hello anp2 class this is a continuation of our discussion of the endocrine system so this is part two of that discussion in the very first part if you recall we discussed the interaction between the hypothalamus and the pituitary gland the pituitary consists of two lobes the anterior and the posterior pituitary so we really kind of went into uh all the details and the disc and the actual interaction between how the hypothalamus uh cooperates or communicates with the pituitary um to release certain hormones in the case of the posterior uh pituitary lobe this would be the release of two important uh hormones such as oxytocin and antidiuretic hormone or adh now if you recall these two hormones were actually secreted by the hypothalamus but then they were released they were stored in the axon terminals within the posterior pituitary and then released from the posterior pituitary into the circulation and then we went on to add um and kind of discuss the interaction between the hypothalamus and the anterior pituitary this is where we talked about six different um releasing hormones or factors and also an inhibiting hormone that is secreted by the hypothalamus and how that controls the release of different hormones from the anterior pituitary so we kind of talked about growth hormone and thyroid stimulating hormone tsh and we discussed uh acth adrenocorticotropic hormone fsh follicle stimulating hormone lh luteinizing hormone and then we also talked about prolactin so those were the the the six different hormones that were released or secreted by uh the anterior pituitary so um and there was a there was a chart that i put together in one of the slides in the part one discussion where you saw the actual interaction between the hypothalamus and the anterior pituitary so what i want you to uh to kind of keep in mind going forward with our discussion in this part two of the endocrine system is really kind of recall that interaction between the hypothalamus and the anterior pituitary i'm going to add a little bit more detail to this now uh our focus here is going to be on the well first it's going to be on the thyroid gland uh where we will discuss the release of t3 and t4 and exactly what it does in terms of what is the response that's brought about uh in the target cells and then we'll definitely discuss the adrenal gland and talk about all the different layers and the different types of corticosteroids that are released and how it plays a role especially in in stress and then the last thing i want to talk about would be the role of the pancreas which is a very important uh it's a digestive and an endocrine organ but of course our focus will be on how the pancreas function as a digestive or i mean as an endocrine organ uh releasing two important hormones namely insulin and glucagon and then of course that should lead to our discussion of uh diabetes okay all right so let's kind of get started um let's let's first focus on the thyroid gland okay now if you recall uh this particular pathway that i've kind of drawn out here on the right uh so if you remember the hypothalamus releases trh thyrotropin releasing hormone and then that's going to be directed at the anterior pituitary which then releases thyroid stimulating hormone tsh so i've i've written out abbreviations in my little uh notes section here so again kind of go back and refer to what these abbreviations really stand for so trh from the hypothalamus prompts the release of tsh thyroid stimulating hormone from the anterior pituitary you always want to ask the question okay so when a hormone is released if you recall this is a chemical that is released into circulation like um the blood circulation as well as in uh lymph circulation or the the in in within the lymphatic vessels and this allows for the distribution or the transport of that hormone uh to distant sites right and that was the cool thing about those hormones that are released from the endocrine gland now again kind of going back to our discussion of uh like the part one series of the endocrine discussion i always asked you to think about okay when a hormone is released uh what would the target cells or the target organ b okay you would define a target organ as one that has a specific receptor for that specific hormone right so if tsh is released from the anterior pituitary what happens next is what i need you to be thinking about okay so the tsh is going to bind very specific receptors on the target organ which obviously since we're talking about thyroid stimulating hormone my target organ will be the thyroid gland in this case now we will discuss a little bit about the anatomy uh and we're also going to go over the the histology of the thyroid gland but there's really two different populations of cells within the thyroid gland specifically the follicular cells these are the cells that have receptors for tsh and when that tsh binds to receptors on the follicular cells within the thyroid gland this is going to prompt remember this is a gland this is an endocrine gland in itself it's going to prompt the release of different hormones in this case uh thyroxine t4 and triado thyronine t3 okay so abbreviated t3 and t4 so these are hormones that are released from these follicular cells within the thyroid gland okay as with any other hormone uh these hormones would then be released into the bloodstream or into the lymph which then would then target a different set of cells right okay there's always got to be a target organ so what's going to be my target cells in the case of your thyroid hormones t3 and t4 well pretty much every cell in the body is targeted by thyroid hormones why because these hormones have a very important response of basically controlling basal metabolic rate bmr so it's the most it's the major metabolic hormone in the body okay so keep this in mind as you can see this is kind of showing you a pathway it's showing you how information is flowing uh and how one step leads to the next step and basically brings about a specific response in each of these target organs so as you can kind of see here we start with hypothalamus we talked about how that prompts the release of tsh from the anterior pituitary and then you always want to ask what's going to be the target organ right so what's going to have those receptors to bind that hormone and so for tsh the target organ was a thyroid gland which then prompts the release of new hormones t3 t4 and that as it enters into the circulation will then find specific receptors for those thyroid hormones in pretty much every cell of the body and ultimately you always want to ask after the target cell um which has those receptors after it binds those hormones well what is the downstream effect or the response of those hormones within that target organ so always keep that in mind what's going to be the final ultimate response or exactly how does that hormone work within the target orbit okay okay so let's talk a little bit about the thyroid gland uh so this is uh associated um it just just it's associated with the with kind of like the trachea it's a butterfly shaped gland uh with basically two lobes and there's a connecting part called the isthmus but if you're looking at a cross section through the thyroid gland you should see these uh functional kind of units or structures called a follicle and within the follicle while outlining the follicle this is where you would see the follicular cells these follicular cells help to produce something called thyroglobulin which then combines with iodine uh to basically form your t3 and your t4 thyroid hormones okay within the follicle you should see a kind of a colloidal kind of structure or a substance um so this is going to be important for actually producing and it's going to be the source of the iodine which then helps to produce your final product namely t3 and t4 okay there's also another population of cells within the thyroid gland called the para follicular cells and i'll show you the histology here in just a second but these guys here the pair of follicular cells do not produce t3 and t4 they do not produce thyroid hormones instead they produce a different hormone called calcitonin which is really important for you to know as well and we'll talk about the the function of all of these hormones um as we build on this story okay so here you go um kind of right about the aorta and you're kind of looking at the aortic arch right there uh associated with the trachea the trachea is this blue structure right there with each of those cartilaginous rings that you can see those c-shaped rings uh here you've got the thyroid gland so the the two lobes with the isthmus and the in between um if you look at a cross-section of the thyroid gland it should look something like this which you have discussed in lab you should be able to identify two populations of cells and each of these functional units so each each of these units right here this is called a follicle and you can kind of see some part of each of these other follicles as you can kind of see there here's one intact follicle if you're looking at the perimeter or the boundary of this follicle each of those cells those are what we call the follicular cells now inside of this follicle you have the colloid the colloid has you know the thyroglobulin with the with iodine and that basically along with the follicular cells is able to generate or to secrete all of that final product which is your t3 and t4 thyroid hormones okay now in between uh adjacent follicles oftentimes you will see a population of cells so this this is in between the follicles right and these guys here these these cells are called parafollicular cells they produce a different hormone called calcitonin so make sure you know this okay what do the follicular cells produce and what does the pair of follicular cells produce okay i'll come back to parafollicular in a little bit i want to still talk about the thyroid hormone because all the t3 and t4 thyroid hormones that are produced here by those follicular cells will then be released into the circulation where you then need to find specific target organs and then we're going to talk about what's the response in those target organs and how what type of response do those thyroid hormones bring about within the cells of a target organ okay all right so here we go here are your two most important um metabolic hormones your thyroid hormones t3 as i said was tri iodo thyronine this is basically the tri comes from the fact that you've got three bound iodine atoms in this uh particular configuration t4 is for thyroxine this is where you have four iodine atoms kind of bound in this format okay um when these two hormones are released into the circulation into the blood uh they are transported by globulin plasma proteins okay and of course each one is going to have its own very specific receptor uh in target cells and notice your target cells are pretty much every cell in the body like i mentioned on a previous slide now of these two different um major uh thyroid hormones uh notice t3 is about 10 times more active than t4 you have more quantity or more concentration of t4 and less of the t3 but t3 is more uh potent so for the most part all the t4 as it enters your target cells it gets converted to the t3 in order to facilitate a response within the target cells so how does this work now remember thyroid hormones actually bind to receptors within the target cell so these are intracellular receptors which means that the the thyroid hormone and its receptor that complex as it enters the cell it will then further enter the nucleus where it's then going to bind to promoter regions associated with a specific gene on the dna contained within the nucleus and it's going to basically regulate gene expression turn on turn off genes and make new proteins and bring about a response in that manner okay now just remember your thyroid hormones are the major metabolic hormones in the body the main function is going to be this controlling or regulating bmr which is basal metabolic rate and also kind of associated with that they help to regulate body temperature as well okay so this uh let's kind of talk a little bit about that in a subsequent slide uh here's a schematic kind of putting together what i already put together on one of those first slides so remember it's the hypothalamus that releases thyrotropin releasing hormone trh which then targets the anterior pituitary uh allowing it to release a tsh thyroid stimulating hormone and then from there that's going to target the the follicular