(A) the cause of the disease

On the basis of biliary obstruction, the disease is characterized by a series of serious complications, such as acute suppurative infection of biliary tract and suppurative infection, biliary hypertension, and a large amount of bacterial endotoxin entering the blood, which leads to multi-bacteria, toxic, anaerobic and aerobic mixed sepsis, endotoxemia, azotemia, hyperbilirubinemia, toxic hepatitis, septic shock and multiple organ failure, among which septic shock, biliary liver abscess, septic septicemia and multiple organ failure are the three main causes of death.

1. Bacterial infection of bile duct

The close connection between Oddi sphincter at the distal end of normal bile duct and hepatocytes on both sides of proximal capillary bile duct constitutes anatomical barriers between intestine and bile duct, bile flow and blood flow respectively. Physiological bile flow prevents bacteria from remaining on bile duct mucosa; At physiological concentration, bile acid salt can inhibit the growth of intestinal flora; Liver kupffer cells and immunoglobulin can form an immune defense barrier, so there are no bacteria in normal bile. When the biliary system is diseased (such as stones, ascaris, stenosis, tumor and cholangiography, etc.). ), can cause a sharp increase in the number of bacteria in bile, and excessive reproduction in the biliary tract, forming persistent bacterial cholangitis. At present, it is believed that bacteria can also enter the biliary tract through lymphatic vessels, portal vein or hepatic artery. The positive rate of bile bacteria culture during AOSC operation can be as high as 95.64% ~ 100%. When the obstructive factors of acute suppurative biliary tract infection are removed by surgery and the clinical cure is confirmed, bacteria still exist in bile for a long time. At present, the cause and mechanism of bile purification are not very clear. The vast majority of bacteria are enterogenous bacteria, and aerobic gram-negative bacilli have the highest positive rate, among which Escherichia coli is the most common. Escherichia coli, Escherichia coli, aerogenes, Pseudomonas aeruginosa, Proteus and Klebsiella are also visible. Gram-positive cocci are mostly streptococcus faecalis, pneumococcus and staphylococcus. With the improvement of culture and separation technology, the detection rate of anaerobic bacteria in bile increased significantly, and the positive rate reached 40% ~ 82%. The strain is also consistent with the intestinal flora, mainly bacteroides, of which Bacteroides fragilis is the most common. Mixed infection of aerobic and anaerobic strains is the bacteriological feature of AFC. A large number of highly toxic toxins produced by bacteria are an important cause of serious systemic infection, shock and multiple organ failure. Bacteria is a necessary factor of acute cholangitis, but not all patients with bacterial cholangitis will get sick. Recently, many clinical and experimental results show that the severity and mortality of sepsis do not depend entirely on the types and virulence of invasive microorganisms.

2. Bile duct obstruction and elevated bile pressure

There are many reasons for biliary obstruction. The common causes in China are: calculus, parasitic infection (ascaris lumbricoides, Clonorchis sinensis) and fibrous stenosis. Other less common causes of obstruction are: anastomotic stricture after cholangioenterostomy, iatrogenic traumatic stricture of bile duct, congenital cystic dilatation of intrahepatic and extrahepatic bile duct, congenital pancreaticobiliary confluence malformation, duodenal diverticulum, primary sclerosing cholangitis, and various biliary instruments. In western countries, secondary bile duct stones and Vater's periampullary tumors are more common. Intraductal hypertension caused by biliary obstruction is the main factor for the occurrence, development and deterioration of AFC. Animal experiments show that if the dog's common bile duct is ligated and Escherichia coli is injected into the bile duct, the dog will have a high fever within 24 hours and die within 2 days. If the same amount of Escherichia coli is injected into the bile duct without ligation, animals will not have symptoms. The experiment also proved that when the internal pressure of bile duct is >: 2.9kPa(30cmH2O), bacteria and their toxins can flow back into the blood, resulting in clinical infection symptoms. The more serious the obstruction, the higher the pressure in the catheter, and the more significant the incidence of bacteremia and endotoxemia. Under the continuous high pressure of bile duct, the destruction of bile-blood barrier is the premise for bacteria in bile duct to return to blood to form bacteremia. By retrograde injection of various tracer substances into bile duct, with the help of light microscope, electron microscope and radionuclide technology, it has been shown that the bile circulation system is in a countercurrent state under high bile duct pressure.

