INTRODUCTION

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

MINICOURSE 1.3 SECTION 1

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.

MINICOURSE 1.3 SECTION 2

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

common trunk 3. right hepatic v. - drains most of the right lobe OBJECTIVES 2, 3 Questions 1. Describe what is meant by a portal triad. 2. What types of cells are found in venous sinusoids and what do they do? 3. Describe the arterial supply of blood to the liver. EXERCISE 2 DISCUSSION OBJECTIVES 2, 3 - Answers 1. A portal triad is an arrangement of three structures within the liver lobule. At the corner of the hexagonally arranged lobule the following structures are seen together: 1. branch of hepatic portal vein 2. branch of hepatic artery 3. bile duct 2. There are two types of cells present within the venous sinusoids. the endothelial cells and the Kupffer cells. The endothelial cells have very large pores which allow for H20 and plasma proteins to pass. The Kupffer cells on the other hand are reticuloendothelial cells capable of phagocytizing foreign matter in blood. 3. Off the abdominal aorta is a main arterial trunk called the celiac trunk. A branch of the celiac trunk is the hepatic artery. Once the hepatic artery enters the substance of the liver, it divides into the left hepatic and right hepatic arteries.

MINICOURSE 1.3 SECTION 3

OBJ. 4. Describe the following functions of the liver: a. production of bile b. production of plasma proteins c. detoxification Functions of the Liver Although this section focuses on the activities of the liver with respect to bile and plasma pro- teins, and the process of detoxification, it should be pointed out that the liver has other functions as well. These functions include:

1. 2. 3. 4.

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

Because proteins are stored for only limited periods of time, any imbalance between the amino acids required and those which are available is handled quite readily by the livers amino acid interconversion capability. Two major categories of proteins produced by the liver are the albumins and the globulins. The albumins are large colloidal protein molecules which have an influence on osmotic pressure, plasma volume and tissue fluid balance. The globulins are involved in many functions such as: the transport of several key substances (iron, copper, lipids); serving as a precursor to fibrin (fibrino- gen); serving as antibodies or immunoglobins (Gamma globulin, IgG, IgE, IgA, IgD, IgM). Furthermore, several proteins concerned with blood coagulation are produced by the liver, such as: 1. 2. 3. 4. 5. Fibrinogen Prothrombin Factor VII Factor IX Factor X

Another function of the liver is detoxification. You will recall from an earlier pharmacology mini- course that in this process, which can manifest itself as either conjugation, oxidation, or reduction, the liver metabolizes the by-products of cellular metabolism and exogenous materials such as drugs. Of particular importance is the removal of ammonia which is toxic to the human organism. This ammonia is removed from amino acids via deamination and converted to a normally non- toxic material called urea. Urea, 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. Because of the vast enzyme system of the liver, this organ plays an important role in drug metabolism. Knowledge of how a drug is handled by the liver is very important in therapeu- tics. As one can imagine, liver damage must be taken into account when drugs that are metabo- lized in the liver are given to a patient. Not all types of liver disease affect drug metabolism equally, since drug metabolism is not uniform throughout the liver. However, those disease states which damage areas which actively metabolize drugs can have serious consequences. In order for a patients ability to metabolize drugs to be compromised, the liver parenchymal cells surrounding the central vein must be damaged. In some cases, such as liver damage associated with alcohol- ism, this area is not damaged and there is little change in the drug metabolizing capabilities. On the other hand, toxic substances like carbon tetrachloride (CC14), a cleaning fluid, specifically damages the parenchymal cells

surrounding the central vein and, therefore, severely compromises an individuals drug metabolizing capacity. EXERCISE 3 OBJECTIVE 4 Questions 1. Describe bile in terms of its: 1. constituents 2. function 2. Name the plasma proteins produced by the liver which are involved in blood coagulation. 3. Which proteins formed by the liver are important to the immune system? 4. What is the most important compound detoxified by the liver under normal circumstances? EXERCISE 3 DISCUSSION OBJECTIVE 4 Answers 1. Bile is a complex solution composed of the bile pigments (bilirubin and biliverdin), bile salts, sodium, potassium, chloride, calcium, cholesterol, water. When bile enters the duodenum, 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. 2. The liver produces the following plasma proteins involved in blood coagulation: 1. 2. 3. 4. 5. Fibrinogen Prothrombin Factor VII Factor IX Factor X

3. Gamma globulin IgE, IgA, IgG, IgD and IgM. 4. Ammonia. It is removed by the metabolic breakdown of drugs and amino acids and is converted into urea.

MINICOURSE 1.3 SECTION 4

OBJ. 5. Describe the pathology of cirrhosis of the liver:

1. Laennec's (portal) 2. 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. As the cellular destruction continues, blood, lymph and bile channels within the liver become distorted and compressed, leading to intrahepatic congestion, portal hypertension and impaired liver function. The fibrous changes within the organ cause it to become firmer and smaller. The surface, however, becomes rough and bumpy because of the development of nodules on the surf ace of the organ. The nodules are regenerated hepatic cells. The two types of cirrhosis considered in this objective have the following distinguishing characteristics: 1. Laennec's portal cirrhosis 1. scar tissue surrounds portal area 2. most commonly due to chronic alcoholism 2. Biliary 1. scarring around bile ducts and lobes of liver 2. 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 fatty metamorphosis seen in liver disorders is not generally a fatty infiltration from non-hepatic sources, but is a deposition of fat resulting from deranged hepatocyte lipid metabolism. It is a common sequela of a large number of liver disorders including infections and intoxications. The prolonged passive congestion of right-sided heart failure tends to cause fatty change due to venous congestion involving the inferior vena cava, 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, they are especially susceptible to damage due to hepatic vein congestion. It is important to remember that cirrhosis is a chronic progressive disease and, although it may be halted in some of its stages, the damage that has already occurred is not reversible. Cirrhosis is the result of a fibroplasia that leads to extensive scarring. 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.

Spider nevi and palmar erythema may be due to a deficiency of the B- complex vitamins. Splenomegaly is due to obstruction of the splenic vein, one of the two major veins forming the hepatic portal vein. Biliary cirrhosis is less common and is due to an obstruction in the bile duct system, such as would be created by a gallstone. It does not destroy the liver as rapidly as portal cirrhosis, but it is also a serious disorder and is one of the causes of jaundice. In this particular situation, it would be called obstructive jaundice. 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. Briefly compare Laennec's and biliary cirrhosis. 2. What are some of the symptomatic changes which occur due to cirrhosis? EXERCISE 4 DISCUSSION OBJECTIVE 4 Answers 1. In Laennec's cirrhosis, common in chronic alcoholism, fatty deposits eventually lead to the development of fibrous scar tissue which surrounds the portal area. In biliary cirrhosis scarring occurs around the bile ducts and lobes of the liver and may lead to jaundice. 2. Some of the symptomatic changes which are seen in cirrhosis are: ascites, esophageal varices, ulcer, hypovitaminosis and splenomegaly.

SECTION 5
OBJ. 6. Describe the gallbladder and its function. OBJ. 7. Describe the anatomy of the biliary tree and the sphincters. The Gallbladder A structure which looks somewhat like a pear lies on the under or visceral surface of the liver. It is called the gallbladder and is composed of three portions termed the neck, the body, and the fundus. The following diagram illustrates the position of the

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

Bile salts are constituents of bile which aid in the digestion of fats via a process called emulsification. In summary: 1. Bile is continually secreted by the liver. 2. Approximately 50 ml of bile may be stored in the gallbladder. 3. Upon gallbladder contraction - bile passes from the gallbladder --> cystic duct -> common bile duct ---> to the duodenum. 4. Bile is composed of bile salts, cholesterol, H20, bilirubin, phospholipids, Na, K, C1, Ca, HCO3. 5. Bile salts 1. cause fat emulsification 2. help in fatty acid absorption 6. Without bile salts - no fat soluble vitamins (A, D, E, K) are absorbed. No vitamin K leads to Factor VII, IX, X, and prothrombin deficiency which leads to coagulation difficulties. OBJECTIVE 6 Question Describe the sequence of events which cause bile to be ejected from the gallbladder. EXERCISE 5 DISCUSSION OBJECTIVE 6 Answer When fats are present within the duodenum, they will stimulate the intestinal mucosa to secrete a substance called cholecystokinin. This cholecystokinin causes gallbladder contraction. When the gallbladder contracts, bile is ejected into the cystic duct which joins the hepatic duct to form the common bile duct which carries bile to the duodenum. Relaxation of the sphincter of Oddi allows for the passage of bile into the duodenum.

