LIVERLiver, largest internal organ of the human body. The liver, which is part of the digestive system, performs more than 500 different functions, all of which are essential to life. Its essential functions include helping the body to digest fats, storing reserves of nutrients, filtering poisons and wastes from the blood, synthesizing a variety of proteins, and regulating the levels of many chemicals found in the bloodstream. The liver is unique among the body’s vital organs in that it can regenerate, or grow back, cells that have been destroyed by some short-term injury or disease. But if the liver is damaged repeatedly over a long period of time, it may undergo irreversible changes that permanently interfere with function.
II. STRUCTURE OF THE LIVER
The human liver is a dark red-brown organ with a soft, spongy texture. It is located at the top of the abdomen, on the right side of the body just below the diaphragm—a sheet of muscle tissue that separates the lungs from the abdominal organs. The lower part of the rib cage covers the liver, protecting it from injury. In a healthy adult, the liver weighs about 1.5 kg (3 lb) and is about 15 cm (6 in) thick.
Despite its many complex functions, the liver is relatively simple in structure. It consists of two main lobes, left and right, which overlap slightly. The right lobe has two smaller lobes attached to it, called the quadrate and caudate lobes.
Each lobe contains many thousands of units called lobules that are the building blocks of the liver. Lobules are six-sided structures each about 1 mm (0.04 in) across. A tiny vein runs through the center of each lobule and eventually drains into the hepatic vein, which carries blood out of the liver. Hundreds of cubed-shaped liver cells, called hepatocytes, are arranged around the lobule's central vein in a radiating pattern. On the outside surface of each lobule are small veins, ducts, and arteries that carry fluids to and from the lobules. As the liver does its work, nutrients are collected, wastes are removed, and chemical substances are released into the body through these vessels.
Unlike most organs, which have a single blood supply, the liver receives blood from two sources. The hepatic artery delivers oxygen-rich blood from the heart, supplying about 25 percent of the liver's blood. The liver also receives oxygen-depleted blood from the hepatic portal vein. This vein, which is the source of 75 percent of the liver's blood supply, carries blood to the liver that has traveled from the digestive tract, where it collects nutrients as food is digested. These nutrients are delivered to the liver for further processing or storage.
Tiny blood vessel branches of the hepatic artery and the hepatic portal vein are found around each liver lobule. This network of blood vessels is responsible for the vast amount of blood that flows through the liver—about 1.4 liters (about 3 pt) every minute. Blood exits the liver through the hepatic vein, which eventually drains into the heart.
III. FUNCTIONS OF THE LIVER
One of the liver’s primary jobs is to store energy in the form of glycogen, which is made from a type of sugar called glucose. The liver removes glucose from the blood when blood glucose levels are high. Through a process called glycogenesis, the liver combines the glucose molecules in long chains to create glycogen, a carbohydrate that provides a stored form of energy. When the amount of glucose in the blood falls below the level required to meet the body’s needs, the liver reverses this reaction, transforming glycogen into glucose.
Another crucial function of the liver is the production of bile, a yellowish-brown liquid containing salts necessary for the digestion of lipids, or fats. These salts are produced within the lobules. Bile leaves the liver through a network of ducts and is transported to the gallbladder, which concentrates the bile and releases it into the small intestine.
Vitamins are also stored in the liver. Drawing on the nutrient-rich blood in the hepatic portal vein, the liver collects and stores supplies of vitamins A, D, E, and K. The B vitamins are also stored here, including a two- to four-year supply of Vitamin B12.
The liver also functions as the body’s chemical factory. Several important proteins found in the blood are produced in the liver. One of these proteins, albumin, helps retain calcium and other important substances in the bloodstream. Albumin also helps regulate the movement of water from the bloodstream into the body’s tissues. The liver also produces globin, one of the two components that form hemoglobin—the oxygen-carrying substance in red blood cells. Certain globulins, a group of proteins that includes antibodies, are produced in the liver, as are the proteins that make up the complement system, a part of the immune system that combines with antibodies to fight invading microorganisms.
Many other chemicals are produced by the liver. These include fibrinogen and prothrombin, which help wounds to heal by enabling blood to form clots, and cholesterol, a key component of cell membranes that transports fats in the bloodstream to body tissues.
In addition to manufacturing chemicals, the liver helps clear toxic substances, such as drugs and alcohol, from the bloodstream. It does this by absorbing the harmful substances, chemically altering them, and then excreting them in the bile.
IV. LIVER DISEASES
A variety of agents, including viruses, drugs, environmental pollutants, genetic disorders, and systemic diseases, can affect the liver. The resulting disorders usually affect one of the three functional components: the hepatocyte (liver cell), the bile secretory (cholangiolar) apparatus, or the blood vascular system. Although an agent tends to cause initial damage in only one of these areas, the resulting disease may in time also involve other components. Thus, although viral hepatitis (inflammation of the liver) predominantly affects hepatocytes, it commonly leads to damaged canaliculi, small channels that transport bile from hepatocytes.
