The Adrenals and their Hormones (8) Flashcards
What are the adrenal/suprarenal glands
Two glands superior of the kidneys embedded in the
perirenal fat
What are the adrenal glands surrounded by
a capsule
what do the adrenal glands consist of
the adrenal medulla- core of the gland and the adrenal cortex - outer layers surrounding the core
What are the 3 cortical zones
the adrenal cortex consists of 3 layers. Outer layer: Zona glomerulosa. Middle layer: Zona Fasciculata. Inner layer: Zona Reticularis
what supplies blood to the adrenal cortex
abdominal aorta and renal arteries
what are the two ways in which the blood passes to the cortical zones
Blood passes through the cells until it reaches the tributary of central vein in the centre of the
medulla. There are some arterioles which flow from the outer capsule to the adrenal medulla
what hormones does the adrenal medulla release
catecholamines
what hormones does the adrenal cortex release
corticosteroids
Structure of the zona fasciculata
recognisable form; lines of cells which run towards the zona reticularis
structure of the zona reticularis and zona glomerulosa
no distinguishable form of cells
What is the medulla made up of
Made up of chromaffin cells (essentially post-ganglionic nerve fibres in a specialised form). This means that there is part of the sympathetic nervous system where the cells innervated by the pre-ganglionic fibres will release their substances, not as neurotransmitters, but as hormones into the general circulation
what do chromaffin cells do (meddle with a cat)
synthesise and release catecholamines
what are catecholamines
polypeptide hormones synthesised from a tyrosine precursor
what catecholamines are produced
Adrenaline (80%). Noradrenaline (20%). Dopamine (very small amounts)
What are the different corticosteroids that are produced by the adrenal cortex
Mineralocorticoids- aldosterone. Glucocorticoids-cortisol. Sex Steroids - androgens and oestrogen
what does the zona glomerulosa synthesis and release
aldosterone
what does the zona fasciculata release
cortisol
what does the zona reticularis release
sex hormones
where are cortisol, androgens and oestrogen synthesised
in the zona fasciculata and zona reticularis
What are the adrenals responsible for the synthesis and release of?
Mineralocorticoids (C21). Glucocorticoids (C21) and androgens
What are the Gonads responsible for the synthesis and release of?
Progestogens (C21). Androgens (C19). Oestrogens (C18)
Explain the synthesis pathway of adrenal cortical hormones (add pic)
Cholesterol is precursor of all of the steroids and is a 21 carbon long molecule. An enzyme converts Cholesterol to Pregnenolone and initiates the process of steroid production. 17-α hydroxylase is an important enzyme as it allows glucocorticoids and androgens to be made from the precursors pregnenolone and progesterone. A dehydrogenase enzyme initiates the mineralocorticoid pathway from pregnenolone.
what is the precursor for the production of aldosterone
progesterone
what are the precursors of oestrogens
androgens
why arent corticosteroids stored
they are lipophilic and can pass easily through the membranes where they bind with intracellular or nuclear membrane receptor. Therefore they cannot be stored, as this will result in excessive binding with receptors and
hence over stimulation
what is androstenedione
a week androgen that can be converted to testosterone and dihydrotestosterone
androgens produced in the adrenal cortex are
weak but they are more powerful in the testes
How is Corticosteroid transported in the blood
The vast majority of corticosteroids are bound to plasma proteins to avoid being taken up by non target cells. Cortisol:75% bound to corticosteroid binding globulin (CBG or Transcortin), 15% bound to albumin, 10% free (unbound) biologically active. Aldosterone: 60% bound to corticosteroid binding globulin and 40% free (unbound)
What do plasma proteins do
The plasma proteins act as a store and transport mechanism – they transport the hormone where
the unbound-bound hormone equilibrium is unbalanced, i.e. where the hormone needs to be
released
The circulating concentraion of corticosteroids
Cortisol is controlled by the hypothalamo-pituitary axis, and is released in pulses , which vary depending on time of day. This is known as circadian rhythm: At 8am its 140 – 690 nmol/ and at its 4pm 80 – 330 nmol/l. Aldosterones are released in pulses, and depend on body positioning: Upright 140 – 560 pmol/l. Nanomoles are 1000x greater than picomoles
Why is body position important for aldosterone amount
aldosterone is involved in the control of fluid and balance
What is the action of aldosterone
It stimulates Na+ reabsorption in the distal convoluted tubule and cortical collecting duct. This is particularly important in the kidneys but is also important in sweat glands, gastric glands and colon. It also stimulates K+ and H+ secretion in the distal convoluted tubule and cortical collecting duct. So it will have an effect on pH regulation of the blood
What is the only way we have of regulating potassium in the blood
Aldosterone stimulating K+ secretion
what is hyperaldesteronism responsible for
high blood pressure
what is the mechanism of action of aldosterone
Aldosterone diffuses into the distal convoluted tubule from the blood. It then binds to an intracellular receptor within the cell; mineralocorticoid receptor (MR).