MINICOURSE 1.3 SECTION 6

OBJ. 8. Describe the formation of gallstones. Gallstones A gallstone is actually a stone-like mass called a calculus, which forms in the gallbladder. This condition has the medical term cholelithiasis. 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. Some underlying causes include: pregnancy, obesity, diabetes, and cholecystitis. In the United States, about 10 to 20 percent of the adult population has gallstones. They are rare in the first two decades of life. The four F's fat, female, fertile (multiparous), and forty characterize the

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

SECTION 7
OBJ. 9. Describe the pancreas in terms of: 1. 2. 3. 4. 5. position duct system exocrine secretion endocrine secretion "diabetes mellitus" relationships

The Pancreas The pancreas is an unusual structure in that it is both exocrine and endocrine in function. This very diffuse structure lies slightly below and behind the

stomach. Various pancreatic secretions which participate in the digestive process flow (from the exocrine portion of the pancreas) down the main pancreatic duct, the duct of Wirsung. This duct, in many people, joins the common bile duct prior to its entrance into the duodenum. The exocrine secretions of the pancreas include: 1. 2. 3. 4. lipase amylase trypsin carboxypeptidase

The endocrine portion, on the other hand, consists of packets or groups of cells called the islets of Langerhans. The islets are composed of two types of cells: 1. alpha cells - secrete glucagon 2. beta cells - secrete insulin Insulin decreases blood glucose level by stimulating the cellular uptake and the metabolism of glucose. In contrast, glucagon increases the blood glucose level by stimulating the conversion of glycogen to glucose in the liver. The rate of their secretion is directly controlled by the concentration of glucose in the blood. Thus, it can be discerned that insulin is directly involved in carbohydrate metabolism, as follows:

increased blood sugar levels

produces

beta cell stimulation ---> insulin secretion

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. Thus, 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- hydrate metabolism, specifically glucose. This disorder usually develops in subjects as a heredi- tary disorder and is manifested in the fully developed form by: 1. 2. 3. 4. 5. 6. 7. 8. 9. weakness lassitude loss of weight hyperglycemia (high blood sugar) ketosis acidosis protein breakdown glycosuria and much, much more.

Although other factors may play a part in the disease, diabetes is probably mainly due to inadequate insulin secretion by the beta cells. The major threats to the diabetic patient arise from the disease's surrounding complications, especially those associated with severe metabolic abnormalities resulting in ketoacidosis as well as complications such as: 1. retinitis 2. renal failure 3. hypertension

4. neuropathy 5. premature atherosclerosis

http://www.ece.ncsu.edu/imaging/MedImg/SIMS/GE1_3.html

Functional Anatomy of the Endocrine Pancreas

The pancreas is an elongated organ nestled next to the first part of the small intestine. 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. The endocrine portion of the pancreas takes the form of many small clusters of cells called islets of Langerhans or, more simply, islets. Humans have roughly one million islets. In standard histological sections of the pancreas, islets are seen as relatively pale-staining groups of cells embedded in a sea of darker-staining exocrine tissue. The image to the right shows three islets in the pancreas of a horse. Pancreatic islets house three major cell types, each of which produces a different endocrine product:
y y y

Alpha cells (A cells) secrete the hormone glucagon. Beta cells (B cells) produce insulin and are the most abundant of the islet cells. Delta cells (D cells) secrete the hormone somatostatin, which is also produced by a number of other endocrine cells in the body.

Interestingly, the different cell types within an islet are not randomly distributed - beta cells occupy the central portion of the islet and are surrounded by a "rind" of alpha and delta cells. Aside from the insulin, glucagon and somatostatin, a number of other "minor" hormones have been identified as products of pancreatic islets cells. Islets are richly vascularized, allowing their secreted hormones ready access to the circulation. Although islets comprise only 1-2% of the mass of the pancreas, they receive about 10 to 15% of the pancreatic blood flow. Additionally, they are innervated by parasympathetic and sympathetic neurons, and nervous signals clearly modulate secretion of insulin and glucagon.

The pancreas is a compound tubular-alveolar gland composed of serous acini (exocrine portion), and islets of Langerhans (endocrine portion). The islets of Langerhans are collections of cell cords separated from the exocrine acinar tissue by a thin connective tissue sheath.

The acini and their ducts resemble a bunch of grapes. The ducts lie in dense connective tissue septa which provide the main support of the gland. The vascular and nervous supply of the acini (and islets) are also located in these septa. Branches of these vessels terminate as capillary networks around the acini and form dense networks within the islets. The capillaries, in both cases, are of the fenestrated type.

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

Pancreatic Histology: Exocrine Tissue

The pancreas is surrounded by a very thin connective tissue capsule that invaginates into the gland to form septae, which serve as scaffolding for large blood vessels. Further, these septae divide the

pancreas into distinctive lobules, as can clearly be seen in the image of mouse pancreas below (H&E). The large spaces between lobules seen in this image are a commonly-observed artifact of fixation.

The Acinus
The exocrine pancreas is classified as a compound tubuloacinous gland. The cells that synthesize and secrete digestive enzymes are arranged in grape-like clusters called acini, very similar to what is seen in salivary glands. In standard histologic sections, most acini are cut obliquely, making it difficult to discern their characteristic shape. In the image of equine pancreas below, one fairlygood cross section through an acinus is circled; note the wedge-shapped cells arranged around a small lumen:

Pancreatic Ducts
Digestive enzymes from acinar cells ultimately are delivered into the duodenum. Secretions from acini flow out of the pancreas through a tree-like series of ducts. Duct cells secrete a watery, bicarbonate-rich fluid which flush the enzymes through the ducts and play a pivotal role in neutralizing acid within the small intestine. Pancreatic ducts are classified into four types which are discussed here beginning with the terminal branches which extend into acini. Intercalated ducts receive secretions from acini. They have flattened cuboidal epithelium that extends up into the lumen of the acinus to form what are calledcentroacinar cells. Intralobular ducts have a classical cuboidal epithelium and, as the name implies, are seen within lobules. They receive secretions from intercalated ducts. Interlobular ducts are found between lobules, within the connective tissue septae. They vary considerably in size. The smaller forms have a cuboidal epithelium, while a columnar epithelium lines the larger ducts. Intralobular ducts transmit secretions from intralobular ducts to the major pancreatic duct. The main pancreatic duct received secretion from interlobular ducts and penetrates through the wall of the duodenum. In some species, including man, the pancreatic duct joins the bile duct prior to entering the intestine. Histologic features of the pancreatic duct system are illustrated in the following images: A longitudinal section through an intercalated duct (Cynomologous monkey pancreas, H&E stain). The duct is running from upper left to lower right. Note the low cuboidal, almost squamous epithelium.

Section of equine pancreas (H&E stain) showing a longitudinal section through anintercalated duct emptying into an intralobular duct. Note the cuboidal epithelium in the intralobular duct.

Small interlobular ducts (equine pancreas; H&E stain): note the columnar epithelium. A thin interlobular septum is seen running horizontally immediately above the duct.

A low magnification image of equine pancreas (H&E stain) showing a large interlobular duct in association with a pancreatic artery (A) and vein (V). An intralobular duct (D) is seen on the right side.

http://www.vivo.colostate.edu/hbooks/pathphys/digestion/pancreas/histo_exo.html

nsulin Synthesis and Secretion

Structure of Insulin
Insulin is a rather small protein, with a molecular weight of about 6000 Daltons. It is composed of two chains held together by disulfide bonds. The figure to the right shows a molecular model of bovine insulin, with the A chain colored blue and the larger B chain green. You can get a better appreciation forthe structure of insulin by manipulating such a model yourself. The amino acid sequence is highly conserved among vertebrates, and insulin from one mammal almost certainly is biologically active in another. Even today, many diabetic patients are treated with insulin extracted from pig pancreas.

Biosynthesis of Insulin
Insulin is synthesized in significant quantities only in beta cells in the pancreas. The insulin mRNA is translated as a single chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. Proinsulin consists of three domains: an amino-terminal B chain, a carboxy-terminal A chain and a connecting peptide in the middle known as the C peptide. Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm. When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C peptide is also secreted into blood, but has no known biological activity.

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. Some neural stimuli (e.g. sight and taste of food) and increased blood concentrations of other fuel molecules, including amino acids and fatty acids, also promote insulin secretion. Our understanding of the mechanisms behind insulin secretion remain somewhat fragmentary. Nonetheless, certain features of this process have been clearly and repeatedly demonstrated, yielding the following model:
y

Glucose is transported into the beta cell by facilitated diffusion through a glucose transporter; elevated concentrations of glucose in extracellular fluid lead to elevated concentrations of glucose within the beta cell. Elevated concentrations of glucose within the beta cell ultimately leads to membrane depolarization and an influx of extracellular calcium. The resulting

increase in intracellular calcium is thought to be one of the primary triggers for exocytosis of insulin-containing secretory granules. The mechanisms by which elevated glucose levels within the beta cell cause depolarization is not clearly established, but seems to result from metabolism of glucose and other fuel molecules within the cell, perhaps sensed as an alteration of ATP:ADP ratio and transduced into alterations in membrane conductance. Increased levels of glucose within beta cells also appears to activate calciumindependent pathways that participate in insulin secretion.

Stimulation of insulin release is readily observed in whole animals or people. The normal fasting blood glucose concentration in humans and most mammals is 80 to 90 mg per 100 ml, associated with very low levels of insulin secretion. 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. Almost immediately after the infusion begins, plasma insulin levels increase dramatically. This initial increase is due to secretion of preformed insulin, which is soon significantly depleted. The secondary rise in insulin reflects the considerable amount of newly synthesized insulin that is released immediately. Clearly, elevated glucose not only simulates insulin secretion, but also transcription of the insulin gene and translation of its mRNA.

