Dianaʼs DiarrheaPhysiology at a Glance: GI Tract Overview & Stomach1. Name the 6 structural layers of any given cross-section of the GI tract from lumen outwards and give a brief description of each12. What are the three saliva secreting glands?23. Which two main nerves control the involuntary part of the swallowing mechanism in conjunction with the ‘swallowing centre’ in medulla and pons?34. What parts of the stomach are (i) at the end of the oesophagus, (ii) at the very to of the stomach where air collects (iii) the bottom of the stomach leading to the pyloric sphincter (iv) the bottom of the stomach body5. Which nerves innervate peristalsis in the pyloric sphincter and upper small intestine?46. What volumes can the stomach vary between when it is empty and full?57. What enzyme group breaks down proteins in the stomach?68. What type of cells produce HCl in the stomach?9. What maintains the right pH balance in the stomach with regards to secretion of HCl?71 1. Mucosal Layer (Epithelium), 2. Lamina Propria (connective tissue containing blood & lymph, 3.Muscularis Mucosa (thin layer of SM for making folds and ridges), 4. Submucosa (connective tissuecontaining more blood and lymph and innervated by the submucosal plexus) 5. Muscularis externa (thickcircular layer of muscle covered by a less thick longitudinal layer, 6. Serosa (outermost layer made up ofsquamous mesothelial cells.2 Parotid, Submandibular and Sublingual glands3 9th cranial (glossopharyngeal) and 10th cranial (vagus) nerves4 Vagus and enteric nerve plexuses5 Varies between 50ml (empty) and 4L (full)6Proteins broken into smaller polypeptides (only partially digested) by pepsins in stomach, these areproduced in inactive form as pepsinogens by chief cells in gastric mucosa (activated by HCl)7 Exchange of intracellular H+ for extracellular K+ using H+/K+ ATPase
10.What stops gastric epithelial cells from digesting themselves, and what mechanism comes into action when there is an increased level of HCl in the stomach?811. What happens during the cephalic stage of gastric secretion? 912.What happens during the gastric stage of gastric secretion?1013.What is the name of the sludge produced by the gastric stage?1114.What factors contribute to an increased rate of stomach emptying? 12Physiology at a Glance - Small Intestines15.What happens during the intestinal stage of gastric secretion?1316.What two things are released when fat is detected in the duodenum?1417.Other than the alkaline mucus in the small intestine, what two substances secreted by the liver and pancreas neutralize the contents?1518.What is the average epithelial cell turnover in the small intestine?1619.What is the main mechanism for absorbtion of water and ions from the intestinal lumen? 178Epithelial cells are coated in an alkaline mucosa which neutralizes the acid before it causes damage to thecells, when the acid level gets too high then prostaglandins are released which cause increased mucosalsecretion and HCO3- levels9 Pre stomach, smell/sight/taste and chewing stimulate the release of Ach and gastrin which stimulates therelease of histamine causing parietal cells to produce more acid10In the stomach, food chemicals and stretch mechanoreceptors stimulate the release of the samechemicals as the cephalic phase, plus mucus and pepsinogen. Vagal stimulation also releases gastrin viagastrin releasing peptide. A lower pH once food has left the stomach ﬁnally inhibits gastrin secretion.11 Chyme - which leaves the stomach and enters the duodenum12Increased volume in the pyloric antrum (pre-pyloric sphincter), increase in pH of chyme. (whereasdistention of duodenum, presence of fats and decrease in pH of chyme inhibit stomach emptying13 Food contents of duodenum stimulate gastric secretion by G cells, secretin released in response to acidstimulation which inhibits gastrin secretion14 Gastric inhibitory peptide (GIP) and cholecystokinin (CCK) which both inhibit gastrin and acid release andstimulate the release of pepsinogen from chief cells15 Bile secreted by the liver and bicarbonate secreted by the pancreas16 6 days, due to the harsh environment17 Na+/K+ ATPase generate an osmotic gradient where cellular Na+ is low, therefore Na+ moves from lumeninto cell. It also means K+ levels are high in the cell.
