In the upper right quadrant of the abdominal cavity is a large red mass that may look like a sleeping giant. It doesn't pulsate, it doesn't move much, only passively, and you don't ordinarily see it secreting anything. This soft, almost jelly-like mass is the liver. Without it the body is kaput. Fortunately, a body can survive on about one-third the amount of liver that the normal person has. What this brooding shapeless hulk of red does is a subject of this minicourse. Where else can a body produce that nice green stuff called bile so easily, and what would a person do without all those plasma proteins to make the minicourse on capillaries come out right and what would the pharmacologist do without the liver to detoxify drugs? The pancreas is something else. It couldn't decide whether to be fish or fowl, so it decided to be both. Exocrine and endocrine. Fortunately, it doesn't try to be both ways in the same way. It is little islets of endocrine in a sea of exocrine. That great explorer Langerhans planted his flag on one of these islets and claimed it for King Endocrine for all time. Being somewhat persnickety he decried that the products of his islets would only be shipped via the good ship Plasma, while the poor exocrine people had to build their own canals which they dressed up with the name ducts. (Liver and onions will be served in the mess hall tonight.)

1.3 Liver, Gallbladder, Pancreas, and Related Organs
On completion of this minicourse you will be able to: 1. Describe the shape and position of the normal liver. 2. Describe the following in terms of location, structure and function: 1. liver lobule 2. portal triad 3. venous drainage of the liver 4. hepatic artery 5. hepatic portal vein 3. Describe the major features of the hepatic portal system. 4. Describe the following functions of the liver: 1. production of bile 2. production of plasma protein 3. detoxification 5. Describe the pathology of cirrhosis of the liver. 1. Laennec's (portal) 2. biliary 6. Describe the gallbladder and its function.

7. Describe the anatomy of the biliary tree and the sphincters. 8. Describe the formation of gallstones. 9. Describe the pancreas in terms of: 1. position 2. duct system 3. exocrine secretions 4. endocrine secretions 5. "diabetes mellitus" relationships

OBJ. 1. Describe the shape and position of the normal liver. Location of the Liver The liver, the largest internal organ in the body, is situated under the diaphragm. It is further protected by the costal cartilage of the ribs. The liver is so large that it occupies most of the right hypochondrium as well as part of the abdomen. It is, for the most part, covered by peritoneum and entirely by connective tissue. The upper surface of the organ fits nicely against the undersurface (inferior aspect) of the diaphragm. There are, on the surface, four lobes: right, left, caudate and quadrate. The Falciform ligament divides the liver into two main lobes, right and left, with the right lobe being the larger and is sub- divided into the right lobe proper, the caudate lobe and the quadrate lobe. The undersurface of the liver, also known as the visceral surface, is more irregular in appear- ance than is the domed convex uppersurface. This irregularity is caused by the fact that the infe- rior surface is in contact with: 1. the lower esophagus 2. the stomach, and 3. the right kidney and adrenal gland
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. (See Figure 1) EXERCISE 1 OBJECTIVE 1 Questions

1. Briefly describe the arrangement of the liver's lobes. 2. Why is the undersurface of the liver so irregular? EXERCISE 1 DISCUSSION OBJECTIVE 1 Answers 1. The liver has two main lobes due to the falciform ligament which divides it. The left lobe is smaller than the right which is further subdivided into the caudate and quadrate lobes. 2. The undersurface is so irregular because this visceral surface is in contact with the lower esophagus, the stomach, the right kidney and the adrenal gland.

OBJ. 2. Describe the following in terms of location, structure and function. a. liver lobule b. portal triad c. venous drainage of the liver d. hepatic artery e. hepatic portal vein OBJ. 3. Describe the major features of the hepatic portal system. Location, Structure and Function of the Liver The liver is essential for life, yet it can suffer extensive damage before malfunction becomes pronounced. Although functionally complex, histologically, the liver is nothing more than a greatly modified tubular gland. Surrounded by a fibrous capsule, the liver is made up of liver lobules (the functional units of the liver). Each lobule is constructed around a central vein that empties into the right and left hepatic veins which then drain into the vena cava. The lobule is composed of cellular plates that radiate from the central vein. Each cellular plate is two cells thick and between the two cells are small bile canaliculi that empty into terminal ducts. To summarize, the internal structure of the liver is based on an arrangement of liver cells into a lobule. The lobule is composed of liver cells, as well as liver sinusoids lined with endothelial bile passageways and, at the lobule's periphery, blood vessels.

(Note the following illustration.) Blood enters the liver from two sources, the hepatic portal vein (do not confuse with hepatic vein) and the hepatic artery. The hepatic portal vein is the venous drainage for the large and small intestine, the stomach and terminal esophagus and the spleen. Since the function of the spleen is to filter out worn out and broken down red blood cells, the splenic vein of the hepatic portal sys- tem carries the products of red cell breakdown to the liver. The mesenteric veins (they drain the large and small intestine) carry deoxygenated blood and the products of intestinal digestion and absorption (amino acids, mono and disaccharides and short chain fatty acids; long chain fatty acids are absorbed via the lymphatic system). Outside the liver these veins come together to form the hepatic portal vein. About 60% of the blood perfusing the liver is from the hepatic portal vein. Entering the liver next to the hepatic portal vein is the hepatic artery. This supplies about 40X of the perfusing blood. These two vessels remain separate in their passage through the liver until they reach the lobule. At each corner of the hexagonal liver lobule is a group of three structures: a branch of the hepatic portal vein, a branch of the hepatic artery, and a bile duct. These three struc- tures comprise the portal

triad. As the two blood vessels leave the portal triad, they empty into the sinusoids. This is a large endothelial lined space and in it the blood from the two sources begins to mix. It percolates through the sinusoids toward the center of the lobule where the central vein is located. It passes through a series of veins that collect from many lobules to enter the right and left hepatic veins which empty into the inferior vena cava. Recall the closeness of the opening of the hepatic-veins to the termination of the inferior vena cava in the right atrium. Some further comments are now in order: l. Portal venules receive blood via the portal veins. These venules empty into either liver sinusoids (located between the cell plates) or into the central vein. 2. Hepatic arterioles are also seen within the interlobular septae. These arterioles provide arterial blood to the septal tissues and may empty into the sinusoids.

3. The venous sinusoids are lined with two different cell types: 1. endothelial cells - have large pores, allows H2O and plasma proteins to pass freely. 2. Kupffer cells - reticuloendothelial cells capable of phagocytizing bacteria and other foreign matter in the blood. 4. The average rate of blood flow through the liver is 1400 ml/min. Measured pressure in the hepatic vein, however, is normally 0 mm Hg, while in the portal vein the pressure is 8 mm Hg. The elevated portal venous and capillary pressures make the liver more susceptible than other organ systems to increases in resistance to circulation; e.g. cirrhosis of the liver. The Hepatic Portal System The liver receives a dual blood supply: 1. from the hepatic artery 2. from the portal vein You will recall that the portal vein carries blood to the sinusoids of the liver from the

alimentary canal. One of the three branches of the celiac trunk (off the aorta) is the hepatic artery. The hepatic artery enters the substance of the liver in front of (anterior to) the portal vein and to the left of the bile duct. Once the artery enters the liver it divides into the left

and right hepatic arteries. The portal vein, arising from the gut, enters the substance of the liver behind not only the bile duct but also the hepatic artery. At the hilum of the liver (portal hepatis) the vein divides into left and right branches. The inferior vena cava receives blood from the liver via a series of hepatic veins which drain the central vein. The hepatic vein series can be enumerated as follows: 1. left hepatic v. - drains left lobe 2. middle hepatic v. - drains central portion and may join the left branch to form a

branch of hepatic artery 3. A portal triad is an arrangement of three structures within the liver lobule. Off the abdominal aorta is a main arterial trunk called the celiac trunk. detoxification Functions of the Liver Although this section focuses on the activities of the liver with respect to bile and plasma pro. Describe the arterial supply of blood to the liver. 3 Questions 1. the endothelial cells and the Kupffer cells. it should be pointed out that the liver has other functions as well. right hepatic v. The endothelial cells have very large pores which allow for H20 and plasma proteins to pass. 2. MINICOURSE 1. branch of hepatic portal vein 2. The Kupffer cells on the other hand are reticuloendothelial cells capable of phagocytizing foreign matter in blood. Describe the following functions of the liver: a.common trunk 3. There are two types of cells present within the venous sinusoids. Describe what is meant by a portal triad. it divides into the left hepatic and right hepatic arteries. At the corner of the hexagonally arranged lobule the following structures are seen together: 1.teins. 3. production of plasma proteins c.3 SECTION 3 OBJ. and the process of detoxification. production of bile b. A branch of the celiac trunk is the hepatic artery. bile duct 2. These functions include: .drains most of the right lobe OBJECTIVES 2. Once the hepatic artery enters the substance of the liver. EXERCISE 2 DISCUSSION OBJECTIVES 2.Answers 1. What types of cells are found in venous sinusoids and what do they do? 3. 4. 3 . .

tion of fat from the intestine. Approximately 250-1000 ml/day are secreted. and HCO. and excreted into tiny bile canaliculi located between the cells. it should be noted. you will recall. converting one type of amino acid to another by the process of transamination) of amino acids which. The second item to be considered is the production of plasma proteins. phospholipids. When food enters the duodenum. These pigments. dietary proteins 3. Bile is an active emulsifying (suspension of fats) agent and thus plays a part in the digestion and absorp. Also found in bile are the bile salts which are sodium and potassium salts of bile acids. containing the substances just mentioned as well as cholesterol. the duodenal orifice of the duct is closed. water. cholecystokinin is released from the intestinal mucosa which will cause gallbladder contraction.bladder where it is stored. the canaliculi come together at the portal triad where the portal ductule is formed. carbohydrate storage amino acid metabolism metabolism of steroidal hormones metabolism of fat Bile is a complex solution secreted by the cells of the liver into the bile duct.e. Bile. These bile ductules coalesce as they approach the surface of the liver (near where the hepatic portal vein and the hepatic artery enter) to form the hepatic duct which emerges from the inferior surface of the liver. Bile does not enter the sinusoids. 3. is secreted into the bile duct which eventually drains into the duodenum. Ca. 2. Bile is formed by the liver cells (the liver cells are epithelial cells). are the breakdown products of hemoglobin. causing the bile to Òback ups and eventually enter the gall. K.1. glucose (glucogenic amino acids) . are the Òbuilding blocksÓ of protein structures. 4. as in between meals. leading to the secretion of bile into the small intestine. metabolic turnover of proteins 2. Na. D3uring periods where the digestive processes are somewhat slowed. The source of the amino acids necessary for this plasma protein production are: 1. Instead. It is golden yellow in color due to the presence of bile pigments (bilirubin and biliverdin). C1. The liver plays an intricate role in the synthesis of these plasma proteins and is able to provide for an interconversion (i.

