TBL5 Adrenals Flashcards
_______ is at risk with left adrenalectomy, so the standard procedure is to immunise for _______ and ______ before surgery to remove the adrenal gland.
Spleen (lymphoid organ)
Immunise for HIB and Pneumococcal
Superior suprarenal artery is a branch of _______.
Middle suprarenal artery comes from _________.
Inferior suprarenal artery comes from _________.
Superior suprarenal artery - inferior phrenic artery
Middle suprarenal artery - abdominal aorta
Inferior suprarenal artery - renal arteries
Left adrenal gland venous drainage
left renal vein
Right adrenal gland venous drainage
directly into the IVC (right side)
3 zones of the adrenal cortex (outer)
zona glomerulosa
zona fasciculata
zona reticularis
Venous outflow of the adrenal gland arises from:
Arterial supply of the adrenal gland:
Venous supply arises from centre of the medulla (inside to outside).
Arterial supply reaches the adrenal medulla by passing through the adrenal cortex. (outside to inside)
Adrenal medulla is made up of ________ cells, that produces catecholamines, mainly _______.
chromaffin cells
- source of catecholamines, mainly adrenaline
Chromaffin cells are innervated by
pre-ganglionic sympathetic nerve fibers
- source of catecholamines
Adrenal cortex hormones
zona glomerulosa - mineralcorticoids (aldosterone)
zona fasciculata - glucocorticoids (cortisol)
zona reticularis - sex steroids
Steroid molecule is derived from the _______ precursor, which is converted to _______ by enzyme _______.
Cholesterol precursor converted to pregnenolene by enzyme P450scc
75% of cortisol is bound to ________, 15% of cortisol to _______ in the blood and 10% are free (bioactive).
75% cortisol bound to CBG/transcortin
15% cortisol bound to albumin
60% of aldosterone bound to _____, 40% free.
aldosterone bound to CBG
Cortisol levels in circulation vary according to ________, whereas aldosterone levels vary according to ________.
Cortisol levels vary according to time of the day.
- higher in the morning
Aldosterone levels vary according to position of body.
Main effects of aldosterone work on the ___________ of the nephron
distal convoluted tubule and cortical collecting ducts
also sweat glands, gastric glands, colon
Main effects of aldosterone
- stimulates Na+ reabsorption
2. increases K+ and H+ excretion
Aldosterone receptors are (intracellular/extracellular).
receptors are intracellular
- aldosterone diffuses from the blood into the epithelial cells to bind to its receptor
Mechanism of action of aldosterone:
- binds to intracellular receptor
- complex moves to the nucleus to act as a _______ to switch on genes
- which code for ______ (protein) to keep the intracellular Na+ concentration low, stimulating Na+ to enter apical membrane and increase reabsorption of Na+.
- also stimulates __________.
- binds intracellular receptor
- complex acts as transcription factor to switch on genes
- coding for Na+/K+ ATPase on the basolateral membrane to reduce intracellular concentration of Na+, increasing reabsorption of Na+ from the tubular fluid
- also stimulates ion channels for K+, Na+ and H+
RAAS is mediated by __________ and _________.
juxtaglomerular apparatus and macula densa
Position/location of juxtaglomerular cells
- found at the tip of the ascending loop of Henle where it touches the afferent arteriole
- found along the lining of the afferent arteriole where it touches the DCT
Position of macula densa cells
- lie in the cell lining of the DCT where it touches the afferent arteriole
Function of juxtaglomerular cells
secrete renin
3 Stimuli for aldosterone release
- Angiotensin II (MAIN)
- ACTH from anterior pituitary gland
- Decrease in Na+ concentration and increase in K+ concentration
Main physiological actions of cortisol
- Protein catabolism (breakdown of muscle)
- Increase blood glucose
- Fat metabolism (lipolysis)
- Enhanced effects of glucagon and catecholamines
Cortisol has effects across various systems.
- renal and cardiovascular effects (increase excretion of water, increased vascular permeability)
- mineralcorticoid effects
- breakdown of bones
- CNS (depression)
- impaired growth
Pharmacological effects of glucocorticoids
associated with the decreased production of certain inflammatory molecules
- anti-inflammatory
- immunosuppressive
- anti-allergic
- associated with the decreased production of prostaglandins, leukotrienes and histamines
Enzyme __________ (in the kidneys) converts cortisol to inactive ______, preventing cortisol from binding to aldosterone receptors.
Enzyme 11b-hydroxysteroid dehydrogenase type 2 converts bioactive cortisol to inactive cortisone
Mechanism of action of cortisol:
- binds to (intracellular/extracellular) receptor
- acts as ______ to increase synthesis of protein _________ which
- has an autocrine action and causes an inhibition of production of ________.