cells within the thyroid gland which then produces thyroid hormones thyroxine t4 and triadothyronine t3 these two hormones then can really get released into the circulation which then targets pretty much every cell in the body thereby bringing about a response uh which m which modulates a bmr and temperature regulation okay now i want to point out something very important here all of the solid arrows these are um this is a stimulation mechanism meaning this is going to have a positive influence right the trh has a positive influence on the anterior pituitary which then releases the tsh tsh then has a positive influence stimulating the thyroid gland to release the thyroid hormones and so on and so forth every time you see the dotted lines this is an inhibition mechanism now i told you this in the in the very first part one discussion of the endocrine system you always want to produce hormones uh in just the right amount to where you're facilitating or bringing about a response or a desired response but after that desired response is produced you always need some kind of a negative feedback mechanism to shut off the production of those hormones if not this process would become um dysregulated in other words you're going to have malfunctioning you're going to have too much over production of the hormone and no way to shut it off which means then you have an uncontrolled response which obviously is undesirable so kind of thinking back to your negative feedback mechanisms here as you produce thyroid hormones and as it controls bmr and metabolic activity of the cells well uh in an increased amount of those thyroid hormones is going to be the controlling factor that can feed back either to the hypothalamus to shut it down and therefore not release the trh or it may shut down the anterior pituitary so that it does not produce tsh without the tsh without the trh well it cannot activate the thyroid gland and therefore it's going to reduce the production of those thyroid hormones so this is negative feedback which is very important in any hormonal regulatory mechanism okay all right so now let's talk about uh those thyroid hormones t3 and t4 when they're released um into the circulation and when they find their specific receptors in the target cells what happens okay what's the response uh of those thyroid hormones within target cells most importantly i've highlighted it here for you it helps to increase bmr or basal metabolic rate and typically any cell that is metabolically active now remember what what this really what this really tells me is uh this is where your cells are utilizing some kind of a substrate typically glucose in the presence of oxygen to form all of that good atp and that's why you have a metabolically active cell that needs obviously atp to sustain all of that metabolic activity but always one of the consequences of byproducts of this metabolic pathway would be production of heat if you think about say if you were exercising vigorously then remember these are your skeletal muscle cells that are metabolically active generating a whole bunch of atp in order to sustain um the activity contraction and relaxation of your skeletal muscle cells therefore facilitating movement and mobility and in this case exercise right okay well when you're exercising vigorously what else are you producing you sweat a lot you produce heat this is one of the consequences of elevating basal metabolic rate of cells within your body okay so your thyroid hormone increases your bmr and therefore subsequently also helps to increase heat production in the body which is great because it helps to maintain your core uh body temperature okay it also has other effects in the body my focus is mostly going to be on part one right here which is how does it control bmr uh so in that in that regard this is table 16.4 from um your marib 11th edition of the textbook and if you kind of look at this table in your textbook there's actually a lot more detail to it i've just highlighted a specific region that you can see here in this box within red in this red box i just kind of want to highlight the main function of these thyroid hormones which is it helps to control bmr like i said and therefore it helps to regulate your uh temperature as well okay so i'm going to discuss two main homeostatic imbalance situations in relation to the thyroid hormone so um let's talk about hyper secretion meaning if you had increased uh levels of your thyroid hormone what's going to happen and likewise if you had hypo secretion which is if you had reduced levels of the thyroid hormone then how is that going to affect your body okay so let's start with hyper secretion on the right here and then kind of discuss reduced secretion of thyroid hormones okay so the case of hyper secretion uh hyper means elevated increase so you're increasing uh the production of those thyroid hormones t3 and t4 what is this going to do to your target cells what's going to how is it going to affect the response of those target cells well if you had too much thyroid hormone then obviously it's going to elevate your bmr way above normal and because you have high metabolic rate of these cells obviously that's going to be accompanied by an increase in body temperature so therefore people that have hyper secretion of thyroid hormones they tend to be hot natured meaning that they oh they heat they overheat pretty pretty quickly or they get they feel um warm or kind of hot pretty easily um in a room for example okay so uh so that's that's how bmr and um overall uh kind of core body temperature or heat production is associated but also think about this because you are increasing your bmr your basal metabolic rate about normal when you eat a meal uh all of those complex carbohydrates are broken down into your simplest monosaccharides such as glucose right and then likewise your proteins are broken down into amino acids um your fats your complex lipids are broken down into fatty acids this is the whole process of like you know digestion that's occurring in your body but all of that good glucose that you're breaking down from those complex carbohydrates because you have an elevated bmr what happens to that glucose you're going to use that glucose within the cells and you're going to convert that and you're going to use that substrate and convert it to form uh atp which is your energy currency that's why to sustain that high elevated bmr uh your body is utilizing all of that glucose pretty quickly uh and generating that atp well in the process that meal is is gone pretty quickly from your body basically because it's utilized right so as a result you always have an increased appetite okay so you're constantly hungry because you have an elevated uh metabolic rate you're utilizing those uh those those reserves the glucose and and maybe even fatty acids and amino acids um so you're constantly hungry but you do not gain much weight because as soon as you eat a meal you are you're breaking it down and then you're utilizing those substrates uh very quickly because you have elevated bmr in other words you're not storing too much excess as a result you most people with hyper secretion of thyroid hormones because they have an elevated bmr they have an increased appetite they're eating more but they're actually experiencing weight loss because um you're not really storing any reserves as like for example a reserve glucose is not stored as glycogen within the liver or the skeletal muscle cells you don't have any excess glucose being stored as fatty acids within um the adipose tissue either so these are some of the characteristics of hyper secretion of the thyroid hormone so likewise what do you think is going to happen if you had reduced secretion hypo secretion of those thyroid hormones okay right the opposite is going to happen so remember you you need those thyroid hormones to have to maintain your bmr your basal metabolic rate if you had less secretion of thyroid hormones well bmr is going to be below normal as a result you don't have much metabolically active cells so it's kind of sluggish so therefore not much heat being generated so decreased body temperature uh people with this condition are going to be gonna have more cold intolerance meaning they're gonna feel more cold um on a normal day okay um because their bmr is lower than normal okay your body tends to um kind of store all of your excess reserves because it's a sluggish metabolic rate so um you have a decreased appetite uh because you have a lower bmr so you're not always all that hungry but whatever you eat is kind of stored as excess storage like glycogen for example okay so this is these are the two main sets of characteristics related to hyper or hypo secretion of thyroid hormones that i need you to understand okay so um let's see let's talk a little bit about some of those homeostatic imbalance situations like for example hyper secretion of thyroid hormones this is mostly associated with a condition called graves disease it's actually an autoimmune disease in the body um so if you remember um the hypothalamus produces trh which then uh directs the anterior pituitary to produce tsh which is thyroid stimulating hormone and the tsh then targets the thyroid gland to produce thyroid hormones like t3 and t4 in this autoimmune condition the body makes abnormal antibodies that are directed against your follicular cells so it's kind of like those antibodies will mimic uh tsh so it appears like as if you have a constant production of tsh except it's not really being made by the anterior pituitary these are antibodies being produced by about by your body in response to this autoimmune condition it's mimicking tsh so therefore you have a constant trigger namely you have that artificial tsh like substance and so this is going to be directed towards that thyroid gland allowing for more and more thyroid hormones t3 and t4 to be produced as a result you see an elevated or a hyper secretion of thyroid hormones symptoms are still the same like we discussed on the previous slide because you have too much of the thyroid hormones it's going to increase your bmr increase your body temperature and so on and so forth okay okay the next condition is related to hypo secretion of thyroid hormones which is right the opposite of what we discussed with graves disease uh so it's going to be a low metabolic rate and so on and so forth um in adults uh this condition can be associated with something called mixed edema um this is also related to another condition where you kind of see an endo enlarged thyroid gland called a goiter um so okay so in this in this particular condition this is actually due to a lack of of iodine okay remember iodine is important to form functional thyroid hormones such as t3 and and t4 so what happens here is you really have uh because you don't have iodine or you have less iodine or a lack of iodine you're actually forming thyroid hormones except it's not functional okay so therefore those thyroid hormones because they're not functional they're not able to regulate uh the metabolic rate the bmr of your of your cells and so this kind of alerts the hypothalamus and the anterior pituitary it gives the false impression that there's actually not much thyroid hormones in the body does that make sense so therefore this is going to cause prompt the release of more and more thyroid hormones from from the thyroid gland except it's all non-functional so you see an accumulation of this non-functional thyroid hormones within the thyroid gland causing an enlarged thyroid gland such as a goiter to manifest itself okay so this is basically um kind of artificially stimulating the production of thyroid or thyroid thyroglobulin except because you don't have iodine to couple with that thyroglobulin you're not able to form uh functional t3 and t4 so those are two important thyroid disorders uh in the body okay now if you remember um our discussion of the thyroid gland just a while ago uh we talked about the follicles and you had um surrounding the follicle you had uh your follicular cells which are important for the production of thyroid hormones but then in between adjacent follicles for the most part you saw uh like a different population of cells in between the follicles and these were called the parafollicular cells they produce an important hormone called calcitonin now i want to i want to use this this slide right here to compare and contrast two important hormones okay so we're going to keep in mind the parafollicular cells and the calcium calcitonin that it