Digestion and Absorption of Nutrients PDF

Chapter 26: digestion and absorption of nutrients Nutritional principles ○ Certain substances are essential constituents of any human diet ○ An optimal diet includes, in addition to sufficient water, adequate calories, proteins, fat, minerals and vitamins Caloric intake and distribution ○ The calori...

Chapter 26: digestion and absorption of nutrients Nutritional principles ○ Certain substances are essential constituents of any human diet ○ An optimal diet includes, in addition to sufficient water, adequate calories, proteins, fat, minerals and vitamins Caloric intake and distribution ○ The caloric value of dietary intake must be approximately equal to the energy expending if body weight is to be maintained ○ In addition to the 2000 kcal/day necessary to meet basal needs, 500-2500 kcal/day (or more) are required to meet the energy demands of daily activities ○ The distribution of the calories among carbohydrate, protein and fat is determined partly by physiologic factors and partly by taste and economic considerations ○ A daily protein intake of 1g/kg body weight to supply the 8 nutritionally essential acids and other amino acids is desirable ○ The source of protein is also important ○ Grade I proteins → animal proteins of meat, fish, dairy products and eggs all contain amino acids including the essential amino acids in approximately the proportions required for protein synthesis and other uses ○ On the other hand, most plant proteins are grade II because they supply different proportions of amino acids and some lack one or more of the essential amino acids ○ The protein needs of vegetarians can be met by ingesting strategic mixtures of grade II proteins, but the intake must often be large because of amino acid wastage ○ Fat is the most compact form of food, since it supplies 9.3 kcal/g ○ However, often it is also the most expensive ○ Indeed, internationally there is a reasonably good positive correlation between fat intake and standard of living ○ Typically, western diets have contained large amounts (100g/d or more) ○ In central and sound american indian communities, where corn (carb) is the dietary staple, adults live without ill effects for years on very low fat intake ○ Therefore, provided the needs for essential fatty acids (FA) are met, a low fat intake does not seem to be harmful, and a diet low in saturated fats is desirable ○ Carbohydrate is the cheapest source of calories and provides 50% of more of the calories in most diets ○ In the average middle class american diet, approximately 50% of calories come from carbohydrates, 15% from protein, and 35% from fat ○ When calculating dietary needs, it is unusual to meet the protein requirement first and then split remaining calories between fat and carbohydrate, depending on taste, income and other factors ○ For example, a 65 kg man who is moderately active needs about 2800 kcal/d to maintain his weight He should at least eat 65 g of protein daily supplying 267 (65x 4.1) kcal. A reasonable figure for fat intake is 50-60 g The rest of the caloric requirement can be met by supplying carbohydrates Digestion and absorption: Carbohydrate digestion ○ Principal dietary carbohydrates are polysaccharides, disaccharides and monosaccharides ○ Starches (glucose polymers) and their derivatives are the only polysaccharides that are digested to any degree in the human GI tract by human enzymes ○ Amylopectin, which typically constitutes around 75% of dietary starch, is a branched molecule, whereas amylose is a straight chain with only a a1:4 linkages ○ The disaccharides lactose (milk sugar) and sucrose (table sugar) are also ingested, along with the monosaccharide fructose and glucose Lactose intolerant ○ In most mammals and in many races of humans, intestinal lactase activity is high at birth, then declines to low levels during childhood and adulthood ○ The low lactase levels are associated with intolerance to milk (lactose intolerance) ○ Most europeans and their american descendant retain sufficient intestinal lactase in adulthood; the incidence of lactase deficiency in northern and western europeans is only about 15% ○ However, the incidence in blacks, american indians, asians and mediterranean population is 70-100% ○ When such individuals ingest daily products, they are unable to digest lactose sufficiently, and so symptoms such as bloating, pain, gas and diarrhea are produced by the unabsorbed osmoles that are subsequently digested by colonic bacteria Proteins and nucleic acid protein digestion ○ Protein digestion begins in the stomach, where pepsin cleaves some of the peptide linkages ○ Like many of the other enzymes