Most acute liver diseases are self-limiting, and liver function returns to normal once the causes are removed or eliminated. In some cases, however, the acute disease process destroys massive areas of liver tissue in a short time, leading to extensive death (necrosis) of hepatic cells. For example, when acute hepatitis lasts for six months or more, a slow but progressive destruction of the surrounding liver cells and bile ducts occurs, a stage called chronic active hepatitis. If hepatocellular damage is severe enough to destroy entire acini (clusters of lobules), healthy tissue is often replaced with fibrous scar tissue. Bile canaliculi and hepatocytes regenerate in an irregular fashion adjacent to the scar tissue and result in a chronic condition called cirrhosis of the liver. Where inflammatory activity continues after the onset of cirrhosis, the disorderly regeneration of hepatocytes and cholangioles may lead to the development of hepatocellular or cholangiolar cancer.
The hepatitis A virus is transmitted almost exclusively via the fecal–oral route, and it thrives in areas where sanitation and food handling are poor and hand washing is infrequent. HAV proliferates in the intestinal tract during the two weeks following the onset of symptoms, but it then disappears. Many infected persons are unaware of being ill, since their disease remains asymptomatic or quite mild. The incubation period of HAV infections, from viral ingestion to the onset of symptoms, averages four to five weeks. Acute illness in an otherwise healthy pregnant woman does not appear to have adverse effects upon the fetus. Persons can become passively immunized against HAV for several months with either the hepatitis A vaccine or a single injection of immunoglobulin. Persons can be actively immunized to HAV by acquiring the virus subsequent to becoming passively immunized, but such infections are either inapparent or very mild.
Hepatitis B virus is present throughout the world in asymptomatic human carriers who may or may not have ongoing liver disease. Formerly, the disease was widely spread by the transfusion of whole blood or blood products, such as the cryoprecipitate used in the treatment of hemophilia. Since the signs of infection have become so readily identifiable, this mode of transmission is much less common, comprising only about 10 percent of cases, compared with 60 percent in the past. Virus particles in carriers are found in bodily secretions, especially saliva and sexual emissions, as well as in blood. The incidence of B antigens is high among persons engaging in promiscuous sexual activity, drug addicts who share syringes, health care workers, and infants of mothers who are carriers. Many newly infected persons develop the acute disease within three weeks to six months after exposure, while some develop an asymptomatic form of hepatitis that may appear only as chronic disease years later. Others eliminate the virus completely without any symptoms beyond the appearance of antibodies to surface antigen, while still others become carriers of surface antigen and thus presumably are infective to others.There are two methods of preventing hepatitis B: passive immunization, through the use of a specific immunoglobulin derived from patients who have successfully overcome an acute HBV infection; and active immunization, through the injection of noninfective, purified HBV surface antigen. The first method is used following specific exposures that carry a high risk of infection, such as using needles contaminated with HBV particles, the ingestion of body secretions likely to be infected, or the birth of an infant to a surface-antigen-positive mother. The second method, active immunization, is used for those who belong to groups with a high risk of HBV infection, such as children living in endemic areas, medical personnel in high-risk specialties, drug addicts, sexually promiscuous persons, and family groups living close to known carriers. Active immunization, involving a series of three injections of vaccine over a period of three to six months, has been shown to confer a high degree of resistance to infection.
Hepatitis C appears to be transmitted in a manner similar to HBV transmission. The incidence for HCV is high among persons engaging in promiscuous sexual activity, intravenous drug users, homosexual males, children living in endemic areas, infants born to infected mothers, health care workers, and hemodialysis patients. The average incubation period of the disease is about seven weeks, and an acute attack of hepatitis C is usually less severe than acute hepatitis B. Hepatitis C, however, is more likely to become chronic than is hepatitis B, and it may recur episodically with acute flares. The two approved treatments for hepatitis C are alpha interferon and ribavirin; only about half of those receiving the drugs respond to them.
The symptoms characteristic of acute hepatitis caused by HAV, HBV, and HCV are essentially similar. Patients often complain of a flulike illness for several days, with chills, fever, headache, cough, nausea, occasional diarrhea, and malaise. Abdominal pain caused by swelling of the liver is a common complaint. As many as half of the infected patients develop only mild symptoms or none at all. A small percentage of patients, especially those with HBV infections, may develop hives, painful skin nodules, acute arthritis, or urinary bleeding caused by the deposition of large immune antigen-antibody complexes in the small blood vessels of adjacent organs. After several days of such symptoms, jaundice commonly develops. At times the jaundice is so mild that it is not noticed by patients, although they often do note that the urine has become dark amber in colour because of the high levels of water-soluble bilirubin transmitted to the kidneys by the bloodstream.
The onset of jaundice usually brings with it a marked improvement in other symptoms. Jaundice lasts about two weeks but may continue for several months, even in those who have complete recovery. Some patients complain of itching during this period, and they notice the light colour of their stools. These symptoms probably result from the compression of bile canaliculi and intralobular bile ducts by the swelling of hepatocytes and Kupffer cells. The changes result in the reduced secretion of bile pigments into the biliary system, their reflux into the bloodstream, and the deposition of bile salts and other biliary constituents in the skin and subcutaneous tissues, a condition called obstructive jaundice. After the phase of jaundice subsides, almost all patients with hepatitis A, and at least 90 percent of those with hepatitis B, recover completely.
