Absorption in GIT part I & II

Dr. Waleed R. Ezzat

Lecture Objectives:

1. Indicate the role of Brunner’s glands in duodenum and ofbile salts in fat digestion and absorption (mechanical,hormonal, and neural).

2. Describe the enterohepatic circulation of bile acids.3. Explain the mechanisms of absorption of the principal

inorganic components of diets.

4. Discuss the molecular basis of membrane transport processes.

5. Explain the factors that determine whether a molecule isabsorbed into the blood or into lymph.

6. Explain the mechanisms by which end products of digestion of proteins, carbohydrates, and fats are absorbed into and through the cells lining the alimentary canal.

7. Define how the motility patterns of the colon subserveits function to desiccate (dehydrate) and evacuate the stool.

Introduction

major types of food. All digestion enzymes are proteins

and absorb daily is about 1.5 liters

about 8-9 liters/day. All but 1.5 liter of this is absorbedin the small intestine

• Stomach is a poor absorptive area. Only a few highlylipid-soluble substances can be absorbed in small quantities (e.g. alcohol and aspirin)

• Villi on the mucosal surface increase the absorptive area by about 10-folds. Combined with the brush borders (Microvilli), on the other hand, increase the absorptivearea of mucosa 1000-fold → 250 m2 area for the entire small intestine

• Absorption through GI mucosa occurs by active transport, diffusion, osmosis, and solvent drag

• Hydrolysis is the basic process of digestion for all three

• The total quantity of fluid that the human body ingest

• The sum of fluid that is absorbed by the intestine is

Absorption of ions

Sodium:• The daily intake of sodium for an average person is 5 to 8 g.

Also 20 to 30 g of sodium are secreted in the intestinalsecretions each day. Hence, the intestines absorbs 25 to 35g of sodium each day. Therefore, severe diarrhea → sodiumdepletion.

• Intestinal Na+ absorption is essential to maintain the internal environment, as well as for sugar and amino acids absorption

• Na+ is absorbed in the gut actively by a mechanism similar to that in gallbladder and the renal tubule. Na+ is transported from inside the epithelial cells and pumped out to the paracellular spaces. While it moves from the intestinallumen to the epithelial cells down its electrochemicalgradient by diffusion

• Water follows Na+ transport (Osmosis)

• Active Na+ absorption is enhanced by the hormonealdosterone especially in the colon, a mechanism similar to that in the renal distal tubule.

Absorption of ions (cont.)

Chloride:• Cl─ absorption accompanies Na+ absorption by passive

3diffusion, Na+- Cl─ cotrasport, or Cl─ - HCO ─ exchange.

Bicarbonate:• In the duodenum and jejunum HCO ─ is absorbed indirectly.

Active absorption of Na+ causes som3

e H+ to be secreted to3 2 3the lumen of the gut. H+ reacts with HCO ─ → H CO→

H O + CO2 2

• In the colon HCO ─ is neutralized also by acid productsformed by bacter

3ia

Calcium:• Ca2+ is actively absorbed especially from the duodenum.

Absorption occurs via a membrane-bound carrier that isactivated by Vitamin D which is produced by the kidney.Vitamin D is activated by parathyroid hormone (PTH, or parathormone). Ca2+ is transported out of the cell by a Ca2+-ATPase active transport system and by a Na+-Ca2+ exchange system

Absorption of ions (cont.)Iron:

• Iron ions (Fe2+) are also actively absorbed from upper intestine (duodenum and jejunum). The ferrous ion (Fe2+) is absorbed more efficiently than the ferric ion (Fe3+). Ascorbic acid (vitamin C) promotes iron absorption by reducing Fe3+ to Fe2+ and by preventing iron from forming insoluble complexes within the chyme.

Free Fe2+ binds intracellularly to apoferritin, an iron-binding protein, to form ferritin, and then is transported into the blood. Free Fe2+ circulate in the blood bound to transferrin, a β-globulin. Iron absorption is in proportion to the body’s available amount of transferrin compared to the amount of ferritin. When iron stores are depleted, transferrin synthesis increases.

Potassium, magnesium, phosphate:

• In general, monovalent ions (such as K+ ) are absorbed with ease and in great quantities to bivalent ions (such as calcium and magnesium).• Fortunately, only small quantities of the bivalent ions are normally required daily by the body.

