Phys 65 - Digestion and Absorption of GI

Diarrhea due to excretion of ions

While still in the deep folds, the epithelial cells secrete NaCl and water into the intestinal lumen. This secretion in turn is reabsorbed by the older epithelial cells outside the folds, thus providing flow of water for absorbing digested food Toxins of cholera and others cause diarrhea by increasing epithelial fold secretion of NaCl to much greater than absorptive capacity causing loss of 5-10 liters of water per day. Extreme diarrheal secretion is initiated by the entry of subunit of cholera toxin into the epithelial cells. This stimulates formation of excess cAMP, which opens tremendous numbers of Cl channels, allowing Cl ions to flow rapidly from inside the cell into the intestinal crypts that then causes sodium channels to open to follow Cl ions as well as causing water to follow via osmosis

Aldosterone and Absorption

Within 1 to 3 hours, aldosterone causes increased activation of enzymes and transport mechanisms for all aspects of sodium absorption by the intestinal epithelium with secondary increases in chloride and water absorption Effect of aldosterone is especially important in the colon because it allows virtually no loss of sodium chloride in the feces and therefore little water loss

Digestion by pancreatic amylase

a-amylase that is much stronger than salivary amylase Therefore, within 15-30 minutes after the chyme emtpies from the stomach into the duodenum and mixes with pancreatic juice, virtually all of the carbs will have become digested. In general, the carbs are almost totally converted into maltose and/or other small glucose polymers before passing beyond the duodenum or upper jejunum.

Hydrolysis of Proteins

same process as fats and carbs Proteolytic enzymes return hydrogen and hydroxyl ions from water molecules to the protein molecules to split them into their constituent amino acids

absorption in the large intestines

About 1500 ml of chyme normally pass through the ileocecal valve each day. Most of the water and electrolytes in this chyme are absorbed in the colon, usually leaving less than 100 ml of fluid to be excreted in the feces Most of the absorption in the large intestine occurs in the proximal half of the colon, giving this portion the name absorbing colon whereas the distal colon functions principally for feces storage

Hydrolysis of Carbs

Almost all the carbs in the diet are either large polysaccharides or disaccharides which are combos of monosaccharides bound to one another by condensation H gone from one, OH gone from the other forming H2O Specific enzymes in the digestive juices of the GI tract return the hydrogen and hydroxyl ions from water to the polysaccharides and thereby separate the monosaccharides from each other R-H and R-OH

Hydrolysis of Fats

Almost the entire fat portion of the diet consists of TG's - 3 fatty acids and a single glycerol. Fat digesting enzymes return three molecules of water to the triglyceride and thereby split the fatty acid molecules away from the glycerol

First step in digestion is emulsification by bile acids and lecithin

Begins by agitation in the stomach to mix the fat with the products of digestion Most of the emulsification occurs in the duodeum via bile that contains a large amount of bile salts and phospholipid lecithin. Polar parts of the bile salts and lecithin molecules are highly soluble in water on the outside of the fat molecules. The fat soluble portions of these liver secretions dissolve in the surface layer of the fat globule, with the polar portions protruding outward that greatly decrease the surface tension of the fat making it more soluble. A major function of bile salts and lecithin, especially the lecithin, in the bile is to make the fat globules readily fragmentable by agitation with water in the small bowel. Each time the diameters of the fat globules are significantly decreased as a result of agitation in the small intestine, the total surface area of the fat increases many fold The lipase enzymes are water soluble compounds and can attack the fat globules only on their surfaces

Absorption of Fats

Bile micelles contain cores of FFA and monoglycerides that are carried to the surfaces of the microvilli of the intestinal brush border and then penetrate into the recesses among the moving villi. Both FFA and monoglycerides diffuse immediately out of the micelles into the epithelial cells which then leaves bile micelles to absorb more fats from the chyme, performing the ferrying function After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the cell's smooth ER to form new TG that are subsequently released in the form of chylomicrons through the base of epithelial cells to flow upward through lymph to the thoracic duct

Carbs are absorbed mainly as monosaccharides

Essentially all of the carbohydrates in the food are absorbed in the form of monosaccharides Most abundant of the absorbed monosaccharides is glucose, usually accounting for more than 80% of carb calories The reason for this is that glucose is the final digestion product of our most abundant carb source, starches The remaining 20% are galactose and fructose

