Question

I am currently studying the intestinal absorption/transport systems, but am confused about one part specifically. There are hydrophilic and lipophilic compounds (to varying degrees), and they get absorbed by different methods.

As far as I can tell there are 3 main ways of absorption in the intestinal wall:

Passive diffusion of lipophilic compounds through the membrane.
Passive diffusion of hydrophilic compounds through pores and gap junctures.
Active transport of larger molecules by transport proteins.
But once a compound passes the enterocyte absorption cells in the lining of the villi of the intestine, there are primarily two paths into systemic circulation:

Capillaries of the blood supply from the hepatic portal vein, leading to the liver and first pass metabolism.
Lymphatic uptake through the extension of the intestinal lymph system in there.
From what I can tell anatomically, both of these are somewhat intertwined/overlapped to an extend — but which properties of a compound determine whether it is primarily taken up by the lymph system (getting it to the blood supply eventually circumventing first pass hepatic metabolism) or wether more of it is taken up by the local portal vein capillaries? Is it small differences outside of the general hydro/lipophilic nature like size etc.?

Please correct me if I'm misunderstanding some of these basic anatomic concepts. I would appreciate if someone can tell me whether there is a set of parameters involved in this biochemical branching.

I just read the lacteals, the lymphatic vessels in the villi, absorb digested fats. Does that mean the more lipophilic a compound is the more likely it is to be absorbed by the lymph over the portal vein capillaries? That sounds a bit too simple for me. There must be more factors involved.

Answer 1

Compounds are absorbed in the intestine depending on their solubility; lipid-soluble nutrients diffuse through the plasma membrane and enter lacteals, bypassing the liver initially, while hydrophilic nutrients are actively transported into capillaries leading to the hepatic portal vein.

Step-by-step explanation:

The route by which a compound is absorbed in the intestine depends on its physicochemical properties. Lipid-soluble nutrients such as fats, fat-soluble vitamins, and certain drugs diffuse through the plasma membrane, are reassembled into triglycerides, and are incorporated into chylomicrons that enter the lacteals of the villi. These then travel through the lymphatic system to the systemic circulation, thus bypassing the hepatic portal vein and first-pass metabolism in the liver. Water-soluble nutrients, on the other hand, require transport molecules or other mechanisms to pass through the intestinal mucosa and enter the portal circulation, which leads directly to the liver.

The capacity for hydrophilic or water-soluble compounds to diffuse through specific pores or to be actively transported across cell membranes is an additional factor determining their absorption pathway. Molecules with high lipid solubility and a low molecular weight are favored for absorption by the lymphatic system, whereas hydrophilic substances tend to enter the portal vein. Active transport mechanisms, which often involve ATP fueling the process, are necessary for most nutrients and are a key factor in their absorption through the intestinal wall.