20.How does K+ move out of the cells in the intestinal wall?1821.Which two proteases break down polysaccharides in the small intestine?1922.What are the products of this reaction broken down into and by what enzymes? 2023.How is Ca2+ absorbed from the lumen?2124.How is Fe2+ absorbed from the lumen? 2225.Which pancreatic enzyme breaks down fats into monoglycerides and fatty acids?2326.What are responsible for emulsifying fat droplets in the intestine?2427.How are fats absorbed into the epithelial membrane? 2528.Which vitamins follow the fat pathway for absorbtion and which follow the water pathway?26Physiology at a Glance: The Liver, Pancreas and Gallbladder29.What is secreted into the duodenum in addition to bile at the junction with thecommon bile duct? 2730. What stimulates the release of pancreatic juice into the duodenum?2818 Using a Cl-/K+ coupled mechanism19 trypsin and chymotrypsin20 Carboxylpeptidase and aminopeptidase break peptides down into single amino acids21Single Ca2+ molecules are able to free ﬂow into cellular wall as intracellular Ca2+ conc. is low, these arethen transported out of the epithelial cells by Ca2+ ATPase22Fe3+ cannot be reabsorbed. Fe2+ makes a soluble compound with ascarbate which can be absorbed viacarrier proteins across epithelium23 lipase24 Bile salts, cholic acid and chenodeoxycholic acid25 They form soluble micelles (hydrophilic outer layer, hydrophobic inner region)26 B12 follows water pathway, Vitamins A, D, E and K follow the fat pathway27Pancreatic juice, consisting of enzymes secreted by acinar cells (amylase, lipase, ribonuclease,deoxyribonuclease)28 Release of CCK (cholesystokinin) by duodenum in response to presence of fats and protein
31. What function does pancreatic juice have other than enzyme based digestion of fats, proteins and carbohydrates?2932. What is the weight of a typical liver?3033. What is the difference between endocrine and exocrine?3134. What are the main functions of the liver? 3235. What is a liver lobule?3336. What do hepatocytes do? 3437. What ultimately happens to the bile salts secreted into the duodenum?3538. Other than storage of bile, what function does the gallbladder have? 36 Physiology at a Glance - Large Intestine 39.Label features A-I on the diagram37 40. Approximately how much chyme enters the colon through the ileocaecal sphincter 38 41.Which nerves/plexuses innervate sympathetic and29It contains H20 and HCO3- so is important in neutralizing acidic chyme. The intestines need to have aneutral environment to foster digestive bacteria needed for breakdown of food into absorbable products.30 At 1kg in most adults, the liver is the largest organ in the body.31 Endocrine refers to hormones that are used internally, exocrine refers to the production of something usedin an external environment32Metabolism and storage of metabolic fuels (e.g. glycogen), Exocrine function: production of bile andalkaline digestive ﬂuids for storage in gallbladder, detoxiﬁcation of noxious substances.33Hexagonal structures of which there are tens of thousands in the liver, each consists of a central veinsurrounded by columnar hepatocytes between which are canaliculi that drain into the bile duct. Portal triadscorner each liver lobule which consist of an artery, vein and bile duct branches).34 Hepatocytes secrete hepatic bile (bile salts, bile pigments, cholesterol, mucus) Liver produces 500mL-1Lbile per day.35 5% end up in faeces, 95% are reabsorbed in some form via active transport in distal ileum36 Concentration of bile by reabsorbtion of Na+, H20, HCO3- and Cl- out of bile.37A = caecum, B = ascending colon, C = transverse colon, D = descending colon, E = sigmoid colon, F =Rectum, G = caecal mesentery, H = transverse mesentery, I = sigmoid mesocolon, J = superior mesentericartery/plexus, K = inferior mesenteric artery/plexus38 Approximately 1.5L of chyme per day, after the colon around 150ml of faeces is left of which 50ml is solid