produces but calcitonin is an antagonist to a different hormone called pth parathyroid hormone now we were talking about the thyroid gland on the reverse aspect of the thyroid gland there are four tiny little pea sized glands which collectively is called the parathyroid gland and it's the parathyroid gland that produces pth again now i'm saying that calcitonin produced by the pair of follicular cells within the thyroid gland is an antagonist to the pth that's produced by the parathyroid gland what do i mean by an antagonist it means that these two hormones calcitonin and pth they are uh opposing in their responses they work against each other in other words if calcitonin does one thing then pth is going to do right the opposite that's why they are antagonists they antagonize each other okay so how does this entire story fit together follow with me uh as i go through my notes here i'm kind of comparing the two different responses okay um so i'm gonna start with pth here okay uh there's always remember for the for the release of any hormone there's always got to be some kind of a stimulus some kind of a trigger an an event that brings about the release of a hormone okay in the case of pth this is my trigger when you see blood levels of calcium start to drop okay so decreasing blood calcium levels is going to prompt the release of parathyroid hormone pth from where from the parathyroid gland what does the pth do this is a classic negative feedback mechanism my problem is right here which is a decrease in the blood calcium levels so the pth is going to do something as explained here it's going to do it's going to bring about this process to correct this problem okay so if you're kind of looking at the trigger a drop in calcium levels in the blood and if you look at the response what's happening this is a drop this is my trigger the response is to correct that drop by increasing blood calcium levels this is a classic negative feedback mechanism where the biological variable in this case was dropping and the response would be to correct that drop by increasing that biological variable since the response is moving in the opposite direction as the original stimulus this is classic negative feedback mechanism almost all hormonal regulation uh is controlled by is con is kind of it revolves around this whole concept of negative feedback okay so we said here's my trigger uh dropping blood calcium levels pth is released pth is then going to have specific receptors right always there's always going to be a specific receptor for any hormone when that pth is released in the bloodstream its receptors are going to be within specific cells within the skeletal within the bone okay bone tissue and there are different populations of bone cells that we talked about in the np1 osteoblast cells osteocytes progenitor cells and we also talked about these guys called osteoclast cells so when pth targets or activates these osteoclast cells these osteoclasts will start to chew up or degrade bone matrix which is called osteoid well what is stored inside of this osteoid again think back to anp1 we talked about all of this stored inside of this osteoid is excess or basically calcium phosphates so because i'm chewing up and degrading some parts of that bone matrix you're going to release soluble calcium from that osteoid what do you do with that with that released calcium well take it and put it back into the bloodstream as a result you're going to start to increase your blood calcium levels that's how pth works okay so remember the trigger is always going to be right the opposite uh from the response that is desired okay so my trigger in the case of pth was a dropping uh blood calcium level and i'm going to correct this by activating the osteoglass putting back all of that soluble calcium into the blood and therefore my response here is going to be an increase in blood calcium levels so now i've corrected this problem correct now just look at this okay look at the right side of this discussion here this response which is increasing blood calcium levels brought about by pth now becomes the trigger for my antagonist to pth what's the antagonist to pth calcitonin right okay so the same this the response of pth which is increasing blood calcium levels as those calcium levels start to keep increasing this now becomes the trigger for calcitonin okay which allows the release of calcitonin if you remember from the parafollicular cells of the thyroid gland what does it do because it's an antagonist it's going to do right the opposite of what pth did it's going to inhibit the osteoglass cells it's going to allow for calcium all of that excess calcium in the blood it's going to cause it to be taken up by the cells within the bone and it's stored within the bone matrix namely the osteoid since i'm pulling it out of the blood and i'm storing it in in the bone matrix what do you think is going to happen to the calcium levels in the blood i'm taking it out of the blood and storing it elsewhere correct so therefore you're going to see a drop in the blood calcium levels okay now as you can imagine i didn't draw it here but you can imagine this response of calcitonin dropping calcium levels in the blood will then become the trigger for pth so as you can see this is going to be a balance between these two antagonistic hormones a balance between pth which brings about an increase in blood calcium levels and that's balanced out by calcitonin which is going to decrease the blood calcium levels so you have an increase on one side and a decrease on the other side so you have two different responses to opposing responses that's why these are antagonistic hormones and you want to balance between what pth is doing and what calcitonin is bringing about and this balance will then accomplish homeostasis within cells because you don't want because remember those calcium levels in blood have to be very tightly regulated you don't want it to become too high if it becomes too high calcitonin is released which then drops the calcium levels in the blood if it becomes too low release the pth to bring those levels of calcium back up so it's going to be a balance between how the pth and the calcitonin work to kind of it's like a like a seesaw till you achieve uh an optimal um operating condition to where you uh you have homeostatic levels of calcium in the blood okay so you're going to see this happen quite a bit oftentimes a pair of hormones or sometimes multiple hormones kind of work together or they oppose each other to bring about that ideal balance okay so i hope you'll understood this whole concept of how cal calcium is regulated in the blood it's very very important for you to understand this it's really a balance between calcitonin and parathyroid hormone but really i'm going to go on to the next slide here uh we already talked about this this is the reverse aspect of the thyroid gland where you see those four parathyroid glands kind of collectively put together which releases the pth pth is the most important hormone that helps to regulate calcium homeostasis in the body obviously its partner in crime would be the antagonistic hormone namely calcitonin which we just talked about okay okay um so i think we've kind of broken down the significance of the thyroid gland um those thyroid hormones and of course the role of calcitonin and how it plays a role with pth and regulating calcium levels so now that we've covered the thyroid gland i believe we want to move on to um the adrenal gland next but okay there's a few more things here that i need to cover and i think this is pretty straightforward so hyper parathyroidism means an increased production of pth from the parathyroid gland uh obviously remember what does pth do pth is going to uh let me go back here just to kind of recall here do you remember what pth did pth is going to increase your blood calcium levels right so if you have too much of pth what is it going to do you're going to have an abnormal increase in blood calcium levels but where did that calcium come from pointer that calcium was uh resorbed from the bone osteoid so if you uh have overactive osteoclasts it's going to degrade too much of the bone matrix uh putting all of that excess calcium back into the blood but as a result the bones would suffer meaning it's good it's going to start to make it more brittle and soft meaning um this could result in um unnecessary fracturing or it becomes more susceptible to fracturing so that's what's kind of explained here with hyperparathyroidism is uh you're going to pull all of that calcium from the bone the bone matrix the osteoclasts are going to degrade the bone matrix to release all that calcium allowing it to be put back into the blood but as a result it's going to soften and compromise the integrity of the bone structure causing easy fracturing okay and also as you see those calcium levels build up in the blood uh as a result of excessive production of pth this has other effects in the body as well especially the nervous system it tends to depress the nervous system and all of that calcium deposits as it circulates through the blood this can cause buildup of calcium in um in the heart in in the valves uh the av valves between the um the atria and the ventricles this could this could cause stenosis or obstruction uh off that opening making it more difficult to pump the blood but that's one one problem and also as that calcium excess calcium in the blood flows through the kidney filtrate this could cause the formation of kidney stones as well okay so um on the other hand what is hypoparathyroidism this is obviously less release of of pth which is kind of like the opposite of hyper parathyroidism okay so the next endocrine gland that i want to discuss would be the adrenal gland um so this is a pair of glands that is associated with the kidneys and it kind of sits on top of the kidneys these are also called suprarenal glands if you're looking at the structure of the adrenal gland there are two major regions you have an outer region which is called the cortex and this is where i'm going to break down the cortex into three sub-regions and talk about the different types of steroidal hormones that are released from each of these three sublayers and then in the core of the adrenal gland is the medulla the medulla is mostly nervous tissue and this is actually part of the autonomics nervous system specifically the sympathetic nervous system and allows for the release of epinephrine and norepinephrine which is uh basically important for the whole uh fight-or-flight response as associated with the sympathetic nervous system and kind of um uh is dictated by that adrenaline rush that you experience when you are in a high activity situation or a very stressful situation so i'm going to talk to you about all these different regions especially the cortex region breaking it down to three sub layers and then what does the medulla do okay so kind of going back to our discussion our very brief discussion of the uh the adrenal gland from our part one of the endocrine system if you recall this is a very similar schematic that i drew out on one of those slides so you can um kind of uh divide or compartmentalize the the outer adrenal cortex into three main sub layers starting with the outermost you have the sauna glomerulosa there's on a fascicular towards the middle and then as you go deeper down towards the adrenal medulla you have the zona reticularis okay so kind of to recall what we discussed in part one we said the hypothalamus releases a corticotropin releasing factor or releasing hormone crh which is then going to target the anterior pituitary to release acth which is adrenocorticotropic hormone again i only have abbreviations written here i'll go back and refer to your textbook or any of my slides in the part 1 series of this endocrine discussion to kind of refresh your memory on what these abbreviations stand for so when the acth is released by the anterior pituitary uh the receptors for that acth are specifically on the cells of the adrenal gland within the adrenal cortex region okay and depending on which receptors it binds and it's going to vary in what type of us steroidal hormones are released uh from each of these different sub layers okay so start starting with um the outermost layer of the adrenal cortex this is the glomerulosa this uh releases a set of hormones called mineralocorticoids specifically i'm going to talk about aldosterone as an example of a mineral of corticoid from that middle layer namely the fascicular this is