okay so we're going to be discussing the second learning objectives for the endocrine lecture uh we'll be talking about the adrenal glands and their hormones um we'll be discussing the stress the short and long-term stress response uh we'll describe the rast system and the heart hormones are involved in blood pressure regulation and describe the anatomy of the pancreas as well as the hormones that it makes and and also state the location and function of the pineal gland and thymus gland so all these we'll be discussing if we we could start with the adrenal glands those are called super renal but adrenal glands um you can see there's a left and a right they have their own blood supply from the abdominal aorta the model you can appreciate this left adrenal right there and right there is your right adrenal if you were to zoom in right here you could actually see an artery going towards the adrenal gland the left one and here you could also see it as well a little harder to see the gland itself because its cadaver is kind of dried up you can appreciate the right adrenal gland there and the left adrenal gland there and you can see the adrenal artery going toward the left on the left side now the adrenal gland is divided into the cortex and the medulla and we'll be discussing those in regards to the hormones that they make and what stimulates them and the targets and the effects of those hormones so we'll start off with the video and then we'll come back and jump into the adrenal gland the organs of the endocrine system secrete hormones directly into the bloodstream to assist in the regulation of various body functions the endocrine glands discussed here are the supra-renal glands the paired supra-renal or adrenal glands are pyramid-shaped endocrine glands located on the superior pole of each kidney these glands receive a rich blood supply from multiple arteries and are drained by a single supra-renal vein the super-renal glands are composed of an outer cortex and an inner medulla the cortex synthesizes more than 25 steroid hormones known collectively as corticosteroids the cortex consists of three layers the zona glomerulosa is the thin outer layer its cells synthesize mineralocorticoids a group of hormones that help regulate electrolyte composition and concentration in body fluids the principal mineralocorticoid is aldosterone which helps regulate sodium and potassium ions in the blood and body fluids the zona fasciculata is the thick middle layer of the cortex it is composed of lipid-rich cells that secrete glucocorticoids these hormones stimulate metabolism of lipids and proteins help regulate glucose levels in the blood and play a role in decreasing inflammation the most common glucocorticoids are cortisol and corticosterone the zona reticularis is the deepest layer of the cortex its cells are arranged in irregular cords and produce adrenal sex hormones including weak androgens and small amounts of estrogens the inner core or medulla of each supra-renal gland consists of large clusters of chromatin cells when stimulated by sympathetic neurons of the autonomic nervous system the medulla secretes the hormones epinephrine and norepinephrine as these hormones circulate they initiate multiple systemic mechanisms that contribute to the body's fight-or-flight response so if we were to uh cut the medulla we would see that it's composed of two layers right you can see it's surrounded by a fibrous capsule most organs have a fibrous capsule connective tissue that surrounds them like the kidney the adrenal glands we could also see that this layer here is good is the cortex and then we could easily distinguish the inner layer of the medulla itself now the cortex is further divided into the gfr the glomerulosa the vesiculata and the reticularis you can see those layers here right you can appreciate you can appreciate the cortex and then the medulla you can see it's divided into the gfr the glomerulosa vesiculata reticularis um and then you've got to appreciate the name of the cells that are found in the medulla those are called chromatin cells now who stimulates the adrenal cortex right so the cortex itself all this especially the first layer is glomerulus of fasciculata are stimulated by acth right adrenal corticotropic hormone that's coming from the anterior pituitary which is regulated by the hypothalamus who stimulates the medulla or at least who simulates the chromatin cells that are found in the medulla well it's not a hormone it's going to be sympathetic innervation as we can see here the third function of the hypothalamus in regards to endocrine sympathetic innervation to the adrenal medulla and then those axons will synapse on those chromatin cells and cause secretion of epinephrine norepinephrine uh which also referred to as adrenaline noradrenaline now if we take a look at the table right so you can appreciate there's three layers in the cortex and then we have the medulla we can start off with the glomerulosa the category is called mineral corticoids there are many uh mineral corticoids aldosterone is one we got to worry about aldosterone targets the kidneys and that increases renal reabsorption of sodium and water especially in the presence of adh and accelerate urinary loss of potassium so always remember that aldosterone will work on the sodium channels of the renal tubules and where when when it reabsorbs the sodium it passively takes in the water with it so it reabsorbs sodium primarily and then takes passive water reabsorption with it uh it is stimulated the glomerulosa by as you can see by angiotensin ii which is that hormone which we've been talking about that's involved in blood pressure regulation which is coming up soon elevated plasma potassium or a full plasma sodium and it's inhibited by amp and vip which are two heart hormones which we'll be discussing uh coming up very soon as well so the fasciculata is the glucocorticoids that's the category uh the type of hormones that we find there there are there's many but the three that indicate is cortisol hydrocortisone and corticosterone now this targets most cells uh it's hormonal effect it says releases amino acids release amino acids from skeletal muscles and lipids from adipose tissue promotes liver formation of glucose and glycogen promotes peripheral utilization of lipids and has an anti-inflammatory effect so and appreciate that this layer is also mainly stimulated by acth which also stimulates the glomerulosa which they left kind of that out but you can see glomerulosa is stimulated by many more things uh acth again that's the hormone that we talk about coming from the anterior pituitary which stimulates your adrenal cortex here specifically they're showing you the production of glucocorticoids protocol corticosteroids for example and again uh that's what they're showing you here the reticularis is also stimulated by acth here you're secreting some androgens a little bit of weak estrogens smaller amounts i mean um and not important in adult men but it does encourage bone growth muscle growth and blood formation in children and women so it is important uh whether you're a male or female usually you get your testosterone from your testes estrogen for your ovaries you could get some of both from here whether you're a male and female but the majority of it is coming from utestes or ovaries when it comes to sex hormones and then the medulla you can see it says epinephrine norepinephrine are the two they're going to be secreted by those chromatin cells which you got to know the name remember you don't know all the cells names that we've discussed and this targets most cells uh hormonal effect increases cardiac activity thus increases heart