Anatomy Of The Human Essay, Research Paper
12-11-00
The endometrium has a cycle and it is linked to the ovarian cycle and it starts with the proliferative phase, which is a phase of growth. During menses the top two thirds of the endometrium is shed and during the proleferative phase it regrows, develops the uterun glands and at about the time of ovulation it switches to the secretory phase, which is characterized by the glands secreting a very thick mucous secretion. It is a time of implantation of a fertilized ovum can take place. If fertilization does not take place then at the end of 14 days the blood vessels in the endometrium begin to constrict, the tissue becomes necrotic and is ultimately shed during menses, and then the cycle repeats. The whole system, the coordination of the ovarian and uterun cycle is under hormonal control, Fig. 19-16. For example, LH starts and builds to a point and then it decreases. During follicular development there is a slight increase in LH then it drops and then there is a peak. Same time course of estrogen ? estrogen increases and has a big peak, has in fact two peaks. The granulosal of the developing follicle secrete estrogen and as the follicle gets bigger the theca develops and it also secretes estrogen. That estrogen feeds back and inhibits LH and FSH. There is a large accumulation of estrogen. Estrogens has lower concentrations as inhibiting LH and FSH. But a switch takes place so that when you have this very large serge of estrogen due to the fact that you have a very large mature follicle, which has many thecal and granulosal cells that are all visibly secreting estrogen. This high concentration of estrogen now suddenly stimulates gonadotropin release and LH. So at low concentration estrogen inhibits LH and FSH but at high concentrations, effectively stimulates it which gives you this large LH surge. It is this large LH surge that induces ovulation of the FSH prime follicle. So you need FSH and LH to ovulate, but it is the primarily the LH peak that stimulates the process. That also serves as the transition between proliferative phase which is driven primarily by estrogen of the endometrium. The secretory phase is driven primarily by progesterone. Progesterone is associated with the luteal phase, the corpus leteum, which is a piece of a follicle that is left behind after ovulation. And it is the progesterone that maintains the endometrium in the secretory phase. It is the sudden drop of both estrogen and progesterone that induces menses. In a case where fertilization has not taken place, you have an increase in a big peak in estrogen, and later peak because the corpus leteum secretes a certain amount of estrogen and lots of progesterone. Both of these will inhibit LH and FSH preventing further follicular development. But once they drop at 28 days, the corpus leteum degenerates therby secreting less and less estrogen and progesterone. So the demise of the corpus leteum signals the end of the secretory phase and menses takes place and the cycle repeats. If fertilization does take place, 19-26, there is large peak of chorionic gonadotropin, which is secreted by the developing placenta and the placenta consists of cells from the trophoblast from the embryoblast and the cells of the endometrium forming the placenta. The first thing that occurs is that there is a large surge of chorionic gonadotropin which will last from several months and that maintains the corpus leteuma and keeps it secreting progesterone and estrogen. That maintains the endometrium in the secretory phase and prevents further follicular development. Over time, if you look at estrogen, the levels climb and suddenly drop and if you look at progesterone it does a very similar thing. Initially as estrogen and progesterone comes from the corpus letuem but after about 2-3 months most of it will come from the placenta. So the maintanence of the high estrogen and progesterone prevents further follicular development for the next nine months and of course maintains the endometrium so the fertilized egg that is in the endometrium does not get shed. The first 14 days represent follicular development, growth of the ovum and the surrounding follicle. It is characterized by increases in production of estrogen and that in turn induces proliferation of the endometrium. Day 14 is ovulation and the switch due ot the surge in LH due to a more progesterone rich environment, which switches the endometrium to the secretory phase and inhibits follicular development. The balance between these hormones is what determines and separates the follicular phase form the luteal phase in terms of the ovary between the proliferative and secretory phase of the endometrium.
