hello and welcome to the review of chapter 78 of guyton hall's medical physiology textbook in this chapter we're going all over the adrenal gland and then also the adrenocortical hormones if you enjoy the chapter please don't forget to give it a like and subscribe to the channel so let's jump straight into it our adrenal glands are located at the superior poles so just in front of the two kidneys and we have two major parts we've got the adrenal medulla in the middle so outlined in the blue in this figure and then also the adrenal cortex
now the adrenal cortex can now be separated into three separate layers so going from the outside in we have the zono glomerulosa which produces aldosterone we've got the zona fasciculata which mainly produces cortisol and then we have the zona reticularis which mainly produces androgens so these hormones so aldosterone cortisol androgens these are all corticosteroids meaning that they are synthesized from cholesterol so these corticosteroids are synthesized from cholesterol the zona glomerulosa which mainly produces aldosterone the other molecules that are produced here called mineralocorticoids and they affect electrolytes the fasciculata layer produces our glucocorticoids meaning that they
increase blood glucose and then the reticularis mainly does androgens which are all sex hormones so if we go into how they're actually formed a little bit they're formed from ldl so low density lipoproteins and the important part here is although cholesterol is used for all of these hormones and the first step in turning cholesterol into one of these steroid hormones is actually converting it into pregnant alone now this reaction is a rate limiting step and this occurs for every single steroid hormone despite the layer now each layer has its own regulatory mechanism for increasing the
synthesis of the hormone from cholesterol and what i mean by that is that for instance if aldosterone needs to increase angiotensin ii will result in an increase in the slow rate limiting step to turn cholesterol into pregnenolone which will then go on to convert into aldosterone whereas in the zona fasciculata cholesterol will be converted into pregnant alone not by angiotensin ii but by acth which increases the sensitivities of cortisol so remember each layer has a big store of cholesterol but they're each independently waiting for their own stimulatory effect to convert cholesterol into either aldosterone cortisol
or androgens now there are multiple mineralocorticoids or steroid hormones that have mineral corticoid effects so aldosterone's the main one but we have deoxy corticosterone corticosterone cortisol and then lastly here cortisone which has very minimal mineral corticoid activity whereas we've got glucocorticoids which if you can go in the reverse of mineralocorticoids we've got cortisol which is very potent same with cortisone and then we've actually got some synthetic drugs which we actually give as steroids prednisone which is four times as potent as cortisol our endogenous steroid and then methylprednisone which is even more potent and then lastly
here the injectable steroid here dexamethasone which you'll see on the clinic floor is highly potent 30 times more potent than cortisol and it has almost no mineral corticoid effects whereas prednisone does have some mineral corticoid effects so there is a little bit of overlap with these two although on the whole glucocorticoids have their own effects and their mineral corticoids have their own effects and they're in separate layers and they're regulated by completely separate mechanisms now the glucocorticoids are bound to proteins within the plasma which means that there is a slow release is slowly degraded whereas
aldosterone is less protein bound only only about 60 percent is protein bounds so they have a shorter half-life and then once these steroids get to the liver that's where they're broken down so they're broken down to be either eliminated in the feces or most of them in the kidneys via the urine so we'll start off with the mineral corticoids so aldosterone is our main one here and we've talked about this more in our renal unit and also some in the circulatory unit as well talking about aldosterone so without aldosterone we actually end up with death
within kind of three days to two weeks and we'll kind of get into exactly why that is so aldosterones or mineralocorticoids their role is to actually increase the secretion of potassium and also hold on to more sodium and water within the body so the two main factors that are going to increase our aldosterone level are angiotensin ii because of the renin-angiotensin aldosterone system and if you have forgotten about that it's going to be too much to go through the entire process during this chapter i do encourage you to go back into the renal chapters to
refresh yourself about that but really the rest system is a major stimulatory effect for our aldosterone so angiotensin ii and also high potassium because aldosterone is going to go to the renal tubular cell and then cause increased secretion of potassium in the principal cells of the collecting tubule and then also hold on to more sodium water so the rest system gets activated whenever we have low blood pressure or also or low blood volume low sodium content then we're going to want to increase our blood volume by holding on to sodium and water so without mineralocorticoids
or without aldosterone what do you think is going to happen well we can't hold on to sodium and water anymore so now we're going to actually excrete more sodium in water than what we want so our blood volume is actually going to reduce and then we also can't excrete our potassium so then potassium levels are going to increase so we end up with hyperkalemia meaning high potassium which can cause arrhythmias and big cardiotoxin can cause heart issues and then we also have low blood volume so we actually end up in a cardiogenic shock state because
