UNIT 8

I. Overview of digestion and absorption (Coincidentally also pages 40-50 in BioDiet)

• The digestive system is involved in getting nutrients from the external to the internal environment.
• We have a tube-within-a-tube body plan and the digestive tube is continuous with our integument
• Therefore, digestion is actually an external process
• There are six general processes involved with digestion:
• ingestion: food goes into the mouth
• propulsion: food is moved through the digestive tract independently from our musculoskeletal movements
  • deglutition: swallowing
  • peristalsis: alternating circular and longitudinal smooth muscle contractions that propel material through the digestive tract; similar to squeezing a toothpaste tube that widens and refills
• mechanical digestion: food is broken down into smaller pieces
  • mastication: chewing
  • churning: stomach movements
  • segmentation: mixing movements in the small intestine
• chemical digestion: enzymes from the salivary glands, pancreas, and intestinal epithelium break large organic molecules (like proteins) down into compounds small enough to be absorbed (e.g. amino acids)
• absorption: digested compounds move through the intestinal wall into the blood and are assimilated into the body
• defecation: elimination of undigested waste outside of the body
• The digestive system consists of a tube with accessory organs attached to it
• The tube has many different portions with different particular characteristics
• You should know the locations and functions of the following parts:

Alimentary Canal Upper alimentary canal mouth pharynx esophagus Gastrointestinal (GI) tract stomach small intestine duodenum jejunum ileum large intestine caecum vermiform appendix colon ascending colon transverse colon descending colon sigmoid (S-shaped) colon rectum anus Accessory glands salivary glands liver and gall bladder pancreas

II. Upper Alimentary Canal

Mouth

• The mouth is the site where digestion begins
• Food is ingested and then masticated (chewed) while the salivary glands (parotid, submandibular, and sublingual) add saliva
• Mastication is the fist mechanical digestion of the food and saliva adds salivary amylase, the first of many digestive enzymes, which is responsible for the primary chemical digestion of carbohydrates
• Saliva also helps to moisten and lubricate the food and contains an enzyme called lysozyme that helps kill bacteria and other microbes
• The teeth assist in mastication and the tongue move food around in the mouth, contains the taste (gustatory) receptors, and helps to keep the teeth clean by removing food particles

Pharynx

• The technical name for the throat is the pharynx
• It consists of three parts, the upper nasopharynx, central oropharynx, and lower laryngopharynx
• The pharynx has several important functions
  • common passageway for air and food
  • begins the movement of food via deglutition (swallowing)
  • contains lymphatic patches called tonsils that provide an immune response
• The inferior portion of the pharynx leads into two tubes, the trachea, for air, and the esophagus for food
• Atop the trachea sits the larynx, and the superior portion of it is the glottis
• The glottis has a flap, called the epiglottis, that closes over the glottis when we swallow so food doesn't go down the "wrong way"

Esophagus

• The esophagus is a muscular tube that takes food through the thorax into the abdomen and the stomach
• It moves the food via peristaltic waves and can even work when we are weightless or upside down
• The bottom part of the esophagus has a thickened ring of circular muscle called the cardiac sphincter
• This opens to let food into the stomach and then closes behind to keep food from moving back up (reflux), which causes a burning sensation commonly called "heartburn"

III. Lower Alimentary canal

Stomach

• The stomach is a storage sac of about 1 litre in volume, though it can expand to as much as 4 litres!
• It has several functions and the first is to store food that we have recently ingested
• The mucosa of the stomach is lined with many microscopic holes that lead to gastric (the term for stomach) pits and branch into gastric glands
  • These glands produce about 2 - 3 litres/day of gastric juice
• The following table outlines the secretions of the stomach:

