Fisiologia Humana Sistema Digestório

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Fisiologia Humana:
Sistema Digestório
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Bibliografia recomendada
Livros-textos:
“Fisiologia” Costanzo, 2007, 3ª Ed. (Ed. Elsevier)
“Berne & Levy: Fundamentos de Fisiologia”, Levy et al, 2006, 4ª Ed. (Ed. Elsevier)
“Fisiologia” Berne et al., 2004 (Ed. Elsevier)
“Tratado de Fisiologia Médica” Guyton & Hall, 2006, 11ª Ed. (Ed. Elsevier)
“Fisiologia”, Aires, M. M., 2008, 3ª Ed. (Ed. Guanabara Koogan)
“Fundamentos de Fisiologia Médica” Johnson, 2003 (Ed. Guanabara Koogan)
“Fisiologia: texto e atlas” Silbernagl e Despopoulos, 2003 (Ed. Artmed)
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Fisiologia do Sistema Digestório
Digestão e absorção de nutrientes de uma dieta ideal
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http://www.lib.mcg.edu/edu/eshuphysio/program/section6/6ch7/s6ch7_4.htm 
O EPITÉLIO ABSORTIVO: INTESTINO DELGADO
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O EPITÉLIO ABSORTIVO: INTESTINO DELGADO
ADAPTAÇÕES ABSORTIVAS
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O EPITÉLIO ABSORTIVO: INTESTINO DELGADO
ADAPTAÇÕES ABSORTIVAS
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O EPITÉLIO ABSORTIVO: INTESTINO DELGADO
ADAPTAÇÕES ABSORTIVAS
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/digestion/smallgut/anatomy.html
junções intercelulares
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http://www.nature.com/nrm/journal/v3/n2/slideshow/nrm726_F3.html
http://www.heuserlab.wustl.edu/v2.0/images/galleries/classics/pages/10.shtml
O EPITÉLIO ABSORTIVO: INTESTINO DELGADO
ADAPTAÇÕES ABSORTIVAS
microvilosidades (borda-em-escova)
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O EPITÉLIO ABSORTIVO: INTESTINO DELGADO
ADAPTAÇÕES ABSORTIVAS
perfusão sangüínea e drenagem linfática
Veja aula online sobre absorção em: http://people.bu.edu/fgarcia/lectures/gi/index.htm 
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Digestão e absorção de carbohidratos
Amilopectina (amido) da batata
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Digestão e absorção de carbohidratos
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Fig. 33-1 Structure of a branched starch molecule and the action of α-amylase. The colored circles represent glucose monomers linked by α-1,4 linkages. The black circles represent glucose units linked by α-1,6 linkages at the branch points. The α-1,6 linkages and terminal α-1,4 bonds cannot be cleaved by α-amylase. Berne et al., 2004
Digestão do amido (amilopectina) ~glicogênio
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Digestão e absorção de amido (~glicogênio)
(-dextrinase)
Johnson, 2004
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Digestão e absorção de carbohidratos:
enzimas do I. D. (borda-em-escova)
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Fig. 7.7 Glucose transport from intestinal lumen into the blood.
Glucose is pumped into the cell through the Na+-coupled glucose symporter (SGLT1), and passes out of the cell by facilitated diffusion mediated by the GLUT-2 uniporter.
The Na+ gradient for glucose symport is maintained by the Na+/K+-ATPase, which keeps the intracellular concentration of Na+ low. SGLT1 is inhibited by phlorizin and GLUT-2 by phloretin. Phloretin-insensitive GLUT-5 catalyzes the uptake of fructose by facilitated diffusion. The fructose is then exported through GLUT-2. 