a cleaning fluid. specifically damages the parenchymal cells . On the other hand.ism. the liver metabolizes the by-products of cellular metabolism and exogenous materials such as drugs. Not all types of liver disease affect drug metabolism equally.gen). Of particular importance is the removal of ammonia which is toxic to the human organism. which has the following structure: is formed during a series of reactions called the urea cycle (Krebs-Henseleit cycle) and is excreted in the urine. 3. IgA. Fibrinogen Prothrombin Factor VII Factor IX Factor X Another function of the liver is detoxification. Two major categories of proteins produced by the liver are the albumins and the globulins. plasma volume and tissue fluid balance.lized in the liver are given to a patient. You will recall from an earlier pharmacology mini. Urea. such as liver damage associated with alcohol. Because of the vast enzyme system of the liver. several proteins concerned with blood coagulation are produced by the liver. toxic substances like carbon tetrachloride (CC14). the liver parenchymal cells surrounding the central vein must be damaged. 4. this organ plays an important role in drug metabolism. In some cases. serving as a precursor to fibrin (fibrino.toxic material called urea. IgE. this area is not damaged and there is little change in the drug metabolizing capabilities. those disease states which damage areas which actively metabolize drugs can have serious consequences.course that in this process. serving as antibodies or immunoglobins (Gamma globulin. As one can imagine. liver damage must be taken into account when drugs that are metabo.Because proteins are stored for only limited periods of time. Knowledge of how a drug is handled by the liver is very important in therapeu. such as: 1. copper. since drug metabolism is not uniform throughout the liver. 5. In order for a patientÕs ability to metabolize drugs to be compromised. The globulins are involved in many functions such as: the transport of several key substances (iron. IgD. 2. Furthermore. which can manifest itself as either conjugation. IgM). IgG. lipids). However. any imbalance between the amino acids required and those which are available is handled quite readily by the liverÕs amino acid interconversion capability. oxidation. or reduction.tics. The albumins are large colloidal protein molecules which have an influence on osmotic pressure. This ammonia is removed from amino acids via deamination and converted to a normally non.

surrounding the central vein and. cholesterol. calcium.3 SECTION 4 OBJ. water. 3. 5. potassium. the bile salts act to separate the fat droplets via a process called emulsification. This emulsification process aids in the digestion and absorption of fats. Fibrinogen Prothrombin Factor VII Factor IX Factor X 3. EXERCISE 3 OBJECTIVE 4 Questions 1. When bile enters the duodenum. Name the plasma proteins produced by the liver which are involved in blood coagulation. Describe bile in terms of its: 1. function 2. chloride. constituents 2. What is the most important compound detoxified by the liver under normal circumstances? EXERCISE 3 DISCUSSION OBJECTIVE 4 Answers 1. IgD and IgM. Bile is a complex solution composed of the bile pigments (bilirubin and biliverdin). Describe the pathology of cirrhosis of the liver: . 4. It is removed by the metabolic breakdown of drugs and amino acids and is converted into urea. Which proteins formed by the liver are important to the immune system? 4. 4. severely compromises an individualÕs drug metabolizing capacity. 5. IgG. Ammonia. sodium. Gamma globulin IgE. therefore. 3. The liver produces the following plasma proteins involved in blood coagulation: 1. 2. 2. MINICOURSE 1. IgA. bile salts.

although it may be halted in some of its stages. The nodules are regenerated hepatic cells. blood. the damage that has already occurred is not reversible.1. . Biliary Cirrhosis of the Liver The term cirrhosis denotes chronic tissue degeneration in which cells are destroyed leading to the formation of fibrous scar tissue. becomes rough and bumpy because of the development of nodules on the surf ace of the organ. Laennec's (portal) 2. scar tissue surrounds portal area 2. lymph and bile channels within the liver become distorted and compressed. The two types of cirrhosis considered in this objective have the following distinguishing characteristics: 1. they are especially susceptible to damage due to hepatic vein congestion. It is important to remember that cirrhosis is a chronic progressive disease and. most commonly due to chronic alcoholism 2. however. Laennec's portal cirrhosis 1. The prolonged passive congestion of right-sided heart failure tends to cause fatty change due to venous congestion involving the inferior vena cava. Biliary 1. The surface. It is a common sequela of a large number of liver disorders including infections and intoxications. The fatty metamorphosis seen in liver disorders is not generally a fatty infiltration from non-hepatic sources. Cirrhosis is the result of a fibroplasia that leads to extensive scarring. portal hypertension and impaired liver function. leading to intrahepatic congestion. scarring around bile ducts and lobes of liver 2. As the cellular destruction continues. rarer than Laennec's cirrhosis Fatty changes in the liver occur under a variety of conditions and may vary from a mild condition seen in caloric restriction to severe forms such as is seen in chronic alcoholism. The fibrous changes within the organ cause it to become firmer and smaller. The etiology is unknown although there is usually associated with it liver cell changes or destruction is unable to inactivate estrogens which leads to testicular atrophy. the hepatic vein and the intrahepatic veins retrograde to the central lobular vein. Because the liver cells surrounding the central vein normally are poorly oxygenated. but is a deposition of fat resulting from deranged hepatocyte lipid metabolism.

OBJ.Spider nevi and palmar erythema may be due to a deficiency of the B. one of the two major veins forming the hepatic portal vein. The jaundice or yellowish tint to the body is caused by the blocked excretion of bilirubin at the level of the bile ducts and its return to the bloodstream. EXERCISE 4 OBJECTIVE 5 Questions 1. Describe the anatomy of the biliary tree and the sphincters. Describe the gallbladder and its function. In biliary cirrhosis scarring occurs around the bile ducts and lobes of the liver and may lead to jaundice. common in chronic alcoholism. 2. such as would be created by a gallstone. hypovitaminosis and splenomegaly. Biliary cirrhosis is less common and is due to an obstruction in the bile duct system. esophageal varices. the body. but it is also a serious disorder and is one of the causes of jaundice. 2. 6.complex vitamins. Some of the symptomatic changes which are seen in cirrhosis are: ascites. What are some of the symptomatic changes which occur due to cirrhosis? EXERCISE 4 DISCUSSION OBJECTIVE 4 Answers 1. fatty deposits eventually lead to the development of fibrous scar tissue which surrounds the portal area. It does not destroy the liver as rapidly as portal cirrhosis. it would be called obstructive jaundice. and the fundus. ulcer. The Gallbladder A structure which looks somewhat like a pear lies on the under or visceral surface of the liver. SECTION 5 OBJ. In this particular situation. Splenomegaly is due to obstruction of the splenic vein. It is called the gallbladder and is composed of three portions termed the neck. Briefly compare Laennec's and biliary cirrhosis. The following diagram illustrates the position of the . 7. In Laennec's cirrhosis.

However. Normally this sphincter is in a contracted or closed configuration. It should be remembered that the cystic artery is a branch of the right hepatic artery. under the influence of cholecystokinin. You will recall that: fats within duodenum ACT TO stimulate cholecystokinin production by duodenum which ACTS TO cause gallbladder contraction and ejection of bile. At this point. This latter structure has a length of about 4-6 cm for it must extend to the second portion of the duodenum. Thus. The Biliary Tree and the Sphincters The left and right hepatic ducts descend from the undersurface of the liver and unite to form the handle of the sling-shot called the common hepatic duct. This structure is then joined by the cystic duct.ter dilates to allow for the passage of bile into the duodenum. Located at the base of the common bile duct is the sphincter of Oddi. As the gallbladder fills the rugae allow it to enlarge and assume its pear-shape appearance. it is located slightly above and behind the pancreatic duct which is also entering this portion of the duodenum. The gallbladder receives its nerve supply via the celiac plexus. . The gallbladder has a capacity of approximately 50 ml of bile.gallbladder 2nd surrounding structures. The inner lining of the gallbladder resembles somewhat that of the stomach with Its rugae and is composed of mucous membranes. the union of the cystic duct with the hepatic ducts forms the common bile duct. This structure receives its arterial supply from the cystic artery while the cystic vein drains the gallbladder directly into the portal vein. the sphinc. where it enters the duodenum. The gallbladder serves as a reservoir for bile produced by the liver.

fertile (multiparous). No vitamin K leads to Factor VII. E. This cholecystokinin causes gallbladder contraction. and forty characterize the . C1. IX. HCO3. Bile is composed of bile salts. D. 8. and prothrombin deficiency which leads to coagulation difficulties. Approximately 50 ml of bile may be stored in the gallbladder. help in fatty acid absorption 6. K. Upon gallbladder contraction . they will stimulate the intestinal mucosa to secrete a substance called cholecystokinin. and cholecystitis. cause fat emulsification 2. EXERCISE 5 DISCUSSION OBJECTIVE 6 Answer When fats are present within the duodenum. Bile is continually secreted by the liver. In the United States. This condition has the medical term cholelithiasis. Some underlying causes include: pregnancy.3 SECTION 6 OBJ. Na. OBJECTIVE 6 Question Describe the sequence of events which cause bile to be ejected from the gallbladder. There is a high incidence of this condition in people over 40 and it accounts for much of the cholecystitis seen in the primary care clinic. The four F's fat. Bile salts 1. H20. 5. In summary: 1. K) are absorbed. Describe the formation of gallstones. phospholipids. MINICOURSE 1. 4.bile passes from the gallbladder --> cystic duct -> common bile duct ---> to the duodenum. 3. When the gallbladder contracts. 2. Relaxation of the sphincter of Oddi allows for the passage of bile into the duodenum. bilirubin.Bile salts are constituents of bile which aid in the digestion of fats via a process called emulsification. X. about 10 to 20 percent of the adult population has gallstones. They are rare in the first two decades of life. diabetes. which forms in the gallbladder. female. obesity. Ca. Without bile salts . cholesterol. Gallstones A gallstone is actually a stone-like mass called a calculus. bile is ejected into the cystic duct which joins the hepatic duct to form the common bile duct which carries bile to the fat soluble vitamins (A.

9. 2. round or oval and often translucent. 4. SECTION 7 OBJ. Because gallstones occur commonly. However. the majority are found in the gallbladder. OBJECTIVE 8 Questions 1. 5. Sometimes. 3. If the ratio of bile acid plus lecithin to cholesterol falls below a certain level. Gallstones are also more frequent in patients with hemolytic disorders. and gallstone formation may occur. they may obstruct this duct which can cause pain from distention and spasm of the biliary tract. They are jet-black. in diameter. Cholesterol stones are classically 1 to 5 cm. They are more prevalent in females who are obese. the relative proportion of cholesterol. position duct system exocrine secretion endocrine secretion "diabetes mellitus" relationships . Gallstones are most frequently found in patients over 40 years of age. 2. bile acids and phospholipids (chiefly lecithin) is of critical importance. Mixed stones contain calcium carbonate as well as calcium bilirubin. These stones are usually associated with a hemolytic disorder. Describe the pancreas in terms of: 1. Also found are pigment stones composed of calcium bilirubin. Describe how cholesterol gallstones are thought to be formed.population with the highest incidence. 2. When the ratio of bile acid plus lecithin to cholesterol falls. pale yellow. The genesis of cholesterol stones is something of a mystery. In about 80 percent of cases cholesterol is the chief component of gallstones. however. Although gallstones may form anywhere in the biliary tract. In which patients are gallstones most frequently seen? OBJECTIVE 8 Answers 1. they are sometimes squeezed into the common bile duct where they may enter the duodenum. bile becomes supersaturated with cholesterol and gallstones may form. the bile becomes supersaturated with cholesterol.

