Transcribed by Stephen Holt Organ Systems 24- Histology of the Digestive Glands by Dr.

Wishe

April 5, 2014

[2] Ok I guess we might as well start. When we do lectures in Septodont theres roughly 40 people. I did a count there are 17 of you were so maybe a couple more will drift in. Maybe. So today Im going to finish up discussing anatomy/histology of the digestive system by dealing with the digestive glands and as everyone realizes theres another lecture after this. This is being done by Dr. Pavlov, finally got his name down pat. And hes going to start the physiology of the digestive system. So besides the tract there are the accessory digestive glands which include the liver, the gallbladder, and the pancreas plus lets not forget the salivary glands inside the oral cavity. The liver is one of the largest organs in the body and the covering of the liver is actually derived from endoderm. In fact the whole digestive tract lining is derived from endoderm and then the stroma of the organ youre going to find blood vessels and nerves, so mesoderm plays a role in forming of your connective tissues, etc. The organ is divided into lobes, namely four different lobes with the right lobe being the largest and you can see peaking out from the ventral surface from the right lobe is this little green structure and thats the gallbladder. So we have a right lobe, a left lobe, a quadrate lobe, and a caudate lobe. This picture comes from one of the anatomy books and shows you the relationship of especially the liver to the rest of the body we see the rib cage and in my discussion of the skeletal components I had mentioned the number of ribs attached directly to the sternum. Those are your true ribs and then you have your false ribs where all the costal cartilages sort of fuse together and attach to the sternum. And peaking out in the corner of this side and this side there are 2 floating ribs we only see one per se. So the rib cage is partially protecting the liver. I think were up to 22 now. But the problem is if you get into an accident of some sort, even a bicycle accident, and you hit the rib cage, the ribs could fracture. And you could create these fractured edges which now point toward the liver and you can hemorrhage from this type of situation. So its protective but you have to take that with a grain of salt. Heres our J shaped stomach, we dont see the pancreas, the small intestine, and finally here is the large intestine or colon and we catch a little piece down there as well. [3] This comes from another anatomy textbook and we are looking at the ventral surface of the liver. Nice view of the right lobe, the left lobe, and heres part of the gallbladder peaking out, and heres the mesentery, falciform ligament which extends from the right lobe of the liver to the ventral body wall and buried in here you see a thickening, that really represents the remnants of your umbilical vein, etc. We dont have a clear cut view of the stomach, but all this mesentery in here where represents the greater omentum which is hanging down like an apron. [4] Some MRIs showing us the position of the liver and its easy to recognize where we are because the vertebrae show up very nicely and the lighter stain, well the grey stained region represents your spinal cord. And these little blotches of white which

Transcribed by Stephen Holt

April 5, 2014

are going around this whole abdominal cavity represents the transverse process which is really forming the rib. And up over here is where the process, the rib should have your costal cartilage and joining someplace in the middle would be your sternum. Sitting right above the vertebrae is a blood vessel, your aorta, and somewhat hidden by the liver is your inferior vena cava. And heres a curvature which occurs in the left side of the body, thats your spleen. And theres some partial showing of the stomach. The bottom picture is a little different location, again we see the vertebrae with the spinal cord, the aorta, and now were catching the kidneys which are sitting at each side of the vertebral column, and the kidneys are behind the parietal peritoneum so theyre really retroperitoneal, and heres your liver once again, and sticking out from the right lobe of the liver happens to be your gallbladder. So you can see positioning of organs very nicely with MRIs or scans. [5] Diagrammatic view of the liver, were now looking at the caudal side and you can see the various lobes. This happens to be the right lobe, left lobe, and associate again with the right lobe is the gallbladder, this is a rather small lobe, the quadrate lobe. And the gallbladder lies right next to it and then we have the caudate lobe and associated with that lobe you have the inferior vena cava. You covered all of this stuff in anatomy and what I did was put up a little smiley faces around the stuff I talked about. I didnt mention the bare area, but theres nothing really covering it per se and it rests up against your diaphragm, ok, lets try that again. Right lobe, left lobe, quadrate, caudate, inferior vena cava, this I did not mention and for this lecture is not that necessarily important. [6] Moving on, now were beginning to see the histological organization of the liver. The top left picture showing you the right and left lobes with the falciform ligament. And in the background is blood vessel, the blue one being the inferior vena cava, the red one being the dorsal aorta. And here again as usual, the gallbladder is peaking out. As you dissect the piece of the liver out, you see a pattern looking like this and the functional unit of the liver is your hepatic globule. A hexagon shaped figure like this. And in the center is your central vein. Now there are different types of terminology that are used, a classic lobule, a portal lobule. And the classic lobule is essentially your six sided figure with a central vein. And each lobule is separated by each other by a connective tissue region. Its like a capsule going around the lobule and in reality the capsule surrounding the entire liver is called Glissons capsule. Then the capsule indents into the organ and surrounds each and every lobule. The portal lobule is represented by this triangle, and with the triangle youre having three central veins interconnected to give you the appearance of a triangle. It doesnt the functioning in anyway, its just a different way of looking at the lobulous structure. And buried in the connective tissue youre going to get some certain expanded areas which well better in another slide called the portal area, the portal canal, in which youll find branches of the hepatic artery, hepatic portal vein, bile duct, nerves, and lymphatic vessels. A lot of connective tissue involved there. This particular diagram is magnifying part of one of these lobules. And here you see the

