Portal Hypertension and Effects of Portal Hypertension Essay Paper
Portal hypertension is an increase in the blood pressure within a system of veins called the portal venous system. Veins coming from the stomach, intestine, spleen, and pancreas merge into the portal vein, which then branches into smaller vessels and travels through the liver. If the vessels in the liver are blocked due to liver damage, blood cannot flow properly through the liver. As a result, high pressure in the portal system develops. This increased pressure in the portal vein may lead to the development of large, swollen veins (varices) within the esophagus, stomach, rectum, or umbilical area (belly button). Varices can rupture and bleed, resulting in potentially life-threatening complications. Portal Hypertension and Effects of Portal Hypertension Essay Paper
In cirrhosis, tissue fibrosis and regeneration increase resistance in the sinusoids and terminal portal venules. However, other potentially reversible factors contribute; they include contractility of sinusoidal lining cells, production of vasoactive substances (eg, endothelins, nitric oxide), various systemic mediators of arteriolar resistance, and possibly swelling of hepatocytes.
Over time, portal hypertension creates portosystemic venous collaterals. They may slightly decrease portal vein pressure but can cause complications. Engorged serpentine submucosal vessels (varices) in the distal esophagus and sometimes in the gastric fundus can rupture, causing sudden, catastrophic GI bleeding. Bleeding rarely occurs unless the portal pressure gradient is > 12 mm Hg. Gastric mucosal vascular congestion (portal hypertensive gastropathy) can cause acute or chronic bleeding independent of varices. Visible abdominal wall collaterals are common; veins radiating from the umbilicus (caput medusae) are much rarer and indicate extensive flow in the umbilical and periumbilical veins. Collaterals around the rectum can cause rectal varices that can bleed.
Portosystemic collaterals shunt blood away from the liver. Thus, less blood reaches the liver when portal flow increases (diminished hepatic reserve). In addition, toxic substances from the intestine are shunted directly to the systemic circulation, contributing to portosystemic encephalopathy. Venous congestion within visceral organs due to portal hypertension contributes to ascites via altered Starling forces. Splenomegaly and hypersplenism commonly occur as a result of increased splenic vein pressure. Thrombocytopenia, leukopenia, and, less commonly, hemolytic anemia may result. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Portal hypertension is often associated with a hyperdynamic circulation. Mechanisms are complex and seem to involve altered sympathetic tone, production of nitric oxide and other endogenous vasodilators, and enhanced activity of humoral factors (eg, glucagon).
Symptoms and Signs
Portal hypertension is asymptomatic; symptoms and signs result from its complications. The most dangerous is acute variceal bleeding. Patients typically present with sudden painless upper GI bleeding, often massive. Bleeding from portal hypertensive gastropathy is often subacute or chronic. Ascites, splenomegaly, or portosystemic encephalopathy may be present.
Usually clinical evaluation
Portal hypertension is assumed to be present when a patient with chronic liver disease has collateral circulation, splenomegaly, ascites, or portosystemic encephalopathy. Proof requires measurement of the hepatic venous pressure gradient, which approximates portal pressure, by a transjugular catheter; however, this procedure is invasive and usually not done. Imaging may help when cirrhosis is suspected. Ultrasonography or CT often reveals dilated intra-abdominal collaterals, and Doppler ultrasonography can determine portal vein patency and flow.
Esophagogastric varices and portal hypertensive gastropathy are best diagnosed by endoscopy, which may also identify predictors of esophagogastric variceal bleeding (eg, red markings on a varix). Portal Hypertension and Effects of Portal Hypertension Essay Paper
Mortality during acute variceal hemorrhage may exceed 50%. Prognosis is predicted by the degree of hepatic reserve and the degree of bleeding. For survivors, the bleeding risk within the next 1 to 2 yr is 50 to 75%. Ongoing endoscopic or drug therapy lowers the bleeding risk but decreases long-term mortality only marginally. For treatment of acute bleeding, see Overview of GI Bleeding : Treatment and Varices : Treatment.
Ongoing endoscopic therapy and surveillance
Nonselective beta-blockers with or without isosorbide mononitrate
Sometimes portal vein shunting
When possible, the underlying disorder is treated. Long-term treatment of esophagogastric varices that have bled is a series of endoscopic banding sessions to obliterate residual varices, then periodic surveillance endoscopy for recurrent varices.
Long-term drug therapy for varices that have bled involves nonselective beta-blockers; these drugs lower portal pressure primarily by diminishing portal flow, although the effects vary. They include propranolol (40 to 80 mg po bid), nadolol (40 to 160 mg po once/day), timolol (10 to 20 po bid), and carvedilol (6.25 to 12.5 mg po bid), with dosage titrated to decrease heart rate by about 25%. Adding isosorbide mononitrate 10 to 20 mg po bid may further reduce portal pressure. Combined long-term endoscopic and drug therapy may be slightly more effective than either alone. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Patients who do not adequately respond to either treatment should be considered for transjugular intrahepatic portosystemic shunting (TIPS) or, less frequently, a surgical portacaval shunt. In TIPS, the shunt is created by placing a stent between the portal and hepatic venous circulation within the liver. (See also the American Association for the Study of Liver Diseases practice guideline The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal Hypertension: Update 2009.) Although TIPS may result in fewer immediate deaths than surgical shunting, particularly during acute bleeding, maintenance of patency may require repeat procedures because the stent may become stenosed or occluded over time. Long-term bene
Portal hypertension is the major complication of cirrhosis and is responsible for complications such as massive gastrointestinal bleeding (oesophageal or gastric varices), ascites, hepatorenal syndrome, and hepatic encephalopathy. Portal hypertension is defined by a raised portal pressure above the normal values of 1–5 mm Hg; clinically significant portal hypertension is defined above the threshold of 12 mm Hg due to the potential development of portal hypertensive bleeding,1 the most serious complication of portal hypertension, as it is associated with high morbidity and mortality rate.2
Prospective studies have shown that more than 90% of cirrhotic patients will develop oesophageal varices sometime in their lifetime and of these 30% will bleed,3,4 and usually once developed, the varices increase from small to large, though regression has been reported with the improvement in liver function and abstinence from alcohol.5,6 The most important predictive factors for the risk of bleeding are severity of liver dysfunction (Child-Pugh classification; see table1), larger size of varices (increased tension of the variceal wall), and presence of red signs on the varices.