This duct. in many people. Various pancreatic secretions which participate in the digestive process flow (from the exocrine portion of the pancreas) down the main pancreatic duct. consists of packets or groups of cells called the islets of Langerhans. The islets are composed of two types of cells: 1. as follows: increased blood sugar levels produces beta cell stimulation ---> insulin secretion . joins the common bile duct prior to its entrance into the duodenum.secrete insulin Insulin decreases blood glucose level by stimulating the cellular uptake and the metabolism of glucose. 3. 4. beta cells .secrete glucagon 2. on the other hand. Thus. it can be discerned that insulin is directly involved in carbohydrate metabolism. the duct of Wirsung. In contrast.The Pancreas The pancreas is an unusual structure in that it is both exocrine and endocrine in function. The rate of their secretion is directly controlled by the concentration of glucose in the blood. lipase amylase trypsin carboxypeptidase The endocrine portion. This very diffuse structure lies slightly below and behind the stomach. alpha cells . 2. The exocrine secretions of the pancreas include: 1. glucagon increases the blood glucose level by stimulating the conversion of glycogen to glucose in the liver.

especially those associated with severe metabolic abnormalities resulting in ketoacidosis as well as complications such as: 1. 2.tary disorder and is manifested in the fully developed form by: 1. 3. 6. the glucagoninsulin balance is important in maintaining proper blood glucose levels. Diabetes mellitus is a disease which is a generalized chronic metabolic disorder involving carbo. much more. specifically glucose. 4. This disorder usually develops in subjects as a heredi. diabetes is probably mainly due to inadequate insulin secretion by the beta cells. 7.hydrate metabolism. retinitis 2. The major threats to the diabetic patient arise from the disease's surrounding complications. 9. 8.produces increase glucose metabolism ---> glycogen ATP yielded or glucose stored as produces reduction of blood glucose levels Glucagon on the other hand exists as an insulin antagonist in that it increases blood sugar levels by increasing glycogen breakdown into glucose. renal failure 3. Thus. weakness lassitude loss of weight hyperglycemia (high blood sugar) ketosis acidosis protein breakdown glycosuria and much. Although other factors may play a part in the disease. hypertension . 5.

premature atherosclerosis http://www. Its gross anatomy and the structure of pancreatic exocrine tissue and ducts are discussed in the context of the digestive system. The endocrine pancreas refers to those cells within the pancreas that synthesize and secrete hormones. Humans have roughly one million islets. The islets of Langerhans are collections of cell cords separated from the exocrine acinar tissue by a thin connective tissue sheath.ncsu. they receive about 10 to 15% of the pancreatic blood flow. which is also produced by a number of other endocrine cells in the body.ece. allowing their secreted hormones ready access to the circulation.4. they are innervated by parasympathetic and sympathetic neurons. the different cell types within an islet are not randomly distributed . each of which produces a different endocrine product: y y y Alpha cells (A cells) secrete the hormone glucagon. The pancreas is a compound tubular-alveolar gland composed of serous acini (exocrine portion). are of the fenestrated type. in both cases. The image to the right shows three islets in the pancreas of a horse. Interestingly. The vascular and nervous supply of the acini (and islets) are also located in these septa. and islets of Langerhans (endocrine portion). Branches of these vessels terminate as capillary networks around the acini and form dense networks within the islets. . The ducts lie in dense connective tissue septa which provide the main support of the gland. more simply. In standard histological sections of the pancreas. glucagon and somatostatin. a number of other "minor" hormones have been identified as products of pancreatic islets cells.html Functional Anatomy of the Endocrine Pancreas The pancreas is an elongated organ nestled next to the first part of the small intestine. Islets are richly vascularized. islets are seen as relatively pale-staining groups of cells embedded in a sea of darker-staining exocrine tissue. Beta cells (B cells) produce insulin and are the most abundant of the islet cells. Aside from the insulin. Delta cells (D cells) secrete the hormone somatostatin. and nervous signals clearly modulate secretion of insulin and glucagon. The endocrine portion of the pancreas takes the form of many small clusters of cells called islets of Langerhans or.beta cells occupy the central portion of the islet and are surrounded by a "rind" of alpha and delta cells. The capillaries. Additionally. Although islets comprise only 1-2% of the mass of the neuropathy 5. The acini and their ducts resemble a bunch of grapes. islets. Pancreatic islets house three major cell types.

downstate. so study both slides #40 and #41. The islets make up only one percent of the total pancreatic mass and are not uniformly distributed within the organ. The pancreas also lacks myoepithelial cells. The different types of secretory cells in the islets of Langerhans are difficult to differentiate in H & E sections. The Islets of Langerhans vary in size and usually appear as round cords of light pink cells. the interlobular ducts can be seen in the connective tissue septa along with some blood vessels. http://www. At 40x magnification note the different appearance of islets and exocrine cells. Locate centroacinar cells of the exocrine pancreas. The nuclei of centroacinar cells appear to be located in the center of the acini and mark the beginning of the intralobular ducts. while mitochondria and the endoplasmic reticulum with its associated basophilic RNA are located basally. Further. A capillary network surrounds the acini but is difficult to distinguish. Find well-defined acini in a well preserved region of the slide. Examine a section of guinea pig pancreas (slide #40).The alveoli (acini) are groups of cells which vary in shape from spheres to elongated tubes and may appear quite irregular in some sections. The acinar cells stain a deep purple and the cords of secretory cells in the islets include alpha (A)-cells filled with red-staining granules containing glucagon and beta (B) cells filled with blue-green staining granules that contain insulin. The ease of identification will depend upon the staining. The acini and ducts are enclosed by a basement membrane. During secretory activity. Note the details of the secretory cells such as the dense basal basophilia and the brightly eosinophilic secretory granules in the apical half of the cells. It often has a collapsed lumen and the cells are cuboidal with little cytoplasmic staining in contrast to acinar cells. narrow. Occasionally longitudinal sections of the first. free portions of the intralobular ducts can be observed emerging from the acini. Distinguish between basophilic exocrine and the slightly acidophilic endocrine tissue. Find the intralobular ducts among the closely packed acini. It is possible to have sections lacking islets. The cells are pyramidal in shape and surround a central lumen which is usually difficult to visualize. acidophilic granules fill the apical portions of the cells. which serve as scaffolding for large blood vessels.html Pancreatic Histology: Exocrine Tissue The pancreas is surrounded by a very thin connective tissue capsule that invaginates into the gland to form septae. The pancreas lacks striated ducts and the intralobular duct is similar to the intercalated duct of salivary glands. Try to find a more or less round cluster of exocrine cells forming an acinus. Finally. The connective tissue capsule may or may not be present but note the thin septa penetrating into the gland. They are responsible for secretion of a bicarbonate-rich which has been especially fixed and stained for this purpose. these septae divide the . dividing it first into lobes and then lobules. These are duct cells which form the junction between the secretory endpiece and the duct. Some regions may be poorly preserved. Examine the human pancreas (slide #41) at low magnification and note its lobular nature.

Duct cells secrete a watery. The smaller forms have a cuboidal epithelium. within the connective tissue septae. Note the low cuboidal. They vary considerably in size. Pancreatic ducts are classified into four types which are discussed here beginning with the terminal branches which extend into acini. almost squamous epithelium. Histologic features of the pancreatic duct system are illustrated in the following images: A longitudinal section through an intercalated duct (Cynomologous monkey pancreas. The cells that synthesize and secrete digestive enzymes are arranged in grape-like clusters called acini. as the name implies.pancreas into distinctive lobules. note the wedge-shapped cells arranged around a small lumen: Pancreatic Ducts Digestive enzymes from acinar cells ultimately are delivered into the duodenum. including man. The Acinus The exocrine pancreas is classified as a compound tubuloacinous gland. bicarbonate-rich fluid which flush the enzymes through the ducts and play a pivotal role in neutralizing acid within the small intestine. H&E stain). In the image of equine pancreas below. Secretions from acini flow out of the pancreas through a tree-like series of ducts. Intralobular ducts transmit secretions from intralobular ducts to the major pancreatic duct. are seen within lobules. as can clearly be seen in the image of mouse pancreas below (H&E). They receive secretions from intercalated ducts. Intercalated ducts receive secretions from acini. most acini are cut obliquely. . making it difficult to discern their characteristic shape. while a columnar epithelium lines the larger ducts. one fairlygood cross section through an acinus is circled. The large spaces between lobules seen in this image are a commonly-observed artifact of fixation. the pancreatic duct joins the bile duct prior to entering the intestine. In some species. The duct is running from upper left to lower right. very similar to what is seen in salivary glands. Interlobular ducts are found between lobules. They have flattened cuboidal epithelium that extends up into the lumen of the acinus to form what are calledcentroacinar cells. In standard histologic sections. The main pancreatic duct received secretion from interlobular ducts and penetrates through the wall of the duodenum. Intralobular ducts have a classical cuboidal epithelium and.

Section of equine pancreas (H&E stain) showing a longitudinal section through anintercalated duct emptying into an intralobular duct. H&E stain): note the columnar epithelium. Note the cuboidal epithelium in the intralobular duct. . Small interlobular ducts (equine pancreas. A thin interlobular septum is seen running horizontally immediately above the duct.

edu/hbooks/pathphys/digestion/pancreas/histo_exo. http://www.colostate.html nsulin Synthesis and Secretion . An intralobular duct (D) is seen on the right low magnification image of equine pancreas (H&E stain) showing a large interlobular duct in association with a pancreatic artery (A) and vein (V).

You can get a better appreciation forthe structure of insulin by manipulating such a model yourself. proinsulin is exposed to several specific endopeptidases which excise the C peptide. The insulin mRNA is translated as a single chain precursor called preproinsulin. a carboxy-terminal A chain and a connecting peptide in the middle known as the C peptide. Proinsulin consists of three domains: an amino-terminal B chain. thereby generating the mature form of insulin. certain features of this process have been clearly and repeatedly demonstrated. Within the endoplasmic reticulum. with a molecular weight of about 6000 Daltons. The resulting . many diabetic patients are treated with insulin extracted from pig pancreas. but has no known biological activity. Elevated concentrations of glucose within the beta cell ultimately leads to membrane depolarization and an influx of extracellular calcium. sight and taste of food) and increased blood concentrations of other fuel molecules. including amino acids and fatty acids. with the A chain colored blue and the larger B chain green. C peptide is also secreted into blood. Even today. also promote insulin secretion. Some neural stimuli (e. Nonetheless. Biosynthesis of Insulin Insulin is synthesized in significant quantities only in beta cells in the pancreas. and insulin from one mammal almost certainly is biologically active in another. The amino acid sequence is highly conserved among vertebrates. When the beta cell is appropriately stimulated. and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. elevated concentrations of glucose in extracellular fluid lead to elevated concentrations of glucose within the beta cell. It is composed of two chains held together by disulfide bonds. insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. Control of Insulin Secretion Insulin is secreted in primarily in response to elevated blood concentrations of glucose. This makes sense because insulin is "in charge" of facilitating glucose entry into cells. yielding the following model: y y Glucose is transported into the beta cell by facilitated diffusion through a glucose transporter. The figure to the right shows a molecular model of bovine insulin.Structure of Insulin Insulin is a rather small protein. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm.g. Our understanding of the mechanisms behind insulin secretion remain somewhat fragmentary.

html nsulin is composed of two peptide chains referred to as the A chain and B chain. Although the amino acid sequence of insulin varies among species. Increased levels of glucose within beta cells also appears to activate calciumindependent pathways that participate in insulin secretion. insulin dimers associate into hexamers. The molecule viewer below can be used to examine the structure of bovine insulin. Indeed. and an additional disulfide is formed within the A chain. which is soon significantly depleted. Insulin molecules have a tendency to form dimers in solution due to hydrogen-bonding between the C-termini of B chains. Setting the Color parameter to "Chain" will color the A chain green and the B chain red. plasma insulin levels increase dramatically.colostate. the A chain consists of 21 amino acids and the B chain of 30 amino but seems to result from metabolism of glucose and other fuel molecules within the cell. . elevated glucose not only simulates insulin secretion. associated with very low levels of insulin secretion. pig insulin has been widely used to treat human patients. Stimulation of insulin release is readily observed in whole animals or people. The secondary rise in insulin reflects the considerable amount of newly synthesized insulin that is released immediately.y increase in intracellular calcium is thought to be one of the primary triggers for exocytosis of insulin-containing secretory granules. The figure to the right depicts the effects on insulin secretion when enough glucose is infused to maintain blood levels two to three times the fasting level for an hour. This initial increase is due to secretion of preformed insulin. certain segments of the molecule are highly conserved. including the positions of the three disulfide bonds. in the presence of zinc ions. but also transcription of the insulin gene and translation of its In most species.A and B chains are linked together by two disulfide bonds. both ends of the A chain and the C-terminal residues of the B chain. Almost immediately after the infusion begins. and insulin from one animal is very likely biologically active in other species. Additionally. These similarities in the amino acid sequence of insulin lead to a three dimensional conformation of insulin that is very similar among species. The mechanisms by which elevated glucose levels within the beta cell cause depolarization is not clearly established. http://www. perhaps sensed as an alteration of ATP:ADP ratio and transduced into alterations in membrane conductance. Clearly. The normal fasting blood glucose concentration in humans and most mammals is 80 to 90 mg per 100 ml.

