Digestive System, Part 7: The Ileum

The border between the jejunum and the ileum is… not a border. Unlike the organs we've been looking at so far, there is no clear demarcation line between jejunum and ileum. They transition smoothly into each other as we travel down the small intestine, becoming progressively less jejunumy and more ileumy as they go. With no anatomical guidepost to demarcate them, the jejunum is arbitrarily designated as the first 2/5ths of the small intestine (not including the duodenum,) and the ileum is said to make up the last 3/5ths.

The two are not very different. You can have your entire jejunum removed, in fact, with little effect on your health. I mean, I wouldn't recommend super-sizing your meals if you don't have a jejunum, but you can live a basically normal life. Over time, the ileum will even adapt itself, becoming more jejunumy in order to take up the slack.¹

Living without an ileum isn't as easy. The jejunum is set in its ways, and finds it harder to take over when the ileum is missing. The ileum also has some specialty skills (most critically, the absorption of our old friend, vitamin B12) that the jejunum isn't very good at.¹

And yet, even though the deeper ileum is the more adaptable of the two, 90-95% of nutrients are absorbed in the jejunum.¹ So, why do we have extra yards of intestine that only do 5-10% of the work? One reason is to provide a backup in case of disease and injury. With redundancy built into our bodies wherever feasible, we can continue to survive and breed even when parts of us are lost or broken.

Jejunum microscopic section
From Histology, A Text and Atlas, 3rd Edition

Ileum microscopic section
From Histology, A Text and Atlas, 3rd Edition

Most critically, however, that extra intestine increases our chances of survival during famine. Remember famine, humanity's old friend who hardly ever calls anymore? Well, it doesn't often call on the industrialized world, anyway. Even today, starvation plagues billions of people in developing nations (which I point out not so you’ll actually do something about it, but because I like to make you feel bad.) During starving times, the efficiency of our nutrient uptake is increased to help compensate.

Most of this efficiency boost comes from efficiency-boosting changes on the intestinal surface, allowing every square centimeter to take up more nutrients than before. But, despite the increased efficiency, the intestines don't lose mass during starvation. That sets the intestine apart from many other organs, which react to starvation with sweeping layoffs—their mass cannibalized to liberate nutrients and to reduce their energy usage.² (That’s the case in mice, anyway. It seems safe to assume the same goes for humans, but I’m not sure you could get an NIH grant to cut starving people open and weigh their intestines. Not until we put Rick Scott in the White House, at least.) The lack of intestinal shrinkage, while the rest of the body is enacting Greek-level austerity, suggests a survival advantage to keeping the lower 3/5ths of the intestine around, even though it only does 5-10% of the work.

That said, small intestine length (as a proportion of gut length) appears to have declined in humans over the past few million years.³ We don’t have hard evidence of the timing, because intestinal mucosa doesn't fossilize, but the decreasing trend in small intestine length is thought to have begun several million years ago, in our Australopithecine ancestors. It's also around this time that fossil evidence indicates we began to butcher animals for their meat.

If this is indeed when the small intestine began to shrink (and it probably is,) then it coincides with the explosive growth trend in human brain size.⁴ Anthropologists, desperate to justify their existence, like to connect these two adaptations with the “expensive tissue hypothesis”⁵. This hypothesis begins with the premise that tissue is expensive to maintain (true,) and therefore our organs won't evolve to be larger unless there's a damn good reason for it (also true.) So far, so good, right? Anyone who's ever had to buy dog food for a mastiff can tell you how expensive carrying a lot of extra mass is.

The hypothesis goes on to state that, as our diets became richer due to hunting and butchering, our gut size decreased. This is, again, hard to deny. Carnivores have shorter guts than herbivores. This is known, Khaleesi. It stands to reason then, that as a species eats a higher proportion of meat, the gut would evolve to be more like that of a carnivore.

Finally, the expensive tissue hypothesis states that it was this decrease in gut mass that provided enough slack in our metabolic requirements to accommodate a larger brain.

Wait, what?

Does anything about that last leap of logic strike you as odd? Beyond the fact that human metabolic requirements have not, in fact, stayed steady over this evolutionary timeframe, but have gone way up as we evolved larger total body mass, doesn't it feel like that last bit, about metabolic slack is... well, totally superfluous? If a species transitions to a richer diet, doesn't that also accommodate a larger brain size, if a metabolic insufficiency was the critical survival pressure that restricted brain growth in the first place?

Do you really need to introduce a completely novel concept about some sort of metabolic master budget that requires one organ to shrink so another can grow? This, despite the fact that most of our organs have grown as we've evolved larger bodies. They just haven't grown proportionally.

Symbolic representation of human evolution. CC José-manuel Benitos

My central problem with the hypothesis is that you don't need the slack from the decreased gut size to explain increased brain size. It may well be a factor, but it isn't required to explain the observed phenomenon. It's clever and compelling—I'll certainly grant it that—but it adds needless complexity to a set of evolutionary pressures that, by themselves, already explain each of the observations perfectly well.

Moreover, if there were a master metabolic budget in mammals, you'd expect to see a negative correlation (one shrinks if another grows) between the size of the most expensive organs, which we don't.⁶ In fact, that relationship tends to be positive, even when you control for fat-free body mass:

 

From Energetics and the evolution of human brain size. Navarrete et al.
Negative correlations in relative organ size of mammal species are noted with a minus sign, positive correlations with a plus sign.

The digestive tract's only negative correlation in mammal species is to fat tissue (and it's not even statistically significant, by grown-up science standards.) The moral of the story is: evolutionary anthropologists have too much fucking free time.