rate blood pressure increases blood pressure glycogen breakdown which we'll be discussing when we talk about in the pancreas um blood glucose levels will also fluctuate releases lipids by adipose tissue um but again we think of this as an adrenal rush that's where we think about increased heart rate increased blood pressure when we are involved in a fight or flight response that's the sympathetic nervous system it says stimulated by during sympathetic activation uh by the sympathetic preganglionic fibers they synapse into the adrenal medulla stimulating those chromatin cells so again that is the short-term response to stress which is the sympathetic innervation to the adrenal medulla stimulating the epinephrine now this table here is kind of showing you the same thing in regards to it just tells you the category and the hormone doesn't really get into the effect so let's talk about the first layer of the glomerulosa remember this layer is the categories mineral corticords the primary hormone is aldosterone i'm sharing the right thing is aldosterone targets the kidneys specifically it targets sodium channels in the kidneys that will reabsorb sodium and passively reabsorbs water uh it also accelerates the loss of potassium into the urine again we talked about what are the regulatory controls what stimulates its uh release versus what inhibits it so again if we take a look here um aldosterone opens up sodium channels in the for now you don't need to worry about where or what is the nephron because we'll deal with that in the kidney but it's in the distal convoluted tubules of the nephrons of the kidney it opens up sodium channels re-absorb sodium chloride as well as takes water in with it again passive reabsorption elimination of potassium ions and hydrogen ions as well again drop in sodium a rise in blood potassium blood volume or blood pressure and geotension ii acth are are things that could stimulate its release and again they're showing you here that it reabsorbs sodium chloride in water and excretes potassium and hydrogen ions in the kidneys now if you have too much secretion of aldosterone that's going to be a problem as you can see the adrenal cortex the globulosa with aldosterone being released it can be stimulated by angiotensin ii acth sympathetic innervation can also stimulate its release also like we said a decrease in sodium and increase in potassium levels in the blood can also cause uh release of aldosterone you know that once aldosterone gets released it increases sodium and water reabsorption and potassium excretion at the kidneys thus this increases blood volume and blood pressure right so always remember that aldosterone just like adh which is that antidiuretic hormone by suppressant both of them influence the blood pressure in this case uh aldosterones influence the sodium channels passively reabsorbing water with it again increases blood volume that's blood pressure you could see that if you have too much production of aldosterone um you don't need to worry about the pathology again but appreciate overproduction of aldosterone can lead to hypertension hypertrophy you know this lipidemia endothelial dysfunction because of the hypertension um inflammation oxidative stress so again you got to maintain normal levels too much of this hormone can cause a lot of problems specifically we think of the hypertension because its ability to raise blood pressure now if we look at the second layers of fasciculata this is where you find the the category is glucocorticoids cortisol corticosterone hydrocortisone are examples and we normally sometimes we use uh steroid creams or even steroid injections in a clinical setting uh again that's the why do we take those to decrease inflammation where we have too much inflammation going on we use glucocorticoids uh synthetically but we also make them right um on the normal circumstances we're secreting the normal amounts uh they're really important because you can see not only they're stimulated by acth which is adrenal corticotropic hormone from the anterior pituitary but their effects are important it affects the metabolism of lipids and proteins and especially carbohydrates right so they're extremely important and again they have that anti-inflammatory effect especially at higher doses now secretion is regulated by negative feedback inhibition of the hypothalamic pituitary adrenal axis so what they're talking about is this right again you can appreciate because hypothalamic meaning the regulatory hormone is corticotropin releasing hormone stimulates the pituitary gland to release adrenocorticotropic hormones specifically the anterior pituitary that goes into the blood and stimulates the adrenal cortex specifically the glomerulosa in the cortex to secrete cortisol or all the other corticosteroids same thing they're showing you here it's called the hpa access again this is important for production of cortisol you can see cortisol once higher levels will um be secreted this will inhibit its own production again through that negative feedback inhibition that we spoke about earlier and again just to go over some of the effects again it causes release of amino acids from skeletal muscle so we're breaking them down lipids from adipose tissue uh promotes liver formation and glucose and glycogen promotes peripheral utilization lipids and anti-inflammatory effects remember it also has a profound effect under the glucose right because it promotes liver formation of glucose and glycogen and we already said stimulated by acth it's involved in hpa axis now this axis is important also for um long-term stress response which we'll be talking about in a second um because if the overproduction of cortisol when we're when the brain is stressed uh cortisol higher levels of cortisol will have a negative impact probably more destructive than aldosterone in the uh on the organs in the mind and the brain and the body so you could see again this is just showing you it's negative feedback once you the cortisol is being produced it goes back after a certain a level has reached and goes and inhibits its own production at the hypothalamus and at the pituitary level now too much overproduction of glucocorticoids is not good because as you can see causes a lot of problems uh from cardiovascular uh you know it promotes atherosclerotic plaques hypertension skeletal muscle uh atrophy um lip and glucose homeostasis is unbalanced so you could your glucose levels will go up you know you get diabetes uh adipose tissue is also influenced bones are influenced by cortisol too much of that could cause osteoporosis uh it suppresses your immune system because remember glucocorticoids like cortisol have an anti-inflammatory effect so too much of it will suppress your immune system and that could lead to problems like autoimmune diseases to develop if you're predisposed and there's an environmental trigger but also infections cancer right because your immune system is important for regulating that and controlling that and if you're suppressing your immune system that could also lead to issues again that's what they're showing you here again you don't need to worry about the pathology just get a good understanding of it and the reticularis is the third layer of the adrenal cortex uh and those cells are called chromatin cells oh sorry we're saying reticularis and those no cells are secreting androgens and some uh small amounts of estrogens under the stimulation of acth these androgens that are being produced here also are important because they stimulate and control the development and maintenance of male secondary sexual characteristics uh like the atoms apple cubics here stuff like that the adrenal