Why does liver failure cause edema

The doctor may prescribe a beta-blocker or nitrate for portal hypertension. Beta-blockers can lower the pressure in the varices and reduce the risk of bleeding. Gastrointestinal bleeding requires an immediate upper endoscopy to look for esophageal varices. The doctor may perform a band-ligation using a special device to compress the varices and stop the bleeding.

People who have had varices in the past may need to take medicine to prevent future episodes. Hepatic encephalopathy is treated by cleansing the bowel with lactulose-a laxative given orally or in enemas.

Antibiotics are added to the treatment if necessary. Patients may be asked to reduce dietary protein intake. Hepatic encephalopathy may improve as other complications of cirrhosis are controlled. Some people with cirrhosis who develop hepatorenal failure must undergo regular hemodialysis treatment, which uses a machine to clean wastes from the blood. Medications are also given to improve blood flow through the kidneys.

Other treatments address the specific causes of cirrhosis. Treatment for cirrhosis caused by hepatitis depends on the specific type of hepatitis. For example, interferon and other antiviral drugs are prescribed for viral hepatitis, and autoimmune hepatitis requires corticosteroids and other drugs that suppress the immune system. Medications are given to treat various symptoms of cirrhosis, such as itching and abdominal pain. When is a liver transplant indicated for cirrhosis?

A liver transplant is considered necessary when complications cannot be controlled by treatment. Liver transplantation is a major operation in which the diseased liver is removed and replaced with a healthy one from an organ donor. A team of health professionals determines the risks and benefits of the procedure for each patient. Survival rates have improved over the past several years because of drugs that suppress the immune system and keep it from attacking and damaging the new liver.

The number of people who need a liver transplant far exceeds the number of available organs. A person needing a transplant must go through a complicated evaluation process before being added to a long transplant waiting list.

Generally, organs are given to people with the best chance of living the longest after a transplant. Survival after a transplant requires intensive follow-up and cooperation on the part of the patient and caregiver.

What causes cirrhosis? Most people who consume alcohol do not suffer damage to the liver. But heavy alcohol use over several years can cause chronic injury to the liver.

The amount of alcohol it takes to damage the liver varies greatly from person to person. For women, consuming two to three drinks-including beer and wine-per day and for men, three to four drinks per day, can lead to liver damage and cirrhosis. In the past, alcohol-related cirrhosis led to more deaths than cirrhosis due to any other cause.

Deaths caused by obesity-related cirrhosis are increasing. Chronic hepatitis C The hepatitis C virus is a liver infection that is spread by contact with an infected person's blood. Chronic hepatitis C causes inflammation and damage to the liver over time that can lead to cirrhosis. Chronic hepatitis B and D The hepatitis B virus is a liver infection that is spread by contact with an infected person's blood, semen, or other body fluid.

Hepatitis B, like hepatitis C, causes liver inflammation and injury that can lead to cirrhosis. The hepatitis B vaccine is given to all infants and many adults to prevent the virus. Hepatitis D is another virus that infects the liver and can lead to cirrhosis, but it occurs only in people who already have hepatitis B.

This increasingly common liver disease is associated with obesity, diabetes, protein malnutrition, coronary artery disease, and corticosteroid medications. Autoimmune hepatitis This form of hepatitis is caused by the body's immune system attacking liver cells and causing inflammation, damage, and eventually cirrhosis.

Researchers believe genetic factors may make some people more prone to autoimmune diseases. About 70 percent of those with autoimmune hepatitis are female.

Diseases that damage or destroy bile ducts Several diseases can damage or destroy the ducts that carry bile from the liver, causing bile to back up in the liver and leading to cirrhosis. In adults, the most common condition in this category is primary biliary cirrhosis, a disease in which the bile ducts become inflamed and damaged and, ultimately, disappear. Secondary biliary cirrhosis can happen if the ducts are mistakenly tied off or injured during gallbladder surgery.

Primary sclerosing cholangitis is another condition that causes damage and scarring of bile ducts. In infants, damaged bile ducts are commonly caused by Alagille syndrome or biliary atresia, conditions in which the ducts are absent or injured.