we don't have blood volume to be pumped around the body so this is the critical portion that is actually why we end up with death quite shortly if you don't actually treat this so mineral corticoids are extremely important in the acute period to prevent death through cardiovascular shock just because of a low blood volume whereas if you have excess aldosterone what's going to happen you're going to hold on to a lot of sodium and water so then you're actually going to increase your blood volume your sodium osmolarity doesn't increase because you're also absorbing water and
also as you increase your blood volume your your blood pressure is going to increase which then does pressure nitrosis and also pressure diuresis so actually equilibrate how much sodium and water gets absorbed and excreted but at the cost of being hypertensive so you have hypertension and then also with excess of aldosterone you're going to be secreting too much potassium so then you end up being hypokalemic meaning that you have low potassium that means that you become weak as it becomes quite hard to stimulate an action potential prolongs the action pitching dual duration and so their
muscles become weak as well so you get hypertension and weakness with hypokalemia and retaining so much sodium and water so that is the clinical scenario with too much mineral corticoids another consequence of too much aldosterone is actually the increased secretion of hydrogen ions via the intercalated cells so then you actually lose too much hydrogen in your urine so that you end up in a metabolic alkalosis state now another function of aldosterone is actually getting rid of potassium in sweat and also absorbing sodium and water from your gastrointestinal system mainly your colon so as you can
imagine too much aldosterone you end up losing too much potassium in your sweat whereas with not enough aldosterone another influence is that you're also poorly absorbing sodium reabsorption in the intestines you end up with diarrhea which further loses more sodium chloride and water so propagating that problem with low aldosterone of having a low blood volume and that's why you end up in circulatory shock so how does aldosterone actually work it's a lipid-soluble molecule remember it's a steroid coming from cholesterol so then it actually diffuses into the interior of the epithelial cells of the renal tubule
now it interacts with the mineralocorticoid receptor which binds to it and then that bound complex goes into the nucleus and then stimulates the production of mrnas which go on to translate into certain proteins now it gets a bit unclear here the mechanism is a little bit unknown but it seems like it increases the expression of the sodium potassium pump on the basolateral surface membrane so then you end up with increased potassium within the cell lower sodium within the cell so then sodium wants to be reabsorbed from the tubular lumen into the cell and the high
potassium within the cell is promoted to be secreted it also seems to increase the production of the sodium transporter on the luminal membrane so really help with the transport of sodium into the cell so ultimately it goes into the cell has a cytoplasmic receptor that then increases transcription within the actual cell itself now it seems like it probably also has non-genomic effects meaning that it doesn't influence the genes and some of its effects because it does seem to increase cyclic amp which we know as a secondary messenger for other effects but these mechanisms are not
well understood so getting into the regulation of aldosterone we've already talked about the main two which is the increased potassium ion concentration increases aldosterone secretion in addition to increased angiotensin ii concentration now if there is an increased sodium ion concentration then there may be a slight decrease in aldosterone because you don't need to retain any sodium in the more and then if there is a secretion of acth that does have a very small effect in the secretion of aldosterone but it has a more permissive role meaning that you need acth to allow aldosterone to be
secreted but purely increasing acth doesn't instantly increase aldosterone it's just needed to be there in order for aldosterone to be able to be secreted and produced so that means if you have no acth then you'll have no aldosterone and you'll end up with hypoaldosteronism but if you have acth you will have aldosterone being able to be synthesized and produced for these other reasons so it's more of just a permissive role and it's just needed in order for it to be produced in the first place so that's really talking about the mineralocorticoids so next up is
talking about the glucocorticoids now glucocorticoids this includes our cortisol corticosterone and then synthetically as protozoan dexamethasone now these guys have four major roles for influencing the animals metabolic system so we have a major role with carbohydrate metabolism major role in protein metabolism fat metabolism and then lastly it has a great immune role as well for anti-inflammatory effects and the thought process here as a general principle is that glucocorticoids want to mobilize all of your precursors so then you have a lot of precursors in your bloodstream meaning a lot of glucose in your bloodstream amino acids
in your bloodstream a lot of fats in your bloodstream ready to be mobilized to areas that need to recover or need energy instantly so the whole point of glucocorticoids is the stress hormone as soon as a stressful event occurs cortisone or cortisol gets released suddenly you're getting all this glucose amino acids lipids in your blood ready to go to wherever it needs for whichever function is required and then the immune function is to dampen the harmful pro-inflammatory effects from any sort of trauma so that's a brief overview so when it comes to carbohydrate metabolism we're
going to increase our blood glucose so it does that by having a genomic effect on the liver cells to actually produce proteins and enzymes to convert amino acids into glucose so we get a lot of gluconeogenesis in the liver it also does that by antagonizing insulin effects which is going to tell the liver to do the opposite so it's going to stop the liver to do gluconeogenesis so it inhibits insulin increases the proteins required for the liver to do gluconeogenesis and then it also mobilizes amino acids from extra hepatic tissues and we'll get to that
