cirrhosis
Introduction
Introduction to cirrhosis Hepatic cirrhosis (hepaticsclerosis) is a clinically common chronic progressive liver disease with diffuse liver damage caused by long-term or repeated action of one or more causes. Histopathologically, there are extensive hepatocyte necrosis, residual hepatocyte nodular regeneration, connective tissue hyperplasia and fibrous septum formation, leading to structural destruction of the hepatic lobule and formation of pseudolobules. The liver gradually deforms and becomes hard and develops into cirrhosis. Clinically, liver function damage and portal hypertension are the main manifestations, and there are multiple systems involved. In the advanced stage, complications such as upper gastrointestinal hemorrhage, hepatic encephalopathy and secondary infection often occur. basic knowledge The proportion of sickness: 0.007% Susceptible people: more common in men aged 20 to 50 Mode of infection: non-infectious Complications: hepatic encephalopathy shock jaundice
Cause
Cause of cirrhosis
There are many causes of cirrhosis, and the main causes are different in different regions. In Europe and America, alcoholic cirrhosis is the main cause. Hepatitis virus cirrhosis is more common in China, followed by schistosomiasis liver fibrosis, and alcoholic cirrhosis is increasing year by year. The study confirmed that the two causes have been applied to the liver successively or simultaneously, and are more likely to produce cirrhosis, such as schistosomiasis or long-term heavy drinkers with hepatitis B.
Disease factor (posthepatitic cirrhosis) (20%):
It refers to the development of viral hepatitis to the later stage of cirrhosis. It is known that hepatitis virus has types such as A, B, C, D, E, etc. In recent years, it is considered that hepatitis A and hepatitis E are not chronic, except for acute severe cases, it does not form. Cirrhosis of the liver, hepatitis B and C easily turn into chronic, ie chronic active hepatitis and cirrhosis.
In 1974, Shikatu reported that HBsAg (hepatitis B surface antigen) can be displayed by immunofluorescence. The cytoplasm containing HBsAg under the microscope is glassy, and the liver cell paste containing HBsAg can be dyed bright by Orecein staining. Orange-red, after years of preservation of liver cirrhosis specimens, this method can also display liver cells containing HBsAg, so that hepatitis B virus-induced cirrhosis has a reliable basis, 10% to 20% of hepatitis B patients are chronic Long-term HBsAg positive, intermittent or persistent abnormal liver function, continuous replication of hepatitis B virus in the liver can infiltrate lymphocytes in the liver, release a large number of cytokines and inflammatory mediators, degenerate liver cells, necrosis, lesions while removing the virus Such as repeated development, can form fibrous septa in the hepatic lobules, regenerate nodules to form cirrhosis, 68% of hepatitis C is a chronic process, 30% of chronic hepatitis C develops into cirrhosis, hepatitis D can and B Simultaneous infection or overlapping infection of hepatitis can slow the replication of hepatitis B virus, but often aggravates the activity of the lesion and accelerates the occurrence of cirrhosis.
Acute severe type of viral hepatitis, hepatocyte mass necrosis fusion, extending from the center of the small leaf to the portal area, causing the mesh stent to collapse, close together, forming a fibrous septum, and creating a bridging phenomenon from the center of the leaflet to the portal area, and forming a large Nodular cirrhosis, cirrhosis of chronic active hepatitis, marked inflammation and fibrosis in the portal area, forming a wide, irregular "active" fibrous septum, extending into the lobes and between the lobes, allowing adjacent Each leaflet is separated and broken by the fibrous septum. Although the liver structure is remodeled, it is not liver cirrhosis, but the stage of liver fibrosis. When inflammation spreads from the edge of the hepatic lobe to the center, it causes spotted necrosis and monocytes. Infiltration, the fibrous septum continues to expand to the center, dividing the hepatic lobules, and the regeneration of hepatocytes to form a regenerative nodule surrounded by connective tissue, which becomes cirrhosis. By the end of the lesion, inflammation and hepatocyte necrosis can completely disappear. However, there are many nodules of different sizes in the fibrous septum, and the nodules are multi-lobular, forming large nodular cirrhosis, such as mild hepatitis lesions, and the course of disease Slower, may be formed small nodular cirrhosis, mixed cirrhosis or cirrhosis obvious regenerative nodules (incomplete cirrhosis partition).
From viral hepatitis to cirrhosis, studies have shown that it has nothing to do with the amount of infectious antigen, but has a significant relationship with viral virulence and human immune status. Genetic factors are related to chronic tendency, and human leukocyte antigens HL-A1, HL-A8 Lack seems to be related, but further research is needed.
Alcoholic cirrhosis (15%):
The incidence of alcoholic cirrhosis in western countries is high, caused by alcohol abuse. In recent years, the consumption of alcohol in China has increased, and the incidence of fatty liver and alcoholic cirrhosis has also increased. According to statistics, the incidence of cirrhosis is proportional to the amount of alcohol consumed and the length of time. Drinking 80g of alcohol per day can cause an increase in serum alanine aminotransferase. Most people who have been drinking alcohol for several weeks to several months may develop fatty liver or alcoholic hepatitis. If you continue to drink a lot for more than 15 years, 75% of cirrhosis can occur. .