parasympathetic nerves in the colon?3942. What are the main functions of the duodenum?4043. What leads to ‘mass movement’ in the colon? 4144. What are the main actions in the ‘defecation reﬂex’? 4245. Why is reabsorbtion in the colon driven by Na+/K+ ATPase? 4346. What are contained in the ‘crypts’ of the colon?4447. What is the role of ‘tight junctions’ between epithelial cells in the colon?4548. Why are there so many bacteria in the colon as opposed to the upper GI tract, where food is more rich in nutrients, and what are the roles of these bacteria?46Scenario Introduction1. According to site of origin, pathogenesis and stool type, name eight classiﬁcations of diarrhoea472. What are the duration of symptoms for acute, persistent and chronic diarrhoea? 4839Sympathetic nerves innervated by superior mesenteric plexus, parasympathetic by pelvic nervesbranching from sacral nerves. Some nervous stimulation from vagus nerve.40Storage of chyme/faeces, reabsorbtion of water and electrolytes. Chyme usually remains in the colon foraround 20 hours, the longest time spent anywhere in the GI tract.41 Distention of the stomach after the consumption a large meal.42 1/ Contraction of rectum, 2/ contraction of external sphincter, relaxation of internal sphincter, 3/reﬂexrelaxation of external sphincter, can be inhibited voluntarily (striated muscle) inducing ʻreverse peristalsisʼ43Because the chyme is isotonic at the start of the colon so reabsorbtion requires an active mechanismworking against the concentration gradient.44 Columnar, absorbtion focussed epithelial cells and mucus secreting goblet cells45Allow diffusion of H20 out of lumen because Na+/K+ ATPase has pumped out sodium and created ahypertonic environment adjacent to the lumen which draws water out, K+ diffuses out into chyme.46The hostile acid environment has been neutralised by pancreatic juice and mucus, so enveloped bacteriacan survive. Bacteria in the colon are responsible for breakdown of bilirubin into non-pigmented bilirubin.Role in vitamin synthesis, breakdown of primary bile salts into secondary bile salts47Origin: Small intestine or large intestine, Pathogenesis: Infectious, functional (no obvious cause),inﬂammatory (allergic response), Stool type: Osmotic (watery), secretory or fatty (steathorrea)48 Acute = 2 weeks, persistent = 2-4 weeks, chronic = over 4 weeks
3. What symptoms are typical of malabsorbtion? 494. What is the commonest cause of malabsorbtion? 505. What are the symptoms of chronic pancreatitis?51The Intestines1. Deﬁne foregut, midgut and hind gut 522. What membranous structure is stretched between the liver/gallbladder and stomach? 533. What membranous structure is stretched from just below the stomach across the intestines? 544. What are the right and left spaces superﬁcial to the colon? 555. What are the divisions of the intestine? 566. Which artery supplies the midgut?577. Which artery supplies the hindgut?588. What is the suspensory ligament of the duodenum?5949Steathorrea, diarrhoea, nutritional deﬁciency (weight loss, anaemia, oedema (albumin deﬁciency), muscleweakness (Ca2+ deﬁciency), sensory loss (B12 deﬁciency)), general malaise, low bone mass50 coeliac disease, immunological reaction to gluten in diet51Relentless abdominal pain, diarrhoea or steatorrhoea, anorexia/weight loss, polyuria, inﬂammation andﬁbrosis lead to slow destruction of the pancreas52 Foregut: ends after entry of common bile duct into duodenum, Midgut: ends 2/3rds of the way along thetransverse colon, Hindgut: Ends halfway down the anal canal.53 Lesser omentum54 Greater omentum55 Right and left paracolic gutters56 Small Intestine (6m) (3-6 hours): Duodenum (5%), Jejunum (roughly 40%) and Ileum (roughly 60%). LargeIntestine (20 hours): Caecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum.57 Superior mesenteric artery58 Inferior mesenteric artery59 Ligament of Treitz