Most protein digestion results from action of pancreatic proteolytic enzymes

Most proteins are digested via proteolytic pancreatic enzymes - trypsin, chymotrypsin, carboxypolypeptidase, and proelastase Both trypsin and chymotrypsin split protein molecules into small polypeptides Carboxypolypeptidases then cleave individual amino acids from the carboxyl ends of polypeptides Proelastase is converted to elastase which then digests elastin fibers that partially hold meats together Most absorbed as di/tripeptides

TG are digested by pancreatic lipase

Pancreatic lipase is in high enough concentrations in the pancreaetic juice to digest all the TG it can reach the enterocytes also have a small amount of enteric lipase End products of fat metabolism is free fatty acids and 2 monoglycerides

Direct absorption of Fatty Acids into the portal blood

Small quantities of short and medium chain fatty acids such as those from butter fat are absorbed directly into the portal blood rather than being converted into TG and absorbed by way of lymphatics short and medium chain fatty acids are more water soluble allowing direct diffusion of these small FA's from the epithelial cells directly into the blood

Carb foods in the diet

Sucrose - cane sugar Lactose - disaccharide of glucose and galactose starches - non-animal foods Diet also contains a large amount of cellulose, but humans do not possess an enzyme capable of breaking it down

Absorption of proteins as dipeptides, tripeptides, and AA

The energy for the transport of AA and di/tripeptides is supplied by a sodium co transport mechanism like glucose After binding, the sodium ion then moves down its electrochemical gradient to the interior of the cell and pulls the AA or peptide along with it called co-transport or secondary active transport of AA and peptides A few AA's are absorbed via facilitated diffusion

Sodium is actively transported through the intestinal membrane

20-30 grams of sodium are secreted in the intestinal secretions each day with an additional 5-8 grams of sodium eaten by a person. To prevent loss of sodium, a person needs to reabsorb 25-35 g of sodium per day. Normally, except in the cases of extreme diarrhea, only 0.5 percent of intestinal sodium is lost in the feces each day because it is rapidly absorbed through the intestinal mucosa. Sodium plays an important role in absorbing amino acids and glucose The motive power for sodium absorption is provided by active transport of sodium from inside the epithelial cells through the basal and lateral walls of these cells into paracellular/intercellular spaces. This reduces the sodium concentration inside the cell Part of the sodium is absorbed along with chloride ion, in fact the negatively charged chloride ions are mainly passively dragged by the positive electrical charges of sodium ions Because the Na concentration in chyme is normally 142, sodium moves down its steep concentration gradient from the chyme through the brush border of the epithelial cell cytoplasm. Sodium is co-transported with glucose and amino acids as well as the sodium (in) - hydrogen (out) exchanger

Proteins of the diet

Dietary proteins are linked by peptide linkages Characteristics of each protein are determined by the types of AA's in the protein molecule and by the sequential arrangements of these AA's

Active absorption of Ca, Iron, K, Mg, and P

Ca ions are actively absorbed into the blood especially from the duodenum, and amount of calcium ion absorption is exactly controlled to supply the daily need of the body for calcium. Affected by parathyroid hormone and Vitamin D. Parathyroid hormone activates Vit D and the activated Vit D in turn greatly enhances calcium absorption Iron ions are actively absorbed in the small intestine Potassium, Mg, and P are actively absorbed through the small intestine In general, monovalent ions are absorbed with ease in greater quantities. Conversely bivalent of ions are normally in only small amounts

Cholesterol ester digestion

Cholesterol esters are a combo of cholesterol and fatty acid the enzyme cholesterol ester hydrolase to hydrolyze the cholesterol ester and phospholipase A2 to hydrolyze the phospholipid Bile salt micelles play the same role in ferrying free cholesterol and phospholipid molecule digestates that they play in ferrying monoglycerides and FFA's

Absorption in the Small Intestine

Consists of several hundred grams of carbs, 100 grams of fats, 50-100 grams of amino acids and ions, and 7-8 liters of water per day The large intestine can absorb still additional water and ions, in lesser amounts

Absorption of other sugars

Galactose is transported by the same mechanism as glucose Fructose transport occurs via facilitated diffusion throughout the intestine, which becomes phosphorylated once inside the cell and then converted to glucose and transported in the blood