Being a steroid hormone, aldosterone passes through cell membranes and binds to intracellular receptors. The hormone-receptor complex is transported to the nucleus and binds to specific DNA. This activates transcription, translation and synthesis of specific proteins. The proteins then act as: ion channels – in the apical membrane, allowing Na+ to be reabsorbed into the distal convoluted tubule form the tubular fluid, and ion pumps – on the basolateral membrane, pumping Na+ into the blood from the distal convoluted tubule, completing the reabsorption.
what is the main mineralcorticoid in humans
aldosterone
What do the cells lining the ascending limb of the loop of Henle touch
the cells that line the afferent arteriole
what happens to plasma osmolality in the presence of aldosterone
Plasma smolality increases. Aldosterone stimulates reabsorption of sodium ions so the concentration of sodium ions in the blood increases
What does the increase in plasma osmolality stimulate
the release of vasopressin
What does vasopressin do in the kidney collecting duct
it increases water reabsorption so the consequence of aldosterone is an expansion of extracellular fluid volume.
What are the juxta-glomerular cells
Specialised cells that line the renal afferent arteriole and contain many secretory granules. The secretory granules contain an enzyme called renin which is important in the production of aldosterone
Where does the main mechanism for controlling aldosterone reside
in the kidney nephrons
give an overview of blood supply in the nephron
the glomerulus receives blood from an afferent arteriole and the blood leaves via an efferent arteriole
what is the juxtaglomerular apparatus
The juxtaglomerular apparatus describes the combination of the juxtaglomerular and macula densa cells.
What are the macula densa cells
They are the cells that line the ascending limb of the loop of Henle which are adjacent to the juxta-glomerular cells. They respond to changes in sodium ion concentration, so they are effectively specialised Na+ sensors.
What is the afferent arteriole adjacent to
the point where the ascending loop of Henle meets the distal convoluted tubule. This is also in close proximity to the glomerulus.
What happens in conditions involving excessive aldosterone ?
Aldosterone increases plasma osmolality which stimulates vasporessin release. This causes an expansion of extracellular fluid. If you have a maintained expansion of extracellular fluid volume this leads to hypertension
What causes renin release from the juxtaglomerula cells in the distal convoluted tubule (3) ?
Decreased renal perfusion pressure (normally associated with decreased arteriole blood pressure).
Increased renal sympathetic activity (direct to juxta-glomerular cells). Decreased Na+ load to top of the loop of Henle.
How does increased renal sympathetic activity cause renin release?
The JGA (juxta-glomerular apparatus) has sympathetic innervation. The sympathetic system is activated when the blood pressure falls. This leads to renin release
How does decreased Na+ loads to top of loop of Henle cause renin release?
Decreased sodium concentration at the top of the loop of Henle. This leads to activation of JGA as it is recognised by the Na+ sensing macula densa cells, which leads to increased renin release.
What is the Renin-Angiotensin-Aldosterone System
liver produces angiotensinogen (a large protein). Renin breaks down angiotensinogen to angiotensin I. Then, ACE (angiotensin converting enzyme) converts angiotensin I to angiotension II. Angiotensin II stimulates the zona glomerulosa to produce aldosterone.
How does Renin stimulate the production and release of aldosterone
via the Renin-Angiotensin-Aldosterone System
what are the effects of angiotensin II
vasoconstriction and stimulates the zona glomerulus of the adrenal cortez to synthesise and release aldosterone.
what other factors affect aldosterone production
Corticotrophin (released from the anterior pituitary gland) enhances the renin-angiotensin system. Increased K+ and decreased Na+ also stimulates aldosterone release.