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin.html
nsulin is composed of two peptide chains referred to as the A chain and B chain.A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids. The molecule viewer below can be used to examine the structure of bovine insulin. Setting the Color parameter to "Chain" will color the A chain green and the B chain red.

Although the amino acid sequence of insulin varies among species, certain segments of the molecule are highly conserved, including the positions of the three disulfide bonds, both ends of the A chain and the C-terminal residues of the B chain. These similarities in the amino acid sequence of insulin lead to a three dimensional conformation of insulin that is very similar among species, and insulin from one animal is very likely biologically active in other species. Indeed, pig insulin has been widely used to treat human patients. Insulin molecules have a tendency to form dimers in solution due to hydrogen-bonding between the C-termini of B chains. Additionally, in the presence of zinc ions, insulin dimers associate into hexamers.

These interactions have important clinical ramifications. Monomers and dimers readily diffuse into blood, whereas hexamers diffuse poorly. Hence, absorption of insulin preparations containing a high proportion of hexamers is delayed and somewhat slow. This phenomenon, among others, has stimulated development of a number of recombinant insulin analogs. The first of these molecules to be marketed - called insulin lispro - is engineered such that lysine and proline residues on the Cterminal end of the B chain are reversed; this modification does not alter receptor binding, but minimizes the tendency to form dimers and hexamers.

Structure of a Pancreatic Beta Cell

Pancreatic beta cells constitute the predominant type of cells in the pancreas, which secretes a hormone called insulin. Insulin regulates the storage of glycogen in the liver and accelerates the oxidation of sugar in cells. So, deterioration of beta cells often results in type I or insulin-dependent diabetes. The pancreas is an elongated exocrine gland located just behind the stomach. Within the pancreas, there are clusters of cells that form the endocrine part of that organ, called the islets of Langerhans. Beta cells are most prevalent in the islets.

1. 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). Another hormone, called C-peptide, is released in the bloodstream during the production of insulin in pancreatic beta cells, giving resistance against neuropathy and other nervous diseases.

Structure
o

Pancreatic beta cells are anatomically and functionally different from pancreas endocrine tissue (unlike beta cells, pancreas endocrine tissue secretes pancreatic enzymes), and they produce insulin and glucagon. The number of pancreatic beta cells varies from hundreds to thousands of cells. Their total weight is only 1 to 2 g, and they make up just 1 to 2 percent of the total mass of the pancreas.

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; it helps to increase blood sugar level in the blood), delta cells that secrete somatostatin (a neurohormone that inhibits the secretion of insulin) and PP cells that secrete pancreatic polypeptide. All these cells are connected

with each other via extracellular spaces and gap junctions so they can send out cellular products between them.

Identification
o

Pancreatic beta cells lack uniformity in size. The diameters of the smallest and largest beta cells are 50 and 300 micrometers, respectively.

Function
o

Pancreatic beta cells do not simultaneously produce and release insulin into the blood. Under the condition of high glucose level, stored insulin is set free in order to restore the normal glucose level in the blood. Pancreatic beta cells also release amylin, which is a hormonal constituent of the pancreas. The function of amylin, or islet amyloid polypeptide (IAPP), is the regulation of the effect of different foods on blood sugar levels.

http://www.ehow.com/about_5855875_structure-pancreatic-beta-cell.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. It has a head (expanded part lying near the duodenum), body and tail. A thin layer of moderately dense connective tissue forms an incomplete capsule around the organ. Septa extending from the capsule divide the pancreas into poorly defined lobules. A stroma of loose connective tissue surrounds the lobules. Larger blood vessels, nerves and ducts lying between the lobules are surrounded by more abundant connective tissue. The pancreas has both an exocrine and an endocrine component. The exocrine part consists of serous acini that make up most of the organ. The endocrine part consists of distinct masses of cells called islets of Langerhans scattered among the serous acini. The islets vary greatly in size, from a few cells to hundreds of cells.

y y y y y

Endocrine Pancreas Exocrine Pancreas Figure 7 - Low power view of the pancreas Figure 8 - High power view of pancreatic acini and islet Figure 9 - high power view of centroacinar cells

y y y

Figure 10 - High power view of an intralobular collecting duct cut in longitudinal section Figure 11 - Intercalated ducts entering an intralobular duct Figure 12 - Excretory duct in the pancreas Figure 13 - Low power view of large excretory duct

Endocrine Pancreas:

The islets of Langerhans make up about 2% of the pancreas, and are most numerous in the tail. There are three principal cells types in the islets. B cells, which make up 60-70% of the islets, secrete insulin. A cells (15-20%) secrete glucagon, and D cells (5-10%) secrete somatostatin. Minor cell types, which secrete a number of other peptides, make up about 5% of the islets. The structure of the endocrine pancreas and the functions of its hormones are discussed in the Endocrine Block.

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. In the apical cytoplasm, they contain acidophilic zymogen granules. These granules contain a number of digestive enzymes in their inactive form, including trypsinogen, chymotrypsinogen, procarboxypeptidase (all for digesting proteins), ribonuclease, deoxyribonuclease, triacylglycerol lipase, phospholipase A2, elastase, and amylase. These products are conveyed by ducts to the small intestine, where enterokinases from the glycocalyx activate trypsinogen by converting it to trypsin. Trypsin in turn activates all the inactive enzymes, including trypsinogen. The activation of trypsinogen within pancreatic cells is inhibited by trypsin inhibitor. The duct system in the pancreas begins within the acini themselves. Cells of the smallest ducts, the intercalated ducts, penetrate right into the center of the acinus. In sections, they can be identified ascentroacinar cells or CA cells. The cells of the intercalated ducts are flattened and take up little stain. 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, which have a cuboidal epithelium. The intralobular collecting ducts form a complex, branching network and eventually drain into larger interlobular or excretory ducts, which are lined with low columnar epithelium. Enteroendocrine cells and an occasional goblet cell can be found in these ducts. THERE ARE NO SECRETORY (STRIATED) DUCTS IN THE PANCREAS. The interlobular ducts drain directly into the main pancreatic duct, which runs the length of the pancreas parallel to its long axis and joins the common bile duct before entering the duodenum. The intercalated ducts secrete a large volume of fluid that is rich in sodium and bicarbonate. The bicarbonate serves to neutralize the acidic chyme that enters the duodenum from the stomach. This establishes the optimum pH in the duodenum for the activity of the major pancreatic enzymes. Two hormones secreted by enteroendocrine cells in the duodenum are major regulators of exocrine pancreatic activity. Secretin stimulates the release of the bicarbonate rich fluid from the intercalated ducts, while cholecystokinin (CCK) stimulates the acinar cells to release their proenzymes. The release of secretin and CCK is stimulated by the entry of acidic chyme into the duodenum.

Figure 7 - Low power view of the pancreas shows a low power view of the pancreas made from slide #53 of your collection. Several lobules, separated by delicate connective tissue septa, can be identified. The connective tissue is not much in evidence, but its location is discernible by the artefactual gaps between lobules. The islets of Langerhans appear as pale-staining islands scattered throughout the organ. Two islets can be easily identified near the top of the field of view. A much smaller one is seen some distance below them. The organization of neither the exocrine acini nor the endocrine islets can be seen at this magnification.

Figure 8 - High power view of pancreatic acini and islet

A higher power view of the pancreas is seen in figure 8 (also from slide #53). The serous acini are closely packed together and do not appear very distinct. However, the red, refractile zymogen granules at the apical ends of their cells stand out. Usually, no lumen is identifiable in the centre of the acini on this slide. Most of an islet of Langerhans is seen at the left, its boundary indicated by asterisks. Islets consist of cords of cells through which numerous fenestrated capillaries course. The images of the pancreas shown in Figures 9 to 13 are all made from slide S49.

Figure 9 - high power view of centroacinar cells

shows a high power view of centroacinar cells lying within pancreatic acini. Near the middle of the field of view, the boundary of a somewhat longitudinally sectioned acinus is indicated by asterisks. An extended section of the intercalated duct lying within that acinus (the pale-staining centroacinar cells) is readily identified. The duct leaves the acinus at the left. CA cells are also seen in many of the surrounding acini.

Figure 10 - High power view of an intralobular collecting duct cut in longitudinal section The
intercalated ducts are short and drain into intralobular collecting ducts, which form a complex, branching network within a lobule. The epithelium is cuboidal. Figure 10 shows a longitudinal section of an intralobular collecting duct extending across most of the field of view. The length of the duct in this section is fortuitous. It lies just above an islet of Langerhans. Note the pale staining of both the islets and the ducts. The apical surfaces of the cells of the surrounding acini appear slightly brighter than the basal surfaces due to the presence of zymogen granules.