concerned with protein digestion, pepsin is secreted in the form of an inactive precursor (proenzyme) and activated in the GI tract ○ The pepsin precursor is called pepsinogen and is activated by gastric acid ○ Pepsin hydrolyzes the bonds between the aromatic amino acids such as phenylalanine or tyrosine and a second amino acid, so the products of peptic digestion are polypeptides of very diverse sizes ○ Because pepsin has a pH optimum of 1.6-3.2, its action is terminated when the gastric contents are mixed with the alkaline pancreatic juice in the duodenum and jejunum ○ The pH of the intestinal contents in the duodenal bulb is a 3.0-4.0, but rapidly rises; in the rest of the duodenum it is about 6.5 ○ In the small intestine, the polypeptides, formed by digestion in the stomach are further digested by the powerful proteolytic enzymes of the pancreas and intestinal mucosa ○ Trypsin, chymotrypsin and elastase act as interior peptide bonds in the peptide molecules and are called endopeptidases ○ These powerful protein splitting enzymes of the pancreatic juice are secreted as inactive proenzymes ○ The formation of the active endopeptidases occurs only when they have reached their site of action, secondary to the action of the brush border hydrolase, enterokinase ○ Thus, trypsinogen is converted to the active enzyme trypsin by enterokinase when the pancreatic juice enters the duodenum ○ Enterokinase contains about 41% polysaccharide and this high polysaccharide content apparently prevents it from being digested itself before it can exert its effect ○ Trypsin converts chymotrypsinogen into chymotrypsin and other proenzymes into active enzymes ○ Trypsin can also activate trypsinogen; therefore, once some trypsin is formed, there is an autocatalytic chain reaction ○ Enterokinase deficiency occurs as a congenital abnormality and leads to protein malnutrition Absorption ○ Absorption of amino acids is rapid in the duodenum and jejunum ○ There is little absorption in the ileum in health, because the majority of the free amino acids have already been assimilated at that point ○ Approximately 50% of the digested protein comes from the ingested food, 25% from proteins in digestive juices and 25% from desquamated mucosal cells ○ Only 2-5% of the protein in the small intestine escapes digestion and absorption ○ Some of this is eventually digested by bacterial action in the colon ○ Almost all of the protein in the stools is NOT of dietary origin but comes from bacteria and cellular debris ○ Evidence suggests that the peptidase activities of the brush border and the mucosal cell cytoplasm are increased by resection of part of the ileum and that they are independently altered starvation ○ Thus, these enzymes appear to be subject to homeostatic regulation ○ In humans, a congenital defect in the mechanism that transports neutral amino acids in the intestinal and renal tubules called Hartnup disease ○ A congenital defect in the transport of basic amino acids causes cystinuria ○ However, most patients do not experience nutritional deficiencies of these amino acids because peptide transport compensates ○ In infants, moderate amounts of undigested proteins are also absorbed ○ The protein antibodies in maternal colostrum are largely secretory immunoglobulins (IgAs), the production of which is increase in the breast in late pregnancy ○ They cross the mammary epithelium by transcytosis and enter the circulation of the infant from the intestine, providing passive immunity against infection ○ Absorption is by endocytosis and subsequent exocytosis ○ Absorption of intact proteins decline sharply after weaning, but adults absorb small quantities ○ Foreign proteins that enter the circulation provoke the formation of antibodies and the antigen-antibody reaction occurring on subsequent entry of more of the same protein may cause allergic symptoms ○ Thus, absorption of proteins from the intestines may explain the occurrence of allergic symptoms after eating certain foods ○ The incidence of food allergy in children is said to be as high as 8% ○ However, in most individuals food allergies do not occur, and there is evidence for a genetic component in susceptibility Lipids: fat digestion ○ A lingual lipase secreted by ebner glands on the dorsal surface of the tongues in some species, and the stomach also secretes a lipase. ○ They are of little quantitative significance for lipid digestion other than in setting of pancreatic insufficiency, but they may generate free fatty acids (FFA) that signal to more distal parts of the GI tracts (causing the release of CCK) ○ Most fat digestion therefore begins in the duodenum, with pancreatic lipase being one of the