going to release glucocorticoids and some primary examples would be hydrocortisone cortisol and so on and so forth and then as you go deeper into the cortex you have this final layer the third layer uh which is the reticularis and this and this secretes uh some basic uh gonadocorticoids like weak androgens which are converted into testosterone so mostly androgens okay collectively mineralocorticoids glucocorticoids and gonadocorticoids all together they form this class of steroids called corticosteroids okay so corticosteroids is the overall class you can break it down into mineralo uh coracoids glucocorticoids and gonadocortacoids um predominantly mineralocorticoids is released from the glomerulosa layer uh glucocorticoids are mostly released or secreted by the fascicular but to a pr to a minimal extent from the reticulitis as well the gonado coracoids mostly are released from the reticularis layer okay so now what i want to do is explain to you um how these corticosteroids are important in two different things uh aldosterone how it plays a role in electrolyte balance our focus is going to be on sodium balance um and consequently if you can control sodium levels um then that's also going to control water levels so sodium and indirectly water balance as well and then uh how the glucocorticoids like cortisol for example are going to play a role in the stress response okay so those are the two main responses of the corticosteroids that i'm going to be focusing on so let's kind of start with the mineral or coracoids but before that let's do some histology and this was discussed in lab um so let's go ahead and kind of show you the different layers here so starting with the outermost region you have an outermost capsule for the entire um adrenal gland right underneath it all of this should be your adrenal cortex region and then deep down right down there should be the adrenal medullary region okay so the cortex like i said can be broken down into the glomerulosa up top towards the middle you have the vesicular and then much deeper down the reticularis reticulitis is right about the adrenal medulla and then if you recall what are the different uh classes of hormones that are released from each of these layers this is definitely something you need to know the glomerular also releases the mineralocorticoids an example here is the aldosterone the fascicular mostly um all of the glucocorticoids like cortisol into a minimal extent even androgens are released by the fascicular the reticular is mostly only androgens and what is the medulla the adrenal medulla release now this is mostly epinephrine and norepinephrine which is really part of what's released by the sympathetic nervous system okay all right so let's go ahead and talk about that outermost layer of the adrenal cortex namely the zono glomerulosa it produces mineralocorticoids and the example i want to really focus on is aldosterone okay this is the most important mineral or coracoid its main function is to control sodium levels and also potassium levels to a certain extent so it's basically controlling concentrations the most important electrolyte in extracellular fluid would be sodium so this is really kind of controlled by aldosterone within the adrenal gland okay so what does it do i've kind of abbreviated here for you on the right aldosterone does two things okay um in terms of sodium it brings about sodium reabsorption from the kidney tibial and puts it back into the blood so i have a a very simplistic schematic kind of drawn out for you here and again this is oversimplified uh look there's different regions of the of the tibial or the kidney tibial um i've only drawn one one little region this is uh not perfectly accurate but it will do for right now when we hit the urinary system much later on you will learn this in much more detail and all the different regions of what exactly is reabsorbed where and so on and so forth but for right now this is again a very very over simplified version of the renal tibial so i've kind of drawn that here in in black okay this is my renal tibial filtrate is passing through this renal tibial and it has a lot of the sodium it has glucose and all that water of course a lot of this needs to be reabsorbed into what you see here on the right in red which is a blood vessel so what i'm showing you here is sodium ions na plus gets reabsorbed notice uh reabsorption is a process where i am removing it from the filtrate within the kidney tibial and i am putting it back into the plasma uh within the blood within the blood vessel so reabsorption is this blue arrow moving from the filtrate into um the plasma into the blood vessel okay so sodium is reabsorbed from the kidney tibial into the blood into the blood plasma as a consequence of aldosterone action always if you reabsorb sodium which is salt water is always going to follow salt so right behind this sodium being reabsorbed into the blood you're also going to pull out water from the kidney tibial and put it into the blood vessel so now if you think about as you pull out that water think about what's going to happen to blood volume then because you are moving water into the blood vessel that's going to increase plasma volume or blood volume and normally when you increase blood volume that's also going to increase blood pressure so okay so now that i'm moving water or quite a bit of that water out of the filtrate and putting it into the blood well that's going to increase blood volume but what is it going to do with to urine output i'm reducing the quantity of the filtrate that is ultimately eliminated as urine as a result urine output will will decrease okay this is how aldosterone works in the body it's going to control for sodium levels so electrolyte concentration but also indirectly it's going to control for water levels between different compartments in the body okay this is really really important of course i'm going to be revisiting the same concept when i um discuss the urinary system a little later on in the semester so you might as well understand how aldosterone works in fact i'm going to be talking about the renin eng to aldosterone mechanism here in just a little bit so just to recap my blue arrow is showing that i am pulling a sodium out of the kidney tibial and putting it back into the bloodstream so moving anything from the tibial into the blood is reabsorption so let's focus on this green arrow here for just a little bit green arrow is moving in the opposite direction so this is where i am pulling something such as potassium ions as it uh builds up here in the blood vessel i can take all of that excess potassium and put it back into the kidney filtrate and therefore that excess potassium then gets eliminated in urine so secretion is the process where i am moving it from the blood vessel from the bloodstream into the kidney filtrate okay into the kidney tibial so it's right the opposite in terms of directionality reabsorption is from the tibial into the blood uh secretion is from the blood back into the tibia okay so aldosterone yes the primary function is sodium reabsorption but it also plays a role in potassium secretion okay so that's what i've simplified using that schematic so now let's talk about a little bit more about how do you regulate aldosterone uh secretion how what's going to prompt the release of aldosterone um from the zonoglomerulosa within the adrenal gland okay there's four different mechanisms uh the renin-eng h2 aldosterone mechanism is the most important but also plasma concentration of potassium acth levels and then a different hormone called enp atrial natural peptide these are all going to be determining factors in controlling or regulating aldosterone release now the rest of these slides this slide and the next slide is basically a kind of a brief summary uh like a word description of of what these factors do what i'm going to do is focus on this schematic right here which brings together all four factors uh the first factor being the renin angiotensin aldosterone pathway the second being what if you start to see a build up of potassium levels or i'm sorry potassium ions uh within the plasma within the blood plasma here's my third factor which is uh acth release and the fourth factor namely anp release how do all four factors here contribute how are they responsible for release of aldosterone okay so that's what i'm going to break down for you um so here are the different uh triggers for uh to prompt the release of aldosterone from um the adrenal gland okay so let's start with the left and work our way towards the right uh in the first scenario this is the renin-ange to um aldosterone pathway or the mechanism so this is in in the trigger would be as you see a drop in blood pressure or blood volume in in the body um as blood pressure drops the kidney has a specialized population of cells called the granular cells which respond to this uh decrease or the drop in blood pressure what is it what is it going to do in response to the drop in blood pressure those cells those granular cells will release a chemical called renin renin is then released and this causes the conversion of ange 1 angiotensin 1 to angiotensin 2. so basically causes the activation of angiotensin ii what does the angiotensin ii do well it's going to target the adrenal cortex specifically the glomerulosa layer which then prompts the release of aldosterone so here you have the renin angiotensin ii aldosterone pathway okay so that's the connection right there renin to eng2 to aldosterone okay then the rest of this we've already talked about in the previous slide what does aldosterone do when aldosterone is released by um the adrenal gland from the glomerulus layer it's going to target the kidney tibial like i showed you in my schematic let me back up uh this schematic right here aldosterone is going to target the kidney tibial which is then going to cause sodium reabsorption from the tibial back into the blood and therefore you see an increase in blood volume and a drop in urine output that's what's explained in the rest of the schematic so aldosterone targets the kidney tibial which causes sodium to be reabsorbed uh right behind that sodium water follows so therefore you're going to see an increase in blood volume and which then typically will lead to an increase in blood pressure so here's my response okay i'm seeing an increase in blood volume which is also tied in with an increase in blood pressure so what was my problem a drop in blood volume or a drop in blood pressure that was my trigger so this is again another example of a negative feedback mechanism i'm going to correct this problem which is a drop in blood volume or blood pressure by responding with the help of aldosterone which increases blood volume and increases blood pressure okay so that's one mechanism for controlling aldosterone release the second is remember aldosterone also does one more thing it helps with a secretion of potassium back into the filtrate so when you start to see elevated levels or excess buildup of potassium ions in the blood plasma it's going to prompt the release of aldosterone and aldosterone let me back up right quick just to show you what does aldosterone do as you see a buildup of potassium levels in the plasma it's going to pull it out pull out all of that excess potassium from the blood and i'm going to secrete it back into the filtrate where you would get rid of that excess potassium uh in the urine okay so that's the other part shown here so you see an increase in potassium levels in the blood i'm going to pull it out of the blood and therefore i'm going to excrete it out as urine okay okay here are other factors that contribute to aldosterone release stress that's a that's a big one um so in response in response to stress um okay remember this is the hypothalamus that releases crh crh is going to target the anterior pituitary which then releases acth adrenocorticotropic hormone the rest of this you should understand acth is going to target the adrenal cortex release aldosterone and then does all of this that's the third pathway namely stress and then the last pathway now notice all of these are solid um arrows solid arrows means stimulation uh all three pathways or all three triggers here would stimulate or in other words it's going to increase the release of aldosterone from the adrenal cortex whereas on the right here you're looking at an inhibitory pathway this is in response to uh an antagonist to aldosterone namely anp atrial natural peptide so what does aldosterone do aldosterone