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Cirrhotic ascites forms as the result of a particular sequence of events (Fig. 1). The current accepted theory of ascites formation is the peripheral arterial vasodilation hypothesis. This does not directly refute older hypotheses, but rather incorporates them into one uniform theory that matches actual hemodynamic data most closely.
Figure 1: Click to Enlarge
Development of portal hypertension is the first abnormality to occur in cirrhotic patients who develop ascites. Cirrhosis itself increases the resistance to blood flow within the liver, thereby causing the development of portal hypertension and shunting of blood to the systemic circulation. Portal pressures higher than 12 mm Hg are generally required for the accumulation of fluid in cirrhosis. This concept is important, because reducing portal pressure to lower than 12 mm Hg is the goal of many modern therapeutic maneuvers. As portal hypertension develops, a local release of vasodilators occurs. These vasodilators affect the splanchnic arteries and thereby decrease the effective arterial blood flow and arterial pressures. The precise agent(s) responsible for vasodilation is a subject of wide debate; however, most the recent literature has focused on the role of nitric oxide. Observations that implicate nitric oxide as the likely mediator of vasodilation in cirrhosis include the following:
1. Increased activity of nitric oxide synthase detected in the arteries of cirrhotic rats 2. High serum nitrite and nitrate levels (an index of nitric oxide synthesis) measured in cirrhotic patients
3. Inhibition of nitric oxide, leading to increased arterial pressure and systemic vascular resistance in animals
Progressive vasodilation leads to the activation of vasoconstrictor and antinatriuretic mechanisms, both in an attempt to restore normal perfusion pressures. Mechanisms involved include the renin-angiotensin system, sympathetic nervous system, and antidiuretic hormone (vasopressin). The ultimate effect is sodium and water retention. In the late stages of cirrhosis, free water accumulation is more pronounced than the sodium retention and leads to a dilutional hyponatremia. This explains why cirrhotic patients with ascites demonstrate urinary sodium retention, increased total body sodium, and dilutional hyponatremia, a challenging concept to many physicians. Liver Cirrhosis Cirrhosis is a chronic medical condition of liver abandoning the usual biochemical functioning of liver in the body. Cirrhosis is resulted from the surrogation of the liver tissues by regenerative nodules and fibrotic scar nodules that lead to the progressive loss of biochemical function of the liver. The common causes of Cirrhosis are hepatitis C, chronic hepatitis B; Wilson's disease, autoimmune hepatitis, hereditary hemochromatosis, alcoholism etc. and this become a crucial health problem of the mankind. The nodule formation and fibrosis lead to the alteration of the ordinary liver structure which obstructs the blood flow throughout the liver is the condition of Cirrhosis. Cirrhosis also leads to an incapability of performing liver biochemical functions. The pathophysiology of cirrhosis, the normal and anatomy of the liver provide the better understanding of the hazards of Cirrhosis. The liver is an important organ in the animal body where also where metabolism of toxins and drugs including alcohol are carried out. The biochemical functions of liver includes the synthesis of blood clotting factors, secretion and synthesis of albumin, the chief blood protein, secretion of bile and modification of its components. In addition, cholesterol metabolism and the conversion of fats and proteins into glucose like primary biochemical functions are also performed by the liver. Thus liver plays an important role in the functioning of the human body and deterioration in its functioning like by cirrhosis is of major biomedical concern and diagnosing the disease and immediate treatment is the best solution. Liver biopsy through a transjugular, percutaneous, fine-needle or laparoscopic approach is the best way to diagnose cirrhosis. On the basis of the results obtained from the histological studies cirrhosis can be divided into macronodular, micronodular, or mixed, but it is unfocused to the etiology and these may loss with the progress of the disease and serological sign are greatly specific. If the laboratory, clinical, and radiological records suggests cirrhosis them there is no requirement of going for liver biopsy. The only treatment of liver cirrhosis is the elimination of the causes and preventing complications of the disease. There is no such treatment to get the liver cirrhosis reversed back to the original healthy liver. Abstaining from alcoholism, timely treatment of hepatitis associated cirrhosis and other cirrhosis causing diseases are the ways for eliminating cirrhosis. If the cause is Wilson's disease then chelation therapy for removing the copper that build up in the body by this disease is effective. Medications including antibiotics are the best ways of preventing the complications of cirrhosis due to different causes. If the complications outbreaks the limit of control then liver transplantation is preferable. With advancement in the biomedical sciences the chances of
survival on liver transplantation or the success of it inflating and thus giving new hope of curing to the cirrhosis sufferers.
Pathophysiology The liver plays a vital role in synthesis of proteins (e.g. albumin, clotting factors and complement), detoxification and storage (e.g. vitamin A). In addition, it participates in the metabolism of lipids and carbohydrates. Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are still fully reversible. The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma, blocking the portal flow of blood through the organ and disturbing normal function. Recent research shows the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile (called myofibroblast) and obstructs blood flow in the circulation. In addition, it secretes TGF-β1, which leads to a fibrotic response and proliferation of connective tissue. Furthermore, it disturbs the balance between matrix metalloproteinases and the naturally occurring inhibitors (TIMP 1 and 2), leading to matrix breakdown and replacement by connective tissue-secreted matrix.
The fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. Portal hypertension is responsible for most severe complications of cirrhosis.