Transcribed by Stephen Holt

April 5, 2014

central veins. And the central veins are more or less in the center of each and every lobule. So the liver has 2 sources of blood, I think I mentioned it yesterday. Hepatic artery which is bringing in oxygenated blood, and the hepatic artery comes from the celiac artery trunk. In essence thats what this red structure is. But theres another blood vessel feeding in the liver called the hepatic portal vein. And thats represented by your blue structure. And this blood is deoxygenated, its really blood thats drained from the lower part of the abdominal cavity. The inferior mesenteric vein joins up with the superior mesenteric vein, in addition youll have the splenic vein and the gastric veins all coming together and now you have your hepatic portal vein. So theyre two sources of blood and you can sort of say that thats the afferent supply of blood from two different sources. Afferent means coming in. And then we have these cells, these are your hepatocytes, hepatic cells, and at one time they used to be described as cords of cells. But this is a cord, its not really a true 3-d structure per se, so the terminology was changed and we no longer use the word cords but plates. And so a plate gives you a much fuller picture and so here we have plates of hepatocytes. And between these arrangements of the hepatocytes, these blue structures represent the sinusoids. And I believe that was discussed in the circulatory system of this course, the sinusoids do not have complete endothelial lining, there are like gaps and there are gaps there purposely to prevent material to leak out, and well touch upon that subject in a short while again. And as you look at this particular picture, there are different zones, and Im just going to arbitrarily draw a couple of lines across like this. This is zone 1, thats 2, and thats 3. Which zone do you think the blood will have the most oxygen, the most nutrients, 1, 2, or 3? One, because this is where the blood is coming directly in whereas zone 3 has the least about of oxygen and nutrients. But by the constant flow of blood, zones 2 and 3 do get a certain amount of material that it needs for survival of the cells and we use two different terms, stroma and parenchyma. The parenchyma is the actual working part of the gland, in other words the hepatocytes. The stroma is the nonworking part of the gland where you have your connective tissue capsule, and septa(?), etc. Oh theres one more picture left in the bottom left corner. And it shows you one hepatocyte and part of another. Now this is your sinusoid and thats your sinusoid and you see that in the endothelial part of the sinusoid there are certain gaps like here and here. That means material can leak out of the sinusoid and where does it leak into? Something called your perisinusoidal space also known as your space of Disse. If you look at your hepatocyte it seems to be modified on both sides with these little microvilli structures for increasing surface area. So lets say oxygen comes into the space, glucose comes into the space and then because of this microvillus arrangement of the hepatocytes, these things can be absorbed into each and every hepatocyte. One of the main functions of the liver, one of the main functions of the hepatocyte, is storage. So glucose is stored, usually built up into glycogen, amino acid is stored, usually built up into protein, and fatty acids are stored, built up into lipids, and then when the body needs these things, the hepatocytes now break down the larger product into these base units, your glucose, amino acid, fatty acid. And send it into the perisinusoidal space or space of Disse and leaks back out into your sinusoids. And keep in mind the sinusoids really extend from the outside of the lobule all the way to the central vein. All the central

