Presentation on theme: "GI tract Function: Obtain food"— Presentation transcript:
1 GI tract Function: Obtain food Digest food- pharynx, stomach, small intestineAbsorb nutrients (monosaccharides,amino acids, fatty acids, monoglycerides)-small intestine, large intestineProtection- large immune defense organ
2 From Gray’s anatomy:“Treves states that, in one hundred cases, the average length of the small intestine in the adult male was 22 feet 6 inches, and in the adult female 23 feet 4 inches: but that it varies very much, the extremes in the male being 31 feet 10 inches, and 15 feet 6 inches. He states that in the adult the length of the bowel is independent of age, height, and weight. “
8 Organization of the GI tract MucosaSurface epithelium, columnar cellsLoose areolar connective tissueThin layer of smooth muscle, muscularis mucosaeSpecializations of mucosaVilliM (microfold) cells- antigen presentation
11 Figure 15—23. Electron micrograph of epithelium of the small intestine Figure 15—23. Electron micrograph of epithelium of the small intestine. Abundant microvilli at the cell apex can be seen to form the brush border. At the left are 2 lymphocytes migrating in the epithelium. In the center is an enteroendocrine cell (E) with its basal secretory granules. x1850.cap
12 Antibody production in GI tract IgA- produced by plasma cells in secretions including saliva, tears, milk, and intestinal secretionsSecreted with “secretory component”, which protects the antibody from digestion
16 Figure 15—33. Some aspects of immunologic protection of the intestine Figure 15—33. Some aspects of immunologic protection of the intestine. A: A condition that is more frequent in the upper tract, such as in the jejunum. There are many IgA-secreting plasma cells, scattered lymphocytes, and some macrophages. Note that the lymphocytes in the epithelial lining are located outside the epithelial cells, and below the tight junctions. B: A condition that is more frequent in the ileum, where aggregates of lymphocytes are located under M cells. The M cells transfer foreign material (microorganisms and macromolecules) to lymphocytes located deep in the cavities of the M cells. Lymphocytes spread the information received from this foreign material to other regions of the digestive tract, and probably to other organs, through blood and lymph.
17 Submucosa Moderately dense connective tissue Plicae circulares, circular folds, valvulae conniventes; valves of KerkringOutfoldings of submucosaBegin in duodenum, 5 cm after pylorus in humanSubmucosal plexusInnervates mucosaInnervates muscularis mucosa
21 Autonomic Reflex 101Afferent sensory into nucleus of the solitary tract (IX, X)Motor outputs fromIX (glossopharyngeal, gag reflex)X (DMV, to everywhere)XII (hypoglossal, to tongue, motor only)To intermediolateral cell column and SNS
23 Stomach 4 regions Cardiac Fundus Body Pylorus Digestion and mixing- food enters as a bolus (ball), leaves 3-4 hr later as a semi-fluid called chymeMechanical churningEnzymes (pepsin, renin, lipase)HClMucousLined with folds called ‘rugae’
24 Gastric glands Surface covered with gastric pits Receive contents of glandsSurface epithelium and cells lining pit produce mucous
26 Cardiac glands 2-4 cm from opening of stomach Wide lumen, often coiled, see glands in X-sectionGastric pits extend ¼ to 1/3 of mucosa surfaceMostly mucous cells, long coiled glands
27 Fundic glands Occupy largest area Produce most of the acid and mucous of stomachShort pits, long simple branched tubular glandsMany cell typesSurface mucousMucous neck cellsChief cells- produce pepsinogenParietal cells- produce HCL, intrinsic factor
28 Pyloric glandsLong pits, short glandsMany enteroendocrine glands
31 Pyloric glandFigure 15—19. Photomicrograph of a section of the pyloric region of the stomach. Note the deep gastric pits with short pyloric glands in the lamina propria. H&E stain. Low magnification. (Courtesy of MF Santos.)
32 Figure 15—17. Electron micrograph of a section of gastric gland in the fundus of the stomach. Note the lumen and the parietal cells, containing abundant mitochondria; chief cells, with extensive rough endoplasmic reticulum; and enteroendocrine cells (closed type), with basal secretory granules. x5300.
33 Figure 15—14. Electron micrograph of an active parietal cell Figure 15—14. Electron micrograph of an active parietal cell. Note the microvilli (MV) protruding into the intracellular canaliculi and the abundant mitochondria (M). x10,200. (Courtesy of S Ito.)
34 Figure 15—15. Composite diagram of a parietal cell, showing the ultrastructural differences between a resting cell (left) and an active cell (right). Note that the tubulovesicles (TV) in the cytoplasm of the resting cell fuse to form microvilli (MV) that fill up the intracellular canaliculi (IC).
37 Clinical correlations Gastric atrophy- loss of mucosa, antibodies produced against parietal cells, can lead to anemia (pernicious)Peptic ulcer- too much acid production relative to mucous protectionNormal stomach HCl- 18 mEq per nightUlcer – 300 mEq per nightGastric ulcerMay result not from too much acid, but from loss of mucous lining- alcohol, aspirin- NSAIDS!