Now is the gastrointestinal tract and associated processes. The GI tract is a tube with associated glands through which food, solid and liquid move, is digested, mechanically and chemically broken down, absorbed and the rest is excreted. The inside of the GI tract is really the outside of the body although there are sphincters, one in the mouth and one in the anus that keep it a closed tube. Nevertheless it is a compartment system with the tube being outside and the body being the inside. Everything that moves from the food from the outside to the inside must pass through an epithelium to be absorbed and materials will be secreted into this tube. In a given time you may have 1200 ml of water and roughly 800 grams of food that enter they system. It goes from the mouth to the stomach. And in the stomach what adds to this rougly 3500 ml of saliva, and gastric secretions. So that the stomach will contain about 5500 ml of material. As that is processed it goes into the small intestine. The SI, you have about 2000 ml of bile and pancreatic secretion plus another 1500 ml of a secretion by the small intestine. It is important to realize that the SI one adds a major absorption from the system, roughly 8500 ml of material are absorbed. The majority of this are the secretions that you dumped into it in order to process the food that you started with. You add about 3500 to 5500 ml but you are absorbing 8500 in the small intestine and then it goes to the large intestine, or colon. And here the last little bit about 500 ml get absorbed and the resulting 100 ml of water and roughly 50 grams of solid waste get excreted in the feces. Fig 17-5,general point: 1) your GI tract and associated glands dump all hell of a lot of stuff into the GI tract in order to process the food. 2) The majority of aborption takes place in the SI and that the colon plays a very minor role in the absorptive process. Lets start first with the mouth.
The mouth has teeth and those teeth mechanically break down the food and mixing of the food with secretions from the salivary glands, ie, saliva. Saliva is a slightly alkaline salt solution, which contains some enzymes, particularly, an alpha amylase and the primary function of this enzyme is to break down sugars. To break down complex sugars into simple sugars which then taste sweet. It has a very minor digestive function, it is more to make food pleasant tasting. The secretion of saliva is under parasympathetic control and the rate of secretion can go from 0.1 ml/min to 4 ml/min. Significant increase by parasympathetic activity. The parasympathetic activity can increase for a number of reasons. 1) an anticipation, when you think of food your mouth begins to water, this is true because of a psychological input into the parasympathetic preganglionic neurons that cause secretion of saliva. The ANS relies on cortical input. This is a cortical input to parasympathetic, which has functional importance b/c one starts producing saliva before you put food in your mouth. So the mouth prepares the food as a boulus, that is a small packet of material mixed with saliva, fluid, water and food which then is passed down into the esophagus and then the stomach. The esophagus is a way for the food to get to the stomach from the mouth and nothing much happens in that transition. The stomach serves to store food, it dissolves it and it partially digests it. The structure of the stomach is complicated consisting of many folds of an epithelium consisting of cells. These folds in the epithelium have grooves which are known as gastric pits and then there are area of fairly smooth epithelium. The cells on the surface secrete primarily mucus which covers the surface of the lining of the stomach. Down in the gastric pits, there are cells that secrete mucus, there are other cells called parietal, there are chief cells and there are endocrine cells, sometimes known as B-cells. These cells are all mixed up in the gastric pit. So the gastric pit has these four kinds of cell mixed together in the pits within the glands. The mucus cells just like the mucus cells on the surface are secreting mucus. That mucus protects the surface, the cells of the epithelium The parietal cells secrete HCL, the chief cells secrete a protein called pepsinogen, which ultimately gets converted to pepsin. And then there are the endocrine and they secrete their product not into the gastric pit but into the blood supply in the stomach. So there are capillaries that underly the epithelium. So the endocrine cells that are secreting into the capillaries, they are endocrine and ductless, and they are secreting a hormone known as gastrin. So these 3 cells types secrete their product into the gastic pit while the endocrine are going the other way into the cardiovascular. But all four cell types are found on the epithelium of the gastric pits. These epithelium lies on top of layers of circular smooth muscle. When we are talking about ANS we talked the enteric plexus, that part of the GI tract and that there are two plexes of nerves, one of which lies in under the mucuso which is called the submucusal plexus, these nerves will affect the endocrine cells in that epithelium. There is the myonteric plexus which controls the smooth muscle that surrounds the outside of the stomach.
