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Transcript
食物的吸收 Absorption 夏 强,PhD 浙江大学医学院生理学系 医学院科研楼C座518室 电话:88208252 Email:[email protected] 学习目标 • 了解人体消化系统与吸收有关的结构 • 能比较消化道对各类营养物质的吸收形式 和机制 • 能应用消化道吸收知识明确促进与抑制一 种营养物质吸收的作用靶点 消化道四大过程: digestion, secretion, absorption, and motility. 消化道的液体平衡 Digestive secretions are mostly water, with the average amounts indicated here. Note that only 100 ml are excreted in feces, so the mechanisms for water absorption are efficient (recall the kidneys’ primary role in water and osmotic homeostasis). 消化道与吸收有关的结构 The gut wall has a layered organization, with the absorptive cells lining the lumen and neural and muscular components below. Blood and lymph vasculature is abundant to transport absorbed nutrients. nutrients 与吸收有关的结构 By projecting into the lumen, the villi increases the surface area for absorption of nutrients. Microvilli [aka brush border] fringe the villi to further increase surface area. 消化与吸收的一般机制 General mechanisms of digestion and absorption 营养物质的吸收部位 Sites of nutrient absorption Major gastrointestinal diseases and nutritional deficiencies Disease Organ Site of Defects in Nutrient Predominant Disease Digestion/Absorption Celiac sprue(脂肪痢) Duodenum and jejunum Fat absorption, lactose hydrolysis Chronic pancreatitis(慢性 Exocrine pancreas 胰腺炎) Fat digestion Surgical resection of ileum (回肠手术切除) Ileum Crohn disease of ileum (Crohn氏病) Cobalamin and bile acid absorption Primary lactase deficiency Small intestine (原发性乳糖酶缺乏) Lactose hydrolysis 糖的吸收 Carbohydrates The three monosaccharide products of carbohydrate digestion— glucose, galactose, and fructose—are absorbed by the small intestine in a two-step process involving their uptake across the apical membrane into the epithelial cell and their coordinated exit across the basolateral membrane. The Na/glucose transporter 1 (SGLT1) is the membrane protein responsible for glucose and galactose uptake at the apical membrane. The exit of all three monosaccharides across the basolateral membrane uses a facilitated sugar transporter (GLUT2). 蛋白质的吸收 Proteins Action of luminal, brush border, and cytosolic peptidases. Pepsin from the stomach and the five pancreatic proteases hydrolyze proteins—both dietary and endogenous—to single amino acids, AA, or to oligopeptides, (AA)n . These reactions occur in the lumen of the stomach or small intestine. Various peptidases at the brush borders of enterocytes then progressively hydrolyze oligopeptides to amino acids. The amino acids are directly taken up by any of several transporters. The enterocyte directly absorbs some of the small oligopeptides through the action of the H /oligopeptide cotransporter (PepT1). These small peptides are digested to amino acids by peptidases in the cytoplasm of the enterocyte. Several Na -independent amino acid transporters move amino acids out of the cell across the basolateral membrane Ann N Y Acad Sci. 2000;915:171-83. Role of M cells in intestinal barrier function. Kucharzik T1, Lügering N, Rautenberg K, Lügering A, Schmidt MA, Stoll R, Domschke W. 完整蛋白质的吸收 Absorption of whole proteins. Both enterocytes and specialized M cells can take up intact proteins. The more abundant enterocytes can endocytose far more total protein than can the M cells. However, the lysosomal proteases in the enterocytes degrade ∼90% of this endocytosed protein. The less abundant M cells take up relatively little intact protein, but approximately half of this emerges intact at the basolateral membrane. There, immunocompetent cells process the target antigens and then transfer them to lymphocytes, thus initiating an immune response 脂肪的吸收 Lipids 乳化脂滴分解成混合微粒 The breakdown of emulsion droplets to mixed micelles 微粒转运脂肪分解产物到肠细胞表面 Micellar transport of lipid breakdown products to the surface of the enterocyte. Mixed micelles carry lipids through the acidic unstirred layer to the surface of the enterocyte. 2-MAG, fatty acids, lysophospholipids, and cholesterol leave the mixed micelle and enter an acidic microenvironment created by an apical Na-H exchanger. The acidity favors the protonation of the fatty acids. The lipids enter the enterocyte by (1) nonionic diffusion, (2) incorporation into the enterocyte membrane (collision), or (3) carriermediated transport. 在肠细胞内的再酯化及乳糜微粒的形成与分泌Re-esterification of digested lipids by the enterocyte and the formation and secretion of chylomicrons. The enterocyte takes up short- and medium-chain fatty acids and glycerol and passes them unchanged into the blood capillaries. The enterocyte also takes up long-chain fatty acids and 2MAG and resynthesizes them into TAG in the SER. The enterocyte also processes cholesterol into cholesteryl esters and lysolecithin into lecithin. The fate of these substances, and the formation of chylomicrons, is illustrated by steps 1 to 8. 