medulla is where you find the chromatin cells and these chromatin cells are not stimulated by a hormone but they're innervated by the [Music] postganglionic fibers of the sympathetic nervous system uh causing a secretion of epinephrine norepinephrine you scream more epinephrine than the norepinephrine again adrenal and noradrenaline together these hormones are called catecholamines now remember norepinephrine can act as a neurotransmitter that's in the brain in the central nervous system in the blood it can act as a hormone such as when it's created from the adrenal medulla again epinephrine epinephrine are referred to as catecholamines again there's your third function as that sympathetic innervation to the adrenal medulla which we talked about which is the uh the fight or flight response uh which is our first initial stress response again referred to as a structure and stress response when you release all that adrenaline which is that all that epinephrine and again once you release that adrenaline or that epinephrine norepinephrine those catecholamines into the bloodstream that is what causes increased cardiac activity blood pressure will rise glycogen breaks down certain increases sugar levels uh glucose levels in the blood uh and also releases lipids by adipose tissue but again the cardiovascular response is what gives you that adrenaline rush again this is a response to the sympathetic fight or fight uh stress response now there's a video you can watch on your own on adrenal glands hormones which we discussed let me briefly just describe the stress response again there's a short term and a long-term stress response we kind of went over both of them right now stress can be positive stress for example no when we're first day of school work we get a little anxiety so we're kind of stressed out that's you know positive stress we all need some good positive stress so we can learn how to cope with the world tolerable stress you know it's a little heavier on you it takes a little toll on you running most of the family member stuff like that grieving versus toxic stress this is really not good right this is a very uh causing a lot of problems and long-term toxic stress will cause a lot of hormonal problems through the apa uh adrenal the accident system that we were talking about before in regards to releasing the cortisol and stuff like that and things like that will be like domestic violence at the home and stuff like that now just to show you that example right so here's the two here's a short term and long-term stress response right short term is the sympathetic innervation to the adrenal medulla coming from the hypothalamus that's the adrenaline rush right once epinephrine gets released into the bloodstream again that glycogens break down to glucose your glucose levels rise increase blood pressure increase breathing rate your respiratory will go up increase metabolic rate uh so now if you have long-term response to stress this is chronic stress especially we're talking about toxic stress that can really be damaging because now you're involving the hormonal response which is basically uh the apa x the access system right which we discussed over here just to go over which is right here the hpa access right if you're if your hypothalamus your brain is chronically stressed out this action system you're making a lot of cortisol corticosteroids right and also stimulating uh not only cortisol released but aldosterone from the cortex as well and that's what we see here and this in this case is showing you that right here they're showing that you're chronically stressed out uh that hypothalamus secretes that regulatory hormone which goes and stimulates acth production and the anterior pituitary and release from there i remember that's made there release from there but influenced by the hypothalamus then that goes into the bloodstream and causes the cortex to start secreting mineral corticoids in the glucocorticoids again we think of aldosterone we think of cortisol you know if we think of a mineral cortisol like aldosterone well what does that do well it's going to increase sodium ion and water by the kidneys reabsorption that increases your blood pressure so it could give you that you know hypertension the glucocorticoids those cases we think like cortisol right so too much cortisol production uh will suppress your immune system as you can see here so you could develop hypertension um you know you could develop diabetes you get immunosuppressed because you're chronically uh secreting these glucocorticoids you develop cancer infections uh cardiovascular disease atherosclerotic plaques which predis position but which accelerates that kidney failure so there's a lot of problems that you could develop from chronic long-term stress which is due to the hypothalamic uh hpa access right the hypothalamic pituitary adrenal access hpa access uh thus you're not only stimulating a lot of glucocorticoids but you're also stimming a lot of mineral coral cords and these things could have a devastating impact chronically short-term response again we mentioned is mainly through adrenal to the medulla through sympathetic innervation and you can see that we discussed these uh what happens when you release norepinephrine epinephrine and there's a short video we could watch real quick on this it's only a minute but does a great job with animation the stress response in stressful situations the body switches on its autonomic nervous system and neurobiological processes in an attempt to maintain homeostasis the body is prepared for its reaction to stress in the brain the hypothalamus is connected to the pituitary gland the hypothalamus stimulated by the sympathetic nervous system releases the hormone corticotrophin releasing factor crf the crf activates the pituitary gland release the adrenocorticotrophic hormone acth this in turn alerts the adrenal glands the adrenal glands are located on top of each kidney the acth from the pituitary gland stimulates the adrenal cortex to release cortisol at the same time neurons in the hypothalamus signal the medulla to release epinephrine adrenaline and norepinephrine nor adrenaline these hormones then push the body into hyper alertness all right so let's go back to the lecture so again that video basically kind of talked about both of them combined i didn't break it down like i said sympathetic innovation to the general maduro but they mentioned through the sympathetic response that's what happens again stress response leads to uh excessive production of the regulatory hormone uh the corticotropin-releasing hormone which thus stimulates acth production and increases secretion of that and thus that increases mineral corticoid and glucocorticoid excessive secretion into the bloodstream again and you can see the effects of that on the body now let's talk about something in regards to blood pressure so long-term regulation of blood pressure is regulated by a hormonal system called the renin-angiotensin aldosterone system so this long-term hormonal regulation of blood pressure called again the renin angiotensin aldosterone system uh is involved in this pathway that we see here right so if your blood pressure falls this pathway kicks in to help regulate or raise your blood pressure back to normal so again uh and there's a typo here i like the diagram but there's one typo random this hormone is coming from the kidney not your adrenal gland it says here but you can see that over here the arrow is pointing to the adrenal gland again renin is coming from the kidney uh that's where it's coming from make sure you know that so just to go over this diagram and show you what's happening uh they're showing