APPROACH TO DIAGNOSIS AND MANAGEMENT OF JAUNDICE AND HEPATO BILIER DISORDERS

APPROACH TO DIAGNOSIS AND MANAGEMENT OF JAUNDICE

AND HEPATO  BILIER DISORDERS

CHAPTER I

INTRODUCTION

Jaundice is a change of skin color, eye sclera or other tissues (mucous membranes), which became yellow due to staining by an increased concentration of bilirubin in the blood circulation. Bilirubin (Bile) is formed as a result of solving hem ring, usually as a result of red blood cell metabolism.

The word jaundice (jaundice) derived from the French word meaning yellow Jaune. Jaundice should be examined under a bright light during the day, by looking at the eye sclera. Jaundice can be divided into two groups: Hemo ¬ lytic jaundice and obstructive jaundice.

Obstructive jaundice, caused by bile duct obstruction (¬ ter so often when a gallstone or cancer of the duct cover koledokus) or liver cell damage (which was finished in hepatitis ¬), speed of formation of bile is normal, but the bilirubin formed does not get through from the blood into the intestine.

Obstructive jaundice, also called cholestasis were divided into 2 of intrahepatic cholestasis and extrahepatic. The most common cause is intrahepatic cholestatic hepatitis, drug toxicity, alcoholic liver disease due to hepatitis and autoimmune diseases, while the most frequent cause of extrahepatic cholestasis is koledokus duct stones and pancreatic cancer. Other causes are relatively rare benign stricture (previous surgery) on koledokus duct, ductal carcinoma koledokus, pancreatitis or pancreatic pseudocyst and sklerosing cholangitis.

                Extra-hepatic biliary obstruction usually require surgery, extraction of gallstones diduktus, or stent insertion, via catheter for drainage and stricture (often malignant) or narrowing of the majority. For non-malignant obstruction operabel, palliative biliary drainage can be done through the stent is placed through the liver (transhepatic) or endoscopic.

Generally, non-obstructive jaundice does not require surgical intervention, whereas obstructive jaundice usually requires surgical intervention or other interventional procedures for treatment.

CHAPTER II

JAUNDICE

DEFINITION II.1 JAUNDICE
Jaundice (derived from French 'Jaune' meaning yellow) or jaundice (Latin for jaundice) is a yellow coloring of the skin, sclera, and mucous membranes by the deposit of bilirubin (bile pigment yellow-orange) on the network. Jaundice is a condition in which tissue yellowish due to deposition of bilirubin occurs when blood levels of bilirubin reaches 2 mg / dL or 35-40 mmol / L.

II.2 SYSTEM ANATOMY HEPATOBILIER
An accurate knowledge of the anatomy of the liver and biliary tract, and its relationship to blood vessels critical to the performance of surgery hepatobilier because there is usually a wide anatomic variations. Classical anatomical description of the biliary tract occurs only in 58% of the population.

Liver, gallbladder, and biliary branches arise from the ventral bud (hepatic diverticulum) from the most caudal foregut early in the fourth week of life. This section is divided into two sections as part of the ventral mesenterik grow between layers: a larger cranial part (pars hepatic) is the origin of the heart / liver, and a smaller caudal part (pars sistika) extended form of the gallbladder, the stem into the cystic duct. Initial relationship between the hepatic diverticulum, and narrowing of the foregut, will form the common bile duct. As a result of changes in the position of the duodenum, bile duct entrance is located around the dorsal aspect of the duodenum.
Biliary system is broadly divided into two components, pathways of hepatic intra-and extra-hepatic. Unit secretion of the liver (hepatocytes and biliary epithelial cells, including gland peribilier), kanalikuli bile, bile duktulus (Hearing canal), and intrahepatic bile duct intrahepatic form a channel in which the extrahepatic bile ducts (right and left), the communist hepatikus duct, cystic duct, bladder bile, and the common bile duct is a component of extrahepatic biliary branching.
Ekstrahepatal bile duct consists of left and right hepatikus duct, common hepatic duct, cystic duct and common bile duct or hepatic duct koledokus.Duktus right and left out of the heart and joined the Communist hepatic hilum to form ducts, usually the anterior bifurcation of the portal vein and the Cosmos proximal hepatic artery close to the right. Duct extrahepatic part of the left tend to be longer. Duct hepatikus communists built left border of Calot triangle and continues with duct koledokus. Division occurs at the level of the cystic duct. Koledokus duct about 8 cm in length and lies between the ligamentum hepatoduodenalis, to the right of the hepatic artery and anterior to the portal vein. Koledokus distal segment of the duct located within the substance of the pancreas. Koledokus duct empties its contents into the duodenum through the ampulla of Vater, surrounded by a muscular orifisiumnya of sphincter of Oddi. Typically, there are common channels of the pancreatic duct and the duct distal koledokus.
The blood supply to the gall bladder is through the arteries sistika; to be divided into anterior and posterior, typically a branch of the right hepatic artery, but the origin of the artery sistika vary. Sistika arteries arise from the Calot triangle (formed by the cystic duct, common hepatic duct and the tip of the liver). Venous drainage of the gallbladder varies, usually into the right branch of portal vein. Lymph flow directly entered into the heart and also to the lymph-nodes along the surface of the portal vein .. Persarafannya derived from the vagus and sympathetic branches of the celiac plexus passes (preganglionic T8-9). Impulses from the liver, gallbladder, and bile ducts melewari through sympathetic afferent nerve and causing pain splanknik colic. Nerves arise from the celiac axis and located along the hepatic artery. Pain sensation is mediated by visceral fibers, sympathetic. Motor stimulus for gallbladder contraction is carried through the branches of the vagus and the celiac ganglion.

