3.4 Small Intestine

Small Intestine

The small intestine is the primary site of digestion. It is divided into three sections: the duodenum, jejunum, and ileum (shown below). After leaving the stomach, the first part of the small intestine that chyme will encounter is the duodenum.

Figure 3.41 Three sections of the small intestine1

The small intestine consists of many layers, which can be seen in the cross section in Figure 3.42 below.

Figure 3.42 Cross section of the small intestine2

Examining these layers more closely, we are going to focus on the lining of the small intestine, known as the epithelium (see Figure 3.42 above), which comes into contact with the chyme and is responsible for absorption. The lumen is the name of the cavity that is considered “outside

the body” that chyme moves through.

The organization of the small intestine is in such a way that it contains circular folds and finger- like projections known as villi. The folds and villi are shown in the next few figures.

Figure 3.43 Folds in the small intestine2

Figure 3.44 Villi in the small intestine3

Figure 3.45 Villi line the surface of the small intestine2,4

If we were to zoom in even closer, we would be able to see that enterocytes (small intestine absorptive cells; a.k.a brush border cells) line villi as shown below. This layer is referred to as the mucosa, and is composed primarily of simple columnar epithelium.

Figure 3.46 Enterocytes line villi4

The side, or membrane, of the enterocyte that faces the lumen is not smooth either. It is lined with microvilli, and is known as the brush border membrane, as shown below.

Figure 3.47 Enterocyte, or small intestinal absorptive cell is lined with microvilli. This lined surface is referred to as the brush border membrane.

Together these features (folds + villi + microvilli) increase the surface area ~600 times versus if it was a smooth tube5. (Note: the symbol ~ is used in place of the word “approximately.” You will see it used other places in this text as well.) More surface area leads to more contact between the chyme and the enterocytes, and thus, increased absorption.

Finally, the surface of the cells on the microvilli are covered with proteins, which helps to catch a molecule-thin layer of water within itself. This layer, called the “unstirred water layer,” has a

number of functions in absorption of nutrients, and will have a direct impact on fat absorption as we will see later6.

Figure 3.48 Unstirred water layer

Now that you have learned about the anatomy of the small intestine, the following subsections go through the different digestive processes that occur there.

Subsections:

• 3.41 Digestive Hormones, Accessory Organs, & Secretions
• 3.42 Carbohydrate Digestion in the Small Intestine
• 3.43 Protein Digestion in the Small Intestine
• 3.44 Lipid Digestion in the Small Intestine

References & Links

• http://commons.wikimedia.org/wiki/Image:Illu_small_intestine_catal%C3%A0.png
• Author unknown, NCI, http://visualsonline.cancer.gov/details.cfm?imageid=1781
• http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/
• http://commons.wikimedia.org/wiki/Image:Gray1061.png
• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s Perspectives in Nutrition. New York, NY: McGraw-Hill.
• http://www.newworldencyclopedia.org/entry/Small_intestine

Digestive Hormones, Accessory Organs & Secretions

Before we go into the digestive details of the small intestine, it is important that you have a basic understanding of the anatomy and physiology of the following digestion accessory organs: pancreas, liver, and gallbladder. Digestion accessory organs assist in digestion, but are not part of the gastrointestinal tract. How are these organs involved?

Upon entering the duodenum, the chyme causes the release of two hormones from the small intestine: secretin and cholecystokinin (CCK) in response to acid and fat, respectively. These

hormones have multiple effects on different tissues. In the pancreas, secretin stimulates the secretion of bicarbonate (HCO₃), while CCK stimulates the secretion of digestive enzymes. The bicarbonate and digestive enzymes released together are collectively known as pancreatic juice, which travels to the small intestine, as shown below.

Figure 3.411 The hormones secretin and CCK stimulate the pancreas to secrete pancreatic juice1

In addition, CCK also stimulates the contraction of the gallbladder causing the secretion of stored bile into the duodenum.

Pancreas

The pancreas is found behind the stomach and just above the transverse colon (part of the large intestine discussed later in this chapter). It is a tadpole-shaped organ consisting of a head, body, and tail. It is a unique organ containing both endocrine and exocrine portions. The smaller, endocrine (hormone-producing) portions contain alpha, beta, delta, and PP cells that secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide respectively. These cells are clustered in groups known as pancreatic islets (traditionally referred to as the Islets of Langerhans). However, the vast majority of the pancreas is made up of grape-like clusters of exocrine cells known as acini (singular = acinus). The cells composing each acinus are known as acinar cells. These acinar cells are responsible for producing enzyme-rich pancreatic juice. Pancreatic juice is released into small ducts that continually merge to form a large main pancreatic duct which delivers pancreatic juice from the pancreas to the duodenum, merging with the common bile duct (from the liver & gallbladder) along the way. The release of pancreatic juice, and bile, is controlled by the hepatopancreatic sphincter. The following video does a nice job of showing and explaining the function of the different pancreatic cells.