① Reflux through hepatocytes: When biliary obstruction and cholestasis occur, hepatocytes can suck bile components into the cytoplasm of hepatocytes through phagocytosis and transport them to the Dissai space.

② Reflux through hepatocyte bypass, clinical observation also found that when many AFC patients were undergoing bile duct decompression and high-pressure bile discharge, their blood pressure increased rapidly and their pulse rate slowed down, which was obviously difficult to be reasonably explained by septic shock alone, indicating that there were neurological factors involved.

3. Endotoxemia and the role of cytokines

Endotoxin is a lipopolysaccharide component in the cell wall of gram-negative bacteria, and its toxicity exists in lipid A. Endotoxin has complex physiological activities and plays an important role in the pathogenesis of AOSC.

Endotoxin (1) directly damages cells and agglutinates leukocytes and platelets. Endotoxin mainly damages platelet membrane, but also damages vascular intima, which makes fibrin deposit on vascular intima and increases vascular resistance. In addition, the coagulation mechanism is seriously hindered, and thromboxane can be released after platelets are destroyed, which strengthens vasoactive substances such as catecholamine and causes peripheral blood vessel contraction and pulmonary circulation changes. Platelet agglutination leads to microcirculation thrombosis, blocking capillaries and increasing capillary permeability. This microvascular disorder can spread all over important organs of the whole body, causing focal necrosis and dysfunction of lung, kidney and liver.

(2) Endotoxin stimulates the macrophage system to produce a polypeptide substance, namely tumor necrosis factor (TNF), and a series of harmful effects involving various mediators occur under the action of TNF:

①TNF activates polymorphonuclear leukocytes to form microthrombus, stimulates vascular endothelial cells to release interleukin and platelet activating factor, makes platelets agglutinate, and promotes disseminated intravascular coagulation (DIC).

② Activated multinucleated leukocytes release a lot of oxygen free radicals and various proteases. The former damages neutrophils and vascular endothelial cells and increases intravascular coagulation, but it also damages tissue cell membrane, mitochondrial membrane and lysosome, seriously damaging cell structure and biological function. The latter damages vascular endothelial cells and fibronectin, releases bradykinin, increases vasodilation and permeability, causes tissue edema and reduces blood volume.

③TNF activates arachidonic acid through the catalytic action of cyclooxygenase to produce thromboxane and prostaglandin. The former causes vasoconstriction and platelet aggregation, while the latter increases vasodilation and permeability.

④TNF also makes arachidonic acid produce leukotrienes with histamine effect through lipoxygenase, which aggravates vascular permeability. In the process of shock, the tissue is seriously ischemic and hypoxic, and its structure is destroyed, releasing many toxic humoral factors, such as histamine, 5- hydroxytryptamine, oxygen free radicals, various proteolytic enzymes, myocardial inhibitory factors, prostaglandins, endopeptides, etc., which further aggravate the tissue damage and form bacterial toxins. Start and activate the vicious circle of mutual promotion of various body fluids. Exotoxin produced by enteropositive cocci also plays a role in contracting blood vessels, dissolving blood cells and agglutinating platelets.

(3) Endotoxin activates the complement reaction: after the complement is over-activated and consumed in large quantities, it loses its biological effects, including the functions of chemotaxis, conditioning and dissolution of bacteria by inflammatory cells, thus aggravating infection and spread. The degradation products of complement stimulate basophils and mast cells to release histamine, which aggravates the damage of vascular wall.

(4) Production of immune complex: Endotoxin produced by some bacteria has antigenicity, and the immune complex formed by its interaction with antibodies is deposited on endothelial cells of various organs, which can cause strong immune response, cause cell degeneration and necrosis, and aggravate multiple organ damage.