Aside from jaundice, the physical examination of patients with acute viral hepatitis may reveal nothing more than a detectable enlargement and, at times, tenderness of the liver. Some also show an enlarged spleen. Signs of confusion or disorientation indicate severe damage to the liver. The diagnosis of hepatitis is confirmed by blood tests that show marked elevations of enzymes (aminotransferases) released from damaged liver cells and by the presence of viral antigens or acute viral antibodies (IgM).
Aside from jaundice, the physical examination of patients with acute viral hepatitis may reveal nothing more than a detectable enlargement and, at times, tenderness of the liver. Some also show an enlarged spleen. Signs of confusion or disorientation indicate severe damage to the liver. The diagnosis of hepatitis is confirmed by blood tests that show marked elevations of enzymes (aminotransferases) released from damaged liver cells and by the presence of viral antigens or acute viral antibodies (IgM).
A small number, perhaps 1 percent, of patients with viral hepatitis, especially the elderly, develop a sudden, severe (fulminant) form of hepatic necrosis that can lead to death. In this form of the disease jaundice increases to high levels during the first 7 to 10 days, spontaneous bleeding occurs because of reductions of blood-clotting proteins, and irrational behaviour, confusion, or coma follow, caused by the accumulation in the central nervous system of the breakdown products of protein normally metabolized by the liver. Beyond supportive measures there is no effective treatment of fulminant hepatic failure except liver transplantation.
Acute hepatitis also may be caused by the overconsumption of alcohol or other poisons, such as commercial solvents (e.g., carbon tetrachloride), acetaminophen, and certain fungi. Such agents are believed to cause hepatitis when the formation of their toxic intermediate metabolites in the liver cell is beyond the capacity of the hepatocyte to conjugate, or join them with another substance for detoxification and excretion.
Acute canalicular (cholestatic) hepatitis is most commonly caused by certain drugs, such as psychopharmacologics, antibiotics, and anabolic steroids or, at times, by hepatitis viruses. The symptoms are generally those of biliary obstruction and include itching, jaundice, and light-coloured stools. Drug-induced cholestasis almost invariably disappears within days or weeks after exposure to the agent is discontinued. Acute congestive liver disease usually results from the sudden engorgement of the liver by fluids after congestive heart failure. The liver may enlarge and become tender. The levels of hepatocytic enzymes in the blood are often greatly increased, and recovery is rapid once the heart failure improves. Jaundice is uncommon in acute hepatic congestion.
3.Chronic active hepatitis
Chronic viral hepatitis B and C can be treated with interferon. Cirrhosis of the liver, and occasionally liver cancer, usually result from a gradual loss of liver function. Chronic hepatitis that is the result of autoimmune disorders usually responds to the administration of immunosuppressive medications and adrenal corticosteroids, which moderate the inflammatory reaction.
4.Liver cirrhosis
The end result of many forms of chronic liver injury is cirrhosis, or scarring of liver tissue in response to previous acinar necrosis and irregular regeneration of liver nodules and bile ducts. Among the congenital disorders producing cirrhosis are Wilson disease, hemochromatosis (over-deposition of iron pigment), cystic fibrosis, biliary atresia (congenital absence of a part of the bile ducts), and alpha1-antitrypsin deficiency, or the congenital absence of a proteolytic enzyme inhibitor that results in the accumulation of abnormal forms of carbohydrate in hepatocytes. In the Western world, cirrhosis of the liver most commonly results from chronic heavy intake of alcohol. This type of cirrhosis is known as Laënnec, or portal, cirrhosis. Chronic viral hepatitis is probably the leading cause of cirrhosis in underdeveloped countries. Primary biliary cirrhosis, a geographically widespread, though uncommon, autoimmune inflammatory disease of bile ducts, is a disorder primarily affecting middle-aged and older women. The inflammation leads to necrosis and gradual disappearance of bile ducts over a period of one or more decades. Secondary biliary cirrhosis results from chronic obstruction or recurrent infection in the extrahepatic bile ducts caused by strictures, gallstones, or tumours. Infestation of the biliary tract with a liver fluke, Clonorchis sinensis, is a cause of secondary biliary cirrhosis in Asia. Cirrhosis occasionally is the result of chronic vascular congestion of the liver in persons with prolonged heart failure and in those with chronic obstruction of the hepatic veins caused by benign blood clots or metastatic cancer.Symptoms of cirrhosis are usually absent during the early stages of the disease. Occasionally, cirrhosis is detected during a physical examination when an enlargement of the liver, spleen, or veins in the upper abdominal wall is found. More often, patients develop symptoms related either to the failure of the liver to perform its functions or to complications caused by the circulatory changes that a cirrhotic liver imposes on the venous blood flow from the intestinal tract (portal hypertension). Thus, common symptoms of cirrhosis include jaundice, resulting from reduced passage of conjugated bilirubin into the biliary tract; increased bleeding, from sequestration of blood platelets in a congested spleen; or deficient production of short-lived coagulation proteins by the liver. There may be certain changes in the skin, such as the appearance of small spiderlike vascular lesions on the hands, arms, or face, a marked reddening of portions of the palms, or enlargement of the breast in females or reduction in testicular size in males. These symptoms are believed to occur because of the liver's inability to metabolize the female sex hormones normally produced by the body. The gradual accumulation of fluid in the