you that the kidney is here kidney produces a hormonal renin why is delivery here because the liver produces plasma proteins uh and angiotensinogen is an example of a plasma protein it has a function in this case it's involved in the rash system the raa s system again standing for renin angiotensin aldosterone system why is the lungs and kidney here because there's an enzyme called ace which is called angiotensin converting enzyme the name is a little ahead of time and the next slide has the name in it uh an ace enzyme is made in the endothelial by the endothelial cells of the vasculature of the mainly in the lungs make sure you know that mainly in the lungs also the kidneys but also in the brain and some few other organs that's why they show you the kidneys and the lung hair mainly the lung that's where it's coming from so what happens is that when when blood pressure falls for whatever reason the kidneys will respond by releasing renin which is a hormone and renin is going to go into the bloodstream and it's going to convert angiotensinogen to angiotensin 1. what happens right remember this is in the blood already so once you get angiotensin 1 the ace enzyme ace which stands for angiotensin-converting enzyme converts angiotensin 1 to angiotensin ii so this is where we find that angiotensin ii that we've been talking about right and we said that that remember remember i said that's an example of one of the things that stimulates adh secretion also aldosterone from the cortex of the adrenal gland so this is where it's at right so you get it because of the renin uh angiotensin aldosterone system so once renin gets secreted converts angiotensinogen to one one gets converted to two because of the ace enzyme once you have angiotensin ii this is the major player in regards to helping you raise that blood pressure back to normal so you can see that it stimulates adhd secretion from the posterior pituitary we know that's made in hypothalamus but it's stored and released from the posterior pituitary and there's angiotensin ii stimulating and secretion we know once it goes into the blood this is the kidney tubule and they're showing you that it stimulates water reabsorption at the kidney tubules it opens up water channels so it raises your blood pressure right we're trying to raise your blood pressure back to normal because it has fallen what else does angiotensin ii does well it's a potent vasoconstricted by itself so it helps raise your blood pressure don't forget adh is also a potent vasoconstrictor which there should be an arrow going that way too so not only is angiotensin ii or vasoconstrictor remember adh is a vasoconstrictor uh angiotensin ii will promote or stimulate aldosterone secretion for the adrenal cortex what happens when aldosterone gets secreted well this is the kidney tubule they're showing you what happens sodium channels open up and reabsorb sodium water goes passively with it and you excrete potassium and chloride goes in with it as well again the sodium channels is what it targets and white reabsorbing sodium to reabsorb water and that helps raise your blood pressure and it also stimulates sympathetic activity because when we learn in the cardiovascular system the smooth blood vessels of the arteries are innervated by sympathetic nervous system and if you stimulate that that causes vasoconstriction and this will come up again in the urinary lecture as well let me show you a video on this and then we'll come back to it now this video will go into a little some some alternative pathways but then it goes back and talks about adh and aldosterone so you don't need to know the alternative paths but definitely note this basic diagram that we see here let's watch this video renin angiotensin aldosterone system the renin-angiotensin-aldosterone system is a classic endocrine system that helps to regulate long-term blood pressure and extracellular volume in the body the system begins with the release of angiotensinogen into circulation by the liver this may be in response to low blood pressure and adverse changes in sodium concentrations an enzyme renin is secreted which cleaves angiotensinogen to form the inactive decapeptide angiotensin one now renin is a hormone it acts as an enzyme but it is a hormone made by the kidney transformation of angiotensin is carried out by angiotensin-converting enzyme or ace this is predominantly found in the pulmonary circulation however ace is also produced in the vascular endothelium of many tissues including the kidney adrenal gland brain and heart the angiotensin converting enzyme converts the inactive precursor angiotensin 1 into the vasoactive peptide angiotensin ii in addition alternative pathways exist that do not rely on either renin or ace in non-renin pathways enzymes like tonin and cathepsin release angiotensin 1 from angiotensinogen and tissue plasminogen activator or tpa and can make angiotensin 2 directly from angiotensinogen this bypasses the midway production of angiotensin 1. enzymes like kinase can form angiotensin ii from angiotensin 1 via an ace independent pathway angiotensin converting enzyme also degrades bradycainen which is required for synthesis of a major vasodilator nitric oxide angiotensin ii binds at1 receptors expressed on the surface of vascular endothelium and impairs nitric oxide synthesis as well reduced bioavailability of nitric oxide combined with the stimulation of at1 receptors on smooth muscle cells causes vasoconstriction in addition to a vasoconstriction effect stimulation of at1 receptor causes the adrenal glands to release the hormone aldosterone resulting in sodium retention combined with vasoconstriction this increases blood pressure in the final stages of ras the kidney reduces the production of renin most of the known actions of angiotensin ii are mediated through the at1 receptors which can be found in the kidney heart vascular smooth muscle cells brain adrenal glands platelets adipocytes and the placenta angiotensin ii type 2 receptors can be found in low levels mainly in the uterus adrenal central nervous system heart and kidney at2 receptors appear to counteract the effects of at1 receptor stimulation another angiotensin ii type receptor is the at4 receptor its stimulation may increase synthesis of the natural inhibitor of tpa called pi1 thereby reducing effective fibrinolysis stimulation of at4 receptor appears also to promote cell growth and proliferation so you don't need to know this video in detail what i care about is you should know this pathway right just they mentioned this pathway but they went into more detail in alternative pathways um again let's just go over one more time so if blood pressure falls remnant will be secreted from the kidney converts angiotensinogen made by the liver to angiotensin one one gets converted to two because you're always making the ace enzyme which is made by endothelial cells mainly in the pulmonary vasculature other organs as well remember endothelial cells simple squamous and then once you make angiotensin ii this is a major player to help raise your blood pressure because it stimulates aldosterone secretion to reabsorb sodium and water passively through the kidney tubules stimulates vasoconstriction at the blood vessel walls simulates adh secretion from the posterior pituitary thus that also causes vasoconstriction and causes secretion reabsorption of water at the kidney tubules and also causes sympathetic activity which further causes vasoconstriction make sure you know this pathway we talked about adh and also vasopressin in regards to its two activities remember it's also a vasoconstrictor uh aldosterone we talked about sodium channels that it uh then it targets