Portal hypertension (PHT) is a condition in which portal venous blood flow is obstructed anteriorly, intrahepatically or posteriorly, and portal venous pressure exceeds 10 mmHg (1 mmHg = 0. 133 kPa). Cirrhosis accounts for more than 80% of the causes of PHT. The portal vein is the confluence of the superior mesenteric vein and the splenic vein. Two-thirds of the blood supply to the liver comes from the portal vein and one-third from the hepatic artery, and 72% of the liver’s oxygen supply is provided by the portal vein. In portal hypertension, the gradient of hepatic and portal venous pressure increases, because there is no venous valve in portal vein, when the pressure after hepatic sinus is higher than portal hypertension, the blood flow changes from hepatic to hepatic.
I. Causes of portal hypertension (a) Increased resistance to hepatic blood flow Increased resistance can be located in the prehepatic (portal vein or splenic vein obstruction), intrahepatic (prehepatic sinusoid, hepatic sinusoid or posthepatic sinusoid) and posthepatic (hepatic vein and inferior vena cava obstruction). In schistosomiasis, for example, it is predominantly anterior hepatic sinusoidal, but later with malnutrition, both hepatic sinusoidal and posterior hepatic sinusoidal pressures can be increased. The hepatic vascular bed can be significantly reduced by compression by fibroplasia and regenerative nodules. The causes of portal hypertension due to increased hepatic blood flow resistance are as follows.
1, hepatic fibrosis Disee interstitial collagen deposition, narrowing of the hepatic sinusoids, reduction of the hepatic vascular bed, collagen under the endothelium of the hepatic sinusoids, the formation of basement membrane, so that the window hole of the endothelium disappears, which not only affects the material exchange between the hepatic sinusoids and hepatocytes, but also increases the resistance to blood flow in the hepatic sinusoids, which Popper called hepatic sinusoidal capillarization.
2.Hepatic sinusoidal compression Hepatocyte swelling, distension and degeneration increase the size of hepatocytes and the proliferation of hepatic nodules, all of which can compress the hepatic sinusoids.
3.Extensive vascular aberrations in regenerative nodules in cirrhosis. The blood supply within the regenerative nodules mainly comes from the portal vein. Within the fibrous septum and regenerative nodules, various vessels such as hepatic artery portal vein and hepatic vein can appear with various anastomoses, mainly hepatic artery – portal vein and portal vein – hepatic vein shunt. The anastomotic branches increase intrahepatic vascular resistance and importantly reduce the blood flow to perfused hepatocytes, aggravate the damage to hepatocytes and elevate portal vascular resistance.
4. Thrombosis Due to inflammation, endothelial factor (ET-1) promotes synthesis and release of platelet-activating factor by hepatic macrophages, and the disease induces platelet agglutination and formation of microthrombi, which aggravates the hepatic microcirculatory disorder. Produce thrombotic obstruction of portal vein and hepatic venous branches and cause obstruction of intrahepatic outflow tract, which plays an important role in raising portal vein resistance.
5, intrahepatic vasoconstriction Constricting substances in the circulating blood, such as norepinephrine, angiotensin, vasopressin, endothelin (ET) can cause intrahepatic vasoconstriction. ET, which has strong vasoconstrictive activity, is significantly elevated in hepatic veins, and there is a significant positive correlation between hepatic venous pressure gradients. In addition, intrahepatic levels of ET-1 can cause myofibroblasts, hepatic sinusoids, portal veins and central veins, increase intrahepatic vascular resistance, and aggravate intrahepatic blood circulation disorders.
6, cytokine action and stellate cell activation During liver damage, activated mononuclear macrophages synthesize and secrete large amounts of TGFβ1, which activates stellate cells that become myofibroblasts expressing α actin (α-SMA) and autocrine large amounts of TGFβ1, causing them to activate and increase in value over and over again. The activated stellate cells are also the main site of ET-1 synthesis, causing their own proliferation and contraction, compressing the hepatic sinusoids, portal vein and central vein, increasing intrahepatic vascular resistance, and aggravating intrahepatic blood circulation disorders.