The secretion into the stomach:
The mucus are the lubrication system and protect the surface from acid. The paritetal cells secrete HCL, it reduces food, breaks it down into chyme ? small particle, slurry of small particles. It denatures protein, it converts pepsinogen to pepsin, which is the active enzyme. And then acid destroys some bacteria that were ingested with the food. The stomach can develop ulcers which are pores and is blamed on the HCL, but most ulcers are not produced because of HCL, they are caused by a bacterial infection by the lining of the stomach and the proper treatment is to take antibiotics. It is rare to have an excessive quantities of HCL that eats hole in your stomach, the mucus protects the surface of the epithelial cells from the HCL. You produce about 2 liters a day of HCL and has a pH of about 0.85. Just to remind you that the pH of plasma is 7.4. So how does HCL release. It is secreted by the parietal cells, and if you look at one it has a luminal surface, that is a surface facing the inside of the stomach and a basolateral side. It turns out that these cells in their luminal surface have a active transport system that secretes hydrogen and absorbs sodium. This is a ATP dependent pump because it is moving H+ ions against an enormous gradient. I can assure you that if H+ ion concentration in the parietal cells was 0.85 that would be a dead cell. So it is moving H+ ions against this enormous gradient and is does so by converting ATP to ADP. It is therefore not surprising that parietal have lots of mitochondria. The mitochondria are the major source of ATP by oxidative phosphorylation. So where does the hydrogen come from? They have capillaries and these capillaries contain CO2. CO2 will diffuse into the cell where it will meet carbonic anhydrase. Where it functions to convert CO2 into bicarbonate. That bicarbonate can diffuse out of the cell and be transported into the plasma or within the red blood cells. Remember also carbonic anydrase is present in the kidney and also present in the pancreas. Carbonic in this case converts CO2 into HCO3 and that H is what gets pumped out by the active pump. Obviously then, there is an accumulation of bicarbonate within the cell and there is a co-transporter system, where the bicarbonate moves out into the cardiovascular system and CL ions moves in. This CL ions keeps on going down its concentration gradient and gets secreted by the H+ ions that is actively pumped. So the only ATP dependent portion of this system is pump that moves the H+ ions across the apical membrane into the lumin of the stomach. Carbonic anhydrase is necessary in effect it takes CO2 converts it into carbonic acid, the H+ gets pumped out and the bicarbonate gets exchanged for CL. That is how the parietal cells are able to secrete HCL. This process is controlled in two ways. It is controlled by Ach, released by nerves of the enteric plexus, specifically that portion that lies underneath the epithelium, the mucusol plexus. It is also stimulated by Ach secreted by parasympathetic nerves. The second control is by gastrin, which is the hormone secreted by the endocrine cells of the gastric pits. As in the production of saliva, the anticipation of food that gets the parasympathetic going, you begin to salivate, it will stimulate the parietal cells to begin to produce HCL and this will be needed for the digestive process. The enteric plexus is more sensitive to the stretch of the stomach, so as the food begins to accumulate in the stomach the wall of the stomach stretches and that will induce cells to secrete acetylcholine which will also stimulate the parietal cells. One of the side effects of gastrin. Gastrin will stimulate the parietal cells as well, what controls gastrin? It turns out that endocrine cells are sensitive to the pH of the stomach. If the H+ ion concentration drops, you get production of gastrin. So if the H+ ion concentration drops you get an increase in gastrin. When you eat protein and they get digested in the stomach, that is, broken down into amino acids by both the HCL and pepsin, amino acids and small peptides will bind hydrogen therefore if you brake down more and more protein, the pH will increase, will become more basic. The H+ ion concentration will drop and that will induce an increase in gastrin and that in turn will stimulate the parietal cells to produce more acid. Conversely, in you don’t have that much protein, if theres not much food in there, then H+ concentration will be high and you will not activate gastrin to further stimulate the parietal cells. So both control systems then regulate the production of HCL by the paritetal cells. As the food moves from the stomach into the small intestine, in particularly enters the duodenum, which is the beginning of the SI, the acidity of this chyme plus the stretching of the duodenum will reflexely inhibit gastrin production. So the acidity and stretching will inhibit gastrin production and effectively inhibit or slow HCL secretion. So that as food begins to move into the duodenum some hours after its in the stomach, with these reflexes will inhibit the parietal cells to reduce the amount of HCL secretion. So this the parietal cells secreting HCL.