Transcribed by Stephen Holt

April 5, 2014

veins join up and they form two major vessels at that point in time, hepatic veins right and left. And both the right and left hepatic vein then feed into the inferior vena cava which carries the blood back to the right atrium. What we also have is your biliary system, which these pictures dont show but well see that somewhere else. [7] This picture is meant to illustrate your classic lobule, your portal lobule, and something called an acinus. Acinus is also known as an alveolus when we talk about glands. So here we have a classic lobule illustrated, essentially your hexagon shape and in the middle in here, ok theres another classic lobule but I seemed to have lost my red pointer in the process. And in the middle of each classic lobule should be your central vein, and these red lines that Im just now drawing happen to be sinusoids. And between the sinusoids you find your hepatic cells, your hepatocytes. We see two additional structures, heres the triangle I referred to before where you do have a connection between three central veins and in this case caught in the middle, when you do something too fancy, its not necessarily the greatest idea. And somewhere in between over here would be your portal area, your portal canal, where you would find branches of the hepatic artery, hepatic portal vein, lymphatics, and nerves. Whereas if you look at the classic lobule arrangement youre going to find that being built into the connective tissue between the hexagons. [8] The bottom picture is basically again showing you your classic lobule, your portal lobule, and I forgot to mention this liver acinus. The functional unit of glands is an alveolus or acinus. So what has been done is you have gotten this little structure interconnecting two central veins sort of an O shaped structure and that has been termed your liver acinus, the functional unit. So there are 3 different ways of looking at the liver. Diagram A is showing you the liver and its difficult to see separations of your lobules but roughly theres one lobule. Depending on the species that youre dealing with the liver lobule may be more or less obvious. In the human liver the connective tissue between the hexagons is minimal. So its hard to see the borders but when it comes to say the pig liver there is a lot of connective tissue and its easier to distinguish the lobules and theres a picture of this in here. This is high power focusing on the portal area, portal triad and this is a branch of the hepatic portal vein, happens to be pretty large branch and here is a small branch of your hepatic artery and your bile duct. In addition youre going to find nerves and lymphatic vessels present as well. [9] The bottom picture does show you the hexagon shaped structure fairly nicely, your central vein, and all the spaces in here represent the sinusoids and the sinusoids are separating the plates of hepatocytes. This is a typical portal area with the various structures and the top picture shows you really the liver vascularity. The red represents the hepatic artery coming in and the purple structure the hepatic portal

Transcribed by Stephen Holt

April 5, 2014

vein and both of these vessels are extending throughout the liver. What you see in green represents the biliary system, now you start off with bile canaliculi but they dont have their own walls so if we were to draw two hexagons, Im going to exaggerate the space between them purposefully, the wall of the bile canaliculus really is really derived from the cells themselves, the hepatocytes. So the cell membrane around the hepatocytes sort of forms the wall of the small thin bile canaliculi. At the same time now we see this blue structure and here are your two hepatic veins coming together to form one and way up here this should be the inferior vena cava. [10] And so this is a good picture showing you the plates or sites and now you can see between 2 hepatocytes this little green structure. Those are the bile canaliculi, and the walls are the walls of the hepatocytes. Then the vessels get larger, and eventually they become bile ducts and exiting from the liver youre going to have a right and left hepatic duct, and by the way the only exocrine function of the liver is to produce bile. Everything else more or less fits into an endocrine type fashion. So these right and left hepatic ducts fuse into one and they join together with a cystic duct which goes to the gallbladder so your bile is then transmitted into the gallbladder. Gallbladder doesnt produce bile it just stores it and when your body needs bile it will be released. So in addition you see the plates of hepatocytes, heres your sinusoids, and these are supposed to be endothelial cells and way down here is a typical portal area with your branch of the hepatic portal vein, your bile duct, etc. [11] So this is a human liver because you can barely see any connective tissue and that would be located right over here. So you can actually de-lineate the classic lobule. Heres your central vein, it is supposed to be in the center but it depends upon the cut and all the spaces you see represent the sinusoids and the cells in between the hepatocytes. [12] This is your pig liver, so you can see immediately that the lobules stand out pretty clearly because of the amount of connective tissue between the lobules and this connective tissue dont forget comes off the outer capsule, Glissons capsule. This is a very large portal area, portal triad, heres a smaller one and again we got defined branches of your hepatic artery, hepatic portal vein, bile duct system, nerves, and lymphatics. [13] Before we get to this, if you were to do a count of number of cells present, about 80% of the cells are the hepatocytes. And theyre fairly large cells with round nuclei and sometimes youll find 2 nuclei per cell. These cells are active, so theyre going to have a full compliment like your mitochondrion, SER, and golgi etc. Just let me check something. Ok. These are pictures of the liver, the one of the left is a liver from a person whos literally an alcoholic. And has consumed quite a bit of liquor