abdominal cavity (ascites), sometimes accompanied by swelling of the ankles, is attributable to portal hypertension and to reduced hepatic production of albumin, while failure of the liver to metabolize amino acids and other products of protein digestion may lead to the state of confusion called hepatic encephalopathy. Loss of appetite, reduction of muscle mass, nausea, vomiting, abdominal pain, and weakness are other symptoms of hepatic cirrhosis. Diabetes in a patient with cirrhosis is frequently caused by hemochromatosis (excessive deposition of iron in tissues, especially in the liver and pancreas), since iron deposits compromise the production of insulin by the islets of Langerhans in the pancreas. Severe spastic disorders of the muscles in the limbs, head, and face suggest the presence of Wilson disease, especially if there is a family history, since the copper deposits characteristic of that disorder are toxic to the liver and to structures in the base of the brain. A history of chronic lung infections or of progressive obstructive lung disease may be present in patients with cystic fibrosis or a deficiency of alpha1-antitrypsin.
A diagnosis of cirrhosis is confirmed by blood tests that show an elevated concentration of hepatocytic enzymes, reduced levels of coagulation proteins, elevated levels of bilirubin, and, most important, reduced amounts of serum albumin (a major protein of human blood plasma) and increases in serum globulin (a specific group of proteins found in blood plasma and including immunoglobulins). Although other tests may also be abnormal in patients with acute liver disease, serum albumin levels are usually not reduced in the acute stage of the disease because that protein is rather long-lived (up to one month) and levels do not decrease until the liver disease becomes chronic. Elevated levels of serum iron or copper support a diagnosis of hemochromatosis or Wilson disease, respectively, while a positive test for serum antibodies to cellular mitochondria is associated almost solely with primary biliary cirrhosis. The presence of HBV surface antigen or of delta agent suggests viral cirrhosis. A biopsy of the liver is the most valuable diagnostic test, since this procedure makes available an actual specimen of liver tissue for microscopic examination. Treatment of cirrhosis of the liver never results in a completely normal organ, since the process of scarring and nodular regeneration is permanent. The process itself, however, can be prevented or its progress halted by managing the precipitating factors of the disease.
5.Hepatic encephalopathy
Hepatic encephalopathy refers to changes in the brain that occur in patients with advanced acute or chronic liver disease. If liver cells are damaged, certain substances that are normally cleansed from the blood by the healthy liver are not removed. These products of cell metabolism are primarily nitrogenous substances derived from protein, especially ammonia, or possibly certain short-chain fatty acids. They pass to the brain where they damage functioning nervous tissue or subvert the actions of neurotransmitters, chemical messengers that carry impulses from one brain cell to another. In acute cases, the brain becomes swollen to the point where normal breathing may cease. Chronic exposure can lead to destruction of nerve cells with replacement by scar tissue (gliosis). A patient with chronic hepatic encephalopathy may develop progressive loss of memory, disorientation, and muscular tremors, leading to a form of chronic dementia. The ingestion of protein invariably aggravates these symptoms. Patients with gastrointestinal bleeding, infection, kidney failure, and constipation and those who are taking certain medications are all at risk of worsened episodes of hepatic encephalopathy.
The treatment of hepatic encephalopathy involves, first, the removal of all drugs that require detoxification in the liver and, second, the reduction of protein intake. Ammonia is a potentially harmful by-product of digestion, and its concentration in the blood can be lowered either through the reduction of intestinal bacteria by administration of enteric antibiotics, which reduce the production of ammonia in the colon or by administration of lactulose, a nonabsorbable carbohydrate whose by-products make the contents of the colon more acidic, creating an environment that reduces the diffusion of ammonia from the intestinal lumen to the portal blood vessels.
6.Portal hypertension
Portal hypertension is the increased pressure in the portal vein and its tributaries. It is the result of impediments to venous flow into the liver, and is brought about by the scarring characteristic of the cirrhotic process. The increased pressure causes feeders of the portal vein to distend markedly, producing varices, or dilations of the veins. When varices are located in superficial tissues, they may rupture and bleed profusely. Varices most commonly occur in the lower esophagus, the stomach, and the perianal region. Esophageal varices are likely to bleed most heavily, and, because of the reduced blood flow in the liver that results and the large amount of protein contained in the blood that is shed into the intestines, profuse bleeding from esophageal varices is frequently associated with the onset of hepatic encephalopathy or coma. Because of their location at the lower end of the esophagus or the upper portion of the stomach, bleeding from varices is often difficult to control. Bleeding may stop spontaneously, but it is likely to recur. Considerable success in stemming such hemorrhage and preventing its recurrence has been achieved by using rubber bands to block the blood supply to each varix or by the injection of sclerosing (hardening) agents into varices during endoscopic visualization. If variceal bleeding persists and if the patient can withstand a long and complex operative procedure, surgical formation of a shunt, or artificial passageway, from the portal vein or one of its feeders to a systemic abdominal vein, such as the vena cava or the left renal vein, or from the hepatic vein to the portal vein may be performed.
