Mechanical Jaundice As Complication Of Cholelithiasis

STATE UNIVERSITY OF MEDICINE AND PHARMACY

" NICOLAE TESTEMITANU"

DEPARTMENT OF Semiotics of general surgery

THESIS

MECHANICAL JAUNDICE AS COMPLICATION OF CHOLELITHIASIS

Presented by:

Student of gruop nr.M1043 Loai Omari

Dean of study:

PHd, Professor Evghenii Gutu

Coordinator:

Assistant Professor Dr.Vladimir Iacub

TABLE OF CONTENTS

1.INTRODUCTION

Cholelithiasis is a clinical challange. In an advanced form of it , the patient are jaundiced , which is almost always caused by hyperbilirubinemia, and is characterized by yellow pigmentation of skin and sclera. Jaundice due to cholelitiasis is a frequent clinical problem in the medical practice especially in adult and it's intrestieng especially because of it's treatment and diagnsis that are different and variable depend on the patient situation .

So this thesis was designed to studu the diagnosis and the treatment of the cholelithiasis and it's complication (jaundice) and even how we can prevent it .

After searching in multiple sources and reading them and after a practical workup with patient that sufferd from this disease (his situation is included in the thesis), I manged to first off all to increase my own knowldge about this disease and to write this thesis .

At the end I want to thank my guide during my work

Dr.Vladimir Iacub I appreciate his effort , and I hope that you will enjoy during reading my thesis.

With All Respect

Loai Omari

2.BIBLIOGRAPHIC RESEARCH

2.1 Anatomical and physiological peculiarities of biliary tree

2.1.1 anatomy of biliary tree

The development of the human biliary tract begins in the third week of

gestation from the embryonic hepatic diverticulum which develops from the foregut. The diverticulum divides into two parts, hepatic and biliary. The primitive bile ducts further divide into caudal and cranial parts. Gallbladder, cystic duct, and CBD develop from the caudal part, and the intrahepatic bile ducts, and the common hepatic duct develop from the cranial part. The smallest bile ducts are tiny bile canaliculi, which are formed by adjacent hepatocytes and are missing true wall structures. These canaliculis form a network which are connected to small bile ductules via canals of Hering. The bile ductules anastomose freely and increase in size to form trabecular ducts, intrahepatic ducts, and eventually the right and left hepatic duct. At the hilum of the liver, these ducts join to form the common hepatic duct (Gilloteaux 1997).[36]

About 3-4 cm after leaving the liver, the cystic duct joins the common hepatic duct to form the CBD. The length of the CBD varies between 5 and 15 cm, depending on where the common hepatic duct and cystic duct are merged, and the normal width is 4-10 mm. [35]

The CBD is divided into supraduodenal, retroduodenal, pancreatic,

and intraduodenal segments. The distal part of the CBD comes into contact with the main pancreatic duct and in about 70% of cases unites to form the major duodenal papilla or papilla of Vater. The intraduodenal part of the CBD and the papilla of Vater are surrounded by a complex network of longitudinal and circular muscle fibers, which form the sphincter of the hepatopancreatic ampulla, or, the sphincter of Oddi [37] The gross anatomy of the extrahepatic biliary tract is described in Figure 1.

The gallbladder is a pear-shaped sac with a capacity of 30-50 ml. It lies in the gallbladder fossa at the junction of the right and left lobes of the liver. The hepatic surface of the gallbladder attaches to the liver by the loose connective tissue of the fibrous capsule of the liver. The gallbladder is divided into three parts: fundus, body, and neck. The wall is 1-2 mm thick, depending on whether the gallbladder is relaxed or not .[38]

The cystic duct connects the neck of gallbladder to the common hepatic duct. It is 1-4 cm long and 5-8 mm wide. The cystic duct typically presents two types of structures: spirally arranged outgrowth of mucosa which forms the valve of Heister, and a smooth part . [39]

Figure 1. Gross anatomy of the extrahepatic biliary tract.

2.1.2 Circulation, lymphatic drainage and innervation of the biliary tract

The extrahepatic biliary tract gets its arterial blood supply from the tributaries of the common hepatic artery: the cystic artery supplies the gallbladder, the cystic duct, and the proximal part of CBD, the right hepatic artery supplies the middle part, and the posterior superior pancreatoduodenal and gastroduodenal arteries supply the retroduodenal part of the duct . [40]

The veins from the hepatic ducts and proximal part of the CBD enter the liver directly. The distal part of the CBD drains to the posterior superior

pancreatoduodenal vein which empties into the portal vein or one of its

tributaries.

The lymphatic vessels from the biliary tract pass to the cystic lymph nodes near the neck of the gallbladder, the nodes of the omental foramen, the hepatic lymph nodes, and eventually to the lymph nodes around the celiac trunk. The lymphatic vessels of the gallbladder and the biliary tract anastomose superiorly with those of the liver and inferiorly with those of the pancreas and duodenum.[38]

The sympathetic nerves of the extrahepatic biliary tract come from the celiac plexus, the parasympathetic nerves come from the vagus nerve and the sensory nerves come from the right phrenic nerve. They pass along the hepatic artery, the portal vein, and CBD.

2.1.3 Anatomical variations of the biliary tree

The normal biliary anatomy is thought to be present in about half of individuals. Anatomical variations are most common in the confluence area, typically concerning the right posterior hepatic duct and its drainage site; these variations are present in approximately 25% of the population. Another common variation is the so-called trifurcation where the right anterior and posterior ducts drain separately into the common hepatic duct, and is present in 11% of the population . [41]

There are three common variants in the anatomy of the cystic duct region: low cystic duct insertion with distal third of the CBD (9%); medial insertion, where the cystic duct drains into the left side of CBD (10-17%); and a parallel course and less angular entry into CBD (1.5-25%) . The potential other routes for the cystic duct drain into the biliary tree are numerous, and it is estimated that only one third of the population has a so-called normal cystic duct anatomy . [43]

The most common duct anomalies and the cystic union types are described in figures 2 and 3.