Figure 3.412 The pancreas has a head, a body, and a tail. It delivers pancreatic juice to the duodenum through the pancreatic duct5.

Required Web LinkVideo: The Pancreas (First 53 seconds)

In addition to pancreatic hormones and enzymes, the pancreas releases bicarbonate. Bicarbonate is a base (high pH) meaning that it can help neutralize an acid (such as gastric juice.) You can find sodium bicarbonate (NaHCO₃, baking soda) on the ruler below to get an idea of its pH.

Figure 3.413 pH of some common items2

The main digestive enzymes in pancreatic juice are listed in the table below. Their function will be discussed further in later subsections.

Table 3.411 Enzymes in pancreatic juice

Liver

The liver is the largest internal, and the most metabolically active, organ in the body. The figure below shows the liver and the other accessory organs position relative to the stomach.

Figure 3.414 Location of digestion accessory organs relative to the stomach3

The liver is made up two major types of cells. The primary liver cells are hepatocytes, which carry out most of the liver’s functions. Hepatic is another term for liver. For example, if you are going to refer to liver concentrations of a certain nutrient, these are often reported as hepatic concentrations. The other major cell type is the hepatic stellate (also known as Ito) cells. These are fat storing cells in the liver.

The liver’s major role in digestion is to produce bile. This is a greenish-yellow fluid that is composed primarily of bile acids, but also contains cholesterol, phospholipids, and the pigments bilirubin and biliverdin. Bile acids are synthesized from cholesterol. The two primary bile acids are chenodeoxycholic acid and cholic acid. In the same way that fatty acids are found in the form of salts, these bile acids can also be found as salts. Because of this, these bile salts are often seen in texts with an (-ate) ending (chenodeoxycholate and cholate) indicating they are in the salt form.

Bile acids, much like phospholipids, have both hydrophobic and hydrophilic portions. This makes them excellent emulsifiers that are instrumental in fat digestion. Bile is then transported to the gallbladder.

Gallbladder

The gallbladder is a small, sac-like organ found just off the liver (see figure 3.413 above). Its primary function is to store and concentrate bile made by the liver. The bile is then transported to the duodenum through the common bile duct.

Why do we need bile?

Bile is important because fat is hydrophobic, but the environment in the lumen of the small intestine is watery. In addition, there is an unstirred water layer that fat must cross to reach the enterocytes in order to be absorbed.

Figure 3.415 Fat is not happy alone in the watery environment of the small intestine.

Triglycerides naturally form large triglyceride droplets to keep the interaction with the watery environment to a minimum. Picture the large droplets of cooking oil that form when you add it to water. This is inefficient for digestion, because enzymes cannot access the interior of the droplet. Bile acts as an emulsifier, or detergent. It, along with phospholipids, breaks the large triglyceride droplets into smaller triglyceride droplets that increase the surface area accessible for triglyceride digestive enzymes, as shown below.

Figure 3.416 Bile acids and phospholipids facilitate the production of smaller triglyceride droplets.

Secretin and CCK also control the production and secretion of bile. Secretin stimulates the flow of bile from the liver to the gallbladder. CCK stimulates the gallbladder to contract, causing bile to be secreted into the duodenum, as shown in Figure 3.417.

Figure 3.417 Secretion stimulates bile flow from liver; CCK stimulates the gallbladder to contract3

References & Links

• Don Bliss, NCI, http://visualsonline.cancer.gov
• http://upload.wikimedia.org/wikipedia/commons/4/46/PH_scale.png 3.http://www.wpclipart.com/medical/anatomy/digestive/Digestive_system_diagram_page.png

.html

• http://www.comparative-hepatology.com/content/6/1/7
• OpenStax, Anatomy & Physiology. OpenStax CNX. Aug 1, 2017 http://cnx.org/contents/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.108

Video

The Pancreas – http://www.youtube.com/watch?v=j5WF8wUFNkI

Carbohydrate Digestion in the Small Intestine

The small intestine is the primary site of carbohydrate digestion. Pancreatic amylase is the primary carbohydrate digesting enzyme. Pancreatic amylase, like salivary amylase, cleaves the glycosidic bonds of carbohydrates, reducing them to simpler carbohydrates, such as glucose, maltose, maltotriose, and α-dextrin (an oligosaccharide containing 1 or more glycosidic bonds which pancreatic amylase unable to cleave1).

The pancreatic amylase products, along with the disaccharides sucrose and lactose, then move to the surface of the enterocyte.