7. Tumour of liver
Portal hypertension is the increased pressure in the portal vein and its tributaries. It is the result of impediments to venous flow into the liver, and is brought about by the scarring characteristic of the cirrhotic process. The increased pressure causes feeders of the portal vein to distend markedly, producing varices, or dilations of the veins. When varices are located in superficial tissues, they may rupture and bleed profusely. Varices most commonly occur in the lower esophagus, the stomach, and the perianal region. Esophageal varices are likely to bleed most heavily, and, because of the reduced blood flow in the liver that results and the large amount of protein contained in the blood that is shed into the intestines, profuse bleeding from esophageal varices is frequently associated with the onset of hepatic encephalopathy or coma. Because of their location at the lower end of the esophagus or the upper portion of the stomach, bleeding from varices is often difficult to control. Bleeding may stop spontaneously, but it is likely to recur. Considerable success in stemming such hemorrhage and preventing its recurrence has been achieved by using rubber bands to block the blood supply to each varix or by the injection of sclerosing (hardening) agents into varices during endoscopic visualization. If variceal bleeding persists and if the patient can withstand a long and complex operative procedure, surgical formation of a shunt, or artificial passageway, from the portal vein or one of its feeders to a systemic abdominal vein, such as the vena cava or the left renal vein, or from the hepatic vein to the portal vein may be performed.
7. Tumour of liver
Liver cancer, usually in hepatocytes and less frequently in cells of bile duct origin, is rare in the Western world and is almost always associated with active cirrhosis, particularly the form found in patients with chronic hepatitis. The survival rate from liver cancer is low. In certain underdeveloped countries, especially in Africa, the incidence of this malignancy is high and is a major cause of death in the population. Most of these cases appear to stem from the prevalence of chronic viral hepatitis or the chronic presence of viruses in the blood (viremia) caused by hepatitis B. Long exposure to certain environmental poisons, such as vinyl chloride or carbon tetrachloride, has also been shown to lead to hepatic cancer.
Cancers arising elsewhere in the body, particularly in abdominal organs, lungs, and lymphoid tissue, commonly lead to metastatic cancer in the liver and are by far the most frequent type of hepatic malignancy. Usually, when such metastases are found, the primary tumour has advanced beyond the stage where it can be removed surgically.
Various benign types of tumours and cysts arise from certain components of the liver, such as the hepatocytes (adenomas) or blood vessels (hemangiomas). While the cause of these lesions is not always clear, hepatic adenomas are associated with the prolonged use of female sex hormones (estrogens). Symptoms of benign tumours depend mainly on their size and their position in relation to the surface of the liver. If they enlarge significantly, patients may experience pain or sensations of heaviness in the upper abdomen. When benign tumours are located close to the surface of the liver, they may rupture through the capsule and bleed freely into the abdominal cavity. Surgery is then required.
Benign cysts (tissue swellings filled with fluid) in the liver may occur as congenital defects or as the result of infections from infestation of the dog tapeworm (Echinococcus granulosus). Abscesses on the liver result from the spread of infection from the biliary tract or from other parts of the body, especially the appendix and the pelvic organs. Specific liver abscesses also result from infections with the intestinal parasite Entamoeba histolytica. Abscesses usually respond well to treatment with specific antibiotics, although surgical drainage is required in some cases.
8. Gallstones
Cholelithiasis, or the formation of gallstones in the gallbladder, is the most common disease of the biliary tract. Gallstones are of three types: stones containing primarily calcium bilirubinate (pigment stones); stones containing 25 percent or more of cholesterol (cholesterol stones); and stones composed of variable mixtures of both bilirubin and cholesterol (mixed gallstones).