- binds to intracellular receptor
- acts as transcription factor to increase synthesis of annexin-1
- which has an autocrine action and causes inhibition of production of prostaglandin
ACTH is produced from precursor _____.
Precursor is broken down into 4 parts.
POMC
- ACTH
- pro-g-MSH
- g-LPH
- B-endorphin
Cortisol is mainly controlled by _______.
ACTH from pituitary gland
hypothalmo-pituitary axis
_____ is a precursor for more potent androgens like testosterone and oestrogen
dehydroepiandrosterone (DHEA)
- reaches its peak serum level at 20-30 years old
Chromaffin cells lying in the adrenal medulla are innervated by ________.
sympathetic pre-ganglionic nerve fibres
_________ stimulates chromaffin cells of the adrenal medulla to secrete _______.
Acetylcholine stimulates chromaffin cells of the adrenal medulla to secrete catecholamines directly into the bloodstream.
Catecholamines are synthesised by chromaffin cells from the precursor _____, which is converted to ______ then to ________.
Tyrosine (precursor) => Dopamine => Noradrenaline => Adrenaline
In chromaffin cells, the enzyme ___________ methylates noradrenaline to adrenaline.
phenyl-N-methyltransferase (PNMT)
________ refers to primary adrenal failure.
Addison’s disease
2 main causes associated with the destruction of adrenal glands in Addison’s disease
- Tuberculosis
2. Autoimmune
Why is there pigmentation in Addison’s disease?
Due to increased MSH levels
- from increased ACTH levels due to the loss of negative feedback by cortisol
Test for Addison’s disease
Synacthen stimulation test
- check cortisol levels when ACTH is administered
3 management steps for Addison’s disease
- Rehydrate with normal saline
- Dextrose to prevent hypoglycemia
- Hormone replacement
__________ refers to an adenoma of the zona glomerulosa cells which produces aldosterone, causing ectopic aldosterone production.
Conn’s syndrome
Clinical signs of Conn’s syndrome (excess Aldosterone)
- Hypertension
- Hypokalaemia
- High aldosterone levels in the presence of suppressed renin levels
___________ is characterised by excess cortisol production from the adrenal cortex.
Cushing’s syndrome
4 causes of Cushing’s syndrome
- Cushing’s disease - ACTH-secreting pituitary adenoma
- Ectopic ACTH production (lung cancer)
- Adrenal adenoma
- Oral steroids (administered)
_________ are tumours of the adrenal gland associated with excessive production of catecholamines.
Phaeochromocytoma
4 investigations done to determine cause of Cushings
- 24h urine collection
- Blood diurnal cortisol levels
- Low dose dexamethasone suppression test
- High dose dexamethasone suppression test
Dexamethasone in the diagnosis of Cushing’s
Dexamethasone provides negative feedback to ACTH production by pituitary gland.
In HDDST, only Cushing’s disease will suppress cortisol levels whereas ectopic ACTH and adrenal tumours will not suppress cortisol levels.
What test is used to differentiate between Cushing’s disease and other types of Cushing’s?
High dose dexamethasone suppression test (HDDST)
Pharmacological drugs used to treat Cushing’s disease are either _________ or _________ drugs. (mode of action)
- enzyme inhibitors
2. receptor-blocking
4 main drugs used as inhibitors of steroid biosynthetic enzymes (treatment for Cushing’s)
- Metyrapone
- Ketoconazole
- Trilostane
- Aminoglutethimide
Metyrapone acts as an inhibitor of ________, blocking the synthesis of _________ and ________. It is often used to control the symptoms of Cushing’s syndrome prior to surgery.
Metyrapone:
- inhibitor of 11B-hydroxylase
- blocks synthesis of aldosterone and cortisol
- side effects include nausea, vomiting and dizziness
Metyrapone can cause (hypotension/hypertension).
Hypertension
- due to the deoxycorticosterone that accumulates in the zona glomerulosa
- has aldosterone-like activity leading to salt retention and increased water reabsorption
Trilostane blocks the activity of __________, thus blocks all three pathways in the adrenal gland.
3b-hydroxysteroid dehydrogenase (enzyme that converts pregnenolene to progesterone)
Ketoconazole (mainly used as a _________ agent) blocks the activity of _________, thus blocking all three pathways in the adrenal gland.
P450scc (enzyme that converts cholesterol to pregnenolene)
Aminoglutethimide inhibits the production of _________ from ________, thus inhibiting all three steroidogenic pathways.