is going to increase blood pressure um and blood volume but what if you had to begin with if you had excessive blood pressure if you had an increase in blood pressure or if you have an increase in blood volume well you don't want to increase it any further that doesn't make any sense right because that's going to be counterproductive if my problem is an increase in blood volume or blood pressure then obviously you want to then shut down aldosterone because aldosterone will only compound this problem by increasing the blood pressure and the blood volume even further which is not good so this is how the heart protects against um this whole pathway in response to the in in response to elevated blood pressure uh the heart has pressure sensors that can that can detect um this increase in blood pressure and it releases a hormone called amp atrial natural peptide and this is an antagonist notice the dotted lines meaning it's going to inhibit shut down the release of aldosterone therefore it shuts down all of this pathway and that's how you would decrease your blood pressure okay on your blood volume so those are your four main factors controlling aldosterone release three of which were stimulation effects meaning increasing aldosterone production the the fourth and the final one which is anp is an antagonist it's going to inhibit the release of aldosterone okay so we've talked about mineral coracoids uh which is released by the zona glomerulosa layer we talked about specifically one mineral or coracoid namely um aldosterone so what i'm going to do here next is talk about that middle layer uh of the adrenal cortex which is the the zona uh fascicular uh this is going to release glucocorticoids and so i'm going to talk about how does this play a role in what type of response do glucocorticoids bring about uh within the cells okay okay glucocorticoids are released in response to a crisis the crisis being stress so their response their response is to stressful situations in the body and what's explained over here is basically how does the body respond to stress always remember in response to stress uh glucocorticoids are released such as cortisol and cortisone and what it does is here's what's listed here all the different uh glucocorticoids hydrocortisone cortisone corticosteroid um and cortisol of course um what does it do the primary effect or response of of any of these glucocorticoids would be to increase the levels of glucose fatty acids and amino acids within the blood to keep these substrates glucose fatty acids and amino acids you want to keep those levels high in the blood where did all of this come from when you eat a meal and it's a combination of uh carbohydrates and lipids and proteins right the carbohydrates get broken down by um digestive processes into your basic building blocks namely monosaccharides such as glucose uh likewise you have your larger proteins that are broken down into amino acids and your larger lipids that are broken down into fatty acids okay so i'm saying in the case of us in a stressful situation when cortisol is released for example it's going to work to make sure that you always have high levels of glucose fatty acids and amino acids in the body so basically what's going to happen is i'm going to break down or metabolize those carbohydrates to release the glucose this is your normal source of glucose is to break it down from the complex carbohydrate right but in a stressful situation you can also use um fatty acids and amino acids and you can convert these two into glucose as well bottom line is keep those levels of glucose as high as possible within the bloodstream okay now why would this be important because then you would use the glucose and divert it to all the major uh pretty much every organ in the body but specifically um regions such as critical regions such as the brain you want to divert all of that glucose to regions such as the brain so that you can generate sufficient amounts of atp atp would be required to negotiate a stressful condition this is called glucose pairing effect this is where you are kind of diverting all of that good glucose to the to the brain to make sure that the brain has enough glucose to generate atp because brain cells neural cells cannot use any other substrate to generate atp they primarily depend on glucose whereas other cells in the body are encouraged to use different substrates like fatty acids and sometimes even amino acids uh to generate the glucose and therefore uh form the atp whenever you use a non-carbohydrate source such as fatty acids or amino acids to generate the atp this is called this process is called gluconeogenesis so genesis is synthesis synthesis of glucose but neo stands for new meaning synthesis of glucose from new sources new sources such as sources such as lipids like fatty acids and proteins such as amino acids okay all right um so again when you're thinking about a stressful situation the bottom line is this you want to make sure that you have high levels in the blood uh you want to have high levels of glucose fatty acids and amino acids the reason why you want these guys is so that it can be converted to the glucose because the primary substrate that most cells prefer to generate atp would be glucose okay um and don't forget the glucose pairing effect as well all right so what what would happen in the body if you had excessive levels of cortisol for example well this is uh going to have an anti-inflammatory effect meaning it's going to inhibit inflammation uh typically any kind of uh steroid uh steroidal hormone is going to depress the immune system kind of kind of reduce the effects of the immune system or can even shut it down depending on the duration of use of steroidal hormones in the body um and again of course can control for inflammatory conditions like arthritis and and allergies okay all right so what i want to talk about next is again kind of build on this concept of stress um so we're going to come back to your glucocorticoids but i also want to tie in at this point how does the adrenal medulla work uh to negotiate a stressful situation because remember those would release those are controlled by the sympathetic nervous system and it releases epinephrine and norepinephrine so let's talk about that again all right before i get to that let's uh and move away from glucocorticoids uh very quickly hyper secretion of glucocorticoids such as cortisol results in a condition called cushing's syndrome uh so of course obviously this is going to have you're going to have elevated levels of blood glucose um persistent in the in the blood because of uh elevated cortisol or glucocorticoid uh levels in the body this could be because of a tumor and the pituitary or in the adrenal cortex uh causing an overproduction of those uh glucocorticoids hypo secretion is right the opposite which is where you have less production of your glucocorticoids obviously has uh right the opposite effect of um hyper secretion so hyper secretion normally associated with cushing's syndrome high post secretion addison's disease okay all right and then remember that last layer of the adrenal cortex which was called uh the zona reticularis this produces gonadocorticoids so very briefly this is where this layer produces uh androgens which are male sex hormones you can convert those androgens into testosterone most of this is to control for uh regulation of secondary sex characteristics uh onset of puberty sex tribes for sure so that's the role of those gonadocorticoids so i've kind of broken down all three layers of the adrenal cortex um the glomerulosa producing mineralocorticoids such as aldosterone which is important for sodium levels water levels and and how it plays a role with controlling blood volume and blood pressure um and then we talk about the middle layer which is the fascicular and that produces all of those glucocorticoids such as cortisol and then the final the deepest layer which is the um reticularis layer which produces gonadocorticoids now i'm not done with that whole concept and discussion of stress just yet so what i want to do is then talk about even further beneath the zona reticularis you have the adrenal medulla and within the medullary region you have a set of cells called the chromophant medullary chromophant cells and these should these produce catacolamines mostly epinephrine and to a certain extent norepinephrine and these two together are part of actually the sympathetic nervous system the effects of epinephrine and norepinephrine in the body um are related to these conditions or these uh factors right here so this is going to bring about vasoconstriction in the blood vessel it causes constriction of it's going to decrease the diameter of the lumen of the blood vessel if you have a constricted blood vessel that's going to make it harder for blood to flow through that constricted blood vessel so it's going to increase the resistance to blood flow every time you increase resistance that's going to increase blood pressure so this is remember this is a characteristic sympathetic response which is the fight of flight response in a stressful situation which obviously you start you have increased heart rate uh increased heart rate and then that's going to kind of increase your blood pressure okay remember in any stressful situation you want those blood glucose levels to be as high as possible and then remember that glucose pairing effect that we talked about where all of that glucose is diverted to or or spared for critical organs in the body namely the brain the heart the cardiac muscle and the the skeletal muscle so what i want to do next is to elaborate a little bit about how your body responds to stress but i'm going to break this down into two different varieties depending on the duration of the stress so short-term stress is controlled by the adrenal medulla by the release of epinephrine and norepinephrine bringing about those different responses in the body okay so short-term stress is controlled by the medulla bringing about vasoconstriction elevated heart rate elevated blood pressure all of that but then long-term stress is controlled by uh the adrenal glands specifically the adrenal cortex which allows for the release of the glucocorticoids such as cortisol and hydrocortisone and all of that and that's how you combat long-term stress so really it's a cooperative effect uh from the adrenal medulla and the adrenal cortex they kind of work together just kind of depending on the severity of the the stressful stimulus whether it's short-term or long-term so let's add a little bit more detail to this this is focus figure 16.2 from your textbook this is really really important for you to understand so i'm going to kind of explain this to you so how does your body combat short-term stress remember for short-term stress this would be the sympathetic nervous system kicking in this needs to be a very quick response um so your sympathetic division of promoting the fight-or-flight response so from the hypothalamus you've got the sympathetic neurons that are then going to target the very inside the core of the adrenal gland namely the adrenal medulla i remember short-term stress is controlled by the adrenal medulla which then prompts the release from those uh chromophil cells uh prompts a release of um epinephrine and more epinephrine and these are neuro hormones that are released into the bloodstream and it has one two three different effects cardiovascular respiratory and metabolic effects very simply uh the cardiovasc within the cardiovascular system the release of these hormones epinephrine and norepinephrine from the uh the medulla the adrenal medulla is going to do two things it's going to increase the heart rate and also going to increase blood pressure within the respiratory system because remember um enough in a fight-or-flight response you want to produce a lot of atp to to uh to sustain that high activity well in order for atp to be uh generated within different cells of the body you're going to need oxygen so therefore respiratory effects of epinephrine and norepinephrine is to bring about bronchodilation meaning this is opening up um airways and therefore you're able to bring in more you're going to inspire or you're going to inhale more oxygen so that's going to increase oxygen uh inspired or brought into the alveolar airspaces which obviously then can be um transported in the bloodstream to different parts of the body so that's the respiratory effects the third is how does epinephrine and norepinephrine bring about