The pancreas is an elongated exocrine gland located just behind the stomach. This phenomenon. Hence. Insulin regulates the storage of glycogen in the liver and accelerates the oxidation of sugar in cells. delta cells that secrete somatostatin (a neurohormone that inhibits the secretion of insulin) and PP cells that secrete pancreatic polypeptide. giving resistance against neuropathy and other nervous diseases.These interactions have important clinical ramifications. Features o The clusters of pancreatic beta cells are enclosed by several types of cells such as alpha cells which secrete glucagon (a hormone whose function is opposite to that insulin. among others. there are clusters of cells that form the endocrine part of that organ. absorption of insulin preparations containing a high proportion of hexamers is delayed and somewhat slow. it helps to increase blood sugar level in the blood). Significance o Pancreatic beta cells generate and release a hormone called insulin that is essential especially for the metabolism of carbohydrates and the regulation of glucose levels in the blood (blood sugar). is released in the bloodstream during the production of insulin in pancreatic beta cells. deterioration of beta cells often results in type I or insulin-dependent diabetes. Structure o Pancreatic beta cells are anatomically and functionally different from pancreas endocrine tissue (unlike beta engineered such that lysine and proline residues on the Cterminal end of the B chain are reversed. Another hormone. pancreas endocrine tissue secretes pancreatic enzymes). has stimulated development of a number of recombinant insulin analogs. Monomers and dimers readily diffuse into blood. Within the pancreas. Beta cells are most prevalent in the islets. called the islets of Langerhans.called insulin lispro . The number of pancreatic beta cells varies from hundreds to thousands of cells. which secretes a hormone called insulin. and they make up just 1 to 2 percent of the total mass of the pancreas. this modification does not alter receptor binding. and they produce insulin and glucagon. 1. All these cells are connected . called C-peptide. but minimizes the tendency to form dimers and hexamers. The first of these molecules to be marketed . Their total weight is only 1 to 2 g. So. whereas hexamers diffuse poorly. Structure of a Pancreatic Beta Cell Pancreatic beta cells constitute the predominant type of cells in the pancreas.

The function of amylin. is the regulation of the effect of different foods on blood sugar levels.ehow.Low power view of large excretory duct Endocrine Pancreas: . http://www.High power view of an intralobular collecting duct cut in longitudinal section Figure 11 . The islets vary greatly in size. respectively.Excretory duct in the pancreas Figure 13 .High power view of pancreatic acini and islet Figure 9 . The pancreas has both an exocrine and an endocrine component. nerves and ducts lying between the lobules are surrounded by more abundant connective tissue.html The Pancreas The pancreas is an elongated gland which extends from the curve of the duodenum across the midline of the body toward the spleen. The diameters of the smallest and largest beta cells are 50 and 300 micrometers.Intercalated ducts entering an intralobular duct Figure 12 . which is a hormonal constituent of the pancreas. It has a head (expanded part lying near the duodenum). Pancreatic beta cells also release amylin. stored insulin is set free in order to restore the normal glucose level in the blood. The endocrine part consists of distinct masses of cells called islets of Langerhans scattered among the serous acini. The exocrine part consists of serous acini that make up most of the organ. Under the condition of high glucose level. Septa extending from the capsule divide the pancreas into poorly defined lobules. Function o Pancreatic beta cells do not simultaneously produce and release insulin into the body and tail. Identification o Pancreatic beta cells lack uniformity in size. A thin layer of moderately dense connective tissue forms an incomplete capsule around the organ.Low power view of the pancreas Figure 8 . y y y y y Endocrine Pancreas Exocrine Pancreas Figure 7 . Larger blood vessels. A stroma of loose connective tissue surrounds the lobules. or islet amyloid polypeptide (IAPP).with each other via extracellular spaces and gap junctions so they can send out cellular products between them.high power view of centroacinar cells y y y y Figure 10 . from a few cells to hundreds of cells.

Two hormones secreted by enteroendocrine cells in the duodenum are major regulators of exocrine pancreatic activity. A cells (15-20%) secrete glucagon. B cells. branching network and eventually drain into larger interlobular or excretory ducts. and amylase. which secrete a number of other peptides. The cells of the intercalated ducts are flattened and take up little stain. Exocrine Pancreas: The cells that make up the serous acini of the pancreas are pyramidal in shape with a broad base and a narrow luminal surface. The activation of trypsinogen within pancreatic cells is inhibited by trypsin inhibitor. THERE ARE NO SECRETORY (STRIATED) DUCTS IN THE PANCREAS. make up about 5% of the islets. which make up 60-70% of the islets. In the apical cytoplasm. Minor cell types. The interlobular ducts drain directly into the main pancreatic duct. elastase. they contain acidophilic zymogen granules. There are three principal cells types in the islets. which runs the length of the pancreas parallel to its long axis and joins the common bile duct before entering the duodenum. including trypsinogen. and D cells (5-10%) secrete somatostatin. they can be identified ascentroacinar cells or CA cells. In sections. secrete insulin. phospholipase A2. deoxyribonuclease. penetrate right into the center of the acinus. The structure of the endocrine pancreas and the functions of its hormones are discussed in the Endocrine Block. The intercalated ducts secrete a large volume of fluid that is rich in sodium and bicarbonate. the intercalated ducts. ribonuclease. triacylglycerol lipase. The release of secretin and CCK is stimulated by the entry of acidic chyme into the duodenum. procarboxypeptidase (all for digesting proteins). This establishes the optimum pH in the duodenum for the activity of the major pancreatic enzymes. while cholecystokinin (CCK) stimulates the acinar cells to release their proenzymes. which have a cuboidal epithelium. which are lined with low columnar epithelium. Enteroendocrine cells and an occasional goblet cell can be found in these ducts. They have elongated nuclei whose long axis is oriented in the direction of the duct. The intercalated ducts are short and drain into the intralobular collecting ducts. These products are conveyed by ducts to the small intestine. Trypsin in turn activates all the inactive enzymes. chymotrypsinogen. Cells of the smallest ducts. The intralobular collecting ducts form a complex. . These granules contain a number of digestive enzymes in their inactive form. Secretin stimulates the release of the bicarbonate rich fluid from the intercalated ducts. where enterokinases from the glycocalyx activate trypsinogen by converting it to trypsin. The duct system in the pancreas begins within the acini themselves. The bicarbonate serves to neutralize the acidic chyme that enters the duodenum from the stomach.The islets of Langerhans make up about 2% of the pancreas. including trypsinogen. and are most numerous in the tail.

the boundary of a somewhat longitudinally sectioned acinus is indicated by asterisks. The images of the pancreas shown in Figures 9 to 13 are all made from slide S49. the red. Most of an islet of Langerhans is seen at the left. The connective tissue is not much in evidence. The duct leaves the acinus at the left. Two islets can be easily identified near the top of the field of view. separated by delicate connective tissue septa. Several lobules. Islets consist of cords of cells through which numerous fenestrated capillaries course. However. no lumen is identifiable in the centre of the acini on this slide. A much smaller one is seen some distance below them. but its location is discernible by the artefactual gaps between lobules. . CA cells are also seen in many of the surrounding acini. An extended section of the intercalated duct lying within that acinus (the pale-staining centroacinar cells) is readily identified. The organization of neither the exocrine acini nor the endocrine islets can be seen at this magnification.Low power view of the pancreas shows a low power view of the pancreas made from slide #53 of your collection. can be identified.High power view of pancreatic acini and islet A higher power view of the pancreas is seen in figure 8 (also from slide #53). Usually. refractile zymogen granules at the apical ends of their cells stand out. The islets of Langerhans appear as pale-staining islands scattered throughout the organ. Figure 8 . its boundary indicated by asterisks.high power view of centroacinar cells shows a high power view of centroacinar cells lying within pancreatic acini. Figure 9 . Near the middle of the field of view. The serous acini are closely packed together and do not appear very distinct.Figure 7 .

Low power view of large excretory duct shows a low power .Intercalated ducts entering an intralobular duct shows some intercalated ducts entering an intralobular collecting duct. It has cuboidal cells whose boundaries are not distinct. are present. The length of the duct in this section is fortuitous. Figure 11 . (The CT is more abundant when ducts or other structures. such as blood vessels and nerves. they appear as pale cells squeezed among the acini. branching network within a lobule. which form a complex. The one indicated by the lower leader of "icd" can be followed for some distance to the left and probably originates from the acinus at the far left of the field of view. It lies just above an islet of Langerhans. Figure 12 . they lie in the connective tissue septa between lobules. The intraloubular duct appears as a distinct oval profile with a prominent lumen containing secretory material (arising from the acini and intercalated ducts). Excretory ducts are also called interlobular ducts. The intercalated ducts are not very distinct.) Excretory ducts are lined with low columnar epithelium which becomes taller as the duct progresses. Figure 10 shows a longitudinal section of an intralobular collecting duct extending across most of the field of view.Figure 10 . Secretory material is present in the lumen. but their round nuclei can be clearly seen.Excretory duct in the pancreas Figure 13 . The cell boundaries of the duct in Figure 12 cannot be distinguished but their slightly oval nuclei are easily seen. Note the pale staining of both the islets and the ducts. The epithelium is cuboidal. shows an excretory duct. The apical surfaces of the cells of the surrounding acini appear slightly brighter than the basal surfaces due to the presence of zymogen granules. It is joined by a duct from the acinus just below the lower leader. The intercalated duct indicated by the upper leader of "icd" appears to originate from the acinus just to its right.High power view of an intralobular collecting duct cut in longitudinal section The intercalated ducts are short and drain into intralobular collecting ducts. and as this name implies.