Figure 11 - Intercalated ducts entering an intralobular duct shows some intercalated ducts entering an intralobular
collecting duct. The intercalated ducts are not very distinct, they appear as pale cells squeezed among the acini. 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 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. The intraloubular duct appears as a distinct oval profile with a prominent lumen containing secretory material (arising from the acini and intercalated ducts). It has cuboidal cells whose boundaries are not distinct, but their round nuclei can be clearly seen. shows an excretory duct. Excretory ducts are also called interlobular ducts, and as this name implies, they lie in the connective tissue septa between lobules. (The CT is more abundant when ducts or other structures, such as blood vessels and nerves, are present.) Excretory ducts are lined with low columnar epithelium which becomes taller as the duct progresses. The cell boundaries of the duct in Figure 12 cannot be distinguished but their slightly oval nuclei are easily seen. Secretory material is present in the lumen.

Figure 12 - Excretory duct in the pancreas

Figure 13 - Low power view of large excretory duct

shows a low power

http://www.courseweb.uottawa.ca/medicine-histology/english/gastrointestinal/Pancreas.htm#Figure 12

Pancreas
Structure of the Pancreas
The pancreas is an elongated organ that lies behind and below the stomach. This mixed gland contains both exocrine and endocrine tissues. The predominant exocrine part consists of grape-like clusters of secretory cells that form sacs known as acini, which connect to ducts that eventually empty into the the first portion of the intestine called duodenum. The smaller part of the gland consists of isolated islands of endocrine tissue known as islets of Langerhans which are dispersed throughout the pancreas.

Hormones Secreted by the Pancreas

The most important hormones secreted by the pancreas are insulin and glucagon. Both play a role in proper metabolism of sugars and starches in the body. Insulin promotes the movement of glucose and other nutrients out of the blood and into cells. When blood glucose rises, insulin, released from the beta cells causes glucose to enter body cells to be used for energy. Also, it sometimes stimulates conversion of glucose to glycogen in the liver. Another pancreatic hormone, glucagon, promotes the movement of glucose into the blood when glucose levels are below normal. It causes the breakdown of stored liver glycogen to glucose, so that the sugar content of blood leaving the liver rises.

Function of the Pancreas

The pancreas is largely responsible for maintaining blood glucose levels. The normal clinical range of blood glucose levels is 70 to 150 mg/dL (milligrams per deciliter). The pancreas can measure blood sugar and if it is high or low, the pancreas releases a hormone to correct the level. Blood glucose must be maintained at a certain level for cells to neither gain or lose water.

Digestive Enzymes Secreted by the Pancreas

The exocrine pancreas secretes the pancreatic juice consisting of two components:

Pancreatic enzymes actively secreted by the acinar cells that form the acini. These pancreactic enzymes are very important because they can almost completely digest food in the absence of all other digestive secretion.

An aqueous alkaline solution rich in sodium bicarbonate (NaHCO3) actively secreted by the duct cells that line the pancreatic ducts. Sodium bicarbonate neutralizes the acidity of the chyme so that won't burn the intestines.

Pancreatic Enzymes
The acinar cells secrete three different types of enzymes:

1. 2. 3.

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. It is caused by gene mutations. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in airway obsturction; chronic respiratory infections; pancreatic insufficiency; maldigestion and salt depletion.

Exocrine Pancreatic Insufficiency A malabsorption condition resulting from greater than 10% reduction in the secretion of pancreatic digestive enzymes ( LIPASE; PROTEASES; and AMYLASE) by the EXOCRINE PANCREAS into the DUODENUM. This condition is often associated with cystic fibrosis and with chronic pancreatitis.

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 due to focal hyperplasia of pancreatic islet cells budding off from the ductal structures and forming new islets of Langerhans.

Pancreatic Cyst A true cyst of the pancreas, distinguished from the much more common pancreatic pseudocyst by possessing a lining of mucous epithelium. Pancreatic cysts are categorized as congenital, retention, neoplastic, parasitic, enterogenous, or dermoid. Congenital cysts occur more frequently as solitary cysts but may be multiple. Retention cysts are gross enlargements of pancreatic ducts secondary to ductal obstruction..Pancreatic pseudocysts account for most of the cystic collections in the pancreas and are often associated with chronic pancreatitis.

http://www.gopetsamerica.com/anatomy/pancreas.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. Where Is the Pancreas Located? The pancreas is located within the upper abdominal cavity in closeproximity to the stomach, liver and small bowel. There are two parts orlobes of the pancreas. The right lobe is located along the descendingpart of the duodenum, which is the first segment of the small bowel(in testine). The left lobe of the pancreas lies next to the stomach.What Is the General Struc

ture of the Pancreas? The feline pancreas is composed of right and left lobes, with a small central portion that join s the lobes.Microscopically, the pancreas consists of cells arranged in to small sections or lo bules. These cells produce a numberof digestive enzymes, and they store them within small granules or packets located within the cell. Two excretoryducts the accessory duct and the pancreatic duct carry these enzymes into the intestine where they aid in thedigestion of food. The anatomic arrangement of these ducts differs slightly between dogs and cats, and amongindividual ani mals. The pancreas also contains unique cells (beta cells) that form the islets of Langerhans, whic h produce insulin. Insulinallows many cells in the body to use blood sugar (glucose); therefo re, it is an important hormone in regulating levelsof glucose in the blood. The pancreas also produces the hormone, glucagon.What Are the Functions of the Pancreas? The pancreas serves two main functions. First it produces and stores digestive enzymes and fluids. Pancreatic juice is secreted (released) into the intestinal tract in response to eating food. Pancreatic juice contains enzymes needed for digesting proteins, carbohydrates, and especially fats. Secondly, the pancreas produces and secretes hormones that are very important in the regulation of blood sugar. When the beta cells of the pancreas detect an increase in the blood sugar concentration, insulin is released directly into the blood where it acts to carry glucose into the body's cells. The higher the blood sugar, the more insulin is secreted. Thus, insulin lowers the blood glucose concentration. The hormone, glucagon, acts to increase blood sugar and is released when blood sugar is low. What Are the Common Diseases of the Pancreas? There are a number of common diseases of the pancreas.

y Pancreatitis. One of the most important, and potentially dangerous diseases is inflammation of the pancreas. Pancreatitis can be difficult to diagnose in cats. It often causes loss of appetite, vomiting, abdominal pain and depression. In severe cases, the condition can be fatal. y Diabetes mellitus. Another important disease of the pancreas is diabetes mellitus or sugar diabetes. This common disorder of cats represents an underproduction or excessively low secretion of insulin. Inadequate production of insulin causes the blood sugar to become too high. Although the circulating level of glucose is high in the blood, many cells cannot use it for energy, and serious side effects develop. y Pancreatic cysts and abscesses. These are less common diseases of the pancreas. Pancreatic abscesses are small pockets of infection that may develop as a complication of pancreatitis.

y Exocrine pancreatic insufficiency. A unique condition called EPI represents a deficiency in digestive pancreatic enzymes. This disease leads to an inability to digest food properly, and is very rare in the cat. y Pancreatic carcinoma. Pancreatic cancers occur infrequently, but are very serious conditions. A cancer of the glandular portion of the pancreas is called pancreatic adenocarcinoma, and it is a highly invasive cancer. Unique pancreatic cancers of the hormonal components of the pancreas develop only rarely in the cat. Insulinoma is a tumor that produces insulin, glucagonomas secrete glucagon, and gastrinomas produce excessive amounts of gastrin hormone. 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), a blood test that assesses production of digestive enzymes y Blood sugar, especially in patients with diabetes y Measurements of glucose and ketones in the urine y Measurement of insulin levels in the blood
http://www.petplace.com/cats/structure-and-function-of-the-pancreas-in-cats/page1.aspx The pancreas is a rather unique organ in the human body. It is part of two different organ systems, the endocrine system and the digestive system. Technically, the pancreas is a large gland. A gland is a structure in the body that secrete hormones. The pancreas creates a wide range of different hormones, some of which are used to trigger internal metabolic reactions, and others which are used to help break down food. This article we'll take a look at the structure and function of the pancreas.

Structure of the pancreas

The pancreas is located just below the stomach. It develops as two separate parts which are fused together early in life. The pancreas is also located near the first part of the small intestine, known as the duodenum.

The pancreas is broken into several different subsections. The head of the pancreas is located nearest to the duodenum. The body of the pancreas is the largest section, located in the center of the gland just below the stomach. The pancreas also has a tail, which is furthest from the duodenum.

The pancreas receives its blood supply from various different arteries. These arteries all have very specific names, depending on where they originate from. Nerve supply to the pancreas is primarily through the vagus nerve.

There is a small duct, or drain, in the pancreas which leads to the common bile duct. This duct is used to drain the execrable hormones which aid in the digestion of food that is passing through the small intestine. In some people, this drain empties directly into the duodenum, however in most people it empties into the common bile duct. The common bile duct is the duct which drains bile from the gallbladder. The enzymes are mixed with bile and then drained into the duodenum.

Another major structure of the pancreas is known as the Islets of Langerhands. These islets are small structures dotted throughout the pancreas, and are responsible for producing insulin, as well as a wide variety of other hormones used by the body. It is estimated that each pancreas contains over one million of these islets.

Function of the pancreas

The pancreas is involved in a wide variety of functions in the endocrine and exocrine system. Lets first take a look at some of the endocrine functions of the pancreas. An endocrine hormone is a hormone produced by a gland (such as the pancreas) which is secreted directly into the blood stream. These hormones include insulin, glucagon, and somatostatin.