9. What is the most signiﬁcant difference in the structure of the epithelium between the small and large intestines?6010.What are the name of the anatomical folds in the membrane of the duodenum?6111.Which surface abdominal region does most of the duodenum lie within? 6212.Which organ does the duodenum encircle on three out of four sides?6313.What is the name of the opening into the duodenum where pancreatic juice and bile are secreted from the pancreas and gallbladder?6414.What is the name of the feature between (13) and the hepatopancreatic ampulla? 6515.What is the main difference between the epithelium of the ileum and duodenum6616.In which surface abdominal regions are the jejunum and ileum located? 6717.Which part of the small intestine contains Peyer’s patches?6818.What are vasa recta?6919.What are the three main structural components of the large intestine which are not found in the small intestine?7020.What is the difference between appendages and diverticula? 7160 Small intestine contains villi whereas large intestine does not61 Plicae circularis62 The umbilical (central) region63 Pancreas64 Major and minor duodenal papillae65 Sphincter of Oddi66 The Ileum lacks the plicae circularis of the duodenum67 Jejunum mostly located in umbilical region, Ileum located in hypogastric/pubic and right inguinal regions68 Lymph nodules involved in fat absorbtion, found uniquely in ileum69 Arcades off the mesenteric arteries which run straight to the gut wall70Haustra (sac like divisions), Epiploic/Omental appendages (fatty tags on surface), Teniae coli (strips oflongitudinal muscle which contract to produce the haustra)71 Appendages are normal fatty pouches in the serosa whereas diverticula are pathological pouches of thewhole gut wall and may signify the presence of a blockage or cancer.
21.Which organ does the corner of the ascending and transverse colon turn just below (at the right colic ﬂexure)?7222.Which part of the large intestine is the appendix attached to?7323.Which part of the pelvis does the caecum sit within?7424.What and where (surface location) is McBurney’s point?7525.Which parts of the the large intestine and small intestine are retroperitoneal and which are intraperitoneal? 7626.What are the names for the anastemoses of blood vessels that supply the ascending and descending colon?77 27.Which parts of the colon are mobile within the peritoneum and which are not?78 28.Where does the superior mesenteric artery arise from?79 29.Where does the inferior mesenteric artery arise from?80 30.Label arteries A-H on the diagram8172 The right lobe of the liver73 The caecum74 The right iliac fossa75The tip of the appendix, it lies 2/3rds of the way down a line drawn from the umbilicus to the anteriorsuperior iliac spine. It is the point of maximum pain in appendicitis.76 Retroperitoneal: Rectum, ascending and descending portions of the colon, duodenum. Intraperitoneal:transverse colon, sigmoid colon, caecum, jejunum and ileum.77 Right colonic or hepatic ﬂexure and left colonic or splenic ﬂexure78Transverse and sigmoid colon are mobile because they have mesenteries and are within the peritoneumwhereas the descending colon is not because it has no mesentery and is retroperitoneal. The transversecolon has a mesentery however it is retroperitoneal.79 The abdominal aorta around L180 The abdominal aorta around L381 A= Ileocaecal artery, B = right colic artery, C=middle colic artery, D=superior mesenteric artery, E= inferiormesenteric artery, F=left colic artery, G= sigmoid artery, H=superior rectal artery
General Histological Organisation and Development of the Gut 1.How does the embryological formation of the gut begin?82 2.What is the importance of the yolk sac? 83 3.What do the head fold and tail fold become and what happens to the the divided halves of the ‘midgut/yolk sac’?844. What is the vitelline duct?855. What embryological feature do the umbilical artery, vein and bladder emerge from?866. The foregut, midgut and hindgut are supplied by which arteries? 877. What is the foregut?888. What is differential growth?899. What is the process of ‘recanalisation’ in relation to formation of the oesophagus? 