After the alcohol enters the liver cells, it is converted into acetaldehyde by the action of alcohol dehydrogenase and microsomal alcohol oxidase, and acetaldehyde is converted into acetic acid. The acetic acid converts the excessive amount of coenzyme I (NAD) into reduced coenzyme I (NADH). Thus, as NAD decreases and NADH increases, the ratio of the two decreases, the carboxylic acid cycle in the mitochondria is inhibited, the esterification of fatty acids increases, the triglyceride increases, the release of triacylglycerol in the liver decreases, and the NADH in the liver is excessive. It also promotes the synthesis of fatty acids, strengthens the body fat to form fatty acids, causes excessive triglyceride in the liver, exceeds the liver's processing capacity, and produces fatty liver. Long-term heavy drinking can further denature, necrosis and subsequent hepatocytes. Inflammation, alcoholic hepatitis occurs on the basis of fatty liver, microscopic degeneration of liver cells and polymorphonuclear leukocytes and mononuclear cell infiltration and bile duct hyperplasia in the portal area of Mallorys alcoholic hyalin Fibrous tissue hyperplasia, and finally the formation of small nodular cirrhosis, alcoholic cirrhosis of the lobular central vein can occur acute sclerosing hyaline necrosis Fibrosis and luminal occlusion aggravate portal hypertension, and the central fibrosis expands to the peripheral part, which can also form a "bridge" phenomenon with the portal area.
Infectious factors (parasitic cirrhosis) (15%):
For example, schistosomiasis or liver flukes live in the portal system, and the eggs are deposited in the liver with portal blood flow, causing small branch embolization of the portal vein. The eggs are larger than the diameter of the hepatic lobular portal vein input branch, so the embolism causes inflammation in the portal area. , granuloma and fibrous tissue hyperplasia, enlarge the portal area, destroy the hepatic lobular boundary plate, affect the hepatocytes at the edge of the lobule, and the hepatocyte regeneration nodules are not obvious, which may be related to the clogging of small branches of the portal vein and the lack of nutrient of hepatocytes. The portal vein is blocked, portal hypertension is obvious, there are significant esophageal varices and splenomegaly, adult cells cause cellular immune response and secrete toxins, which is the cause of intrahepatic granuloma formation. The eggs cause humoral immune response and produce antigen-antibody complexes. It may be the cause of inflammation and fibrosis in and around the portal vein of the liver. Parasitic cirrhosis is morphologically a regenerative nodule with no significant cirrhosis.
Toxic cirrhosis (10%):
Chemical damage to the liver can be divided into two categories: one is a direct poison to the liver, such as carbon tetrachloride, methotrexate, etc.; the other is an indirect poison of the liver, such poisons have nothing to do with the dose, Patients with specific qualities first cause allergic reactions and then cause liver damage. A small number of patients can cause cirrhosis, such as isonicotinyl, iproniazid, halothane, which is similar to post-hepatitis cirrhosis. Carbon tetrachloride is The direct poison of the liver, the damage to the liver is directly proportional to the size of the drug, causing diffuse fatty infiltration of the liver and necrosis of the lobular center. Carbon tetrachloride itself is not a toxic substance, and acts as a drug-metabolizing enzyme, such as P-450. The microsomal enzyme system removes one chlorine atom from carbon tetrachloride and forms chloroform, ie, chloroform, which becomes highly toxic to the drug metabolism enzyme system of the endoplasmic reticulum and microsomes of hepatocytes (generating trichloromethyl free radicals) And chlorine free radicals, causing lipid peroxidation and hepatocyte damage in hepatocyte biofilms. Due to the destruction of micro-structures in hepatocytes, the reduction of drug-metabolizing enzymes reduces the metabolism of carbon tetrachloride. The continued weak damage to the liver, patients after recovery, pluripotent liver function returned to normal, only repeated or prolonged exposure to carbon tetrachloride only large nodular cirrhosis occasionally occur.
Animal experiments repeatedly give rats carbon tetrachloride, so that drug accumulation can cause cirrhosis.
Methotrexate is an antifolate drug commonly used in the treatment of leukemia, lymphoma, psoriasis (psoriasis), etc. It has been reported to cause small nodular cirrhosis.
Biliary cirrhosis (15%):
The cause and pathogenesis of primary biliary cirrhosis (unclear biliary cirrhosis) is unclear and may be related to autoimmunity. Secondary biliary cirrhosis is caused by various causes of bile duct obstruction, including stones, tumors, benign stenosis. And external pressure and congenital for various reasons, the acquired bile duct occlusion, mostly caused by benign diseases, because malignant tumors mostly die before the patient develops cirrhosis.
Complete bile duct obstruction caused by various reasons, the course of disease can form cirrhosis within 3 to 12 months, the incidence rate is about 10% of such patients.