When blood glucose rises.htm#Figure 12 Pancreas Structure of the Pancreas The pancreas is an elongated organ that lies behind and below the stomach. it sometimes stimulates conversion of glucose to glycogen in the liver. This mixed gland contains both exocrine and endocrine tissues. the pancreas releases a hormone to correct the level. The predominant exocrine part consists of grape-like clusters of secretory cells that form sacs known as acini. Also. insulin. Hormones Secreted by the Pancreas The most important hormones secreted by the pancreas are insulin and glucagon. It causes the breakdown of stored liver glycogen to glucose. Insulin promotes the movement of glucose and other nutrients out of the blood and into cells. so that the sugar content of blood leaving the liver rises.courseweb. The pancreas can measure blood sugar and if it is high or low. Function of the Pancreas The pancreas is largely responsible for maintaining blood glucose levels. released from the beta cells causes glucose to enter body cells to be used for Blood glucose must be maintained at a certain level for cells to neither gain or lose water. The normal clinical range of blood glucose levels is 70 to 150 mg/dL (milligrams per deciliter).uottawa. Another pancreatic hormone. The smaller part of the gland consists of isolated islands of endocrine tissue known as islets of Langerhans which are dispersed throughout the pancreas.http://www. Both play a role in proper metabolism of sugars and starches in the body. promotes the movement of glucose into the blood when glucose levels are below normal. Digestive Enzymes Secreted by the Pancreas The exocrine pancreas secretes the pancreatic juice consisting of two components: . which connect to ducts that eventually empty into the the first portion of the intestine called duodenum. glucagon.

y Pancreatic enzymes actively secreted by the acinar cells that form the maldigestion and salt depletion. Retention cysts are gross enlargements of pancreatic ducts secondary to ductal obstruction. Proteolytic enzymes for protein digestion Pancreatic amylase for carbohydrate digestion Pancreatic lipase for fat digestion3 Pancreatic Diseases y Cystic Fibrosis An autosomal recessive genetic disease of the exocrine glands.. Congenital cysts occur more frequently as solitary cysts but may be multiple. 3. neoplastic.gopetsamerica. The right lobe is located along the descendingpart of the duodenum. and AMYLASE) by the EXOCRINE PANCREAS into the DUODENUM. enterogenous. pancreatic insufficiency. distinguished from the much more common pancreatic pseudocyst by possessing a lining of mucous epithelium.aspx What Is the Pancreas? The pancreas is a gland located in the abdominal cavity that servesimportant functions relat ed to digestion and the production of certainhormones. http://www.Pancreatic pseudocysts account for most of the cystic collections in the pancreas and are often associated with chronic pancreatitis. 2. Pancreatic cysts are categorized as congenital. liver and small bowel. y Nesidioblastosis An inherited autosomal recessive syndrome characterized by the disorganized formation of new islets in the pancreas and persistent hyperinsulinemia hypoglycemia of infancy. It is caused by gene mutations. chronic respiratory infections. y An aqueous alkaline solution rich in sodium bicarbonate (NaHCO3) actively secreted by the duct cells that line the pancreatic ducts. The left lobe of the pancreas lies next to the stomach. This condition is often associated with cystic fibrosis and with chronic pancreatitis. which is the first segment of the small bowel(in testine). retention. Pancreatic Enzymes The acinar cells secrete three different types of enzymes: 1. There are two parts orlobes of the pancreas. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in airway obsturction. y Exocrine Pancreatic Insufficiency A malabsorption condition resulting from greater than 10% reduction in the secretion of pancreatic digestive enzymes ( LIPASE. y Pancreatic Cyst A true cyst of the pancreas. Where Is the Pancreas Located? The pancreas is located within the upper abdominal cavity in closeproximity to the stomach. It is due to focal hyperplasia of pancreatic islet cells budding off from the ductal structures and forming new islets of Langerhans. These pancreactic enzymes are very important because they can almost completely digest food in the absence of all other digestive secretion.What Is the General Struc . parasitic. or dermoid. PROTEASES. Sodium bicarbonate neutralizes the acidity of the chyme so that won't burn the intestines.

with a small central portion that join s the lobes. Pancreatic juice is secreted (released) into the intestinal tract in response to eating food. These are less common diseases of the pancreas. Two excretoryducts ± the accessory duct and the pancreatic duct ± carry these enzymes into the intestine where they aid in thedigestion of food. It often causes loss of appetite. When the beta cells of the pancreas detect an increase in the blood sugar concentration. The pancreas also contains unique cells (beta cells) that form the islets of Langerhans. many cells cannot use it for energy. therefo re. glucagon. The anatomic arrangement of these ducts differs slightly between dogs and cats. insulin is released directly into the blood where it acts to carry glucose into the body's cells. acts to increase blood sugar and is released when blood sugar is low. In severe cases. Pancreatic juice contains enzymes needed for digesting proteins. y Pancreatitis. and amongindividual ani mals. the pancreas consists of cells arranged in to small sections or lo bules. glucagon. Another important disease of the pancreas is diabetes mellitus or sugar diabetes. it is an important hormone in regulating levelsof glucose in the blood. carbohydrates. y Diabetes mellitus. One of the most important. What Are the Common Diseases of the Pancreas? There are a number of common diseases of the pancreas. Pancreatitis can be difficult to diagnose in cats. and potentially dangerous diseases is inflammation of the pancreas. Secondly.ture of the Pancreas? The feline pancreas is composed of right and left lobes. Inadequate production of insulin causes the blood sugar to become too high. and they store them within small granules or packets located within the cell. insulin lowers the blood glucose concentration. These cells produce a numberof digestive enzymes.What Are the Functions of the Pancreas? The pancreas serves two main functions. the condition can be fatal. The higher the blood sugar. abdominal pain and depression. This common disorder of cats represents an underproduction or excessively low secretion of insulin. The pancreas also produces the hormone. Although the circulating level of glucose is high in the blood. The hormone. Pancreatic abscesses are small pockets of infection that may develop as a complication of pancreatitis. First it produces and stores digestive enzymes and fluids. the pancreas produces and secretes hormones that are very important in the regulation of blood sugar. and serious side effects develop. whic h produce insulin. . y Pancreatic cysts and abscesses. Insulinallows many cells in the body to use blood sugar (glucose). Thus. and especially fats.Microscopically. vomiting. the more insulin is secreted.

and it is a highly invasive cancer. but are very serious conditions. glucagonomas secrete glucagon. Insulinoma is a tumor that produces insulin. Pancreatic cancers occur infrequently. The pancreas creates a wide range of different hormones. and is very rare in the cat. It is part of two different organ systems. What Types of Diagnostic Tests Are Used to Evaluate the Pancreas? Commonly used tests in evaluation of the pancreas include the following y Abdominal radiographs (x-rays) y Abdominal ultrasound y Lipase and amylase levels in the blood y Trypsin-like immunoreactivity (TLI). Unique pancreatic cancers of the hormonal components of the pancreas develop only rarely in the cat. This article we'll take a look at the structure and function of the pancreas. the endocrine system and the digestive system. Structure of the pancreas .aspx The pancreas is a rather unique organ in the human body. A gland is a structure in the body that secrete Exocrine pancreatic insufficiency. especially in patients with diabetes y Measurements of glucose and ketones in the urine y Measurement of insulin levels in the blood http://www. some of which are used to trigger internal metabolic reactions. the pancreas is a large gland. and gastrinomas produce excessive amounts of gastrin hormone. y Pancreatic carcinoma. A unique condition called EPI represents a deficiency in digestive pancreatic enzymes.petplace. A cancer of the glandular portion of the pancreas is called pancreatic adenocarcinoma. and others which are used to help break down food. a blood test that assesses production of digestive enzymes y Blood sugar. This disease leads to an inability to digest food properly. Technically.

The common bile duct is the duct which drains bile from the gallbladder. or drain. this drain empties directly into the duodenum. as well as a wide variety of other hormones used by the body. These hormones include insulin. These islets are small structures dotted throughout the pancreas. glucagon. in the pancreas which leads to the common bile duct. The body of the pancreas is the largest section. It is estimated that each pancreas contains over one million of these islets. The pancreas also has a tail. The enzymes are mixed with bile and then drained into the duodenum. Nerve supply to the pancreas is primarily through the vagus nerve. which is furthest from the duodenum. It develops as two separate parts which are fused together early in life. The pancreas receives its blood supply from various different arteries. Another major structure of the pancreas is known as the Islets of Langerhands. This duct is used to drain the execrable hormones which aid in the digestion of food that is passing through the small intestine. Function of the pancreas The pancreas is involved in a wide variety of functions in the endocrine and exocrine system. There is a small duct.The pancreas is located just below the stomach. located in the center of the gland just below the stomach. Lets first take a look at some of the endocrine functions of the pancreas. and are responsible for producing insulin. . The head of the pancreas is located nearest to the duodenum. The pancreas is broken into several different subsections. The pancreas is also located near the first part of the small intestine. An endocrine hormone is a hormone produced by a gland (such as the pancreas) which is secreted directly into the blood stream. These arteries all have very specific names. depending on where they originate from. In some people. and somatostatin. however in most people it empties into the common bile duct. known as the duodenum.

Two blood vessels enter the liver. causing much damage. It has a very complex structure and has many functions related to your metabolism. These enzymes are used to aid digestion of food. enzymes are produced which are transported to the duodenum. In the case of the pancreas. Exocrine glands do not secrete hormones directly into the bloodstream. It consists of two lobes which are wedge-shaped. which is formed by the liver cells. Each lobe is further divided into many small lobules. forming bile ducts. each being about the size of a pin-head. working closely with nearly every fundamental system and process in the human body. These bile ducts all eventually unite. http://www. bile capillaries and lymph capillaries. Without enough insulin. pancreatic amylase. forming a common duct that opens into the duodenum. Some of these hormones include pancreatic lipase. Two ducts originate in the liver. Rather. with bile channels and blood channels between them. namely the hepatic portal vein with dissolved food substances from the small intestine. which then joins the pancreatic duct. but this can get rather complicated. and the hepatic artery.helium. and these unite to form the common hepatic duct which opens. which then unite. the two continue as the general bile duct. Insulin is responsible for regulating the amount of sugar which is absorbed into the cells of the body. and this collects in the bile capillaries. in the hollow side of the duodenum (the first section of the small intestine). the sugar remains in your bloodstream where it can cause significant health problems. which gives off a branch. . Where a cystic duct joins the hepatic duct.Insulin is famous for being the hormone which is deficient in people with diabetes. The functions of the liver are varied. and is the storage place for bile. in particular homeostasis and the regulation of blood sugar. the pancreas is also subject to becoming cancerous. The pancreas is also an exocrine gland. with the pancreatic duct. and consisting of many liver cells. on its way toward the hepatic duct. they secrete hormones into organs. forming the main hepatic duct. so I'll leave a discussion of diabetes alone for now). The gall bladder lies inside the liver. the cystic duct. and is situated slightly below the diaphragm and anterior to the stomach. The cystic duct leads into the gall bladder. The liver cells secrete the Liver Cell Structure And Function The liver is the largest gland in the body. People with diabetes do not produce enough insulin (or are resistant to its effects. The pancreas is an extremely important organ in your body. Permeating the entire liver structure is a system of blood capillaries. The right lobe of the liver is larger than the left lobe. As is the case with many organs in the body. and trypsin. with oxygenated blood from the lungs. Damage to the pancreas can often be quite significant hormones and digestive enzymes can be inappropriately released into the surrounding area.

etc. The liver has several structures that help it carry out important human biomechanical processes. 13. Forms bile: bile consists of bile salts and the excretory bile pigments. All cells contain the same copy of DNA molecules. Storage of vitamins such as vitamin A and D. 7. 2. 3. Making heparin: this is a substance that prevents the blood from clotting as it travels through the blood system. 12. it is changed into a carbohydrate that can be used. carbohydrates and proteins. the orange-red pigment in plants.causes the excess glucose to turn into glycogen. Regulation of amino acids: a supply of amino acids in the blood is kept at a normal as required or sent to fat storage sites if not needed straight away.excreted by the pancreas . The main blood proteins include fibrinogen. Forms cholesterol: this fatty substance is used in the cells. and excess coming from the gut is stored as glycogen.1%. the hemoglobin is converted into bile pigments and the iron atoms are saved for future use. Removal of hemoglobin molecules: when red blood cells die. leading to heart attacks. etc. Regulation of blood sugar: The level of blood sugar stays at around 0. Any spare which has not been absorbed cannot be stored but is converted into the waste products. each tissue cell processes different functions carried out by genetic information. called urea when at the liver.essortment. toxins. The liver extracts many harmful materials from the blood and excretes them in the bile or from the kidneys. Storage of blood: the liver can swell to hold huge amounts of blood which can be released into the circulation if the body suddenly needs more. albumens and globulins. This is carried round the body in the blood and warms less active regions. http://www. 10. Excess amounts in the blood can cause the blood vessels to become blocked. if it is wounded. 5.g. e. The remainder of the amino acid molecule is not wasted. 4. the heart metabolizes and produces different proteins than the liver. For instance. 11. Formation of red blood cells in the young embryo while it is developing in the womb. and is then sent to the kidneys to be removed from the body as urine. Forms plasma proteins: the plasma proteins are used in blood clotting and in keeping the blood plasma constant.html Structure of Liver Cells The liver is a vital organ that cleans the blood and metabolizes macromolecules like lipids. Vitamin B12 is also stored in the liver. 9. It is important to speed up the digestion of lipids. The hormone called insulin . etc. Regulation of lipids: Lipids are extracted from the blood and changed to carbohydrates. Vitamin A is also made in the liver from carotene. 6. However. Removals of hormones. even though they contain the same DNA. Production of heat: the liver is one of the hardest working regions of the body and produces a lot of waste heat. prothrombin. 8.1. .