So what the hell goes on in the ileum? (Remember the ileum? It’s an article about the ileum.)

Well, the ileum is great at absorbing vitamin B-12. When we last visited with B-12, it was leaving the stomach and being liberated from its Haptocorrin escort, only to be snatched up by intrinsic factor (IF). While we were busy laughing at evolutionary anthropologists, IF has been chaperoning B-12 through the jejunum. Now, in the ileum, receptors on enterocytes (the cells lining the intestine) recognize the IF/B12 pair and, in the presence of a calcium ion, pull the whole damn thing inside the cell by endocytosis—essentially sucking it into a hot pocket whose crust is made from the cell's own membrane and whose filling is B-12 (see below.) The B-12 hot pocket moves to special digestive structures in the enterocyte cells called lysosomes. Inside the lysosomes, the IF is digested away, exposing B-12 for transport and use within the body.⁷

From Course Outlines, Cherokee High School, NJ
(I take em' where I can find 'em, people.)

Vitamin, mineral, and water absorption that began in earnest in the jejunum continues in the ileum.  Vitamins that dissolve in fat ( A, D, E, and K) usually sneak into the enterocytes alongside small triglycerides and fatty acids, and sneak out into the blood or lymph the same way.⁸ Water soluble vitamins other than B12 (C, B1, B2, Niacin, B6, Folate) are taken up by a variety of means, including carrier-mediated transport, similar to that of B12. In the ileum, this process often relies on the presence of a sodium ion in order to function. It’s not quite like the transport of sugar we described in the jejunum, however. In the case of carrier-mediated transport, the ion is only there to activate the process, not to drag the vitamin along with it ⁹ (if it did, that would be “cotransport.")

And then there are minerals. When we last saw them, minerals were being dissolved or liberated from protein complexes in the stomach. Proteases (proteins that cleave proteins—the Benedict Arnolds of molecular biology) continue that process in the small intestines, releasing minerals for absorption.

Absorption rates for many minerals are actually pretty pathetic.¹⁰ What’s more, some minerals like to mess with the absorption of other minerals, competing for or inhibiting their uptake. For example, you can develop an iron deficiency from getting too much zinc, because they're both trying to get into you through the same door and the excess of zinc is blocking the way. That, by the way, is why mega-dose vitamin pills are a bad idea: because minerals are assholes.

Okay, okay. The real reason is, your mineral uptake systems aren't terribly specific (though I still say minerals are assholes.) How nonspecific are they? To give an example, the same metal transporter (DMT1) which takes up essential iron also transports toxic lead into our bodies.¹¹ Uhh, oops, I guess? In fairness to DMT1, it's an honest mistake. It’s not like DMT1 is trying to poison us. It just mistakes lead for a vital nutrient. Maybe it needs glasses or something.

Modes of mineral transport include cotransport (iron, phosphorus,) which we've already discussed in the context of sugars and vitamins, and active transport (calcium, copper,) which requires the expenditure of cellular energy to actively pump minerals through the enterocytes. And then there’s the lazy-but-effective method of just letting minerals diffuse from the intestines into the bloodstream on their own. Minerals are small, and they can slip between enterocyte cells and sneak into the bloodstream that way. This method, in fact, can be the dominant mode of absorption if we've just eaten a meal that’s high in some minerals, such as calcium.¹² You hear that, zinc? You could take a lesson here.

And that's the ileum. Things start to get shitty next time, as we take our first plunge into the colon. Punnery!

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If you enjoyed this little jaunt through your ileum, why not sample the other articles in this series? And be sure to tell all your friends who are into poop jokes.

Digestive System, Part 1: Teeth and Spit
Digestive System, Part 2: Swallowing
Digestive System, Part 3: Down the Tubes
Digestive System, Part 4: B-12 as Temptress
Digestive System, Part 5: The Duodenum
Digestive System, Part 6: The Jejunum
Digestive System, Part 7: The Ileum (this article)
Digestive System, Part 8: Liver and Cecum
Digestive System, Part 9: The Colon
Digestive System, Part 10: The Bitter End
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Citations and References

1. Nutrition & Diet Therapy, 7th Ed, pg 542
2. Ferraris, et al. Chronic but Not Acute Energy Restriction Increases Intestinal Nutrient Transport in Mice. The Journal of Nutrition. 2001 Mar; 131(3):779-86.
3. Human Evolutionary Biology, pg. 538
4. Rogers AR, Lecture. http://content.csbs.utah.edu/~rogers/ant1050/Lectures/brains-2x3.pdf
5. Aiello, Wheeler. The Expensive-Tissue Hypothesis. Current Anthropology. Vol. 36, No. 2, pg. 199-221 
6. Navarrete, et al. Energetics and the evolution of human brain size. Nature 480, 91-93.
7. Andersen, et al. Structural basis for receptor recognition of vitamin-B12-intrinsic factor complexes. Nature. 2010 Mar 18; 464(7287):445-8.
8. Understanding Medical Physiology: A Textbook for Medical Students, 4th Edition, pg. 340
9. Hamid M. Intestinal absorption of water-soluble vitamins in health and disease. Biochemical Journal. (2011) 437, 357-372.
10. Human Nutrition. Cambridge University Press. Pg. 29
11. Bressler, et al. Divalent metal transporter 1 in lead and cadmium transport. Annals of the New York Academy of Sciences. 2004 Mar; 1012:142-52.
12. Pathophysiology of the Digestive System. Colorado State University Hypertextbook. http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/absorb_minerals.html