(5) Damage of oxygen free radicals to the body: The basic pathological processes of AFC (biliary obstruction, infection, endotoxic shock and organ failure, tissue ischemia/reperfusion) can cause the production of oxygen free radicals and peroxides. The lipid peroxidation of oxygen free radicals can change the fluidity of biofilm, affect the activities of various enzymes embedded in biofilm, change the ion channels of biofilm and cause a large number of extracellular calcium ions to flow in. It causes the destruction of mitochondria and lysosomes, and oxygen free radicals can also catalyze membrane phospholipids to release arachidonic acid and platelet activating factor, which has a chemotactic effect on white blood cells, thus causing a large number of white blood cells to accumulate, aggravating inflammatory reactions, and these white blood cells produce a large number of oxygen free radicals, forming a vicious circle, causing serious damage to body tissues and hepatobiliary systems.

4. Hyperbilirubinemia

The pressure of bile secretion in normal liver is 3. 1kPa(32cmH2O). When the pressure of bile duct exceeds about 3.43kPa(35cmH2O), the epithelial cells of hepatic capillary bile duct are necrotic and ruptured, and bile flows back into the blood through hepatic sinuses or lymphatic vessels, that is, bile reflux, and a large amount of bound and unbound bilirubin in bile enters the blood circulation, which mainly causes hyperbilirubinemia due to the increase of bound bilirubin. If bile duct hypertension and severe suppurative infection are not controlled in time, the damage to liver tissue will be more serious, the ability of liver cells to absorb unbound bilirubin will drop sharply, and unbound bilirubin will increase significantly. Hyperbilirubinemia is a factor that can not be ignored in aggravating AFC, and its harm is not completely clear. What is certain is that:

(1) The progressive increase of bilirubin can lead to the deposition of bilirubin in various organs, forming bile thrombosis and affecting the functions of major organs.

② Bile acid can inhibit the growth of Escherichia coli in intestinal cavity and remove endotoxin. When obstructive jaundice occurs, bile acids in the intestine are deficient, Escherichia coli proliferates, and a large amount of endotoxin is released. The gastrointestinal mucosa of AFC is seriously damaged, which leads to the absorption and migration of bacteria and endotoxin to portal vein. In addition, with obstructive jaundice and biliary tract infection, the function of removing bacteria and toxins from hepatic reticuloendothelial system is weakened, and bacteria and toxins in portal vein easily enter systemic circulation, which aggravates the degree of biliary endotoxemia.

③ Absence of cholic acid in intestine makes fat-soluble vitamins unable to be absorbed, among which vitamin K is an essential component for liver to synthesize prothrombin, which can lead to disorder of coagulation mechanism.

5. Physical reaction

(1) Abnormal body reaction: Clinically, it is often noticed that the patient's bile duct suppurative infection during operation is not completely consistent with the severity of its clinical manifestations. It is often difficult to correct sepsis and improve the prognosis of patients only by taking anti-bacterial measures. The above phenomenon shows that factors other than pathogenic microorganisms must play a leading role in the pathogenesis of sepsis. In recent years, the accumulated clinical and animal experimental research data at the cellular and molecular levels reveal more and more clearly that the clinical and pathological manifestations of sepsis are the result of acute physiological disorder in vivo caused by the abnormal response of the host to various infectious and non-infectious injury factors. Organ and tissue damage and secondary infection caused by serious diseases are important initiating factors, but various endogenous media reactions caused by various injury drivers in the body are also very important in mediating sepsis and multiple organ dysfunction.