These factors are combined in the North Italian Endoscopic Club Index for the prediction of the first bleeding. It is important to realise that patients with small varices and no red signs and Child-Pugh C score have a risk of 20% for first bleeding compared with a patient with Child-Pugh A score, large varices, and moderate red signs who has a 24% risk and a Child-Pugh C patient with small varices and moderate red signs who has a risk of 36%, thus underlying the importance of the liver function impairment. Portal Hypertension and Effects of Portal Hypertension Essay Paper
However 30% of patients will first bleed without these risk factors.4 Increased variceal pressure has been shown to add to this model.7 Moreover, 5%–50% of cirrhotic patients (depending on the severity of the underlying liver dysfunction) with acute variceal bleeding will die often during the first days after the initial episode.2 Predictive factors of failure to control bleeding are active bleeding at endoscopy spurting or oozing (usually at the oesophagogastric junction), severity of liver disease,8 raised portal pressure hepatic venous pressure gradient (HVPG) ⩾20 mm Hg measured early after admission,9 and presence of bacterial infection.10 There is a high rate of early rebleeding in the first weeks after bleeding, which without specific treatment occurs in up to 50% within six weeks of admission.11 Although mortality from acute variceal bleeding has been decreasing,12,13 it still remains high (5%–35%) depending on the severity of liver disease and the age of the patient.
There is a well documented association of variceal haemorrhage and bacterial infections10,14,15 that may represent a causal relationship. A hypothesis suggests infection is the triggering factor for the variceal bleeding.16 Two crucial steps for the onset of haemorrhage, which are related to the release of endotoxin into the systemic circulation, are vasoconstrictor induced contraction of stellate cells and worsening of haemostasis. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Portal hypertensive gastropathy (PHG) is a term used to describe the endoscopic appearance of the gastric mucosa, with characteristic mosaic-like pattern with or without cherry red spots, and is a common finding in patients with portal hypertension. Histologically there are dilated capillaries and venules in the mucosa and submucosa without erosion, inflammation, or fibrinous thrombi.17 The pathogenesis is not clearly defined and its prevalence parallels the severity of portal hypertension. It can progress from mild to severe and vice versa or even disappear completely, but bleeding is relatively uncommon and rarely severe.18 The same vasoactive agents used for variceal bleeding are used for PHG bleeding.19 In an uncontrolled study, somatostatin and octreotide has been shown effective in the context of acute bleeding from PHG.20 Endoscopic treatment does not have a role, whereas transjugular intrahepatic portosystemic shunts (TIPSs) and shunt surgery should be only used as a last resort and in patients where the benefit outweighs the risk. Only non-selective β-blockers can prevent first and secondary bleeding from PHG.21
ACUTE VARICEAL BLEEDING
(1) General management
The cirrhotic patient is a complicated one who requires intensive nursing care and careful medical assessment. In particular, effective resuscitation, accurate diagnosis, and early treatment can reduce mortality.22 The initial priority is the protection of airway to prevent aspiration, with intubation to be considered in patients with impaired level of consciousness and severe uncontrolled bleeding particularly for endoscopy. A normal central venous pressure should be maintained (avoidance of prolonged hypovolaemia is very important to avoid the complications of renal failure and infection), but over transfusion (according to data from animal models) should be avoided because of the risk for rebound increase in portal pressure, with subsequently increased risk of poor control of bleeding. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Most importantly, prophylaxis of bacterial infection with oral quinolones or intravenous broad spectrum antibiotics has been shown not only to reduce infectious complications (relative risk (RR) 0.39; 95% confidence interval (CI) 0.32 to 0.48) but also to reduce mortality (RR 0.39; 95% CI 0.32 to 0.48).24 The effect on mortality is greater than that seen with specific vasoactive drugs versus placebo. Maintenance of renal function is of prime importance and therefore terlipressin may have an added role, as with albumin it can reverse hepatorenal syndrome.25
(2) Specific therapy
The data on drugs favour the use of terlipressin (2 mg every four hours for the initial 24 hours and 1 mg four hourly for the next 24 hours; some units prolong its use to five days), as it is the only drug to have shown a reduction in mortality in acute variceal bleeding.26 Interestingly, early (before hospital admission) administration of terlipressin—plus glycerine trinitrate—improved the control of bleeding and reduced mortality.27,28 A Cochrane review on somatostatin and its analogues has only shown a reduction of one unit in terms of transfusion requirements.29 Recently, recombinant activated factor VII is related with transient improvement of haemostasis in the setting of acute variceal bleeding; further testing is needed.30,31
Endoscopic therapy has been considered the mainstay of specific treatment for acute variceal bleeding32 (provided that such facilities are available), with some authors emphasising the need for expert and rapid control of haemorrhage.33
Although randomised trials of sclerotherapy32 versus banding ligation have shown that ligation is more effective (pooled odds ratio (OR) 0.51; 95% CI 0.34 to 0.79) in controlling bleeding,34 there is no statistical difference in survival. As placement of the banding device requires extubation after the diagnostic endoscopy and then reintubation, this probably increases the risks of endoscopy, but this has not been assessed formally. The choice of technique should be left up to the experience of the operator, and the particular circumstances found during diagnostic endoscopy.