How does angiotensin regulate ions
If the blood plasma sodium ion concentration falls, it has a direct effect in stimulating aldosterone production - so there is more sodium reabsorption and sodium concentration returns to normal. Aldosterone is also the main mechanism for regulating potassium in our bodies - an increase in potassium concentration stimulates aldosterone production leading to increased secretion of potassium
What does aldosterone production lead to
increased Na+ reabsorption in the distal convoluted tubule, therefore increasing water reabsorption which increases the volume of the (blood) – increasing BP.
What can chronic extracellular fluid increase lead to
hypertension which can be treated with ACE inhibitors which are the main antihypertensives used.
What are the metabolic effects of cortisol
Stimulates peripheral protein catabolism. Hepatic gluconeogenesis. Increased blood glucose. Fat metabolism (Lypolysis in adipose tissue). Enhances effects of glucagon and catecholamines.
What is the main glucocorticoid in humans
Cortisol is a glucocorticoid synthesised in the cortex of the adrenal glands.
Why are the arms and legs really thin in Cushing’s syndrome
Cortisol stimulates peripheral protein catabolism so excessive production of cortisol causes a lot of muscle loss
What are the renal and cardiovascular effects of cortisol
Excretion of water load. Increased vascular permeability
what are the other effects of cortisol
Mineralcorticoid effects and some effects on bone an CNS growth
What are the effects of large (pharmacological) amounts of cortisol
anti-inflammatory action, immunosuppressive action and anti-allergic action
What do the effects of large amounts of cortisol result from?
decreased production of molecules such as prostaglandins, leukotrienes and histamines. they may also affect movement and function of leukocytes and the production of interleukins.
What is the mineralocorticoid receptor?
It is what aldosterone binds to. Aldosterone acts almost entirely on the mineralocorticoid receptor (MR). Cortisol binds to the Glucocorticoid Receptors and the Mineralocorticoid Receptors equally.
what enzyme in the kidney converts bioactive cortisol to cortisone (inactive)
11b-hydroxysteroid dehydrogenase 2
Why isnt cortisol constantly binding with mineralocorticoid receptor despite having a concentration in the blood 1000x that of aldosterone?
the receptor is located with an enzyme which removes cortisol from the environment by converting it to cortisone
What is the mechanism of action of cortisol
Cortisol binds to intracellular receptor, and the complex is transported to the nucleus where it binds to
DNA stimulating protein synthesis. Annexin 1 and annexin 1 receptor are synthesised. Annexin 1 leaves the cell and has an autocrine effect, preventing prostaglanding synthesis by blocking arachidonic acid production
what does cortisol play an important role in
in the endocrine response to stress
How is cortisol controlled (hypothalamo-pituitary-adrenal axis)
Corticotrophin- releasing hormone (CRH), and Vasopressin are control hormones released by the
hypothalamus, which control the release of corticotrophin. Corticotrophin (ACTH) is released from the adenohypophysis and has a short auto-negative feedback loop to the hypothalamus (inhibiting CRH and vasopressin release). Cortisol has negative feedback effects direct to the pituitary (inhibiting cortiocotrophin release) and indirectly to the hypothalamus (inhibiting CRH and vasopressinrelease).
What stimulates cortisol release
Stressors via brain nerve pathway and circadium rhythm (biological clock) stimulate the release of
CRH and vasopressin from the hypothalamus, therefore increasing cortisol (and small amounts of
androgen) release.
What is the circadian rhythm for cortisol
it originates from the biological clock and resides in the suprachiasmatic nucleus. Because of the variation in cortisol levels with time, blood sampling should be arranged so that it is taken at times when cortisol levels are expected to be at its highest or lowest.
What is Dehydroepiandrosterone (DHEA) ?
A very weak androgen. Precursor for androgens and oestrogens. Converted to active hormones within target cells (which have appropriate enzymes). Peak serum levels at 20-30 years, then decreasing steadily with increasing age. Particularly important in post-menopausal women as a precursor for oestrogen (and androgen) synthesis by target tissue in the absence of ovarian steroids