Inherited diseases Cystic fibrosis, alpha-1 antitrypsin deficiency, hemochromatosis, Wilson disease, galactosemia, and glycogen storage diseases are inherited diseases that interfere with how the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.

Cirrhosis can result from these conditions. Drugs, toxins, and infections Other causes of cirrhosis include drug reactions, prolonged exposure to toxic chemicals, parasitic infections, and repeated bouts of heart failure with liver congestion. Complications of Cirrhosis Because the liver becomes lumpy and stiff in cirrhosis, blood cannot flow through it easily, so pressure builds up in the vein that brings blood to the liver.

Edema and ascites When liver damage progresses to an advanced stage, fluid collects in the legs, called edema, and in the abdomen, called ascites. Ascites can lead to bacterial peritonitis, a serious infection. Bruising and bleeding When the liver slows or stops producing the proteins needed for blood clotting, a person will bruise or bleed easily.

Portal hypertension Normally, blood from the intestines and spleen is carried to the liver through the portal vein.

But cirrhosis slows the normal flow of blood, which increases the pressure in the portal vein. Spontaneous bacterial peritonitis. Hepatorenal syndrome. Hepatic hydrothorax. Fluid retention in cirrhosis: pathophysiology and management. Kashani , A. Oxford Academic. Revision received:. Cite Cite A. Select Format Select format. Permissions Icon Permissions.

Abstract Accumulation of fluid as ascites is the most common complication of cirrhosis. Table 1 Classification of ascites. Severity 4. Open in new tab. Figure 1. Open in new tab Download slide. Figure 2. Pathophysiology of spontaneous bacterial peritonitis. Figure 3. Table 2 Findings suggesting secondary peritonitis.

Ascitic fluid culture result is not monomicrobial. Table 4 Summary of the most promising treatment options for HRS. Table 5 Treatments for hepatic hydrothorax. Type of treatment. Terlipressin 4 mg i. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Google Scholar Crossref. Search ADS. Natural history of patients hospitalized for management of cirrhotic ascites.

The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Clinical practice guidelines for the management of cirrhotic patients with ascites. Google Scholar PubMed.

Increased hepatic resistance: a new target in the pharmacologic therapy of portal hypertension. Renal sodium retention in portal hypertension and hepatorenal reflex: from practice to science. Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites.

Beneficial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis. A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis.

Randomized trial comparing, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis. Transjugular intrahepatic portosystemic shunt in refractory ascites: a meta-analysis.

Transjugular intrahepatic portosystemic shunts: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. A comparison of paracentesis and transjugular intrahepatic portosystemic shunting in patients with ascites.

Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Randomized controlled study of TIPS versus paracentesis plus albumin in cirrhosis with severe ascites.

Long-term patency is expected with covered TIPS stents: this effect may not always be desirable! TIPS versus peritoneovenous shunt in the treatment of medically intractable ascites: a prospective randomized trial. Randomized, comparative study of oral ofloxacin versus intravenous cefotaxime in spontaneous bacterial peritonitis.

Effect of cisapride on intestinal bacterial overgrowth and bacterial translocation in cirrhosis. Intestinal mucosal oxidative damage and bacterial translocation in cirrhotic rats. A sequential study of serum bacterial DNA in patients with advanced cirrhosis and ascites. Clinical significance of the evaluation of hepatic reticuloendothelial removal capacity in patients with cirrhosis. Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis.

Low C3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis. Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Improved method for bacteriological diagnosis of spontaneous bacterial peritonitis.

Culture-negative neutrocytic ascites: a less severe variant of spontaneous bacterial peritonitis. Nosocomial spontaneous bacterial peritonitis and bacteremia in cirrhotic patients: impact of isolate type on prognosis and characteristics of infection. Spontaneous vs secondary bacterial peritonitis. Differentiation by response of ascitic fluid neutrophil count to antimicrobial therapy. Usefulness of urine strip test in the rapid diagnosis of spontaneous bacterial peritonitis.

Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections. Two different dosages of cefotaxime in the treatment of spontaneous bacterial peritonitis in cirrhosis: results of a prospective, randomized, multicenter study. Randomized trial comparing ceftriaxone with cefonicid for treatment of spontaneous bacterial peritonitis in cirrhotic patients.

Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. Norfloxacin versus ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage.

Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Trimethoprim-sulfamethoxazole versus norfloxacin in the prophylaxis of spontaneous bacterial peritonitis in cirrhosis.

Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis.

Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites. Reduction in renal blood flow following acute increase in the portal pressure: evidence for the existence of a hepatorenal reflex in man?

For this reason, the investigation of the pathogenesis of brain edema has been frequently hampered by the presence of various degrees of intracranial hypertension in different studies. Rapid development of brain edema in a patient with fulminant hepatic failure. On the right, the TC scanner made at admission was normal.

On the left, the TC scanner performed 8 hours later shows evident signs of brain edema. The cranium is a space with a fixed, non-distensible volume.

This distribution is important as small increases in cell volume will lead to large increases in the total volume of the brain. Intracranial hypertension is the result of an increase in volume in one or more of the previous compartments, without equivalent reduction of the others Monro-Kelly doctrine. Brain compliance has several important qualities see figure 2.

First, compliance is lower when the increase in volume is acute, which can leave no time for compensating mechanisms to develop. Second, when the increase in volume is continuous, compliance decreases progressively with time, leading ultimately to increased intracranial pressure.

Third, when compliance is low, a small increase in volume, for example of cerebral blood volume, can lead to large increases of intracranial pressure. Relation between increase of volume and intracranial pressure compliance. Continuous increases of volume leads to progressively larger increases of intracranial pressure.

Even though the increase of volume is the same in A and B, the lower brain compliance results in higher increases of pressure in B. The curve will be steeper when the insult is acute, due to a lesser capacity of compensation. In ALF, intracranial hypertension is usually the manifestation of an increase in water content of brain tissue. Cerebral imaging has shown a reduction of cerebrospinal fluid in ALF.

Astrocyte swelling is a common finding in neuropathological studies of brain autopsy material from patients with ALF 10 and from animal models of brain edema due to ALF. Tight junctions that characterize endothelial cells of brain capillaries were intact in all ultrastructural studies, excluding a gross disruption of the blood-brain barrier in ALF. Several functional studies have shown increased permeability to inulin, 16 sucrose, 16 GABA and analogues, 17 , 18 Trypan blue 15 , 19 or horseradish peroxidase 12 in different animal models of ALF and even in the rat 24 hours after portacaval anastomosis PCA.

For many years, several hypotheses have tried to independently explain the occurrence of brain swelling in ALF. In the last decade, however, we have witnessed a progressive convergence of previously excluding theories to a more rational context, based on solid research observations. A critical role for ammonia is now evident. First, hyperammonemia alone appears sufficient as a cause of brain edema, as brain edema is seen in hyperammonemic patients with genetic disorders of urea cycle enzymes who do not have other alterations of liver function.

An osmotic disturbance of the astrocyte as a result of ammonia is an observation that finds most support in clinical and experimental data. The main pathway for detoxification of ammonia is through formation of glutamine as the brain lacks a complete urea cycle. Because glutamine is a compound with osmotic properties, its accumulation within the astrocyte has been proposed as one of the mechanism leading to astrocyte swelling. The presence of increased brain glutamine levels in animal models and patients with ALF or hyperammonemia has been confirmed in multiple studies.

Accumulation of glutamine alone, however, does not provide a complete explanation for the development of brain edema. Mild hypothermia 32 and indomethacin administration, 39 for example, reduce brain swelling and intracranial hypertension in ammonia-infused PCA rats, despite similar increases of glutamine in brain. Other elements must be present to account for the development of brain swelling.

One possibility would be the involvement of other organic osmoles, such as alanine. Alanine, which can be generated from transamination of glutamine, is also increased in the rat brain of ALF models. An alteration of the blood-brain barrier could explain a vasogenic theory for brain edema in ALF. Notably, functional abnormalities of the blood-brain barrier have been described in various experimental models.

