Lecture 3. The Adrenal Gland Flashcards
Learning Outcomes
*Describe the Location & gross anatomy
*Explain the physiology of the adrenal cortex & adrenal medulla
–Morphology
–Hormones
–Disorders of adrenal function
*Relate adrenal function to other aspects of physiology (an “integrative” approach)
Anatomy of the Adrenal Glands
So let’s start by looking at the anatomy of the adrenals.
Uh, we have two of these adrenal glands, one sitting on top of each kidney.
And adrenal literally means it’s on the kidney. They’re very small tissue.
Um, size of talking about 5 to 10g each.
So not very big. And they’re surrounded in a fibrous capsule, uh, encased in fat.
That’s why often in these kind of textbook pictures that you can see on the right of this slide here,
the adrenals are often coloured in a sort of yellowish colour.
And there are two main functional regions. As I briefly mentioned in the previous slide, we have the cortex.
And cortex literally means the outside. And we have the adrenal medulla.
The medulla literally means the insides. So we’ve got an inner bit and an outer bit.
And the two different subregions of the adrenal um have very, very different cell types and release very, very different sorts of hormones.
And the final point to make on this slide, in passing, I kind of introduce you to this concept last week, given, of course, the endocrine tissues.
Their role is to produce hormones which are signalling molecules released into the blood.
It should come as no surprise that, like every other endocrine tissue,
the adrenals have a very, very good rich blood supply.
So they are surrounded by a very dense capillary network.
Anatomy of the Adrenal Glands*Above kidneys
*Approx 5-10g each
*Enclosed in fibrous capsule surrounded by fat
*Contain 2 major functional regions
–Adrenal cortex
–Adrenal medulla
–Cortex and medulla possess different cell type(s) with distinct morphology and endocrine function
*Rich blood supply
–Arterial blood enters cortex and passes through cords of cells
–Blood exits via venules of the medulla
–Permits interaction between cortex and medulla
The Adrenal Cortex
Let’s start off by looking at the adrenal cortex, the outside part of your adrenal glands.
And the top right of this slide here is just a very simplistic cartoon that I’ve drawn in PowerPoints.
And this shows you a kind of cross-section.
So if you cut down to the middle of the adrenals, just emphasising that the cortex is on the outside, the medulla is in the middle.
And then the bit that I’ve highlighted in that red rectangle is then enlarged in the textbook picture on the bottom right it slides.
So the adrenal cortex is the largest of the two subdivisions of the adrenal glands.
And about three quarters of the adrenal tissue mass is made up by the adrenal cortex.
And if you look down the microscope, um, at the cells of the adrenal cortex, you will see that they contain lots of fat droplets.
And that should initially give you a clue as to the type of hormone that these, um, cells produced.
And they produced steroids. And steroids are not stored as hormones in vesicles.
they are synthesised from scratch, from lipids that are stored within the cells that produce them
So the cells of the adrenal cortex produce steroid hormones.
it’s worth pointing out that there are three different subregions just within the adrenal cortex.
We have the zona glomerulosa a small part
but nonetheless very important part which produces a type of hormones called mineralocorticoids
The main parts are about three quarters of the adrenal cortex is made up by region called the zona fasciculata (75%) And these produce glucocorticoids
And then finally there’s a region called the zona reticularis
And these produce sex steroids. So androgenic like hormones both in men and women.
- the mineralocorticoid and the glucocorticoids, are both essential for life. if you were unable to make these hormones, you wouldn’t survive.
*Approx 75% of adrenals
*Characterised by intracellular lipid droplets
–Steroid hormone synthesis!
*3 subregions, each of which secrete different hormones (all steroids)
–Zona glomerulosa (10%); mineralocorticoids
–Zona fasciculata (75%); glucocorticoids
–Zona reticularis (15%); sex steroids
*NB mineralocorticoids and glucocorticoids are essential for life
General Properties of Steroid Hormones (Revision)
General Properties of Steroid Hormones (Revision)
*Synthesised from cholesterol
*Little storage in endocrine cells
–de novo synthesis follows cell stimulus
–but, stores of cholesterol present in the cells can be rapidly metabolised
*Mostly transported bound to plasma proteins
*Steroids are lipophilic and so diffuse across the cell membrane into the blood
*Bind to intracellular receptors
*Slow, long-term actions
–Regulation of transcription
Mineralocorticoids
And so if we start at the top of this slide here.