(2) Weakening of immune defense function: The damage of systemic and local immune defense system caused by this disease is an important factor affecting the deterioration of infection, and phagocytosis is the most important defense function in human body. Cooper cells on the wall of hepatic sinus account for 70% of the whole body macrophage system, that is, reticular endothelial system, which has a powerful function of removing macromolecules such as microorganisms, toxins and immune complexes. It is an important barrier to prevent these foreign bodies from entering the blood from the bile duct or from the blood into the bile duct. Bile duct obstruction, hypertension and infection can weaken the phagocytic function of Kupffer cells. The liver tissue of AFC can be severely inflamed and necrotic in the hepatic sinuses, and the structure and function of kupffer cells are even damaged by liver fibrosis, atrophy or biliary cirrhosis caused by repeated acute and chronic infections in the past. The opsonin and fibronectin in plasma are humoral mediators that promote phagocytosis of macrophage system. In the process of infection, their contents in blood decrease, which indirectly reflects the decline of immune function, and the cellular and humoral immune mechanisms of patients with obstructive jaundice are inhibited. The longer the jaundice deepens, the more serious the immune damage will be. Experiments have also proved that the cellular immune function of obstructive jaundice animals is impaired, mainly because the ability of T lymphocytes to recognize antigens is inhibited, which may be related to cell-mediated immune deficiency or the production of some inhibitory factors.

(2) Pathogenesis

The location and degree of the lesion are related to the location, scope, integrity, duration, bacterial virulence, patient's physique, nutritional status, complications and timely treatment.

Acute suppurative infection of bile duct, when the high pressure in bile duct can not be relieved in time, the inflammation will increase rapidly and spread to the surrounding liver tissue, causing suppurative hepatitis around all bile ducts near the obstruction, and then most tiny liver abscesses will be formed due to multiple focal necrosis and liquefaction. Hepatobiliary ducts at all levels can also directly enter the liver tissue due to severe degeneration, gangrene or perforation of the wall, accelerating the development of hepatitis and abscess formation.

Micro-abscesses continue to develop, expand or fuse into abscesses of different sizes in the liver. Superficial patients often break into adjacent body cavities or tissues to form extrahepatic purulent infections or abscesses, such as subphrenic abscess, localized or diffuse purulent peritonitis, pericardial empyema, empyema, pleural-pulmonary-bronchial purulent fistula and abdominal abscess. Bile peritonitis caused by gangrene and perforation of extrahepatic bile duct or gallbladder caused by obstruction at the lower end of bile duct is also very common.

In the development of liver abscess, it can also corrode and damage the blood vessel wall (mostly portal vein or hepatic vein branch). If the abscess communicates with the bile duct, bile duct bleeding, bile duct wall erosion and ulcer will occur, and the damage of blood vessels is also one of the reasons for bile duct bleeding.

Bacteria, toxins and infectious substances in bile duct, such as gallstones, ascaris or eggs, can directly enter the blood circulation through bile duct-hepatic sinus fistula, bile duct-hepatic abscess-vascular fistula or bile duct-vascular fistula, causing severe endotoxemia, various septicemia and septic septicemia, and causing acute suppurative injury of multiple system organs. Common are acute suppurative pneumonia, lung abscess, interstitial pneumonia, pulmonary edema, nephritis and kidney. Pericarditis, splenitis, encephalitis, gastrointestinal mucosal congestion, erosion and bleeding. These serious systemic infectious injuries are the pathological basis leading to serious diseases, irreversible shock and multiple organ failure.

It should be pointed out that the pathological changes of liver and biliary tract in acute cholangitis and biliary sepsis are varied, but the gross and microscopic pathological changes of hepatobiliary system are not necessarily consistent with the severity of patients' clinical manifestations. There is no constant difference in the clinical manifestations of patients with biliary obstruction with or without purulent bile in the bile duct tree, and there is no obvious correlation between the pathological changes of the liver and the etiology, clinical manifestations and laboratory results of biliary obstruction.

There is no uniform classification for AOSC. In order to meet the actual needs of medical treatment, it can be classified according to pathological characteristics, disease process and clinical manifestations.

1. Pathological classification

(1) Cholangitis due to common bile duct obstruction: AFC mainly occurs in common bile duct obstruction, accounting for more than 80%, and the pathological scope affects the whole biliary system. Bile hypertension and obstructive jaundice appeared earlier and developed rapidly, and soon became total bile cholangitis.