What about the chief cells? The chief cells secrete an inactive protease, pepsinogen, and it is inactive because you cant have a bunch of active proteases sloshing because they will digest themselves, so when it is in the inactive form, which when secreted in the stomach and in the presence of H+ ions, it is converted to pepsin, which is a protease. Now pepsin, works on protein, digesting them, breaking them apart into peptides and amino acids but it also converts more pepsinogen to pepsin. Here is the case of a positive feedback loop. The more pepsin produced, the more pepsinogen that is going to get converted to pepsin. So the H+ ion will convert pepsinogen into pepsin. So the H+ ion will convert pepsinogen to pepsin, but the pepsin turns around and converts a lot more pepsinogen into the active form. This process in the activity of the enzyme is tuned to function at very low pH, high H+ ion concentration. Enzymes are very sensitive to pH and are highly tuned. Pepsin only works at low pH, high H+ ion concentration. As it moves into the instestine, the pH will rises to more alkaline condition, the pepsin becomes inactivated. So low H+ will inactivate pepsin and reduce the conversion of pepsinogen to pepsin. Again the chief cells are controlled by the enteric plexus and in a similar manner, the parietal cells. The stomach is surrounded by two layers of smooth muscle and it functions to create the waves, peristaltic waves. So contraction has sweeped from top of the stomach to the duodenum, the beginning of the small intestine. There are roughly three waves per minute and as the waves come down over the stomach and gets close to the duodenum, a sphinctor between the stomach and the duodenum closes. But it does not close completely, so there is a little squirt of material that leaves the stomach and enters the duodenum. So called pyloric valve, basically restricts the amount of material moving from the stomach into the duodenum to a relatively small amount. So these peristaltic waves serve to mix the contents of the stomach, the pepsin, the food, the HCL, allowing some breakdown of food to take place and every now and again a squirt of material will move from the duodenum. The next important part of the GI tract is the SI and it is the largest, and it is the place where almost all the absorption takes place. The beginning in the duodenum, you have a very acidic material that enters from the stomach and in the duodenum gets mixed with the secretions of the pancreas and the liver. Specifically the pancrean is a dual gland, it is exocrine and also has an endocrine component which is crucial in the regulation of metabolism and digestion secreting insulin and glucogon. The liver secretes bile which is an important substance for the digestion of fats. Like the stomach the SI has a very highly convoluted epithelium That epithelium is in a very long tube. So it is a very highly folded epithelium surrounded by two layers of smooth muscle similar to the stomach. If you look at the epithelium it has a very characteristic structure which is in Fig.17-7, it is characterized by the series of folds out into the lumen known as the villi, and each is a villus and a series of pits similar to the gastric pits that go into the submucosa and they are called the crypts of Liberkuhn.The villus is where absorption takes place in the SI and the crypts of Liberkuhn are secretory glands in the similar way to the gastic pits. For example, the villus is well supplied by blood vessels, capillaries as well as ducts of the lymphatic, that portion ofhte cardiovascular system that picks up interstitial fluid and carries through and back to the heart, it is another way to reach the heart, and it goes through what is called lymph and it goes through lymph nodes. So the lymphatic system is very important in the digestive process of fats. The primary absorption takes place in the villus and secretion in the crypts of Lieberkuhn. One other thing, not only is it very folded by the cells of the epithelium themselves, they have what’s called brush border, which is the apical membrane which faces the interior of the SI has many fine projections increasing the surface area for absorption. This epithelium is contained within the normal digestive structure both circular and longitudinal smooth muscle controlled by the enteric plexus. But here in the small intestine unlike the stomach the contractions are not peristaltic. In the stomach the peristaltic is a wave of contraction that moves over the stomach pushing the material toward the pyloric sphinctor. In the SI the smooth muscle just contracts in place, there are no waves of contraction, it is a process called segmentation. So segmentation means that the SI will have places of contraction, they will relax and the next place will squeeze. So how the chyme move if it is not pushed. Because you are absorbing things as you go along, because its the pressure gradients because there is stuff coming all the time and as you are absorbing things there less material here and so it is simply pushed along. The segmentation simply serves to fix the contents. To facilitate the exposure of food stuff to the epithelium and the enzymes within the SI.