Glucose-Na Co-transport

In the absence of sodium transport through intestinal membrane, virtually no glucose can be absorbed Active transport of sodium ions through the basolateral membrane of the intestinal epithelial cells into the blood, thereby decreasing the sodium inside the cells. This decrease of sodium inside the cells causes sodium from the intestinal lumen to move through the brush border of the epithelial cells via a secondary active transport mechanism. Sodium ion combines with a transport protein, but the transport protein will not transport sodium without another substance, such as glucose Thus low concentrations of sodium within the cell literally drags sodium to the interior of the cell and along with it the glucose at the same time

Absorption of Chloride ions in the small intestine

In the upper part of the small intestine, chloride ion absorption is rapid and occurs mainly by diffusion (follows sodium) Chloride is also absorbed across the brush border in parts of the ileum and large intestine by a brush border membrane chloride-bicarb exchanger Chloride exits the cell on the basolateral membrane through the chloride channels

Absorption/secretion of Electrolytes and Water

Large intestine has a high capacity for sodium absorption, and the electrical potential gradient created by absorption of sodium causes chloride absorption as well. Tight junctions between epithelial cells prevent significant amounts of back diffusion of ions, thus allowing the large intestinal mucosa to absorb sodium ions far more completely In addition, as occurs in the distal portion of the small intestine, the mucosa of the large intestine secretes bicarb ions while it simultaneously absorbs an equal number of chloride ions in an exchange transport process

fats in the diet

Neutral fats known as TG's that contain a glycerol nucleus and three fatty acids - animal origin Phospholipids and cholesterol esters contain fatty acid and can therefore be considered fats. Cholesterol however is a sterol compound that contains no fatty acid, but it does exhibit some of the physical and chemical characteristics of fats plus it is derived from fats A small amount of TG are digested in the stomach by lingual lipase that is secreted by the lingual glands in the mouth and swallowed with saliva

Bacterial Action in the colon

Numerous bacteria, especially colon bacilli, are present even normally in the absorbing colon. They are capable of digesting small amounts of cellulose, this way providing a few calories of extra nutrition for the body Other substances formed as a result of bacterial activity are vitamin K, vitamin B12, thiamine, riboflavin, and various gases that contribute to flatus in the colon especially CO2, hydrogen gas, and methane Bacteria formed vitamin K is especially important because the amount of this vitamin in the daily ingested foods in normally insufficient to maintain adequate blood coagulation

Osmosis of Water

Osmosis of water occurs because a large osmotic gradient has been created by the elevated concentration of ions in the paracellular space. Much of this osmosis occurs through the tight junctions between the apical borders of the epithelial cells (paracellular) but much also occurs through the cells themselves (transcellular)

Digestion of Proteins in the stomach

Pepsin, the important peptic enzyme of the stomach, is most active at a pH of 2-3 and inactive above 5 Pepsin can digest collagen that is a major constituent of the intercellular connective tissue of meats, therefore for the digestive enzymes of the digestive tract to penetrate meats and digest other meat proteins, it is necessary that the collagen fibers be digested Pepsin only initiates the process of protein digestion, usually providing only 10-20 percent of total protein digestion to convert the protein to proteoses, peptones, and a few polypeptides

Folds of Kerckring, Villi, and Microvilli

Plicae circulares - folds of kerckring and valvulae conniventes which increase the surface area of the absorptive mucosa about threefold in the duodenum and jejunum Villi project 1 mm from the surface of the mucosa on the surface of plicae circulares. The villi lie close to one another in the upper small intestines that they touch in most areas and increase the surface area up to 10 fold Each villus is characterized by a brush border consisting of as many as 1000 microvilli 1 micrometer in length and 0.1 micrometers in diameter that increase the surface area 20 fold the three aspects of the small intestine combined increase the total surface area of the small intestine close to 1000 fold Villi - advantageous arrangement of the vascular system for absorption of fluid and dissolved material into the portal blood and the arrangement of the central lacteal lymph vessels for absorption of fat Pinocytotic vesicular transport is preset in the enterocytes Extending from the epithelial cell body into each microvillus of the brush border are multiple actin filaments that contract rhythmically to cause continual movement of the microvilli, keeping them constantly exposed to new quantities of intestinal fluid

Digestion of Carbs in the Mouth and Stomach

Saliva contains a-amylase (ptyalin) secreted by the parotid glands that hydrolyzes starch into the disaccharide maltose and other polymers of glucose Starch digestion sometimes continues in the body and fundus of the stomach for as long as 1 hour before the food becomes mixed with stomach secretions because the acid inhibits amylase On the average, before food and its accompanying saliva do become completely mixed with the gastric secretions as much as 30-40% of the starches will have been hydrolyzed to form maltose