The main physiological stimulus for the production of these hormones is a decrease in blood pressure.
And as you may remember from your kidney, your renal physiology lectures,
a decrease in blood pressure stimulates the production of a molecule called angiotensin two, and angiotensin two acts on the zona glomerulosa.
angiotensin two, has receptors in the adrenal cortex on the cells that produce mineralocorticoid.
It binds to those receptors, and it stimulates the production and release of the main mineralocorticoid hormone, which is called aldosterone
And the net effect of this is to raise blood pressure.
Okay, so the simplest take home message from this slide.
What does aldosterone do?. It increases blood pressure.
And it does it through two parallel pathways, one that involves working on the smooth muscle vasculature.
The other involves working, um, on the kidneys.
Now to increase blood pressure. There are two things you can do. You can increase blood volume.
The more volume you have, the more pressure that you have.
You can also cause constriction of the blood vessels, but those are the two ways in which you can increase blood pressure.
aldosterone works on both of these.
First of all, it works on smooth muscle in the vasculature, and it increases the sensitivity of the smooth muscle to vasoconstricts.
So it has a net effect of causing constriction of the arterials.
And again by causing constriction of the vasculature, that in itself increases blood pressure.
But it also acts on the kidneys to increase blood volume.
And aldosterone causes an increase in the reabsorption, of sodium.
So the retention of sodium in the body by the kidneys and then by increasing the amount of sodium, , that’s retained.
We get as a part of that kidney mechanism, we get an increase in the excretion of other cations, particularly potassium and hydrogen.
But the increased retention of sodium ions causes an increase.
Retention in the kidneys of water by osmosis
and that increase in retention of water causes an increase in blood volume, and that increases our blood pressure
So for mineralocorticoids the main example is a hormone called aldosterone.
It’s stimulated by low blood pressure. Its net effect is to increase blood pressure back to homeostatic levels.
And it does this by two parallel pathways.
It causes an increase in constriction of the blood vessels, but it also causes an increased,
blood volume by signalling to the kidneys and causing them to retain more water in our bodies.
*Regulate homeostatic control of minerals (Na+, K+/H+)
–Cation exchange
–Also see lecture notes on kidney physiology
*1ry mineralocorticoid = aldosterone
–Different to ‘classical’ neuroendocrine regulation
–Part of renin-angiotensin-aldosterone system (RAAS)
–Stimulated by ↑ angiotensin II
–Essential for Na+ maintenance
*In plasma, mostly bound to albumin
Disorders of Aldosterone Secretion
So What happens if the normal physiology of the aldosterone goes awry?
Well, there’s really just one main clinical, um, situation in which we have a disorder about the aldosterone, production and secretion.
And this is where we get an overproduction. Um, and this is called Conn’s syndrome.
And it’s usually related to an overactivity of cells of the zona glomerulosa cells that produce aldosterone.
But it can also, uh, result from an excess of renin secretion
renin is an enzyme that’s important for the production of angiotensin two and therefore stimulation of derived from the adrenal cortex,
What are the symptoms?
Remember, the main net effect of the aldosterone hormone is to increase blood pressure.
Therefore, it should be quite obvious that if we have too much of this hormone, we’re going to have a hypertension.
So an increase, um, to a very high level of blood pressure.
And this is usually secondary partly to vasoconstriction but also to excess water retention.
The other symptom of alkalosis is perhaps a little bit less obvious,
but if you look back on the previous slide, it actually makes quite logical sense.
So the way in which aldosterone triggers water retention is by signalling to the kidneys and making them retain more sodium ions,
and by osmosis, that increased retention of sodium ions causes the increase in water retention.
However, to cause that increase in sodium ion retention, you also get in parallel to that and increase loss of potassium and hydrogen ions.
And so if you get an increase loss of hydrogen ions,
you are essentially changing the acidity of the body environment by losing hydrogen ions and protons.
You are basically causing your body contents to become more alkaline.
And that is where we get our alkalosis from in this particular case.
So the hypertension should be quite obvious. The alkalosis is a little bit more subtle.