Furthermore, no beneficial effects of corticosteroid therapy, a measure supposed to improve blood-brain barrier permeability, were seen in patients with ALF and intracranial hypertension. Total brain glutamate levels were found to be decreased in ALF 26 , 36 , 37 and in hyperammonemia. The increase of extracellular glutamate probably results from the impairment of glutamate re-uptake by astrocytes, given that decreased expression of astrocytic glutamate transporters as well as decreased astrocytic glutamate re-uptake have been shown in various experimental models.

A role for glutamate in the pathogenesis of brain edema in ALF is suggested by 1 glutamate induces astrocytes swelling when injected into the brain or in isolated preparations 59 - 61 2 brain extracellular glutamate correlates positively with severity of HE and brain water content in some ALF models, 41 , 48 and 3 administration of glutamate antagonists has been reported to increase survival 62 and to ameliorate brain edema 63 in rodents with acute ammonia intoxication.

Despite these observations, the exact role of glutamate in the production of brain edema in ALF requires further investigation. A potential role for oxidative and nitrosative stress in the pathogenesis of brain edema in ALF is being increasingly explored. In the clinical setting, treatment with the antioxidant N-acetylcysteine was associated with less frequent progression to coma and brain edema in patients with ALF.

An ammonia-induced increase of hemeoxygenase-1 gene expression, which is considered the best gene-marker of oxidative stress, also supports this assumption. Evidence for nitrosative stress arises also from cellular studies, where exposure of isolated astrocytes to ammonia resulted in increased nitration of protein tyrosine residues.

Even though of considerable interest, further in vitro and in vivo work is needed in order to clarify the role of oxidative and nitrosative stress in the pathogenesis of brain edema in ALF. In patients with ALF, a wide spectrum of values of CBF has been reported, ranging from abnormally low to abnormally high levels.

Thus, the wide spectrum of CBF in ALF is more likely to reflect a real situation where CBF is subjected to the influence of multiple factors, 80 such as disease severity, systemic haemodynamics or extrahepatic complications. Despite these variations, it is now well accepted that cerebral oxidative metabolism is preserved in ALF, 81 , 82 with CBF usually higher than the metabolic needs of the brain the so-called luxury perfusion.

In the following paragraphs, we will examine how the normal coupling between CBF and brain metabolism is altered in ALF, and how changes of CBF can influence the development of intracranial hypertension and brain edema in ALF. In normal conditions, CBF varies according to the metabolic requirements of the brain, 83 increasing or decreasing in parallel with brain activity.

This autoregulation occurs independently of changes in mean arterial pressure or cardiac output, whenever blood pressure varies within the limits of 60 to mmHg. In patients with ALF, cerebral hyperemia has been associated with deeper coma, increased brain edema and higher mortality. The mechanism by which CBF can influence brain edema deserves further attention.

Changes in CBF and cerebral autoregulation in ALF could favour water flux into the brain by affecting mainly several components of the Starling equation. Also, given that autoregulation is lost in ALF as a consequence of cerebral arteriolar vasodilatation, 86 variations in systemic arterial pressure will greatly influence the hydrostatic pressure in the capillaries.

Second, an increase in CBF would result in increased ammonia delivery to the brain. Finally, an increase in CBF could lead to a larger capillary membrane area A if new capillaries were opened capillary recruitment , but the relevance of such mechanism in the brain is controversial.

The net consequence of an increase in blood flow is to raise ammonia delivery to the brain. Indeed, small increases in blood flow will greatly increase ammonia delivery to the brain in a hyperammonemic state Figure 3. Influence of cerebral blood flow on ammonia delivery to the brain. The right panel shows calculated absolute values of ammonia delivery for different values of cerebral blood flow and levels of plasma ammonia.

With increased ammonia levels, an increase in cerebral blood flow leads to disproportionate increases of ammonia delivery to the brain. All clinicians recognize that multiple factors can potentially influence the development of HE. Thus, it is not surprising that a wide array of factors can affect the expression of brain edema and intracranial hypertension in the clinical setting. Infection is a well-known precipitant of hepatic encephalopathy in chronic liver disease.

Receptors for some cytokines such as IL-1 have been described in brain capillaries, suggesting that cytokines could exerts their effects in the brain even without crossing the blood-brain barrier. Improvement of brain edema and control of intracranial pressure after total hepatectomy has been reported in patients with ALF. Temperature is a component of the systemic inflammatory response syndrome.