A defect of SGLT1 causes glucose/galactose malabsorption. Adjacent cells are connected by impermeable tight junctions, which prevent solutes from crossing the epithelium. However, leakage of salts (Na+ and Cl-) through tight junctions induces diarrhea as a result of inhibition of water absorption. Diarrhea is also induced by laxatives
such as phenolphthalein, which is an irritant cathartic for the colon. Thick arrows indicate the binding sites for inhibitors. Baynes, 2004 chp. 7
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Digestão e absorção de carboidratos
enzimas e transportadores do I. D. presentes nas microvilosidades (borda-em-escova)
Fig. 33-2 Functions of the major brush border oligosaccharidases. The glucose, galactose, and fructose molecules released by enzymatic hydrolysis are then transported into the epithelial cell by specific transport proteins. The glucose-galactose transporter is also known as SGLT1 and the fructose transporter as GLUT5. G, Glucose; Ga, galactose; F, fructose. (From Gray GM: N Engl J Med 292:1225, 1975.) Berne et al., 2004
SGLT1
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Fig. 33-4 Absorption of glucose, galactose, and fructose in the upper small intestine. Glucose and galactose enter the epithelial cell at the brush border against a concentration gradient via the SGLT1 transport protein; the Na+ gradient provides the energy for monosaccharide entry. Facilitated transport of fructose across the brush border membrane is mediated by GLUT5. Glucose, galactose, and fructose leave the cell at the basolateral membrane by facilitated transport via a common transporter, GLUT2. Berne et al., 2004
Digestão e absorção de carboidratos
enzimas e transportadores do I. D. presentes nas microvilosidades (borda-em-escova)
Berne et al., 2004
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Digestão e absorção de carbohidratos
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Digestão e absorção de outros carbohidratos:
enzimas do I. D. (borda-em-escova)
Johnson, 2004
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Digestão e absorção de carboidratos
enzimas e transportadores do I. D. presentes nas microvilosidades (borda-em-escova)
Fig. 33-2 Functions of the major brush border oligosaccharidases. The glucose, galactose, and fructose molecules released by enzymatic hydrolysis are then transported into the epithelial cell by specific transport proteins. The glucose-galactose transporter is also known as SGLT1 and the fructose transporter as GLUT5. G, Glucose; Ga, galactose; F, fructose. (From Gray GM: N Engl J Med 292:1225, 1975.) 
SGLT1
Berne et al., 2004
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Fig. 33-4 Absorption of glucose, galactose, and fructose in the upper small intestine. Glucose and galactose enter the epithelial cell at the brush border against a concentration gradient via the SGLT1 transport protein; the Na+ gradient provides the energy for monosaccharide entry. Facilitated transport of fructose across the brush border membrane is mediated by GLUT5. Glucose, galactose, and fructose leave the cell at the basolateral membrane by facilitated transport via a common transporter, GLUT2. 
Absorção de carboidratos
transportadores do I. D. presentes nas microvilosidades
Berne et al., 2004
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Digestão de proteínas e absorção de AAS
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Digestão de proteínas e absorção de AAS
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Digestão de proteínas e absorção de AAS
http://www.lib.mcg.edu/edu/eshuphysio/program/section6/6ch7/s6ch7_8.htm 
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Fig. 33-6 The hierarchy of proteases and peptidases that functions in the small intestine. The pancreatic proteases convert dietary proteins to oligopeptides. Brush border peptidases then convert the oligopeptides to amino acids (about 70%) and dipeptides and tripeptides (about 30%). The amino acids are taken up across the brush border membrane by amino acid transporters and the small peptides by a peptide transporter. In the cytosol of the enterocyte, dipeptides and tripeptides are cleaved to single amino acids. (From Van Dyke RW: Mechanisms of digestion and absorption of food. In Sleisenger MH, Fordtran JS, editors: Gastrointestinal disease, ed 4, Philadelphia, 1989, WB Saunders.) 
Berne et al., 2004
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Digestão de proteínas e absorção de AAS
mecanismos celulares (BES/enterócitos)
http://people.bu.edu/fgarcia/lectures/gi/sld009.htm 
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Absorção de di- e tripeptídeos
mecanismos celulares (BES/enterócitos)
Fig. 33-7 A wide variety of dipeptides and tripeptides is taken up across the brush border plasma membrane by a single type of H+-powered secondary active transport protein. The H+ gradient is created by Na+-H+ exchangers in the brush border membrane. In the epithelial cell cytosol, peptidases cleave most of the dipeptides and tripeptides to single amino acids, which leave the cell at the basolateral membrane by facilitated transport. 
Berne et al., 2004
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Digestão e absorção de lipídeos
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Digestão e absorção de lipídeos
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Lingual Lipase 
Lingual lipase is secreted by Ebner's glands located at the root of the tongue and the parotid glands. Lingual lipase is structurally different from pancreatic lipase. It is more specific for medium fatty acids and therefore is more important in the digestion of milk fat in the newborn. Because pancreatic function has not matured in the newborn, lingual
lipase assumes an important role. It does not need colipase for activity and continues to be active in the stomach because its optimal pH is around 4. Recent work has questioned the significance of lingual lipase in the adult human. 