II.3 PHYSIOLOGY bilirubin metabolism
Previous division of the stages of bilirubin metabolism which takes place in three phases; prehepatik, intrahepatic, and pascahepatik still relevant, even necessary to explain the existence of an additional phase in the stages of bilirubin metabolism. Phasing add 2 new phase again so that the phasing metabolic bilirtibin into 5 phases. ie phase 1). Formation of bilirubin, 2). Plasma transport, 3). Liver uptake, 4). Conjugation, and 5). biliary Eskresi

Phase Prahepatik

1. Bilirubin formation. Approximately 250 to 350 mg of bilirubin, or about 4 mg per kg body weight per day are formed; 70-80% comes from the breakdown of red blood cells mature. While the remaining 20-30% (early labeled billirubin) comes from other heme proteins that are primarily in the bone marrow and liver. Part of the heme protein is broken down into iron and biliverdin products between the enzyme-mediated hemeoksigenase. Another enzyme, biliverdin reductase, converting biliverdin to bilirubin. This stage occurs mainly in the reticuloendothelial system cells (mononuclear phagocytic). Increased red blood cell hemolysis is a major cause increased formation of bilirubin. Early labeled bilirubin formation is increased in several disorders with ineffective erythropoiesis, but is clinically less important.

2. Plasma transport. Bilirubin is insoluble in water, hence no conjugated bilirubin in plasma is bound to transport and can not be albuinin through the glomerular membrane, hence it does not appear in the urine. Bond weakening in some circumstances such as acidosis, and some materials such as certain antibiotics, salicylates compete on the albumin binding sites.

Intrahepatic phase.

3. Liver uptake. Making process is not conjugated bilirubin by the liver in detail and the importance of binding proteins such as ligandin or Y protein, is unclear. Bilirubin-making through active transport and running quickly, but not including the taking of albumin.

4. Conjugation. The free bilirubin is concentrated in the liver cells have to form conjugates with bilirubin diglukuronida glukuronik acid or bilirubin bilirubin conjugation or director. This reaction is catalyzed by the microsomal enzyme glukuronil-transferase which produces water-soluble bilirubin. In some circumstances this reaction produces only monoglukuronida bilirubin, with the second glukuronik acid added to the bile duct through a different enzyme systems, but this reaction is not considered to be physiological. Biliruibin conjugation other than diglukuronid also formed but its usefulness is not clear.

Phase Pascahepatik

5. Bilirubin Eskresi. Conjugation of bilirubin released into the kanalilculus with other materials. Other organic anions or drugs can affect this complex process. In the intestinal bacterial flora to "dekonyugasi" and reduce the bilirubin into sterkobilinogen.dan to remove most of the stool that gives brown color. Some is absorbed and released back into the bile, and small amounts reach the urine as Urobilinogen. The kidneys can not remove bilirubin diglukuronida but unkonyugasi. This explains the dark color of urine is typical of the disorder liepatoselular or intrahepatic cholestasis. No conjugated bilirubin is not soluble in water but soluble in fat. Therefore, conjugated bilirubin can not pass the blood-brain barrier or into the placenta. In liver cells, conjugated bilirubin was undergoing a process of conjugation with sugar melaltii glukuroniltransferase enzymes and bile soluble in the liquid.

