Absorption – Digestion and Absorption

00:00 Now, how in the world do we get these small little monosaccharides across the intestinal lumen.

00:09 For this you're going need specific transporters, we've already covered one, which is the SGLT1.

00:16 But there are a few others that are present as well.

00:20 The SGLT1 transporters allow for the transport of two sodium ions to get either glucose or galactose across the intestinal wall.

00:35 What sets up the driving force for this is the basolateral sodium potassium ATPase creating a gradient for sodium to want to come across the intestinal lumen membrane.

00:46 This allows then for that driving force to move galactose or glucose with it.

00:54 Interestingly, besides glucose and galactalose, a little bit of water is moved across as well.

01:01 You'll notice though that not all of the various monosaccharides are listed here.

01:07 You only have glucose and galactose.

01:10 Other monosaccharides such as fructose use a diffusional transporter such as a GLUT5 in order to move it into the enterocytes.

01:20 But it doesn't matter if you use an SGLT1 or GLUT5, you're all going to exit via GLUT2 transporter on the basolateral membrane.

01:30 So this for then the reabsorption of these monosaccharides.

01:36 Now, peptides and amino acids are transported across the enterocyte in a similar manner.

01:42 So for apical transport, you can get a little bit of phagocytosis.

01:49 The majority of them are transported via amino acid and small peptide transporters.

01:56 The two most common are the sodium hydrogen exchanger.

02:00 The PepT1 transporter transports small either di- or tripeptides across the intestinal luminal wall.

02:10 Those then need to be broken down further into individual amino acids for transport.

02:15 Now, amino acid transporters usually will be divided into various categories, such as basic, neutral, acidic amino acid transporters to get them across.

02:26 I've just listed the generic ones here rather than to break them down into their individual transporters, whether that be along the apical membrane or the basolateral membrane.

02:43 Fat absorption, which is one of our most complex topics.

02:47 We'll spend a few minutes on here.

02:49 The first thing to think about is that short and medium chain fatty acids can make it across the enterocyte and that is because they are lipophilic.

02:59 A lipid molecule easily crosses a membrane because you remember that you have this fatty acid tails of the phospholipids in terms of a bilayer.

03:10 They are more easily able to cross.

03:14 Larger amounts of fats need to be processed before they can absorbed.

03:21 So they form usually something called a mixed micelles.

03:24 And this is very similar to creating a membrane.

03:28 You will have a head that will be hydrophilic, which means it's water-loving and their tails will be hydrophobic or water-hating.

03:41 And they will want to clump together in these small little droplets.

03:46 As these droplets start to go towards the enterocytes, there is a small pH change that starts off this digestive process.

03:57 What happens is these micelles then are broken down.

04:02 And therefore either they need to be in terms of long chain fatty acids, cholesterol or things like the glycerol backbone.

04:11 These fats are absorbed then across that enterocyte apical membrane into the cytosol of the enterocyte.

04:20 However, to get these out of the cell across the basolateral membrane, we need to repackage them and we repackage them into something called a chylomicron.

04:33 And they will be going into the lymphatic circulation and from the lymphatic circulation, will later be processed by the liver.

04:44 So if we go through this process one more time, we have mixed micelles, as they get close to the enterocyte, there is a pH change, and they start to break up into their individual contents that involve things like long chain fatty acids, cholesterol, so forth.

05:03 Then, they can move across the apical membrane into the enterocyte.

05:06 Then, we need to repackage them into chylomicrons.

05:10 And finally, they will move out of the cell as a chylomicron and be picked up by the lymphatic circulation.

05:16 The short chain fatty acids were picked up the portal system.

05:24 Okay, so how do we ingest short chain fatty acids elsewhere in the GI system.

05:31 Because we were only talking about the small intestine with that first set.

05:35 In the large intestine, only short chain fatty acids can be absorbed.

05:39 And this done through a short chain fatty acid transporter.

05:42 In this case, you take short chain fatty acids, couple them with sodium and this allows for a contransport of these fatty acids across the apical membrane.

05:56 Where does the driving force for the sodium come from? And that's from the basolateral sodium potassium ATPase.

06:06 So you have this natural movement of sodium across the large intestinal wall that helps the transport effects.

06:16 Now, you'll notice that there are other transporters located on that system and we'll talk about those in a minute in how they help you get water across the apical membrane as well.

06:29 So we can summarize carbohydrate, protein and lipid metabolism.

06:35 You can see that most of the absorption occur in the duodenum.

06:42 The jejunum and the ileum also participate in absorption of these macronutrients, but the majority of it occurs in the early portion of the small intestine.