most important enzymes involved ○ This enzyme hydrolyzes the 1 and 3 bonds of the triglycerides (triacylglycerols) with relative ease but acts on the 2 bonds at a very low rate, so the principal products of tis actions are FFA and 2 monoglycerides (2monoacylglycerols) Malabsorption syndrome ○ The digestive and absorptive functions of the Small intestines are essential for life ○ However, the digestive and absorptive capacity of the intestine is larger than needed for normal function (anatomic reserve) ○ Removal of short segments of the jejunum or ileum generally does not cause severe symptoms, and compensatory hypertrophy and hyperplasia of the remaining mucosa occur ○ However when more than 50% of the small intestine is resected or bypassed (short gut syndrome), the absorption of nutrients and vitamins is so compromised that it is very difficult to prevent malnutrition and wasting (malabsorption) ○ Resection of the terminal ileum also prevents the absorption of bile acids and this lead in turn to deficient fat absorption ○ It also causes diarrhea because the unabsorbed bile acids enter the colon, where they activate chloride secretion Short chain fatty acids in the colon ○ Short fatty acid chains (SCFAs) are produced in the colon and absorbed from it ○ SCFAs are 2-5carbon weak acids that have an average normal concentration of about 80 mmol/L in the lumen ○ About 60% of this total is acetate, 25% propionate and 15% butyrate ○ They are formed by the action of colonic bacteria (fermentation) on complex carbohydrates, resistant starches and other components of the dietary fiber, that is, the material that escapes digestion in the upper GI tract and enters the colon ○ Absorbed SCFAs are metabolized and make a significant contribution to the total caloric intake ○ In addition, they exert a trophic effect on the colonic epithelial cells; combat inflammation; and are absorbed in part by exchange for H+, helping maintain acid-base equilibrium ○ SCFAs are absorbed by specific transporters present in colonic epithelial cells ○ SCFAs also promote absorption of Na+ Absorption of minerals and vitamins ○ A number of minerals must be ingested daily for the maintenance of health ○ Besides those for which recommended daily dietary allowances have been set, a variety of different trace elements should be included ○ Trace elements are defined as elements found in tissues in minute amounts ○ In many cases, the mechanisms that provide for their uptake from the diet are poorly understood ○ In humans, iron deficiency causes anemia ○ Cobalt is part of the vitamin B12 molecule, and vitamin B12 deficiency leads to megaloblastic anemia ○ Iodine deficiency causes thyroid disorders ○ Zinc deficiency causes skin ulcers, depressed immune responses and hypogonadal dwarfism ○ Copper deficiency causes anemia and changes in ossification ○ Chromium deficiency causes insulin resistance ○ Fluorine deficiency increases the incidence of dental caries ○ Sodium and potassium are also essential minerals, but listing them is academic because it is very difficult to prepare a sodium free or potassium free duet ○ A low salt diet is, however, well tolerated for prolonged periods because of the compensatory mechanisms that converse Na+ Iron ○ In adults, the amount of iron lost from the body is relatively small ○ The losses are generally well unregulated, and total body stores of iron are regulated by changes in the rate at which it is absorbed from the intestine ○ Men lose about.6 mg/d, largely in stools ○ Premenopausal women have a variable, larger loss averaging about twice this value because of additional iron lost during menstruation ○ The average daily iron intake in the US and europe is about 20 mg, but the amount absorbed is equal only to the losses ○ Thus, amount of iron absorbed is normally about 3-6% of the amount ingested ○ Various dietary factors affect the availability of iron for absorption; for example, the phytic acid found in cereals reacts with iron to form insoluble compounds in the intestine, as do phosphates and oxalates ○ Almost all iron absorption occurs in the duodenum ○ Transport of Fe2+ into the enterocytes occurs via divalent metal transporter 1 (DMT1) ○ Some is stored in ferritin, and the remainder is transported out of the enterocytes by a basolateral transported named ferroportin A protein called hephaestin (Hp) is associated with ferroportin 1 It is not a transporter itself, but it facilitates basolateral transport. In the plasma, Fe2+ is converted to Fe 3+ and bound to the iron transport protein transferrin. This protein has 2 iron binding sites Normally, transferrin is about 35% saturated with iron and the normal plasma