Figure 2. The common variants in bile duct anatomy. A, long cystic duct with

low fusion. B, high fusion. C, accessory hepatic duct (trifurcation). D, cystic

duct entering right hepatic duct. E, cholecystohepatic duct. [42]

Figure 3. The common cystic duct unions. A, angular (75%). B, parallel (20%).

C, spiral/medial (5%).

True anatomical variations of the gallbladder are extremely rare. Agenesis, duplication and left-sided position are described in literature. The operating surgeon needs only to be aware of these entities as they have only a limited clinical significance.

2.1.4 physiology of the biliary tract

Bile is a complex mixture of organic and inorganic components. The main organic components are bile acids, phospholipids, cholesterol, and bile pigments. Bile acids account for about 50% of the organic components. Four bile acids are present in the bile and they are synthetized from cholesterol.

Cholic and chenodeoxycholic are the primary bile acids and are synthesized in the liver. Within the lumen of the intestine, bacteria dehydroxylate secondary bile acids, deoxycholic and lithocholic acids. All four are returned to the liver in the portal blood and secreted into the bile.

Phospholipids, primarily lecithins, account for about 30-40% of the organic components. Cholesterol makes up approximately 4% of the organic material in the bile. Bile pigments, mainly bilirubin, account for about 2% of the organic compounds.

The major parts of the biliary tract which participate actively in the control of bile flow are the gallbladder and the sphincter of Oddi. Bile is continuously produced by the hepatocytes in the liver, and under a normal physiological condition, the bile flow averages about 500-1000 ml per day. The secretion of bile acids carries water and electrolytes into the bile by osmotic filtration, additional water and electrolytes are added by the cells lining the ducts [37] . This latter secretory component is stimulated by secretin. The hepatic end of the biliary system is closed; thus the secretion generates hydrostatic pressure within the ducts. During the interdigestive period, the gallbladder is flaccid and the sphincter of Oddi is closed; this permits the bile flow into the gallbladder. The gallbladder does not simply fill passively, periodical contractions, mediated mainly by motilin, partially empty the concentrated bile, which permits the diluted bile to enter the gallbladder. [44]

During the interdigestive period, vasoactive intestinal peptide and nitric oxide possibly promote the relaxation of the gallbladder wall to allow the filling[45] . Between meals, bile is actively concentrated by the gallbladder epithelium as much as tenfold. Na+, Cl-, and HCO3- are reabsorbed, and water follows down the osmotic gradient. The gallbladder also secretes mucus and slightly acidifies the bile. After the meal, the major stimulus for gallbladder contraction is cholecystokinin (CCK) released by fat and protein digestion products within the lumen of the duodenum. The gallbladder contraction is also stimulated by vagal activity during all phases of digestion. CCK has two principal actions: relaxation of the sphincter of Oddi and contraction of the smooth muscle within the gallbladder wall. Several other hormones, released from different sources, may modulate the effect of CCK, affect the relaxation of the sphincter of Oddi, or the motility of the gallbladder[45] . During normal postprandial gallbladder emptying, 50-90% of the contents is expelled .[46]

2.2 The epidemiology of the cholelithiasis disease

The prevalence of cholelithiasis is affected by many factors, including ethnicity, sex , comorbidities, and genetics.

2.2.1 United States statistics

In the US ., about 20 million people (10-20% of adults) have cholelithiasis . Each year 1-3% of people develop cholelithiasis and about 1-3% of people become symptomatic . Each year, in the US , about 500 thousands people develop symptoms or complications of gallstones requiring removing of the gallbladder.

Gallstone sickness is responsible for about 10thousands deaths annually in the US . About 7 thousands deaths are due to acute gallstone complications , like acute pancreatitis. approximately 2000-3000 deaths are caused by gallbladder cancers (80 persents of which occur in the setting of gallstone disease with chronic cholecystitis). anyway gallstone operation is relatively not dangerous, cholecystectomy is a very common procedure, and its rare complications result in several hundred deaths annually.

2.2.2 International statistics

The prevalence of cholesterol cholelithiasis in other Western cultures is the same in the US , but it is lower in Asia and Africa.

A Swedish epidemiologic study found that the incidence of gallstones was 1.39 per 100 person-years. [5]  In an Italian study, 20% of women had stones, and 14% of men had stones. In a Danish study, gallstone prevalence in persons aged 30 years was 1.8% for men and 4.8% for women; gallstone prevalence in persons aged 60 years was 12.9% for men and 22.4% for women.

The prevalence of choledocholithiasis is higher internationally than in the US , mainly because of the additional problem of primary common bile duct stones caused by parasitic infestation with liver flukes such as Clonorchis sinensis.

2.2.3 Race, sex, and age-related demographics

Prevalence of gallstones is highest in people of northern European descent, and in Hispanic populations and Native American populations.[6] Prevalence of gallstones is lower in Asians and African Americans.

Women are more likely to develop cholesterol gallstones than men, especially during their reproductive years, when the incidence of gallstones in women is 2-3 more than in men. The difference appears to be mainle due to estrogen, which increases biliary cholesterol secretion. [7]

Risk of developing gallstones increases with age. Gallstones are uncommon in childhood period in the absence of congenital anomalies or hemolytic disorders. Beginning at puberty, the concentration of cholesterol in bile increases. After age 15 years, the prevalence of gallstones in Unaited states women increases by about 1% annually , in men, the rate is less, about 0.5% annualy . Gallstones continue to form during adult life, and the prevalence is greatest at older age. The incidence in women decrease with menopause, but new stone formation in men and women continues at a rate of about 0.4% per year until late in life.

Among individuals undergoing cholecystectomy for symptomatic cholelithiasis, 8-15% of patients younger than 60 years have common bile duct stones, compared with 15-60% of patients older than 60 years.

2.3 The definition of cholelithiasis and the etiopathogenesis of stone formation

Cholelithiasis (Gallstones): Stones appear when substances in the bile harden. Gallstones varing in sizes can be small or large . It can be single stone or multiple stones.