1. Ohm's law states that the change in pressure (ΔP) along a blood vessel is a function of the resistance to blood flow (R) and the rate of blood flow (Q) as expressed in the following
equation: ΔP = R x Q In a healthy individual, the liver is a very low resistance organ which passively receives whatever blood flow is coming from the mesenteric bed, a value that changes over the course of the day. The liver is able to accommodate these changes in blood flow without an increase in portal pressures by decreasing the resistance n the liver through the recruitment of additional hepatic sinusoids. Thus, the ΔP does not change despite an increase in Q because the R is reduced. One needs to understand how changes in both the resistance to blood flow in the portal system and volume of blood flow in the portal system in patients with cirrhosis combine to produce portal hypertension. 2. Resistance to blood flow is expressed by Poiseuille's law: R – 8nL / πr4 the most important variable affecting resistance is the radius based on the fact it's input is raised to the fourth power. For example, if the radius is reduced by ½ there is a 16-fold increase in resistance. L is the length of the vessel and n is the coefficient of viscosity both of which are constant under physiologic conditions. Patients with cirrhosis have an increase in resistance to blood flow through the liver at the level of the sinusoids and the hepatic and portal venules. This is predominantly due to fibrosis and regenerative nodules compressing/obliterating these vessels. The increased resistance to blood flow in portal hypertension may be pre-hepatic (such as blockage of the portal vein), intra-hepatic (pre-sinusoidal, sinusoidal, or post-sinusoidal), or post-hepatic (such as blockage of the IVC). See below. 3. There is also an increased rate of blood flow to the splanchnic circulation in patients with cirrhosis. Patients with cirrhosis have a hyperdynamic circulation marked by low peripheral vascular resistance and high cardiac output. Studies have shown that there is a 50% increase in flow to the GI tract, pancreas, and spleen in patients with cirrhosis. This hyperdynamic circulation is due to an elevated level of vasodilators is due to an elevated level of vasodilators (such as glucagon) in the blood and a decreased vascular sensitivity to vasoconstriction. The elevated levels of vasodilators are due to decreased hepatic metabolism due to shunting around the liver from the presence of collaterals and due to an increase in the production of local vasodilators (such as nitric oxide) by endothelial cells. 4. Thus, patients with cirrhosis develop portal hypertension both because on increased vascular resistance within the liver and increased splanchnic/portal blood flow.
Clinicoepidemiological Pattern of Esophageal Varices in Cirrhotic Patients in Hospital Raja Perempuan Zainab II (HRPZ II) Kota Bharu Kelantan S S Thein, S Rosemi, C H Nor Aizal, Y Y Lee, P Rajesh, A Fazlina Gas
SUMMARY INTRODUCTION Gastroesophageal variceal bleeding, a major complication of portal hypertension resulting from cirrhosis, accounts for 10–30% of all cases of upper gastrointestinal tract bleeding. MATERIALS AND METHODS Retrospective analysis of 60 patients who were diagnosed Liver Cirrhosis by ultrasound and were followed up in the Gastroenterology clinic of HRPZ II from January 2002 till December 2007. oesophagealgastroduodenoscope (OGDS) was performed on these patients. OBJECTIVE To assess the outcome of liver cirrhosis with esophageal varices who underwent Endoscopic Variceal Ligation (EVL) from January 2002 till December 2007. RESULTS There were 43 males (72%) and 17 females (28%). The commonest cause of liver cirrhosis in this cohort was Hepatitis B (52%, 31 patients). The cause was undetermined An
in 12 patients (20%). Eight patients (13%) had hepatitis C. Four patients had associated hepatoma, hepatits B and hepatitis C co-infection (three patients, 5%), alcohol and autoimmune hepatits (one patient, 2%). Forty-three (72%) patients had esophageal varices while 17 (28%) did not havetroenterology Unit, Department of Medicine, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia visible esophageal varices on endoscopy. Twelve patients (27%) presented with haemorrhage and all acute variceal
these patients had only one episode of variceal haemorrhage. There was no reported case of rebleeding. Thirty percent had large varices, 17% had moderately sized varices while 23% had small sized esophageal varices. For patients who presented with variceal haemorrhage 10 patients (83%) had large size varices, one patient (8%) had moderate and small size varices respectively. patients (38%) were Twenty-three
Child’s A liver cirrhosis, 15 patients (25%) Child’s B, 7 patients (12%) were Child’s C. Out of the 12 patients who
presented with variceal haemorrhage six patients (56%), three patients (25%) and two patients (16%) were in Child’s A, Child’s B and Child’s C respectively. Of the patients who had varices but did not bleed, eight patients (47%) had only one endoscopic variceal occasion, seven patients ligation (EVL)
received beta blocker (propanolol) for primary prophylaxis for portal hypertension while nine patients (75%) received beta blocker (propanolol) for secondary prophylaxis. Twenty-two follow-up. patients (37%) defaulted
CONCLUSION Commonest cause of liver cirrhosis in this study was chronic hepatitis B infection. proportion of patients Only a small
(41%) had 2 EVL occasions while one patient (6%) had 3 EVL occasions. Only three patients (6%) had successfully obliterated esophageal varices. Twenty-eight patients (65%)
(5%) had complete variceal eradication. Patients have poor compliance to beta blocker therapy
Med J Malaysia Vol 63 Supplement B August 2008
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