iron level is about 130 in men and 110 in women ○ The most common cause of the hereditary forms is a mutated HFE gene that is common in the white population ○ It is located on the short arm of chromosome 6 and is closely linked to the HLAA locus ○ It is still unknown precisely how mutations in HFE cause hemochromatosis, but individuals who are homogenous for HFE mutations absorb excess amounts of iron because HFE normally inhibits expression of the duodenal transporters that participate in iron uptake ○ Acquired hemochromatosis occurs when the iron regulating system is overwhelmed by excess iron loads due to chronic destruction of red blood cells, liver disease or repeated transfusions in diseases such as intractable anemia ○ If hereditary hemochromatosis is diagnosed before excessive amounts of iron accumulate in the tissues, life expectancy can be prolonged substantially bt repeated withdrawal of blood Vitamins ○ Vitamins were discovered when it was observed that certain diets otherwise adequate in calories, essential amino acids, fats, and minerals failed to maintain health (for example,in sailors engaged in long voyages without access to fresh fruits and vegetables) ○ The term vitamin has now come to refer to any organic dietary constituent necessary for life, health, and growth that does not function by supplying energy and which cannot be synthesized endogenously (at least in adequate amounts) ○ Most vitamins are absorbed in upper small intestine, but vitamin B12 is absorbed in the ileum ○ This vitamin binds to intrinsic factor, a protein secreted by the parietal cells of the stomach, and the complex is the form that is absorbed across the ileal mucosa Obesity ○ Obesity is the most common and most expensive nutritional problem in the US ○ A convenient and reliable indicator of body fat is the body mass index (BMI), which is body weight (in kg) divided by the square hight (in meters) ○ Values above 25 are abnormal ○ Individuals with values 25-30 are considered overweight ○ And those with values over 30 are obese ○ In the united states, 34% of the population is overweight and 34% is obese ○ The incidence of obesity is also increasing in other countries ○ Indeed, the world watch institute has estimated that although starvation continues to be a problem in many parts of the world, the number of overweight people in the world is now as great as the number of underfed ○ Obesity is a problem because of its complications ○ It is associated with accelerated atherosclerosis and an increased incidence of gallbladder and other diseases ○ Its association with Type 2 diabetes is especially striking ○ As weight increases, insulin resistance increases and frank diabetes appears Leptin and Ghrelin ○ Leptin and Ghrelin are peripheral factors that act reciprocally on food intake, and have emerged as critical regulators in this regard ○ Both activate their receptors in the hypothalamus that initiate signally cascades leading to changes in food intake ○ Leptin is produced by adipose tissue and signals the status of fat stores therein. As adipocytes increase in size, they release greater quantities of leptin and this tends to decrease food intake, in part by increasing the expression of other anorexigenic factors in the hypothalamus such as proopiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), neurotension, and corticotropin releasing hormone (CRH) ○ Leptin also stimulates metabolic rate ○ Animal studies have shown that it is possible to become resistant to the effects of leptin, however and in this setting, food intake persists despite adequate (or even growing) adipose stores– obesity therefore results ○ Ghrelin on the other hand, is a predominantly fast acting orexin that stimulates food intake ○ It is produced mainly by the stomach, as well as other tissues such as the pancreas and adrenal glands in responses to changes in nutritional status – circulating ghrelin levels increase preprandially, then decrease after a meal ○ It is believed to be involved primarily in meal initiation, unlike the longer term effects of leptin ○ Like leptin, however, the effects of ghrelin are produced mostly via actions in the hypothalamus ○ It increases and/or release of central orexins, including neuropeptide Y and cannabinoids and expresses the ability of leptin to stimulate the anorexigenic factors ○ Loss of activity of ghrelin may account for the effectiveness of gastric bypass procedures for obesity ○ Its secretion may also be inhibited by leptin, underscoring the reciprocity of these hormones ○ There is also some evidence to suggest, however that the ability of leptin to reduce ghrelin secretion is lost in the setting of obesity