as well with the protein metabolism portion so because of all of this we're producing a lot of glucose and since we've also antagonized insulin or produced a little bit of insulin resistance we now have less glucose uptake by our tissues so ultimately we can end up in this adrenal diabetic state meaning that we have this relative insulin resistance we have high blood glucose it's not responding to the insulin because the cortisols getting all that glucose ready for whichever stressful event is occurring so when it comes to protein metabolism as we've already preluded to protein metabolism
is altered by glucocorticoids by actually increasing the amount of amino acids within the blood so then their liver has more amino acids to convert into glucose and those amino acids can also be converted into proteins and areas that are required for protein synthesis but really ultimately all of the cells in the body except for the liver protein synthesis is reduced and there's increased catabolism of the proteins in the cells so we're really liberating all the proteins putting all the cells on hold in terms of synthesizing proteins getting those amino acids up in the body and
then also allowing the liver to also produce its own protein so plasma proteins actually remain the same if not increase while this other cells extra hepatic cells lose their proteins and there's also a conversion of those amino acids into glucose and then lastly here in terms of metabolism we got effects on fat metabolism so fatty acids from adipose tissue get mobilized so then we end up with more free fatty acids in the blood that fatty acids are actually going to be promoted to be used as the primary energy source to then have a conservation of
our blood glucose and glycogen so then we have free fatty acids and a stressful event for energy utilization now with excessive cortisol for a long period of time ironically there's actually increased adiposity within certain regions so as you get fat deposits forming in particular sites so such as in people the chest and head regions and in dogs they often get a little muffin top over their pelvis it seems to be due to an increased food intake because once you if you've ever been on steroids yourself then you do get increased hunger you know you can
think of it as trying to increase those precursors are in the blood ready for a stressful event which is what the steroid hormone does in the body so cortisol just gets released during any of these stressful events there's a little list of it here trauma infection intense heat cold surgery etc etc just mobilizing these tissues getting them ready to be used if needed now we also have this fourth role on the immune system where it has an anti-inflammatory effect and they give a nice little precursor about inflammation before going into the anti-inflammatory effects to talk
about inflammation itself so remember inflammation starts off with the damage of cell tissues releasing pro-inflammatory chemicals which includes bradykinin histamine prostaglandins leukotrienes which then result in an increased blood flow to the area increased permeability of the capillary so there's leakage of plasma out also attracts leukocytes to the area and allows them to leak out to the damaged tissue and then eventually fibrous tissue starts to form as well now the there is an issue with inflammation where it can cause excessive damage than the actual trauma itself so too much inflammation or pro-inflammatory states are actually damaging
so steroids help to have an anti-inflammatory effect and prevent that from actually spiraling out of control and that even if inflammation has started steroids are still able to stop that process in its tracks and also really reduce the inflammation that's present and it does that through these five main mechanisms here so number one is stabilizing lysosomal membranes so stabilizing the membranes that have all these pro-inflammatory enzymes within the proteolytic enzymes which will get released and cause the damage cause the increased permeability of the capillaries and promote inflammation so that leads into the second effect which
is reducing the permeability of the capillaries mainly by preventing those proteolytic enzymes from being released its third effect is through the reduction and migration of white blood cells to the area fourth is the suppression of their immune system mainly actually t lymphocytes so they actually suppress t lymphocytes specifically and then fifth is actually reducing fevers by actually preventing the release of interleukin-1 which helps to actually promote a fever so then overall cortisol has this great short-term effect of mobilizing all of our precursors or our nutrients getting fatty acids in the blood for energy utilization glucose
in the bloodstream amino acids in the bloodstream and then having these anti-inflammatory roles to prevent excessive inflammation of our tissues so short term this is all great but you could think about long term issues of this uh dramatic you know you don't want to be breaking down your proteins creating a lot of glucose in your liver having altered fat metabolism and you don't want to be too anti-inflammatory for too long or else you end up being immunosuppressed so excessive cortisol is definitely bad short-term cortisol is obviously used for us who wouldn't have it so cortisol
can also be used in allergic reactions and the main thing behind this is that you're not actually stopping the antigen from binding to the antibody you're just stopping that inflammatory process after that so you're stopping the serious potentially tissue damaging fatal consequences of an allergic reaction and since cortisol is a steroid and remember it gets into the cytoplasm interacts with the receptor then causes gene transcription translation etc the effects and other it takes about 45 to 60 minutes for the proteins to be synthesized for the role of glucocorticoids so now we get to the regulation