Insulin is famous for being the hormone which is deficient in people with diabetes. People with diabetes do not produce enough insulin (or are resistant to its effects, but this can get rather complicated, so I'll leave a discussion of diabetes alone for now). Insulin is responsible for regulating the amount of sugar which is absorbed into the cells of the body. Without enough insulin, the sugar remains in your bloodstream where it can cause significant health problems.

The pancreas is also an exocrine gland. Exocrine glands do not secrete hormones directly into the bloodstream. Rather, they secrete hormones into organs. In the case of the pancreas, enzymes are produced which are transported to the duodenum. These enzymes are used to aid digestion of food. Some of these hormones include pancreatic lipase, pancreatic amylase, and trypsin.

The pancreas is an extremely important organ in your body. It has a very complex structure and has many functions related to your metabolism. Damage to the pancreas can often be quite significant hormones and digestive enzymes can be inappropriately released into the surrounding area, causing much damage. As is the case with many organs in the body, the pancreas is also subject to becoming cancerous. http://www.helium.com/items/1290173-structure-and-function-of-the-pancreas

Liver Cell Structure And Function

The liver is the largest gland in the body, and is situated slightly below the diaphragm and anterior to the stomach. It consists of two lobes which are wedge-shaped. Two blood vessels enter the liver, namely the hepatic portal vein with dissolved food substances from the small intestine, and the hepatic artery, with oxygenated blood from the lungs. Two ducts originate in the liver, and these unite to form the common hepatic duct which opens, with the pancreatic duct, in the hollow side of the duodenum (the first section of the small intestine). The gall bladder lies inside the liver, and is the storage place for bile, which is formed by the liver cells. The right lobe of the liver is larger than the left lobe. Each lobe is further divided into many small lobules, each being about the size of a pin-head, and consisting of many liver cells, with bile channels and blood channels between them. Permeating the entire liver structure is a system of blood capillaries, bile capillaries and lymph capillaries. The liver cells secrete the bile, and this collects in the bile capillaries, which then unite, forming bile ducts. These bile ducts all eventually unite, forming the main hepatic duct, which gives off a branch, the cystic duct, on its way toward the hepatic duct. The cystic duct leads into the gall bladder. Where a cystic duct joins the hepatic duct, the two continue as the general bile duct, which then joins the pancreatic duct, forming a common duct that opens into the duodenum. The functions of the liver are varied, working closely with nearly every fundamental system and process in the human body, in particular homeostasis and the regulation of blood sugar.

1. Regulation of blood sugar: The level of blood sugar stays at around 0.1%, and excess coming from the gut is stored as glycogen. The hormone called insulin - excreted by the pancreas - causes the excess glucose to turn into glycogen. 2. Regulation of lipids: Lipids are extracted from the blood and changed to carbohydrates, etc. as required or sent to fat storage sites if not needed straight away. 3. Regulation of amino acids: a supply of amino acids in the blood is kept at a normal level. Any spare which has not been absorbed cannot be stored but is converted into the waste products, called urea when at the liver, and is then sent to the kidneys to be removed from the body as urine. The remainder of the amino acid molecule is not wasted; it is changed into a carbohydrate that can be used. 4. Production of heat: the liver is one of the hardest working regions of the body and produces a lot of waste heat. This is carried round the body in the blood and warms less active regions. 5. Forms bile: bile consists of bile salts and the excretory bile pigments. It is important to speed up the digestion of lipids. 6. Forms cholesterol: this fatty substance is used in the cells. Excess amounts in the blood can cause the blood vessels to become blocked, leading to heart attacks, etc. 7. Removals of hormones, toxins, etc. The liver extracts many harmful materials from the blood and excretes them in the bile or from the kidneys. 8. Formation of red blood cells in the young embryo while it is developing in the womb. 9. Making heparin: this is a substance that prevents the blood from clotting as it travels through the blood system. 10. Removal of hemoglobin molecules: when red blood cells die, the hemoglobin is converted into bile pigments and the iron atoms are saved for future use. 11. 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, e.g. if it is wounded. 12. Forms plasma proteins: the plasma proteins are used in blood clotting and in keeping the blood plasma constant. The main blood proteins include fibrinogen, prothrombin, albumens and globulins. 13. Storage of vitamins such as vitamin A and D. Vitamin A is also made in the liver from carotene, the orange-red pigment in plants. Vitamin B12 is also stored in the liver.

http://www.essortment.com/liver-cell-structure-function-61506.html

Structure of Liver Cells

The liver is a vital organ that cleans the blood and metabolizes macromolecules like lipids, carbohydrates and proteins. All cells contain the same copy of DNA molecules. However, each tissue cell processes different functions carried out by genetic information. For instance, the heart metabolizes and produces different proteins than the liver, even though they contain the same DNA. The liver has several structures that help it carry out important human biomechanical processes.

1. Liver Function
o

Without a liver, the human body would not be able to store carbohydrates, synthesize proteins or metabolize toxins from drugs. It is a necessary organ required for life, so it's no surprise that the liver has outstanding healing capabilities and regeneration. The liver will even heal after long term abuse or damage. The liver is the largest gland in the body, and it sits on the right side under the rib cage for protection.

Hepatocytes
o

Hepatocytes are the main cell for protein synthesis. They are also responsible for recycling lipoproteins. HDL ("good") cholesterol carry fatty acids back to the liver, where is recycled, broken down and reused when necessary. Hepatocytes are also responsible for synthesis and breakdown of lipids from triglycerides. Overall, the cells create homeostasis for the body's fatty tissue deposits and circulating protein for energy and storage.

Kupffer Cells
o

Kupffer cells are specialized macrophages. A macrophage is a cell that is a part of the immune system. Macrophages circulate the body and destroy foreign microbes, protecting the body from infection. Kupffer cells breakdown old red blood cells and secrete the waste in the bile for removal from the body.

Stellate Cells
o

Stellate cells are part of the nervous system. They innervate the organ to provide a connection between the brain and the liver. It helps with pain and sensory information from the liver to provide communication. Stellate cells play a role in scar tissue formed when liver damage occurs. When the liver starts to degenerate, stellate cells become active and signal it for repair. Constant repair leads to scar tissue and eventual cirrhosis, which is a hardening of the liver.

Mitochondria
o

Mitochondria are located in most human cells, but there is an elevated number in liver cells. Mitochondria play a large role in metabolism of proteins, carbohydrates and lipids. Because a large portion of the process is only located in the liver cell, they contain a large amount of mitochondria to keep up with the body's demand for energy and synthesis.

http://www.ehow.com/about_5201581_structure-liver-cells.html Structure of the Liver

The liver consists of four sections, or lobes. There are two main lobes--the right lobe, which is by far the larger, and the left lobe. Two small lobes lie behind the right lobe. Each lobe is made up of multisided units called lobules. Most livers have between 50,000 and 100,000 lobules. Each lobule consists of a central vein surrounded by tiny liver cells grouped in sheets or bundles. These cells perform the work of the liver. Cavities known as sinusoids separate the groups of cells within a lobule. The sinusoids give the liver a spongy texture and enable it to hold large amounts of blood.

The liver has an unusual blood supply system. Like other organs, the liver receives blood containing oxygen from the heart. This blood enters the liver through the hepatic artery. The liver also receives blood filled with nutrients, or digested food particles, from the small intestine. This blood enters the liver through the portal vein. In the liver, 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. They also filter out wastes and poisons. At the same time, they secrete sugar, vitamins, minerals, and other substances into the blood. The sinusoids drain into the central veins, which join to form the hepatic vein. Blood leaves the liver through the hepatic vein.

Each lobule also contains bile capillaries, tiny tubes that carry the bile secreted by the liver cells. The bile capillaries join to form bile ducts, which carry bile out of the liver. Soon after leaving the liver, the bile ducts join together, forming the hepatic duct. The liver manufactures bile continuously, even if the small intestine is not digesting food. Excess bile flows into the gall bladder, where it is stored for later use. Bile

The structure and function of liver cells

The liver is the largest internal organ of the body, weighing about 1.36Kg, located in the right upper quadrant of the abdomen. It consists of two major lobes (left and right) and two minor lobes (caudate and quadrate). The liver is involved in the normal physiological functions of many organs and systems of the body such as the cardiovascular and immune systems.

Many important substances are secreted into the gastro-intestinal tract by it, as well as storing and processing of nutrients, synthesizing new molecules, and detoxifying harmful chemicals. The liver is the only solid organ which can regenerate itself.