• In the stomach proteins begin their digestion
  • This requires copious amounts of acid to produce the appropriate environment for pepsin, the enzyme that digests protein
  • The acid also helps to destroy most microbes that we swallow
  • However, this also creates a dangerous situation for the mucosal cells, because they could be destroyed by the acid too
  • Fortunately, they are protected by a thick layer of mucus that also contains bicarbonate to neutralize the acid
• After 20 minutes to 2 hours in the stomach, the food has formed a semi-liquid, acidic material called chyme, due to mechanical and chemical digestion
• There is another valve at the distal end of the stomach that regulates the movement of food into the duodenum, the pyloric sphincter.
• You might be interested to know that the only vital function of the stomach is the secretion of intrinsic factor
  • This compound is necessary for the absorption of vitamin B₁₂, which is needed for normal hemoglobin production
  • Without intrinsic factor we would end up with a potentially life-threatening condition called pernicious anemia

Small Intestine

Duodenum

• The small intestine measures about 6 meters in total length
• The first part, the duodenum, is the shortest, measuring only about 15 cm
• It begins at the pyloric sphincter and ends at the common duct of the pancreas and liver (see below)
• The duodenum receives chyme from the stomach, bile from the liver, and pancreatic juice from the pancreas

Jejunum

• The jejunum makes up 40% of the remaining small intestine
• It is the site of both digestion and absorption, though there is a bias towards digestion
• Both the jejunum and ileum contain inner folds of their mucosa called villi (singular = villus)
• This greatly increases the surface area for absorption
• Digestive enzymes continue to work on the food here until they are broken down into their simplest forms (see pancreas below)
• Mixing movements called segmentation assist in this process
• Once completely broken down, the nutrients are absorbed through the simple columnar epithelium into the blood and lymphatic vessels of the underlying submucosa
• Most nutrients are transported in the blood, but some larger proteins and fat-soluble compounds travel in the lymphatic system instead

Ileum

• The remaining 60% of the small intestine is the ileum.
• The function here is the same as the jejunum, but with a bias towards absorption
• The end of the ileum is marked by the ileocaecal valve, which regulated the movement of undigested material into the large intestine

Large Intestine

• The large intestine is responsible for the formation of the feces
  • Liquid, undigested material passes into the large intestine from the small intestine
• Larger and slower-moving, the large intestine dehydrates the fecal matter by reabsorbing water into the blood
• Without this function we would dehydrate in just a few days. About half of the volume of the colon is a "friendly" bacteria called E. coli, which helps to break down undigested food and soften the stools
• It also produces vitamin K which is then absorbed
• E. coli in colon can be dangerous if it enters the upper digestive tract and then the blood, as we saw recently in Walkerton, Ontario
• Formed feces are stored in the rectum until defecation occurs
• The caecum is simply a receiving area for material from the small intestine and the vermiform (worm-shaped) appendix is a finger-like extension from the caecum
  • It contains significant amounts of lymphatic tissue which help us defend against microbes in the GI tract

Accessory Glands

Liver

• The liver takes up much of the space in the upper abdominal cavity
• After the skin, it is the second largest organ in the body
• It has over 200 functions organize
• The only digestive function of the liver is to produce bile, which emulsifies fats
  • Because fats are not water soluble they are difficult to digest because the enzyme that chemically digests it is water soluble
  • Emulsification is a process by which bile salts coat tiny fat droplets to prevent them from joining with others to form larger ones
  • This maximizes the surface area for the digestive enzymes to work
  • Bile salts also contain cholesterol and bile pigments which give bile its green colour
  • Bile is produced at a regular rate and excess amounts are stores in the gall bladder, a sac under the right lobe of the liver
• Functions of the liver
• metabolism of carbohydrates, lipids, and proteins
  • conversion, synthesis, storage, release
  • formation of urea and plasma proteins
• storage of organic compounds (especially glycogen), vitamins (A,D, B₁₂), minerals (e.g. iron)
• phagocytosis (white blood cells eating) of damaged red blood cells and foreign matter
• detoxification of intrinsic metabolites (e.g. ammonia) and extrinsic toxins (e.g. alcohol)
• production and secretion of bile for emulsification of fats

Pancreas

• The pancreas is located deep to the stomach
• It is both and exocrine (secretes into ducts) and an endocrine (secretes into extracellular spaces) gland
• The pancreas produces about 1.2 - 1.5 litres/day of pancreatic juice
• This fluid enters the small intestine along with bile, at the end of the duodenum
  • Most of the digestive enzymes are produced and secreted by the pancreas
  • In addition, it also secretes bicarbonate to neutralize stomach acid in the chyme
• The secretions are summarized in the following table:

I. Overview of digestion and absorption (pages 40-50 in BioDiet)

So far in this unit, we have examined the structure and overall function of the organs that make up the digestive system. Now we will investigate the entire chemical processing (enzymatic breakdown and absorption) of each class of foodstuffs as it moves through the GI tract.