(b) Hyperdynamic circulation is the result of increased resistance to blood flow in portal hypertension and is a persistent factor in portal hypertension. As a result of systemic hyperdynamic circulation and active visceral congestion, which leads to increased portal blood flow, a variety of vasodilators such as NO, PGI2, glucagon, INF-α and endotoxins mediate this process. It has been shown that NO production, increases in association with portal hypertension, and PGI2 has a role in vasodilation in portal hypertension.
Second, about Budd-Chiari syndrome (BCS) hepatic vein (HV)/inferior vena cava (IVC) obstruction syndrome, the clinical manifestation is most prominent with hepatomegaly, right upper abdominal pain and progressive intractable ascites.
The incidence of BCS is low in European and American countries and relatively high in Asian and African countries; Japan accounts for 4.9% of all patients with portal hypertension, India accounts for 7%-9%, and 17.3% of patients with chronic liver disease in Nepal have OBCS. BCS can occur at any age, with a high incidence after 10 years of age and a higher incidence in the 30-40 age group.
The etiology of microhepatic venous trunk/short inferior hepatic vena cava is obstructed by various nature of obstruction leading to hepatic venous flow, mainly thrombotic obstruction, membranous obstruction and segmental stenosis or occlusion (intravascular luminal bulge, foreign compression, etc.). In Europe and the United States, thrombosis is the most common cause, and is classified as simple thrombosis, inflammatory thrombosis or aneurysmal thrombosis, while in Asia and Africa, membranous obstruction of the inferior vena cava is common, and can be clinically classified into the following types.
(a) Explosive type: complete obstruction of the main trunk of the hepatic vein at the same time, most of them die of explosive liver failure in a few hours or days after the onset of the disease.
(b) Acute type: the duration of the disease is mostly within 1 month, manifested by sudden onset of severe epigastric pain, nausea, vomiting, abdominal distention, hepatomegaly and rapidly increasing ascites. Jaundice is generally mild, mild enlargement of the spleen, often fever, can progress to acute liver failure, often die within 8 weeks, easily misdiagnosed as acute heavy hepatitis.
(iii) Subacute type: the duration of the disease is mostly around 6 months, with hepatomegaly, hepatic pain, intractable massive ascites, swelling of the lower limbs and multiple sites of deep and superficial venous tortuous dilatation. Inferior vena cava obstruction syndrome such as superficial venous anger in lower chest and low back is an important sign of the disease. The more 1/3 patients have splenomegaly and jaundice, and if the renal veins are affected, it may cause hematuria, proteinuria, oliguria, anuria and azotemia in severe cases.
(d) Chronic type: 60% to 70%. The duration of the disease is more than 1 year, mainly seen in patients with membranous obstruction. The disease progresses slowly, manifesting as portal hypertension and inferior vena cava hypertension syndrome, bleeding from esophageal varices may occur, and liver failure signs such as hepatic encephalopathy and hepatorenal syndrome appear in the late stage, which is often misdiagnosed as cirrhosis.
Double cannulation angiography (IVCG+SVCG) of hepatic veins and superior and inferior vena cava is the “gold standard”for the diagnosis of BCS, and is also one of the essential tests before surgical treatment of patients.
Small intrahepatic veno-occlusive disease (VOD), now called sinusoidal obstruction syndrome (SOS), can also cause hepatic veno-inferior vena cava obstruction syndrome, SOS is an independent clinical disease, especially associated with the ingestion of plants with pyrrolo-biphane alkaloids (such as wild lily, millipede and comfrey family plants) and receiving chemotherapy, radiotherapy, immunosuppressive therapy. The pathological changes of SOS are mainly caused by obstruction of the hepatic sinusoidal outflow tract due to endothelial injury of the hepatic sinusoids, which in turn leads to endothelial inflammation, fibroplasia, and intimal thickening of the intrahepatic lobular central and lobular inferior vena cava, resulting in progressive, centripetal, nonthrombotic narrowing and occlusion of small veins.
Third, regarding portal vein disease, portal vein lesions are not uncommon. These lesions include portal vein thrombosis, portal vein stenosis, portal vein hemangioma and intrahepatic venous arteriovenous fistula, which can cause partial or complete portal vein obstruction or increased portal venous blood flow and are an important cause of non-cirrhotic portal hypertension.
(A) Portal vein thrombosis (PVT) is the most common cause and the most important mechanism of portal vein obstruction.
