Portal Hypertension-Pola 060810

PATHOPHYSIOLOGY
Mediators in Portal Pressure:
• Nitric Oxide (NO) ‐derived from endothelial
NO synthase, is produced in response to
shear stress , inflammation and other stimuli
in the sinusoids and leads to hepatic
vasodilation
o In cirrhosis decreased NO availability
is thought to contribute to hepatic
vascular resistance causing portal
hypertension ; the effects are
probably minor since NO donors do
not change significantly the pressure
• Endothelin‐1 (ET‐1): also released by endothelial cells; promotes vasoconstriction and may also
paradoxically promote vasodilatation
• Carbon monoxide, norepinephrine, angiotensin, prostaglandins, thomboxane, leukotrienes, hydrogen
sulfide
Hemodynamics of Portal Hypertension
o Typically involves increases in portal resistance and inflow (Ohm’s law)
o Pressure gradient in the portal circulation is a function of portal flow are resistance to flow
o causes collaterals to form from the high pressure veins to the low pressure veins that are
insufficient for normalizing portal pressure and cause complications such as esophageal varices.
Mechanical Factors‐ difficult to fix
o fibrosis, nodularity of cirrhotic liver, distortion of vascular architecture,
remodeling in systemic and splanchnic vasculature from chronic increases in flow and shear stress
Vascular Factors ‐ important, potentially reversible, targets for therapies
o intrahepatic vasoconstriction, contributes to increased resistance
o splanchnic vasodilation
o systemic vasodilation