In the early stage of bile duct obstruction, the color of bile darkens, but it quickly becomes white. Due to cholestasis and bile duct dilatation, the pressure in the bile duct increases, bile secretion is inhibited, and bile can change from green to white, forming a so-called "white bile", microscope. It can be seen that the small bile duct in the portal area is highly dilated, and even the bile duct is ruptured. The bile overflow causes necrosis and inflammation in the portal area and the peripheral area of the hepatic lobules. The necrotic foci is filled with bile overflowing the bile duct to form a "biliary pool", which is a mechanical bile duct obstruction. One characteristic is that the lesion continues to progress, and the necrosis and inflammatory stimulation in the peripheral area proliferates the fibrous tissue in the portal area, and extends to form a fibrous septum between the small leaves. The fibrous septa of each portal area is connected to each other, and the hepatic lobules are segmented and incomplete. Separate cirrhosis, and post-hepatitis cirrhosis, alcoholic cirrhosis from the center to the portal area fibrous septum, but the lesions continue to develop, in the late stage, there may be fibrous septa and hepatocyte regeneration nodules in the portal area to the central area of the lobules And lose its characteristic performance, so that it is indistinguishable from other cirrhosis in pathological and clinical manifestations. Portal hypertension and ascites may occur.
The principle of biliary obstruction to form cirrhosis may be due to the compression of the bile duct and the extravasation of bile in the liver, the ischemic necrosis of the hepatocytes, the expansion of the fibrous tissue to the bile duct, and the dissemination of the lobes, and the formation of cirrhosis. Incomplete bile duct obstruction rarely develops into biliary cirrhosis.
It is known that bile duct infection is not a necessary condition for the formation of cirrhosis. It is reported that the development of complete bile duct obstruction without infection is more common in patients with biliary cirrhosis.
Circulatory disorder (congestive) cirrhosis (10%):
Chronic congestive heart failure caused by various heart diseases, constrictive pericarditis, etc., the liver is in a state of congestion and hypoxia for a long time, eventually forming cirrhosis, Budd-chiari syndrome is caused by chronic obstruction of hepatic vein caused by long-term liver congestion, Liver cirrhosis that is identical to cardiogenicity also occurs.
When the heart is insufficiency, due to the decrease of blood volume in the heart, the blood perfusion in the liver decreases, and the blood oxygen content in the margin of the hepatic lobules is higher. When flowing to the center of the hepatic lobules, the oxygen content is progressively reduced, and the cardiac dysfunction is accompanied by the central venous pressure. Increased, central vein and its surrounding hepatic sinus dilatation, congestion, compression of liver cells, hepatocyte degeneration, atrophy, and even hemorrhagic necrosis, hypoxia and necrosis can stimulate collagen hyperplasia, fibrosis, and even central venous sclerosis fibrosis, gradually From the center to the periphery, the cellulose of the adjacent leaflets are connected to each other, that is, the center-to-center fiber barrier, and the portal area is relatively less infringed, which is characteristic of circulatory cirrhosis, and the progress of portal fibrosis continues in the later stage. The continuous regeneration of the liver parenchyma and the recurrence of the bile duct eventually lose the characteristics of congestive cirrhosis. This type of cirrhosis is small nodular or incompletely divided cirrhosis in pathological morphology.
Malnutritional cirrhosis has long been considered to cause cirrhosis, but there has been no direct evidence. Animal experiments lack protein, and choline and vitamin diets can cause cirrhosis, but the lesions are reversible. And the lack of secondary changes in the blood vessels often found in patients with cirrhosis, some authors observed patients with malignant malnutrition (Kwashiorkor), found that their liver damage is fatty liver, does not occur cirrhosis, only children occasionally liver diffuse Sexual fibrosis, like cirrhosis, when given a protein-rich diet, the lesion can be reversed and the liver returns to normal, only in some cases may have mild fibrosis, so whether malnutrition can directly cause cirrhosis Certainly, most believe that nutritional disorders reduce the liver's resistance to other pathogenic factors, such as chronic specific or non-specific enteritis, in addition to causing digestion, absorption and malnutrition, the toxins produced by the pathogen in the intestine enter the liver through the portal vein, the liver can not Clear it, leading to degeneration and necrosis of hepatocytes to form cirrhosis, so it is recognized Malnutrition is an indirect cause of cirrhosis, as well as cirrhosis caused by small bowel bypass surgery. Some people think it is due to malnutrition, lack of basic amino acids or vitamin E, imbalance of sugar and protein in the diet and absorption from food. A large number of toxic peptides and choline acid toxic to the liver.
Other causes of cirrhosis (5%):
1, congenital enzyme deficiency: anti-1-trypsin deficiency (1-antitrypsin deficiency, AT1-AT), 1-AT is glycoprotein, is the main component of 1 globulin, the disease is autosomal dominant genetic disease Normal human serum sputum 1-AT is 2.3mg/ml, and the patient has only (0.2-0.4) mg/ml. The cause of cirrhosis caused by 1-AT deficiency is not known. It is speculated that 1-AT may have toxic effects on hepatocytes, or Hepatocytes are less tolerant to poisons, liver lesions are large nodules or small nodular cirrhosis, and glycoprotein deposits are found in hepatic cell rough endoplasmic reticulum (the site of 1-AT production). Inclusion bodies positive for PAS staining are meaningful for diagnosis.
Congenital galactose-1-phosphate-uridyl-transferase deficiency is a rare disease that causes galactosemia in children. Common babies have cirrhosis several months after birth, and the liver has Severe fat infiltration and active regeneration can form large nodular cirrhosis and ascites and portal hypertension. The pathogenesis is still unclear and may be related to the accumulation of 1-galactosamine in the liver.