06:54 Ions such as calcium, iron, some of the B vitamins also are primarily absorbed in the small intestine in the duodenum.

07:06 Although calcium can be absorbed throughout the small intestine.

07:13 Bile acids are absorbed later in the small intestine.

07:18 Your primary portion is in the ileum.

07:22 Vitamin B12 or cobalamin is very specialized and it is reabsorbed in the small intestine, the later portion, and we'll go through that process in more detail in a subsequent slide because it involves something called intrinsic factor, which is released from the parietal cells of your stomach.

07:45 Okay, let's go through calcium and iron absorption next.

07:51 Calcium absorption occurs via calcium transporters.

07:56 And so that can be increased via vitamin D synthesis because this helps form some of the calcium-binding proteins that are available.

08:05 So to get calcium across the apical wall, into the cytosol, you need to then bind it to something.

08:13 And then you can use a pump such as a calcium ATPase to pump it across the basolateral membrane.

08:23 A little bit of calcium can be transported across the tight junctions or paracellularly, but this is a smaller amount in comparison to the transporter mechanism that we've talked about earlier.

08:37 So this binding process within the cytosol seems to be an extra step.

08:44 So you first transport calcium across the apical membrane and then bind it.

08:49 So why would you want to bind it? Well, you can't have too high of calcium concentrations in any cell.

08:56 If calcium concentrations get too high, you'll actually become cytotoxic or could even damage the cell.

09:03 So what we do is we move it across the enterocyte.

09:06 We bind it up, then transport it closer to basolateral membrane where we can transport it out.

09:13 Iron molecules too will move across the apical membrane.

09:16 They do these through specialized transporters as you can see here.

09:22 But once again we have to bind iron as well before we move it across to the basolateral component to transport it out of the cell.

09:30 So again, a multiple step process for both calcium and iron.

09:35 You need to have transporters available to get it across the apical membrane.

09:39 You need to bind them up in the cytosol, take them over to the basolateral side.

09:44 Release them, so they can be then transported out.

09:49 We also have heme in this particular diagram because heme allows for also the liberation of iron within the cell.

09:59 So besides taking iron directly from the intestinal lumen, we can reabsorb heme and that heme then can processed within the cytosol, liberating its ion of iron, so that they can then be bound transported to the basolateral side of the membrane and then transported across.

10:20 Now, vitamin B12 or cobalamin is going to be a very difficult process to kind of think about.

10:26 And so we'll spend a few slides discussing this at this particular point.

10:29 So cobalamin is in food and it's going to eventually be bound to various substrates and we're going to have to liberate it from its bound substrates in the stomach.

10:42 The stomach liberation process involves increases in both pepsin and acidity.

10:48 And that will help dissociate cobalamin from its other food substrates.

10:55 There is a special protein that's produced called haptocorrin.

11:00 Haptocorrin is released in the stomach and will bind cobalamin.

11:04 Parietal cells release intrinsic factor, but intrinsic factor does not initially bind to the cobalamin.

11:13 Then, proteases are released from the pancreas as well as things like bicarb.

11:19 This will eventually cause cobalamin to be released from the haptocorrin and that is when intrinsic factor now binds to cobalamin.

11:29 So even though intrinsic factor is released in the stomach, this does not help its absorption or transport until it gets into the lower part of the small intestine.

11:42 That process can be seen over here in this larger diagram where you need to have intrinsic factor bound to cobalamin for you to be able to absorb this particular vitamin.

11:55 Now, what happens in terms of water balance? Well, water balance is an important aspect because you need to make sure you intake enough water in any particular day.

12:06 But in terms of secretions, we secrete a lot of substances into the GI system, so we can recycle that particular amount of water.

12:13 So it's going to be a balance between bringing water in or absorbing it.

12:17 And then reabsorbing these secretions.

12:21 The small intestine is the major player in this, absorbing about 80% of the water.

12:30 The later amount of 20% is absorbed in the large intestine.

12:38 This large intestinal water though is regulated.

12:42 So there are hormones such as aldosterone that is released when there is low amounts of volumes in the bloodstream that will then tell the small intestine and the large intestine to reabsorb more water.

12:57 That's most active in the large intestine.

13:00 But you can see here an example in any given day, you might intake about 2.5 liters of water.

13:08 You have salivary secretions, which is about a liter or a liter and half, gastric secretions is about 2 liters, biliary secretions and pancreatic secretions together is about another 2 liters, and intestinal secretions, about 1 liter.

13:25 That's a lot of liters, huh? So what you have here is a large amount of secretions per day, all being reabsorbed by both the small and large intestine, with the large intestine having some regulatory ability to either reabsorb a lot more water when you're dehdydrated than you're normally hydrated.