I highly recommend you read the "Fantasitc Voyage" in BioDiet, starting on page 41. This will help you imagine the same journey your food takes in your body.

Here, we'll focus only on the chemical digestion of the nutrients, but don't forget there is also mechanical digestion

The digestion and absorption of the macronutrients is included in those chapters in Human Nutrition:

Carbohydrates - Chapter 4, pages 149 - 157

Lipids - Chapter 5, pages 197 - 205

Proteins - Chapter 6, pages 234 - 237

Vitamins - Chapter 9

Minerals - Chapter 10 and 11

II. Chemical digestion

After foodstuffs have spent even a short time in the stomach, they are unrecognizable They are still mostly the starchy foods, meat proteins, fats that we ingested Only their appearance has been changed by mechanical digestive activities By contrast, the products of chemical digestion are the chemical building blocks of the ingested foods and are very different molecules chemically Mechanism of Chemical Digestion: Enzymatic Hydrolysis Chemical digestion is a catabolic process in which large food molecules are broken down to monomers (chemical building blocks), which are small enough to be absorbed by the GI tract lining Chemical digestion is accomplished by enzymes secreted by both intrinsic and accessory glands into the lumen of the alimentary canal The enzymatic breakdown of any type of food molecule is hydrolysis because it involves addition of a water molecule to each molecular bond to be broken (lysed)

III. Absorption of nutrients

• Up to 10L of food, drink, and GI secretions enter the alimentary canal daily, but only 1L or less reaches the large intestine
• Virtually all of the foodstuffs, 80% of the electrolytes, and most of the water are absorbed in the small intestine
  • Although absorption occurs all along the length of the small intestine, most of it is completed by the time chyme reaches the ileum
  • Hence, the major absorptive role of the ileum is to reclaim bile salts to be recycled back to the liver for re-secretion
• At the end of the ileum, all that remains is some water, indigestible food materials (largely plant fibers such as cellulose), and millions of bacteria
• This debris is passed on to the large intestine
• Most nutrients are absorbed through the mucosa of the intestinal villi by active transport processes driven directly or indirectly (secondarily) by metabolic energy (ATP)
  • They then enter the capillary blood in the villus to be transported in the hepatic portal vein to the liver
  • The exception is some of the lipid digestion products, which are absorbed passively by diffusion and then enter the lacteal in the villus to be carried to the blood via lymphatic fluid
• Because the epithelial cells of the intestinal mucosa are joined at their luminal surfaces by tight junctions, substances cannot move between the cells
• Consequently, materials must pass through the epithelial cells and into the interstitial fluid abutting their basal membranes (via transepithelial transport) if they are to enter the blood capillaries

IV. Digestion and absorption of proteins

Digestion

• Proteins digested in the GI tract include not only dietary proteins (typically about 125g per day), but also 15 - 25g of enzyme proteins secreted into the GI tract lumen by its various glands and (probably) an equal amount of protein derived from sloughed and disintegrating mucosal cells
• In healthy individuals, virtually all of this protein is digested all the way to its amino acid monomers
• Protein digestion begins in the stomach when pepsinogen secreted by the chief cells is activated to pepsin (actually a group of protein-digesting enzymes)
  • Pepsin functions optimally in the acidic pH range found in the stomach: 1.5 - 2.5
  • It preferentially cleaves bonds involving the amino acids tyrosine and phenylalanine so that proteins are broken into polypeptides and small numbers of free amino acids
  • Pepsin, which hydrolyzes 10 - 15% of ingested protein, is inactivated by the high pH in the duodenum, so its proteolytic activity is restricted to the stomach
• Rennin (the enzyme that coagulates milk protein) is not produced in adults
• Protein fragments entering the small intestine from the stomach are greeted by a host of proteolytic enzymes
  • Trypsin and chymotrypsin secreted by the pancreas cleave the proteins into smaller peptides, which in turn become the grist for other enzymes
  • The pancreatic and brush border enzyme carboxypeptidase splits off one amino acid at a time from the end of the polypeptide chain that bears the carboxyl group
  • Other brush border enzymes such as aminopeptidase and dipeptidase liberate the final amino acid products
  • Aminopeptidase digests a protein, one amino acid at a time, by working from the amine end
  • Both carboxypeptidase and aminopeptidase can independently dismantle a protein, but the teamwork between these enzymes and between trypsin and chymotrypsin, which attack the more internal parts of the protein, speeds up the process tremendously

