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Pathophysiology
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.
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.
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.
Pathophysiology
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.