Hydrolysis of Disaccharides and Small Glucose polymers into monosaccharides in intestinal epithelial enzymes

The enterocytes lining the villi of the small intestine contain four enzymes (lactase, sucrase, maltase, and a-dextrinase) which are capable of splitting the disaccharides lactose, sucrose, and maltose, plus other small glucose polymers into their constituent monosaccharides. These enzymes are located in the enterocytes covering the intestinal microvilli brush border, so the disaccharides are digested as they come in contact with these enterocytes Lactose - galactose and glucose the final products of carb digestion are monosaccharides Glucose represents more than 80% of the final products of carbohydrate digestion and galactose and fructose each represent seldom more than 10%

Composition of Feces

The feces normally are about three fourth water and one fourth solid mater that is composed of 30% dead bacteria, 20-40% fat and organic matter, 2-3% protein, and 30% undigested roughage from food and dried constituents of digestive juices Brown color of feces is caused by stercobilin and urobilin The actual odoriferous products include indole, skatole, mercaptans and hydrogen sulfide

Bile salts form micelles that accelerate its digestion

The hydrolysis of TG is a highly reversible process, therefore accumulation of monoglycerides and FFA's in the vicinity of digesting fats quickly blocks further digestion Bile salts, when in high concentrations in water, have the propensity to form micelles, which are small spherical cylindrical globules of fat and bile salts The sterol nucleus encompasses the fat digestate, forming a small fat globule in the middle with polar groups of bile salts projecting outward to cover the surface of the micelle , polar groups are negatively charged to allow water soluble Bile salt micelles also act as a transport medium to carry the monoglycerides and free fatty acids, both of which would otherwise be relatively insoluble, to the brush border of the intestinal epithelial cells

Maximum absorption capacity of the large intestine

The large intestine can absorb a max of 5-8 liters of fluid and electrolytes each day. When the total quantity entering the large intestine through the ileocecal valve exceeds this amount, the excess appears in the feces as diarrhea

Digestion of peptides by peptidases in the enterocytes that line the intestinal villi

The last digestive stage of proteins in the small intestine is achieved by the enterocytes that line the villi of the small intestine These cells have a brush border that consists of hundreds of microvilli projecting from the surface of the cell and have peptidases that protrude through the membranes to the exterior where they contact intestinal fluids aminopolypeptidase and several dipeptidases that succeed in splitting the remaining larger polypeptides into tri/dipeptides and a few amino acids. Both the AA and di/tripeptides are easily transported into the enterocyte In the cytosol, the remaining di/tripeptides are broken down to amino acids that then pass into the blood More than 99% of the final digestive products that are absorbed are amino acids

Anatomical Basis of Absorption

Total quantity of fluid that must be absorbed each day by the intestines is equal to the ingested fluid (1.5 liters) plus that secreted in the various GI secretions (7 liters) to a total of 8-9 liters per day. All but 1.5 is absorbed in the small intestines The stomach is a poor absorptive area of the GI tract because it lacks the typical villus type of absorptive membrane and also because the junctions between the epithelial cells are tight junctions. Only a few substances such as alcohol and aspirin can be absorbed in small quantities

Isosmotic Absorption

Water is transported through the intestines entirely by diffusion When chyme is dilute enough, water is absorbed through the intestinal mucosa into the blood of the villi almost entirely by osmosis Conversely water can also be transported in the opposite direction from plasma into chyme. This occurs especially when hyperosmotic solutions are discharged from the stomach into the duodenum

Absorption of Bicarb ions in the duodenum and jejunum

When sodium ions are absorbed, moderate amounts of hydrogen ions are secreted into the lumen of the gut in exchange for some of the sodium that combine with bicarb ions to form carbonic acid which then dissociates to CO2 and H2O Water remains in the chyme and CO2 is readily absorbed into the blood and expired by the lungs. ** active absorption of bicarb ions

Secretion of Bicarb ions in the ileum and large intestine - simultaneous absorption of chloride ions

epithelial cells on the surface of the villi in the ileum, as well as on the surfaces of the large intestines, have a special capability of secreting bicarb ions in exchange for absorption of chloride ions