Glycogen storage disease can occur in small nodular cirrhosis, especially type III, which is associated with starch-1,6-glycosidase deficiency.
2, metabolic cirrhosis: hepato-lenticular degeneration (hepato-lenticular degeneration), also known as wilson disease, is an autosomal recessive copper metabolism disorder caused by cirrhosis and brain degeneration, due to a large number of copper salts Deposition in the liver causes damage to the liver tissue, the liver usually shrinks, the texture is hard, and it is a large nodular cirrhosis.
Hemochromatosis: a rare metabolic disease, an autosomal recessive disorder. On the basis of genetic disorders, there is iron metabolism disorder, so that the small intestine absorbs too much iron. Iron deposits in the liver, pancreas, heart, kidney, The spleen, skin, etc. cause cell destruction, fibrous tissue hyperplasia and organ dysfunction, showing skin pigmentation, diabetes and cirrhosis.
3, hereditary hemorrhagic telangiectasia (hemorrhagic telangiectasia): autosomal dominant genetic disease, liver cirrhosis as part of this disease, a large number of expanded thin-walled capillaries can be seen in the fibrous septum of the liver.
Pancreatic fibrocystic disease is a systemic mucus secretion abnormality, which can cause liver fat infiltration, abnormal mucus obstructs the pancreatic duct, also causes bile duct obstruction, and forms biliary cirrhosis. In addition, congenital syphilis can also cause liver. hardening.
Pathogenesis
1, pathological process
There are many causes of cirrhosis, and its pathogenesis and pathogenesis are also different. Some have pathways through chronic hepatitis (such as viral hepatitis and toxic hepatitis); some have large vesicular hepatic steatosis pathways (such as alcoholic liver disease). Some; long-term intrahepatic, external cholestasis or hepatic venous return disorder, the pathway leading to fibrosis in the portal area or central lobules, regardless of the cause, which pathway involves hepatocyte inflammatory necrosis, Three interrelated pathological processes such as nodular hepatocyte regeneration and liver fibrosis.
(1) Inflammatory necrosis of hepatocytes: The liver may undergo degeneration and necrosis of diffuse hepatocytes in the long-term or repeated biological, physical, chemical, metabolite or immune damage, and the hepatic lobular structure is destroyed, collapsed, if inflammation Necrosis continues, various inflammatory cells infiltrate, will release various cytokines, promote the increase of extracellular matrix, especially collagen production. Therefore, hepatocyte inflammatory necrosis is not only the initiating factor of the occurrence and development of cirrhosis And throughout the entire process of the disease.
(2) Hepatocyte regeneration: Hepatocyte regeneration is a process of compensatory repair after liver injury, but due to the fracture or collapse of hepatic lobular fiber scaffold, regenerative hepatocytes cannot grow along the original scaffold in a single-cell cable-like arrangement, forming multiple layers. The nodular hepatocyte mass (regenerated liver nodules) with mutually squeezed cells, no portal area around the nodules, lack of normal blood circulation supply, regenerative liver cell morphology varies, often with steatosis or atrophy, regenerative nodules Compression, pulling the surrounding blood vessels, bile ducts, causing blood flow to be blocked, causing the portal vein pressure to rise.
(3) Liver fibrosis and pseudolobular formation: Liver fibrosis refers to the proliferation of interstitial cells (lipid cells, fibroblasts, inflammatory immune effector cells, etc.) outside the hepatocytes and excessive production of extracellular interstitial components. Decreased degradation, resulting in massive deposition in the liver, extracellular matrix including collagen (I, III, IV, V, VI), glycoprotein (fibronectin, laminin) and proteoglycan (chondroitin sulfate, sulfated skin Element, hyaluronic acid) is composed of three types of macromolecules, which are distributed in the liver interstitial, the basement membrane of hepatocytes and blood vessels, type I and III collagen are distributed in the portal area, type IV is located in the lobular vessels, and the basement membrane of the bile duct is located at the V-type. Hepatic sinusoids and portal veins; fibronectin, laminin and hyaluronic acid are extracellular non-collagen components, which have a connecting and fixing effect and connect with collagen to form a network structure, which affects the composition of liver cells. Gene expression, the liver in the hepatitis virus, alcohol and its intermediate metabolite acetaldehyde, schistosomiasis eggs, hypoxia or immune damage, causing acute, chronic, inflammatory necrosis, activation of the mononuclear-macrophage system Various cytokines such as platelet-derived growth factor, transforming growth factor, tumor necrosis factor, IL-1, etc., act on fat-storing cells, fibroblasts, promote differentiation and secretion, produce a large amount of collagen fibers, and the proportion of various types of collagen With the change of distribution, the ratio of type I/III collagen increased, and a large amount of type I and type IV collagen was deposited in the Disse cavity, which reduced or even disappeared the number and size of the "window" between the sinusoidal endothelial cells, forming a "jugularization" of the liver sinus. It causes the portal pressure to increase, and at the same time hinders the exchange of nutrients between the liver cells and the liver sinus, further aggravating the damage of the liver cells. The proliferating collagen fiber tissue extends from the portal area-the portal area or the portal area-central vein to form a fiber interval. Not only surrounds the regenerative liver nodules, but also re-segmented the remaining hepatic lobules (one or several) and changed into pseudo-lobes to form typical morphological changes of cirrhosis. The liver cells in the pseudolobules do not have a normal blood circulation supply system. Under the continuous action of inflammation, it can cause hepatocyte re-necrosis and collagen fibrosis, so repeated development, the formation of false leaflets is more and more Lesions continue to increase, leading to the liver, blood circulation disorders and liver can be deteriorating.