II.4 EPIDEMIOLOGY JAUNDICE

The prevalence of jaundice is varied according to age and gender. Newborns and older adults are most often affected. The cause of jaundice may also vary according to age. Approximately 20% of newborns have jaundice in the first week of life, mainly due to the immaturity of the process of conjugation in the liver. Congenital abnormalities, hemolytic disorders and dekek conjugation is also responsible for causing jaundice in infants and children. Hepatitis A virus is a common cause of jaundice in children of school age.

Jaundice in male gender is usually caused by cirrhosis, chronic hepatitis B, hepatoma, pancreatic carcinoma, and cholangitis. While the woman is the cause of terseringnya gallstones, biliary cirrhosis and carcinoma of the gallbladder.

II.5 CLASSIFICATION OF JAUNDICE

The presence of jaundice that almost all organs showed an impaired secretion of bilirubin. Based on the cause, jaundice can be divided into three, namely:

1. Pre-hepatic jaundice

This type of jaundice occurs because of damage or intravascular hemolysis RBC, for example in cases of hemolytic anemia led to the formation of excess bilirubin. Hemolysis can be caused by blood parasites, eg, Babesia sp., And Anaplasma sp. According to Price and Wilson (2002), which is not conjugated bilirubin is not soluble in water so it is not excreted in the urine and does not happen but there was an increase Urobilinogen bilirubinuria. This causes the color of urine and feces to be dark. Jaundice caused by conjugated hyperbilirubinemia was mild and pale yellow. An example is the incidence of leptospirosis in dogs by infection with Leptospira grippotyphosa.

2. Hepatic jaundice

This type of jaundice occurs in the liver due to decreased uptake and conjugation by hepatocytes that failed to form conjugated bilirubin. Failure was caused by damage to the hepatocyte cells, acute or chronic hepatitis and use of drugs that affect the decision of bilirubin by liver cells. Conjugated bilirubin interference can be caused by deficiency of the enzyme as a catalyst glukoronil transferase (Price and Wilson 2002). Jaundice

3. Post-hepatic jaundice

The mechanism of post-hepatic jaundice is a decrease in the secretion of conjugated bilirubin conjugated hyperbilirubinemia so that result. Conjugated bilirubin is insoluble in water, so it is excreted into the urine (bilirubinuria) through the kidneys, but Urobilinogen be reduced so that the color of pale feces. Factors causing impaired secretion of bilirubin can be functional as well as factors choledocus duct obstruction caused by cholelithiasis, parasitic infestation, liver tumors, and inflammation resulting in fibrosis.

Migration of larvae through the liver is common in domestic animals. Nematode larvae through the liver can cause inflammation and hepatocellular necrosis (liver cell nekrosa). Former infection is then replaced with fibrous connective tissue (scar tissue) that often occurs in the liver capsule. Adult worms that had been moved to the bile duct and cause cholangitis or cholangiohepatitis that will impact the blockage / obstruction of the bile duct. Examples of nematodes that attack the liver dog is Capillaria hepatica. Cestoda is berhabitat worms in dogs hepatobiliary system, among others, Echinococcus granulosus and Taenia hydatigena. Are trematode worms in the bile duct berhabitat dogs include Dicrocoelium dendriticum, Ophisthorcis tenuicollis, Pseudamphistomum truncatum, Methorcis conjunctus, M. albidus, Parametorchis complexus, and others.

Obstructive jaundice is always designated as the post-hepatic since the defect lies in the metabolic pathway of bilirubin through hepatocyte. Other forms of jaundice was appointed as non-obstructive jaundice. This form is due to defect of hepatocytes (hepatic jaundice) or a pre-hepatic conditions.

CHAPTER III

Obstructive jaundice

III.1 Definition

Obstructive jaundice is the failure of the flow of bilirubin into the duodenum, where these conditions will cause pathological changes in hepatocytes and ampulla of Vater. Thus, obstructive jaundice is jaundice / yellow caused by the obstruction that blocks the flow of bilirubin into the jejunum.

Bile flow resistance caused by mechanical obstruction causing obstructive jaundice is referred to as cholestatic bile ducts, dilated before occlusion. Alkalifosfatase enzyme activity will increase and this is a sign of cholestasis. Bacterial infection with cholangitis and abscess formation and accompanying fever and septicemia are not infrequently encountered as a complication of obstructive jaundice.

III.2 Etiology

Obstructive jaundice caused by two major groups, namely intrahepatic and extrahepatic. The cause of intrahepatic obstructive jaundice are:

1. Obstructive jaundice is associated with hepatocellular disease, such as Steatohepatitis, acute viral hepatitis A, hepatitis B or with jaundice and fibrosis, decompensated cirrhosis and hepatitis due to drugs.