Here, the brush border enzyme α-dextrinase starts working on α-dextrin, breaking off one glucose unit at a time. Three other brush border enzymes hydrolyze sucrose, lactose, and maltose into monosaccharides. Sucrase splits sucrose into one molecule of fructose and one molecule of glucose; maltase breaks down maltose into two glucose molecules; and lactase breaks down lactose into one molecule of glucose and one molecule of galactose2. Insufficient lactase can lead to lactose intolerance (discussed in a later chapter.) The products from these brush border enzymes are the single monosaccharides glucose, fructose, and galactose that are ready for absorption into the enterocyte1.

Figure 3.423 Disaccharidases on the outside of the enterocyte.

Figure 3.424 Carbohydrates are broken down into their monomers in a series of steps2.

References & Links

• Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.
• OpenStax, Anatomy & Physiology. OpenStax CNX. Aug 1, 2017 http://cnx.org/contents/14fb4ad7-39a1-4eee-ab6e-3ef2482e3e22@8.108

Protein Digestion in the Small Intestine

The small intestine is the major site of protein digestion by proteases (enzymes that cleave proteins). The pancreas secretes a number of proteases into the duodenum where they must be activated before they can cleave peptide bonds1. This activation occurs through an activation cascade. A cascade is a series of reactions in which one step activates the next in a sequence that results in an amplification of the response. An example of a cascade is shown below.

Figure 3.431 An example of a cascade, with one event leading to many more events

In the above example, A activates B, B activates C, D, and E, C activates F and G, D activates H and I, and E activates K and L. Cascades also help to serve as control points for certain process. In the protease cascade, the activation of B is really important because it starts the cascade.

The protease activation scheme starts with the enzyme enteropeptidase (secreted from the intestinal brush border) that converts trypsinogen (released by the pancreas) to trypsin. Trypsin can activate all the proteases (including itself) as shown in the 2 figures below.

Figure 3.432 Protease activation cascade

Figure 3.433 The protease activation cascade

The products of the action of the activated proteases on proteins are dipeptides, tripeptides, and individual amino acids, as shown below.

Figure 3.434 Products of pancreatic proteases

At the brush border, much like disaccharidases, there are peptidases that cleave some peptides down to amino acids. Not all peptides are cleaved to individual amino acid, because small

peptides can be taken up into the enterocyte, thus, the peptides do not need to be completely broken down to individual amino acids. Thus, the end products of protein digestion are primarily dipeptides and tripeptides, along with individual amino acids1.

Figure 3.435 Peptidases are produced by the brush border to cleave some peptides into amino acids

References & Links

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.

Lipid Digestion in the Small Intestine

The small intestine is the major site for lipid digestion. There are specific enzymes for the digestion of triglycerides, phospholipids, and the removal of esters from cholesterol. We will look at each in this section. Refer back to sections 2.35, 2.36, and 2.36 for a review of these structures.

Triglycerides

The pancreas secretes pancreatic lipase into the duodenum as part of pancreatic juice. This major triglyceride digestion enzyme preferentially cleaves two fatty acids from triglycerides. This cleavage results in the formation of a monoglyceride and two free fatty acids as shown in Figures 3.441 & 3.442.

Figure 3.441 Pancreatic lipase cleaves the sn-1 and sn-3 fatty acids of triglycerides

Figure 3.442 The products of pancreatic lipase are a 2-monoglyceride and two free fatty acids

Phospholipids

The enzyme phospholipase A₂ cleaves the fatty acid of lecithin, producing lysolecithin and a free fatty acid. This is depicted in Figures 3.444 & 3.445.

Figure 3.444 Phospholipase A₂ cleaves the C-2 fatty acid of lecithin

Figure 3.445 Products of phospholipase A₂ cleavage

Cholesterol Esters

The fatty acid in cholesterol esters is cleaved by the enzyme, cholesterol esterase, producing cholesterol and a free fatty acid.

Figure 3.446 Cholesterol esterase cleaves fatty acids off of cholesterol

Figure 3.447 Products of cholesterol esterase

Formation of Mixed Micelles

If nothing else happened at this point, the monoglycerides and fatty acids produced by pancreatic lipase would form micelles. The hydrophilic heads would be outward and the fatty acids would be buried on the interior. These micelles are not sufficiently water-soluble to cross the unstirred water layer to get to the brush border of enterocytes. Thus, mixed micelles are formed containing cholesterol, bile acids, and lysolecithin in addition to the monoglycerides and fatty acids, as illustrated below1.

Figure 3.448 Normal (left) and mixed (right) micelles

Mixed micelles are more water-soluble, allowing them to cross the unstirred water layer to the brush border of enterocytes for absorption.

Figure 3.449 Mixed micelles can cross the unstirred water layer for absorption into the enterocytes

After digestion of carbohydrates, proteins, and fats is complete, the products below are ready for uptake into the enterocyte. This will be discussed in the next chapter.

Figure 3.55 Macronutrient digestion products ready for uptake into the enterocyte

References & Links

1. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.