Pigment stones are more common in certain parts of Asia than in the Western world, and they usually occur in persons who have forms of anemia caused by the rapid destruction of red blood cells (hemolysis). Hemolytic disease results from the hereditary or acquired acquisition of abnormal forms of hemoglobin or from abnormalities of the red blood cell membrane in disorders such as sickle cell anemia, thalassemia, or acquired hemolytic anemias. Increased destruction of red blood cells leads to abnormally large amounts of bilirubin, the hemoglobin derivative, in the liver and the consequent secretion into the biliary tract of increased amounts of the water-soluble conjugate, bilirubin diglucuronide, a pigment that is normally secreted in the urine. In the biliary tract, particularly in the gallbladder, some of this bilirubin diglucuronide is broken down by enzymes into water-insoluble bilirubin, which then tends to form stones. There are two types of pigment stones, black and brown. Black stones tend to form mainly in the gallbladder and occur in sterile bile, while brown stones may occur in any part of the biliary tract in patients with chronic biliary infections and stasis (stagnation of blood). The reasons for the increased incidence of pigment stones among persons with cirrhosis of the liver and the elderly are not clear, although increased red blood cell destruction may play a part. The occurrence of pigment stones is slightly more common in women.Cholesterol and mixed stones occur when the proportion of cholesterol in bile exceeds the capacity of bile acids and the phospholipid lecithin to contain the total amount of cholesterol in micellar colloidal solution. When this critical micellar concentration is surpassed and the solution is saturated, crystalline particles of cholesterol are formed. The resulting gallstones contain large amounts of crystalline cholesterol and smaller quantities of calcium bilirubinate. Pure cholesterol gallstones are rare.
Cholesterol gallstones occur about twice as frequently in women as they do in men, and at younger ages. Those at increased risk of cholesterol gallstones include persons who are obese, on diets high in caloric content or in cholesterol, diabetic, or taking female sex hormones. Each of these factors favours increased concentrations of cholesterol in bile. In addition, some persons are unable, for genetic reasons, to convert sufficient amounts of cholesterol to bile acids, thus favouring the increased formation of stones. Some illnesses, such as Crohn disease, reduce the capacity of the lower small intestine to reabsorb bile acids, leading to deficits of bile acids that cannot be overcome by hepatic synthesis alone. During pregnancy, the ratio of chenodeoxycholic acid to cholic acid in hepatic bile is reduced, thus making bile more prone to produce stones. Decreased flow of bile in the gallbladder, a condition that occurs late in pregnancy, in persons on diets low in fat, and among diabetics, also appears to favour the formation of cholesterol stones. Occasionally, some persons produce lithogenic bile, which results from reduced concentrations of phospholipids.
Symptoms are likely to be absent in about half of all patients who have gallstones. When they do appear, symptoms are caused by obstruction of a portion of the biliary tract, most commonly the cystic duct at the point where it emerges from the gallbladder. This obstruction leads to painful contraction of the gallbladder, swelling of its wall, and acute inflammation (cholecystitis). During an attack of cholecystitis, patients are often found to have fever, sharp pain in the upper abdomen (which also may be felt in the right shoulder region), tenderness over the region of the gallbladder, and elevations of the white blood cell count. If the obstruction of the neck of the gallbladder is prolonged, bacterial infections may appear, leading to formation of an abscess. Patients with bacterial infections in the gallbladder or bile ducts commonly have severe shaking chills, with high, spiking fevers. Jaundice does not occur with gallstone complications unless the stones become impacted and obstruct the common bile duct, thus slowing or interrupting the free passage of bile from the liver to the intestine. This jaundice is associated with a marked lightening of stool colour, caused by the absence of bile pigments in the intestine, and a change in the colour of urine to a dark amber, caused by large quantities of conjugated bilirubin.
Gallstones are easy to diagnose since canaliculi, small channels, in the gallbladder can be easily detected by ultrasonography. Enlargement of the gallbladder and bile ducts (resulting from obstruction) also can be detected by this method.
If gallstones are discovered on routine examination or during abdominal surgery for other reasons, and if the patient has no history of gallstone symptoms, nothing probably needs to be done. The situation is different, however, in persons who are clearly symptomatic or who are suffering acute complications, such as cholecystitis or abscesses. The traditional treatment in these cases is surgical removal of the diseased gallbladder and exploration of the bile ducts by X rays at the time of surgery for stones. Once the gallbladder and ductal stones are removed, there is little likelihood that cholesterol or black pigment stones will recur, although brown pigment stones may occasionally recur in the bile ducts after cholecystectomy.
Cholesterol gallstones can be dissolved without surgery as long as the gallbladder has retained its ability to concentrate bile and the cystic duct is unobstructed. This is accomplished by regular oral administration of drugs made from bile acids called urosodiol and chenodiol. The ingestion of these medications increases the amount of bile acids in hepatic bile and increases the ratio of bile acids to cholesterol, thus changing the bile from lithogenic to nonlithogenic. This medication must be continued for more than one year for the cholesterol gallstones to be completely dissolved and then continued permanently at reduced doses to prevent the reappearance of stones. Only a small percentage of patients are willing to undergo this permanent treatment, and the use of bile acids is confined either to those who strongly oppose surgery or those for whom surgery imposes great risk. Pigment stones do not respond to bile acid therapy.