Gallstones can obstruct the flow of bile if they stocked in any of the bile ducts that is responsible for passing the bile from the liver to the small intestine. That includes the hepatic ducts, which take of the bile out of the liver; the cystic duct, which catty the bile to and from the gallbladder; and the common bile duct, which take of the bile from the cystic and hepatic ducts to the small intestine. Bile material intercepted in the ducts can lead inflammation in the gallbladder , the ducts, or, rarely, the liver. Other ducts open into the common bile duct, including the pancreatic duct, which carries digestive enzymes out of the pancreas. If a gallstone blocks the opening to that duct, digestive enzymes can become intercepted in the pancreas and cause an extremely painful inflammation it's name is gallstone pancreatitis. If any of these ducts remain blocked for a significant period of time, severe damage or infections can occur, affecting the gallbladder, liver, or pancreas.

Gallstone attacks appear often occur postprandial , especially a fatty fod . Symptoms can include pain which can remains for several hours in the upper, back , or under the right shoulder with nausea , vomiting, abdominal distention or indigestion. These symptoms can excerbate those of other problems, like heart attack, so accurate diagnosis is important.[26]

They are divided into two major types: cholesterol stones account for 80% of the total, with pigment stones comprising the remaining 20%. Cholesterol gallstones usually contain >50% cholesterol monohydrate plus an admixture of calcium salts, bile pigments, proteins, and fatty acids, the latter in “brown” pigment stones. Pigment stones are composed primarily of calcium bilirubinate; they contain <20% cholesterol and are classified into “black” and “brown” types, the latter forming secondary to chronic biliary infection. [25]

Figure 4.

CHOLESTEROL STONES AND BILIARY SLUDGE

Cholesterol is essentially water insoluble and requires aqueous dispersion into either micelles or vesicles, both of which require the presence of a second lipid to solubilize the cholesterol. Cholesterol and phospholipids are secreted into bile as unilamellar bilayered vesicles, which are converted into mixed micelles consisting of bile acids, phospholipids, and cholesterol by the action of bile acids. If there is an excess of cholesterol in relation to phospholipids and bile acids, unstable cholesterol-rich vesicles remain, which aggregate into large multilamellar vesicles from which cholesterol crystals precipitate (Figure 5).

FIGURE 5. Scheme showing pathogenesis of cholesterol gallstone formation. Conditions or factors that increase the ratio of cholesterol to bile acids and phospholipids (lecithin) favor gallstone formation. HMG-CoAR, hydroxymethylglutaryl–coenzyme A reductase; 7-α-OHase, cholesterol, 7α-hydroxylase; MDR3, multidrug resistance– associated protein 3, also called phospholipid export pump.

There are several important mechanisms in the formation of lithogenic (stone-forming) bile. The most important is increased biliary secretion of cholesterol. This may occur in association with obesity, high-caloric and cholesterol-rich diets, or drugs (e.g., clofibrate) and may result from increased activity of HMG-CoA reductase, the ratelimiting enzyme of hepatic cholesterol synthesis, and increased hepatic uptake of cholesterol from blood. In patients with gallstones, dietary cholesterol increases biliary cholesterol secretion. This does not occur in non-gallstone patients on high-cholesterol diets. In addition to environmental factors such as high-caloric and cholesterol-rich diets, genetic factors play an important role in gallstone disease. A large study of symptomatic gallstones in Swedish twins provided strong evidence for a role of genetic factors in gallstone pathogenesis. Genetic factors accounted for 25%, shared environmental factors for 13%, and individual environmental factors for 62% of the phenotypic variation among monozygotic twins.. Thus an excess of biliary cholesterol in relation to bile acids and phospholipids is primarily due to hypersecretion of cholesterol, but hyposecretion of bile acids or phospholipids may contribute. An additional disturbance of bile acid metabolism that is likely to contribute to supersaturation of bile with cholesterol is enhanced conversion of cholic acid to deoxy-cholic acid, with replacement of the cholic acid pool by an expanded deoxycholic acid pool. It may result from enhanced dehydroxylation of cholic acid and increased absorption of newly formed deoxycholic acid. An increased deoxycholate secretion is associated with hypersecretion of cholesterol into bile. While supersaturation of bile with cholesterol is an important prerequisite for gallstone formation, it is generally not sufficient by itself to produce cholesterol precipitation in vivo. Most individuals with supersaturated bile do not develop stones because the time required for cholesterol crystals to nucleate and grow is longer than the time bile spends in the gallbladder. An important mechanism is nucleation of cholesterol monohydrate crystals, which is greatly accelerated in human lithogenic bile. Accelerated nucleation of cholesterol monohydrate in bile may be due to either an excess of pronucleating factors or a deficiency of antinucleating factors. Mucin and certain non-mucin glycoproteins, principally immunoglobulins, appear to be pronucleating factors, while apolipoproteins AI and AII and other glycoproteins appear to be antinucleating factors. Cholesterol monohydrate crystal nucleation and crystal growth probably occur within the mucin gel layer. Vesicle fusion leads to liquid crystals, which, in turn, nucleate into solid cholesterol monohydrate crystals. Continued growth of the crystals occurs by direct nucleation of cholesterol molecules from supersaturated unilamellar or multilamellar biliary vesicles.

A third important mechanism in cholesterol gallstone formation is gallbladder hypomotility. If the gallbladder emptied all supersaturated or crystal-containing bile completely, stones would not be able to grow. A high percentage of patients with gallstones exhibits abnormalities of gallbladder emptying. Ultrasonographic studies show that gallstone patients display an increased gallbladder volume during fasting and also after a test meal (residual volume) and that fractional emptying after gallbladder stimulation is decreased. Gallbladder emptying is

a major determinant of gallstone recurrence in patients who underwent biliary lithotripsy.