metabolic effects remember in any stressful condition it is to make sure that you have blood glucose levels as high as possible and of course that glucose is going to be diverted to critical cells of the body like skeletal muscle and cardiac muscle and brain cells neuronal cells um to increase your overall metabolic basal metabolic rate so those are the three different effects the responses of epinephrine and norepinephrine in the body in response to short-term stress which is all dictated by the sympathetic division of the autonomic nervous system it's dictating the fight-or-flight response by releasing epinephrine um and norepinephrine okay so this is short-term stress right how does the body combat long-term stress then okay this is where the adrenal cortex comes comes into place remember the medulla right there in the middle that responded to short-term stress by releasing epinephrine and norepinephrine for long-term stress though chronic stress this would be the adrenal cortex specifically that middle layer which is the zona fascicular releasing your corticosteroids okay so in response to um long-term stress the hypothalamus releases crh uh prompting the release of acth from the anterior pituitary then targets my adrenal cortex specifically the xana fascicular layer releasing corticoster i'm sorry a glucocorticoid such as cortisol okay it also prompts for prompts the release of mineralocorticoids like aldosterone ah from the zona glamorous loss as well let's first start with the glucocorticoids like cortisol okay because this is uh kind of relevant to the long-term stress response so the most important thing remember in a stressful situation is metabolic effects so this is going to make sure that you have enough glucose levels in the blood okay so it's going to do two things here because we're talking about this is the long haul right this is for long-term effects of stress um this is where you're going to start to break down complex lipids like fat and it's also going to start to break down proteins so when proteins are broken down into amino acids you can use those amino acids to generate glucose this is all for long-term stress response you can also break down fats stored in adipose tissue and convert that into anti-blood glucose okay so bottom line is you want to make sure those glucose levels remain as high as possible in the blood so this will be the metabolic effects of those glucocorticoids okay uh now remember the glomerulosa when it releases mineral or coracoids like aldosterone what is it going to do remember aldosterone is going to bring about sodium reabsorption from the tibial kidney tibial into the bloodstream at the same time waterfall of salt i said so therefore you're going to see water also being reabsorbed from the tibial into the bloodstream and therefore you're going to increase your blood volume and also indirectly increase your blood pressure so those are the metabolic effects um of how your body combats uh long-term stress so remember short-term stress is uh is ka is um controlled uh by the adrenal medulla by releasing epinephrine and norepinephrine those fight-or-flight hormones and long-term stress is controlled by the adrenal cortex by mostly controlling for the release of glucocorticoids from the adrenal cortex okay so the last important endocrine gland that i want to discuss is the pancreas okay so this is both a digestive and an endocrine organ if you're looking at a cross section of the pancreas which you should have covered in lab uh all of this surrounding tissue right here this is a digestive tissue called acinar tissue these are the ones these are the cells that are going to produce digestive enzymes which obviously we're not discussing in this video this would be part of the digestive system that comes up a little later on our focus is on each of these units right here which is called a pancreatic eyelid um within the pancreatic arter so that's the endocrine portion of the pancreas within the pancreatic eyelid there are two main populations of cells you've got your alpha cells which produce uh glucagon and glucagon is a hyper glycemic hormone meaning this is one hyper meaning increased so this is going to glucagon is going to increase your uh blood glucose levels okay uh beta cells on the other hand produce insulin and this is right the opposite it's a hypo glycemic hormone meaning this is going to reduce or decrease uh the blood glucose levels so as you can kind of already see here glucagon and insulin are antagonistic to each other glucagon is going to increase the glucose levels in the blood and insulin does right the opposite opposing the effects of glucagon uh by reducing the blood glucose levels okay so you can kind of see both those populations of cells uh typically you're darker staining cells are your alpha cells which produce glucagon and then the lighter cells would be your um beta cells which produce insulin okay so what i want to do is to explain the response of glucagon and insulin within the cells of your body and exactly what does it do and how does how do these two hormones oppose each other so how are they antagonistic to each other okay so let's uh start with insulin insulin is produced by those beta cells within uh the pancreas and it's a hypo glycemic agent meaning it's going to reduce uh the blood glucose levels okay now already from the previous slide you should have gathered that glucagon is an antagonist to insulin in other words it opposes insulin so glucagon is one such antagonist but really there are many other antagonists in the body uh two insulin epinephrine growth hormone uh your thyroid hormones like thyroxine fatifah cortisol any of these hormones would be would have an anti-insulin response or have anti-insulin effects in the cells so therefore we really need to understand what response does insulin bring about um in the body okay and then i'm going to compare this with uh and kind of contrast it against glucagon as a primary antagonist to that insulin um so this is a word slide which kind of explains um [Music] what's the main stimulus of the trigger for insulin production i'm going to explain to you what's the fed state different anti-insulin hormones uh kind of have repeated it over here as well uh and then i'm gonna explain to you exactly how glucose uh brings about a response uh within cells and there's three different things that actually happen i believe i have this summarized on one of these next slides um i think it's it's a slide after this uh glucagon on the other hand like i said is a hyper glycemic agent meaning it's one that's going to increase your blood glucose levels it's going to work right the opposite of insulin and this is released in not the fed state but the fasted state and then i'm going to explain to you these two concepts of glycogenolysis and gluconeogenesis um and how that relates to glucagon okay just remember insulin and glucagon are antagonistic to each other i actually have my own um note slide right here which kind of puts both of these um hormones into perspective and how they actually counteract the effects or the responses of each other so i've got insulin explained on the left and then it's antagonist namely glucagon explained on the right super important very very um vital and critical that you understand the responses of insulin and glucagon within the body when is it released what is its response so it's always the same story it's always a negative feedback mechanism there's always got to be some kind of a trigger or a stimulus that prompts the release of each of those hormones and that's kind of what you see here in blue and then i've explained what are the different steps that occur after that and then ultimately how do you counteract this trigger because that's your negative feedback mechanism is what kind of response is brought about with respect to that particular uh hormone so let's start with incident on the left okay okay insulin is released in the body in response to a state called the fed state okay so what do i mean by this when i've just eaten a meal and all of that food containing hopefully a balanced diet which we all try to do i think for the most part um so say you've eaten a meal that's composed of you know some part carbohydrates and then proteins and lipids well as it um go through all the different digestive organs uh this is going to go through the digestive process where you're going to break down all those carbohydrates into monosaccharides like glucose and fructose and galactose all of your complex lipids are broken down into fatty acids and glycerol and monoglycerides and then of course you've got your larger proteins that are broken down into your simplest uh amino acids so all of this is happening right okay so that's why this is called the fed state because you've just eaten a meal okay now remember the rest and digest system is the parasympathetic division of the autonomic nervous system so prompted by the parasympathetic division in response to all of this food that you've just eaten and as it goes through the stomach and all the other digestive organs you're going to facilitate digestion and you're going to start breaking down all of those food groups those organic molecules into their simplest building blocks so therefore all those carbs get broken down into glucose right which is absorbed by the blood and that's why you see an increase in blood glucose levels which makes sense all of that glucose was broken down from those complex carbohydrates and this is all happening in the fed state so this becomes my trigger so in response to uh elevated or increasing levels of glucose in the blood the beta cells of the pancreas will release insulin okay so insulin is released in response to this trigger right here which is increasing blood glucose levels what does insulin do it works in three different ways uh insulin is going to take all of that glucose from the blood and it's going to move it out of the blood that's the bottom line okay it's going to do three different things well first it's going to get all of that glucose out of the blood and it's going to divert it into all the different cells of your body so this is what we call cellular uptake of glucose so i'm going to move it out of the blood into the different cells of your body right so let's say skeletal muscle cells um any cell of your body because why are we moving this into the cell because the glucose is used as a substrate for this whole concept of cellular respiration which then allows for um a production of atp cancers this is why you would use glucose as a substrate to generate atp to power all the needs um the the the work that needs to be done uh in different cells of the body okay so once you move that glucose into the cell most of that glucose is used to generate atp but what if you have excess glucose so this is where you will divert all of that excess glucose to the liver where you would convert that glucose to a storage form called glycogen so this is the creation or synthesis or genesis of glycogen does that make sense genesis is synthesis so i'm taking that glucose and i'm converting it to glycogen this process is called glycogenesis meaning genesis or synthesis of glycogen okay now what if you still have excess glucose okay this is really where it gets interesting you would move all of that excess like glucose into adipose tissue where it then gets converted into fatty acids unfortunately and it gets stored obviously as excess fat adipose tissue right that's why you cannot overdo those carbohydrates in the meal because that's going to cause retention of all of that excess glucose as fatty acids and starts to manifest as all of those extra layers that are not so desirable okay so those are the three ways by which insulin would act bottom line is i'm going to take all of that glucose that's building up in the blood and i'm going to move it out of the blood and put it into the cells and do one of these three different things so because i'm moving it out of the blood what do you think would happen to glucose levels in the blood well the response then would be to drop those blood glucose levels and i hope you understand why because i'm moving those gluco that glucose into different cells of the body and that's why you see a drop in blood glucose levels classic negative feedback mechanism here's my trigger i'm seeing an increase in blood glucose levels when insulin kicks in it's going to correct this problem increase in blood glucose levels by decreasing blood glucose levels so this is an opposite