html Structure of the Liver The liver consists of four sections. protecting the body from infection. Stellate Cells o Stellate cells are part of the nervous system. A macrophage is a cell that is a part of the immune system.1. These cells perform the work of the liver. Hepatocytes o Hepatocytes are the main cell for protein synthesis. Kupffer cells breakdown old red blood cells and secrete the waste in the bile for removal from the body. broken down and reused when necessary. There are two main lobes--the right lobe. stellate cells become active and signal it for repair. which is by far the larger. Mitochondria play a large role in metabolism of proteins. It helps with pain and sensory information from the liver to provide communication. They are also responsible for recycling lipoproteins. the cells create homeostasis for the body's fatty tissue deposits and circulating protein for energy and storage. Most livers have between 50. Mitochondria o Mitochondria are located in most human cells. http://www. It is a necessary organ required for life. Liver Function o Without a liver. carbohydrates and lipids. so it's no surprise that the liver has outstanding healing capabilities and regeneration. which is a hardening of the liver. . The liver will even heal after long term abuse or damage. The liver is the largest gland in the body. HDL ("good") cholesterol carry fatty acids back to the liver. They innervate the organ to provide a connection between the brain and the liver. and it sits on the right side under the rib cage for protection.ehow. Each lobe is made up of multisided units called lobules. The sinusoids give the liver a spongy texture and enable it to hold large amounts of blood. Macrophages circulate the body and destroy foreign microbes.000 lobules. where is recycled. they contain a large amount of mitochondria to keep up with the body's demand for energy and synthesis. Hepatocytes are also responsible for synthesis and breakdown of lipids from triglycerides. but there is an elevated number in liver cells. synthesize proteins or metabolize toxins from drugs. Two small lobes lie behind the right lobe. Each lobule consists of a central vein surrounded by tiny liver cells grouped in sheets or Kupffer Cells o Kupffer cells are specialized macrophages. Overall. Stellate cells play a role in scar tissue formed when liver damage occurs. Constant repair leads to scar tissue and eventual cirrhosis. the human body would not be able to store carbohydrates. Because a large portion of the process is only located in the liver cell. When the liver starts to degenerate. and the left lobe. or lobes. Cavities known as sinusoids separate the groups of cells within a lobule.000 and 100.

tiny tubes that carry the bile secreted by the liver cells. which carry bile out of the liver. or digested food particles. The liver is involved in the normal physiological functions of many organs and systems of the body such as the cardiovascular and immune systems. Blood leaves the liver through the hepatic vein. and detoxifying harmful chemicals. The sinusoids drain into the central veins. the bile ducts join together. Like other organs. Many important substances are secreted into the gastro-intestinal tract by it. The bile capillaries join to form bile ducts.36Kg. minerals. This blood enters the liver through the portal vein. the hepatic artery and the portal vein branch into a network of tiny blood vessels that empty into the sinusoids. The liver cells absorb nutrients and oxygen from the blood as it flows through the sinusoids. which join to form the hepatic vein. It consists of two major lobes (left and right) and two minor lobes (caudate and quadrate). forming the hepatic duct. They also filter out wastes and poisons. Bile The structure and function of liver cells The liver is the largest internal organ of the body. where it is stored for later use. The liver also receives blood filled with nutrients. Excess bile flows into the gall bladder. from the small intestine. the liver receives blood containing oxygen from the heart. Each lobule also contains bile capillaries.The liver has an unusual blood supply system. This blood enters the liver through the hepatic artery. In the liver. Soon after leaving the liver. . they secrete sugar. weighing about 1. located in the right upper quadrant of the abdomen. The liver manufactures bile continuously. vitamins. as well as storing and processing of nutrients. The liver is the only solid organ which can regenerate itself. At the same time. even if the small intestine is not digesting food. and other substances into the blood. synthesizing new molecules.

but this storage function is usually short term. and by-products of metabolism if accumulated become toxic. and is converted by the liver and kidneys. Sinusoids are low pressure vascular channels that receive blood from arteries supplying the liver. The gallbladder's function is to store and concentrate the bile produced by the liver until it is needed in the small intestine.Many ingested substances are harmful to the body's cells. . the cellular process of engulfing solid particles such as bacteria and cell debris. Bile helps to neutralize and dilute stomach acid and emulsify fats to aid in digestion.and K). The close association of liver cells and the circulation allows absorption of nutrients from digestion as well as secretion of many products into the blood. For example. and supplements. to obtain the active form of the vitamin.Hepatocytes can remove sugar from the blood and store it as a substance called glycogen. + Storage . + Nutrient Inter-conversion . and allow substances to enter and leave the blood stream. is biologically inert. E. The liver is closely associated with the gallbladder which is situated in a depression on the inferior surface of the liver. The liver detoxifies many substances by altering their structure to make them less toxic or make their elimination easier. and iron are stored as well. Functions of the Liver: + Bile production . and it performs many metabolic and secretory functions. Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose by the body. which functions in calcium maintenance.The main functional cell in the liver is called a hepatocyte.the liver can convert some nutrients into others. food. copper. The cells are polygonal in shape and arranged in one to two cell thick plates separated by fine vascular sinusoids through which blood flows. + Detoxification . this occurs when ingested nutrients are not always in the proportion needed by the tissues.The liver produces and secretes about 600-1000 ml of bile each day. + Phagocytosis . Blood flow into the liver sinusoids comes from terminal branches of both the hepatic portal vein and hepatic artery. The hepatocytes will then break down proteins and form lipids and glucose. vitamins (A. It is a pear-shaped sac and is filled with stored bile. D. They are highly permeable. Fats. Vitamin D obtained from sun exposure. a person who is on a diet that is excessively high in protein and inadequate amounts of carbohydrates and lipids.

such as albumins. waste products and other debris that enters the liver through the circulation. known as Kupffer cells. The inferior and posterior surfaces are divided into four lobes by five fossae. which are arranged in the form of the letter H. known as the right and left lobes. The left limb of the H marks on these surfaces the division of liver into right and left lobes. These come from networks in the stomach. lie along the sinusoid walls and phagocytize nonfunctioning blood cells." The tributaries of the portal vein include (1) the right and left "gastric veins" from the stomach. and the rectum. Falciform Ligament The falciform ligament is the line of attachment that divides the liver into two parts.The liver produces blood plasma Right Liver Lobe The right liver lobe is the larger of the two lobes by six times. (2) the "superior mesenteric vein" from the small intestine. pancreas. The left limb of the H marks on these surfaces the division of liver into right and left lobes. sigmoid colon. bacteria. intestines. Its largest tributary is the "inferior mesenteric vein. and transverse colon. Coronary Ligament The coronary ligament are the folds of peritoneum connecting the posterior surface of the liver and the diaphragm. pancreas. The corresponding arteries of the same names are taking oxygenated blood to these sites in paths parallel to those of the veins. There. Abdominal Veins and Arteries Veins usually carry blood straight to the atria of the heart." These empty into the "inferior vena cava. After passing through the portal veins of the liver. and carry blood from these organs through a "portal vein" to the liver. and clotting factors. blood is carried through a series of merging vessels into the "hepatic veins. + Synthesis . ascending colon." and return the blood into circulation. which are released into the circulation." called the "hepatic portal system. The inferior and posterior surfaces are divided into four lobes by five fossae. and spleen. globulins. . and (3) the "splenic vein" from a number of merging veins from the spleen. but those of the abdominal tissues are exceptions. fibrinogen. and part of the stomach. which are arranged in the form of the letter H. the blood enters capillarylike "hepatic sinusoids. Left Liver Lobe The left liver lobe is the smaller and flatter of the two liver lobes. http://www.helium.Hepatic phagocytic cells." which brings blood up from the descending colon.

the right lobe is separated from the smaller left lobe by the falciform ligament. less functional. Any disease that attacks liver cells such as viral hepatitis or chemicals affecting the liver such as seen in chronic alcohol abuse may bring about sclerosis. Gallbladder The gallbladder is an active storage shed. Qaudrate Lobe The qaudrate lobe is situated on the visceral surface of the right lobe to the left of the fissure for the gallbladder. The falciform ligament is responsible for attaching the liver to the anterior abdominal wall and the diaphragm by way of the coronary ligament. portal vein lymphatics. Although the liver is the largest internal organ of the body. Cirrhosis is often accompanied by the presence of ammonia from the hepatic portal vein on into systemic circulation. Liver (An Overview) The liver has two major lobes and two minor lobes. The gallbladder is a small. an irreversible liver disease destroys large numbers of liver lobules and replaces them with a permanent type of connective tissue from hepatocytes called regenerative nodules. A ligamentum teres is continuous along the free border of the falciform ligament and is a remnant of the umbilical vein of the fetus. The canaliculi are drained peripherally by bile ducts which in turn drain into hepatic ducts that carry bile away from the liver. blood travels in the sinusoids and bile travels in the opposite direction so blood and bile never mix in the lobules of the liver under normal conditions. This is due to the fact that hepatocytes. In the middle of each lobule is a central vein and at the periphery of each lobule are branches of the hepatic portal vein and hepatic artery. The central veins of the lobules will converge to form two hepatic veins which will carry blood from the liver to the inferior vena cava. pear-shaped sac which is situated just below the liver and is . The plate structure of the liver and high permeability of the sinusoids allow each hepatocyte to be in close contact with the blood. and nerves enter the liver and where the hepatic ducts exit. The porta of the liver is where the hepatic artery. and on the left by the fissure of the ductus venosus. Arterial blood and portal venous blood. which absorbs mineral salts and water received from the liver and converts it into a thick. Anteriorly.Caudate Lobe The caudate lobe is situated upon the dorsal surface of the right lobe bounded by the inferior vena cava. opening into spaces between hepatic plates. Cirrhosis. the caudate lobe is near the inferior vena cava. Bile is produced in the liver by the hepatocytes and secreted into thin channels called bile canaliculi located within each hepatic plate." to be released when food is present in the stomach. These nodules don't have the plate-like structure of normal liver tissue and are consequently. it is only one to two cells thick. mucus substance called "bile. Inferiorly. or liver cells. are only one to two cells thick and separated from each other by large capillary spaces called sinusoids. the upper layer of which is exposed as if the liver were to be pulled away from the diaphragm. The hepatic plates are arranged into functional units called liver lobules. and the quadrate lobe is adjacent to the gallbladder. As a result. containing nutrient molecules absorbed in the gastrointestinal tract mix as the blood flows from the periphery of the lobule to the central vein.