Biliary sludge is a thick mucous material that upon microscopic examination reveals lecithin-cholesterol crystals, cholesterol monohydrate crystals, calcium bilirubinate, and mucin gels. Biliary sludge typically forms a crescent-like layer in the most dependent portion of the gallbladder and is recognized by characteristic echoes on ultrasonography The presence of biliary sludge implies two abnormalities: (1) the normal balance between gallbladder mucin secretion and elimination has become deranged and (2) nucleation of biliary solutes has occurred. That biliary sludge may be a precursor form of gallstone disease is evident from several observations. In one study, 96 patients with gallbladder sludge were followed prospectively by serial ultrasound studies. In 18%, biliary sludge disappeared and did not recur for at least 2 years. In 60%, biliary sludge disappeared and reappeared; in 14%, gallstones (8% asymptomatic, 6% symptomatic) developed, and in 6%, severe biliary pain with or without acute pancreatitis occurred. In 12 patients, cholecystectomies were performed, 6 for gallstone- associated biliary pain and 3 in symptomatic patients with sludge but without gallstones who had prior attacks of pancreatitis; the latter did not recur after cholecystectomy. It should be emphasized that biliary sludge can develop with disorders that cause gallbladder hypomotility, i.e., surgery, burns, total parenteral nutrition, pregnancy, and oral contraceptives—all of which are associated with gallstone formation.

However, the presence of biliary sludge implies supersaturation of bile with either cholesterol or calcium bilirubinate.

Two other conditions are associated with cholesterol stone or biliary sludge formation: pregnancy and very low calorie diet. There appear to be two key changes during pregnancy that contribute to a “cholelithogenic state”: (1) a marked increase in cholesterol saturation during the third trimester and (2)sluggish gallbladder contraction in response to a standard meal, resulting in impaired gallbladder emptying.

That these changes are related to pregnancy per se is supported by several studies that show reversal of these abnormalities quite rapidly after delivery. During pregnancy, gallbladder sludge develops in 20–0% of women and gallstones in 5–12%. Although biliary sludge is a common finding during pregnancy, it is usually asymptomatic and often resolves spontaneously after delivery. Gallstones, which are less common than sludge and frequently associated with biliary colic, may also disappear after delivery because of spontaneous dissolution related to bile becoming unsaturated with cholesterol post partum. Approximately 10–20% of persons with rapid weight reduction achieved through very low calorie dieting develop gallstones. In a study involving 600 patients who completed a 16-week, 520-kcal/d diet, UDCA in a dosage of 600 mg/d proved highly effective in preventing gallstone formation; gallstones developed in only 3% of UDCA recipients, compared to 28% of placebo-treated patients.

To summarize, cholesterol gallstone disease occurs because of several

defects, which include (1) bile supersaturation with cholesterol, (2) nucleation of cholesterol monohydrate with subsequent crystal retention

and stone growth, and (3) abnormal gallbladder motor function with delayed emptying and stasis. Other important factors known to predispose

to cholesterol stone formation are summarized in Table-1.

PIGMENT STONES

Black pigment stones are composed of either pure calcium bilirubinate or polymer-like complexes with calcium and mucin glycoproteins. They are more common in patients who have chronic hemolytic states (with increased conjugated bilirubin in bile), liver cirrhosis, Gilbert’s syndrome, or cystic fibrosis. Gallbladder stones in patients with ileal diseases, ileal resection, or ileal bypass generally are also black pigment stones. Enterohepatic recycling of bilirubin in ileal disease states contributes to their pathogenesis. Brown pigment stones are composed of calcium salts of unconjugated biliru-bin with varying amounts of cholesterol and protein. They are caused by the presence of increased amounts of unconjugated, insoluble bilirubin in bile that precipitates to form stones. Deconjugation of an excess of soluble bilirubin mono- and diglucuronides may be mediated by endogenous β-glucuronidase but may also occur by spontaneous hydrolysis. Sometimes, the enzyme is also produced when bile is chronically infected by bacteria, and such stones are brown. Pigment stone formation is especially prominent in Asians and is often associated associated with infections in the gallbladder and biliary tree .[25]

2.4 Complications of the cholelithiasis disease

There are three following groups of complications of the cholelithiasis : mechnical , infectious and degenerative.

2.4.1 Mechanical complications

Hydrops

Obstruction of the cystic duct by an impacted stone can result in hydrops , in which the gallbladder becomes filled with a clear or whitish mucoid material. The hydrops appears sudden, usually after biliary colic. There is no pain but only a round , elastic and mobile mass in the right upper quadrant can be observed.

Biliary Fistulas

May be : cholecysto-choledochal and cholecystoenteric .

Cholecysto-choledochal fistula is a consequence of Mirizzi Syndrom. It's definition include impaction of a stone in the neck of the gallbladder , mechanical obstruction the of the common hepatic duct by the stone, and intermittent or constant jaundice. (Figure 6)

Figure 6 :

Cholecystoenteric fistula , If the acutly inflamed gallbladder becomes adherent to adjacent stomach, duodenum, or colon. And necrosis develops , perforation may occur into the lumen of the gut wwith further formation of the cholecystoenteric fistula .

Gallstone Ileus

If the stone is large enough, it may become obstacle in a portion of the gastrointestinal tract and cause a mechanical small bowel obstrucion. This condition called gallstones ileus , it's relatively rare. Gallstone ileus in the level of doudenoum is named "Bouveret's Syndrome"

Secondary choledocholithiasis

Is a consequence of the gallbladder stones migration in the CBD through the dilated cystic duct. There are three main variants og evolution of the common duct stones:

Up to 50% CBD stones remain asymptomatic.

Stones pass through CBD and sphincter of Oddi and produce simple biliary colic or pancreatitis.

Gallstones , transversing duct , often prevented from reaching the duodenum by narrowing in the Vater's ampulla and my cause CBD obstracion . [27,28,29]

2.4.2 Infetion complications

Cholangitis

Presents an inflammation of the bile ducts. There are 2 main causes: bacterial infection and block to flow of bile, which can be partial, or less commonly complete.

The predominant organisms in bile (in decreasing frequency) are E.coli , Klebsiella , Pseudomonas , Proteus and other anaerobes. The symptoms of cholangitis (sometimes referred to as Charcot's triad) are pain (biliary colic), jaundice , chills and fever.