The main functional cell in the liver is called a hepatocyte, and it performs many metabolic and secretory functions. The cells are polygonal in shape and arranged in one to two cell thick plates separated by fine vascular sinusoids through which blood flows. Sinusoids are low pressure vascular channels that receive blood from arteries supplying the liver. They are highly permeable, and allow substances to enter and leave the blood stream. 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. Blood flow into the liver sinusoids comes from terminal branches of both the hepatic portal vein and hepatic artery. The liver is closely associated with the gallbladder which is situated in a depression on the inferior surface of the liver. It is a pear-shaped sac and is filled with stored bile. The gallbladder's function is to store and concentrate the bile produced by the liver until it is needed in the small intestine. Functions of the Liver: + Bile production - The liver produces and secretes about 600-1000 ml of bile each day. Bile helps to neutralize and dilute stomach acid and emulsify fats to aid in digestion. + Storage - Hepatocytes can remove sugar from the blood and store it as a substance called glycogen. Glycogen forms an energy reserve that can be quickly mobilized to meet a sudden need for glucose by the body. Fats, vitamins (A, B12, D, E,and K), copper, and iron are stored as well, but this storage function is usually short term. + Nutrient Inter-conversion - the liver can convert some nutrients into others, this occurs when ingested nutrients are not always in the proportion needed by the tissues. For example, a person who is on a diet that is excessively high in protein and inadequate amounts of carbohydrates and lipids. The hepatocytes will then break down proteins and form lipids and glucose. Vitamin D obtained from sun exposure, food, and supplements, is biologically inert, and is converted by the liver and kidneys, to obtain the active form of the vitamin, which functions in calcium maintenance. + Detoxification - Many ingested substances are harmful to the body's cells, and by-products of metabolism if accumulated become toxic. The liver detoxifies many substances by altering their structure to make them less toxic or make their elimination easier. + Phagocytosis - is the cellular process of engulfing solid particles such as bacteria and cell debris.

Hepatic phagocytic cells, known as Kupffer cells, lie along the sinusoid walls and phagocytize nonfunctioning blood cells, bacteria, waste products and other debris that enters the liver through the circulation. + Synthesis - The liver produces blood plasma proteins, such as albumins, fibrinogen, globulins, and clotting factors, which are released into the circulation. http://www.helium.com/items/1606236-the-structure-and-function-of-the-liver

Right Liver Lobe

The right liver lobe is the larger of the two lobes by six times. The inferior and posterior surfaces are divided into four lobes by five fossae, which are arranged in the form of the letter H. The left limb of the H marks on these surfaces the division of liver into right and left lobes.

Left Liver Lobe

The left liver lobe is the smaller and flatter of the two liver lobes. The inferior and posterior surfaces are divided into four lobes by five fossae, which are arranged in the form of the letter H. The left limb of the H marks on these surfaces the division of liver into right and left lobes.

Abdominal Veins and Arteries

Veins usually carry blood straight to the atria of the heart, but those of the abdominal tissues are exceptions. These come from networks in the stomach, intestines, pancreas, and spleen, and carry blood from these organs through a "portal vein" to the liver. There, the blood enters capillarylike "hepatic sinusoids," called the "hepatic portal system." The tributaries of the portal vein include (1) the right and left "gastric veins" from the stomach; (2) the "superior mesenteric vein" from the small intestine, ascending colon, and transverse colon, and (3) the "splenic vein" from a number of merging veins from the spleen, pancreas, and part of the stomach. Its largest tributary is the "inferior mesenteric vein," which brings blood up from the descending colon, sigmoid colon, and the rectum. After passing through the portal veins of the liver, blood is carried through a series of merging vessels into the "hepatic veins." These empty into the "inferior vena cava," and return the blood into circulation. The corresponding arteries of the same names are taking oxygenated blood to these sites in paths parallel to those of the veins.

Falciform Ligament
The falciform ligament is the line of attachment that divides the liver into two parts, known as the right and left lobes.

Coronary Ligament
The coronary ligament are the folds of peritoneum connecting the posterior surface of the liver and the diaphragm.

Caudate Lobe
The caudate lobe is situated upon the dorsal surface of the right lobe bounded by the inferior vena cava, and on the left by the fissure of the ductus venosus.

Qaudrate Lobe
The qaudrate lobe is situated on the visceral surface of the right lobe to the left of the fissure for the gallbladder.

Liver (An Overview)

The liver has two major lobes and two minor lobes. Anteriorly, the right lobe is separated from the smaller left lobe by the falciform ligament. Inferiorly, the caudate lobe is near the inferior vena cava, and the quadrate lobe is adjacent to 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, the upper layer of which is exposed as if the liver were to be pulled away from the diaphragm. 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 porta of the liver is where the hepatic artery, portal vein lymphatics, and nerves enter the liver and where the hepatic ducts exit. Although the liver is the largest internal organ of the body, it is only one to two cells thick. This is due to the fact that hepatocytes, or liver cells, are only one to two cells thick and separated from each other by large capillary spaces called sinusoids. The plate structure of the liver and high permeability of the sinusoids allow each hepatocyte to be in close contact with the blood. The hepatic plates are arranged into functional units called liver lobules. 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, opening into spaces between hepatic plates. Arterial blood and portal venous blood, containing nutrient molecules absorbed in the gastrointestinal tract mix as the blood flows from the periphery of the lobule to the central vein. 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. Bile is produced in the liver by the hepatocytes and secreted into thin channels called bile canaliculi located within each hepatic plate. The canaliculi are drained peripherally by bile ducts which in turn drain into hepatic ducts that carry bile away from the liver. As a result, 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. Cirrhosis, 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. These nodules don't have the plate-like structure of normal liver tissue and are consequently, less functional. Cirrhosis is often accompanied by the presence of ammonia from the hepatic portal vein on into systemic circulation. 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, which absorbs mineral salts and water received from the liver and converts it into a thick, mucus substance called "bile," to be released when food is present in the stomach. The gallbladder is a small, pear-shaped sac which is situated just below the liver and is

attached to it by tissues. 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. It has a capacity of around one and one-half fluid ounces. When food leaves the stomach, a secretion causes the gallbladder to contract and expel its contents into the duodenum, where the bile disperses the fats in the food into liquid. Pythagoras, the 6th Century BC Greek mathematician, believed that life is based on the four elements of earth, air, fire and water which correspond to the body's "humors": blood (hot and moist), phlegm (cold and moist), yellow bile (hot and dry) and black bile (cold and dry). The perfect or imperfect balance of these humors supposedly determined one's health and intelligence. We still speak in terms of "melancholia" (excess black bile, leading to depression) and "phlegmatic" (sluggish or impassive) and scientists have named the heavy mucus secreted in the respiratory passages - phlegm. Pythagoras was kind of a "square". Oh, come on; where's your sense of "humor"?

Bile Duct
Within the liver lobules, there are many fine "bile canals" that receive secretions from the hepatic cells. The canals of neighboring lobules unite to form larger ducts, and these converge to become the "hepatic ducts." They merge, in turn, to form the "common hepatic duct." The "common bile duct" is formed by the union of the common hepatic and the cystic ducts. It leads to the duodenum, where its exit is guarded by a sphincter muscle. This sphincter normally remains contracted until the bile is needed, so that bile collects in the common bile duct and backs up to the cystic duct. When this happens, the bile flows into the gallbladder and is stored there.

Sinusoids
The sinusoids are capillary-like vessels which the blood is conveyed to the inferior vena cava by the hepatic veins.

Inferior Vena Cava

The inferior vena cava is a large vein ascending through the abdomen. It collects blood from the hepatic veins, the lumbar veins, gonadal veins, renal veins, and phrenic veins. These vessels usually drain regions that are supplied by arteries with corresponding names. The inferior vena cava enters the heart through the right atrium.

The chemical structure of the liver The liver is composed of liver cells, and extensive vascular network, was reddish-brown, soft and crisp, vulnerable to violence and rupture caused fatal bleeding. Minimal liver cells, it is necessary to see through the microscope. Liver about 2.5 billion liver cells, liver cells 5000 Hepatic Lobules one, the human liver Hepatic Lobules total of around 500,000, liver cells polygon diameter of about 20 to 30 microns, 6-8 face, volume of about 4,900 square micron, under different physiological conditions of the there are small differences, such as hunger, the largest volume of liver cells. Each cell surface can be divided into liver sinusoidal surface, the surface of liver cells and cowardice of the three. Liver cells it contains many complicated fine structure: If liver cells, liver cytoplasm, mitochondria, endoplasmic reticulum and lysosomes, Gorky's body, and drink vacuole of particulate