2. Obstructive jaundice associated with Alagille's syndrome duktopenia like, progressive familial cholestatic type 1, "bile duct paucity non sindromic", hepatotoxic drugs, chronic rejection after liver transplantation, and advanced stages of primary biliary cirrhosis.

The cause of extrahepatic obstructive jaundice is divided into two parts:

1. Cholestasis associated with damage to the gall bladder is an advanced stage of primary biliary cirrhosis, and hepatotoxic drugs.

2. Cholestasis or obstruction-related changes in portal tract as koledokus duct stones, strictures of the gallbladder, primary sclerosing cholangitis, pancreatic carcinoma, and chronic pancreatitis.

III.3 Pathophysiology

Bile is a secretion of multi-function with an array of functions, including digestion and absorption of lipids in the intestine, elimination of environmental toxins, carcinogens, drugs, and metabolites, and provide the primary pathway of endogenous excretion of various components and product metabolites, such as cholesterol, bilirubin, and various hormone.

On the obstruction jaundice, reflecting the absence patofisiologisnya effect of bile components (the most important bilirubin, bile salts, and lipids) in the small intestine, and its reserves, which led to the spill in the systemic circulation. Stool usually become pale due to lack of bilirubin that reaches the small intestine. The absence of bile salts can cause malabsorption, resulting in steatorrhea and deficiency of fat soluble vitamins (A, D, K), vitamin K deficiency can reduce the levels of prothrombin. On prolonged cholestasis, as vitamin D and Ca malabsorption can lead to osteoporosis or osteomalacia.

Retention of bilirubin cause hyperbilirubinemia mixture. Some conjugated bilirubin reaches and darkens the color of urine. High-level circulation associated with bile salts, but not the cause, pruritus. Cholesterol and phospholipid retention causes hyperlipidemia because of malabsorption of fat (although increased liver and decreased synthesis of cholesterol esterification also has a share), triglyceride levels were largely unaffected.

Cholestatic liver disease characterized by the accumulation of hepatotoxic substances, mitochondrial dysfunction and impaired liver antioxidant defenses. Storage of hydrophobic bile acids indicate the main cause of hepatotoxicity with changes in a number of important cell functions, such as mitochondrial energy production. Disorders of mitochondrial metabolism and the accumulation of hydrophobic bile acids are associated with increased production of oxygen free radical species and the development of oxidative damage.

III.4 RISK FACTORS

Tansfusi history of blood, sharing needles, tattoo, work at high risk for hepatitis B, previous surgery can be a risk factor for hepatitis yagn can cause hepatitis as the etiology of intrahepatic obstructive jaundice. Food and medicine, for example Clofibrate stimulates the formation of gallstones; alcohol, CCl4, high-cholesterol diet will also stimulate the formation of gallstones. Besides, alcohol will also cause fatty liver disease.

III.5 DIAGNOSIS

The first step approach to diagnosis of patients with jaundice is through anamnesis, physical examination and a careful examination of liver physiology.

III.5.1 History

Jaundice, dark urine, pale stools and pruritus is a general feature of obstructive jaundice. Dicolorisation (jaundice) or a history of jaundice seen in the inspection when the serum bilirubin level> 2.5 mg / dl. Changes in urine color, urine color so dark as tea. Changes in stool color, becoming pale as putty in the examination at least 3 times in a row. In patients with symptoms of pruritus was also arise due to accumulation of bilirubin in cholestatic director. Kolelitiasis can sometimes be accompanied by hemolytic anemia. Pain, especially in the upper right abdominal region, is more often caused by mechanical obstruction. Biliary colic is a common symptom of intermittent pain in the epigastric area (subxyphoid) radiating to the subcostal dextra, dextra scapula, and neck. The emergence of pain in biliary obstruction is felt especially after eating fatty foods, followed nausea, vomiting. Symptoms of anorexia and kaheksia more common in malignancy (Ca caput pancreas or liver Ca) rather than obstruction of biliary stones.

 History of fever, biliary colic, and intermittent jaundice may be suspected cholangitis / koledokolitiasis. Weight loss, abdominal mass, pain radiating to the back, the deeper the jaundice, pancreatic carcinoma may arise. Jaundice is in (with a greenish hue), which fluctuate in intensity may be due to peri-ampulla carcinoma. Dilated palpable gallbladder in patients with jaundice are also suspected of an extrahepatic malignancy (Couvoissier law).