2, pathological classification
Due to the etiology, degree of inflammation and development of the disease, cirrhosis can present different pathological types. At present, the pathological classification determined by the International Hepatobiliary Conference in 1974 is still used. According to the size of the nodules, the morphology is divided into 4 types.
(1) Small nodular cirrhosis: the size of the nodules is relatively uniform, generally 3 to 5 mm, the maximum is not more than 1 cm, the fiber is finer, and the size of the pseudolobule is the same. This type of cirrhosis is most common.
(2) Large tuberous sclerosis: the nodules are coarse and uneven, and the diameter is generally 1 to 3 cm. The main nodules are large nodules. The maximum diameter can reach 3 to 5 cm. The nodules are composed of multiple small leaves. The width of the gap is different, generally wider, and the size of the pseudolobules is different. This type of cirrhosis is caused by large pieces of liver necrosis.
(3) large and small nodular mixed cirrhosis: for the above two types of mixed type, the ratio of large nodules and small nodules are roughly equal, this type of cirrhosis is also very common.
(4) Incompletely divided cirrhosis: also known as regenerative nodular cirrhosis, characterized by fibroplasia, extending into the lobes, but the liver lobes are not completely separated; fibrous tissue can surround multiple livers The lobules form a large multi-lobular nodule, and the regeneration in the nodule is not obvious. The cause of this type is mainly schistosomiasis in China.
There are 520 cases of liver cirrhosis in foreign countries, 58.8% of large nodules, 12.2% of large nodules, 9.2% of small nodules, 6.7% of small nodules. , 12.2% of the mixed type of equal size nodules, China is still more common in small nodular cirrhosis, Tongji Hospital 51 cases of cirrhosis autopsy, 32 cases of small nodular cirrhosis, only 2 cases of large nodular cirrhosis Liang Boqiang et al reported 80 cases of cirrhosis autopsy results, small nodular type 58.75%, large nodular type 23.75%, in some cases, the above classification is not fixed, small nodular cirrhosis can be transformed through regeneration For large nodular or mixed cirrhosis, the etiology has a certain correlation with morphological changes, such as common eosinophils in hepatitis B cirrhosis, but also in alcoholic cirrhosis; steatosis and Mallory bodies are common in alcoholic Cirrhosis of the liver is also seen in Wilson's disease; yellow tumor-like changes are seen in biliary cirrhosis; PAS-positive bodies are found in 1-AT deficiency.
3. Pathophysiology
The pathophysiological changes in cirrhosis are extensive and complex, involving almost all systemic organs in the body. Here, only the changes in blood circulation dynamics during cirrhosis are introduced.
(1) Portal venous hyperemia and intrahepatic and external shunt: under the long-term effects of various pathogenic factors as described above, the liver parenchyma and its capillary network are completely destroyed and reconstructed, and the regenerative liver nodule can be Compresses the portal vein and hepatic vein branches around it, narrowing, interrupting or occluding the blood vessels; abnormal proliferation and scar contraction of the fibrous septum and transformation of the lipid storage cells into fibroblasts in the gap of Disse, resulting in a large amount of collagen fibers, resulting in hepatic sinus capillaries Vascularization is also an important factor in the increase of portal system resistance. When the portal vein blood flow enters the hepatic sinus, it stagnates, and the posterior sinus hepatic vein outflow is also blocked, gradually forming portal hypertension.
Due to portal vein blood flow obstructive congestion, all organs within the portal system drainage are affected, such as spleen congestion and swelling, gastrointestinal congestion and edema, pancreas, gallbladder also have corresponding changes, severely affect the function of these organs Different degrees of morphological changes can occur, and as the disease progresses, portal obstructive hyperemia can change the direction of portal blood flow, and there is reverse hepatic blood flow. The liver also changes from portal blood supply to hepatic artery blood supply. Lord, and liver blood flow is still reduced, from 25% of normal heart output to 13%.
When the portal vein is congested, the intrahepatic sinus pressure is increased, so that the liquid component in the hepatic sinus enters the sinus space a lot, thus forming a large amount of lymph fluid. The hepatic hilar lymph node, the chyle pool, and the thoracic duct drainage volume are too large, which can cause lymphatic The tube ruptures to form chylothorax ascites; the hepatic capsule lymphatic anastomosis branch, leaking into the abdominal cavity from the surface of the liver capsule, can form ascites; through the diaphragmatic lymphatic, flowing through the mediastinum or pleura, affecting the pleural lymphatic return, forming a pleural cavity liquid.