Transcribed by Stephen Holt

April 5, 2014

and as you look at it you see all these nodules bulging from the liver surface. And the overall organizational structure is lost. And heres a more internal picture, this is cut and so these are supposed to be your liver lobules. Youll notice a lot of blue area, that means there has also been a tremendous increase in connective tissue. [14] Here we have 2 different powers of the liver, this is highly magnified and heres your central vein and you can see feeding into the central vein happens to be the blood present in the sinusoids and this is a fairly decent picture of your hepatocytes. Picture on the right is concentrating more on this area being your hepatic area, hepatic triad, etc. [15] Now there are other cells that are present besides your hepatocytes and Kupffer cells. We haveoh I didnt talk about Kupffer cells. Besides hepatocytes we have Kupffer cells. And when connective tissue was discussed or epithelium, the Kupffer cells should have been mentioned, I dont remember if it was, but its nothing more than a macrophage. And these cells arent really completely labeled but heres your endothelial cell lining the sinusoid and Im just going to call this cell and that cell for argument sake your Kupffer cell. Theyre actually pretty large and theyre on the luminal surface of the sinusoid and remember this being a macrophage it comes from the monocytes in your bone marrow. They could be fixed or mobile depends on what is happening. There are other cells, one cell type is called an Ito cell, I-T-O, they sort of stellate shape which mean they have processes and these cells tend to store vitamin A specifically. They also tend to have a lot of lipid droplets in their cytoplasm and then finally we have something called pit cells. And these pit cells are natural killer cells, theyre not phagocytic in nature, but they play a role in terms of the immune system, in essence they happen to be large granule lymphocytes. And again Ill call your attention to the spaciousness in here, thats the space of Disse, and heres your microvilli on both sides of the hepatocyte. You see the nucleus and the various organelles present. And this area right in here is showing you the formation of a bio canaliculus. And so you can see the wall is really being derived from the neighboring hepatocytes. [16] Heres a nice picture, high power, these are the sinusoids, these are your hepatocytes, and then you see this dark cell with a blue arrow, heres another one, theyre all over the place, those are your Kupffer cells. And when someone injects like carbon particles into the animal these cells pick up the foreign material, they ingest it, and they try to get rid of it. So theyre fairly large cells. [17] We already spoke about an afferent blood supply thats the hepatic artery coming in and the hepatic portal vein coming in as well. One has oxygen, the other one doesnt. The hepatic artery is also carrying in nutrients whereas the hepatic portal vein is carrying waste products. Then theres an efferent blood supply, so once the

Transcribed by Stephen Holt

April 5, 2014

blood comes in and is now situated in your sinusoids the blood passes through the sinusoids to the central veins. And I already mentioned the central veins fuse together to form your hepatic veins and the hepatic veins empty into the inferior vena cava. So the liver produces bile, its a pigment, and it happens to be derived from breakdown of hemoglobin. And Im sure Dr. Pavlov is going to go into the formation of the bile because thats more of a physiological concept. So what are the functions of the liver? One we already mentioned, the production of bile. And thats the digestive function. And the rest I tend to put into your endocrine type function, and when we mention the word endocrine, that means whatever the cells are producing they are releasing into the circulation. So in essence when glucose, amino acids, fatty acids pass into the space of Disse and are picked up by the hepatocytes, thats an endocrine function. You might think its digestive but its not. But the same thin when the more complex molecules are broken down like glucose, that goes back into the space of Disse into the sinusoid so thats an endocrine function as well. Theres a lymphatic function where the hepatocytes remove your IGA from the blood and the reason that happens is the hepatocytes have receptors for IGA. And in terms of lymph, youre actually getting 25 to 50 percent of the lymph in the body being produced in the liver and being sent back to the thoracic duct and eventually it enters the heart. Metabolic function is associated again with your endocrine type function because youre involving your blood, the circulation. We dont think of the liver being involved with calcium, but it really is. Vitamin D is found within the liver, if the body needs more calcium the vitamin D is released stimulating saving more calcium instead of getting rid of it and putting the calcium in the area like bone. So hepatocytes synthesize vitamin D. You also find associated with the liver ion products like transferrin and so from the hepatocyte you have transferrin going back and forth between the hepatocytes and the circulation. If you do a blood test, it depends what the doctor is looking for, he will look for the presence of ion. If you dont have enough ion, that means youre not necessarily going to have enough hemoglobin so you might be anemic. If you have too much, that leads to a different set of problems. So the fact that fatty acids enter the liver you can technically say that the hepatocytes regulate, metabolize, transport fatty acids and triglycerides. Triglycerides if youre levels are high means youve consumed too much in terms of fats and then the fats will break down and lead to increase of glucose in body. The liver is related to the kidney. Ill be doing the kidney, thats the next topic and as a result the kidney takes ammonia which comes from the breakdown of proteins, sends it to the liver. If ammonia stayed in your body you would die. And the hepatocytes detoxify it if you will. And convert it to urea and thats whats eliminated by the kidneys. Theyre various other proteins that are produced by the liver, we wont get into that. So much for the liver you can spend a long time talking about the liver. Now were going to concentrate on the gallbladder. Histologically the gallbladder has a simple columnar epithelial lining, a lamina propia. But it does not have a muscularis mucosa. It does not have a submucosa. There is a muscularis externa however and the organ could be covered by a serosa or adventitia. The part of the gallbladder facing the abdominal cavity has the serosa. The part of the gallbladder imbedded in the right lobe of the liver has the adventitia. And I had mentioned yesterday about the release of cholecystokinin. And cholecystokinin will