Acute cholecystitis

Cholecystitis is defined as inflammation of the gallbladder that occurs most commonly because of an obstruction of the cystic duct from cholelithiasis. Ninety percent of cases involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% of cases representing acalculous cholecystitis.

Risk factors for cholecystitis mirror those for cholelithiasis and include increasing age, female sex, certain ethnic groups, obesity or rapid weight loss, drugs, and pregnancy. Although bile cultures are positive for bacteria in 50-75% of cases, bacterial proliferation may be a result of cholecystitis and not the precipitating factor.

Acalculous cholecystitis is related to conditions associated with biliary stasis, including debilitation, major surgery, severe trauma, sepsis, long-term total parenteral nutrition (TPN), and prolonged fasting. Other causes of acalculous cholecystitis include cardiac events; sickle cell disease; Salmonella infections; diabetes mellitus; and cytomegalovirus, cryptosporidiosis, or microsporidiosis infections in patients with AIDS.

Uncomplicated cholecystitis has an excellent prognosis, with a very low mortality rate. Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. Some 25-30% of patients either require surgery or develop some complication. [27,28,29]

2.4.3 Degenerative complications

Carcinoma Of The Gallbladder

The cholellithiasis must be considered as precancerous disease. Carcinoma of the gallbladder is associated with gallstones in 90% of cases, and the risk of malignant degeneration correlates with the length of time gallstones have been present. [27,28,29]

2.4.4 Mechanical Jaundice

Obstructive (mechanical) jaundice is a condition in which there is blockage of the flow of bile out of the liver. This results in redirection of excess bile and its by-products into the blood, and bile excretion from the body is incomplete. Bile contains many by-products, one of which is bilirubin, a pigment derived from dead red blood cells. Bilirubin is yellow, and this gives the characteristic yellow appearance of jaundice in the skin, eyes, and mucous membranes (see Figure 7). Symptoms of obstructive jaundice include yellow eyes and skin, abdominal pain, and fever. So Any type of obstruction that blocks the flow of bile from the liver can cause obstructive jaundice. Most commonly, gallstones create the blockage. [30,31]

Figure 7.

2.5 Clinical and Laboratory data of mechanical jaundice due to cholelithiasis

bilirubin: it doesn't matter the cause of cholestasis because it's almost always lead to elevation of the serum bilirubin values especially direct. But,the degree of hyperbilirubinemia cannot help reliably distinguish between the causes of obstruction.

So we have to take in consideration which type of bilirubin is elevated direct or indirect bilirubin. In the early stages of obstruction and with incomplete or interrupted obstruction, bilirubin levels may only be mildly elevated. Initially, an increase in the conjugated bilirubin level occurs without affecting the unconjugated bilirubin level because obstruction of the Common Bile Duct inhibits excretion of the conjugated bilirubin inside the duodenum. Direct bilirubin that does reach the intestine is deconjugated by intestinal bacteria. Indirect bilirubin, is different from the conjugated form, it easily crosses the intestinal epithelial barrier into the blood. It accumulates in the blood because the uptake mechanism and the hepatic cells are overburdened by bilirubin that has already been conjugated but cannot be excreted. Therefore, indirect bilirubin levels rise even in persons with obstructive jaundice. [32,33,34]

Serum transaminases: Levels of these are usually only moderately elevated in patients with cholestasis but it can be markedly increased, especially if cholangitis is present.

Usually, (AST) levels are not elevated except if a secondary acute parenchymal damage is present. When the elevations occur, they are usually only mild to moderate (< 10 times the upper reference limit). Anyway , when extra-hepatic obstruction occurs acutely, AST values may quickly increase to more than 10 times the normal value, and then they fall after approximately 72 h. With time and progressive hepato-cyte damage caused by distended biliary ductules, an increase in AST levels may be seen . A 3-fold or more increase in ALT strongly suggests pancreatitis. [32,33,34]

Alkaline phosphatase (ALP): A membrane-bound enzyme localized to the bile canalicular pole of hepatocytes, ALP is markedly increase in patients with biliary obstruction. Anyway , high levels of this enzyme are not specific to gall stones . To know whether the enzyme is likely to be of hepatic origin, measure gamma-glutamyl transpeptidase (GGT) or 5-prime-nucleotidase. These values tend to parallel the ALP levels in patients with liver disease. GGT is used most commonly. While it is part of the normal evaluation of biliary obstruction, the degree of inceasing of ALP cannot be used to reliably discriminate between extrahepatic and intrahepatic causes of biliary obstruction.

Extrahepatic obstruction: ALP levels are elevated in nearly 100% of patients, except in some cases of incomplete or intermittent obstruction. Values are usually greater than 3 times the upper limit of the reference range, and in most typical cases, they exceed 5 times the upper limit. An elevation less than 3 times the upper limit is evidence against complete extrahepatic obstruction. [32,33,34]

GGT: These values of the GGt will increase in case of blocking of the biliary tract . Levels parallel the levels of ALP and 5-prime-nucleotidase in conditions associated with cholestasis. The extreme sensitivity of GGT, as opposed to ALP, limits its usefulness; however, the level helps distinguish hepatobiliary disease as the cause of an isolated rise in ALP.

Prothrombin time (PT): This may be prolonged due to malabsorption of vit.K. stabilizing of the PT by parenteral administration of vit.K may help distinguish hepatocellular failure from Gall stone .

Hepatitis serology: Because differentiating viral hepatitis from extrahepatic obstructive causes may be difficult, include serologic assays for acute viral hepatitis in the investigation of all patients with cholestasis.

Antimitochondrial antibody: The presence it , in high titers, is indicative of PBC. They will not be in patients with mechanical biliary obstruction or PSC.

Urine bilirubin: Urine bilirubin normally is absent. When it is appear that's mean only direct bilirubin is passed into the urine. This may be shown changing the color of the urine to dark in patients with obstructive jaundice or jaundice due to hepatocellular injury. Anyway , reagent strips are very sensitive to bilirubin, detecting as little as 0.05 mg/dL. Thus , urine bilirubin can be seen even in the absence of hyperbilirubinemia or clinical jaundice. [32]

2.6 Diagnosis of Gallstones

Abdominal Radiography. Althought supine and upright abdominal radiographs are essential in the early evaluation of patients with an acute abdomen , their usefulness is limited in patients with cholelithiasis. Visualization of gall stones on plain abdominal radiographs is possible only in the 20% of patients whose stones are grossly clacified. So the important role has contrasted x-ray examinations.