When the portal hypertension reaches a certain level after a certain period of time, there will be intrahepatic and external shunting. This shunt is the compensatory mechanism of the body, which is the reflexive congestion of the shunt portal system. The intrahepatic shunt is the portal vein in the fibrous septum. The traffic branch between the hepatic veins causes the portal blood flow to bypass the hepatic lobule, and enters the hepatic vein through the traffic branch. The extrahepatic shunt is located in the usually closed portal-cavity system communication branch. These traffic branches gradually expand and open. The collateral circulation is formed, and part of the portal vein blood flows into the vena cava through the traffic branch and flows back into the heart. The common collateral circulation has the following groups:
1 The portal vein of the portal vein and the esophageal vein of the vena cava system, the azygous vein, and the intercostal vein traffic branch open and expand, forming the fundus and esophageal varices.
2 The umbilical vein and the paraumbilical vein closed after birth are reopened when the portal vein pressure is too high. The abdominal vein enters the superior vena cava and forms the umbilical and abdominal varices.
The superior iliac vein of the portal vein and the iliac vein and the infraorbital vein of the vena cava form a dilated vein.
4 There are many small branches between the retroperitoneal portal vein and the inferior vena cava (Retzius vein).
5 portal vein can communicate with the left renal vein through the splenic vein, gastric vein, pancreatic vein, left adrenal vein.
In addition, there are many portal veins and aortic veins in the liver without peritoneal coverage. In recent years, the literature reports that in addition to the esophagus, the intestinal varices outside the fundus, called ectopic varicose veins, including the duodenum, jejunum The ileum, colon, rectum, and even the abdominal cavity, pelvis, bladder, and vagina can be divided into varicose veins. The most clinically significant is esophageal and gastric varices. The rupture of hemorrhage is the most common complication of cirrhotic portal hypertension. And the cause of death, ectopic varicose veins are relatively rare, and its rupture and hemorrhage is seen in the duodenum, colon, and occasionally intra-abdominal hemorrhage, which may cause clinical diagnosis difficulties.
In the liver of the cirrhosis, the intrahepatic and extrahepatic shunts of the portal blood flow, so that the uptake, utilization, metabolism of the various cells and the uptake, degradation and blocking of the Kupffer cells are obviously weakened, thereby causing a large amount of harmful substances or toxins. In particular, the high rate of liver uptake, substances that do not enter or rarely enter the systemic circulation normally enter the systemic circulation, leading to a series of pathophysiological phenomena such as endotoxemia, hyperammonemia, hypercholesterolemia, amino acid imbalance, Bacteremia and spontaneous peritonitis, glucagonemia and increased blood levels of intestinal peptides, resulting in a series of secondary pathophysiological changes and the prolongation of half-life in certain drugs (such as propranolol) .
(2) Active visceral hyperemia and high-power circulation: Animal experiments have shown that body fluids play an important role in the mechanism of visceral hyperkinetic circulation. To this end, Benoit proposed a shunt vasoactive substance shunt hypothesis derived from the stomach, intestine, and pancreas. There are many vasoactive substances. Because of their high uptake rate in normal liver, these vasoactive substances are reduced in the liver during liver lesions and portal vein shunting, and enter the systemic circulation in large quantities. Currently, glucagon, nitric oxide , bile acid, calcitonin gene-related peptide, vasoactive intestinal peptide, parathyroid hormone, prostacyclin, isoleucine, histidine peptide, substance P, etc., Thomas and other studies have shown that in cirrhosis In the high-intensity visceral hyperdynamic circulation of portal hypertension, the role of glucagon is 30%. Studies have also shown that bile acids have a strong dilating effect on intestinal vasculature. In recent years, Tongji Hospital has played a role in the high-power circulation of nitric oxide in cirrhosis. Systematic studies have confirmed that cirrhosis in rats produces increased nitric oxide, elevated plasma nitric oxide levels, and is associated with high power cycling. The parameters are related, and nitric oxide synthase inhibitors can improve the high dynamic circulation state. The study also suggests that endotoxin may participate in the liver by inducing the synthesis of nitric oxide synthase, increasing the production and release of nitric oxide. Hardened portal hypertension, visceral hyperdynamic circulation, in addition to the reduced sensitivity of visceral vascular bed to vasoactive substances and antagonism of vasoactive substances to vasoactive substances are also involved in visceral hyperemia and high power circulation, it is reported that Glucagon has the effects of antagonizing norepinephrine, angiotensin, and vasopressin.
It has been observed that early kidney cirrhosis has sodium retention, resulting in increased plasma volume, involvement in visceral hyperemia and high power circulation. Sodium water retention may be related to the following mechanisms:
1 liver function decline, antidiuretic hormone, aldosterone, estrogen and other inactivation in the liver is weakened.
In 2 cases of venous congestion, the effective blood volume is insufficient, resulting in a decrease in atrial peptide secretion, and a decrease in the synthesis of atrial peptides in the liver.
3 The synthesis and release of the liver slowed down, causing dilation of blood vessels and a decrease in the production of bradykinin regulating renal blood flow.
4 kidney synthesis of prostaglandins (diastolic blood vessels) deficiency and other related to renal sodium disorders.