(2) Intrahepatic bile duct obstructive cholangitis: mainly cholangitis caused by intrahepatic bile duct stones combined with bile duct stenosis. Because the lesions are often confined to one leaf or one segment of the liver, although there is serious infection, there is no obvious abdominal pain, and jaundice is often rare. The clinical symptoms of this type of cholangitis are relatively hidden. At the same time, due to bile duct obstruction, infected lesions in the liver can not be smoothly drained, local bile ducts dilate, biliary hypertension soon appears, and the bile-blood barrier is destroyed.

(3) Pancreatic cholangitis: Acute biliary tract infection can lead to acute pancreatitis. On the contrary, when pancreatitis occurs, pancreatic juice flows back into bile duct, causing pancreatic cholangitis or cholecystitis. In this kind of patients, pancreatitis and cholangitis often coexist at the same time, which increases the complexity and severity of pathology.

(4) Bile reflux cholangitis: Recurrent reflux cholangitis can be caused after biliary-intestinal fistula or biliary-intestinal drainage, especially after choledochoduodenectomy, because intestinal contents and bacteria enter the biliary tract, especially when biliary obstruction occurs.

(5) Parasitic cholangitis: Most common clinical parasitic cholangitis is caused by biliary ascaris, accounting for about 8% ~ 12% of biliary diseases. After the ascaris enters the biliary tract, the ascaris stimulates the sphincter at the end of the common bile duct, and the patient has paroxysmal pain. Acute suppurative cholangitis can be caused by bacterial infection and obstruction caused by ascaris lumbricoides, and Clonorchis sinensis passes through the first branch. Parasitic in the hepatobiliary duct and gallbladder, causing biliary obstruction and infection can lead to acute cholangitis, severe cases can lead to obstructive jaundice and liver abscess, and acute cholangitis can also occur after hepatic echinococcosis breaks into the biliary tract, and severe biliary infection can cause toxic shock.

(6) Iatrogenic cholangitis: With the development of endoscopic technology and interventional therapy, corresponding operations such as PTC, PTCD, ERCP, EST, T-tube cholangiography, T-tube sinus cholangioscopy, etc. The incidence of postoperative acute cholangitis is increasing, especially in the case of biliary obstruction or infection.

2. Clinical classification

(1) fulminant type: some AFC can rapidly develop into septic shock and biliary septicemia, and then turn into disseminated intravascular coagulation (DIC) or multiple organ system failure (MODS). The pathological change of hepatobiliary system is acute cellulitis, and the patient quickly develops into a fatal complication.

(2) Recurrent type: such as piston-like obstruction or incomplete obstruction of bile duct caused by stones or ascaris lumbricoides, poor drainage of infected bile, and acute, subacute and chronic lesions of hepatobiliary system can appear alternately and continue to develop. Bile hypertension causes inflammation around the capillary bile duct and bile duct, focal necrosis and diffuse biliary liver abscess, and the infection can also spread to the larger internal and external bile duct walls, causing bile duct wall ulcers and full-thickness necrosis perforation, forming subphrenic or liver. Intrahepatic or perihepatic abscess may be a potential focus of purulent bacteria, which makes acute cholangitis recur many times. The vascular and bile duct fistula of the infected focus can lead to biliary tract infection and periodic massive bleeding.

(3) Delayed type: In the case of incomplete bile duct obstruction and chronic inflammation, inflammatory granuloma and fibrous healing appear on the bile duct wall, and then develop into pathological changes such as cicatricial bile duct stenosis, biliary cirrhosis and focal liver atrophy. These changes are usually combined with the hidden purulent lesions in the liver. With the gradual decompensation of liver function, the clinical course of acute suppurative cholangitis is prolonged, and eventually it develops into various irreversible pathological damages of the whole hepatobiliary system with poor prognosis.

(4) Diffuse type: AOSC infection becomes systemic sepsis. Due to the spread of infected blood, acute suppurative inflammation or abscess formation of liver, lung, kidney, spleen, meninges and other organs occurs, and multiple organs and systems fail under the repeated attack of acute suppurative cholangitis.

The above types can appear alternately or in combination in the onset of individual patients, and individual differences can occur in each attack due to different priorities, severity and pathological characteristics. Therefore, every time a patient visits a doctor, he should carry out individualized treatment according to the specific situation at that time.