uh in the kidney tubules that's causing water reabsorption with it talked about that and then this these diagrams here kind of just go over the pathway and tells you the same thing we just went over same thing here same thing there now this rast system remember the rash system is involved in helping regulate your blood pressure long term it only raises your blood pressure it doesn't lower it right so the rat system's goal is to help raise your blood pressure when your blood pressure drops that's why it says decrease in blood pressure the goal of the rast system is to help raise your blood pressure and it does it through that pathway that we just showed you now the rast system is counter balanced by something hormones called natural peptide that are made in the heart walls right in the atriums and the ventricles of the heart and we're going to take a look at those because those hormones these natural peptides which are made by the heart will counteract the rast system so the rat system's goal is to help raise your blood pressure when it falls versus the natural peptides which are made by the heart uh act to lower your blood pressure when your blood pressure is goes up too high right that's why damage of the heart could cause problems because you're not secreting these hormones so these are the hormones that the heart secretes right it's called the bnp and amp uh b stan b is b type nitrite peptide a's a type nitrogen peptide the amp comes from the atrium walls of the heart and the ventricles will secrete the bnp now these two hormones natural peptides made by the heart are secreted in response to hypertension high blood volume high blood pressure so when the when the volume expands and the pressure expands within the atrium of ventricles they secrete these hormones once they're secreted amp and bmp they promote vasodilation and excretion of sodium and water into the urine they also inhibit renin and aldosterone release so they're inhibiting the rast system which makes sense right because the rice system is there to raise your blood pressure these two hormones are there to lower your blood pressure and amp and bmp are elevated in chronic heart failure which will make sense and bnp is especially important for diagnostic therapeutic and prognostic implication when it comes to heart failure so they usually measure the bnp levels to see how how your heart failure has been progressing but under normal circumstances they both rate lower your blood pressure right so you could see here's amp coming from the myocardium of the heart atrial walls and there's bmp coming from the myocardium and the ventricular walls what do they do well here they both do the same thing but you can see it causes vasodilation and excretion of sodium and water into the urine so it's not reabsorbing it which is the opposite of the rast system remember the rat system was there to vasoconstrict and retain water and sodium here it's the opposite but you don't need the whole pathway all it does it causes vasodilation uh secretion of sodium water into the urine yes it also suppresses thirst but i care about the vasodilation and the secretion of sodium and water into the urine and that lowers your blood pressure this diagram just shows some pathology but it basically talks about the same thing that we were talking about before again too much angiotensin ii can lead to increase in blood pressure increase in aldosterone secretion hypertension increases sodium intake hypertrophy of the heart because of the pounding of the blood pressure increased by fibrosis so you could see that you know the you know if you have too much secretion of one thing versus the other that could cause a lot of pathology to develop again these two hormonal systems the ras and the natural peptide system of the heart both maintain your blood pressure long term um one raises it the other one lowers it and then cushing's there's also some pathology here that you can see in regards to cushing's uh basically this is when there's too much cortisol production now you could get a tumor of the adrenal cortex or the adrenal medulla and that's not good because it could cause overproduction of those hormones um but you know cushing's usually uh because of prolonged cortisol exposure again a lot of elderly patients can get this because of too much cortisol that they're taking uh you can't be you shouldn't be exposed to too much synthetic uh corticosteroids or glucocorticoids i should say in uh long term right chronically should be short term so in cushing so if you're making too much cortisol or you've been exposed to too much cortisol these glucocorticoids you could see that they damage your organs too right it causes mental health issues vascular issues your osteoporosis it you know it suppresses your immune system so you're supposed to susceptible to cancer and infections and diabetes because it raises your glucose levels so you can see that damages this is characteristic for uh cushing's syndrome they get a buffalo hump and they have like a round moving phase again this is again uh develop if you take high doses of cortisol medications for for prolonged periods of time is one example the pineal gland uh is part of the epithalamus which is located back here now the pineal gland is important because it produces a hormone called melatonin right so it secretes melatonin the name of the cells are called pinealocytes and they secrete the hormone called melatonin now melatonin is important for many things as you can see in this diagram melatonin has a lot of factors right the main factor that i care about for you guys always remember that it's very common out there and everyone knows is that it helps regulate your circadian rhythm so it helps regulate it what is your circadian rhythm remember this is your sleep wake cycle so when you go to sleep at night you're producing more melatonin when you wake up in the morning you'll start making less melatonin throughout the day so again this hormone is help regulating your sleep wake cycle referred to as your circadian rhythm but it also has antioxidant anti-inflammatory into cancer effects as you can see uh you know from neurogenesis to immune defense to sleep promotion um you know even vaso motor control which is your blood vessels even melatonin is also given as a prophylactic for migraines stuff like that but uh you know you know you can take melatonin over the counter it causes a tolerance eventually you don't really want to mess too much melatonin because you're already making your own so you don't want to mess the balance of your own production of melatonin uh but you know get you you get you a little drowsy and then eventually you know you could build up tolerance and it won't work anymore so short-term use of melatonin could be okay for sleeping uh long-term eventually you will develop a tolerance but always remember it helps regulate your circadian rhythm but it has multiple other functions as you can see here and then your thymus gland before we get to the pancreas the last is your thymus gland remember your thymus gland we talked about in the blood lecture as well because it's part of the lymphoid organ it's a has it's an endocrine gland slash lymphoid organ it's an endocrine gland because it makes a hormone called thymus in which we're going to take a look at and it's a lymphoid organ because it's involved in t cell production and maturation which are the t lymphocytes now initially the thymus gland is a large gland in the fetus right and the fetus is you can see it here it's a yellow it's not normally yellow but the you know the color it is so you can see the large thymus gland on the superior aspect of the heart which is all