Oral Cholecystography. This test is based on the escretion of contrast by the liver into bile with gallbladder visualization after reabsorption of water and solutes and bile concentration. Alhough the accuracy for oral cholecystography is high, several important conditions lead to unsatisfactory examination, including malabsorption, diarrea, jaundice or hepatic dysfunction.

Cholecysto-Cholangiography. It has an advantage , because allow visualization of CBD as well as gllbladder . Nonopacification is a highly reliabic indication of gallbladder stone disease.

Endoscopic Retrograde CholangioPancreatography ERCP. It is involves cannulating the sphinctir of Oddi under direct vision through a side-viewing duodenoscope. It usuallt the preferred method of examination of biliary tree in patients with presumed choledocholelithiasis.

Figure 8

Percutaneous Transhepatic Cholangiography. It's performed by passing a fine needle through skin and righ hepatic lobe into the lumen of bile duct. Water soluble contrast material is injected, and x-ray films are taken.

Intraoperative Cholangiography. In most instances, his is performed by the placing of a small catheter through the cystic duct and instilling 10 to 20 ml of water soluble contrast.

Fistulo-Cholangiography. Is made in the posoperative periof with instilling of contrast through tube, placed in the CBD during surgery.

Abdominal Ultrasonography. Is the preferred test for evaluating patients with suspected cholelithiasis or cholecysitis. Although abdominal ultrasonography is most useful in identifiying gall stones, it may also facilitate the diagnosis of cholecystitis. Diagnosis accuracy and sensitivity for cholelithiasis exceeds 95%. Information obtained from ultrasonography includes size and shape of the gallbladder, gallbladder wall thickness, and the presence of pericholecystic fluid collectons.

Hepatobiliary Scintigraphy. With 99mTc provides information on tha passability of bile ducts, including the cysic duct.

CT Scan. More expensive and less sensitive than ultrasonography for detecting gallbladder stones, but superior for demonstrating stones in the distal CBD.

[27 ,28, 29]

2.7 Treatment

2.7.1 Approach Considerations

The treatment of gallstones depends on the level of the disease. Ideally, interventions in the lithogenic state could inhibit gallstone formation, although, currently, this option is limited to a few special circumstances. Asymptomatic gallstones may be managed expectantly.

When the gallstones started to be symptomatic, surgical intervention with cholecystectomy is usually indicated, although, in some cases, medical treatment may be considered. In uncomplicated cholelithiasis with biliary colic, medical management may be a useful alternative to cholecystectomy in selected patients, particularly those for whom surgery is a high risk. Medical treatment, except pain control, is not initiated in the ED.

Medical treatments for gallstones, used alone or in combination, include the following:

Oral bile salt therapy (ursodeoxycholic acid)

Contact dissolution

Extracorporeal shockwave lithotripsy

Medical management is more effective in patients with good gallbladder function who have small stones < 1 cm with a high cholesterol content. Bile salt therapy may be required for more than 6 months and has a success rate 50%> .

2.7.2 Treatment of Asymptomatic Cholelithiasis

Treatment of cholelithiasis with out symptoms by surgery without medically complicating diseases is discouraged. The risk of complications arising from interventions is higher than the risk of symptomatic disease.

Persons with DM and women in pregnancy should have to be monitored to determine if they become symptomatic or develop complications.

However, cholecystectomy for asymptomatic gallstones may be offered for those patients:

stones 2 cm < in size

Patients with nonfunctional or calcified (porcelain) gallbladder observed on imaging studies and who are at high risk of gallbladder carcinoma

Pressence of spinal cord injuries or sensory neuropathies affecting the abdomen

pressence SCanemia in whom the distinction between painful crisis and cholecystitis may be difficult

Patients with risk factors for complications of cholelithiasis may be presented elective cholecystectomy, even if the patients withour symptoms of cholelithiasis. These groups include people with specific conditions such :

Cirrhosis

Portal HTNs

Children

Transplant candidates

Diabetes with minor symptoms

Patients with a calcified or porcelain gallbladder should consider elective cholecystectomy due to the possibly increased risk of carcinoma (25%). Refer to a surgeon for removal as an outpatient procedure.

2.7.3 Medical dissolution of the Stones

Ursodeoxycholic acid – ursodiol- is a gallstone dissolution drug . In humans , long-term administration of ursodeoxycholic acid decrease cholesterol saturation of bile, both by decreasing liver cholesterol secretion and by decreasing the cleaner effect of bile salts in the gallbladder Desaturation of bile prevents crystals from forming and, in fact, may allow gradual extraction of cholesterol from existing stones.

In patients with established cholesterol gallstones, treatment with ursodeoxycholic acid at a dose of 8-10 mg/kg/d PO divided bid/tid may result in gradual gallstone dissolution. This intervention typically requires 6-18 months and is successful only with small, purely cholesterol stones. Patients remain at risk for gallstone complications until dissolution is completed. The recurrence rate is 50% within 5 years. Moreover, after discontinuation of treatment, most patients form new gallstones over the subsequent 5-10 years.

2.7.4 Management of Patient with Symptomatic Cholelithiasis

In patients with symptomatic gallstones, we should look for the options for operative and non-operative intervention , emergency physicians should refer patients to their primary care provider and surgical consultant for outpatient follow-up.

Cholecystectomy

Removal of the gallbladder is generally indicated in patients who had previous symptoms or complications of cholelithiasis, except of the patient's age and general health make the risk of surgery contraindicated . In some cases of gallbladder empyema, temporary drainage of pus from the gallbladder -cholecystostomy- may be done to allow stabilization and to permit later cholecystectomy under elective circumstances.