A cumulative meta-analysis of trials of sclerotherapy versus vasoactive drugs clearly shows the consistent effect over time of the superiority of sclerotherapy for control of bleeding (OR 1.384; 95% CI 0.977 to 1.962) and also similar pattern for hospital or 42 day mortality (pooled OR 1.354; 1.032 to 1.777) but the effect is weak. A recent meta-analysis,35 which excluded one randomised trial36 and included another that was difficult to obtain the correct numbers for37 (and also did not confine the evaluation of efficacy to seven days but to six weeks), suggested drugs were equivalent. However, this interpretation is open to question as assessment should be only during the emergency period. In addition the evidence for efficacy of drugs on their own is very weak except for terlipressin. Finally, trials of sclerotherapy versus standard therapy (drugs ± balloon) showed the superiority of sclerotherapy. Portal Hypertension and Effects of Portal Hypertension Essay Paper
To date the best evidence for efficacy in treating acute variceal bleeding is drugs combined with endoscopic treatment. Randomised trials have shown the greatest effect on control of bleeding (for initial five day control) but strangely no effect on mortality.38 This apparent paradox may be explained by the great variability in the efficacy rates of sclerotherapy used on its own in this group of studies,27 and makes the interpretation of meta-analysis difficult.
(3) Rescue therapy
There is no accepted definition regarding failure of drug and endoscopic therapy for acute variceal bleeding, but most units will only use two sessions of emergency endoscopic therapy.39 The rescue therapy of choice today is TIPS and if this is not available, staple transection of the oesophagus. TIPS is very effective in stopping bleeding in over 90% of the patients.40 Sources of continued bleeding or early rebleeding are often oesophageal ulcers caused by previous endoscopic therapy which is why endoscopic therapy should be limited in the acute setting. There are no randomised trials comparing TIPS with surgical treatments in uncontrolled variceal haemorrhage. It has been shown in uncontrolled studies that TIPS is highly effective in stopping variceal haemorrhage,41–45 but on the other hand TIPS in uncontrolled variceal bleeding still has a high mortality.46 Prognosis is poor if patients have developed sepsis, required inotropic support and ventilation (often due to aspiration), and if they have deteriorating liver and renal function,47 which still is a scenario when a TIPS could be placed. The technical expertise now exists to place TIPS in virtually any patient, even when portal vein thrombosis is present. Thus issues of the utility of treatment arise.47 Established renal failure in a cirrhotic who has had uncontrollable bleeding is in our unit a contraindication to TIPS placement.
When TIPS is not available, alternative options are injections of tissue adhesives (Histoacryl, Bucrylate) or fibrin glue, or endoscopic detachable snare (Endoloops). There are no controlled data for these therapies. If there is a skilled operator it is certainly worth attempting in the absence of TIPS, particularly when the patient is a poor candidate for surgery. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Gastric varices can be found alone or in combination with oesophageal varices and the incidence of bleeding in most series is less than 10%.44 Patients with gastric variceal haemorrhage bleed more profusely, require more transfusions, have a higher risk of rebleeding, and have a higher mortality compared with those who bleed from oesophageal varices.48 The optimal treatment of gastric varices is not known. Sclerotherapy and banding are not useful. Bucrylate has shown better results than sclerosants in a study with 27 patients bleeding from oesophagogastric varices,49 and in another study was reported superior to ethanolamine, although the survival advantage of Bucrylate seemed partially related to increased early rebleeding rates in the ethanolamine group.50 In a recent randomised trial of 37 patients cyanoacrylate was more effective than alcohol injection in achieving faster obliteration of gastric varices, and appeared more useful in controlling acute gastric variceal bleeding, reducing the need for rescue surgery while mortality was similar in the two groups.51 Nevertheless, reports of cerebral and pulmonary embolism with tissue adhesives constitute a major drawback coupled with the expertise in their use. The protocol for tissue adhesives must be well worked out.
Bovine thrombin has been used as intravariceal injection and in a study with 11 cases initial haemostasis was achieved in all patients and after a median follow up of nine months; only one patient rebled from gastric varices. The substitution of bovine with recombinant thrombin is expected to overcome the problem for possible transmission of the agent responsible for bovine spongiform encephalopathy.52 The combination of fibrinogen with thrombin was evaluated in a small study giving very good results in controlling gastric variceal bleeding.53
Unfortunately in all these studies there are considerable rebleeding rates; hence for patients with rebleeding or uncontrolled bleeding, there is the option of TIPS or surgery. TIPSs have been shown to be as effective for gastric bleeding as for esophageal variceal bleeding, having high success rates for initial haemostasis and acceptable rebleeding rates. Portal Hypertension and Effects of Portal Hypertension Essay Paper
What are the treatment options for portal hypertension?