Absorption

• Several types of carriers transport the different amino acids resulting from protein digestion
  • These carriers, like those for glucose and galactose, are coupled to the active transport of sodium
  • Short chains of two or three amino acids (dipeptides and tripeptides, respectively) are also actively absorbed, but are digested to their amino acids within the epithelial cells before entering the capillary blood by diffusion

V. Digestion and absorption of carbohydrates

Digestion

• Most of us ingest between 200 and 600 grams of carbohydrate foods each day
• Monosaccharides (simple sugars), the monomers of carbohydrates, are absorbed immediately
  • Only three of these are common in our diet: glucose, fructose, and galactose
• The more complex carbohydrates that our digestive system is able to break down to monosaccharides are the disaccharides sucrose (table sugar), lactose (milk sugar), and maltose (grain sugar) and the polysaccharides glycogen and starch
  • In the average diet, most digestible carbohydrates are in the form of starch, with smaller amounts of disaccharides and monosaccharides
  • Humans lack enzymes capable of breaking down most other polysaccharides, such as cellulose
    • Indigestible polysaccharides do not nourish us but they do help move the food along the GI tract by providing bulk, or fibre
• Chemical digestion of starch (and perhaps glycogen) begins in the mouth
• Salivary amylase, present in saliva, splits starch into oligosaccharides, smaller fragments of two to eight linked monosaccharides (in this case glucose molecules)
  • Salivary amylase works best in the slightly acid to neutral environment (pH of 6.75 - 7.00) maintained in the mouth by the buffering effects of bicarbonate and phosphate ions in saliva
  • Starch digestion continues until amylase is inactivated by stomach acid and broken apart by the stomach's protein-digesting enzymes
  • Generally speaking, the larger the meal, the longer amylase continues to work in the stomach because foodstuffs in its relatively immobile fundus are poorly mixed with gastric juices
• Starchy foods and other digestible carbohydrates that escape being broken down by salivary amylase are acted on by pancreatic amylase in the small intestine
  • Within about ten minutes of entering the small intestine, starch is entirely converted to various oligosaccharides, mostly maltose
  • Intestinal brush border enzymes further digest these products to monosaccharides
  • Because the colon does not secrete digestive enzymes, chemical digestion ends in the small intestine
  • Resident colon bacteria do break down and metabolize the residual complex carbohydrates further, adding much to their own nutrition but essentially nothing to ours

Lactose intolerance

• In some people, intestinal lactase is present at birth but then becomes deficient, probably due to genetic factors
  • The person becomes intolerant of milk products (the source of lactose), and undigested lactose creates osmotic gradients that not only prevent water from being absorbed in the small and large intestines but also pull water from the interstitial space into the intestines
  • The result is diarrhea
  • Bacterial metabolism of the undigested solutes produces large amounts of gas that result in bouts of bloating, flatulence, and cramping pain
• The solution to this problem is simple: add lactase enzyme drops or pills to your milk or take a lactose tablet before meals containing milk products

Absorption

• The monosaccharides glucose and galactose, liberated by the breakdown of starch and disaccharides, are transported into the epithelial cells by common protein carriers and then move by facilitated diffusion into the capillary blood
  • The carriers, which are located very close to the disaccharidase enzymes on the microvilli, combine with the monosaccharides as soon as the disaccharides are broken down
  • These sugars are conveyed by secondary active transport coupled to sodium ion transport (cotransport)
  • By contrast, fructose moves entirely by facilitated diffusion