Absorption of Vitamins

• Fat-soluble vitamins (A, D, E, and K) are absorbed along with other lipids in the proximal small intestine.

• Water-soluble vitamins (C, and the B vitamins biotin, folic acid, nicotinic acid, B6 [pyridoxine],B2 [riboflavin], and B1 [thiamine]) are absorbed by facilitated transport or a Na+-dependent active transport system in the proximal small intestine.

• Vitamin B12 absorption is complex. Gastric parietal cells secrete a B12-binding protein called intrinsic factor that binds with vitamin B12 inthe duodenum. The intrinsic factor-B12 complexbinds to a receptor on ileal enterocytes beforeabsorption.

Absorption of carbohydrates• All carbohydrates are absorbed as monosaccharides (80% as

glucose). All carbohydrates must be digested to glucose,galactose, and fructose for absorption to proceed

brush border hydrolize oligosaccharides to glucose• Maltase, lactase, dextrinase, and sucrase in the intestinal

• Glucose is transported by Na+ co-transport mechanism(Sodium-Glucose cotransporter, SGLT1) from intestinal lumen to the epithelial cells

• Once inside the epithelial cell, glucose exit the cell via othertransport proteins (GLUT2) by facilitated diffusion acrossthe cells’ basolateral membrane into the paracellular space

• Galactose is transported by a similar mechanism as glucose

• Fructose is transported exclusively by facilitated diffusionvia GLUT5, as it is converted into glucose on its way throughthe epithelial cells

• Lactose intolerance: a disorder result from the absence of lactase and, thus, the inability to hydrolize lactose to glucose and galactose for absorption. Lactose and H2O remain in the lumen of the GI tract and cause osmotic diarrhea

Absorption of proteins

free amino acids• Proteins are absorbed as dipeptides, tripeptides, and few

• Transportation of free amino acids is by sodium co-transport mechanism similar to glucose and galactose

• At least 5 types of transport proteins have been isolatedup to now. Three for the absorption of basic, acidic, neutral amino acids, and at least two other different polypeptide transporters exist.

diffusion in the same way as fructose• Some free amino acids are transported by facilitated

• Dipeptides and tripeptides are absorbed faster than freeamino acids. They are transported by H+-dependentcotransport in the luminal membrane

• After the dipeptides and tripeptides are transported intothe intestinal cells, cytoplasmic peptidases hydrolize themto amino acids

• The amino acids are then transported from cells to bloodby facilitated diffusion

Absorption of fats

• Micelles reach the microvilli of the intestinal epithelial cells carrying monoglycerides, free fatty acids, and cholesterol. Glycerol is hydrophilic and is not contained in the micelles.

• Monoglycerides, fatty acids, cholesterol and fat-solublevitamins passively diffuse from micelles to the interior of the epithelial cell leaving the bile micelles in the chyme

• Without micelles only 40-50% of fat is normally absorbed• In the enterocyte’s smooth endoplasmic reticulum, new

triglycerides are formed (reesterification), and lipids are then packaged inside apoproteins to form chylomicrons

• Chylomicrons are subsequently released through the base ofthe epithelial cell by exocytosis. As they are too large to enter the capillaries, they are transferred to lymph vessels→ to the thoracic lymph duct → back into the circulation

• Short and medium-chain fatty acids (10-12 carbon atoms orless) can be absorbed directly into the portal blood as they are more water soluble and will not be reconverted to triglycerides

• Almost all digested lipid are totally reabsorbed by the time the chyme reaches the midjejunum. Any malabsorption of lipids → steatorrhea

Fate of the micelles (the entero- hepatic circulation)• 94% of bile salts are reabsorbed into the blood from the

small intestine, half by diffusion and the second half by active sodium-bile salt co-transport in the distal ileum (similar to glucose co-transport)

converted to deoxycholic acid and lithocholic acid• The remaining 6% of bile salts enter the colon and are

• From portal blood hepatocytes absorb almost all bile saltson the first passage and then re-secrete bile salts intothe bile

the feces. The total bile salt pool is approximately 3.5 g• Bile salt re-circulate 18 times before being carried out in

• As bile salts themselves are choleretic agents, therefore,the greater the bile salts in the enterohepatic circulation,the greater the rate of bile secretion

• Resection of terminal ileum →↑ fat content in stool as liver cannot produce sufficient compensation

Absorption in the colon• Out of 1500 ml of chyme normally pass through the

ileocecal valve into the large intestine each day, onlyless than 100 ml of fluid will be left and excreted inthe feces.

