Medical Aspirin absorption in stomach and intestine is confusing.

[sameeralord]

Hello everyone,

Aspirin(acetylsalicylic acid) is a weak acid. So in the acidic PH of stomach it must be more in nonionised form. In the alkaline PH of intestine it must be more in ionised form. Now my note says something is more absorbed if it is in non ionised form, this makes sense because lipid soluble substances can easily go through plasma membrane. But with asprin the absorption is actually more in the intestine. I can understand it is more soluble in intestine, but if it is ionised how can it go through plasma membrane of intestinal villi cells and reach portal circulation. Thanks

 

[Dr_Morbius]

Just because something is ionized doesn't mean your intestine won't absorb it at all. Your intestine absorbs salt and other ionized substances just fine. It isn't a black and white situation.

 

[bobze]

That's actually a really good question Sameera and a hard one to answer. Its not really a simple answer.

Aspirin and couple other weak organic acids don't follow normal kinetics across lipid membranes. Contrary to Dr. Morbius statement, it is "pretty black and white" at least from the standpoint of the lumen of the small intestine (sorry mate :), not trying to specifically call you out, lol).

Even assuming a rather liberal more acidic leaning pH of 7.5 of the SI (to keep the numbers easy with Aspirin's pKa of 3.5) the ratio of HA/A- is about 1/10,000. That's pretty steep. Generally when the pH is 4 log scales above the pK, you would consider (for a weak acid) that it is completely ionized.

In fact, if you make these assumptions with /most/ weak acids, as far as pharmaceuticals are concerned, you turn out to be right (kinetically speak) the vast majority of the time. However a few weak acids (can't think of any weak bases off the top of my head that violate this rule, but I'm dead tired) are an exception to the rule. Sameera--

The general explanation has to do with micoenvironments at the surface of the enterocytes, where the pH only there favors the unionized form (HA) long enough that it is absorbed across the membrane. What follows is a Le Chatelier's-esq equilibrium where once crossed the Aspirin is swept away across the cell, into the vasculature and out into the body. This tends to pull, in a Le Chatelier-esq fashion, the reaction across the membrane along for Aspirin absorption. If you haven't noticed in your medical career yet--everything can just about get related to Le Chatelier :P (or "more surface area" the second best answer in biology, lol)

Anyway, that's the conventional explanation. There have been some monocarboxylic acid transports that have been identified and suggested as possible receptor-mediated absorption mechanism--Though this hasn't really seemed to pan out IIRC.

Tomorrow, if you are interested, I can find the papers for you about it when I take a study break. Though knowing you are studying for boards--TBH exactly why aspirin behaves this way, is a waste of time for you to understand. Since the chemists and pharmacologists are still arguing about it, its not really relevant to a clinician. Especially considering that however it gets across, we know it works empirically--And well, it can't get much better than that kind of evidence. You'd probably be better just knowing that its an exception to the rule here and moving on with your studies :)

Hope that helps

 

[sameeralord]

That's actually a really good question Sameera and a hard one to answer. Its not really a simple answer.

Aspirin and couple other weak organic acids don't follow normal kinetics across lipid membranes. Contrary to Dr. Morbius statement, it is "pretty black and white" at least from the standpoint of the lumen of the small intestine (sorry mate :), not trying to specifically call you out, lol).

Even assuming a rather liberal more acidic leaning pH of 7.5 of the SI (to keep the numbers easy with Aspirin's pKa of 3.5) the ratio of HA/A- is about 1/10,000. That's pretty steep. Generally when the pH is 4 log scales above the pK, you would consider (for a weak acid) that it is completely ionized.

In fact, if you make these assumptions with /most/ weak acids, as far as pharmaceuticals are concerned, you turn out to be right (kinetically speak) the vast majority of the time. However a few weak acids (can't think of any weak bases off the top of my head that violate this rule, but I'm dead tired) are an exception to the rule.


Sameera--

The general explanation has to do with micoenvironments at the surface of the enterocytes, where the pH only there favors the unionized form (HA) long enough that it is absorbed across the membrane. What follows is a Le Chatelier's-esq equilibrium where once crossed the Aspirin is swept away across the cell, into the vasculature and out into the body. This tends to pull, in a Le Chatelier-esq fashion, the reaction across the membrane along for Aspirin absorption. If you haven't noticed in your medical career yet--everything can just about get related to Le Chatelier :P (or "more surface area" the second best answer in biology, lol)

Anyway, that's the conventional explanation. There have been some monocarboxylic acid transports that have been identified and suggested as possible receptor-mediated absorption mechanism--Though this hasn't really seemed to pan out IIRC.

Tomorrow, if you are interested, I can find the papers for you about it when I take a study break. Though knowing you are studying for boards--TBH exactly why aspirin behaves this way, is a waste of time for you to understand. Since the chemists and pharmacologists are still arguing about it, its not really relevant to a clinician. Especially considering that however it gets across, we know it works empirically--And well, it can't get much better than that kind of evidence. You'd probably be better just knowing that its an exception to the rule here and moving on with your studies :)

Hope that helps

Thanks Bobze It's a good thing you are around in these forums.