But if you understand how to steer and works then it should become clear to you.
///
*Overproduction may result from,
–Zona glomerulosa cell hyperactivity (Conn’s syndrome)
–Excessive renin secretion
*Symptoms include,
–Na+ retention, K+/H+ loss
–Hypertension (2ry to Na+/water retention)
–Alkalosis (due to H+ loss)
Glucocorticoids
we’re going to spend most time on these because this is the one where the physiology is perhaps most complex.
But it also has a really important physiological role in terms of metabolic physiology,
but also relates to, um, things like stress and disease as well.
So glucocorticoids have many different physiological functions.
The main one is a metabolic function and
the net effect of glucocorticoids and the effect that gives them the name “gluco”
is that they cause a net increase in plasma glucose concentration.
So it’s this effect on glucose that gives them the name glucocorticoids.
But they also do other things as well. They tend to cause an increase in appetite.
Um they are important in the long term chronic stress response.
Um, they are related to immune function and inflammation.
So a high concentrations glucocorticoids can actually suppress the immune system and will actually suppress inflammatory responses as well.
These can be made use of therapeutically.
So what are the main glucocorticoids?
in humans the main glucocorticoid is a hormone called cortisol.
The feedback loop regulating cortisol production.
Um, is shown on the right of this slide. And hopefully you recognise this basic pattern of negative feedback loop.
And this is a negative feedback loop that’s typical of one that involves the anterior pituitary gland.
So to talk you through it here we have the hypothalamus at the top of the feedback loop.
If you remember the hypothalamus is this region sitting right at the base of the brain that acts
together with the pituitary gland to form the main control centre for most of the endocrine system.
And the hypothalamus releases a hormone called CRH.
And this acts on a cell type called the corticotroph cell within the anterior pituitary gland.
And it stimulates the corticotroph cell to produce its own hormone called ACTH.
And ATCH then travels through the blood to act on the zona fasciculata, the largest region of the adrenal cortex.
It acts on receptors there, and it stimulates these cells to produce cortisol.
And cortisol has all these various downstream physiological functions,
but one of its functions is also to close this negative feedback loop by inhibiting both CRH and ACTH production.
Okay. So that’s a classical negative feedback loop that in normal physiology keeps a nice homeostatic balance within this system.
What happens at the level of stress.
essentially in a situation of stress that can be either physiological or psychological,
stress acts at the level of the hypothalamus to cause an increase of CRH production and makes it much less sensitive to cortisol negative feedback.
So you get a permanent increase in CRH, which causes a long term increase in ACH and therefore a prolonged increase in cortisol.
And that’s the main, chronic stress response that we see in our bodies.
*Multiple physiological roles
–Metabolism (see next slide)
–↑ Appetite
–Stress response (NB stress not just psychological, but also e.g. due to trauma, infection)
–Immunosuppression
–Reduce inflammation & allergic responses
–Weak mineralocorticoid activity (NB higher blood conc, so has physical importance)
*1ry glucocorticoid in humans = cortisol
*Others = corticosterone, cortisone
*In plasma, 75% bound to transcortin (liver glycoprotein), 15% to albumin, 10% free/unbound
Glucocorticoids: Regulation of Metabolism
So now we’ve talked about how the glucocorticoids are regulated and given you an overview of what they can do.
Let’s focus on their main physiological function, which is their role in terms of metabolism and plasma glucose concentration.
So the most important take home message from this slide is to read text at the bottom right of this slide.
So to remind you the overall effect of cortisol is to increase plasma glucose concentration.
And it does this by acting on three different tissues within the body on the adipocytes , particularly white adipocytes which are fat cells,
on the skeletal muscle and acting on the liver and in the skeletal muscle. The overall effect of cortisol is to cause the breakdown of protein.
So proteolysis and that proteolysis causes a release of amino acids from the skeletal muscle into the blood.
On the adipocytes, the fat cells, it acts slightly differently depending upon where the fat cells are within the body, but on the peripheral depots of fat cells,
so particularly those that are found in the subcutaneous region, in the arms and the legs,
it causes lipolysis, a breakdown of fat, and this lipolysis causes a release of fatty acids into the blood.