钙的吸收 Calcium Calcium 钙在十二指肠的主动吸收 Active Ca uptake in the duodenum. The small intestine absorbs Ca by two mechanisms. The passive, paracellular absorption of Ca occurs throughout the small intestine. This pathway predominates, but it is not under the control of vitamin D. The second mechanism—the active, transcellular absorption of Ca —occurs only in the duodenum. Ca enters the cell across the apical membrane through a channel. Inside the cell, the Ca is buffered by binding proteins, such as calbindin, and is also taken up into intracellular organelles, such as the endoplasmic reticulum 铁的吸收 Iron Iron 非血红素铁与血红素铁在十二指肠的吸收 Absorption of nonheme and heme iron in the duodenum. The absorption of nonheme iron occurs almost exclusively as Fe2+, which crosses the duodenal apical membrane through DMT1, driven by a H gradient, which is maintained by Na-H exchange. Heme enters the enterocyte by an unknown mechanism. Inside the cell, heme oxygenase releases Fe3+, which is then reduced to Fe2+. Cytoplasmic Fe2+ then binds to mobilferrin for transit across the cell to the basolateral membrane. Fe2+ probably exits the enterocyte through basolateral ferroportin. The ferroxidase activity of hephaestin converts Fe to Fe for carriage in the blood plasma bound to transferrin. 钠的吸收 Sodium 钠主动吸收模式 Modes of active Na absorption by the intestine. A, Nutrient-coupled Na absorption occurs in the villous cells of the jejunum and ileum and is the primary mechanism for postprandial Na absorption. The thickness of the arrows in the inset indicates the relative magnitude of the Na absorptive flux through this pathway. B, Electroneutral Na-H exchange at the apical membrane, in the absence of Cl-HCO exchange, is stimulated by the high pH of the HCO -rich luminal contents. C, Na-H and Cl-HCO exchange is coupled by a change in intracellular pH that results in electroneutral NaCl absorption, which is the primary mechanism for interdigestive Na absorption. D, In electrogenic Na absorption, the apical step of Na movement occurs through the ENaC. CA, carbonic anhydrase. 氯的吸收 Chloride Modes of Cl absorption by the intestine. A, In voltage-dependent Cl absorption, Cl may passively diffuse from lumen to blood across the tight junctions, driven by the lumen-negative transepithelial voltage (paracellular route). Alternatively, Cl may diffuse through apical and basolateral Cl channels. The thickness of the arrows in the inset indicates the relative magnitude of the Cl absorptive flux through this pathway. B, In the absence of a parallel Na-H exchanger, electroneutral Cl-HCO exchange at the apical membrane results in Cl absorption and HCO secretion. C, Electroneutral NaCl absorption can mediate Cl absorption in the interdigestive period. pH couples the two exchangers. CA, carbonic anhydrase. 腺细胞生电性氯分泌的机制 Cellular mechanism of electrogenic Cl secretion by crypt cells. The basolateral Na/K/Cl cotransporter brings Cl into the crypt cell; the Cl exits across the apical Cl channel. Secretagogues may open preexisting Cl channels or may cause subapical vesicles to fuse with the apical membrane, thus delivering new Cl channels. The paracellular pathway allows Na movement from blood to lumen, driven by the lumennegative transepithelial voltage. The thickness of the arrows in the inset indicates that the magnitude of the Cl secretory flux through this pathway is the same throughout the intestine. 钾的吸收与分泌 Potassium 钾分泌与吸收的细胞机制 Cellular mechanisms of K secretion and absorption. A, This mechanism pertains only to the small intestine, which is a net absorber of K through solvent drag across tight junctions. The thickness of the arrows in the inset indicates the relative magnitude of the K flux through this pathway. B, The colon is a net secretor of K . The primary mechanism is passive K secretion through tight junctions, which occurs throughout the colon. The driving force is a lumen-negative transepithelial voltage. C, Another mechanism of K secretion throughout the colon is a transcellular process that involves the basolateral uptake of K through the Na-K pump and the Na/K/Cl cotransporter, followed by the efflux of K through apical K channels. D, Confined to the distal colon is a transcellular mechanism of K absorption that is mediated by an apical H-K pump. 谢谢专注!