Digestão e absorção de lipídeos
http://www.lib.mcg.edu/edu/eshuphysio/program/section6/6ch6/s6ch6_10.htm 
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Digestão e absorção de lipídeos
Gastric Lipase 
The warmth of the stomach is important in liquidizing most of the dietary lipids. Because fats tend to separate into an oily phase, they are emptied from the stomach later than other gastric contents. Peristaltic contractions can aid emulsification. Emulsified lipid droplets are formed by mechanical agitation in the gut in the presence of lingual and gastric lipases. Gland cells of the fundic stomach secrete a gastric lipase that is the main preduodenal lipase in the adult. Lingual and gastric lipase begin lipid digestion by hydrolyzing triacylglycerols containing short-, medium-, and generally unsaturated long-chain fatty acids to form free fatty acids and 1,2 diacylglycerols by hydrolyzing ester bonds. Because of the buffering action and the broad range of optimal pH ( 3.0 to 6.0) of dietary proteins, lipases remain active after the eating of a meal and are not readily destroyed. These preduodenal lipases appear to be especially important during the neonatal period. During this time pancreatic lipase is not yet very active and milk fat must be digested. About 30% of the dietary triacylglycerol milk fat contains short- and medium-chain fatty acids that are split off the triacylglycerols. These hydrophilic fatty acids can be absorbed through the stomach mucosa to eventually reach the portal vein. Longer chain fatty acids pass onto the duodenum for digestion. 
http://www.lib.mcg.edu/edu/eshuphysio/program/section6/6ch6/s6ch6_10.htm 
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Pancreatic Lipase 
Pancreatic lipase (glycerol ester hydrolase) is secreted in active form into the duodenum (see top figure). It is active on drops or emulsions of triglycerides operating at the interface between the aqeous phase and oil phase. Because pancreatic lipase is almost completely inactivated by bile acid, colipase, a protein present in the pancreatic juice, is activated by trypsin and prevents the inactivation of lipase. Bile acids bind to the triglyceride-containing oil droplet, and prevent pancreatic lipase from binding. Colipase displaces bile acids from the surface of the oil droplet and thus allows a pancreatic lipase molecule to bind to each colipase. The lipase-colipase complex is very active, cleaving I and II fatty acids from triglycerides at the surface of the droplet. Colipase also has a site that binds to the bile acid micelle and this enables products of lipase and other compounds in the fat droplet to be transferred to the bile acid micelle to be emulsified. Pancreatic lipase hydrolyzes emulsified fat to fatty acids and 2-monoglycerides. Bile acids form micelles (an aggregation of small molecules) with products of fat digestion, especially 2-monoglycerides. 2-Monoglyceride molecules tend to have their polar parts facing the aqueous, exterior part of the micelle and the hydrophobic acyl chains in the interior of the micelle. Extremely hydrophobic molecules, long-chain fatty acids, and cholesterol, tend to aggregate toward the interior of the micelle. Much of the micelle's surface is covered with bile acids that have their nonpolar ends facing toward the interior. Although bile acids are poor emulsifying agents, they can emulsify dietary fats with the aid of lecithin, a phospholipid, which is present in high concentration in the bile. The emulsion droplets formed have a large surface area on which lipolytic enzymes can act. Lipid digestive products in the micelle are rapidly exchanged with lipid digestion products in the aqueous phase surrounding the micelle. Micelles keep the surrounding aqueous solution saturated with 2-monoglycerides, fatty acids, and cholesterol lysophosphatides. Micelles do not contain intact triglycerides; they have been hydrolyzed earlier to free fatty acids and 2-monoglycerides. 
Digestão e absorção de lipídeos
http://www.lib.mcg.edu/edu/eshuphysio/program/section6/6ch6/s6ch6_10.htm 
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Digestão e absorção de triglicerídeos
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Fig. 33-19 Lipid absorption in the small intestine. Mixed micelles of bile acids and lipid digestion products diffuse through the unstirred layer and among the microvilli. As digestion products are absorbed from free solution by the enterocytes, more digestion products partition out of the micelles. The ability of micelles to diffuse among the microvilli makes the whole surface of the brush border available for lipid absorption. Transport proteins mediate the facilitated transport of fatty acids and cholesterol across the brush border plasma membrane. In the cytosol of the epithelial cell, fatty acids are bound to fatty acid-binding protein and cholesterol is bound to sterol carrier proteins. 
Digestão e absorção de triglicerídeos
Berne et al., 2004
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http://cwx.prenhall.com/bookbind/pubbooks/mcmurrygob/medialib/media_portfolio/25.html 
Absorção de lipídeos da dieta
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Fig. 33-21 Absorption of bile acids by epithelial cells of the terminal ileum. Bile acids are absorbed both by simple diffusion and by Na+-powered secondary active transport. Conjugated bile acids are absorbed avidly by active transport. Unconjugated bile acids are absorbed chiefly by simple diffusion. In the cytosol of the epithelial cells, bile acids are bound to specific binding proteins. The mechanisms of transport of bile acids across the basolateral membrane remain to be elucidated
Absorção de sais biliares no íleo terminal
Berne et al., 2004
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http://www.cli-online.com/index.php?id=2120 
Comparação por ordem de diâmetro entre as lipoproteínas
quilomícrons
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http://www.cm.utexas.edu/academic/courses/Fall1997/CH339K/Browning/lec34/lec34.htm 
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Mucosa em repouso
Absorção de NaCl ativada
Mecanismos absortivos do epitélio do intestino delgado
Água e NaCl
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Mecanismos absortivos do epitélio do intestino delgado
Água e NaCl
Movimento de água
Visão integrada
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Mecanismos absortivos do epitélio do intestino delgado
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MECANISMOS DE ABSORÇÃO DE CÁLCIO PELO ID
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Cellular mechanisms of Ca2+ absorption in the small intestine. Ca2+ crosses the brush border plasma membrane via Ca2+ channels. In the cytosol of the enterocyte, Ca2+ is bound to calbindin. Ca2+ is extruded across the basolateral membrane by a Ca2+-ATPase and an Na+-Ca2+ exchange mechanism. Some Ca2+ is transported through the cytosol in membrane vesicles and released at the basolateral membrane by exocytosis.