components. Each has its fine structure is extremely important and complex functions, which ensures the existence of human life, that people can live. Liver cells It is the function of replication of genetic information. Hepatitis, hepatitis C virus invasive liver cells, the virus genes in the DNA of liver cells combine (integration). Once integration is difficult HBsAg clearance, which carry long HBsAg. Mitochondria Each liver cell mitochondria of 1000-2000, of which more than 70 certificates of enzymes and coenzyme, such as ALT (SGPT or ALT, or aminotransferase), respiratory enzyme cells, and adenosine triphosphate. When hunger, systemic hypoxia, or cholestatic hepatitis, mitochondria is the first and most sensitive of the victim, extreme swelling caused elevated liver transaminases, biochemical disorder. Endoplasmic reticulum The cytoplasm of the hepatocytes was flat or bubble tubular cystic structure. The rough endoplasmic reticulum and smooth endoplasmic reticulum two. The rough endoplasmic reticulum protein synthesis of liver cells is a base, and can be a surplus of a few amino acid to another amino acid. Hepatic uptake of amino acid protein synthesis very quickly. Generally, albumin is the rough endoplasmic omentum on the synthesis of multi-synuclein. Slide endoplasmic reticulum widely distributed in the cytoplasm of liver, often with the rough endoplasmic reticulum and Golgi's body linked to the three functions are closely linked. Slide endoplasmic reticulum is the rough endoplasmic reticulum of 2.5 to 3.2 times. The membrane has many enzymes, such as oxidoreductase of hydrolysis enzymes, synthetic enzyme, and so on. The glycogen synthesis and decomposition, fat metabolism, hormone metabolism, drug metabolism and detoxification process and the synthesis of bile are smooth endoplasmic reticulum conducted. Furthermore, the uptake of liver cells in many organic smooth endoplasmic online Synthesis, decomposition, the integration of biochemical reactions. Hepatitis, the endoplasmic reticulum damage reduction in albumin production, protein metabolism, resulting in the patients with serum albumin and globulin ratio (A / G) inversion, flocculation test and turbidity test abnormalities. Because of fibrinogen and thrombin original manufacturer reduced, resulting in bleeding tendency. Because glycogen reduced, leading to low blood sugar. As detoxification weakened, leading to enhanced toxicity of drugs. Since bilirubin metabolism, indirectly blush of bile into direct bilirubin, the process is in the endoplasmic reticulum, the endoplasmic reticulum in liver cell damage, jaundice, resulting in the skin, sclera stained. Lysosomes Liver cells in lysosomes containing rich, mainly distributed in the hepatic duct near capillary cytoplasm, a single membrane surrounding the dense body, 0.4 microns in diameter, contains a variety of digestive enzymes can analyze protein, sugar, fat, such as nucleic acid and phosphoric acid. Degenerative aging can digest the endoplasmic reticulum, mitochondria, cells and others. Foreign bodies, thereby maintaining the content of liver cell self-renewal, has been hailed as the cell's "digestive system" and "cleaners." Obstructive jaundice, bile pigment lysosomal actively involved in the transfer, hepatitis, oxygen, increased cholesterol or partial hepatectomy, the lysosome increased significantly. Hepatitis viruses can cause direct damage to the lysosome and adjacent normal liver cells and dissolved necrosis. Gorky's body Each liver cells about 50 Gorky's body found in the vicinity of liver cells, accounting for 10% of the volume of the cytoplasm. Gorky's body and liver cells and exocrine and endocrine functions are closely related, such as bile secretion on its closely related. While participation of the cytoplasmic membrane

glycoprotein and the initial formation of lysosomes. Liver cell protein and lipoprotein synthesis, part of the body transferred to Gorky's storage processing, sinus further into the perirenal space. Microsomal Particulate body is the main enzyme catalase and peroxidase. To prevent hydrogen peroxide accumulation in the cell. Microsomal can be reduced coenzyme oxidation. Also in the microsomal metabolism of alcohol and gluconeogenesis and the enzymes. And also on cholesterol metabolism. Hepatocellular carcinoma cells of the particulate reduction. Drink vacuole With absorption and intracellular transport of material function.

Part 1. Understanding normal liver cell structure and function

What is the relationship between liver cell structure and function? The liver, the body's largest organ, performs many vital functions. It converts food into chemicals required for life, it makes numerous compounds used throughout the body, and it detoxifies and rids the body of poisonous substances (e.g., see Part 2). The proper performance of the hepatocyte relies on its specific cellular architecture, a combination of its structure and function. These cells form a barrier between the internal and external liver environments by bonding themselves together with specialized structures called tight junctions. These junctions in turn divide the cell surface into two domains: the basolateral and apical. 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), the complex molecular "soap" stored in the gallbladder that helps us absorb dietary fats and remove waste products. Because these two surfaces are in contact with vastly different environments, they each perform specific tasks. For example, the basolateral surface communicates with the blood either by releasing compounds the liver has made for delivery to other organs, or by retrieving compounds from the blood for the liver's use or detoxification. The apical surface similarly "communicates" with the bile by releasing substances destined for excretion. To perform these surface-specific tasks, the basolateral and apical domains have their own unique set of molecular machinery. How is this machinery specifically delivered to its proper cellular home? This is the fundamental question my research addresses. The role of MAL proteins in regulating apical delivery. Our long-term goal is to understand how hepatic cells establish and maintain their polarity. Our focus is to identify regulators of apical plasma membrane (PM) delivery. Unlike simple epithelial cells that directly target proteins from the TGN to the apical PM, hepatocytes use an indirect pathway: proteins are first delivered to the basolateral domain, then selectively internalized and transcytosed to the apical surface. MAL and MAL2 have been identified as regulators of direct and indirect apical delivery, respectively. We have previously shown that indirect sorting in hepatocytes requires cholesterol and glycosphingolipids. 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, we have been examining how MAL proteolipids function in apical PM sorting in polarized hepatic cells.

Part 2. Alterations in liver structure and function associated with alcoholic liver disease
Why study alcoholic liver disease? Approximately 75% of all Americans consume alcohol, and 100,000 deaths per year are attributed to alcohol consumption. Of those deaths, more than 20,000 are caused by liver cirrhosis, the seventh largest cause of death among Americans. Although alcoholic liver disease is a major biomedical health concern in the United States, little is known about how alcohol induces liver injury. 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, but also from other liver diseases (e.g., hepatitis, liver cancer) that lead to cirrhosis.

Why study alcohol-induced liver damage in WIF-B cells? The liver is the major site of alcohol metabolism, and thus, the most susceptible organ to alcohol-induced injury. In the early stages of the disease, a fatty liver develops which can lead to hepatocyte injury, liver fibrosis, and ultimately to cirrhosis. Although the disease progression is well described in patients, it is not understood why and how this progression occurs. Traditionally, animal models (e.g., rats, primates) have been used to describe physiological responses to alcohol consumption, but these approaches can be problematic. Animals can vary significantly in their responses to alcohol, and it is often difficult and expensive to do animal studies. Thus, many researchers are trying to find alternative strategies to study alcohol-induced liver damage. We have been developing one such alternative strategy: WIF-B cells.These cells maintain their liver-specific structure and functions in vitro and efficiently metabolize alcohol like intact liver. Also importantly, they exhibit the same cellular alterations as seen in alcohol-exposed livers. We are examining the effects of alcohol exposure on membrane trafficking with respect to alcohol-induced alterations in microtubule modifications and dynamics.

http://biology.cua.edu/faculty/tuma.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. 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. It weighs about three pounds and is shaped like a football that is flat on one side. The liver performs many jobs in your body. It processes what you eat and drink into energy and nutrients your body can use. The liver also removes harmful substances from your blood. How does alcohol affect the liver? Alcohol can damage or destroy liver cells. The liver breaks down alcohol so it can be removed from your body. Your liver can become injured or seriously damaged if you drink more alcohol than it can process. What are the different types of alcohol-related liver disease? There are three main types of alcohol-related liver disease: fatty liver disease, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver disease Fatty liver disease is the build up of extra fat in liver cells. It is the earliest stage of alcohol-related liver disease. There are usually no symptoms. If symptoms do occur, they may include fatigue, weakness, and weight loss. Almost all heavy drinkers have fatty liver disease. However, if they stop drinking, fatty liver disease will usually go away. Alcoholic hepatitis Alcoholic hepatitis causes the liver to swell and become damaged. Symptoms may include loss of appetite, nausea, vomiting, abdominal pain, fever and jaundice. Up to 35 percent of heavy drinkers develop alcoholic hepatitis. Alcoholic hepatitis can be mild or severe. If it is mild, liver damage may be reversed. If it is severe, it may occur suddenly and quickly lead to serious complications including liver failure and death. Alcoholic cirrhosis Alcoholic cirrhosis is the scarring of the liver -- hard scar tissue replaces soft healthy tissue. It is the most serious type of alcohol-related liver disease. Symptoms of cirrhosis are similar to those of alcoholic hepatitis. Between 10 and 20 percent of heavy drinkers develop cirrhosis. The damage from cirrhosis cannot be reversed and can cause liver failure. Not drinking alcohol can help prevent further damage. How does alcohol-related liver disease progress?

Many heavy drinkers will progress from fatty liver disease to alcoholic hepatitis to alcoholic cirrhosis over time. However, some heavy drinkers may develop cirrhosis without having alcoholic hepatitis first. Others may have alcoholic hepatitis but never have symptoms. Heavy drinkers who also have a chronic liver disease such as hepatitis C are at high risk for developing cirrhosis. What are the complications of alcohol-related liver disease? Complications from alcohol-related liver disease usually occur after years of heavy drinking. The complications can be serious. 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. Blood tests may be used to rule out other liver diseases. Your doctor also may need to do a liver biopsy. During a biopsy, a small piece of liver tissue is removed and studied in the lab. How is alcohol-related liver disease treated? Treatment for alcohol-related liver disease requires a healthy diet including avoiding alcohol. Your doctor may suggest changes in your diet to help your liver recover from the alcohol-related damage. Treatment may require you to participate in an alcohol recovery program. Medications may be needed to manage the complications caused by your liver damage. In advance cases of alcoholic cirrhosis, a liver transplant may be needed. Those with alcohol-related liver disease need to stop drinking alcohol to be considered for a liver transplant. http://www.liverfoundation.org/abouttheliver/info/alcohol/

Alcohol and Liver Disease

Drinking too much alcohol can lead to three types of liver conditions - fatty liver, hepatitis, and cirrhosis. You are unlikely to develop these problems if you drink within the recommended safe limits detailed below. For all types of liver disease caused by alcohol, the main treatment is to stop drinking alcohol completely.