And then the final action of the cortisol is on the liver, and it stimulates the liver to take up the amino acids in these fatty acids from
the bloods and convert them into glucose by a process called gluconeogenesis.
So it breaks down protein into skeletal muscle, causing release of amino acids into the blood.
It breaks down fat within your peripheral fat tissue, causing release of fatty acids into the blood.
And it acts on the liver and stimulates the liver to take up these amino acids
and fatty acids and then convert them biochemically into new glucose molecules.
thats how cortisol causes a net increase in plasma glucose concentration.
Disorders of Cortisol Secretion
So what can happen if cortisol secretion goes wrong?
Well, we have clinical situations where there are either too much or too little cortisol produced.
And the main situation where we have an excess of cortisol is a disease called Cushing’s syndrome.
And this like many cases where we get abnormally high hormone concentration, is usually caused by some kind of localised tumour.
And so it could be a tumour within the adrenal cortex.
Or it could be a tumour found for example within the Corticotroph cells of the pituitary gland.
Why does this happen? Well, if you have a tumour in a particular cell type,
that cell type tends to divide quite rapidly and become hyperactive and become less responsive to normal physiological control mechanisms.
So if you have too much of a cell type, but not cell type is hyperactive.
And that cell type is a hormone producing cell, then that is why in these situations you get lots and lots of a particular hormone produced.
It’s very difficult for the body to actually then bring back down to normal homeostatic levels.
So a tumour is the most common cause of Cushing’s syndrome.
But sometimes you can also have a Cushing’s like syndrome caused by people
having a high dosage of glucocorticoid therapy for a prolonged period of time.
Usually, glucocorticoids are only given orally for short periods of time to prevent this happening.
But it is possible that if you take tablets of a high concentration of these drugs for a long period of time, you can get the Cushing’s like syndrome.
So what would be the symptoms of having too much cortisol for a prolonged period of time?
Well, remember, the main physiological function of cortisol is to raise plasma glucose concentration.
So if you have high levels of cortisol for a long period of time, it stands to reason that you’re going to have high blood sugar concentrations.
Okay. And that is basically diabetes mellitus.
So patients with Cushing’s syndrome have symptoms of diabetes mellitus because they have high levels of plasma glucose for a long period of time.
They also have, an increased susceptibility to infection.
And this may seem a little bit odd, but if you go back to the previous slide, remember that a high dose of cortisol can suppress the immune system.
So if you have lots of cortisol in a pathological situation like this for a long period of time, that prolonged high concentration of cortisol,
as well as having metabolic effects by raising plasma glucose, will also tend to suppress the immune system.
And if your immune system is suppressed, that makes you slightly more susceptible to infection.
So again, not quite such an obvious symptom, but one that makes sense if you understand the basic physiology of how this hormone works.
It can also affect the physical appearance of these patients.
And sometimes you still see described in textbooks this phrase melon on toothpicks, which isn’t a particularly pleasant description,
but actually is quite a graphical way of describing how these patients can look in severe cases.
And it refers to the way in which cortisol acts on fat cells throughout the body.
The toothpicks part refers to these patients having very thin arms and legs.
And that is because if you remember back to the previous slide,
cortisol acts on fat cells in peripheral tissues and causes a breakdown of the fat that stored and therefore in these particular tissues,
particularly your arms and legs, your peripheral limbs. You get a breakdown of fat and therefore you get very thin limbs.
However, cortisol acts on fat cells, stores within your midriff and your abdomen, and actually causes deposition of increased fat.
So these patients, if uncontrolled, tend to have very thin arms and legs in an excess of adiposity of fat deposition around their abdomen.
And that’s the melon part. So that’s Cushing’s disease.
If you have an abnormally high amount of cortisol, there is also a disease where you get an abnormally low amount of cortisol production.
And that’s called Addison’s disease. And this is caused by decreased function of the adrenal cortex.
And there are various mechanisms that can cause a decreased function of an endocrine tissue one is some kind of localised physical damage.
And it may be damaged the adrenal gland itself or possibly to the pituitary cells that stimulate the adrenal glands.
And one possible mechanism by which you can get localised destruction or decrease function of a tissue is in the case of an autoimmune disease.
And if you remember we talked about autoimmune diseases causing a decrease in thyroid function last week.