Calcitriol 
(Horm. Derivado da Vitamina D3) - rins
Ca++
Ca++
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(carne vermelha)
(vegetais e cereais)
MECANISMOS DE ABSORÇÃO DE FERRO PELO
DUODENO E JEJUNO PROXIMAL
transferrina
intestinal lumen
duodeno (pH)
A current view of the absorption of iron by intestinal epithelial cells. Berne et al., 2004
DCT1: transportador luminal de ferro; IREG1: transportador basolateral de ferro
Fe++ ferroso (reduzido) Fe+++ férrico (oxidado)
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http://www.mds.qmw.ac.uk/biomed/kb/metabolism/Micronutrients_files/frame.htm
As Vitaminas hidrossolúveis (quando ingeridas em altas doses) são absorvidas por difusão simples e por mecanimos de transporte de membrana específicos.
Absorção de Vitaminas
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http://www.mds.qmw.ac.uk/biomed/kb/metabolism/Micronutrients_files/frame.htm
As Vitaminas hidrossolúveis (quando ingeridas em altas doses) são absorvidas por difusão simples e por mecanimos de transporte de membrana específicos.
As Vitaminas lipossolúveis (A, D, E e K), dissolvidas nas micelas, deixam o intestino pela lifa juntamente com outros lipídeos absorvidos da dieta.
Absorção de Vitaminas
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Fig. 33-19 Lipid absorption in the small intestine. Mixed micelles of bile acids and lipid digestion products diffuse through the
unstirred layer and among the microvilli. As digestion products are absorbed from free solution by the enterocytes, more digestion products partition out of the micelles. The ability of micelles to diffuse among the microvilli makes the whole surface of the brush border available for lipid absorption. Transport proteins mediate the facilitated transport of fatty acids and cholesterol across the brush border plasma membrane. In the cytosol of the epithelial cell, fatty acids are bound to fatty acid-binding protein and cholesterol is bound to sterol carrier proteins. 
Transporte das Vitaminas lipossolúveis para a borda-em-escova para absorção
Vitaminas lipossolúveis (A, D, E e K)
camada estacionária de água (barreira para a difusão de lipídeos)
Berne et al., 2004
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Absorption and transportation
Vitamin E contained in food is absorbed by the body in the intestines after the formation of mixed micelles by bile acids. Vitamin E is then transported by chylomicron to the liver. It is generally assumed that all tocopherols are absorbed equally in the intestines, but only   -tocopherol is selectively transported by alfa   -TTP (  alfa -tocopherol transfer protein) to blood because of the high affinity of the transfer protein in the liver for   alfa-tocopherol http://www.eisai.co.jp/evita_e/ekiso4.html 
Exemplo de transporte: Vitamina E
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http://www.mds.qmw.ac.uk/biomed/kb/metabolism/Micronutrients_files/frame.htm
As Vitaminas hidrossolúveis (quando ingeridas em altas doses) são absorvidas por difusão simples e por mecanimos de transporte de membrana específicos.
As Vitaminas lipossolúveis (A, D, E e K), dissolvidas nas micelas, deixam o intestino pela lifa juntamente com outros lipídeos absorvidos da dieta.
Absorção de Vitaminas
A Vitamina B12 é absorvida no íleo distal por receptores específicos para o complexo Vit. B12 + Fator Íntrinseco, secretado pelas células parietais. Surge no sangue porta ligada à transcobalamina II (uma globulina) e é armazenada no fígado. A falta do FI leva à anemia perniciosa.
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célula parietal
absorção da Vitamina B12
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http://www.uq.edu.au/vdu/HDUAnaemiaMegaloblastic.htm e http://www.animatedmedical.com/Pernanem/pernanem.html e http://www-ermm.cbcu.cam.ac.uk/03006434h.htm 
Fator Intrínseco e a absorção da Vit. B12
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