9010.What causes the greater curvature of the stomach in terms of development?9182 During week 3 of development, the ﬂat trilaminar embryonic disc folds under cranially, caudally andlaterally, incorporating part of the yolk sac.83Nutritional function before the placenta develops, start of blood development, posterior part of the yolk sacwill become the gut.84 The lateral folds make up the abdominal wall, the space enclosed becomes the peritoneal cavity and thebit left out of the abdominal wall becomes the umbilical cord.85Diverticulum which connects the dorsal part of the yolk sac with the remnant of the yolk sac at the front, iteventually dissapear86 Allantois87 Foregut - coeliac artery, Midgut - superior mesenteric artery, Hindgut - Inferior mesenteric artery88 Mouth all the way down to duodenum, includes liver and pancreas and biliary apparatus89 Ventral and dorsal mesogastrium are spaces in the embryo which become mesentery when the ventralmesogastrium is lost (differentially)90The oesophagus forms as a tube which is initially ﬁlled with cells in some areas, recanalisation refers toapoptosis of these cells to open the tube up and make the oesophagus91Posterior half of the stomach ʻtubeʼ grows faster than the anterior part (differential growth) and then thewhole structure ʻrotatesʼ to the stomachʼs ﬁnal position.
11.Which mesogastrium is lost when the liver forms? 9212.What does the hepatic diverticulum give rise to?9313.What pathological effect could result from an ‘annular pancreas’? 9414.What is physiological umbilical herniation?9515.What is Meckel’s diverticulum? 96Digestion and Absorbtion of Nutrients1. How do long chain fatty enter the blood circulation from the GI tract?972. Describe the variation in cells in a small intestine villus epithelium?983. Which pumps and ion channels in the intestinal lumen epithelium are involved in sugar absorbtion? 994. Which pancreatic enzymes aid duodenal breakdown of proteins? 1005. Which pumps and transporters take peptides from the lumen to the circulation? 10192 Posterior mesogastrium disappears and leaves lesser sac as space below the liver93 Liver and gallbladder and hepatic vessels94An annular pancreas is development of the pancreas at an abnormal angle which can cause constriction ofthe duodenum95Normal part of development around 6 weeks where liver expands with rapid growth and ﬁlls the peritonealcavity, pushing the gut down the umbilicus and rotating it as this happens. By week 10 the rest of the embryohas grown allowing the gut back in and rotating it again, this giver rise to the rotations in the fully formed gut96A usually asymptomatic deformity. A bulge in the small intestine which is all that remains of the vestigalduct or yolk sac. Can become inﬂamed and mimic appendicitis symptoms. Can lead to ﬁstula in umbilicus.97 First absorbed into lymph by lacteals in the small intestine then enter bloodstream via thoracic duct98Goblet cells throughout, absorptive cells in upper 2/3, stem cells in ʻcryptʼ region for continual epithelialrenewal99Basolateral Na/K ATPase create osmotic gradient which makes Na+ diffuse into the cell, bringing with itglucose and galactose (products of carbohydrate breakdown). Single ion basolateral channels remove these.100 Carboxypeptidases, trypsin, chymotrypsin101Similar to glucose absorbtion, a concentration gradient is created by Na+/K+ ATPase which brings aminoacids, Na+ and H+ ions from the limen to the epithelial cells
6. What does the basolateral side of the epithelium do differently depending on concentration gradient?1027. What are used to carry vitamins A and E from the intestine to the liver? 1038. How are vitamins B and C absorbed? 104Salt and Water Balance 1 & 21. What are the average volumes for secretion of: saliva, gastric ﬂuid, bile, pancreatic juice, intestinal ﬂuid per day?1052. How much ﬂuid is absorbed by the small intestine per day? 1063. Where are the Na/K ATPase pumps on the lumen epithelial cells?1074. What causes absorbtion of water from the intestinal lumen into the submucosa? 1085. Why does glucose accumulate in epithelial cells without going back into lumen? 