this lungs here a little lungs over there there's a diaphragm a huge liver but again if you open up a baby as we see in this uh dissection here you can appreciate that it's huge there's a huge thymus gland on top of the heart now as you become an adolescent this thymus gland starts atrophying and becomes non-functional and then it gets replaced by some scar tissue and some adipose tissue it's non-functional it's not functioning anymore usually by time you become an adolescent so if you crack a chest open of an adult you won't see the thymus gland on top you might see a lot of adipose tissue on top of the heart on the superior aspect you will not find a thymus gland so why was that important so again here it shows you that the fibrous gland uh it basically um secretes a hormonal thymusin and thymussin promotes the replication and the maturation of the t cells which are t lymphocytes so just to go and give you a little history about lymphocytes lymphocytes are a type of white blood cell or leukocyte which we'll learn more in detail in the blood lecture leukocytes specifically t lymphocytes which are a type of leukocyte which is a white blood cell uh specifically the t lymphocytes will migrate early on these stem cells to the thymus that's why it's enlarged throughout childhood all the way through adolescence because they will replicate there and they mature there and you can see the the thymus and hormone the thymic hormone specifically the name is called thymosin is being secreted there to promote their replication and maturation so why do they do that they do that to recognize their own self antigens um that process doesn't work right you know you could develop autoimmune disease as well because of that but there are other reasons for autoimmune diseases example genetics some genetic predispositions and environmental triggers that could cause it um but we developed when these t cells mature these memory t cells that are coming from here um they last forever or until your elderly years as long as you maintain a strong immune system those memory t cells will last forever and this is just another picture of the fibers and we'll talk more about t cells in detail um in the blood lecture and here you can see a huge thymus gland so here's the thyroid right much different that's in the neck you can see a huge thymus gland is a lung lung heart diaphragm huge liver liver looks huge and then the pancreas the pancreas is an endocrine slash exocrine organ it's the only gland that has exocrine and endocrine function uh anatomically it's between the spleen and the duodenum which is this initial portion of the small intestine it's posterior to the stomach you can see it has three parts the tail the body and the head and it has a huge pancreatic duct and it also has an accessory duct all right so it's pancreatic duct was all this there's your accessory again tail body head same thing here here's the tail here's the body here's the head there's the pancreatic duct and there's your accessory duct this cadaver is a little hard to see we're seeing from an inferior view of the pancreas you can see the duodenum there's the head of the pancreas there's the body and there's the tail going this way and it's posterior to the stomach so they kind of lifted the stomach upward to show you the infrared portion of it so if you look at the pancreas again the pancreas lies between the spleen duodenum it's retroperitoneal meaning it's behind the peritoneum which we'll discuss more in detail in the gi lecture posterior to the stomach has a head body and tail and it's the only gland in your body that's endocrine and exocrine in function about ten percent of the pancreas endocrine but ninety percent of the pancreas is exocrine function now when we say now we'll discuss in this lecture we'll be discussing only the endocrine portion of it the exocrine the 90 exocrine that has to do with the gi lecture because it makes uh the pancreas makes a lot of pancreatic enzymes for digestion a lot of mucus production uh and you need pancreas to help the digestion but we'll focus on that um in the gi lecture for this lectures purpose we'll focus on the endocrine part but let's watch a video and then we'll come back and talk about it this will be the last video the organs of the endocrine system secrete hormones directly into the bloodstream to assist in the regulation of various body functions the endocrine gland discussed here is the pancreas the pancreas is an elongated organ situated between the duodenum of the small intestine and the spleen inferior and posterior to the stomach it is both an exocrine and endocrine gland the pancreas consists primarily of exocrine acid our cells and their associated ducts organized in glandular clusters pancreatic acini secrete enzyme-rich pancreatic juice via the pancreatic ducts into the duodenum to aid chemical digestion scattered among the asinine are small clusters of endocrine cells known as pancreatic islets or islets of langerhans each pancreatic islet contains four types of cells alpha beta delta and f cells that release hormones into the bloodstream when blood glucose levels decline alpha cells secrete glucagon a hormone that stimulates the liver to break down stored glycogen and release glucose into the bloodstream when blood levels of glucose and amino acids rise such as after a meal beta cells secrete insulin insulin stimulates cells to absorb glucose and amino acids from the blood and to store excess nutrients delta cells synthesize somatostatin this hormone inhibits the release of insulin and glucagon and slows the activities of digestive organs thereby slowing the entry of nutrients into the bloodstream f cells secrete pancreatic polypeptide to suppress and regulate somatostatin secretion by delta cells together these pancreatic hormones provide for the orderly uptake and processing of nutrients okay so let's talk about the endocrine portion of the pancreas remember the pancreas endocrine portion because it's about 10 of the pancreas which is involving these pancreatic isolates or isolates or langerhans these pancreatic isolates will contain four types of cells uh the alpha cell beta cell delta cell and f cell the two that are really important are the alpha and beta cells because they are the ones making the hormones insulin and glucagon which basically regulate glucose levels in the blood we'll mention the delta and f cells afterwards but we'll focus on the alpha and beta cells which were more important so again the alpha cells will be secreting a hormone called glucagon and the beta cells will be secreting a hormonal insulin now before we move any further in terms of what glucagon and insulin do i need to explain what is glycogen let me explain glycogen real quick so glycogen see here glycogen is a complex carbohydrate it's a starch and our body makes glycogen and stores it in the liver mainly and then skeletal muscle doesn't show it here you should know that from skeletal muscle lecture that you know skeletal muscle inside the cells store glycogen uh but the main reservoir for glycogen and our body stores it is in the liver and when our body needs glucose it breaks down the glycogen to extract that glucose also from skeletal muscle but mainly from the liver so now we know what glycogen is so let's go and read what happens so you can appreciate let me just magnify this part here you can see the alpha cells make sure i'm sharing the right screen you can see alpha cells will secrete the hormone glucagon primary targets is liver and adipose tissue uh what does glucagon do for you well it mobilizes lipid reserves mainly it starts breaking down the glycogen it promotes glucose synthesis and glycogen