So what are the Intestinal secretions? One is mucus. The material entering the SI from the stomach is very acidic so the epithelium of the SI also needs protection and lubrication. The second major secretion from the crypts of Lieberkuhn is water and salts. It produces about two liters per day. This secretion is an active process, an energy dependent process of moving water and salts into the lumen of the SI. As mentioned earlier, the SI dumps a lot of stuff in, about two liters a day. Now sometimes certain bacteria such as ecoli or certain so called enterotoxins, such as toerotoxins by mechanisms which are not clear increase this rate of this secretion. And if you increase of the secretion you can overcome the ability of the SI to absorb all that material and that results in diarrhea. The major danger from tolera is the dehydration because you are pumping out all this water out into the lumen of the SI. One of the major secretory products is in fact water and salts ? important point. It is the movement of the salt that pulls the water by osmosis. Another major secretion into the SI, the duodenum, comes from the pancreas. There are two major secretions from the pancreas, 1) the Zymoges ? inactive enzymes packaged together and in fact pancreatic cells with the cells use. The zymogens are these packed enzymes consisting of amylases which digest starches, there are 3 lipases and many proteases, some DNAases and RNAases. These are all packaged in inactive form, they get secreted, they get dumped into the SI and they become activated. For example, one of the proteases is trypsinogen, which gets converted to trypsin once it reaches the interior, the lumen of the SI becuae there are enzymes known as enterokinases that line the surface of the SI that activate by breaking, cleaving a chunk off the trypsinogen and converting it to the active form of trypsin. It turns out that trypsin, aside form digestin proteins, it is a protease, will also activate many of the other enzymes that were secreted as zymogens. So the pancreas secretes zymogens, which is a package of inactive enzymes just for chewing up material. It gets into the lumen of SI, the trypsinogen gets converted to trypsin and that process, trypsin ? activates many of these enzymes. Now in addtion, the second major secretion of the pancreas is bicarbonate. The chyme that enters the SI, the duodenum, it is very acid because it is coming from the stomach. By the time you reach the end of the SI the chyme gets basic. In part it is due to bicarbonate ions secreted by duct cells of the pancreas. So how does the pancreatic duct cells secrete bicarbonate. They do so because they have a very active, as do all cells a sodium, potassium pump and they also have in the luminal membrane and ATP dependent pump that is secreting bicarbonate and bringing in chloride. So where does the bicarbonate come from. CO2? carbonic anydrase ? bicarbonate, so what happens ot the hydrogen. In the basolateral membrane there is a co-transporter that is driven by the inward movement of sodium which of course it wants to go into the cell because of the concentration gradient so it is like a water wheel. Sodium moves in and the hydrogen is secreted in the basolateral membrane. This is a co-transport system, which does not directly require ATP. It requires the gradient established by the sodium, potassium pump. But the transporter in the apical membrane use ATP, so it is a ATP dependent pump, so both these are ATP dependent. So again it is no surprise that pancreatic cells that are secreting bicarbonate have lots of mitochondria. These pancreatic secretions are controlled by hormones. Just like the gastric pits, the crypts of Lieberkuhn in addition to have cells that move water and salt into the lumen have endocrine cells. And they secrete three major hormones. 1) choliocystokinase (CCK) ? stimulates zymogen release, the cells of the pancrease synthesize zymogens and package them in granules and CCK released by cell in the crypts of Lieberkuhn stimulate the aster? Cells to release their zymogen. So what stimulates CCK? The presence of amino acids and fates in the SI stimulates CCK production which of course stimulates zymogen. As the level of amino acids and fats drop, the production of CCK drops and the amount of zymogen release will drop. 2) secretin? stimulates both bicarbonate and zymogen. It is sensitive to increase in H+ ion concentration in the chyme in the SI. So the more material that comes from the stomach with more H+ ions the more secretin will be produced and that will then stimulate bicarbonate and zymogen production. Secretin also has one other function and that is to inhibit gastrin. So as the food moves into the SI you get an inhibtion of HCl production from the stomach. 3) GIP, glucosedependent insulinotropic proteins? stimulated by the glucose and fats. It is secreted by the endocrine cells by the crypts of Lieberkuhn and it causes pancrease to secrete insulin. So these are the major hormones secreted by the crypts of Liberkuhn that controls pancreatic