1096. How much of the glucose in the chyme is reabsorbed in the small intestine?1107. Which molecule in a glucose co-transporter attaches to the pump ﬁrst and therefore drives absorbtion of the other? 1118. What is the normal blood glucose and normal concentration of glucose in the gut lumen without having recently eaten? 112102 Can allow for transport of sodium and glucose either in or out of the cell depending on the gradient103 Transported in chylomicrons (fat droplets) in the lymph, which are used to transport fat around the body104Similar to sugars and peptides, vitamin C and B are transported in Na+ co-transporters according tosodium gradient created by Na/K ATPase across the lumen epithelium105 Saliva - 1.5L/day, gastric - 2L/day, 500ml/day, pancreatic secretion 1.5L/day, intestinal 1.5L/day106 8L/day107 Across the basal and lateral sides of the cell (i.e. all 3 sides but not the lumen)108Na+ is pumped out of the lumen by Na/K ATPase creating osmotic potential in the submucosa around theepithelial cells into which water diffuses across apical and basal membranes. The pressure builds up andforces ﬂuid further into the submucosal ﬂuid and ultimately the circulation.109 Glucose transport is driven by sodium movement in Na+/Glucose co-transporters,110 100%, none gets into the colon111 Sodium attaches ﬁrst and is released last from the transporter, pushing glucose out. It is driven by anosmotic gradient from the lumen to the submucosa112 5mmol in the blood and 0.5mmol in the lumen
9. What happens in glucose glalactose malabsorbtion?11310.What is the difference between GLUT1 and GLUT5? 11411.Which transport protein in particular is responsible for transporting glucose across the basolateral membrane into the submucosa?11512.What is the effect of sweeteners like saccharin and sucrulose on the lumen epithelium?11613.Which peptide found in the crypts of the lumen epithelium is responsible for the up-regulation of GLUT2 and though to cause obesity? 11714.What may lead to excessive uptake of fructose? 11815.How is glucose-galactose malabsorbtion diagnosed?11916.What two things are required for normal intestinal uptake of sugars?12017.What is coeliac disease? 12118.Which substance blocks the sodium channels in the colon?122113SGLT1 transport protein (the Sodium/Glucose co-transporter) fails to transport glucose from the lumen tothe epithelial cell.114 GLUT1 found in the red blood cells and does not transport fructose, whereas GLUT5 is found in the gutand can transport many different sugars including fructose115 GLUT2, glucose uniport116 Up-regulation of transport proteins such as GLUT2 mean more glucose is absorbed117 Glucagon-like-peptide 1 (GLP 1)118 Fructose is absorbed by GLUT2 channels, GLP 1 is responsible for up-regulation of glut 2, so havingmore GLP1 = you will absorb more fructose119 Hydrogen breath test is the most simple way of determining carbohydrate breakdown. If carbs are brokendown in the colon, hydrogen is produced, which does not happen if they are broken down in the smallintestine. Carbs only reach the colon if there is some problem absorbing them in the small intestine. Thelevels of H2 in the patientʼs breath are measured after a glucose meal and again after a fructose meal. In thecase of fructose, they will not have hugely raised H2 because fructose can be absorbed by GLUT2, but afterglucose the H2 levels will rise because glucose absorbtion relies on SGLT1.120 Presence of SGLT1 channel and an Na+ gradient across the apical membrane121An autoimmune disorder caused by a hypersensitivity to wheat (gluten). The inﬂammatory reactionattacks the intestinal submucosa leading to ʻsloughingʼ (shedding dead matter) of the epithelial cells sotherefore the intestine cannot function properly because its villi and crypts have been destroyed.122 Amiloride (K+ sparing diuretic which blocks sodium uniporter Enac)
