosa mainly produce?
mostly aldosterone
what does the zona fasciculata mainly produce?
Cortisol
what does the zona reticularis mainly produce?
Cortisol and sex steroids
what molecule is the precursor for corticosteroid production?
Cholesterol
what determines what hormones are produced in different regions?
different enzymes are present in the mitochondria in different regions of the adrenal gland.
what enzyme converts cholesterol into pregnenolone, the common step in all of the steroid hormone pathways?
Desmolase, P450scc
which hormones bind to the corticosteroid binding globulin (CBG)?
aldosterone and cortisol
describe the distribution of aldosterone in the blood
40% free (bioactive)
15% bound to CBG
45% bound to Albumin
describe the distribution of cortisol in the blood
10% free (bioactive)
80% bound to CBG
10% bound to Albumin
If a hormone is heavily plasma protein bound, a small change in binding/release of hormone from plasma protein all cause….?
massive pharmacological impact as percentage change in receptor binding will be bigger as percentage change in free concentration is larger.
which is present in higher concentration in the blood, aldosterone or cortisol?
1000x more cortisol
what is cortisol’s diurnal rhythm?
highest in the morning, lowest before going to bed
which receptor does cortisol bind to?
Glucocorticoid receptor AND Mineralocorticoid receptor
which receptor does aldosterone bind to?
mineralocorticoid receptor
to stop cortisol having its effects on the mineralocorticoid receptor, what do cells in the kidney and placenta do?
They inactivate cortisol to cortisone using the enzyme 11b hydroxysteroid dehydrogenase 2.
This ensures the kidneys function normally and no cortisol from the mother reaches the foetus.
what is the juxtaglomerular apparatus?
Granular cells lining the afferent arteriole of the glomerulus are in close proximity to macula densa cells (Na+ sensors) of the DCT.
what do granular/juxtaglomerular cells lining the afferent arteriole do?
secrete renin in response to:
- decrease in blood pressure
- sympathetic innervation
- low sodium concentration in the DCT
what does renin do?
promotes sodium reuptake into the blood hence increasing BP as water osmotically follows.
describe the renin angiotensin system
Renin converts angiotensinogen produced by the liver to Angiotensin I. Angiotensin converting enzyme (ACE) in the kidney and lungs convert angiotensin I to Angiotensin II has its biological effects.
what causes aldosterone release?
- low blood sodium
- high blood potassium
- Angiotensin II
describe the hypothalamo-pituitary-adrenocortical axis?
Stressors from higher areas in the brain cause the hypothalamus to secrete corticotropin releasing hormone causing the anterior pituitary to release ACTH into the blood. this causes cortisol secretion which negatively feedbacks to the hypothalamus and pituitary.
what does aldosterone do in the DCT and Collecting duct?
By binding to the MR it acts as a TF causing production of more sodium channels to be placed on the apical membrane and more NaK symporters to be placed on the basolateral membrane so more sodium reabsorbed.
what does supra physiological effect mean?
effect when in excess
at normal physiological levels how does cortisol bind to its receptors?
MR is high bound to cortisol
GR is partially bound to cortisol
physiological actions of cortisol?
- increases glucose stores (glycogenesis)
- increases readily available glucose (gluconeogenesis)
- decreases absorption of glucose (more in blood)
- decreases energy stores
- increases fatty acids in blood
- helps imprint stressor memory in hippocampus by increasing number of serotonin receptors in the dentate gyrus.
- anti inflammatory
at higher cortisol levels, ie when chronically stressed, how does the binding of cortisol change?
MR highly bound to cortisol and GR also highly bound to cortisol.
supra physiological actions of cortisol?
- anti inflammatory
- immunosuppressive
- impairing of memory
which organ is at risk when doing a adrenalectomy?
Spleen, it is heavily vascularised hence damage may cause severe blood loss meaning a splenectomy must be done.
which vaccines must be given before an adrenalectomy?
HIB and Pneumovax as immunity of these is established in the spleen (due to blood T cell and B cell interactions), hence if removed in emergency, immunity cannot be acquired after surgery.
what does the zone reticularis produce?
predominantly androgens and some cortisol, hence this is usually negligible.
what does desmolase do?
converts cholesterol (27c) to pregnenolone (21c) by cleavage of side carbon chain.
how is cortisol produced from pregnenolone?
in the zona fasciculata, pregnenolone is converted to progesterone by oxidation to a ketone. progesterone is converted to 17OH Progesterone then to deoxycortisol then to cortisol by 3 consecutive oxidation reactions.
what is ACTH?
adrenocorticotropic hormone, produced by the anterior pituitary. It originates as POMC - pro-olio-melanocortin. POMC is cleaved to form ACTH, MSH and endorphins.
MSH is melanocyte stimulating hormone.
how does cortisol negatively feedback?
binds to GRs in the pituitary and hypothalamus.
what does ACTH do?
upon binding to GPCRs, it stimulates P450scc enzymes and 17, 21, 11 hydroxylases leading to cortisol production
how does the renin angiotensin system trigger aldosterone release?
turns on aldosterone pathway within adrenal cortex, activating 21,11,18 hydroxylases. this leads to increased salt retention.
What is Addison’s Disease?
Primary adrenal failure leading to low levels of cortisol.
main causes for addisons?
- autoimmune (most common in UK)
- TB (worldwide)
why does tanning occur in addisons?
low cortisol levels mean high ACTH meaning high MSH. this stimulates melanin production, even in mucous membranes which is rare!
features of addisons disease?
- increased pigmentation
- autoimmune conditions like vitiligo may coexist
- low blood pressure due to no cortisol or aldosterone
- low sodium
- high potassium
urgent treatment of addisonian crisis to prevent death?
- normal saline to replace lost salt (low salt reabsorption) and water, increasing BP
- intravenous dextrose to prevent hypoglycaemia
- hydrocortisone steroids given/ tablets to replace hormone
biological actions of excess cortisol?
- impaired glucose tolerance eg Diabetes
- weight gain
- thin skin easily bruised and stretch marks (Striae)
- proximal myopathy
- mental changes (depression)
- hypertension
- fat redistribution eg moon face and interscapular fat pad
what is the biological cause of the symptoms of excess cortisol?
causes increased fat production and loss of protein/
loss of protein leads to bruising and stretch marks as cannot repair effectively even after wound.
proximal myopathy due to loss of protein in central muscles, this often means the patient cannot and up without support of arms.
cortisol also has effects on the brain.
hirsutism and acne can also occur as overproduction od androgens.
what is Cushing’s syndrome?
excess of glucocorticoids. caused by:
- excess oral steroids
- Cushings disease (pituitary adenoma)
- Ectopic ACTH production eg from lung cancer
- adrenal tumour
clinical signs of Cushing’s?
- diabetes
- hypertension
- osteoporosis due to loss of protein from bones
- centripetal obesity
- proximal myopathy
- immunosuppressant, reactivation of diseases
- moon face
- thin skin
what is the difference between Cushing’s Disease and Cushing’s Syndrome?
Syndrome is any cause
CUSHINGS DISEASE is due to only pituitary adenoma.
What is Conn’s Syndrome?
aldosterone producing adenoma leading to excess aldosterone produced:
- high sodium retention therefore:
- hypertension
- oedema
- low potassium