The effects of portal hypertension can be managed through diet, medications, endoscopic therapy, surgery, or radiology. Once the bleeding episode has been stabilized, treatment options are prescribed based on the severity of the symptoms and on how well your liver is functioning.
First level of treatment
When you are first diagnosed with variceal bleeding, you may be treated with endoscopic therapy or medications. Dietary and lifestyle changes are also important.
Endoscopic therapy consists of either sclerotherapy or banding. Sclerotherapy is a procedure performed by a gastroenterologist in which a solution is injected into the bleeding varices to stop or control the risk of bleeding. Banding is a procedure in which a gastroenterologist uses rubber bands to block the blood supply to each varix (enlarged vein).
Medications such as beta blockers or nitrates may be prescribed alone or in combination with endoscopic therapy to reduce the pressure in your varices and further reduce the risk of recurrent bleeding.
Medications such as propranolol and isosorbide may be prescribed to lower the pressure in the portal vein and reduce the risk of recurrent bleeding.
The drug lactulose can help treat confusion and other mental changes associated with encephalopathy. This medication has the ability to increase the amount of bowel movements you will have per day.
Dietary and lifestyle changes
Maintaining good nutritional habits and keeping a healthy lifestyle will help your liver function properly. Some of the things you can do to improve the function of your liver include the following: Portal Hypertension and Effects of Portal Hypertension Essay Paper
Do not use alcohol or street drugs.
Do not take any over-the-counter or prescription drugs without first consulting with your physician or nurse. Some medications may make liver disease worse, and they may interfere with the positive effects of your other prescription medications.
Follow the dietary guidelines given to you by your physician or nurse. Follow a low-sodium (salt) diet. You will probably be required to consume no more than 2 grams of sodium per day. Reduced protein intake is required only if confusion is a symptom. Your dietitian will help you create a meal plan that helps you follow these dietary guidelines.
Second level of treatment
If the first level of treatment does not successfully control your variceal bleeding, you may require one of the following decompression procedures to reduce the pressure in these veins.
Transjugular intrahepatic portosystemic shunt (TIPS): A radiological procedure in which a stent (a tubular device) is placed in the middle of the liver.
Distal splenorenal shunt (DSRS): A surgical procedure that connects the splenic vein to the left kidney vein in order to reduce pressure in your varices and control bleeding.
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What happens during the TIPS procedure?
During the TIPS procedure, a radiologist makes a tunnel through the liver with a needle, connecting the portal vein (the vein that carries blood from the digestive organs to the liver) to one of the hepatic veins (the 3 veins that carry blood from the liver). A metal stent is placed in this tunnel to keep the tunnel open. Portal Hypertension and Effects of Portal Hypertension Essay Paper
The TIPS procedure reroutes blood flow in the liver and reduces pressure in all abnormal veins, not only in the stomach and esophagus, but also in the bowel and the liver.
The TIPS procedure is not a surgical procedure. The radiologist performs the procedure within the vessels under X-ray guidance. The procedure lasts 1 to 3 hours. You should expect to stay in the hospital 1 to 2 days after the procedure.
The TIPS procedure controls bleeding immediately in over 90% of patients. However, in about 30% of patients, the shunt may narrow, causing varices to bleed again at a later time.
What are potential complications of the TIPS procedure?
Shunt narrowing or occlusion (blockage) can occur any time after the procedure, and most frequently within the first year. Follow-up ultrasound examinations are performed frequently after the TIPS procedure to detect these complications. The signs of occlusion include increased ascites or recurrent bleeding. This condition can be treated by a radiologist who re-expands the shunt with a balloon or repeats the procedure to place a new stent.
Encephalopathy, or mental changes caused by abnormal functioning of the brain that occur with severe liver disease, is another potential complication. Encephalopathy can be worse when blood flow to the liver is reduced by TIPS, which may result in toxic substances reaching the brain without being metabolized first by the liver. This condition can be treated with medications, diet or by replacing the shunt.
What happens during the DSRS procedure?
The DSRS is a surgical procedure. During the surgery, the vein from the spleen (called the splenic vein) is detached from the portal vein and attached to the left kidney (renal) vein. This surgery selectively reduces the pressure in your varices and controls the bleeding. Portal Hypertension and Effects of Portal Hypertension Essay Paper
A general anesthetic is given to you before the surgery. The surgery lasts about 4 hours. You should expect to stay in the hospital from 7 to 10 days.
DSRS controls bleeding in over 90% of patients; the highest risk of any recurrent bleeding is in the first month. However, the DSRS procedure provides good long-term control of bleeding.
A potential complication of the DSRS surgery is ascites (an accumulation of fluid in the abdomen). This can be treated with diuretics and restricted sodium intake.
What is the follow-up care after the TIPS or DSRS procedures?
Follow-up medical care may differ from hospital to hospital. The following are some general guidelines for scheduling follow-up care:
Ten days after your hospital discharge date, you will meet with your surgeon or hepatologist and nurse coordinator to evaluate your progress. Lab work will be done at this time.
Six weeks after the TIPS procedure (and again 3 months after the procedure), you will have an ultrasound so your physician can check that the shunt is functioning properly. You will have an angiogram only if the ultrasound indicates that there is a problem. You will also have lab work done at these times and visit the surgeon or hepatologist and nurse coordinator.
Six weeks after the DSRS procedure (and again 3 months after the procedure), you will meet with the surgeon and nurse coordinator to evaluate your progress. Lab work will be done at this time.