PVT in combination with portal vein is uncommon, but its incidence increases abruptly after splenectomy and/or bypass. PVT occurs in 7% of patients with hematologic disease after splenectomy and is prone to occur after splenectomy and/or portosystemic shunt with a rapid increase in platelets, especially in those with normal preoperative platelet counts. cirrhosis combined with hepatocellular carcinoma (HCC) often results in the formation of cancer clots in the portal vein.
Etiology.
1.Direct injury to portal vein Umbiliculitis, intraumbilical vein cannulation, intra-abdominal inflammation (appendicitis, biliary tract infection, pancreatitis, neonatal peritonitis, inflammatory bowel disease, etc.)
2.Direct pathogenic factors sepsis, dehydration, multiple exchange transfusion, blood hypercoagulability, pregnancy, long-term use of contraceptives.
(B) Portal vein hemangioma portal vein hemangioma (PVA) is also known as portal vein hemangioma-like dilatation.
Etiology: (1) portal hypertension; (2) congenital defect of portal vein wall; (3) acute pancreatitis overflow enzyme digestion, damage to the vessel wall, so that the local portal vein expansion.
(3) Portal vein stenosis can be congenital or caused by peritoneal fibrosis, fibrous tissue encapsulating portal vein; tumor or enlarged lymph node compression.
(D) Portal-arterial fistula Portal-arterial fistula can be congenital or occur after trauma, liver puncture or other invasive examinations; primary hepatocellular carcinoma invading and destroying the arterial and venous walls, or hepatic aneurysm breaking into the portal vein can form a vascular fistula.
(E) Septic portal phlebitis is a purulent inflammation of the main trunk of the portal vein and its branches, which often coexists with bacterial liver abscess. Now it is rare.
Clinical manifestations of portal hypertension
(A) Portal-somatic collateral circulation and variceal rupture; the most important ones are varices in the submucosa of the lower esophagus, gastric fundus, near the cardia, varices of the abdominal wall showing, periumbilical veins showing, varices of hemorrhoids, ectopic varices.
(ii) splenomegaly and hypersplenism with leukocyte thrombocytopenia; (iii) ascites with hypoplastic plasma protein; (iv) hepatic encephalopathy; (v) portal hypertensive gastropathy and enteropathy.
V. Treatment of the main complications of portal hypertension.
(A) prevention and treatment of bleeding drug therapy is aimed at reducing portal pressure and preventing bleeding, also used for acute bleeding from ruptured esophageal and fundic varices and prevention of rebleeding after hemostasis. Endoscopic treatment is used for prevention of acute bleeding from esophagogastric varices and for those who cannot stop bleeding with drugs. Surgery is used for certain hemorrhage that cannot be stopped by drugs and endoscopy, and can also be used to prevent rebleeding after improving liver function.
1, drug treatment propranolol (insulin) can block β receptors, make the visceral vasoconstriction, reduce the blood flow in the portal vein and its lateral odd vein, slow down the heart rate and reduce the amount of cardiac bleeding, reduce portal pressure. It is indicated for Child-Pugh grade A compensated cirrhosis, but is not effective in about 30% of cases of grade C decompensated cirrhosis, and should be used with caution because it may occasionally increase blood ammonia. 20mg/dose, 3 times/day. The dose should be reduced by about 25% of the heart rate, if the heart rate is 60 times/min, the dose should be reduced by half.
It should be noted that the early application of antiviral therapy to patients with hepatitis B cirrhosis with portal hypertension is beneficial to slow down the progress of portal hypertension.
2.Treatment of ruptured esophageal and fundic veins haemorrhage Octreotide (Sunning), 0.1mg added to 25% GS 20ml intravenously, 0.5mg added to 5% sugar water 1000ml intravenously to maintain 24h.
Terlipressin, 2mg in 6h drip, reduced to 1mg in continuous drip after hemostasis (24~36h), 70% hemostasis rate. Posterior pituitary hormone, once 20µ dissolved in 5% glucose solution 200ml at 0.2-0.4µ/min slow drip, for 12-24h, if bleeding control, 24h after half drip, if rebleeding can be increased to 0.5-0.6µ/min, cautiously used in ischemic heart disease over 50 years old, but with nitroglycerin The combination with nitroglycerin can improve the hemodynamics of body circulation.