III.5.2. PHYSICAL EXAMINATION

The physical examination includes touching the heart, gallbladder, spleen, look for signs of liver cirrhosis stigmata, such as spider naevi, palmar erythema, scratch mark on the skin because of pruritus, signs of ascites. . Enlarged liver in hepatitis, Ca hepatic, biliary obstruction, liver dam due to heart failure. Decreases in hepatic cirrhosis. Anemia and an enlarged spleen can be found in patients with hemolytic anemia. Showed an enlarged gall bladder obstruction in the distal bile duct is more commonly caused by a tumor (known as Courvoisier's law).

Courvoisier's law

"The gall bladder is not palpable in the jaundice may be caused by gallbladder stones." This usually indicates a stricture of neoplastic tumors (pancreatic tumors, ampulla, duodenum, CBD), stricture, chronic pancreatitis, or portal lymphadenopathy.

On examination found the punctum maximum tenderness in the anatomic location of the gallbladder. Murphy sign is positive, if the tenderness increased when the patient took a deep breath because of an inflamed gallbladder fingertips touched the examination and the patient stops breathing. Murphy's sign positive cholangitis, cholecystitis, koledokolelitiasis infected.

III.5.3. Examination support

A. hematology

Increased levels of serum bilirubin with excess conjugated bilirubin fractions. Serum gamma glutamyl transpeptidase (GGT) was also increased in cholestasis.

Generally, in patients with gallbladder stone disease hyperbilirubinemia lower than patients with malignant extra-hepatic obstruction. Serum bilirubin usually <20 mg / dL. Alkaline phosphatase increased 10 times the normal amount. Transaminase also suddenly increased 10 times the normal value and decreases rapidly as the cause of the obstruction is removed.

Increased leukocytes occurs in cholangitis. Pancreatic carcinoma and other cancers obstruction, serum bilirubin increased to 35-40 mg / dL, alkaline phosphatase increased 10 times the normal value, but transamin remained normal.

Tumor markers such as CA 19-9, CEA and CA-125 usually elevated in pancreatic carcinoma, kolangiokarsinoma, and peri-ampulla carcinoma, but these markers are not specific and may be elevated in benign diseases other hepatobilier branching.

2. imaging

The purpose of imaging is made: (1) ensure the existence of extrahepatic obstruction (ie verify whether post-hepatic jaundice due to comparison hepatic), (2) to determine the level of obstruction, (3) to identify the specific cause of obstruction, (4) provide complementary information with respect to underlying diagnosis (eg, staging information in the case of malignancy)

Ultrasound: shows the size of the bile duct, defining the level of obstruction, to identify causes and provide other information sehubuungan with the disease (eg, hepatic metastasis, gallbladder, hepatic parenkimal change).

Ultrasound: identification of duct obstruction with an accuracy of 95%, showed gallbladder stones and bile duct is dilated, but not reliable for small stones or strictures. Also can show a tumor, cyst or abscess in the pancreas, liver and surrounding structures.

CT: give viasualisasi good for the liver, gallbladder, pancreas, kidney and retroperitoneum; comparison between intra-and extrahepatic obstruction with an accuracy of 95%. CT with contrast is used to assess biliary malignancy.

ERCP (Endoscopic Retrograde Cholangio Pancreatography): provides direct visualization of the level of obstruction. With the help of an endoscope through the mouth of the papilla Vater contrast inserted into the bile duct and pancreatic duct. Another advantage is that once the examination is to assess whether there are abnormalities in the mouth of the papilla Vater, eg tumor or a stricture. Limitations that may arise in this investigation is when the mouth of the papilla can not be entered into the cannula. But this procedure is invasive and can cause complications such as cholangitis, biliary leak, pancreatitis and bleeding.

PTC: The bile duct obstruction in the distal part, the image of the channel can be visualized by examination proksimalnya Transhepatic percutaneous cholangiography (PTC). This check is performed by injecting contrast through the needle is inserted toward the liver hilum and the right side of the patient. Contrast is injected when the needle is believed to be in the bile ducts. Computed Tomography (CT) is a radiological examination to show serial liver slices. Liver abnormalities could be shown to the right location.

EUS (Endoscopic ultrasound): has a variety of applications, such as staging of gastrointestinal malignancy, evaluation of submucosal tumors and developed into an important modality in the evaluation pankreatikobilier system. EUS is also useful for detecting and staging tumors ampulla, mikrolitiasis detection, koledokolitiasis and evaluation of benign bile duct strictures or malignant. EUS can also be used for cyst aspiration and biopsy of solid lesions.