Arroyo study believes that vasodilators cause small arterial dilatation as a trigger for renal dysfunction. Because of the relative filling of the resistance vessels, the renal compensatory sodium water retention increases the plasma volume. When this compensation mechanism is still insufficient to maintain When the blood circulation is stable, the endogenous neurohormone vasoconstrictor system is continuously activated to maintain blood pressure, but the system activation is detrimental to the renal perfusion and filtration rate, sodium water retention is further aggravated, visceral active congestion and high power Circulation is the result of portal hypertension in cirrhosis, and it is also one of the reasons for the persistence of portal hypertension, and it aggravates intrahepatic shunt.
(3) arteriovenous short circuit and effective plasma volume reduction: under the action of vasodilators, not only the visceral arteries are dilated, but also the peripheral skin and muscle arterioles are dilated, so that the peripheral vascular resistance is reduced, the blood volume is relatively insufficient, and the liver When hardening, the plasma volume increases, but it is isolated from the visceral vascular bed, thus reducing the effective plasma volume. In addition, the anterior capillaries of the capillaries open under the action of vasoactive substances, forming a short circuit of the arteriovenous vein. These pathophysiological changes lead to blood circulation of various organs in the body. The kinetics change.
1 increased cardiac output: due to decreased peripheral vascular resistance, effective blood volume is relatively insufficient, central vein and mean arterial pressure are reduced, in order to compensate for this hemodynamic disorder, and cardiac output and cardiac index increase, cycle time Shortened, clinical manifestations of tachycardia, systolic murmur, myocardial hypertrophy, but rarely cardiac insufficiency.
2 pulmonary arteriovenous shunt and hypoxemia: blood gas analysis of patients with decompensated liver cirrhosis, often found that arterial oxygen saturation and arterial oxygen pressure decreased and hypercapnia caused by hyperventilation These are mainly related to pulmonary circulatory dysmotility in cirrhosis. Radiology and autopsy have shown that there is often arteriovenous fistula formation in the lungs during cirrhosis, and Martinine et al continue to instill intravenous histamine in patients with cirrhosis with circulatory abnormalities. It was found that the pulmonary-intravenous venous flow was significantly increased, and the alveolar-arterial oxygen difference was increased. It is now believed that hypoxemia is mainly related to the arteriovenous shunt in the lung and/or peripheral blood vessels; other causes The aerobic dissociation curve was shifted to the right, the lung diffusion-perfusion ratio was imbalanced, and the lung ventilation perfusion ratio was abnormal.
Pulmonary circulatory abnormalities in cirrhosis include pulmonary hypertension. The cause may be a shunt between the portal vein and the pulmonary artery, causing intestinal toxins such as endotoxin, histamine, etc. to enter the pulmonary artery, causing pulmonary artery contraction and high pressure portal veins. Blood flow directly into the pulmonary artery and other related.
3 renal hemodynamic changes: renal dysfunction is related to the degree of cirrhosis, renal venous flow (RPF) and glomerular filtration rate (GFR) are normal, accompanied by ascites, especially stubborn In both ascites and concurrent hepatorenal syndrome, both RPF and GFR were moderately and severely reduced. Although renal function was severely impaired, pathological morphology was not changed.
Decreased renal blood flow is the pathophysiological basis for the abnormalities of RPF and GFR. The mechanism of renal blood flow reduction can be summarized as: insufficient circulating blood volume; renal vasoconstriction; renal blood flow from the cortex to the medulla.
Prevention
Cirrhosis prevention
The cause of cirrhosis is complicated, the most common is viral hepatitis. The incidence of viral hepatitis is high in China. Therefore, it is extremely important to prevent viral hepatitis. Pay attention to hygiene, strict disinfection of equipment, strict screening of blood donors, and vaccination against hepatitis vaccine. All are important measures to control drinking, reasonable nutrition, and avoid the use of drugs that damage the liver. It should also be noted that patients with cirrhosis that have been found should be given appropriate protective measures, such as appropriate reduction of labor intensity, prevention of complications, and maintenance of health. And extend life.
Complication
Cirrhosis complications Complications, hepatic encephalopathy, shock, jaundice
Liver cirrhosis often dies due to complications.
1. Hepatic encephalopathy.
2, upper gastrointestinal bleeding: cirrhosis upper gastrointestinal bleeding, most due to esophagus, gastric varices rupture, but should consider whether complicated with peptic ulcer, acute bleeding erosive gastritis, cardia tear syndrome and other gastric mucosal lesions, The variceal bleeding of varicose veins is mostly caused by rougher and harder or angular food wounds. The esophagus is eroded by acid reflux, severe vomiting, etc., and hematemesis and black stools occur. If the amount of bleeding is small, only black stools, if A large amount of hemorrhage can cause shock. In the case of hepatic ischemia and hypoxia, liver function is often deteriorated. Hemorrhage causes loss of plasma protein, which can lead to the formation of ascites. The blood can be induced in the intestine by bacterial decomposition and ammonia is absorbed by the intestinal mucosa. Sexual encephalopathy can even lead to death, and the original swollen spleen can be reduced or even inaccessible after hemorrhage.