9.Jaundice
9.Jaundice
Jaundice, or yellowing of the skin, sclera (outer layer of the eyeball), and mucous membranes, occurs whenever the level of bilirubin in the blood is significantly above normal. This condition is evident in three different types of disorders, more than one of which may be present simultaneously in a single person. The first type, unconjugated, or hemolytic, jaundice, appears when the amount of bilirubin produced from hemoglobin by the destruction of red blood cells or muscle tissue (myoglobin) exceeds the normal capacity of the liver to transport it or when the ability of the liver to conjugate normal amounts of bilirubin into bilirubin diglucuronide is significantly reduced by inadequate intracellular transport or enzyme systems. The second type, hepatocellular jaundice, arises when liver cells are damaged so severely that their ability to transport bilirubin diglucuronide into the biliary system is reduced, allowing some of this yellow pigment to regurgitate into the bloodstream. The third type, cholestatic, or obstructive jaundice, occurs when essentially normal liver cells are unable to transport bilirubin either through the capillary membrane of the liver, because of damage in that area, or through the biliary tract, because of anatomical obstructions (closure or absence of an opening, gallstones, cancer).Unconjugated jaundice: Unconjugated, or hemolytic, jaundice is characterized by the absence of bile pigments in the urine and by normal stool colour. The colour of the urine is normal because the bilirubin in the blood is unconjugated to glucuronic acid and therefore bound to blood albumin and insoluble in water. Thus the bilirubin is not filtered by the kidneys. The colour of stools remains normal because much of the bilirubin in the blood is filtered normally by the liver and enters the intestine promptly by way of the biliary system. Hemolytic diseases in newborns may lead to serious brain damage (kernicterus) if the unconjugated bilirubin crosses into the brain stem and destroys vital nuclei. The exposure to blue light of infants at risk for kernicterus converts the bilirubin to harmless and colourless degradation products. Unconjugated hyperbilirubinemia also occurs in many newborns, especially if they are premature, when the bilirubin transport enzyme systems are not fully developed. This disorder is self-limited, may require occasional exposures to blue light, and usually disappears within the first two weeks of extrauterine life. Gilbert disease, a fairly common hereditary deficiency in the hepatic transport protein ligandin and the conjugating enzyme glucuronyl transferase, results in a harmless lifelong tendency to mild degrees of unconjugated jaundice, especially during periods of fasting or fatigue.
Hepatocellular jaundice: Hepatocellular jaundice, present in all types of hepatitis and cirrhosis and in congestive liver disease, is characterized by dark amber urine and normal or slightly paler than normal stools. Because much of the bilirubin in the blood already has been conjugated by the endoplasmic reticulum of the hepatocyte, it is water-soluble and can be filtered by the kidneys. Stools are usually normal because some bile pigment also manages to be excreted into the biliary tract and intestine.
Cholestatic jaundice: Cholestatic jaundice is also distinguished by amber-coloured urine, but the colour of the stools is likely to be very pale (clay-coloured) due to the failure of bile pigments to pass into the intestine. Itching of the skin is commonly associated with this condition. Cholestasis occurs in many types of hepatitis, especially those caused by certain drugs, and in diseases that primarily damage small bile passages in the liver (intraheptic cholestasis). Cholestatic jaundice also occurs in patients with obstructive disorders of the biliary tract outside of the liver (extrahepatic cholestasis). It is often impossible to determine the level of obstruction by means of examination alone, and more sophisticated imaging techniques are required to locate the site of damage.
For people with severe liver disease or impending liver failure, organ transplantation may be an option. Unlike some organ transplants, such as kidney transplants, liver transplants are complex procedures that have not had high long-term success rates. Fortunately, new techniques and drugs are improving the outcome of liver transplants. Current success rates range between 60 and 80 percent, with more than half of recent transplant recipients surviving more than five years. Most of these people have an excellent prognosis for leading healthy, normal lives.
For people with severe liver disease or impending liver failure, organ transplantation may be an option. Unlike some organ transplants, such as kidney transplants, liver transplants are complex procedures that have not had high long-term success rates. Fortunately, new techniques and drugs are improving the outcome of liver transplants. Current success rates range between 60 and 80 percent, with more than half of recent transplant recipients surviving more than five years. Most of these people have an excellent prognosis for leading healthy, normal lives.
PANCREAS
Pancreas is a composite gland lying transversely across the posterior wall of the abdomen. It varies in length from 15 to 20 cm (6 to 8 in) and has a breadth of about 3.8 cm (about 1.5 in) and a thickness of from 1.3 to 2.5 cm (0.5 to 1 in). Its usual weight is about 85 gm (about 3 oz), and its head lies in the concavity of the duodenum.
The pancreas has both an exocrine and an endocrine secretion. The exocrine secretion is made up of a number of enzymes that are discharged into the intestine to aid in digestion. The endocrine secretion, insulin, is important in the metabolism of sugar in the body (see Sugar Metabolism). Insulin is produced in small groups of especially modified glandular cells in the pancreas; these cell groups are known as the islets of Langerhans. The failure of these cells to secrete sufficient amounts of insulin causes diabetes melitus.
For people with severe liver disease or impending liver failure, organ transplantation may be an option. Unlike some organ transplants, such as kidney transplants, liver transplants are complex procedures that have not had high long-term success rates. Fortunately, new techniques and drugs are improving the outcome of liver transplants. Current success rates range between 60 and 80 percent, with more than half of recent transplant recipients surviving more than five years. Most of these people have an excellent prognosis for leading healthy, normal lives.