• Most of the absorption in the large intestine occurs inthe proximal one half of the colon (i.e. absorbingcolon), whereas the distal colon functions principally for feces storage (storage colon).

• Colonic absorption+is mainly fo

–r Na+, Cl-, and water with

net secretion of K and HCO3+. Aldosterone enabl

+es the

colon to absorb all of the Na in exchange with K .

bacterial3action in the large intestine.• The HCO – helps neutralize the acidic end products of

• The absorption capacity of the colon makes rectalinstillation a practical route for drug administrationsuch as anesthetics, sedatives, tranquilizers, and steroids.

• The maximal capacity for the large intestinalabsorption is 5 to 8 liters of fluid and electrolytes perday. Massive tap water enemas can cause water intoxication.

Absorption in the colon (cont.)• Some enteric microorganisms synthesize vitamin K, a

number of B complex vitamins, and folic acid. These compounds can be absorbed in significant amounts into the portal circulation.

• Short chain fatty acids (2-5 carbon atoms) producedby the action of bacteria in the colon are ofphysiological importance (trophic effect on the colonic epithelial cells, combat inflammation, and are absorbed in part for exchange for H+; so helping to maintain acid-base equilibrium).

• Ammonia is also produced in the colon and absorbed,however, it is removed by the liver (detoxified by conversion to urea) in the first passage.

• In the terminal ileum, Cl- is the primary ion secretedinto the intestinal lumen through Cl- channels. Na+ issecreted into the lumen passively following Cl-. H2O follows NaCl to maintain isosmotic conditions.Toxins from bacteria such as Vibrio cholerae and E.coli cause diarrhea by stimulating Cl- secretion.

Defecation• From the cecum to the sigmoid, mass movements replace

the propulsive movements. These movements usually occur only 1-3 times per day.

• Mass movement is initiated by constrictive ring in thetransverse colon. Then, rapidly, the 20 or morecentimeters of colon distal to the constrictive ringcontract as a unit, propelling the fecal material in thissegment all together further down the colon. Anothermass movement then follows farther along the colon.

• The appearance of mass movements is initiated bycolonic distension or by gastrocolic and duodenocolicreflexes. These reflexes result from distention of thestomach and duodenum.

• The rectum is mostly empty of feces, partly because ofthe weak functional sphincter at the juncture betweenthe sigmoid colon and the rectum, and the presence ofsharp angulation at this point that contributes additionalresistance to filling of the rectum.

• When mass movements have forced a mass of feces intothe rectum, the desire for defecation is felt, withreflex contraction of the rectum and relaxation of the anal sphincters.

Defecation (cont.)

• Expulsion of fecal matter through the anus is prevented by theexternal anal sphincter that is kept continuously constrictedunless conscious signals inhibit the constriction.

• Defecation is initiated by defecation reflexes. Reflexes include;

1. Intrinsic reflex. Rectal distention → initiation of myentericplexus reflex → peristaltic waves in the descending colon, sigmoid, and rectum + relaxation of the internal anal sphincter → forcing feces toward the anus.

2. Parasympathetic defecation reflex. Afferent signals fromthe rectum → sacral parasympathetic efferent reflex to thedescending colon, sigmoid, rectum, and anus → intensifiedperistaltic waves and relaxation of the internal anal sphincter.

• The defecation reflexes can purposely be activated by ValsalvaManeuver. Reflexes initiated in this way are almost never aseffective as those that arise naturally.

• In newborn babies and in some people with transected spinalcords, defecation reflexes cause automatic emptying of thecolon because of lack of conscious control exercised throughvoluntary contraction or relaxation of the external analsphincter.

Test Question

Q. Regarding the small intestine:

A. Is a site of mechanical but not chemical digestion.B. Lack of bile is likely to cause steatorrhea.C. Does not secrete hormones.D. Lacks goblet cells.E. Contains 3 regions of equal length