effect right it's an opposite response uh in comparison to the trigger that's why it's a negative feedback mechanism so therefore what does insulin do the response of insulin is to decrease or reduce blood glucose levels and that's why it's a hypoglycemic hormone or a hypoglycemic agent okay hypoglycemic meaning reduction or reduced blood glucose levels okay okay now just like our example uh on a previous slide where we talked about uh the antagonistic behavior of parathyroid hormone and [Music] calcitonin right in regulating blood calcium levels well it's the same concept here okay the response of insulin now becomes the trigger for glucagon okay so those decreasing blood glucose levels becomes the trigger for the release of glucagon from the alpha cells of the pancreas so different population of cells okay now this is called the fasted state because okay in the fed state where you have a lot of glucose you're breaking down complex carbs converting it into glucose and that's why you released insulin and then this whole process is going to take about two to three hours or so to where you're moving all of that glucose out of the blood and diverting it into the cells and basically you're using up all of that glucose and that's why your blood glucose levels are dropping so that brings about the fasted state meaning you're in between meals typically about two to three hours after you've eaten a meal this is when glucagon is released because now think about it the glucose levels in the blood are dropping but your cells still need to pro to make atp to uh to sustain all of that cellular activity so where so that's going to alert the body and release glucagon because glucagon is going to do right the opposite of insulin all it's going to do is reverse all of these three steps to bring about an increase in blood glucose levels okay so let's talk about this so the trigger in this case for glucagon would be dropping blood glucose levels causes the release of glucagon from those alpha cells of the pancreas so what is it going to do work in opposition to insulin it's going to reduce cellular uptake of glucose meaning it's not going to divert that glucose into the cells instead it's going to keep that glucose in the blood and therefore it's going to keep those blood glucose levels high and then remember all of that excess that was stored in the liver you had glycogen is the storage form well back convert it convert that glucose back into blue i'm sorry convert the glycogen back into glucose and put it into the bloodstream okay and then same thing with the um adipose looks like i'm missing an arrow here this would be converting those fatty acids back into that excess glucose and putting it back into uh the bloodstream okay so this uh in i'm going to explain these two processes here uh glycogen converted to glucose this would be breaking down glycogen into glucose that's why this is glycogen or lysis lysis meaning breakdown taking the fatty acids and converting it back into glucose this would be generating glucose from a new source a non-carbohydrate source the non-carbohydrate source in this case is a lipid like a fatty acid so that's why this is called gluconeogenesis okay um okay so by these three different steps here okay what i just accomplished is i um was able to uh put all i'm gonna generate all of that glucose and i'm going to divert it into the blood therefore increasing blood glucose levels ah this is therefore called a hyper glycemic agent now obviously the response of glucagon which is increasing blood glucose levels would then serve as a trigger for insulin and so now i basically have a feed forward loop between glucagon and insulin which kind of balances out the effects of each other maintaining homeostatic levels of glucose in the blood making sure that it does not drop too much and does not increase too much so it's always going to be a balance between those two hormones that that tends to maintain homeostasis in the body okay i went ahead and put in that arrow that was missing just a while ago so again i just want to kind of point out these three processes shown in green let's just kind of work with with this here first so remember converting glycogen back to glucose would be kind of breaking that glycogen which is a larger form to glucose that's why this is glycogenolysis lysis of glycogen okay and then converting a non-carbohydrate source such as fatty acids which is a lipid okay converting it into glucose would be creating glucose from a non-carbohydrate source or a new source that's why this is gluconeogenesis okay and then uh on on this end of things uh converting the glucose to glycogen is creation of glycogen so therefore glycogenesis okay so make sure you know these three terms because that's really important so hopefully you understand the interplay and the balance between insulin and glucagon this is a classic example of how they are antagonistic to each other uh just remember the main response of each of those hormones uh remember if you remember insulin is one that decreases blood glucose levels because glucagon is antagonistic to insulin glucagon is going to do right the opposite of this by increasing blood glucose levels okay um okay so now that we've talked about the role of insulin and glucagon let's go ahead um and put this all together using this schematic this is from your textbook so okay so you've got two feedback loops here okay so this is balance this is your normal blood glucose levels um so i'm going to look at what's going on on the top here first and then discuss the this bottom loop okay so what if i have a homostatic imbalance condition here's my trigger or my stimulus where i'm starting to see an increase in blood glucose levels right so it's not normal anymore it's an elevated blood glucose level remember this would this would be something you see in the fed state when you've just eaten a meal so in response to this stimulus the pancreas will release insulin okay think back to my previous slide but put this all together um when the insulin is released this is going to do several different things if you remember the most important thing is to take all of this elevated glucose level in the blood and diverted into different cells within the body which allows for atp generation basically i'm getting it out of the blood any excess glucose like i said was taken to the liver where you would convert that excess glucose into glycogen this process was called glycogenesis creation of glycogen what you don't quite see here is the adipose tissue um represented that glucose could also be converted into fatty acids um and kind of stored in that in that storage form bottom line is because the insulin is removing this excess glucose from the blood and diverting it either to the cells or to the liver what happens to those blood glucose levels it starts to drop coming back to a balanced homeostatic condition so then on the bottom let's look at the opposite scenario which is where you're seeing my trigger in this case is dropping blood glucose levels now this is what you typically would see in the fasted state like between meals when those glucose levels in the blood are really starting to drop why is that the case because the insulin has already moved all those cells i'm sorry moved all of that glucose into the cells or it's been stored already so that's why you're seeing the drop in blood glucose levels in response to this the pancreas will release the glucagon and glucagon works right the opposite of what you see here it's going to prevent cellular uptake but then also it's going to convert that storage form glycogen back to the glucose this is called glyco glycogena okay because you can you're breaking it down into glucose uh also in the in the adipose tissue fatty acids gets converted back into glucose so this would be gluconeogenesis and because you are breaking it down into glucose and you're putting it back into the bloodstream that's going to bring all of that glucose levels in the blood back to its normal homeostatic balance condition okay okay so now that we've talked about the pancreas and those two important hormones namely the namely insulin and glucagon and what it does to the body i'm going to then wrap this up with our discussion on uh diabetes mellitus dm okay so remember what is insulin do insulin is one that it's a hypo glycemic agent so therefore it's going to reduce blood glucose levels this is how insulin would work what if i have a problem with insulin what if i have a complete absence or hyposecretion of insulin this would result in type 1 diabetes or if the insulin is produced but is it somehow non functional or has less activity so hyperactivity this will result in type 2 diabetes regardless we have a problem with insulin so if you do not have insulin what does insulin do it's reducing blood glucose levels in the absence of insulin or when it's non-functional it's going to have right the opposite effect and so in case of diabetes because you have non-functional insulin uh you would start to see an increase in blood glucose levels okay so that's the that's the bottom line of the pathology of diabetes there's a little bit more that we need to add to this discussion now think about this as your blood glucose levels start to increase remember all of that blood um makes its way through the kidneys which then means that that blood becomes part of the kidney filtrate and as it gets filtered through the through the kidney tibials right all of that excess glucose uh in the filtrate kind of makes its way and spills over into other urine this condition is where you see excess glucose in the urine is called glycosyria um here are the three important signs that are characteristic of diabetes mellitus polyuria okay this is where you have a huge urine output and i'll explain why in just a little bit polydipsia this is excessive thirst and polyphasia which is excessive hunger okay so those are your three cardinal signs i'm going to use the next schematic to put all of these different concepts together to tie them all together so this kind of makes sense okay here's another word slide uh which kind of explains um this whole production of ketones and this will make sense when i get to my schematic and the build up of ketones because it's um it's an acidic i mean because it's an acid this can cause something called ketoacidosis which is a problem so let me go ahead and explain the whole concept of diabetes and this is a very important schematic okay so remember in the case of um diabetes you're seeing an insulin deficit this could be because of um reduced or zero production of insulin or hypo activity of insulin so we have a problem with insulin okay all right so i'm going to kind of work my way from the left towards the right and explain what happens how does your body respond to this problem which is a drop in insulin levels okay what does insulin do if you had normal insulin it would uh divert all of the glucose from the blood into the different cells of the body where you so it's going to increase cellular uptake right and this is going to uh basically be used to then then generate atp okay but here's my problem i don't have enough insulin or it is non-functional in the case of diabetes so therefore pretty much all cells and tissues are going to experience this problem without the insulin i'm not able to um kind of divert that glucose into the cell so i have less glucose uptake and so therefore if i have less being taken up by the cells this is why i'm starting to see a buildup of glucose within the blood this is called hyperglycemia okay so which is uh increased blood glucose levels so i'm kind of breaking this down to different compound or different um uh topics here um this red part is showing me uh what's going on in the blood and then everything here in the yellow would be what's what are the changes occurring in the urine and then this last part here on the bottom which is all of the different symptoms associated with those changes um in the blood in the urine okay so because of the lack of insulin you are not able to divert that glucose into the blood and uh sorry glucose into the cells and so therefore you're seeing a buildup of glucose in the blood this is hyper glycemia and remember we just said in the previous slide all of that excess glucose in the blood as it makes its way through the kidney uh and becomes part of the filtrate well all of that excess glucose then spills out uh in in the urine and this condition is called glycosuria now uh in the kinetic bills glucose because