38 NSAIDS and ulcersNSAIDs inhibit the COX-1 enzyme, ultimately reducing prostaglandin synthesis which is required formucous and bicarbonate production.Inhibition of stomach acid secretion.
39 Role of Bacteria-2005 Nobel in Physiology or Medicine (announced October 3, 2005)Barry Marshall, Robin WarrenHelicobacter pyloriOld thinking- treat ulcers with antihistamines (Zantac, ranitidineH2 antagonists, etc) to reduce acid secretion50% relapse rate/6 months, 95% relapse rate 2 yrsAntihistamines and antibiotics, 12% relapse for duodenal ulcer, 13% for gastric ulcerNow also use proton pump blockers (Nexium)
40 Incidence of H. pylori infection Helicobacter pylori may be transmitted orally by means of fecal contaminated food or waterIFHII: About Helicobacter pylori. International Foundation for Helicobacter and Intestinal Immunology
41 Table 4: Estimated Ulceration Prevalence Per 1,000,000 People Per Year Source: Non-linear optimization by author, based on various studies subject to the constraints listed in Table 3 Scenario Duodenal Ulcer Gastric Ulcer Both Types of Ulcers No Ulcer TOTALS (people) Neither NSAID user nor H. pylori infection 0 651,288 NSAID user only 671 51,035 51,706 Both NSAID user and H. pylori infection 7,092 822 3 7,377 15,294 H. pylori infection only 2,862 3,484 67 275,300 281,712 9,953 4,977 70 985,000 1,000,000
42 Small intestine General organization DuodenumJejunumIleumVilli- finger like projections of the mucosa
50 Intestinal epithelial cells are short lived Cells differentiate in crypts or glands from stem cellsCells go through 5-6 divisions before reaching terminal cell stageCells (except Paneth cells) translocate to villus and then tip of villusAfter 2-5 days cells reach villus tip and apoptosis begins
53 Figure 15—22. Electron micrograph of an absorptive epithelial cell of the small intestine. Note the accumulation of mitochondria in its apex. The luminal surface is covered with microvilli (shown in transverse section in the inset). Actin filaments, sectioned transversely, constitute the principal structural feature in the core of the microvilli. x6300. (Courtesy of KR Porter.)
54 Microvilli 3000 per cell 0.5-0.1 um diameter Extensive actin microfilament networkFound only in absorptive cells of SI, thyroid, proximal convoluted tubule
56 Figure 15—24. Structure of a microvillus Figure 15—24. Structure of a microvillus. A cytoskeleton of actin filaments, associated with other proteins, keeps the shape of the microvillus. The actin filaments are continuous with the microfilaments of the terminal web (see Chapter 4), which also contains intermediate filaments. Note that in this location actin filaments have a structural role and are not related to movement, as is usually the case when these microfilaments are present. To fulfill its supportive role, actin is associated with other proteins that link the microfilaments to one another to fibrin, and to the cell membrane and a specific protein–villin–in its tip.
58 Figure 15—40. Electron micrograph of epithelial cells of the large intestine. Note the microvilli at the luminal surface, the well-developed Golgi complex, and dilated intercellular spaces filled by interdigitating membrane leaflets, a sign of active water transport. x3900.
70 Figure 15—25. Lipid absorption in the small intestine Figure 15—25. Lipid absorption in the small intestine. Lipase promotes the hydrolysis of lipids to monoglycerides and fatty acids in the intestinal lumen. These compounds are stabilized in an emulsion by the action of bile acids. The products of hydrolysis cross the microvilli membranes passively and are collected in the cisternae of the smooth endoplasmic reticulum (SER), where they are resynthesized to triglycerides. These triglycerides are surrounded by a thin layer of proteins that form particles called chylomicrons (0.2—1 micrometers in diameter). Chylomicrons are transferred to the Golgi complex and then migrate to the lateral membrane, cross it by a process of membrane fusion (exocytosis), and flow into the extracellular space in the direction of the blood and lymphatic vessels. Most chylomicrons go to the lymph; a few go to the blood vessels. The long-chain lipids (>C12) go mainly to the lymphatic vessels. Fatty acids of fewer than 10—12 carbon atoms are not reesterified to triglycerides but leave the cell directly and enter the blood vessels. RER, rough endoplasmic reticulum. (Based on results of Friedman HI, Cardell RR Jr: Anat Rec 1977;188:77.)
71 Figure 15—26. Electron micrograph of intestinal epithelium in the lipid-absorption phase. Note the accumulation of lipid droplets in vesicles of the smooth endoplasmic reticulum. These vesicles fuse near the nucleus, forming larger lipid droplets that migrate laterally and cross the cell membrane to the extracellular space (arrows). x5000. (Courtesy of HI Friedman.)