Three lumen tube, especially the first bleeding hemostasis rate of up to 80%, re-bleeding rate of 40% to 50%. If the heart rate is 52 beats/min in sinus bradycardia, then posterior pituitary hormone and nitroglycerin should be used instead.
Omeprazole (Loxacol) 40 mg should be given drip after admission to the hospital for ruptured esophagogastric fundic varices, and famotidine may also be given twice daily. The first bleeding should be supplemented with 1/3 to 1/2 of the bleeding volume.
Tissue adhesives, sclerotherapy, skin ring ligation and metal clips for varicose veins under direct emergency endoscopic view are optional on the basis of the above.
Transjugular intrahepatic portal – body shunt (TIPSS), due to the high incidence of hepatic encephalopathy and hepatic myelopathy, and the reduced perfusion of the liver, is prone to liver failure, unless waiting for liver transplantation is not advocated.
3, surgical treatment Child -Pugh grade C surgical mortality is significantly higher than grade A, B, surgical mortality rate is more than 60%, in bleeding control, liver function is significantly restored elective surgery can be reduced to 10%. Usually, emergency surgery is considered to be indicated for: (1) bleeding that cannot be controlled by endoscopic sclerotherapy or ligation; (2) bleeding that occurs during long-term sclerotherapy; (3) bleeding from varices in the fundus or portal hypertensive gastric disease, and for which drug therapy has failed; and (4) rebleeding, especially repeated bleeding. The surgical procedures can be categorized into three types: bypass, dissection and liver transplantation. To reduce surgical trauma, flow dissection is often preferred, including splenectomy with peripheral vascular dissection of the fundus, splenectomy, peripheral vascular dissection of the cardia and transverse lower esophagus, and transverse lower esophagus with a tubular anastomosis and removal of the spleen.
（The main treatment of ascites in cirrhosis is sodium restriction (2g/day) and oral diuretics, and most of them do not require fluid intake restriction. Common chronic hyponatremia rarely has serious harmful effects, and rapid correction of hyponatremia may be more harmful. Fluid intake should be restricted in those with serum sodium <120 mmol/L. Symptoms of hyponatremia usually do not occur until blood sodium is <110 mmol/L.
The recommended diuretic regimen is ambrisentin (spironolactone) and tachyphylaxis (furosemide), which can be increased in a 100mg/40mg ratio, a ratio that is conducive to maintaining normal blood potassium levels. The maximum doses are 400 mg/d and 160 mg/d. Tachyphylaxis may be suspended in the presence of low blood sodium. Patients with cirrhosis have good bioavailability of oral tachyphylaxis and can usually take it orally. Salt restriction and the diuretic regimen described above are effective in most patients with ascites.
Those who do not respond to a salt-restricted diet and high-dose diuretic therapy or whose medications do not prevent recurrence after treatment with discharge ascites become refractory ascites. Portal hypertension, hypoproteinemia and ascites infection are the most important causes of intractable ascites, and medical factors such as diuretics and lapses in sodium and water restriction cannot be ignored. The management steps of intractable ascites can be summarized as follows.
1, laparoscopic fluid release with albumin in the 1940s laparoscopic fluid release was the only approach, which was replaced by the continuous development of diuretics because of its serious complications. 1985 it was confirmed that in the case of supplemental albumin, 4-6L of ascites was safe for each release of ascites in patients with tension ascites resistant to diuretics, and the electrolytes and serum creatinine changes were significantly reduced after the release of fluid supplemented with albumin 10g/2L.
In 1994, the authors summarized 21 patients treated with this method, and the serum urea nitrogen and creatinine were significantly reduced after treatment, and hyponatremia was improved, and complications appeared significantly reduced in the treatment group, especially renal function counted well and hyponatremia. Some scholars believe that too much input of albumin does more harm than good, and suggest that it is not necessary to input albumin when releasing fluid less than 5L, such as a large amount of ascites can be infused with albumin 5-10g per 2L ascites.