Six months after either the TIPS or DSRS procedure, you will have an ultrasound to make sure the shunt is working properly. You will also visit the surgeon or hepatologist and nurse coordinator to evaluate your progress. Lab work and a galactose liver function test will also be done at this time.
Twelve months after either procedure, you will have another ultrasound of the shunt. You will also have an angiogram so your physician can check the pressure within your veins across the shunt. You will meet with your surgeon or hepatologist and the nurse coordinator. Lab work and a galactose liver function test will be done at this time.
If the shunt is working well, every 6 months after the first year of follow-up appointments you will have an ultrasound and lab work, and you will visit with your physician and nurse coordinator.
More frequent follow-up visits may be necessary, depending on your condition. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Attend all follow-up appointments as scheduled to ensure that the shunt is functioning properly. Be sure to follow the dietary recommendations that your healthcare providers give you.
What are other treatment procedures for portal hypertension?
Liver transplant is done in cases of end-stage liver disease.
Devascularization is a surgical procedure that removes the bleeding varices. This procedure is done when a TIPS or a surgical shunt is not possible or is unsuccessful in controlling the bleeding.
The accumulation of fluid in the abdomen (called ascites) sometimes needs to be directly removed. This procedure is called paracentesis.
Portal hypertension (PHT) is most commonly observed in patients with liver cirrhosis and is a major driver for associated complications, such as variceal bleeding, ascites or hepatic encephalopathy. Current PHT treatment strategies orientate on the existence and characterization of oesophageal varices, which strongly correlate with the hepatic venous pressure gradient (HVPG)—the gold standard for quantification of PHT. For prevention of variceal bleeding, oral non-selective beta blockers (NSBBs) are used, while, in acute bleeding situations, intravenous somatostatin, octreotide or terlipressin are available . These drugs aim to decrease portal pressure; however, not all patients achieve a haemodynamic response, which is defined by a HVPG decrease >10% of baseline. Thus, current research intensively seeks new treatment options for PHT. Most experimental strategies aim at structural (liver fibrosis) and/or dynamic (endothelial dysfunction, hyperdynamic circulation) factors, which contribute to the severity of PHT. In this review, we summarize close to 100 different pharmacotherapies and their potential for future use in PHT. Portal Hypertension and Effects of Portal Hypertension Essay Paper
The dynamic component of PHT is attributed to an increase in splanchnic arterial vasodilation and intrahepatic vascular resistance, which is at least partly mediated via adrenergic receptors. The established therapy with beta blockers counteracts the increased cardiac output (via β1) and substantially increases splanchnic resistance (via β2), which together reduces portal pressure [2,3]. Furthermore, α-receptor antagonism has been shown to additionally reduce intrahepatic resistance.
While there exists a plethora of beta-blocking agents, only a few NSBBs (propranolol, nadolol and carvedilol) are currently recommended for the treatment of PHT . Notably, selective β1 blockade might even increase portal pressure, which has been shown for nebivolol in experimental cirrhosis . On the other hand, additional α-receptor antagonism supports the NSBB-mediated decrease in HVPG. This has been demonstrated in clinical studies by the use of carvedilol (combined non-selective β and α1-blockade) [5–7] or by add-on therapy with the α1-antagonist prazosin [8,9].
Yet, according to a meta-analysis, haemodynamic response rates to NSBBs are only 46% . Furthermore, beta-blocker therapy increases the risk of arterial hypotension, which is especially of concern when combined with α-antagonism (e.g. carvedilol) and in decompensated patients, where NSBB therapy might be even detrimental [2,11]. Thus, research aims to refine adrenoceptor pharmacotherapy.
In experimental cholestatic cirrhosis, short-term therapy with the α2 antagonist BRL44408 significantly decreased portal pressure and did not alter systemic haemodynamics even without NSBB cotherapy, which, however, has been published in only two abstracts so far [12,13]. Portal Hypertension and Effects of Portal Hypertension Essay Paper
While NSBB effects are mediated via β1 and β2 adrenoceptors, recent studies also shed light upon the lesser known β3 adrenoceptor, which is up-regulated in experimental and human cirrhosis. Stimulation of β3 adrenoceptors leads to relaxation of hepatic stellate cells (HSCs) and intrahepatic vasodilation via activation of the adenylyl cyclase and by inhibition of Rho-kinase. Accordingly, in cirrhotic rodent models, two studies measured significant declines in portal pressure after treatment with the β3 agonists CGP12177A and SR58611A, respectively [14,15].
Improving adrenergic vascular contractility in the splanchnic area can also be achieved by neuropeptide Y, which seems to be especially effective in PHT [16,17]. Accordingly, treatment with neuropeptide Y in cirrhotic rats translated into a significant amelioration of the portal hypertensive syndrome and PHT without changing mean arterial pressure . In line, also administration of zolmitriptan, which mediates mesenteric vasoconstriction not via beta blockade, but via the 5-HT1 receptor, dose-dependently reduced portal pressure. Although this portal hypotensive effect was of short duration, co-administration with NSBBs synergistically prolonged and enhanced the decrease in portal pressure .