In patients with gallbladder stones who are suspected to have concurrent common bile duct stones, the surgeon can perform intraoperative cholangiography at the time of cholecystectomy. The common bile duct can be explored using a choledochoscope. If common duct stones are found, they can usually be extracted intraoperatively. Alternatively, the surgeon can create a fistula between the distal bile duct and the adjacent duodenum (choledochoduodenostomy), allowing stones to pass harmlessly into the intestine.

Open vs laparoscopic cholecystectomy

 Laparoscopic cholecystectomy was the preface of the minimally invasive revolution, which has affected all areas of modern surgical practice. In our days , open cholecystectomy is mainly reserved for special situations. [16,17]

The traditional open approach to cholecystectomy employed a large, right subcostal incision. In contrast, laparoscopic cholecystectomy employs 4 very small incisions. Recovery time and postoperative pain are diminished markedly by the laparoscopic approach.

Currently, laparoscopic cholecystectomy is commonly performed in an outpatient setting. By reducing inpatient stay and time lost from work, the laparoscopic approach has also reduced the cost of cholecystectomy.[18]

In its guidelines for the clinical application of laparoscopic biliary tract surgery, the Society of American Gastrointestinal and Endoscopic Surgeons states that patients with symptomatic cholelithiasis are eligible for laparoscopic surgery. Cholelithiasis patients whose laparoscopic cholecystectomy was uncomplicated may be sent home the same day if postoperative pain and nausea are well controlled. Patients older than 50 years may be at greater risk of readmission.[19]

During laparoscopic cholecystectomy, a surgeon must remoce stones that might escape through a perforated gallbladder. Conversion to an open procedure might be required in certain cases.

In patients in whom gallstones have been lost in the peritoneal cavity, the current recommendation is follow-up by US examinations for 12 months. Most of the complications (usually, abscess formation around the stone) occur within this time frame.

The most dangerous and morbid complication of cholecystectomy is damage to the common bile duct. Bile duct injuries increased in incidence with the advent of laparoscopic cholecystectomy, but the incidence of this complication has since declined as experience and training in minimally invasive surgery have improved.[20]

Routine cholangiography is only of minimal help in preventing common bile duct injury. However, good evidence indicates that it leads to intraoperative detection of such injuries.

Figure 9

Cholecystostomy

In patients who are critically ill with gallbladder empyema and sepsis, cholecystectomy can be treacherous. In this circumstance, the surgeon may elect to perform cholecystostomy, a minimal procedure involving placement of a drainage tube in the gallbladder. This usually results in clinical improvement. Once the patient stabilizes, definitive cholecystectomy can be performed under elective circumstances.

Cholecystostomy also can be performed in some cases by invasive radiologists under CT-scan guidance. This approach eliminates the need for anesthesia and is especially appealing in a patient who is clinically unstable.

Figure 10

Endoscopic sphincterotomy

If surgical removal of common bile duct stones is not immediately feasible, endoscopic retrograde sphincterotomy can be used. In this procedure, the endoscopist cannulates the bile duct via the papilla of Vater. Using an electrocautery sphincterotome, the endoscopist makes an incision measuring approximately 1 cm through the sphincter of Oddi and the intraduodenal portion of the common bile duct, creating an opening through which stones can be extracted.

Endoscopic retrograde sphincterotomy is especially useful in patients who are critically ill with ascending cholangitis caused by impaction of a gallstone in the ampulla of Vater. Other indications for the procedure are as follows:

Removal of common bile duct stones inadvertently left behind during previous cholecystectomy

Preoperative clearing of stones from the common bile duct to eliminate the need for intraoperative common bile duct exploration, especially in situations where the surgeon's expertise in laparoscopic bile duct exploration is limited or the patient's anesthesia risk is high

Preventing recurrence of acute gallstone pancreatitis or other complications of choledocholithiasis in patients who are too sick at present to undergo elective cholecystectomy or whose long-term prognosis is poor

Intraoperative endoscopic sphincterotomy (IOES) during laparoscopic cholecystectomy has been suggested as an alternative treatment to preoperative endoscopic sphincterotomy (POES) followed by laparoscopic cholecystectomy; this is because IOES is as effective and safe as POES and results in a significantly shorter hospital stay. [21]

Endoscopic Retrograde Cholangiopancreatography

ERCP can be used both to diagnose and treat conditions in the liver, gallbladder, bile ducts and pancreas. It involves using an endoscope, which is a thin, flexible telescope, with a tiny camera and light on the end. This is inserted through the mouth, down the throat into the stomach and allows doctors to inject dye through the tube to help the area to show up more clearly on the X-ray pictures (cholangiopancreatography) that are taken of the pancreatic and bile ducts.

As well as helping to diagnose conditions, ERCP can be used to treat problems such as gallstones, narrowings and tumours and can also be used to take biopsies. You will be asked to avoid food or drink for a period of time before the procedure and be given a sedative as well as local anaesthetic to numb the back of your throat. The procedure normally takes between thirty minutes and an hour to complete.

2.7.5 Prevention of Gallstones

Ursodeoxycholic acid treatment can prevent gallstone formation. This has been demonstrated in the setting of rapid weight loss caused by very low-calorie diets or by bariatric surgery, which are associated with a high risk of new cholesterol gallstones (20-30% within 4 mo). Administration of ursodeoxycholic acid at a dose of 600 mg daily for 16 weeks reduces the incidence of gallstones by 80% in this setting.

Recommending dietary changes of decreased fat intake is prudent; this may decrease the incidence of biliary colic attacks. However, it has not been shown to cause dissolution of stones.

2.7.6 Diet and Activity

Little evidence suggests that dietary composition affects the natural history of gallstone disease in humans. Obese patients who undertake aggressive weight-loss programs or undergo bariatric surgery are at risk to develop gallstones; short-term prophylaxis with ursodeoxycholic acid should be considered. Regular exercise may reduce the frequency of cholecystectomy.