Aminoglutethimide:
- inhibits production of pregnenolene from cholesterol (similar to Ketoconazole)
- usually use to treat adrenocortical carcinomas and prostatic cancer
Congenital adrenal hyperplasia
Enzyme disorders related to steroid synthesis in the cortex
Conn’s syndrome is caused by excess _________ production, and suppressed ________ levels.
Conn’s syndrome:
- excess aldosterone levels
- suppressed renin levels (Due to raised BP)
How does Conn’s syndrome cause hypertension?
- Excess aldosterone
- Increased Na+ reabsorption
- Increased extracellular fluid volume
=> Hypertension
Conn’s syndrome can cause hypertension and ____________.
hypokalaemic alkalosis
- increased excretion of K+ and H+
Treatment for Conn’s syndrome:
- Surgery to remove the adrenal adenoma
- ____________ (e.g. spironolactone) which compete with aldosterone for receptor binding
Aldosterone receptor antagonists (e.g. spironolactone)
_______________ is an inherited disease of high BP due to a mutation in the aldosterone-activated sodium channel in the apical membrane.
Liddle’s syndrome
- causes apical Na+ channel to be constantly switched on
=> allows continuous reabsorption of Na+
2 main enzyme disorders in Congenital Adrenal hyperplasia
- 21-hydroxylase deficiency (Complete/Partial)
2. 11B-hydroxylase deficiency
In complete 21-hydroxylase deficiency (congenital adrenal hyperplasia), the synthesis of _______ and _________ is inhibited, but there is an excess production of _________.
21-hydroxylase deficiency:
- aldosterone and cortisol synthesis inhibited
- excess sex steroids
- commonly presents as a neonate with salt-losing Addisonian crisis associated with hypotension
In 11B-hydroxylase deficiency (congenital adrenal hyperplasia), _________ is produced in large amounts, and this may lead to hypertension and hypokalaemia.
There is also low levels of cortisol and excess androgens.
11B-hydroxylase converts 11-deoxycorticosteorne to corticosterone.
11-deoxycorticosterone has mineralcortcoid effects
=> excess leads to hypertension and hypokaelemia.
Clinical features of Cushing’s syndrome (excessive cortisol levels and high metabolism)
- Proximal myopathy
- Moon face, buffalo hump, lemon on stick appearance
- Centripetal obesity
- Hypertension
- Protein catabolism leading to loss of collagen in skin, causing red striae, thin skin and bruising
- osteoporosis (bone breakdown)
- Diabetes
Why does cortisol lead to high BP?
Cortisol has mineralcorticoid effects
- can bind aldosterone receptors and saturate it in the presence of excess cortisol in Cushing’s
____________ is a catecholamine-secreting tumour in the adrenal medulla.
Phaeochromocytomas
Phaeochromocytomas
- Effect of excess catecholamines are ________ and is associated with a sudden series of effects. (i.e. occurs in acute attacks, which gets more often as the tumour develops until there is long-term high BP, sweating, tachycardia, etc.)
effect of excess catecholamines are paroxysmal (sudden release)
- episodic attacks
Treatment of phaeochromocytomas
- Alpha- blockades to reduce BP
- Beta-blockades to prevent tachycardia
- Surgery to remove the tumour eventually
4 main types of anti-hypertensive drugs
- ACE inhibitors
- Beta-blockers
- Calcium channel blockers
- Diuretics
5 main types of diuretic drugs that can be used
- Osmotic diuretics
- K+ sparing diuretics
- Carbonic anhydrase inhibitors
- Loop diuretics
- Thiazides
Osmotic diuretics work along the _____________ by decreasing the reabsorption of certain molecules.
=> less water is absorbed
=> more water is excreted
=> reduce BP
Osmotic diuretics
- proximal convoluted tubule
- decreases reabsorption of molecules
- to increase water excretion
Mode of action of
carbonic anhydrase inhibitors
- Carbonic anhydrase enzyme stimulates production of H2CO3 and break it down into H+ and HCO3-
- Blocking carbonic anhydrase decreases H+ secretion and Na+ reabsorption
- Works along the proximal convoluted tubule
Loop diuretics mode of action
- Work along ascending loop of Henle
- blocks the triple co-transporter (Na+ Cl- K+)
- reduces Na+ reabsorption
Example of loop diuretic
Furosemide
Thiazides mode of action
- Work on the distal convoluted tubule
- Blocks apical membrane transport system
- Prevents reabsorption of Na+
K+ sparing diuretics mode of action
- Works on distal convoluted tubule to prevent excretion of K+
Examples of osmotic diuretics
Glucose, mannitol
Diuretics that work on PCT
- Osmotic diuretics
2. Carbonic anhydrase inhibitors
Diuretics that work on DCT
- Thiazides
2. K+ sparing diuretics