For people with severe liver disease or impending liver failure, organ transplantation may be an option. Unlike some organ transplants, such as kidney transplants, liver transplants are complex procedures that have not had high long-term success rates. Fortunately, new techniques and drugs are improving the outcome of liver transplants. Current success rates range between 60 and 80 percent, with more than half of recent transplant recipients surviving more than five years. Most of these people have an excellent prognosis for leading healthy, normal lives.
PANCREAS
Pancreas is a composite gland lying transversely across the posterior wall of the abdomen. It varies in length from 15 to 20 cm (6 to 8 in) and has a breadth of about 3.8 cm (about 1.5 in) and a thickness of from 1.3 to 2.5 cm (0.5 to 1 in). Its usual weight is about 85 gm (about 3 oz), and its head lies in the concavity of the duodenum.The pancreas has both an exocrine and an endocrine secretion. The exocrine secretion is made up of a number of enzymes that are discharged into the intestine to aid in digestion. The endocrine secretion, insulin, is important in the metabolism of sugar in the body (see Sugar Metabolism). Insulin is produced in small groups of especially modified glandular cells in the pancreas; these cell groups are known as the islets of Langerhans. The failure of these cells to secrete sufficient amounts of insulin causes diabetes melitus.
The body coordinates the various steps of digestion so that the process proceeds smoothly and cells obtain a steady supply of nutrients and energy. The central nervous system and various glands control activities that regulate the digestive process, such as the secretion of enzymes and fluids. For example, the presence of food in the esophagus, stomach, or intestines triggers peristalsis. Food entering the stomach also stimulates the central nervous system to initiate the release of gastric juice. And as hydrochloric acid passes from the stomach, the small intestine produces secretin, a substance that simulates secretion of pancreatic juice.
DISEASES OF PANCREAS
1.Pancreatitis
DISEASES OF PANCREAS
1.Pancreatitis
Localized, severe abdominal and midback pain resulting from enzyme leakage, tissue damage, and nerve irritation is the most common symptom of acute pancreatitis. In severe cases, respiratory failure, shock, and even death may occur. The severity of the symptoms generally depends on the extent of the damage to the pancreas. The diagnosis is confirmed by the detection of elevated levels of pancreatic enzymes (amylase and lipase) in the blood and, if islet cell function is disturbed by the inflammatory process, elevated blood glucose levels. Ultrasonographic or computed tomographic (CT) scans of the upper abdomen usually reveal an enlarged and swollen pancreas. Sustained pain, often with fever, suggests the presence of a pseudocyst or abscess caused by localized areas of destruction and infections in the pancreas.
Acute pancreatitis is treated primarily by supportive therapy, with replacement of fluid and sodium and control of pain. In severe cases, washing necrotic material and active enzymes from the abdominal cavity during surgery may be beneficial. Following recovery from an acute attack, the prevention of further attacks should be the primary goal. Thus, the removal of gallstones, cessation of alcohol consumption, a low-fat diet, and discontinuation of toxic drugs (thiazide diuretics, immunosuppressives, and corticosteroids, for example) can be helpful measures. In instances where repeated attacks of acute pancreatitis have resulted in strictures (scars) of the main pancreatic duct, surgical repair may decrease the number of further attacks.
2.Chronic pancreatitis
3.Cystic fibrosis
Cystic fibrosis is inherited, but it is not expressed unless both members of a pair of homologous, or corresponding, chromosomes carry the trait. The major functional abnormality in persons with the disease appears to be the elaboration by mucous glands throughout the body of secretions containing greater than normal concentrations of protein and calcium. This imbalance leads to increased viscosity of the secretions of mucus and organic constituents in gland ducts. The resulting plugging process in the pancreas almost invariably causes destruction and scarring of the acinar tissue, usually without damaging the islets of Langerhans. A similar process in the hepatic biliary system produces a form of cirrhosis. In cystic fibrosis, the resulting pancreatic insufficiency usually can be treated by the oral replacement of pancreatic enzymes.
4. Cancer of Pancreas
Pancreatic cancer arises primarily from the ductal system of the pancreas. The incidence of pancreatic cancer has increased slightly (somewhat more in men than in women) and now exceeds cancer of the stomach. Risk factors include age, race, gender, a diet high in fat, smoking, diabetes, family history, exposure to pesticides, certain dyes and chemicals, ulcers, and chronic pancreatitis. Upper abdominal pain, often radiating to the back, and weight loss are the most common symptoms of pancreatic cancer. Obstructive jaundice is a frequent symptom when the head of the pancreas is involved. The diagnosis is readily made in most cases by CT scan, at times supplemented by biopsy. There is no effective treatment. If the tumour is localized and has not invaded blood vessels and nerves surrounding the pancreas, it occasionally can be removed surgically. Jaundice and intestinal obstruction can be relieved temporarily by surgical bypass procedures. Radiation and chemotherapy have shown some promise as therapeutic agents if they are started promptly in the course of the disease and are continued for long periods.