3, infection: due to the body's immune function decline, hypersplenism and the establishment of collateral circulation between the portal vein, increased the chance of pathogenic microorganisms invading the body, it is easy to concurrent with various infections, such as bronchitis, pneumonia, tuberculous peritonitis , primary peritonitis, biliary tract infection and Gram-negative bacilli sepsis, primary peritonitis refers to acute peritoneal inflammation of the peritoneal cavity of patients with cirrhosis, the incidence of 3% to 10%, mostly occurs in a large number The patients with ascites are mostly caused by Escherichia coli. The reason is that the phagocytosis of phagocytic cells is weakened during cirrhosis, the bacteria in the intestines are abnormally propagated, enter the abdominal cavity through the intestinal wall, and the bacteria can be changed due to changes in the structure of the blood vessels inside and outside the liver. Infection caused by collateral circulation or bacterial lymphatic leakage from the subcapsular or hepatic hilum lymph node into the abdominal cavity, clinical manifestations of fever, abdominal pain, abdominal distension, abdominal wall tenderness and rebound tenderness, increased ascites, increased white blood cells Ascites is turbid, and it is exudate or between exudate and leakage. Ascites culture can grow bacteria, and a few patients have no abdominal pain and fever. Manifested as hypotension or shock, refractory ascites and progressive liver failure.
4, liver and kidney syndrome: cirrhosis with refractory ascites failed to properly treat or poor efficacy, prone to liver and kidney syndrome, characterized by oliguria or no urine, hyponatremia and low sodium, kidney without device The qualitative change is also called functional renal failure, and its pathogenesis is not completely clear. The research results prove that:
(1) glomerular filtration rate and renal blood flow decreased, respectively, 20 ~ 50ml / min (normal 120ml / min) and 250 ~ 500ml / min (normal 600ml ~ 800ml / min).
(2) The blood flow in the kidney of patients with hepatorenal syndrome was redistributed. The test of p-amino hippuric acid (PAH) showed that the blood flow of renal medulla was more than that of renal cortex. The liver and kidney were proved by 133Xe elution technique. The renal cortical blood flow of the syndrome is reduced, the interlobular artery and the proximal arch artery are vasospasm, and the angiographic vessels are completely normal after the same patient dies.
(3) Kidney transplantation can be performed in the kidney of patients with hepatorenal syndrome, and the kidney function after transplantation is completely restored; the renal function of patients with hepatorenal syndrome is completely restored after liver transplantation, indicating that the renal lesion is functional. It is reversible.
In recent years, with the further study of hepatorenal syndrome, it is found that the mechanism is mainly due to the reduction of effective blood volume caused by cirrhosis ascites, the decrease of renal blood flow, the decrease of glomerular filtration rate, and the renal functional renal failure. Factors involved in the reduction of renal blood flow include: 1 renin-angiotensin system: in the decompensated period of cirrhosis, due to effective hypovolemia and reduced renal perfusion, activation of the renin-angiotensin system, Decreased inrogen inactivation, elevated plasma angiotensin levels, renal vasoconstriction, decreased glomerular filtration rate, 2 kallikrein-kinin system: slow synthase and synthesis of kidney synthesis E2;
550ml200ml
(1)
Disse
(2)
(3)--ADH
69.9%39.2%2/3(-FP)>200ng/ml-FPCT
Symptom
2050()
(25)
1, general symptoms
;;
2
(1)
(2)()
(3)18.6%17.7%
5-
24%41%45%76%
(4)
(5)()
(6)
3
4
B12(Evans)
5
(ICG)99mTc-MAA2060µm99mTc-MAA;;
6
17.151.3µmol/L68.485.5µmol/L342.0µmol/L
(1)(carotinemia)A
(2)35mm23mm3;20671mm
;
(3)
(4)
(5)(Muehrcke line)Terry
(6)
7
8
9
(1)pHK H pH
(2);
10
13cm2cm
11
12
5%10%;;;
13
()
(1)()
(2)()
Examine
Laboratory inspection
14.0×109/L(4000)50×109/L(50000)
2/
31.018100/mm325g/L
4
(1)
<30g/L(4050)g/L>40g/L(2030g/L)0.50.71(1.32.51)
;1(12)()(6)
(54%61%)(1 4%6%2 7%9%)(10%13%)(17%22%)1
34100µmol/L
(2)
(3)ALTAST(GPTGOT)
(MAO)MAO80%MAOMAO
(ChE)ChE
(4)K
(5)(ADA)ADAALTALTADAADA()ADA
(6)(P--P)P--P(0.64±0.11)U/ml
(7)(HA)HAHAHAHAHA
(8)(IR-pH)IR-pH
(9)
(BSP)5mg/kg45min<5%>10%10%
(ICG)0.5mg/kg15min(7.83±4.31)%20%BSP1.68%
(10);-
(11)(AFP)AFP300ng/mlAFP
(12)
70%80%
ET
A.IgGTB
B.
C.-
Film degree exam
1
2
3
4X
5X
619899m113m
7X(CT)>65%;<6%
8
9
10
Diagnosis
diagnosis
1()>2cmP--P
2
Differential diagnosis
1
(1)
(2)40
(3)
(4)
(5)
2
(1)53%
(2)
(3)
(4)10×109/L(3.0×109/L)