2, their own ascites concentrated intravenous transfusion ascites protein composition is basically similar to plasma, concentrated transfusion can not only increase the effective blood volume, improve renal function, inhibit aldosterone and anti-diuretic hormone secretion, but also greatly reduce the application of exogenous albumin, prevent the production of albumin antibodies and save money. This method utilizes the limited permeability of semi-permeable membranes to retain protein components with molecular weights greater than 6000.
Ascites can usually be concentrated to 2-6 times, and sodium salts are eliminated in large quantities. The advantages are: (1) 20-60 g of the patient’s own albumin can be replenished each time, (2) increase in effective blood volume and reduction in renal compression, significant improvement in renal blood flow, increased urine output and increased sensitivity to diuretic fluids, and (3) elimination of sodium retention and removal of other low molecular toxic substances without significant effect on plasma electrolytes.
Adverse reactions and complications may include fever, chills, infection, and upper gastrointestinal bleeding. However, they can be prevented with careful prevention, such as preoperative intraperitoneal or intestinal antibiotic application and appropriate portal pressure-lowering drugs. We have also performed concentrated retransfusion of celiac fluid in dozens of cases, which is also quite safe and effective. Due to the large amount of their own protein supplementation, the patients not only have obvious elimination of symptoms after surgery, and the quality of life has improved significantly.
3, their own ascites concentrated intraperitoneal retransfusion to their own ascites intravenous retransfusion does not adapt to the refractory ascites patients, using their own ascites concentrated intraperitoneal retransfusion, can also achieve very good results. It can eliminate 3000-5000ml of ascites each time, and also eliminate small molecules including sodium ions. For patients with elevated creatinine and urea nitrogen, concentrated intraperitoneal transfer from the abdominal cavity to the abdominal cavity can also be used first, followed by concentrated intravenous transfer, which not only solves the problem of renal insufficiency, but also enables safe intravenous transfer of ascites. In a small number of patients who are not comfortable with intravenous infusion, this method can be used instead, and the symptoms can be rapidly eliminated, the growth of ascites is significantly delayed, and the general condition is significantly improved. It is presumed that the elimination of sodium retention and increased renal blood flow played a role.
4, cancerous ascites centrifugal concentration back into the cancerous ascites development is fast, the symptoms are serious, the ascites quickly recovered after the release of fluid. Due to the loss of plasma protein and the reduction of effective circulation, the patient will further fail. We have adopted the method of centrifugal concentration and reinfusion, which has achieved good results. The ascites was drained by 4-6L and centrifuged for 15min at 2500rpm/min with a large number of centrifuges to precipitate the cellular components in the ascites, including cancer cells, and the supernatant night was separated for concentration and then returned by intravenous infusion. At the same time, combined with intraperitoneal chemotherapy, many patients got complete control of ascites.
5.Transcervical intrahepatic portal stent shunt This method has poor long-term efficacy, with a high incidence of stent occlusion and other complications at 3 months after surgery. A recent randomized trial reported that patients undergoing this procedure had a higher morbidity and mortality rate than the drug treatment group.
The Denver tube consists of an intraperitoneal catheter with multiple lateral holes, an intravenous catheter and an elastic chamber with two unidirectional valves from the abdominal cavity to the vein. The chamber can be manually pressed. When the abdominal fluid hydrostatic pressure is greater than the central venous pressure of 3 cm water column, the valves open and the ascites flows into the superior vena cava. It increases blood volume, cardiac output by more than 50% and renal blood flow by 40%, and has a certain spontaneous diuretic effect, which is better with diuretics.
The indications are: (1) cirrhotic ascites that is not effective after strict medical treatment or surgical reduction of portal pressure; (2) refractory ascites that is not suitable for surgical shunt and abdominal decompression of cancerous ascites. We have performed Denver tube placement in more than 30 cases of refractory ascites that could not be controlled by retraction. These patients recovered rapidly after surgery, did not need to discharge ascites repeatedly, could take care of themselves, and their quality of life improved significantly, with the longest survival exceeding 2 years.
7, the emergence of ascites in liver transplantation mostly indicates that cirrhosis has entered the advanced stage, and intractable ascites indicates that liver disease has entered the end stage. For patients with intractable ascites, liver transplantation is a more ideal treatment method and is an indication for liver transplantation. In developed countries and regions, liver transplantation is also included in the routine clinical procedures.