For staging of chronic liver disease, a variety of different tools are available, including physical examination, laboratory tests, imaging techniques, and hemodynamic measurements ( Figure 2). Imaging techniques comprise endoscopy, ultrasound, determination of liver stiffness, computed tomography, and magnetic resonance imaging (MRI). Physical examination includes important parameters of the Child–Pugh classification 8. If there are no signs of jaundice, ascites, or encephalopathy, the patient has a good chance of being in a compensated stage of cirrhosis with a 10-year survival of above 50%, while clinical signs of decompensation indicate a mortality of more than 75% within the next 5 years 9. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Endoscopy is still the best method to assess the existence of varices in the upper intestinal tract as well as their size and potential to bleed or rebleed 10. While in any patient with suspected liver cirrhosis a standard examination used to include endoscopy, new guidelines recommend abstaining from early endoscopy in patients with liver stiffness <20 kPa and platelet count >150 G/L 11, 12. These patients have a high probability of being free of esophageal varices 13. However, endoscopy retains its central role as the entrance test for the initiation of primary and secondary prophylaxis of variceal bleeding in patients with higher stiffness values or a lower platelet count, and it is still the central method for the assessment of variceal bleeding and hemostasis 12.
In addition, elastographic techniques enable estimation of the degree of liver fibrosis via transient elastography (TE), acoustic radiation force impulse imaging (ARFI), or shear wave elastography (SWE) 14, 15. Determination of liver stiffness has by now become an important tool for screening of fibrosis and portal hypertension in patients with liver disease. Fibrosis leads to an increased stiffness of the liver. In organs with higher stiffness, shear waves travel with a higher speed through tissues. By delivering pulses, shear waves can be induced to assess their speed as an indirect measure of fibrosis. There are different systems using mechanical 50 Hz pulses (TE), a focused ultrasound pulse to deform internal tissue (AFRI and SWE), or a two-dimensional gradient-recalled-echo sequence analyzed by certain algorithms (magnetic resonance [MR] elastography).
The most extensive experience to date exists for TE, a stand-alone technique based on shear wave speed measurement, not integrated into ultrasound devices 16– 18. Values below 5.2–9.5 kPa (TE) or 1.22–1.63 m/s (ARFI) can rule out significant liver fibrosis, whereas higher values may be falsely positive with respect to cirrhosis assessment because of obstructive cholestasis, liver congestion, severe liver inflammation, or infiltrative liver disease 16, 17. However, many of these obscuring conditions can be assessed or ruled out by using ultrasound-based techniques such as SWE or AFRI. SWE has shown slightly better sensitivity and specificity for liver fibrosis and portal hypertension when compared to TE 19. Nevertheless, observing standardized conditions like fasting state is important 20. By combining liver and spleen SWE, portal hypertension can be excluded with a very high probability 21 on the one hand or assessed in its clinically significant form on the other 22. Furthermore, ultrasound-based techniques allow for hepatocellular carcinoma (HCC) screening. Portal Hypertension and Effects of Portal Hypertension Essay Paper
The different systems have pros and cons. TE is available in many centers and is excellently validated but may have a high failure rate in obese patients or in patients with ascites. AFRI allows ultrasound guidance for the region of interest but is less validated, and high body weight may also be a problem. MR elastography allows one to cover a large sampling volume, but it is affected by iron deposition, high body mass index, and massive ascites 23.
Ultrasound allows a more sensitive and specific assessment of ascites than clinical examination together with assessment of size, surface, and echotexture of the liver.
Similar to ultrasound, computed tomography and MRI are relevant for the diagnosis of HCC. This is important, since liver fibrosis or cirrhosis is a precancerous condition. Of all imaging devices, MRI has the broadest potential for staging liver disease with respect to morphology, including the biliary system, tissue texture, perfusion, formation of collaterals, function of hepatic cells 24– 26, and quantification of steatosis or fibrosis 27, 28. However, it is expensive and not always available. We recently showed how MRI can be used to measure fat-free muscle area as a prognostic marker of sarcopenia, correlated with survival 29 in patients with liver cirrhosis.
Among hemodynamic measurements, assessment of the hepatic venous pressure gradient (HVPG) 30 is the most important in chronic liver disease. Developed in the 1950s 31 and later modified by Groszmann et al. 32, it has become the gold standard for indirect assessment of the degree of portal hypertension. The HVPG value closely correlates with the portal vein pressure, especially in alcoholic liver disease 33, which in turn shows a significant correlation with blood pressure in esophageal varices 34. HVPG values above 5 mmHg are regarded as portal hypertension. Measurement of the HVPG adds prognostic information to standard laboratory and clinical evaluations in advanced liver disease 35, 36. Patients with compensated cirrhosis and HVPG <10 mmHg have a rather low risk of developing varices or decompensation of liver function 37. It is generally accepted that esophageal varices do not bleed if HVPG remains below 12 mmHg and that a reduction of HVPG by more than 20%, regardless of the baseline value, considerably reduces the risk of bleeding from varices. Thus, measurement of HVPG has repeatedly been advocated as a means to tailor the treatment for variceal bleeding 35, 38. There is a good correlation between liver stiffness, as assessed by TE, and HVPG 39. Values below 14 kPa exclude clinically significant portal hypertension (HVPG ≥10 mmHg) with high sensitivity and specificity 40. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Since the introduction of the Child–Turcotte classification 8 and its modification according to Pugh et al. 41, it has been repeatedly shown that, in patients with liver cirrhosis, laboratory values reflecting hepatocyte function, e.g. uptake and secretion of bilirubin or synthesis of proteins, allow prediction of the probability of survival. Thus, serum levels of bilirubin, albumin, or clotting factors have been used for decades to stage chronic liver disease. They are part of the model for end-stage liver disease (MELD) system 42 as well as of the Child–Pugh classification 41.