Transcribed by Stephen Holt

April 5, 2014

stimulate the gallbladder to release the bile. And up here you will a right and a left hepatic duct coming together to form a common bile duct and this is actually a cystic duct that joins the common bile duct. So the bile is produced in the liver, and then it goes into the organ for storage. When needed the bile is released and comes down this what is referred to as a common bile duct and empties into the duodenum together with the main pancreatic duct in this little raised area called here they say major duodenal papilla. But it has another name as well. Ampulla of Vater. And then heres a minor papilla to which the accessory duct enters. [18] Here we have an ultrasound, this is the gallbladder and what youre seeing in the gallbladder are gallstones, theyre calcific deposits. And depending on where or how large they are they could not bother you, they can block a duct, and once that happens you feel pain. And so you have to get rid of the gallstones one way or the other. One way is called lithotripsy, where they literally put you into a shock machine and create shockwaves in the hope of breaking up these stones into smaller particles. How successful that is is another story and the worst scenario is you have them removed surgically. [19] And here we have the gallbladder when its sort of empty, its contracted. Heres a picture of the gallbladder stretched; thats means it would be filled with bile. [20] Pancreas. Heres your duodenum, most of which is retroperitoneal. Its C-shaped and sitting in the duodenal loop is the head of the pancreas. The pancreas narrows down to a neck, it gets wider forming a body, and finally it narrows down again to a tail which rests up against the spleen. Pancreas is divided into many lobules, it is retroperitoneal, has a very thin type of capsule. On the bottom is a separate picture of the pancreas, the head, the neck, the body, and the tail. And you can see this long duct coming down, thats the main pancreatic duct, the duct that were seeing and up here is a smaller duct, a minor duct, which is called the duct of Santorini. And the reason you have two excretory ducts is because the pancreas initially developed as two separate bodies. And the bodies came together so each body had a duct. [21] Nice picture again. Showing you the duodenal loop, the pancreas, and again heres your Ampulla of Vater showing you the bile duct entering and the duct of Wirsung. And heres your minor papilla. [22] Histologically, the picture on the left is a low power, and most of these cells are exocrine in nature. So the pancreas has 2 functions, one exocrine to release enzymes to help the intestinal mucosa which also releases enzymes to complete the process of digestion. And then scattered throughout youre going to find these little localized, call them islets or islands if you will. And thats the endocrine of portion

Transcribed by Stephen Holt

April 5, 2014

of the pancreas, the parts that releases the glucagon and insulin. And the alpha cells are the ones that release the glucagon, the beta cells release the insulin, and the percentage of beta cells far outweighs of your alpha cells. And then theres a d cell, or delta cell which releases somatostatin which controls the alpha and beta if there is too much of either hormone released, it sort of shuts it down. In addition, the somatostatin does reduce the motility of the digestive tract. The picture on the right is showing you the exocrine portion of the pancreas and this is really the secretion being released into a duct system whereas the islets release their secretions into the capillaries and eventually into your actual vascular system. [23] You saw this picture, somebody had it on the conference exam, these are your serous cells, these represent the exocrine portion of the pancreas. [24] Here we just have a higher power of the islet of Langerhans, just by looking at this you cant tell which cell is which, you need to do special staining. [25] A little diagram combining both. Heres your arrangement of serous cells, your alveolus, up here is your islets. Whats interesting about the pancreas is that within the gland itself, within the alveolus, you have the presence of the central acinar cells. Theyre actually in the lumen and so the duct system begins in the lumen and then the duct system exits the lumen, forms intercalated duct, etc, etc,. [26] And this is just a high power showing you your serous cells, your intercalated duct, I mean your central acinar duct feeding into your intercalated duct. And well go more into your duct system when we do salivary glands.