breakdown in the liver so it breaks down the glycogen elevates glucose so it starts elevating levels of glucose because alpha cells only circulate glucagon when you're hypoglycemic meaning below the normal levels of glucose and what it stimulates glycogen secretion from alpha cells what says it here stimulated by low blood glucose concentrations right if you're hypoglycemic your gluca you will secrete glucagon to start helping you break the glycogen in your liver mainly in your liver to break down to glucose remember it's ulcer foam is going to muscle which is mainly more used when you're at the gym and stuff like that beta cells on the other hand screen insulin insulin targets most cells in your body you should say all cells because most cells in our body use glucose what does this do well it facilitates uptake of glucose so once insulin attaches to those extracellular insulin receptors it's going to cause glucose channels to open and the target cells will absorb glucose and then it says stimulates formation and storage of lipids and glycogen so it's actually building up glycogen right so it's also doing that as well and what stimulates insulin secretion well high levels of glucose if you're hyper glycemic above the normal levels of glucose you will secrete insulin so after you eat a meal for example right if you're if you eat a meal your glucose level rise insulin gets secreted goes to target cells in your body to allow glucose to be absorbed that's its main purpose uh it's also stimulated by parasympathetic stimulation to a certain degree and high levels of some amino acids inhibited by gh and ih from delta cells and by sympathetic activation but let's look at these charts over here oh and by the way here's delta in f cells delta f cells uh the hormones referred to as somatostatin the ghih primary targets is other isolate cells digestive epithelium hormonal effect inhibits insulin and glucagon secretion so it's inhibiting both right so again intimidating both insulin and glucagon slows rates of nutrient absorption and enzyme secretion alone digestive tract uh what regulatory control stimulated by protein-rich meal mechanism unclear the f cells secrete something called pancreatic polypeptide this targets primary digestive organs has specific functions more in terms of inhibiting gallbladder contraction regulates production of pancreatic enzymes uh influences rate of nutrient absorption by the gi tract so again this is something we also discussed more in detail in the gi lecture but it's part of the endocrine because it does help regulate digestive organs this is stimulated by protein-rich meal and by parasympathetic stimulation because parasympathetic is what stimulates the gi function but again focus on alpha and beta cells they're really important and make sure you know what they do let me get out of this slide here and share sure so let's take a look um some histology and then we'll come back and recap on those cells so again normally this is a pancreatic isolate this is where we find the alpha beta delta and f cells same thing here we could see these little eyes isolates or pancreatic isolate or isolated lagrange and all the other cells that are outside of it are called acidity cells which are responsible for the exocrine portion which we deal with in gi lecture again these are the acinite cells and the isolates are where we find the alpha beta delta and our cells so you should be able to recognize that this is coming from pancreas you should be able to recognize these as pancreatic isolates and make sure you know the type of cells that are found in these pancreatic isolates remember the acidity has to do with exocrine function they are the ones making the pancreatic enzymes and mucus production that's being secreted into the gi tract by the pancreatic duct without dealing with that here here we see a isolated langer hand right or pancreatic isolate here again this is probably the best histology showing you that sometimes you'll see multiple isolates these isolates only make up ten percent of the pancreas the pancreat pancreatic acid cells make up 90 of the pancreas again to reiterate don't get glycogen confused with glucagon remember glucagon is the hormone secreted by the alpha cells it breaks down the glycogen in the liver the starch right and also found the skeletal muscle and then i like this diagram here because it shows you exactly what you need to know for what glycogen and excuse me for glucagon and insulin need to do so again under normal homeostasis your blood glucose levels are normal if you go below you don't need to know the average but if you go below 70 you're hypoglycemic if you go above about 110 you're hyperglycemic again if you just ate a meal of course your glucose levels are going to go up in your blood right so that stimulates insulin secretion from the beta cells first thing insulin does well attaches to insulin receptors those extracellular insulin receptors and all target cells what does that do well it promotes glucose reabsorp absorption into the cell and you need glucose to make atp production remember atp is which drives the energy within the cells and the organelles we also need the mitochondria for that but without glucose we cannot get those atps increased conversion of glucose to glycogen so you're building up glycogen levels in the liver and skeletal muscle you're building up their glycogen reserves right it promotes lipid amino acid absorption and protein synthesis and increases triglyceride synthesis uh in regards into to the adipose tissue and then the alpha cell secrete glucagon and remember glucagon is secreted when you're hypoglycemic if you go below the normal levels glucagon will start breaking down the glycogen and turning into glucose not only in the liver but you can see in skeletal muscle as well remember the liver is a main reservoir deposit for glycogen it also increases breakdown of fat of the fats to fatty acids and increases synthesis and release of glucose by the liver which again we talked about now just this is something just for educational purposes but if you're if you have your star if you haven't eaten all day long where do you get your glucose from well you get it from glycogen right so if you have anything all day long no sugar at all no carbohydrates right because that's where we get our glucose from we're we're basically breaking down the glycogen in our body eventually that glycogen reservoir can be depleted and then what happens if we're starving we starve ourselves eventually we'll need to break down proteins uh first lipids and then proteins could be broken down to get glucose out of that we don't try to do that long term again because it could change the ph of the blood oh that's why we need at least some amount of glue at least complex carbohydrates in our in our in our diet so again showing you here insulin builds up the glycogen levels in the liver and glucagon breaks them down you can see glucocorticoids also break down glycogen that's why the how that's how they increase glucose levels in the blood because they have an influence on breaking down the glycogen also appreciate that you could um that if you look at this slide is showing you glucagon being secreted and insulin secreted and how they have that effect on the glycogen levels in the liver remember glucagon breaks it down insulin builds up the glycogen levels and then just to go over a little bit of diabetes diabetes mellitus is glucose diet is sugar diabetes there's two types type one diabetes and type two type one is insulin dependent diabetes and type two is insulin independent although eventually you could become dependent on insulin if you don't control the