73 Properties of lipoproteins in blood circulation Source: After M. S. Brown and J. L. Goldstein, The Pharmacological Basis of Therapeutics. 7th ed., A. G. Gilman, L. S. Goodman, T. W. Rall, and F. Murad, Eds. (Macmillan, 1985), p Biochemistry, BergLipoproteinsMajor core lipidsApoproteinsMechanism of lipid deliveryChylomicronDietary triacylglycerolsB-48, C, EHydrolysis by lipoprotein lipaseVery low density lipoprotein (VLDL)Endogenous triacylglycerolsB-100, C, EIntermediate-density lipoprotein (IDL)Endogenous cholesterol estersB-100, EReceptor-mediated endocytosis by liver and conversion into LDLLow-density lipoprotein (LDL)B-100Receptor-mediated endocytosis by liver and other tissuesHigh-density lipoprotein (HDL)ATransfer of cholesterol esters to IDL and LDL
74 Intestinal crypts Paneth cells- lie at the base of the crypts Produce antibacterial and antifungal peptides called cryptidins or a-defensinsPaneth cell dysfunction may contribute to Crohn’s disease
77 Western blot for cryptidin Paneth cells secrete crytidin in response to bacteria (LPS, lipopolysaccharide)Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol (2):113-8
79 Figure 15—28. Section treated immunohistochemically to demonstrate the presence of lysozyme in the Paneth’s cells of the small intestine (arrowheads) and the macrophages (M) of the connective tissue. Medium magnification.
80 Figure 15—29. Electron micrograph of a Paneth’s cell Figure 15—29. Electron micrograph of a Paneth’s cell. Note the basal nucleus with prominent nucleolus, abundant rough endoplasmic reticulum, and large secretory granules with a protein core surrounded by a halo of polysaccharide-rich material. These granules contain lysozyme, a lytic enzyme involved in the regulation of intestinal bacteria. x3000.
81 Factors involved in barrier functions for gastrointestinal tract Low pH of gastric juiceMucusIntestinal motilityTight junctionsRegeneration of epithelial cellsAntimicrobial peptides (e.g. defensins)Antimicrobial proteins (e.g. lysozyme and lactoferrin)Paneth cellsPhagocytic cellsLymphocytesAntibodiesGut-associated lymphoid tissuesM cellsNormal floraAyabe T, Ashida T, Kohgo Y, Kono T. The role of Paneth cells and their antimicrobial peptides in innate host defense. Trends Microbiol :394-8.
83 Enteroendocrine cells Located in stomach and small intestineProduce several different types of peptide hormones
84 Figure 15—18. Electron micrograph of an enteroendocrine cell (open type) of the human duodenum. Note the microvilli in its apex. x6900. (Courtesy of AGE Pearse.)
85 Figure 15—23. Electron micrograph of epithelium of the small intestine Figure 15—23. Electron micrograph of epithelium of the small intestine. Abundant microvilli at the cell apex can be seen to form the brush border. At the left are 2 lymphocytes migrating in the epithelium. In the center is an enteroendocrine cell (E) with its basal secretory granules. x1850.
86 Enteroendocrine hormones Cell typestimulusTarget/actiongastrinG- pylorusVagus nerveInc HCL prod.Inc contractionsecretinS- SmallIntestineLow pHInc HCO3- from pancreascholecystokininI- Small IntestineFatty acidsContraction of gall bladdersomatostatinD- pylorus, duodenumHigh gastrinReduce gastrin secretionReduce HCL secretion
89 Apomucin, mucous associated polypeptide- 8 genes encoding apomucins in humans O-glycan chains are attached throughout the polypeptide called apomucin and encoded by the MUC-2 gene. The extensive glycosylation allows mucin to hydrate and gelatinize upon secretion.
90 Figure 15—21. Photomicrograph of the epithelium covering the small intestine. A: Columnar epithelial cells with the brush border (arrowhead) interspersed with mucus-secreting goblet cells. The PAS-hematoxylin staining gives a positive reaction for the glycoproteins present in mucus and the brush border. Medium magnification. B: Numerous absorptive cells with their brush borders and the clearly visible intercellular limits. PT stain. High magnification.
91 Figure 15—39. Section of a large intestinal gland showing its absorptive and mucous goblet cells. Observe that the goblet cells are secreting and beginning to fill the lumen of the gland with its secretions. The microvilli in the absorptive cells participate in the process of water absorption. PT stain. High magnification.
92 Other specializations Brunner’s glandsOnly in duodenum, secrete alkaline mucousOnly found in eutherian mammalsMicrofold (M) cellsMicrofolds rather than microvilliNo glycocalyxForm epithelium of lymphatic nodulesLymphoid nodulesPeyer’s patches- each patch, nodulesBursa of Fabricius- in birds, site of B lymphocytes
93 Large intestine No villi No digestive enzymes secreted Lots of lymphoid tissue in submucosaPrimary function is water reabsorption