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Why do many parasites affect the liver?

Stephen G. Kayes kayes at SUNGCG.USOUTHAL.EDU
Fri Sep 15 13:47:07 EST 1995

On 15 Sep 1995, Graham Clark wrote:

>        <snip, snip, cut, cut>

> To which Stephen Kayes replied:
> -Katy:
> -    I suspect that you hit the reason with the bloodstream going to the 
> -liver.  Remember that the liver has a double blood supply, namely the 
> -hepatic artery and the hepatic portal system which drains the intestinal 
> -tract.  The blood contained within the portal supply contains the 
> -majority of nutrients absorbed from the host's  food supply and thus, is 
> -extremely attractive to parasites capable of an intravascular existance.  
> I don't believe that it is that simple. I can think of three distinct
> scenarios for parasites that affect the liver (somewhat simplified below):
> 1. Organisms like Entamoeba histolytica that end up in the liver as a 
> function of the blood flow from the intestines, and when in the liver 
> cause disease (in this example amebic liver abscess). The liver is not 
> part of the normal life-cycle of the organism.
	As might be expected from a glib generality, there are exceptions 
but there are interesting relations that must be considered.  Graham is 
correct.  But as regards the disease caused by Entamoeba, liver abscess 
from this organim is far less common than is amebic hepatitis which is 
caused by a toxin released from the parasite which is then transported to 
the liver by the hepatic portal system.  E.h. is after all an intestinal 
parasite that can invade any tissue of the body.  The liver "just happens 
to be connected to the GI track and thus, when E.h. invades the submucosa 
of the bowel wall and enters the blood stream the ameba are swept to the 
liver where they can then resume eating tissue cells, such as hepatocytes 
and can elicit some rather stricking histopathological responses.
> 2. Organisms like the malaria parasites where there is a specific life-
> cycle stage that occurs in the liver. In this case there is presumably a 
> specific tropism for the liver without which the parasite would be cleared 
> from the bloodstream.
	Again I agree with Graham but the fact that the malaria parasite 
has a tropism for hepatocytes (translated: there are receptors on the 
liver cell surface that attach to the malaria organism and result in its 
internalizaton.  The liver is where the few invaders from the mosquito 
undergo their first rounds of asexual multiplication.  And what better 
place to do so but in the liver which is where the body stores much of 
its glycogen (remember carbohydrates are the easiest substrate to use for 
energy) derived from ingested food, in the gut which travels by the 
portal system to the liver.  Did natural selection choose liver cells for 
this aspect of the life cycle.  Makes sense to me based on the very large 
amount of blood flowing through the liver at any one time and the fact 
that the sinusoids are lacking continouus basement membranes which allow 
the parasites to actually touch hepatocytes without having to leave the 
blood stream.

> 3. (which is somewhat like '1') Organisms that affect the liver but never
> actually reside there, like schistosomes. Schisto worms live in the 
> mesenteric veins and shed eggs some of which end up in the liver (among
> other places) via the blood stream, where they cause granulomas and 
> disease.

	Again, Graham is correct but I ask why do Schistomes (at least 
mansoni and japonicum) choose the inferior and superior mesenterics? 
Because they drain the intestines and can steal from the host's raw 
nutrients.  These parasites too, are reproducing at intense rates and 
need a good source of raw materials.  After the infections become 
established and the bowel wall becomes fibrotically scarred, eggs can no 
longer penetrate and pass to the outside (to keep the life cycle going) 
so they back up in the parasites local environment and blood flow sweeps 
them into the hepatic portal system from the mesenterics and  into the 
liver.  I still vote that this gut-liver axis is an extremely beneficial 
site for endoparasites to practice their crafts.  And Mother nature (in 
the guise of natural selection) would promote such a busines plan.

> In none of these cases is it clear that it is the nutrient richness that
> determines the parasite's 'attraction' to the liver although it is likely
> that the blood flow does have a lot to do with how they end up there.
> Is this a reasonable conclusion?
> Graham

	End of Graham's text with my comments inserted.

	The bottom line is that both Graham and I have a certain gestahlt 
of the internal relationships of host-parasite interactions.  Our 
differing interests and backgrounds flavor how we think about the same 
things.  Thats why there is no one single way to train a parasitologist.  
You never know who might just see the obviously missed insight into the 
host-parasite relationship that all the clasically trained people just 
passed over and over.  In closing, Katy, your rather simplistic question 
is really excellent and I hope it continues to promote a dialogue on site 
selection by parasites.  

	Steve Kayes
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