19.Other than EnaC, how is Na+ reabsorbed in the colon? 12320.Given the answer to (19), how does pH compare between the two sides of the epithelium?12421.What serves to balance out the pH change caused by (19)?12522.What is the process of ‘double exchange’?12623.What are the ratios of liquid:solid of chyme entering the colon and faeces leaving it? 12724.How do crypts suck in faeces to dehydrate it?12825.What does aldosterone stimulate in colonic epithelial cells?12926.Which molecules act as second messengers to activate the following channels Cl-, Cl-/HCO3-, Na+/H+, Na+/K+ATPase?13027.How is chloride transported against its electrochemical gradient into epithelial cells across the basolateral membrane before it can be secreted?13128.What causes apical chloride channels to open? 132123Na+/H+ antiporters, driven by ʻelectroneutral exchangeʼ (swapping one charged substance for another ofthe same charge)124 Because of the Na+ gradient, Na+ moved into the epithelium and H+ is driven out into the lumen,meaning the lumen is more acidic and the epithelium more alkaline125 Cl-/HCO3- anti-porters absorb Cl- from the lumen and pump HCO3- into the lumen which acts as a bufferfor the excess H+126The process which is created by the export of H+ and HCO3- into the lumen, creating carbonic acid,which dissociates into water in the presence of carbonic anhydrase, leading to more water in the lumenalﬂuid. The presence of more water in the lumen heightens the osmotic gradient between the lumen andepithelium meaning more water gets reabsorbed from the lumen into the epithelium.127 When chyme enters the colon it is 20:1 liquid:solid, when it leaves as faeces it it 2:1 (roughly 50g-100g ofsolid per day)128Crypts create an osmotic pressure across their walls which draws water into the crypt space andreabsorbs it. So there is an osmotic gradient coupled with large suction force.129Aldosterone (higher in a low salt diet, lower in high salt diet) stimulates autocoid (protein messenger)secretion from myoﬁbroblasts (smooth muscle), which causes epithelial cell proliferation and adhesion.Aldosterone also increases the rate of sodium absorbtion, as in the kidney.130 Cl- channels are activated by cAMP, the rest are activated by Ca2+131Transported into the cells by a co-transporter which takes Na+, Cl- and K+ into the cell, the positivecharge of the Na+ and K+ (which are both going down gradients) carries negative Cl- against its gradient.132 stimulation by cAMP or Ca2+
29.How is Na+ secreted into the lumen? 13330.What happens to the CFTR channel in Cystic Fibrosis?13431.Which channels secrete H+ into the interstitial ﬂuid from epithelial cells in the pancreas and liver? 13532.Which channel secretes HCO3- into the lumen from epithelial cells in the pancreas and liver? 13633.How are proteins secreted by the pancreas or salivary glands? 13734.What stimulates enzyme secretion from the pancreas?13835.Why (chemically) is trypsinogen an inactive enzyme when it is released? 13936.Why is squatting a more effective posture for defecation than sitting? 14037.What are the three main categories of laxative?14138.Which type of laxative would you not use to clear out the colon for an endoscopy?142133 Through tight junctions between epithelial cells134 It is blocked, so whilst CF can lead to respiratory failure it does protect against cholera symptoms135 Na+/H+ exchangers, and H+/K+ATPase exhangers136HCO3-/Cl- exchanger, so a failure in CFTR and so reduced lumenal Cl- can cause a failure in alkalinesecretion too137Vesicles containing protein are formed in the Golgi body (protein packaging organelle) then exocytosisthrough plasma membrane.138 Cholecystokinin (CCK) and vagal nerve activity139 Trypsinogen is a pancreatic enzyme but is in its inactive form because it has been so densely packed into vesicles to cross the membrane. For it to be activated it must be hydrated in the lumen, having left thevesicles and expanded, then converted by an enzyme into its active form trypsin.140When sitting, the angle of the anal canal is sharp against the rectum. When squatting, the angle is moreobtuse (straighter) which allows pressure from the abdominal muscles and diaphragm to be directly (linearly)transmitted through the anus.141 1/ bulk forming (bran, methyl cellulose) 2/ Stimulant (castor oil), 3/ Osmotic laxatives (lactulose)142Bulk laxatives, because they ﬁll up the colon with indigestible ʻbulkʼ which aids ﬂow but will not clear thecolon of material