you have excess glucose uh kind of like uh like sodium glucose also tends to pull water okay but it's going to pull water excess water into the kidney tibials uh kind of acts um to because i'm pulling water into the kidney tibial this is going to increase your overall urine output this condition is called polyurea so if you're eliminating uh excess kind of water from your body uh by increasing the urine output then what does that mean it means that your overall going to get dehydrated because you're eliminating too much water from the body too quickly so therefore this excess urine but it's going to result in dehydration of the cells which then obviously would uh trigger kind of a sensor and the hypothalamus of the brain which then prompts water intake so therefore you feel thirsty this is polydipsia okay so let me kind of put this back into perspective one more time because of the lack of insulin you are going to have you're going to see a buildup of glucose within the blood called hyperglycemia that's going to spill all that excess glucose is going to spill out into the urine called glycouria because of that excess glucose flowing through the kidney tibial that's going to pull all of the water back into the kidney tibial um increasing diuresis meaning increasing urine output this is called polyurea this condition is polyurea because you are in um releasing more water from the body lost as urine therefore your cells and other tissues are going to start to get dehydrated prompting the thirst reflex meaning you're going to want to drink more water which is polydipsia okay so that's one part of the story okay uh the rest of this let's focus on three important different organs the liver the skeletal muscle and the adipose tissue okay so when you have less insulin uh remember what's what's happening here is you're not able the insulin is important to move the glucose into the into the cells uh without that insulin i'm not able to move it into the cells and therefore i don't have enough glucose as a substrate inside of the cell to generate atp so your body goes into this crisis mode thinking well i don't have enough glucose well in fact you actually do have too much glucose except the glucose is stuck in the blood plasma you're not able to move it into all the different cells and tissues of the body because you have an insulin deficit okay so in the meantime um all the cells of your body are going into this panic mode going okay where's all the glucose uh i'm not because the cells are not seeing the glucose you're not able to move it into the cells so in the absence of all of that glucose this is where the liver kicks in remember excess glucose is stored as glycogen in the liver right so what the liver does is it takes that storage form glycogen and it breaks it down into glucose so this process if you remember was called glycogenolysis uh it's not gluconeogenesis that was a mistake in your textbook so that should be glycogenolysis where you're breaking down lysis breaking down the glycogen into glucose does that make sense dear um and this is only going to compound the problem okay because what what happens here is all of that glucose that you're creating in the liver is only going to build up even further in the bloodstream resulting in more hyperglycemia regardless all of this glucose is still going to be stuck in the blood plasma you are not able to move it into the cells because you don't have enough insulin to do the job okay likewise skeletal muscle um it can then start to break down all of that muscle mass namely proteins proteins are converted into amino acids and then amino acids can be converted into glucose so this is creating glucose from a non-traditional non-carbohydrate source such as amino acids so therefore this is an example of gluconeogenesis again both glycogenolysis occurring in the liver and gluconeogenesis occurring in the skeletal muscle both of those are going to cause an increase in glucose which you put back into the blood and so that's only going to compound the problem okay so again your body or your cells of the body are thinking where's or where's the glucose i don't i don't see the glucose i don't have enough glucose to generate atp and so your body is tricked into thinking that there is no not enough glucose when in fact there is too much glucose like i said except it is unable to move out of the bloodstream you're not able to redirect it into the cells in the tissues because you don't have that trigger namely insulin to move to cause cellular uptake where it can be utilized for atp generation so therefore what do your cells do to compensate this is where in the absence of glucose which is what your cells are thinking that there's not enough glucose so in the absence of glucose or reduced levels of glucose your body will then divert or most of the cells of your body will look for a second source a backup source to generate atp always your backup source right behind glucose will be um lipids or fatty acids and then if all else fails uh of course use proteins and amino acids to generate that atp so as your backup uh source of atp this is what's happening um adipose or adipocytes will start to break down complex fats this is lipolysis and then in the liver so this is basically lipid metabolism i'm breaking down um complex lipids into fatty acids and then the fatty acids can then be used to generate glucose within the cells and therefore be used to generate atp okay um so one of the byproducts of this whole lipid metabolic pathway would be a generation of something called ketones or ketone bodies now ketones are acidic um it's an acid an acid is one that's going to generate free hydrogen ions so therefore what happens to the blood ph it's going to start becoming acidic it's going to start dropping because of the accumulation of those ketone bodies in the blood okay where are those ketone bodies coming from because of the fact that you are breaking down fats to generate that atp okay so that's one of the byproducts of this of this metabolic pathway so this results in a drop in ph of the blood plasma resulting in acidosis because it's caused by ketone body accumulation this is also called keto acidosis okay now those ketone bodies are just like the just like the excess glucose right uh same same concept here the excess ketone bodies in the blood then spill over into the urine resulting in keto urea like glycosuria in this case and the ketones they tend to pull cations into the kidney tubules what's a carry on it's a positively charged ion in other words it's going to pull positively charged ions such as sodium potassium hydrogen uh it's going to pull it into the kidney table where it is eliminated as urine you do not want to lose all of that sodium especially sodium so this is this is a negative effect of ketoacidosis and keto urea okay so ketoacidosis in itself is going to really mess up blood ph that's not good but then also as it's all of those ketone bodies as they spill into urea urine and then starts to pull out all of the sodium ions and potassium ions that's going to have other effects here in the body okay um sodium and potassium is very important for the generation and maintenance of the resting membrane potential any imbalances in those ions would cause um uh excitability um so therefore and this can kind of really cause changes in the in the nervous system it can cause um abnormalities in how the cardiac muscle functions resulting in uh heart arrhythmias okay and also um as you see build up of those uh ketones which is acidic um in the blood this is going to increase your weight and depth of breathing meaning you you're trying to eliminate all of those ketones um through increasing pre increased breathing kind of like how you would eliminate carbon dioxide so that in essence is kind of all the characteristics and the the features associated with uh diabetes mellitus okay so make sure you understand uh all of these different features uh hyperglycemia glycosyria the three cardinal signs i forgot to mention this one right here the three cardinal signs of diabetes would be polyurea which is increasing your urine output uh which causes dehydration like i said therefore increasing thirst which is a consumption of water polydipsia and then also this polyphasia which is an increase in appetite because you are losing muscle mass you're breaking down muscle um proteins um to to generate the glucose and you're also breaking down lipids complex fats uh to to kind of help with the generation of glucose again as a result this causes um an increased appetite this is called polyphasia okay so i think we've covered everything related to the pancreas the last thing i want to talk about is um a few more things to wrap up this discussion with the endocrine system uh gonads in the placenta okay we will discuss this in much more detail when we get to the end of the semester in our discussion of the reproductive system but for right now uh the female gonads are called ovaries which produce two important hormones estrogens and progesterone and that kind of explains you what all of those hormones do and of course the male gonads are called testes which produce testosterone and they also have an important role to play in the body i'm going to let you all kind of look at all of that it's pretty straightforward and then there are other hormones that are produced by many other organs in the body some of this you've already heard and others we've not really discussed just yet um adipose tissue releases a hormone called leptin this is very important in controlling uh the feeling of being hungry or controlling appetite okay in the gi tract we will talk about three important hormones gastrin secretin and cholecystokinin cck gastroenterol is what it's called collectively and this plays a huge role in uh controlling the release of pancreatic juices bile secretions from the liver uh and basically helps with the whole digestive process we've already talked about enp in a previous slide in relation to how it is an antagonist uh to aldosterone if you recall so what does a p do it's going to basically um kind of decrease your blood pressure your blood volume and then your blood pressure in the kidneys erythropoietin this was really this was in relation to rbc production renin we talked about this briefly in the previous slide it's important as part of the renin-ange aldosterone mechanism there are several hormones in the skin that helps in the production of vitamin d and then the thymus we'll talk about this a little later on with the lymphatic system and the immune system plays a huge role in the development of t lymphocytic cells to moderate the immune response so that wraps up part two of our discussion of the endocrine system um where we really kind of focused on antagonistic kind of behaviors of certain sets of hormones like we discussed the role of calcitonin and parathyroid hormone and then later on just just a while ago we talked about insulin and and glucagon our emphasis for this part two was mostly uh the the thyroid gland and its main uh response in the body which is controlling uh regulating um basal metabolic rate and heat production and then we went on to discuss uh the adrenal gland and there were many different regions of the adrenal glands so pay attention to that the adrenal cortex with its three different sub layers collectively secreting corticosteroids so you need to know all three layers and the different types of hormones that are produced from those three layers of the adrenal cortex and then of course the adrenal medulla releasing epinephrine and norepinephrine as part of the sympathetic nervous system response and then we kind of tie this all in together talk about uh how the body works in terms of stress so for short-term stress this would be the adrenal medulla with the fight-or-flight response if it's long-term stress this would be the corticosteroids like cortisol and hydrocortisone released by um the adrenal cortex in moderating long-term stress so pay attention to cardiovascular effects respiratory effects metabolic effects uh as moderated by um the medulla and the in the cortex in in regulating stress okay in the body and of course the last thing we talked about was the role of the pancreas you absolutely need to know uh the response of insulin versus um glucagon and how they are antagonistic to each other and how they kind of balance out each other okay so that really just kind of wraps up the endocrine system i hope this made sense to you and i hope you found this useful thank you