VI. Digestion and absorption of lipids

Digestion

Although the Health Canada recommends a low-fat diet, the amount of lipids (fats) ingested daily varies tremendously among adults, ranging from 30 g to 150 g or more The small intestine is essentially the sole site of lipid digestion because the pancreas is the only significant source of fat-digesting enzymes, or lipases Neutral fats (triglycerides or triacylglycerols) are the most abundant fats in the diet Because triglycerides and their breakdown products are insoluble in water, fats need special "pretreatment" with bile salts to be digested and absorbed in the watery environment of the small intestine

• In aqueous solutions, triglycerides aggregate to form large fat globules, and only the triglyceride molecules at the surfaces of such fatty masses are accessible to the water-soluble lipase enzymes
• This problem is quickly resolved because as the fat globules enter the duodenum, they are coated with detergent-like bile salts
  • Bile salts have both nonpolar and polar regions
  • Their nonpolar (hydrophobic) parts cling to the fat molecules, and their polar (ionized hydrophilic) parts allow them to repel each other and to interact with water
  • As a result, fatty droplets are pulled off the large fat globules, and a stable emulsion - an aqueous suspension of fatty droplets, each about 1�m in diameter - is formed
  • The process of emulsification does not break chemical bonds
  • It just reduces the attraction between fat molecules so that they can be more widely dispersed
  • This process vastly increases so that the surface area the number of triglyceride molecules exposed to the pancreatic lipases increases greatlty
  • Without bile, lipids would be incompletely digested in the time food is in the small intestine
• The pancreatic lipases catalyze the breakdown of fats by cleaving off two of the fatty acid chains, thus yielding free fatty acids and monoglycerides (glycerol with one fatty acid chain attached)
• Fat-soluble vitamins that ride with fats require no digestion

Absorption

Just as bile salts accelerate lipid digestion, they are also essential for the absorption of its end products As the water-insoluble products of fat digestion - the monoglycerides and free fatty acids - are liberated by lipase activity, they quickly become associated with bile salts and lecithin (a phospholipid found in bile) to form micelles Micelles are collections of fatty elements clustered together with bile salts in such a way that the polar (hydrophilic) ends of the molecules face the water and the nonpolar portions form the core Also nestled in the hydrophobic core are cholesterol molecules and fat-soluble vitamins Although micelles are similar to emulsion droplets, they are much smaller "vehicles" and easily diffuse between microvilli to come into close contact with the mucosal cell surface The various lipid substances then leave the micelles and move through the lipid phase of the plasma membrane by simple diffusion Without the micelles, the lipids simply float on the surface of the chyme (like oil on water), inaccessible to the absorptive surfaces of the epithelial cells Generally, fat absorption is completed in the ileum, but in the absence of bile (as might occur when a gallstone blocks the cystic duct) it happens so slowly that most of the fat passes into the large intestine and is lost in feces (steatorrhea)

• Once inside the epithelial cells, the free fatty acids and monoglycerides are resynthesized into triglycerides
• The triglycerides are then combined with phospholipids and cholesterol, and coated with a "skin" of proteins to form water-soluble lipoprotein droplets called chylomicrons
  • These are processed by the Golgi apparatus for extrusion from the cell
  • This series of events is quite different from the absorption of amino acids and simple sugars, which pass through the epithelial cells unchanged
• Although a few free fatty acids enter the capillary blood, the milky-white chylomicrons are too large to pass through the basement membranes of the blood capillaries and instead enter the more permeable lacteals
  • Thus, most fat enters the lymphatic stream and is eventually emptied into the venous blood in the neck region via the thoracic duct, which drains the digestive viscera
  • While in the bloodstream, the triglycerides of the chylomicrons are hydrolyzed to free fatty acids and glycerol by lipoprotein lipase, an enzyme associated with the capillary endothelium
  • The fatty acids and glycerol can then pass through the capillary walls to be used by tissue cells for energy or stored as fats in adipose tissue
  • The residual chylomicron material is combined with proteins by the liver cells, and these "new" lipoproteins are used to transport cholesterol in the blood