The example being Hashimoto’s disease where you get an autoimmune destruction of the thyroid tissue.
Similarly, you could get an autoimmune condition that causes a decrease in the function of your adrenal cortex.
And this would be one potential thing that causes a decrease of cortisol production, as you see in Addison’s.
What would be the symptoms of this?
Well, again, remember, the main overall net effect physiologically of cortisol is to raise blood glucose concentration.
So in the disease where you get abnormally low cortisol secretion,
it stands to reason that a hyperglycaemia low plasma glucose concentration is likely to be one of the key, um, symptoms.
Related to that, you can also have lethargy and lassitude,
particularly if you’ve got a low blood glucose concentration that causes reduction in the activity of the brain tissue.
Uh, you can also get a loss of weight. And this is secondary to the fact that high concentrations of cortisol tend to stimulate appetite.
So if you have a low concentration of cortisol for a long period of time,
you may well get a reduction in appetite and therefore a secondary loss of weight as a result of that.
Cushing’s Syndrome
–↑ Plasma cortisol caused by e.g.
*Adrenal tumour
*↑ ACTH secretion (e.g. pituitary tumour, ↓ cortisol feedback sensitivity)
*Medication
–Symptoms include
*Diabetes mellitus (↑ gluconeogenesis)
*↑ Susceptibility to infection
*Muscle wasting, thin skin (↑ protein catabolism)
*Facial and trunk obesity (fat redistribution & ↑ appetite)
Addison’s Disease
–↓ Function of adrenal cortex caused by e.g.
*Damage to adrenal or pituitary gland
*Autoimmune disease
–Symptoms include
*Hypoglycaemia
*Lethargy, lassitude
*Loss of weigh
Adrenocortical Sex Steroids
So the final part of the adrenal cortex I want to mention, is the zona reticularis the part that produces sex steroids.
Now, when compared to the amount of sex steroid produced by the gonads, the amount of sex steroids produced by the adrenal cortex is very low.
And so in most physiological cases,
the physiological consequence of these steroids produced by the cortex are actually not particularly well known and probably don’t have a major, physiological function. The primarily pre-androgen
So testosterone like sex steroids are produced.
And this occurs in both men and women and in fact, in women, the source of circulating androgens, about half of it comes from the adrenal cortex.
But in men, because there’s so much testosterone produced by the testes,
the amount of androgen produced by the adrenal cortex is absolutely negligible.
And so it probably has very little, if any, physiological significance.
And partly because of this, um, more dubious physiological significance,
the functional significance is much less understood compared to the other adrenal cortex hormones.
People have suggested that these androgenic hormones may be important for the regulation,
of female secondary sexual characteristics, for example, body hair, particularly around puberty.
These hormones may be involved in a pre pubertal growth spurt in both boys and girls.
Um, but again, in normal healthy physiology, the physiological significance is not well understood and is probably quite minor.
*Stimulation of zona reticularis by ACTH
*Low level of steroid secretion when compared to gonads
*Primarily produces “pre-androgens”, which are converted to testosterone in target tissues
–NB In women, source of approx ½ androgens
–Negligible relevance in men
*Functional significance poorly understood
–Female 2ry sexual characteristics (esp body hair)?
–Mid-childhood growth spurt (pre-puberty)?
–Actions become more apparent in disease (esp ↑ secretion)
Disorders of Adrenal Androgen Secretion
However, um, you can see a consequence of these hormones (Adrenocortical Sex Steroids) in certain diseases, particularly if we get excessive androgen production.
And if we have a situation where you have too much of these androgens produced from your adrenal cortex,
then usually this would be caused by an elevation of ACTH from the pituitary gland.
You tend to get symptoms that can be, um, discernable, particularly in women, where otherwise you have a relatively low concentration of testosterone.
And these symptoms include things like acne, male pattern baldness, hirsutism which means essentially an excess, of body hair.
And if it occurs early on in childhood, you may get a precocious puberty.
And precocious puberty is basically an early onset of puberty.
So there’s a range of possible symptoms if you have an overproduction of these hormones.
But this clinical situation is relatively rare. And in normal physiological circumstances, the role of these hormones is probably minimal.