The MELD consists of serum levels of bilirubin and creatinine and prothrombin time determined as an international normalized ratio (INR). Initially developed to determine the prognosis of patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) 42, 43, it is now used to assess organ allocation priority for liver transplantation. It can be calculated easily, has been validated prospectively in different cohorts, and contains no clinical parameters based on subjective assessment. Nevertheless, MELD is only slightly superior to the Child–Pugh model in the prediction of survival 44, 45. The addition of further parameters such as sodium 46, hepatic encephalopathy 45, or sarcopenia 47 to MELD has been described to further improve prognosis with marginal effects.
Impairment of kidney function, such as sodium handling, occurs early in patients with liver disease 48, and elevated creatinine levels—or, more importantly, an increase in serum creatinine by ≥0.3 mg/dL – are independent markers for negative patient outcome 49.
Patients with liver cirrhosis are prone to systemic inflammation, where mostly cytokines of the innate immune system are involved 50. This paves the way towards fatal dysfunction of organs, now coined acute-on-chronic liver failure (ACLF) 51. Thus, signs of inflammation, such as high leukocyte count and elevated C-reactive protein, are additional important prognostic parameters 52. Interestingly, there is a subgroup of patients who, even after TIPS insertion, show an increased or unchanged liver stiffness. These are patients with high levels of proinflammatory cytokines. They have a bad outcome 53. Thus, dynamics in liver stiffness may be an easy read-out to assess inflammation and prognosis in TIPS patients. Furthermore, the individual genetic background with respect to genes coding for proteins involved in the immune response may predispose patients to infections, ACLF, and decompensation 54– 58. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Many of the above-mentioned parameters are part of staging systems for liver cirrhosis designed to distinguish between compensated and decompensated disease at different states 59. If it is true that the intestine is important for the initiation and perpetuation of liver disease (see below), we will also need some sort of staging for intestinal dysfunction in patients with liver disease in the future.
The different staging systems mentioned above, such as the degree of fibrosis, HVPG, ongoing etiology, Child–Pugh, dynamics of kidney dysfunction, or signs of inflammation, are partly interrelated. Thus, HVPG increases with the degree of cirrhosis 60, 61 or the degree of decompensation as assessed by the Child–Pugh score. However, the correlation is loose, and the prognostic value of HVPG is partly independent of the Child–Pugh system 62, 63. Therefore, there is always the question of how to integrate different parameters or scores into an appropriate and simple bedside system. Clinical judgment is quite accurate for advanced liver disease. Jaundice and ascites are markers of bad prognosis. In this situation, bleeding, infections, overt encephalopathy, and deterioration of kidney function denote high risk of death. Determination of HVPG and/or of liver stiffness may improve long-term prognosis in patients with compensated cirrhosis 59, and HVPG alone is an independent prognostic marker in patients with decompensated cirrhosis and variceal bleeding 36, 62, 63. In the future, we will probably have to adapt to more complex systems 59, 64 which might improve prognosis and therapy. No matter which stage of disease, the interruption of etiology, be it alcohol intake or viremia, is crucial.
What causes portal hypertension?
The most common cause of portal hypertension is cirrhosis, or scarring of the liver. Cirrhosis results from the healing of a liver injury caused by hepatitis, alcohol abuse or other causes of liver damage. In cirrhosis, the scar tissue blocks the flow of blood through the liver and slows its processing functions. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Portal hypertension may also be caused by thrombosis, or a blood clot that develops in the portal vein.
What are the symptoms of portal hypertension?
The onset of portal hypertension may not always be associated with specific symptoms that identify what is happening in the liver. But if you have liver disease that leads to cirrhosis, the chance of developing portal hypertension is high.
The main symptoms and complications of portal hypertension include:
Gastrointestinal bleeding: Black, tarry stools or blood in the stools; or vomiting of blood due to the spontaneous rupture and bleeding from varices.
Ascites: An accumulation of fluid in the abdomen.
Encephalopathy: Confusion and forgetfulness caused by poor liver function and the diversion of blood flow away from your liver.
Reduced levels of platelets or decreased white blood cell count.
What is cirrhosis and portal hypertension?
Cirrhosis is a form of liver disease. It occurs when cells in your liver become damaged and your body can’t repair them. As the liver cells die, scar tissue forms. A buildup of scar tissue prevents proper blood flow. A normal liver is able to filter wastes and poisons to get them out of your body. If scar tissue keeps blood from flowing through your liver, it can’t get filtered. This causes poisons and wastes to build up in your body.
Portal hypertension is a leading side effect of cirrhosis. Your body carries blood to your liver through a major blood vessel called the portal vein. Cirrhosis slows your blood flow and puts stress on the portal vein. This causes high blood pressure known as portal hypertension.
Symptoms of cirrhosis
Cirrhosis is a condition that happens over time. You may not have any symptoms in the early stages. Contact your doctor if you begin to notice the following symptoms or signs. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Loss of appetite.
Unplanned weight loss.
Weakness and fatigue.
Jaundice (yellowing of your skin and eyes).
Menstrual problems (in women).
Mental confusion, such as a hard time focusing or remembering.
Swelling or bloating in your stomach, due to fluids collecting.
What causes cirrhosis?
There are three main causes of cirrhosis.
Alcohol-related liver disease. Drinking too much alcohol can lead to cirrhosis. This includes long-term alcohol use and frequent binge drinking.