phlegm (cold and moist). We still speak in terms of "melancholia" (excess black bile." They merge. The canals of neighboring lobules unite to form larger ducts. yellow bile (hot and dry) and black bile (cold and dry). Gorky's body.000. it is necessary to see through the microscope. the surface of liver cells and cowardice of the three.attached to it by tissues. mitochondria. under different physiological conditions of the there are small differences. Each cell surface can be divided into liver sinusoidal surface. leading to depression) and "phlegmatic" (sluggish or impassive) and scientists have named the heavy mucus secreted in the respiratory passages .5 billion liver cells. the 6th Century BC Greek mathematician. to form the "common hepatic duct. and these converge to become the "hepatic ducts. the bile flows into the gallbladder and is stored there. liver cells polygon diameter of about 20 to 30 microns. and phrenic veins. such as hunger. and drink vacuole of particulate . The chemical structure of the liver The liver is composed of liver cells. liver cytoplasm. there are many fine "bile canals" that receive secretions from the hepatic cells. soft and crisp.900 square micron.phlegm. gonadal veins. believed that life is based on the four elements of earth. Liver cells it contains many complicated fine structure: If liver cells. vulnerable to violence and rupture caused fatal bleeding. Oh. When this happens. Minimal liver cells. the human liver Hepatic Lobules total of around 500. the largest volume of liver cells. where its exit is guarded by a sphincter muscle. volume of about 4. was reddish-brown. endoplasmic reticulum and lysosomes. and extensive vascular network. It collects blood from the hepatic veins. The perfect or imperfect balance of these humors supposedly determined one's health and intelligence. When food leaves the stomach. It stores bile and then releases it when food passes from the stomach to the duodenum (the first part of the small intestine) to help in the process of digestion. where the bile disperses the fats in the food into liquid. where's your sense of "humor"? Bile Duct Within the liver lobules. the lumbar veins. 6-8 face. liver cells 5000 Hepatic Lobules one. Sinusoids The sinusoids are capillary-like vessels which the blood is conveyed to the inferior vena cava by the hepatic veins. Pythagoras was kind of a "square". renal veins. It has a capacity of around one and one-half fluid ounces. It leads to the duodenum. fire and water which correspond to the body's "humors": blood (hot and moist). This sphincter normally remains contracted until the bile is needed. air. Pythagoras." The "common bile duct" is formed by the union of the common hepatic and the cystic ducts. Liver about 2. so that bile collects in the common bile duct and backs up to the cystic duct. Inferior Vena Cava The inferior vena cava is a large vein ascending through the abdomen. in turn. come on. a secretion causes the gallbladder to contract and expel its contents into the duodenum. The inferior vena cava enters the heart through the right atrium. These vessels usually drain regions that are supplied by arteries with corresponding names.

the lysosome increased significantly. such as bile secretion on its closely related. or aminotransferase). the uptake of liver cells in many organic smooth endoplasmic online Synthesis.2 times. and adenosine triphosphate. resulting in bleeding tendency. the endoplasmic reticulum in liver cell damage. Lysosomes Liver cells in lysosomes containing rich. While participation of the cytoplasmic membrane . As detoxification weakened. Degenerative aging can digest the endoplasmic reticulum. bile pigment lysosomal actively involved in the transfer. Slide endoplasmic reticulum is the rough endoplasmic reticulum of 2. protein metabolism. The glycogen synthesis and decomposition. mainly distributed in the hepatic duct near capillary cytoplasm. of which more than 70 certificates of enzymes and coenzyme. resulting in the skin. mitochondria is the first and most sensitive of the victim. has been hailed as the cell's "digestive system" and "cleaners. hormone metabolism. Since bilirubin metabolism. fat. mitochondria. extreme swelling caused elevated liver transaminases. respiratory enzyme cells. 0. When hunger. jaundice. hepatitis. Because of fibrinogen and thrombin original manufacturer reduced. the endoplasmic reticulum damage reduction in albumin production. systemic hypoxia.4 microns in diameter. synthetic enzyme. drug metabolism and detoxification process and the synthesis of bile are smooth endoplasmic reticulum conducted. and so on. leading to enhanced toxicity of drugs. Hepatitis. Hepatitis. the integration of biochemical reactions. Generally. contains a variety of digestive enzymes can analyze protein. increased cholesterol or partial hepatectomy. oxygen. sclera stained. hepatitis C virus invasive liver cells. decomposition. flocculation test and turbidity test abnormalities. The rough endoplasmic reticulum protein synthesis of liver cells is a base. such as ALT (SGPT or ALT." Obstructive jaundice. Endoplasmic reticulum The cytoplasm of the hepatocytes was flat or bubble tubular cystic structure. accounting for 10% of the volume of the cytoplasm. The rough endoplasmic reticulum and smooth endoplasmic reticulum two. Liver cells It is the function of replication of genetic information. albumin is the rough endoplasmic omentum on the synthesis of multi-synuclein. Gorky's body and liver cells and exocrine and endocrine functions are closely related. Because glycogen reduced. thereby maintaining the content of liver cell self-renewal. leading to low blood sugar. Hepatic uptake of amino acid protein synthesis very quickly. or cholestatic hepatitis. sugar. Hepatitis viruses can cause direct damage to the lysosome and adjacent normal liver cells and dissolved necrosis. Foreign bodies. Gorky's body Each liver cells about 50 Gorky's body found in the vicinity of liver cells. such as oxidoreductase of hydrolysis enzymes. biochemical disorder. resulting in the patients with serum albumin and globulin ratio (A / G) inversion. Furthermore.components. Mitochondria Each liver cell mitochondria of 1000-2000. and can be a surplus of a few amino acid to another amino acid. Slide endoplasmic reticulum widely distributed in the cytoplasm of liver. fat metabolism. the virus genes in the DNA of liver cells combine (integration). such as nucleic acid and phosphoric acid. The membrane has many enzymes. that people can live. which ensures the existence of human life. Once integration is difficult HBsAg clearance. which carry long HBsAg. the process is in the endoplasmic reticulum.5 to 3. indirectly blush of bile into direct bilirubin. often with the rough endoplasmic reticulum and Golgi's body linked to the three functions are closely linked. Each has its fine structure is extremely important and complex functions. a single membrane surrounding the dense body. cells and others.

Microsomal Particulate body is the main enzyme catalase and peroxidase. To perform these surface-specific tasks. Liver cell protein and lipoprotein synthesis. it makes numerous compounds used throughout the body.g. Defining how alcohol consumption changes liver cell structure and function is critical for the development of effective treatments for patients suffering not only from alcoholic liver disease. and it detoxifies and rids the body of poisonous substances (e. The proper performance of the hepatocyte relies on its specific cellular architecture.g. performs many vital functions. Because these two surfaces are in contact with vastly different environments..000 deaths per year are attributed to alcohol consumption. we have been examining how MAL proteolipids function in apical PM sorting in polarized hepatic cells.000 are caused by liver cirrhosis. respectively. liver cancer) that lead to cirrhosis. the basolateral and apical domains have their own unique set of molecular machinery. a combination of its structure and function. Because MAL and MAL2 have been identified as important regulators of apical PM delivery in both pathways and because their activity requires cholesterol and glycosphingolipids. Unlike simple epithelial cells that directly target proteins from the TGN to the apical PM. Microsomal can be reduced coenzyme oxidation. How is this machinery specifically delivered to its proper cellular home? This is the fundamental question my research addresses. It converts food into chemicals required for life. To prevent hydrogen peroxide accumulation in the cell. We have previously shown that indirect sorting in hepatocytes requires cholesterol and glycosphingolipids. or by retrieving compounds from the blood for the liver's use or detoxification. more than 20. Drink vacuole With absorption and intracellular transport of material function. the body's largest organ. These cells form a barrier between the internal and external liver environments by bonding themselves together with specialized structures called tight junctions. Part 2. Although alcoholic liver disease is a major biomedical health concern in the United States. little is known about how alcohol induces liver injury. and 100. Of those deaths.. MAL and MAL2 have been identified as regulators of direct and indirect apical delivery. but also from other liver diseases (e. see Part 2).glycoprotein and the initial formation of lysosomes. the basolateral surface communicates with the blood either by releasing compounds the liver has made for delivery to other organs. Part 1. The role of MAL proteins in regulating apical delivery. Alterations in liver structure and function associated with alcoholic liver disease Why study alcoholic liver disease? Approximately 75% of all Americans consume alcohol. Hepatocellular carcinoma cells of the particulate reduction. they each perform specific tasks. . sinus further into the perirenal space. hepatitis. the complex molecular "soap" stored in the gallbladder that helps us absorb dietary fats and remove waste products. The basolateral cell surface faces the blood that flows through the liver (the internal environment) whereas the apical surface faces the bile (the external environment). hepatocytes use an indirect pathway: proteins are first delivered to the basolateral domain. Our long-term goal is to understand how hepatic cells establish and maintain their polarity. Also in the microsomal metabolism of alcohol and gluconeogenesis and the enzymes. For example. Our focus is to identify regulators of apical plasma membrane (PM) delivery. the seventh largest cause of death among Americans. Understanding normal liver cell structure and function What is the relationship between liver cell structure and function? The liver. then selectively internalized and transcytosed to the apical surface. And also on cholesterol metabolism. part of the body transferred to Gorky's storage processing. The apical surface similarly "communicates" with the bile by releasing substances destined for excretion. These junctions in turn divide the cell surface into two domains: the basolateral and apical.

It weighs about three pounds and is shaped like a football that is flat on one side. What are the different types of alcohol-related liver disease? There are three main types of alcohol-related liver disease: fatty liver disease. abdominal pain. Almost all heavy drinkers have fatty liver disease.. Up to 35 percent of heavy drinkers develop alcoholic hepatitis. Between 10 and 20 percent of heavy drinkers develop cirrhosis. It is the most serious type of alcohol-related liver disease. How does alcohol affect the liver? Alcohol can damage or destroy liver cells. and it is often difficult and expensive to do animal studies.Why study alcohol-induced liver damage in WIF-B cells? The liver is the major site of alcohol metabolism. and thus. http://biology. Thus. If it is severe. Alcoholic cirrhosis Alcoholic cirrhosis is the scarring of the liver -. Fatty liver disease Fatty liver disease is the build up of extra fat in liver cells. Alcoholic hepatitis can be mild or severe. Animals can vary significantly in their responses to alcohol. It is the earliest stage of alcohol-related liver disease. it may occur suddenly and quickly lead to serious complications including liver failure and death. The liver breaks down alcohol so it can be removed from your body. We are examining the effects of alcohol exposure on membrane trafficking with respect to alcohol-induced alterations in microtubule modifications and dynamics.These cells maintain their liver-specific structure and functions in vitro and efficiently metabolize alcohol like intact liver. It processes what you eat and drink into energy and nutrients your body can use. it is not understood why and how this progression occurs. a fatty liver develops which can lead to hepatocyte injury. weakness. fatty liver disease will usually go away. if they stop drinking. liver fibrosis. they exhibit the same cellular alterations as seen in alcohol-exposed livers.hard scar tissue replaces soft healthy tissue.cfm Alcohol-Related Liver Disease Explore this section to learn more about the ways in which alcohol affects the liver and how alcoholinduced liver disease is diagnosed and treated. and weight loss. Alcoholic hepatitis Alcoholic hepatitis causes the liver to swell and become damaged. and ultimately to cirrhosis. The liver also removes harmful substances from your blood. Symptoms may include loss of appetite. many researchers are trying to find alternative strategies to study alcohol-induced liver damage. Although the disease progression is well described in patients. If it is mild. and alcoholic cirrhosis. If symptoms do occur. alcoholic hepatitis. There are usually no symptoms. Not drinking alcohol can help prevent further damage. The liver performs many jobs in your body. However. fever and jaundice. liver damage may be reversed. Your liver can become injured or seriously damaged if you drink more alcohol than it can process. Symptoms of cirrhosis are similar to those of alcoholic hepatitis.cua. vomiting. Traditionally. primates) have been used to describe physiological responses to alcohol consumption.g. but these approaches can be problematic. Also importantly. We have been developing one such alternative strategy: WIF-B cells. The damage from cirrhosis cannot be reversed and can cause liver failure. Why is the liver important? The liver is the second largest organ in your body and is located under your rib cage on the right side. they may include fatigue. animal models (e. the most susceptible organ to alcohol-induced injury. In the early stages of the disease. rats. How does alcohol-related liver disease progress? .