blood sugar levels now type one is called insulin dependent because what happens is that it's an autoimmune disease type 1 remember now your immune system is attacking these beta cells and totally destroying them whatever again you might have some genetic predisposition but also environmental triggers that could trigger it from bacterial infections viral infections toxins pesticides um so again your white blood cells are totally destroying these beta cells so you become totally insulin dependent early on and type two you could have it during childhood again child diabetes is on the rise because of obesity but again combination here you get of insulin resistance insulin deficiency most diabetics have some type of family history because there is some genetic a lot of genetic predisposition but again if you you don't need to have the family history to develop type 2 diabetes if your lifestyle puts you in a position for a diabetes for example you know going to the gym you're eating western diet you know fast food you know controlling your intake and carbohydrates all that stuff can promote insulin resistance insulin deficiency what do they mean by insulin deficiency well think about it if you're chronically hyperglycemic because you can't control your sugar levels because if you can't control your diet or your eating habits uh you're going to deplete the you're you're stressing out those beta cells so you're depleting the the insulin eventually so you go from changing your diet and that doesn't work and then you're not working out and then you go to take the pills which help you with diabetes and then eventually if you don't control your sugar levels with that then you're gonna go into insulin right so there's this a progression that could go and all you got to do is control the sugar you control the sugar you prevent the diabetes you prevent the insulin deficiency and insulin resistance what are the insulin resistance well if you're chronically hyperglycemic that kind of destroys or causes those insulin receptors on the target cells to be de dysfunctional so that means that insulin when attaches to it it doesn't allow the cells to absorb glucose and those glucose gets stuck in the blood that's not good because of your chronic hypoglycemic it destroys your blood vessel walls it damages endothelial cells and as you can see you know chronic diabetes chronic height chronic high levels of glucose in the blood uh causes diabetic rhinopathy it's a leading cause of blindness diabetic cardiomyopathy heart failure you get silent heart attacks and destroys the nerve endings but you do get heart disease it promotes atherosclerotic plaques diabetic nephropathy destroys your kidneys that's what you need to dialysis to to kidney transplants diabetic neuropathy damages uh the nerve cells especially in your lower extremities so you get shooting or numbness depending on the severity a peripheral vascular disease or destroyed the blood vessels they grow abnormally as you can see that just examples of some diabetes mellitus in terms of symptoms signs and symptoms there's some genetic disposition for a native americans and hispanics uh and blacks compared to whites so there's some genetic predispositions but remember it also it's dependent on your lifestyle right uh and then diabetic rhetoric there's many causes of retinopathy as you can see here this retina is normal this is an abnormal retina these blood vessels have grown abnormally because the person cannot control the sugar levels because they control they cannot control their eating habits and blood vessels grow abnormally not just in the retina but this happens in the kidneys and you're at hard in your lower extremities and when they grow up normally they tend to bleed they tend to clot and you can see that uh that's what's happening they tend to bleed they get these floaters and eventually if they don't control their sugar levels this could these these yellow spots are laser treatments to stop the blood vessels from bleeding but eventually your your retina will detach and you will go blind right so [Music] uh with your poor eating habits eventually this could happen to you same thing with the kidneys right the kidneys don't regenerate really well unlike some other organs the kidneys uh if you know if you if you if you chronically abuse them you can see they can atrophy they don't work well and that could lead to kidney or dialysis or eventually transplant as you can see diabetic neuropathy the schwann cells that are in the peripheral nervous system they get due to the chronic hyperglycemia that causes oxidative stress this oxidative stress damages the myelin sheaths that are made by those schwann cells this causes the neuropathy the shooting pain the numbness it also causes vascular dysfunction it damages the endothelial cells thus you don't get good circulation especially into the lower extremities and then this is just showing you that they get a lot of peripheral vascular or peripheral artery disease not only they get platformation but the blood vessels don't flow right if you're also if you're chronically hyperglycemic you're also immunosuppressed that also suppresses your immune system of your chronically hyperglycemic which predisposes you to infections so if you have poor blood flow to the lower extremities because of the chronic hypertension chronic hyperglycemia chronic sugar uh high levels of sugar in your blood not only you have poor vasculature but you have your immunosuppressed and that predisposes you and then you have nerve damage because of the myelin sheath that's being damaged by the oxidative stress due to the hyperglycemia all that you know basically develops into foot ulcers and chronic tissue that leads to that can lead to sepsis or osteomyelitis eventually they have to do um amputations because you don't want to get sepsis because that could kill you or osteomyelitis this is an inflammatory infection of the bones but that's infection in your blood and then all organs can be susceptible and then these slides here don't stress too much but do appreciate that adipose tissue um also secretes leptin and resistant leptin helps with the feedback control appetite uh and then resistance reduces insulin sensitivity so adipose tissue when we think of it um i mean again they're called adipocytes or triglycerides uh but they do secrete hormones as well especially you know visceral adipose tissue which we find in the abdomen uh referred to as visceral adipose tissue that could cause a lot of problems um and you can see it could cause a lot of problems in regards to it could lead to high inflammation high blood pressure type 2 diabetes atherosclerosis so having a leptin is one thing right leptin and and resistant are too important hormones for appetite stuff like that and insulin sensitivity but you could see that if you have too much especially visceral adipose tissue in your abdomen you're going to release a lot of other things and that promotes inflammation hypertension diabetes atherosclerosis so having too much abdominal visceral adipose tissue it's going to give you something called metabolic disease that predisposes you to all these things and then these tables here are good to have because they go over the organ and some of the hormones uh that we talked about uh this these also talks about the same thing hormones of the reproductive system more in detail which will also be covering a reproductive lecture this is some terminology and this goes into clinical implications of endocrine malfunctions in regards to some pathology with that we did discuss with diabetes insipidus to diabetes mellitus stuff like that and then these lies are just for reference