Fatty liver disease. This occurs when too much fat builds up in your liver. People who are overweight or obese, or have diabetes, high cholesterol, or high blood pressure are more at risk for this disease.
Hepatitis B and C. These are viral infections that you can contract.
Minor causes of cirrhosis include:
certain genetic diseases, such as Wilson disease or autoimmune hepatitis
continued exposure to toxic chemicals
infections caused by parasites
continued use of certain medicines
certain congenital heart defects or chronic heart failure.
How is cirrhosis and portal hypertension diagnosed?
To diagnose cirrhosis, your doctor will begin with a physical exam. They also will review your symptoms, health history, and lifestyle. Tests are needed to check your liver and confirm diagnosis. These include blood and imaging tests. Blood tests can detect hepatitis, abnormal enzyme levels, or abnormal blood cells. Imaging tests look at and take pictures of your liver. In some cases, your doctor may do a biopsy on your liver. This involves taking a sample of liver tissue to look at it in the lab.
If you have cirrhosis, your doctor will likely check for portal hypertension. They will check your stomach for extra fluid (ascites). They will check for swelling or pressure in the blood vessels around your portal vein. The doctor may perform other lab or imaging tests to diagnose portal hypertension. They also may do an endoscopy.
Can cirrhosis be prevented or avoided?
Some people can make lifestyle changes to help prevent cirrhosis. These include drinking safe amounts of alcohol, maintaining a healthy diet, and protecting yourself from hepatitis. If you are overweight or obese, talk to your doctor about how to safely lose weight. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Cirrhosis and portal hypertension treatment
The goal for cirrhosis treatment is to relieve symptoms and prevent further damage. Treatment also can avoid or manage complications caused by cirrhosis. With this condition, blood can’t flow normally through the portal vein. The blood has to return to your heart through other blood vessels. Most often it goes through blood vessels in your stomach, esophagus, or intestines. These vessels then swell due to the increased amount of blood flowing through them. This puts pressure on the vessels and can cause them to burst. Bleeding from a broken blood vessel is serious and can be fatal.
Your doctor may prescribe medicine to help prevent your blood vessels from bursting. These medicines have some side effects and may interact with other medicines. They are not suitable for everyone. Your doctor may prescribe medicine to lower your blood pressure if you have portal hypertension. If you have hepatitis, your doctor will prescribe an antiviral medicine. You may need other medicines, depending on the cause of cirrhosis.
If medicine isn’t enough, you may need surgery. Surgery can decrease pressure by interrupting the blood flow in your blood vessels. The doctor or surgeon will insert a long tube through your mouth to your stomach. Then, they will place rubber bands or hardened chemicals in the swollen blood vessels to block them off. Another type of procedure, called TIPS (transjugular intrahepatic portosystemic shunt), may be done in some cases. Portal Hypertension and Effects of Portal Hypertension Essay Paper
People who have portal hypertension may need surgery to connect certain blood vessels. If a blood vessel does burst, you will need surgery to stop the bleeding and repair it.
If surgery doesn’t work or you have liver failure, you may need a liver transplant.
Living with cirrhosis and portal hypertension
There is no cure for cirrhosis. Work with your doctor on a treatment plan to manage symptoms and help prevent more damage. You should not drink any alcohol. It continues to damage your liver. Talk with your doctor before taking any medicines. This includes antibiotics, birth control pills, and over-the-counter drugs, such as acetaminophen. It’s also important to take good care of yourself. Ask your doctor if you should follow a special diet. You may need to watch how much sugar and protein you eat. If you have swelling or are retaining fluid, avoid salt or sodium.
Your doctor may recommend screening for liver cancer. If left untreated, cirrhosis can get worse and be life threatening. It can cause a coma, liver failure, or death.
WebMD helps you understand portal hypertension.
What Causes Portal Hypertension?
The most common cause of portal hypertension is cirrhosis of the liver. Cirrhosis is scarring which accompanies the healing of liver injury caused by hepatitis, alcohol, or other less common causes of liver damage. In cirrhosis, the scar tissue blocks the flow of blood through the liver. Portal Hypertension and Effects of Portal Hypertension Essay Paper
Other causes of portal hypertension include blood clots in the portal vein, blockages of the veins that carry the blood from the liver to the heart, a parasitic infection called schistosomiasis, and focal nodular hyperplasia, a disease seen in people infected with HIV, the virus that may lead to AIDS. Sometimes the cause is unknown.
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What Are the Symptoms of Portal Hypertension?
The onset of portal hypertension may not always be associated with specific symptoms that identify what is happening in the liver. But if you have liver disease that leads to cirrhosis, the chance of developing portal hypertension is high.
The main symptoms and complications of portal hypertension include:
Gastrointestinal bleeding marked by black, tarry stools or blood in the stools, or vomiting of blood due to the spontaneous rupture and hemorrhage from varices
Ascites (an accumulation of fluid in the abdomen)
Encephalopathy or confusion and forgetfulness caused by poor liver function
Reduced levels of platelets, blood cells that help form blood clots, or white blood cells, the cells that fight infection
How Is Portal Hypertension Diagnosed?
Usually, doctors make the diagnosis of portal hypertension based on the presence of ascites or of dilated veins or varices as seen during a physical exam of the abdomen or the anus. Various lab tests, X-ray tests, and endoscopic exams may also be used. Portal Hypertension and Effects of Portal Hypertension Essay Paper
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