Wednesday, 17 October 2007

What is the pathogenesis of ascites in cirrhosis?

In advance: I'm aiming for medical students with this one, so apologies for assuming a certain level of terminology and understanding!

Recall that fluid filtration across capillary membranes is governed by Starling forces. Conceive of a system consisting blood in the capillaries, fluid in the interstitium, and a capillary wall that is capable of allowing a filtration of water in either direction. The forces tending towards pushing fluid out of the capillary - and thus making (interstitial) oedema - are the capillary hydrostatic pressure and the interstitial oncotic pressure. And the forces pulling water back into the capillary are of the interstitial hydrostatic pressure and the capillary oncotic pressure.

Which way the fluid will flow will depend on which set of forces is the stronger. Clearly, in ascites formation, the forces tending to push fluid out of the capillaries must be winning - either because the 'outward' forces are stronger than usual, or because the 'inward' forces are weaker than usual. I've found this a really good schema by which to think of the problem, since this works for pleural effusions, pedal oedema, and many other causes of fluid 'overload'.

In ascites, there are actually three mechanisms underlying the disturbance of the above forces.
  • Most obviously, the deranged liver architecture, characteristic of cirrhosis, partially obstructs the normal blood flow of the gut's portal venous system. This leads to portal hypertension (an increase in pressure in these veins). This increases the hydrostatic pressure in these veins, which tends towards local oedema formation (ascites).
  • Then, there is a decreased serum albumin concentration. Normally, the liver is responsible for manufacturing enough albumin for the serum. Obviously, if the liver is failing, this function is often compromised. This leads to decreased capillary osmotic pressure.
  • Finally, there is salt and water retention in cirrhosis, secondary to increased aldosterone secretion. The immediate cause for this hyperaldosteronism seems to be decreased renal perfusion, but the cause of this is a little unclear. It may simply be due to decreased intravascular volume from the above two causes. But there is increasing evidence arguing that portal hypertension somehow stimulates nitric oxide (NO) release. NO is a vasodilator, and the arterial dilation that ensues leads to relative (rather than absolute) arterial underfilling. This will of course lead to renal underperfusion, thus activating the renin-angiotensin system. Anyway, whatever the cause of the hyperaldosteronism, the result is increased capillary osmotic pressure.

So the net effect is an increased capillary hydrostatic pressure and a decreased capillary oncotic pressure. These are just the requirements for oedema to form. Obviously, the second and third mechanisms are in operation everywhere, which accounts for oedema formation in places other than the abdomen (e.g. pedal oedema). But all three mechanisms are firing in the portal venous system. This is why ascites is so much more common in liver cirrhosis than in other cases of fluid overload, like cardiac failure or nephrotic syndrome. In fact, cirrhosis accounts for about 75% of ascites cases.

Hope that helps!

1 comment:

  1. Hi great post! Could you clarify what you mean by relative arterial underfilling with nitric oxide being a cause of renal hypoperfusion?