Whereas hypothermia has been shown to exert beneficial effects in decreasing brain edema and intracranial pressure in patients 90 and animal models, 32 , 48 of ALF, hyperthermia is a deleterious event.

Hyperthermia was shown to precede surges of intracranial pressure in patients with ALF, , to increase cerebral blood flow in dogs, and to increase blood-brain barrier permeability in some animal models. Episodes of agitation often precede surges of intracranial pressure in patients with ALF, making the prevention and treatment of agitation an important aspect in the management of these patients. Agitation may reflect increase extra-cellular brain glutamate levels.

Changes in arterial pressure will influence CBF and intracranial pressure in the patient with ALF that has a loss of cerebral autoregulation and poor brain compliance. In this setting, even small increases of arterial pressure may lead to increased cerebral blood volume and intracranial hypertension. On the other hand, a decrease of arterial pressure in the patient with intracranial hypertension could lead to brain hypoxia.

Thus, monitoring of intracranial pressure and of jugular bulb oxygen saturation has been proposed to tailor the treatment with vasoactive drugs in ALF patients. Even though cerebral energy metabolism seems to be preserved until the last stages of the disease, brain metabolism of glucose is altered in ALF. Lactate is increased in the plasma of patients with ALF and was initially interpreted to be the result of tissue hypoxia.

Subsequent studies showed increased lactate production in the brain 64 and led the authors to postulate a pathological supply dependency of oxygen to the brain. First, Tofteng and cols. Based on these findings, the authors proposed that lactate may be implicated in the cerebral vasodilatation and surges of intracranial pressure in ALF. Second, Zwingman and cols. Based on these findings, the authors suggested that alterations of cellular glucose-and energy metabolism rather than the intracellular astrocytic accumulation of glutamine were the major cause of HE and brain edema in that model.

Further studies to investigate the role of glucose and lactate in HE and brain edema are needed, and could have important repercussions in the clinical management of these patients. Sodium concentration is the main factor determining plasma osmolarity under normal conditions. The relatively high frequency of central pontyne myelinolysis in hyponatremic cirrhotic subjects after liver transplantation is probably a reflection of the profound alteration of osmoregulation and osmo-compensation in the brain of these patients.

The consequences of hyponatremia were studied in experimental models. In the rat with portacaval anastomosis, induction of chronic hyponatremia by 1-desaminoDarginine vasopresin treatment decreased the levels of brain organic osmolytes. Importantly, infusion of ammonia resulted in a higher degree of brain edema in hyponatremic compared to normonatremic rats, despite an attenuated rise of glutamine in the former. These observations suggest that chronic hyponatremia makes the brain more vulnerable to an ammonia-induced osmotic disturbance with subsequent brain swelling.

In contrast, increasing plasma osmolarity by infusion of hypertonic saline has been observed to reduce intracranial hypertension in ALF, 93 its use is being evaluated in ongoing clinical trials. Alterations of potassium could also influence HE by altering normal ammonia metabolism.

Hypokalemia increases renal ammoniagenesis and seems to result in both increased urinary excretion and venous secretion of ammonia as seen in humans with chronic potassium depletion.

A highly orchestrated interorgan metabolism and trafficking of ammonia and glutamine is present in physiological conditions. Chronic and acute liver failure result in hyperammonemia and leads to an important disturbance of normal body nitrogen homeostasis for review see. Even though glutamine synthetase activity in skeletal muscle is low, its relative increased mass compared to other organs that contain this enzyme makes the muscle one of the main glutamine synthesizing organs. Due to the increased plasma ammonia levels in liver failure, the muscle becomes an important ammonia detoxifying organ.

Gastrointestinal bleeding is a known precipitant of HE. The liver damage done by cirrhosis generally can't be undone. But if liver cirrhosis is diagnosed early and the cause is treated, further damage can be limited and, rarely, reversed.

The liver is your largest internal organ. About the size of a football, it's located mainly in the upper right portion of your abdomen, beneath the diaphragm and above your stomach. Cirrhosis often has no signs or symptoms until liver damage is extensive. When signs and symptoms do occur, they may include:.

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