2.7.7 Long-Term Monitoring

Following cholecystectomy, about 5-10% of patients develop chronic diarrhea. This is usually attributed to bile salts. The frequency of enterohepatic circulation of bile salts increases after the gallbladder is removed, resulting in more bile salt reaching the colon. In the colon, bile salts stimulate mucosal secretion of salt and water. Postcholecystectomy diarrhea is usually mild and can be managed with occasional use of over-the-counter antidiarrheal agents, such as loperamide. More frequent diarrhea can be treated with daily administration of a bile acid-binding resin (eg, colestipol, cholestyramine, colesevelam).

Following cholecystectomy, a few individuals experience recurrent pain resembling biliary colic. The term postcholecystectomy syndrome is sometimes used for this condition. Many patients with postcholecystectomy syndrome have long-term functional pain that was originally misdiagnosed as being of biliary origin. [22] Persistence of symptoms following cholecystectomy is unsurprising. Diagnostic and therapeutic efforts should be directed at the true cause.

Some individuals with postcholecystectomy syndrome have an underlying motility disorder of the sphincter of Oddi, termed biliary dyskinesia, in which the sphincter fails to relax normally following ingestion of a meal. The diagnosis can be established in specialized centers by endoscopic biliary manometry. In established cases of biliary dyskinesia, endoscopic retrograde sphincterotomy is usually effective in relieving the symptoms.

3.Case Report

Patient C, 77 years old, resident of Chisinau city was hospitalized in aseptic surgery department of Municipal Clinical Hospital nr.1 in emergency with the following compliance complaints: fever 39-40⁰C, shiver, pain in the right hypochondrium, jaundice of the teguments and hyperchrome urine. He is considered ill for 60 days, when appeared the pain in the right hypocondrium, with fever and intermitent shiver. In the ambulatory is performed abdominal CT where was suspected mechanic jaundice with unidentified origin (lithiasis? or tumour?). The primary general medical examination revealed a medium gravity of the patient , poor jaundice of the teguments, conscious, active, HR – 65 beats per minute, BP 120/70 mmHg. Painless abdomen, no enlargement in the volume, with no irritation of the peritoneum. The liver had no palpable signs of enlargement, with no pain.

The primary laboratory examination reveals the followings: leucocytosis of 17,8×109 /l , with a weak shifting to the left of the leukocyte formula, speed of sedimentation of red blood cells – 23; biochemical examination – total bilirubin of 95 mcm/l (conjugated-50, free- 45), ALT – 92n/l, AST – 165n/l, urea – 9,2 , creatinine – 152.

So, was noticed an inflammatory reaction, which was confirmed laboratory. The specialist in internal medicine established a severe cardiac disease: Ischemic cardiomyopathy. Aggravated angina pectoris, II functional class. Chronic heart failure II (NYHA).

Abdominal CT revealed the followings: tomographic data of air in the biliary pathways figure 12 , gallstones figure11 . Choledocholithiasis, Mechanic block of the main billiary way. Hepatic hemangioma S-V. Hypodense mass in S-VIII. Tissular inclusions at the level of the biliar ducts in the hepatic hil (neoplastic process is not excluded – Klatschin tumour). Parapancreatic abcess. Intra- and extrahepatic biliar ducts are enlarged up to 25 mm.

Figure 11.

Figure 12.

Due to the gathered information from the clinical examination, history of the disease as well the laboratory and instrumental examinations was established the diagnosis of: Cholelithiasis disease. Choledocholithiasis. Mechanical jaundice, Acute purulent cholangitis, Ischemic cardiopathy, Aggravated angina pectoris, II functional class, And Chronic heart failure II (NYHA). By council was decided to prepare the patient for the urgent postponed surgery considering the basic disease, cardiac comorbidity and the patient’s age.

The surgery was performed under general anesthesia with myorelaxation: right subcostal laparotomy. Anterograde cholecystectomy. Disrupture of the pathologycal connection between the cholecyst and choledocho and choledocho-lythotomia , „T” type drainage of the main biliar duct. Drainage of the peritoneal cavity.

During the exploration of the abdomainal cavity was established the followings: cholestatic liver and inflamatory hyperplastic process which involves the colecyst, hepatoduodenal ligament, duodenum and the hepatic flexure of the colon. Enlargement of the choledocho up to 12 mm and closed adhered to the cholecyst. Many stones were palpatory discovered in the main bile duct. A fistula between the choledoco and cholecyst was observed during the preparation – Mirizzi syndrome III type by Csendes. A stone blocked completely the passage through the choledoch at the level of this fistula. The stones and pus were eliminated from the main bile duct during the rupture of the pathological connection. Toilet of the biliary ducts. The proximal and distal permiability of the choledocho was preserved. „T” type drainage Kehr in the main bile way was installed.

Postoperative period was favorable. The post-operator treatment was composed from: antibiotherapy, analgesics, detoxification infusional therapy and symptomatics. Laboratory tests in the 6s day after surgery were following: Hb – 119; Er – 3,8; leukocytes 8,2; bilirubin 17,5; AlAT – 30; AsAT – 42. The patient was discharged from hospital in the 11-th day after surgery with the tube into the main bile duct.

The drenage from the choledocho was removed after 30 days from surgery. The fistulography, which was done previously, point to normal passage of the bile through the biliary ways figure13 .

Figure 13.

As a conclusion of the case we observed that :

The clinical manifestations of the mechanical jaundice due to the stone in the main bile duct are often associated with inflammation of the biliary tract with development of acute cholangitis which is confirmed by tha laboratory Data and an air which is accumulated in the way of the biliary tract which can be seen by CT.

The curative management of tha patient with mechanical jaundice due to stone in the main bile duct is depend on the time which was passed considering that the patient is sick with this disease and also depend on the general status of the patient and the comorbidities that he may suffer from.

Mirizzi syndrome in case of mechanical jaundice is often appear as a result of blocking of the Hartman bile Cyst with a stone that lead to inflammation.

All the time after extraction of the stone from the common bile duct we must insert an drainage tube into the biliary tract .

4.Conclusions

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Author , Jennifer Lynn Bonheur, MD Attending Physician, Division of Gastroenterology, Lenox Hill Hospital

Peter F Ells, MD Associate Professor, Division of Gastroenterology-Hepatology, Albany Medical Center

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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