Magnetic Resonance-Pancreatography Cholangio (MRCP) is a new visualization technique, non-invasive in biliary and pancreatic duct system. This is especially useful in patients with contraindications to do ERCP. A good visualization of the biliary anatomy allows the invasive nature of ERCP without. Unlike ERCP, MRCP is a purely diagnostic.

III.6 MANAGEMENT

Medical

Medical treatment is used according to the etiology of jaundice. In the case of gallstones, the patient may be given ursodeoycholic acid 10 mg / kg / day to reduce the secretion of biliary cholesterol. In patients with symptoms of pruritus can be administered bile acid-binding resins (cholestyramine or colestipol) and antihistamines.

Surgery

Basically the management of patients with obstructive jaundice aims to eliminate the cause of the blockage or divert the flow of bile. Such actions may include measures such as surgical removal of a stone or tumor resection. Attempts to remove the blockage can act either through the papilla Vater endoscopy or by laparoscopy. Conservative management can be performed among others by providing a low-fat diet, antispasmodic drugs, analgesics and antibiotics if accompanied by cholecystitis.

If surgery is not possible to eliminate the cause of the blockage, drainage action is intended to be obstructed bile flow. Drainage can be carried out by bodies such as nasobilier pipe fitting, pipe or T in the duct koledokus kolesistotomi. Internal drainage can be done by creating a shortcut biliodigestif. This can be either internal drainage kolesisto-jejunostomi, koledoko-duodenostomi, koledoko-jejunostomi or hepatiko-jejunostomi.

III.7 COMPLICATIONS

Complications that can be experienced by patients with obstructive jaundice include liver failure, cirrhosis of the liver, diarrhea, pruritus, coagulopathy, malabsorption syndrome, renal failure, hypercholesterolemia, and deficiency of vitamin K.

1. Ascending cholangitis

Presence of symptoms of intermittent pain, fever, and jaundice. Cholangitis can cause liver abscess.

2. Coagulopathy

This is caused by a deficiency of vitamin K due to absorbed. In this situation, patients can be given FFP (fresh frozen plasma).

3. Hepatorenal syndrome

The causes may include bile salts and pigments that are nerotoksik, endotoxin and inflammatory mediators.

CHAPTER IV

CONCLUSION

Obstructive jaundice is jaundice / yellow caused by the obstruction that blocks the flow of bilirubin into the jejunum. Obstructive jaundice caused by two major groups, namely intrahepatic and extrahepatic. The cause of extrahepatic obstructive jaundice is divided into two parts: Cholestasis associated with damage to the gall bladder is an advanced stage of primary biliary cirrhosis, and hepatotoxic drugs; cholestasis or obstruction-related changes in portal tract as koledokus duct stones, strictures of the gallbladder, primary sclerosing cholangitis, pancreatic carcinoma and chronic pancreatitis. The first step approach to diagnosis of patients with jaundice is through anamnesis, physical examination and a careful examination of liver physiology. Basically the management of patients with obstructive jaundice aims to eliminate the cause of the blockage or divert the flow of bile. Surgery may be appropriate etiology of jaundice. If therapy is inadequate, then the complications that can occur in these patients is liver failure, cirrhosis of the liver, diarrhea, pruritus, coagulopathy, malabsorption syndrome, renal failure, hypercholesterolemia, and deficiency of vitamin K.

REFERENCES

1. Doherty, M.Gerard. Current Surgical Diagnosis and Treatment, Ed 12, USA : The Mc.Graw-Hill  

        Companies Inc.2006. hlm 549-551

2. Grace P, Borley N. At a Glance Ilmu Bedah. Edisi ketiga.Jakarta : Erlangga.2006. hlm 40-41

3. Reksoprodjo S. Kumpulan Kuliah Ilmu Bedah. Jakarta : Binarupa Aksara. 2000. Hlm 76-77.

4. Samsuhidajat R, De Jong W. Buku ajar Ilmu bedah Edisi 2. Jakarta : EGC.2004. hlm 198-200.

5. Schwartz, Shires, Spencer. Intisari Prinsip-Prinsip Ilmu Bedah, Edisi 6. Jakarta : EGC.2000. hlm 358-

        360.

6. Sabiston, David C. Buku Ajar Bedah bagian 2. Jakarta: EGC 1994. Hlm 157-160.

7. www.emedicinehealth.com

8. www.medicastore.com

9. www.wikipedia.com