What does the liver do?

The liver is in the upper right part of the abdomen. Its functions include: y Storing glycogen, a chemical made from sugars. When required, glycogen is broken down into glucose which is released into the bloodstream. y Helping to process fats and proteins from digested food. y Making proteins that are essential for blood to clot (clotting factors). y Processing many medicines which you may take. y Helping to remove or process alcohol, poisons and toxins from the body. y Making bile which passes from the liver to the gut and helps to digest fats.

What happens when you drink alcohol?

When you drink alcohol, it is absorbed into the bloodstream from the stomach and intestines. All blood from the stomach and intestines first goes through the liver before circulating around the whole body. So, the highest concentration of alcohol is in the blood flowing through the liver. Liver cells contain enzymes (chemicals) which process (metabolise) alcohol. The enzymes break down alcohol into other chemicals which in turn are then broken down into water and carbon dioxide. These are then passed out in the urine and from the lungs. The liver cells can process only a certain amount of alcohol per hour. So, if you drink alcohol faster than your liver can deal with it, the level of alcohol in your bloodstream rises.

What are the problems of drinking too much alcohol?

Your liver and body can usually cope with drinking a small amount of alcohol. Indeed, drinking a small amount of alcohol (1-2 units per day) may help to prevent heart disease and stroke. However, drinking over the recommended limits (detailed below) can be harmful. If you drink heavily you have an increased risk of developing: y Serious liver problems (alcoholic liver disease). y Some stomach disorders. y Pancreatitis (severe inflammation of the pancreas). y Mental health problems, including depression and anxiety.

y y y y y

y y y y

Sexual difficulties such as impotence. Muscle and heart muscle disease. High blood pressure. Damage to nervous tissue. Accidents - drinking alcohol is associated with a much increased risk of accidents. In particular, injury and death from fire and car crashes. About 1 in 7 road deaths are caused by drinking alcohol. Some cancers (mouth, gullet, liver, colon and breast). Obesity (alcohol has many calories). Damage to an unborn baby in pregnant women. Alcohol dependence (addiction).

In the UK, deaths due to alcohol-related diseases (particularly liver disease) have risen considerably over the last 20 years or so. This is because heavy drinking and binge drinking have become more common. The rest of this leaflet is about alcoholic liver disease. See separate leaflets called 'Alcohol and Sensible Drinking' which deals with general aspects of alcohol, and 'Alcoholism and Problem Drinking' which includes information on alcohol dependence.

What is alcoholic liver disease?

Drinking too much alcohol can lead to three types of liver conditions - fatty liver, hepatitis, and cirrhosis. Any, or all, of these conditions can occur at the same time in the same person. Fatty liver A build-up of fat occurs within liver cells in most people who regularly drink heavily. In itself, fatty liver is not usually serious and does not cause symptoms. Fatty liver will usually reverse if you stop drinking heavily. However, in some people the fatty liver progresses and develops into hepatitis. Alcoholic hepatitis Hepatitis means inflammation of the liver. The inflammation can range from mild to severe. y Mild hepatitis may not cause any symptoms. The only indication of inflammation may be an abnormal level of liver enzymes in the blood which can be detected by a blood test. However, in some cases the hepatitis becomes persistent (chronic), which can gradually damage the liver and eventually cause cirrhosis. y A more severe hepatitis tends to cause symptoms such as feeling sick, jaundice (yellowing of the skin, caused by a high level of bilirubin - a chemical normally metabolised in the liver), generally feeling unwell and, sometimes, pain over the liver. y A very severe bout of alcoholic hepatitis can quickly lead to liver failure. This can cause deep jaundice, blood clotting problems, confusion, coma, bleeding into the guts, and is often fatal. 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. Alcoholic cirrhosis Cirrhosis is a condition where normal liver tissue is replaced by scar tissue (fibrosis). The scarring tends to be a gradual process. The scar tissue affects the normal structure and regrowth of liver cells. Liver cells become damaged and die as scar tissue gradually develops. So, the liver gradually loses its ability to function well. 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.

About 1 in 10 heavy drinkers will eventually develop cirrhosis. It tends to occur after 10 or more years of heavy drinking. Note: cirrhosis can develop in people who have never had alcoholic hepatitis. Cirrhosis can happen from many causes other than alcohol. For example, persistent viral hepatitis and some hereditary and metabolic diseases. If you have another persistent liver disease, and drink heavily, you are likely to increase your risk of developing cirrhosis. Cirrhosis can lead to end-stage liver disease (liver failure). However, in the early stages of the condition, often there are no symptoms. You can get by with a reduced number of working liver cells. But, as more and more liver cells die, and more and more scar tissue builds up, symptoms start to appear. The eventual symptoms and complications are similar to a severe episode of hepatitis (listed above). However, unlike a bout of severe hepatitis, the symptoms and complications tend to develop slowly. See separate leaflet called 'Cirrhosis' for more details. 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. But, as a rule, the heavier you drink, and the more regularly that you drink, the more your risk of developing hepatitis and/or cirrhosis. The scaring and damage of cirrhosis is usually permanent and cannot be reversed. However, recent research has led to a greater understanding of cirrhosis. Research suggests that it may be possible to develop medicines in the future which can reverse the scarring process of cirrhosis.

How is alcoholic liver disease diagnosed?

A doctor may suspect that you have liver problems from your symptoms, and a physical examination. (For example, they may detect that your liver is enlarged, or that you are retaining fluid.) They may especially think of liver problems as a cause of your symptoms if you have a history of heavy alcohol drinking. Some tests may be done: y Blood tests may show abnormal liver function. (See separate leaflet called 'Blood Test - Liver Function Tests' for details.) y An ultrasound scan may show that you have a damaged liver. y To confirm the diagnosis, a biopsy (small sample) of the liver may be taken to be looked at under the microscope. (See separate leaflet called 'Biopsy - Liver' for details.) The scarring of the liver caused by cirrhosis, or the typical features of liver cells with alcoholic hepatitis can be seen on a biopsy sample.

What is the treatment for alcoholic liver disease?

For all types of liver disease caused by alcohol, you should stop drinking alcohol completely. Also, you may be referred to a dietician to review your diet. This is because many people who drink heavily do not eat properly and need advice on getting back into eating a healthy diet. Vitamin supplements may be prescribed for a while.

y y y

If you have fatty liver, or alcoholic hepatitis which is not severe, you should fully recover from these conditions if you stop drinking alcohol. If you have severe hepatitis and require hospital admission, you may require intensive care treatment. Some people with severe hepatitis will die. If you have cirrhosis, stopping drinking alcohol can improve your outlook. It depends on how severe the cirrhosis has become. If cirrhosis is diagnosed when it is not too advanced, and you stop drinking alcohol, the cirrhosis is unlikely to progress. However, the cirrhosis and symptoms will usually get worse if you continue to drink alcohol. In severe cases where the scarring is extensive, and the liver can barely function, then a liver transplant may be the only option.

Preventing alcoholic liver disease

You are very unlikely to develop liver problems caused by alcohol if you drink within the recommended safe limits. 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). y Women should drink no more than 14 units of alcohol per week (and no more than three units in any one day). y Pregnant women. The exact amount that is safe is not known. Therefore, advice from the Department of Health is that pregnant women and women trying to become pregnant should not drink at all. If you do chose to drink when you are pregnant then limit it to one or two units, once or twice a week. And never binge drink or get drunk. In general, the more you drink above the safe limits, the more harmful alcohol is likely to be. And remember, binge drinking can be harmful even though the weekly total may not seem too high. For example, if you only drink alcohol once or twice a week, but when you do you drink 4-5 pints of beer each time, or a bottle of wine each time, then this is a risk to your health. One unit of alcohol is 10 ml (1 cl) by volume, or 8 g by weight, of pure alcohol. 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), or o a small pub measure (25 ml) of spirits (40% alcohol by volume), 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), or o a standard pub measure (35 ml) of spirits (40% alcohol by volume) But remember, many wines and beers are stronger than the more traditional ordinary strengths. A more accurate way of calculating units is as follows. The percentage alcohol by volume (% abv) of a drink equals the number of units in one litre of that drink. For example: y Strong beer at 6% abv has six units in one litre. If you drink half a litre (500 ml) - just under a pint - then you have had three units. y Wine at 14% abv has 14 units in one litre. If you drink a quarter of a litre (250 ml) - two small glasses - then you have had three and a half units. Some other examples Three pints of beer, three times per week, is at least 18-20 units per week. That is nearly the upper weekly safe limit for a man. However, each drinking session of three pints is at least six units, which is more than the safe limit advised for any one day. Another example: a 750 ml bottle of 12% wine contains nine units. If you drink two bottles of 12% wine over a week, that is 18 units. This is above the upper safe limit for a woman.

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