VII. Absorption of micronutrients and water

Vitamins

• The small intestine absorbs dietary vitamins, and the large intestine absorbs some of the K and B vitamins made by its enteric bacteria
• As already noted, fat-soluble vitamins (A, D, E, and K) dissolve in dietary fats, become incorporated into the micelles, and move across the villus epithelium by passive diffusion
• It follows that taking supplements containing fat-soluble vitamins without simultaneously eating some fat-containing food results in little or no absorption of these vitamins
• Most water-soluble vitamins (B vitamins and vitamin C) are absorbed easily by diffusion
• The exception is vitamin B₁₂ , which is a very large, charged molecule
• Vitamin B₁₂ binds to intrinsic factor, produced by the stomach
• The vitamin B₁₂ - intrinsic factor complex then binds to specific mucosal receptor sites in the terminal ileum, which trigger its active uptake by endocytosis

Electrolytes

• Absorbed electrolytes come from both ingested foods and gastrointestinal secretions
• Most ions are actively absorbed along the entire length of the small intestine
• However, iron and calcium absorption is largely limited to the duodenum
• Absorption of sodium ions in the small intestine is coupled to active absorption of glucose and amino acids
• For the most part, anions passively follow the electrical potential established by sodium transport
  • That is, Na⁺ is actively pumped out of the epithelial cells by a Na⁺/K⁺ pump after entering those cells
  • Chloride ions are also transported actively, and in the terminus of the small intestine HCO₃^- is actively secreted into the lumen in exchange for Cl^-
• Potassium ions move across the intestinal mucosa by simple diffusion in response to osmotic gradients
  • As water is absorbed from the lumen, the resulting rise in potassium levels in chyme creates a concentration gradient for its absorption
  • Thus, anything that interferes with water absorption (resulting in diarrhea) not only reduces potassium absorption but also "pulls" K⁺ from the interstitial space into the intestinal lumen
• For most nutrients, the amount reaching the intestine is the amount absorbed, regardless of the nutritional state of the body
• Absorption of iron and calcium is intimately related to the body's need for them at the time
  • Ionic iron, essential for hemoglobin production, is actively transported into the mucosal cells, where it binds to the protein ferritin
    • This phenomenon is called the mucosal iron barrier
    • The intracellular iron-ferritin complexes then serve as local storehouses for iron
    • When body reserves of iron are adequate, little is allowed to pass into the portal blood, and most of the stored iron is lost as the epithelial cells later slough off
    • However, when iron reserves are depleted (as during acute or chronic hemorrhage), iron uptake from the intestine and its release to the blood are accelerated
    • Menstrual bleeding is a major route of iron loss in females, and the intestinal epithelial cells of women have about four times as many iron transport proteins as do those of men
    • In the blood, iron binds to transferrin, a plasma protein that transports it in the circulation
  • Calcium absorption is closely related to blood levels of ionic calcium
    • It is locally regulated by the active form of vitamin D, which acts as a cofactor to facilitate active calcium absorption
    • Decreased blood levels of ionic calcium prompt parathyroid hormone (PTH) release from the parathyroid glands
    • Besides facilitating the release of calcium ions from bone matrix and enhancing the reabsorption of calcium by the kidneys, PTH stimulates activation of vitamin D by the kidneys, which in turn accelerates calcium ion absorption in the small intestine

Water

• Approximately 9L of water, mostly derived from GI tract secretions, enter the small intestine daily
  • Water is the most abundant substance in chyme, and 95% of it is absorbed in the small intestine by osmosis
  • The normal rate of water absorption is 300 to 400ml per hour
  • Water moves freely in both directions across the intestinal mucosa, but net osmosis occurs whenever a concentration gradient is established by the active transport of solutes (particularly Na⁺) into the mucosal cells
  • Thus, water uptake is effectively coupled to solute uptake and, in turn, affects the rate of absorption of substances that normally pass by diffusion
  • As water moves into the mucosal cells, these substances follow along their concentration gradients