*Excessive production
–Usually, ↑ ACTH secretion
–Alternatives inc. adrenal tumour
*Symptoms inc,
–Acne–Baldness
–Hirsuitism
–Altered gonadal physiology
–Precocious puberty
The Adrenal Medulla
Now I briefly want to go on to the adrenal medulla, which is the middle part of your adrenal glands.
Um, and the cell types found within the adrenal medulla,
a completely different in terms of their morphology and their function compared to the cells in the adrenal cortex.
And the main cell type in your adrenal medulla is called the chromaffin cell,
and chromaffin cells are often considered to be a specialised form of a sympathetic post ganglion neurone.
So some of you may be thinking what is a sympathetic post ganglia neurone?
It’s something that would have been, I’m sure, explain to you in first year physiology in the neuroscience lectures.
But just to remind you where you are looking at the autonomic nervous system, you have two main branches.
You have the sympathetic nervous system, which can cause the so-called fight or flight response.
And you have the parasympathetic that causes the so called rest or digest response, the parasympathetic nerve innervation of the peripheral tissues.
You have a single neurone that goes from your central nervous system and directly innervates that peripheral tissue.
However, for the sympathetic nervous system you have two nerve cells in in theory, so one after the other.
And the join of these two nerve cells is called a ganglion.
So a pre ganglion neurone is the first of these two nerve cells that goes from the central nervous system to that ganglion.
Where is the post ganglion nerve is the one that goes from that ganglion and innervates the peripheral tissue.
So why do people think that the chromaffin cells, of the adrenal medulla is like a post ganglionic sympathetic nerve.
Well, firstly the hormones that it produces are adrenaline and noradrenaline and the
neurotransmitter produced by a post ganglionic sympathetic nerve noradrenaline.
Secondly, and perhaps more importantly, the way in which these hormones,
are regulated is by neuronal input from a preganglionic sympathetic nerve.
And on the right of this slide is a little cartoon showing you, part of this process.
So at the top in red this represents a blood capillary.
The square bit in the middle represents a chromaffin cell in the adrenal medulla.
And this bit right at the bottom here represents the nerve terminal of a pre ganglion sympathetic neurone.
And as you may remember the neurotransmitter that’s released by a pre sympathetic kind of neurone is acetylcholine abbreviated to ACH.
And so here we have a signal going through this preganglionic nerve causing the release of acetylcholine which is a neurotransmitter that travels across the small gap and regulates receptors on the chromaffin cells and stimulates chromaffin cells to release either adrenaline or noradrenaline. You don’t get both from the same chromaffin cell.
About 80% of them will release adrenaline. About 20% of them release nordrenaline.
And these are adrenal amines
And as we talked about briefly, um, last week adrenal amines are found stored in vesicles within the cytoplasm of these chromaffin cells.
when acetylcholine binds to its receptors.
That causes a release of adrenaline or noradrenaline by a classical exocytosis mechanism.
*1ry cell type = chromaffin cells
–Considered as specialised sympathetic postganglionic neurones
*Contain sympathomimetic catecholamines
–Adrenaline (80%), noradrenaline (20%)
–Derived from tyrosine, via dopamine
–Stored in vesicles
–Released by exocytosis
*Catecholamine secretion mediated by splanchic nerves
–Stimulated by e.g. stress, pain, cold, anxiety
*Functional importance in sympathetic “fight or flight” response to acute stress
Action of Adrenal Medullary Catecholamines
So what are the functions of these hormones adrenaline and noradrenaline.
Well, for the purposes of this module, they do pretty much the same thing in direct contrast to the steroid hormones in the adrenal cortex that have this slow, prolonged action that we talked about last week.
Adrenaline and noradrenaline have a very rapid onset of action and a short duration of action.
so it is really quite short and only lasts for a few minutes.
They act through plasma membrane receptors rather than just cellular receptors,
and they have a whole range of different effects, many of which hopefully you already know about.
If you aren’t sure what something like adrenaline does, remember it’s part of the sympathetic nervous system.
The sympathetic nervous system drives a so called fight or flight response.
So what was required in a fight or flight response where you need to be physically active and alert?
Well, your heart rate increases and the contraction of the heart increases so the blood goes around the body quicker.
And this is important, of course, because it enables more oxygen to get to your skeletal muscle.