Treatment may require you to participate in an alcohol recovery program. How is alcohol-related liver disease treated? Treatment for alcohol-related liver disease requires a healthy diet including avoiding alcohol. Medications may be needed to manage the complications caused by your liver damage. Blood tests may be used to rule out other liver diseases. some heavy drinkers may develop cirrhosis without having alcoholic hepatitis first. They may include: y build up of fluid in the abdomen y bleeding from veins in the esophagus or stomach y enlarged spleen y high blood pressure in the liver y brain disorders and coma y kidney failure y liver cancer How is alcohol-related liver disease diagnosed? Alcohol-related liver disease may be suspected based on medical conditions related to alcohol abuse. In advance cases of alcoholic cirrhosis. Heavy drinkers who also have a chronic liver disease such as hepatitis C are at high risk for developing cirrhosis. a small piece of liver tissue is removed and studied in the lab. Your doctor also may need to do a liver biopsy. The complications can be serious. http://www. For all types of liver disease caused by alcohol.Many heavy drinkers will progress from fatty liver disease to alcoholic hepatitis to alcoholic cirrhosis over time.fatty Alcohol and Liver Disease Drinking too much alcohol can lead to three types of liver conditions . hepatitis. During a biopsy. Your doctor may suggest changes in your diet to help your liver recover from the alcohol-related damage. Others may have alcoholic hepatitis but never have symptoms. Those with alcohol-related liver disease need to stop drinking alcohol to be considered for a liver transplant. the main treatment is to stop drinking alcohol completely. What are the complications of alcohol-related liver disease? Complications from alcohol-related liver disease usually occur after years of heavy drinking. and cirrhosis. However. a liver transplant may be needed. What does the liver do? . You are unlikely to develop these problems if you drink within the recommended safe limits detailed below.liverfoundation.

These are then passed out in the urine and from the lungs. However. drinking over the recommended limits (detailed below) can be harmful. . poisons and toxins from the body. it is absorbed into the bloodstream from the stomach and intestines. y Processing many medicines which you may take. All blood from the stomach and intestines first goes through the liver before circulating around the whole body. the level of alcohol in your bloodstream rises. The liver cells can process only a certain amount of alcohol per hour. if you drink alcohol faster than your liver can deal with it. Indeed. Its functions include: y Storing glycogen.The liver is in the upper right part of the abdomen. the highest concentration of alcohol is in the blood flowing through the liver. Liver cells contain enzymes (chemicals) which process (metabolise) alcohol. What happens when you drink alcohol? When you drink alcohol. y Making bile which passes from the liver to the gut and helps to digest fats. If you drink heavily you have an increased risk of developing: y Serious liver problems (alcoholic liver disease). So. What are the problems of drinking too much alcohol? Your liver and body can usually cope with drinking a small amount of alcohol. y Mental health problems. So. When required. a chemical made from sugars. y Some stomach disorders. The enzymes break down alcohol into other chemicals which in turn are then broken down into water and carbon dioxide. y Making proteins that are essential for blood to clot (clotting factors). glycogen is broken down into glucose which is released into the bloodstream. y Helping to remove or process alcohol. y Pancreatitis (severe inflammation of the pancreas). drinking a small amount of alcohol (1-2 units per day) may help to prevent heart disease and stroke. y Helping to process fats and proteins from digested food. including depression and anxiety.

and cirrhosis. generally feeling unwell and. deaths due to alcohol-related diseases (particularly liver disease) have risen considerably over the last 20 years or so. caused by a high level of bilirubin . or all. Alcohol dependence (addiction). Liver cells become damaged and die as scar tissue gradually develops. This can cause deep jaundice. Accidents . However. confusion. and is often fatal. blood clotting problems. hepatitis. See separate leaflets called 'Alcohol and Sensible Drinking' which deals with general aspects of alcohol. of these conditions can occur at the same time in the same person. Obesity (alcohol has many calories). bleeding into the guts. Muscle and heart muscle disease. which can gradually damage the liver and eventually cause cirrhosis. In the UK. colon and breast). Some cancers (mouth. gullet. In particular. This is because heavy drinking and binge drinking have become more common. .fatty liver. Damage to an unborn baby in pregnant women. fatty liver is not usually serious and does not cause symptoms. pain over the liver. About 1 in 7 road deaths are caused by drinking alcohol. jaundice (yellowing of the skin. The scarring tends to be a gradual process.a chemical normally metabolised in the liver). y A very severe bout of alcoholic hepatitis can quickly lead to liver failure. What is alcoholic liver disease? Drinking too much alcohol can lead to three types of liver conditions . The only indication of inflammation may be an abnormal level of liver enzymes in the blood which can be detected by a blood test. High blood pressure. Alcoholic hepatitis Hepatitis means inflammation of the liver. injury and death from fire and car crashes. However. The inflammation can range from mild to severe. Damage to nervous tissue. The rest of this leaflet is about alcoholic liver disease. The scar tissue affects the normal structure and regrowth of liver cells. The scar tissue can also affect the blood flow through the liver which can cause back pressure in the blood vessels which bring blood to the liver. sometimes. Alcoholic cirrhosis Cirrhosis is a condition where normal liver tissue is replaced by scar tissue (fibrosis).drinking alcohol is associated with a much increased risk of accidents. y The main treatment for alcoholic hepatitis is to provide adequate nutrition (this sometimes involves passing liquid feeds through a tube in the stomach) and steroids. Fatty liver A build-up of fat occurs within liver cells in most people who regularly drink heavily. coma. Any. liver. the liver gradually loses its ability to function well. in some cases the hepatitis becomes persistent (chronic). So. in some people the fatty liver progresses and develops into hepatitis. In itself. y A more severe hepatitis tends to cause symptoms such as feeling sick. and 'Alcoholism and Problem Drinking' which includes information on alcohol dependence. Fatty liver will usually reverse if you stop drinking heavily.y y y y y y y y y Sexual difficulties such as impotence. y Mild hepatitis may not cause any symptoms.

and the more regularly that you drink. However. The scaring and damage of cirrhosis is usually permanent and cannot be reversed. a biopsy (small sample) of the liver may be taken to be looked at under the microscope. Note: cirrhosis can develop in people who have never had alcoholic hepatitis. Vitamin supplements may be prescribed for a while. or the typical features of liver cells with alcoholic hepatitis can be seen on a biopsy sample. See separate leaflet called 'Cirrhosis' for more details. . However. persistent viral hepatitis and some hereditary and metabolic diseases. Some tests may be done: y Blood tests may show abnormal liver function. as more and more liver cells die. But. you are likely to increase your risk of developing cirrhosis.About 1 in 10 heavy drinkers will eventually develop cirrhosis. Cirrhosis can lead to end-stage liver disease (liver failure). What is the treatment for alcoholic liver disease? For all types of liver disease caused by alcohol. and a physical examination. recent research has led to a greater understanding of cirrhosis. Also.Liver' for details. Cirrhosis can happen from many causes other than alcohol. you may be referred to a dietician to review your diet. in the early stages of the condition. symptoms start to appear. The eventual symptoms and complications are similar to a severe episode of hepatitis (listed above). You can get by with a reduced number of working liver cells. unlike a bout of severe hepatitis. or that you are retaining fluid. the more your risk of developing hepatitis and/or cirrhosis. But. It is not clear why some people are more prone for their liver cells to be damaged by alcohol and to develop hepatitis and/or cirrhosis.) y An ultrasound scan may show that you have a damaged liver. (See separate leaflet called 'Blood Test . you should stop drinking alcohol completely. However. (For example. Research suggests that it may be possible to develop medicines in the future which can reverse the scarring process of cirrhosis. This is because many people who drink heavily do not eat properly and need advice on getting back into eating a healthy diet. the heavier you drink. often there are no symptoms. as a rule. and more and more scar tissue builds up.Liver Function Tests' for details. and drink heavily. (See separate leaflet called 'Biopsy . y To confirm the diagnosis. they may detect that your liver is enlarged. If you have another persistent liver disease. For example. It tends to occur after 10 or more years of heavy drinking. How is alcoholic liver disease diagnosed? A doctor may suspect that you have liver problems from your symptoms. the symptoms and complications tend to develop slowly.) They may especially think of liver problems as a cause of your symptoms if you have a history of heavy alcohol drinking.) The scarring of the liver caused by cirrhosis.

then you have had three and a half units. you should fully recover from these conditions if you stop drinking alcohol. the cirrhosis is unlikely to progress. stopping drinking alcohol can improve your outlook. and you stop drinking alcohol. And never binge drink or get drunk. If you drink a quarter of a litre (250 ml) . This is above the upper safe limit for a woman. then this is a risk to your health. If you drink two bottles of 12% wine over a week. Some other examples Three pints of beer. If you have severe hepatitis and require hospital admission. Another example: a 750 ml bottle of 12% wine contains nine units. you may require intensive care treatment. However. y Women should drink no more than 14 units of alcohol per week (and no more than three units in any one day). binge drinking can be harmful even though the weekly total may not seem too high. or alcoholic hepatitis which is not severe. And remember. In general. the more harmful alcohol is likely to be. or 8 g by weight. One unit of alcohol is 10 ml (1 cl) by volume.just under a pint . and the liver can barely function. but when you do you drink 4-5 pints of beer each time. A more accurate way of calculating units is as follows. For example: y One unit of alcohol is about equal to: o half a pint of ordinary strength beer or cider (3-4% alcohol by volume). is at least 18-20 units per week. of pure alcohol. That is: y Men should drink no more than 21 units of alcohol per week (and no more than four units in any one day). or a bottle of wine each time. That is nearly the upper weekly safe limit for a man. If you drink half a litre (500 ml) . If you have cirrhosis. . If cirrhosis is diagnosed when it is not too advanced. For example. or o a standard pub measure (50 ml) of fortified wine such as sherry or port (20% alcohol by volume) y There are one and a half units of alcohol in: o a small glass (125 ml) of ordinary strength wine (12% alcohol by volume). If you do chose to drink when you are pregnant then limit it to one or two units. y Pregnant women. or o a standard pub measure (35 ml) of spirits (40% alcohol by volume) But remember.two small glasses . It depends on how severe the cirrhosis has become. the cirrhosis and symptoms will usually get worse if you continue to drink alcohol. that is 18 units. For example: y Strong beer at 6% abv has six units in one litre. y Wine at 14% abv has 14 units in one litre.then you have had three units. once or twice a week. In severe cases where the scarring is extensive. However. The exact amount that is safe is not known. or o a small pub measure (25 ml) of spirits (40% alcohol by volume). Some people with severe hepatitis will die. each drinking session of three pints is at least six units.y y y If you have fatty liver. the more you drink above the safe limits. Preventing alcoholic liver disease You are very unlikely to develop liver problems caused by alcohol if you drink within the recommended safe limits. which is more than the safe limit advised for any one day. Therefore. then a liver transplant may be the only option. The percentage alcohol by volume (% abv) of a drink equals the number of units in one litre of that drink. many wines and beers are stronger than the more traditional ordinary strengths. if you only drink alcohol once or twice a week. advice from the Department of Health is that pregnant women and women trying to become pregnant should not drink at all. three times per week.

But. you should not drink alcohol at all if: y You have already developed early cirrhosis. . Your doctor will advise for each specific condition. y You have chronic hepatitis or certain other liver problems.