of glucocorticoids and it mainly comes from acth so aldosterone is mainly throughout geotension2 high potassium whereas glucocorticoids is through acth also known as corticotropin or adrenocorticotropin now acth is produced by the anterior pituitary gland and it is stimulated to be released from the hypothalamus so just like our other hormones we have this kind of double system so hypothalamus it's linked closely to the limbic system in areas which will sense any stresses once stresses occur in the body they're going to stimulate the hypothalamus to then produce corticotropin releasing factor that then ends up in the anterior
pituitary gland that stimulates the production of acth into the bloodstream ac th goes the adrenal cortex and then stimulates release of cortisol cortisol then causes these major effects so gluconeogenesis increased glucose protein mobilization fat mobilization and then anti-inflammatory effects and then also has a negative feedback on itself now cortisol actually inhibits both the release of acth and also corticotropin releasing factor crf so this negative feedback helps to prevent the spiraling out of control and this kind of relates also to any defects that causes an increased cortisol you can have an issue where you have a
tumor in your adrenal cortex that is producing too much cortisol or you can have a tumor in the anterior pituitary or the hypothalamus which can obviously downstream result in the increased cortisol now one of the main differentiators between these either central meaning hypothalamus or anterior pituitary with the pituitary being the more common one versus primary hyper adrenal corticism and the adrenal gland producing too much cortisol due to a tumor on it all of these are going to have high cortisol but only the primary problem of the adrenal cortex is going to inhibit acth formation whereas
these guys the central hyperadrenal corticism diseases are going to have a high acth in the bloodstream which is stimulating the excess cortisol you can kind of diagnose that either by testing endogenous acth which is also not perfect just as every test is not 100 perfect but you can also give dexamethasone as a suppression test to see if you're able to suppress the acth that's being formed so you can give dexamethasone to see if you're able to suppress the production of cortisol by suppressing acth and that helps to differentiate which kind of problem you have here
obviously you can do an abdominal ultrasound to see if there's a mass on the adrenal gland you can do mri sort of for masses in the brain you can also end up with hydrogenic hyper adrenocorticism by giving too much steroids for another problem and hyperadrenal corticism meaning high cortisol in the body or high glucocorticoids is called cushing's syndrome which we are jumping a little bit forward here but cushing syndrome results in increased protein metabolism muscle weakness local adiposity where you start to accumulate fat deposits in certain regions you end up with fatty livers you end
up with that insulin antagonism increasing the glucose production in the liver and then you also end up with immunosuppression so you can get life-threatening infections now before going into more abnormalities of the adrenal system there is a little bit about pomc or pre-opio melanocortin now this molecule pomc is a pre-pro hormone that gets produced whenever the th gets synthesized just because it's right next to the gene for acth now in the normal body it doesn't really matter it doesn't do much but if there is high expression of acth you will get high expression of pomc
which can result in increased melanocytes stimulating hormone or msh all these other molecules like beta lipotropin beta endorphin essentially this may result in increased melanin deposition now in some animals they actually have a large pars intermedia which produces a lot of this msh or melanocyte stimulating hormone because they may be in arctic regions when they want to actually sense the light produce less melanin to become a lighter color and then when there is no light produce more melanin to become darker color and then there's a little portion here about adreno androgens there is a whole
chapter on it further on but essentially these are the six hormones that can that are produced by the adrenal cortex you know there's some progesterone estrogen produced here and then the other androgens goes off and gets converted into testosterone and extra adrenal tissue such as the testes so some disorders of the adrenal cortical system we have hypoadrenalism which is addison's disease so we've already talked about this edison's disease is adrenal insufficiency you can get that either because of lack of acth which means you will not have any mineral corticoids or glucocorticoids or due to an
autoimmune condition against your adrenal glands so once again the same thing will occur due to that your mineralocorticoid deficiency will result in a pretty life-threatening circulatory shock and then also hypokalemia glucocorticoid deficiency will result in a difficulty in maintaining blood glucose concentrations weakness etc and then being susceptible to any stressful event since you can't respond to it the life-threatening mineralocorticoid deficiency needs to be treated first and then you just maintain them with drugs going forward and then we've talked about cushing's syndrome now just do youtube policies we won't be able to look at the next
page here but there is just a little bit about cons disease as well so cohn's diseases hyperaldosteronism just meaning increased aldosterone due to a mass on the adrenal gland we've already talked about this this is going to cause hypertension hypokalemia so that's the end of the chapter i hope you enjoyed it now here's some questions for you number one list the layers of the adrenal gland and the hormones produced in each layer two what is the two main consequences of low aldosterone and then three list four functions of cortisol so that's the end of the
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