39.What is the mechanism of lactulose in relieving constipation?14340.How does mineral oil/parafﬁn work as a laxative?14441.What are loperamide and diphenoxylate? 145GI System at a Glance1. What is the most common way for a diverticulum to form in the colon wall? 1462. Which 3 structural features of the duodenum contribute to increased surfacearea?1473. Where are the preferred uptake sites for: Iron, folic acid, bile salts & vitamin B12,water and electrolytes1484. Where does most of the liquid in the small intestine come from? 1495. What substance in the digestive system inhibits amylase (starch to sugar enzyme)and activates pepsinogen (pepsin enzyme, protein digestion)?1506. What is an enterocyte?1517. What is intrinsic factor? 1528. Which vitamin can be synthesised in the intestine by commensal bacteria? 153143Lactulose is an osmotic laxative, osmotic laxatives work by stimulating the myenteric plexus to increaseperistalsis, reduce absorbtion of salt and water to increase faeces volume, may inhibit the Na+ pump andincrease prostaglandins and cAMP, adding to this effect.144 Parafﬁn oil droplets block the crypt lumens and prevent them from sucking ﬂuid out of the faeces145 Opioid anti-motility agents, used to treat diarrhea146 Penetrating artery though the muscularis mucosa created space for diverticulum to form outside ofcircular layer of smooth muscle, pushes artery out of the way.147 Villi, microvilli and plicae circulares148 Iron (duodenum), folic acid (jejunum), bile salts & vitamin B12 (ileum), water and electrolytes (colon)149Most of the liquid in the intestinal lumen does NOT come from food but is secreted by digestive exocrineglands. It is subsequently reabsorbed by the colon to maintain ﬂuid balance.150 Stomach acid, this initiates protein digestion. Only sugar/carb digestion begins in the mouth.151 An simple columnar epithelial cell found in the small intestine and colon152A glycoprotein produced by the stomach which binds vitamin B12 and protects it from breakdown in theproximal intestine. In the terminal ileum, vitamin B is released and absorbed153 Vitamin K
9. What and where is CFTR in the intestinal lumen? 15410.How does HCO3- come to be in the intestinal lumen?15511.What might stimulate secretion of water into the lumen?15612.What receptors does serotonin act on to increase or decrease secretion? 15713.What do opioids do? 15814.What does cholera toxin A do? 15915.How does heat-stable enterotoxin E-coli cause diarrhoea?160154CFTR stands for cystic ﬁbrosis transmembrane regulator, this is a Cl- channel present only on the apicalside of the membrane, it is regulated by cAMP. (other chloride channels are regulated by cGMP)155It is secreted by the pancreas and goblet cells but also through an apical HCO3-/Cl- exchanger andproduced from water and Co2 by the presence of carbonic anhydrase in the lumen.156Enteric hormones, cytokines, bacterial and viral toxins, prostaglandins, vasoactive peptide (VIP).(Misoprosol, a prostaglandin, is used therapeutically to counteract ulcerogenic effects of some other drugs(e.g. NSAIDs).157 5HT3 (stimulate vomiting, depolarize plasma membrane) or 5HT4 (increase cellular levels of cAMP)158 Inhibit intestinal secretion and may promote reabsorbtion by reducing intestinal mobility159Irreversibly activates adenyl cyclase, generating excess cAMP which stimulates mass secretion of Cl-through CFTRs, followed by K+ and Na+ because of the electrochemical gradient created, followed by H20because of the osmotic gradient created. Result is watery diarrhoea.160Stimulates cell surface receptors that have guanyl cyclase activity and produces excess cGMP whichstimulates cl- secretion, the rest of the mechanism is the same as cholera (14)