And it helps to, pick up, carbon dioxide and waste products in that skeletal muscle.
If you need to be physically active, then you need a ready, rapid, form of energy that the skeletal muscle can use.
So you want an increase of glucose within the blood.
And adrenaline does this by causing a breakdown of a storage molecule glycogen from the liver, but also fat from your adipocytes.
You need to get more oxygen to your muscles.
So therefore your respiration rate tends to increase. So you get more oxygen coming into your body and more carbon dioxide, expelled. You also get a change in your blood flow,
so you get less blood flowing to your internal visceral organs because things like
digestion are not important to you if you need to be highly physically active,
but you get more blood flow going to your skeletal muscle again, so you get more oxygen, more glucose going to that muscle so it can be more active.
*Rapid, transient effect (compared to steroids)
–Short half life (t½) = few mins
*Act via plasma membrane adrenoceptors
*Multiple receptor subtypes allow tissue specificity of effect
*Effects of adrenaline include,
–↑ heart rate & cardiac contractility
–Breakdown of glycogen and fat
–↑ O2 consumption
–↑ skeletal muscle blood flow
Disorders of Adrenal Medulla Function
What are the disorders? Well, there’s only really one clinical disorder of the adrenal medulla, but it’s something that can be quite serious.
And this is something called pheochromocytoma. And it’s an abnormally high amount of adrenaline production.
So how can you get an abnormal high amount of hormone production?
Well, just like we’ve described beforehand, that would usually be caused by a localised tumour.
And indeed a localised tumour of the chromaffin cells is what causes pheochromocytoma
what would be the symptoms?
Well, we’ve just discussed what adrenaline does in terms of its effect on the cardiovascular system,
its effects on, regulating blood sugar concentration.
So if you have too much adrenaline, it should be quite predictable that you will tend to have severe hypertension.
So severe increase in blood pressure, a hyperglycaemia a raised plasma glucose concentration.
Your metabolic rates will, um, be very high.
You’re more susceptible to arrhythmias. So that’s abnormal., heart beat and heart rates and also things like anxiety.
Central effects can occur as well. So if you have an abnormally high action in the adrenal tumour, then that can be quite clinically serious.
But the final point I want to get across is this last bullet point on the slide here.
We all know about adrenaline. Everyone has heard of adrenaline.
We all know that it’s something that can stimulate physical activity and alertness.
However, one thing that most people are not aware of is that adrenaline and the adrenal medulla are not actually essential for life.
So whereas in the adrenal cortex We’ve talked about the mineralocorticoids and the glucocorticoids being essential for life.
Actually, adrenaline only accounts for about 20% of the overall sympathetic nervous system response.
Most of our sympathetic response physiologically comes from direct neural innervation of tissues, and only about 20% comes from adrenaline.
So if we were unable to make adrenaline, we would still survive.
And you may not notice a huge difference. Um, our sympathetic response would be a little bit lower, but actually wouldn’t change by an awful amount.
*Pheochromocytoma: tumour of chromaffin cells (→ ↑ catecholamine output)
–Severe hypertension
–Hyperglycaemia
–↑ metabolic rate
–Arrhythmias
–Anxiety
*NB Under activity of the adrenal medulla is not a clinical problem (adrenal medulla is not essential for life)
Summary
Okay, so to summarise the key points, um, of this lecture, we start off by looking at the, um, the anatomy of the adrenal glands.
And I mentioned to you that there are two main subdivisions of the adrenals.
We have the adrenal cortex around the outside, the adrenal medulla.
within the inside the adrenal cortex produces steroid hormones, uh, the main ones being aldosterone
which is a mineralocorticoid regulating blood pressure, and cortisol, a glucocorticoid representing primarily blood glucose concentration.
The main hormone from the adrenal medulla is adrenaline,
which has important physiological roles and can be clinically very serious if you have too much of it.
But in normal physiological situations, it’s not essential for life.
*Adrenals have different functional regions: cortex (x3) and medulla
*Aldosterone = main mineralocorticoid; regulates ion absorption
*Cortisol = main glucocorticoid; regulates stress response, metabolism, immune function, inflammation etc
*Adrenal sex steroids have subtle effects cf gonadal steroids
*Adrenaline & noradrenaline regulate sympathetic response to stress
