Pathophysiology of Portal Hypertension

							                   Pathophysiology of Portal Hypertension

                                      John F. Reinus, MD



Portal hypertension is usually the result of             within the diseased liver is limited by fibrosis      Notes
hepatic fibrosis and nodular regeneration (cir-          so that the intrahepatic circulation can’t relax
rhosis) caused by chronic necroinflammatory              to accommodate more blood flow. Under these
liver injury. Increased portal blood pressure            circumstances, portal pressure continues to rise
has effects on systemic hemodynamics, fluid              and a worsening cycle of vasodilation, volume
and electrolyte balance and renal perfusion that         expansion and rising portal pressure develops.
result in significant physiologic derangements
and morbidity.                                           The inability of the cirrhotic liver to accommo-
                                                         date constantly increasing portal blood flow has
Portal blood pressure is described by Ohm’s              two important pathophysiologic consequences
Law: P = Q x R, where P is portal pressure, Q is         with the effect of decompressing the portal cir-
blood flow and R is vascular resistance. Flow            culation. First, blood begins to flow around the
(Q) through the portal circuit is determined by          liver through available collaterals that gradually
venous return from the splanchnic organs and is          enlarge, and, in the case of esophageal varices,
not effectively limited by rises in portal venous        often rupture and bleed. Second, increasing por-
pressure. Normal portal vessels are highly com-          tal pressure reduces blood volume by forcing a
pliant to accommodate increases in flow. In              plasma transudate out of the hepatic sinusoids.
response to shear-induced upregulation of endo-          This fluid sweats off the surface of the liver into
thelial nitric oxide synthase (eNOS), portal ves-        the abdominal cavity, eventually overwhelming
sels dilate and vascular resistance falls as flow        the lymphatic return to the systemic circulation
rises, maintaining a stable portal blood pressure.       and accumulating as ascites.
Resistance to flow (R) is proportional to 1/r4,
where r is the vascular radius. Small changes in         Decreased effective renal blood flow is a major
blood vessel size, including failure of vessels to       consequence of the circulatory changes that
dilate in response to increased portal blood flow        develop in patients with portal hypertension.
(reduced compliance), may cause a significant            Abnormally elevated portal pressure and sec-
increase in portal blood pressure.                       ondary vasodilation with decreased effective
                                                         plasma volume are responsible for a functional
Systemic and splanchnic vasodilation are direct          form of chronic prerenal azotemia referred to
physiologic consequences of increased portal             as type-II hepatorenal syndrome. Eventually,
pressure. When portal pressure rises, initial            affected patients may develop oliguric renal fail-
reflex vasoconstriction of the mesenteric arte-          ure, or type-I hepatorenal syndrome.
rial circulation causes intestinal hypoxia that
leads to upregulation of VEGF and eNOS, and              References
consequent vasodilation. At the same time, por-
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                                                              kidney injury in cirrhosis. Hepatology
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plasma volume. The immediate consequence of              3.   Wiest R and Groszmann RJ. Nitric oxide
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portal blood flow (Q). Venous compliance

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4.   Schrier RW, Arroyo V, Bernardi M, et al.            Notes
     Peripheral arterial vasodilation hypoth-
     esis – a proposal for the initiation of renal
     sodium and water retention in cirrhosis.
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