LECTURE NR. 1
Gastric and duodenal ulcer
Elements of anatomy and physiology 3011 The stomach is the most dilated part of the digestive tube, having a capacity of 1000– 1500 ml in the adult. It It is situated between the end of the oesophagus and the duodenum – the beginning of the small intestine. It lies in the epigastric, umbilical, and left hypochondrial regions of the abdomen, and occupupies a recess boundnded by the upper abdominal viscera, the anterior abdominal wall and the diaphragm..
Macroscopic anatomy
The stomach has : two openings, two curvatures, two surfaces and two omenta.
1. Openings
Gastro-oesophageal unction The oesophagus communicates with the stomach via the cardiac ori.ce, which is situated on the left of the midline at the level of T10. The intraabdominal oesophagus !antrum cardiacum" is short and conical. #fter passingthrough the diaphragm it curves sharply to theleft, and becomes continuous with the cardiac orifice of the stomach. The right margin of the oesophagus is continuous with the lesser curvature of the stomach, while the left margin $oins the greater curvature at an acute angle !incisura cardiaca". Gastroduodenal unction 9 The pylorus forms the gastric outlet and communicates with the duodenum. It lies to the right of the midline at the level of the upper border of %1 and may be identified on the surface of the stomach by a circular groove !duodenopyloric constriction" covering the front of the organ.
!.!. Cur"atures
Lesser cur"ature #Cur"atura $entriculi %inor& This e&tends from the cardiac to the pyloric orifices, thus forming the right or posterior border of the stomach. It is a continuation of the right border of the oesophagus and lies inin front of the right crus of the diaphragm. It crosses the body of %1 and ends at the pylorus. # welldemarcated notch, the incisura angularis, is seen distally although its position varies with the state of distension of the stomach. #ttached to the lesser curvature are the two layers of the hepatogastric ligament !lesser omentum". 'etween these two layers are the left gastric artery and the right gastric branch of the hepatic artery.
11 Greater cur"ature #Cur"atura $entriculi %aor& This is directed mainly forward, and is four to five times longer than the lesser curvature. It ststarts frfrom ththe inincicisusura cardidiaca anand archehes babac(c(wardrd, upupwardrd, anand to ththe leleftft) ththee highestpoint of the conve&ity is on a level with the si&th left costal cartilage. It then descends downwards and forwards, with a slight conve&ity to the left as low as the cartilage of the ninth rib,before turning to the right, to end at the pylorus. *irectly opposite the incisura angularis of the lesser curvature, the greater curvature presents a dilatation, which is the left e&tremity of ththe pypyloloric papartrt) ththis didilalatattatioion is lilimiteted on ththe ririghght by a slislighght grgrooooveve, ththe susulclcusus intermedius, which is about +.5 cm, from the duodenopyloric constrictiction. The portionn between the sulcus intermedius and the duodenopyloric is termed the pyloric antrum.with the duodenum. It lies to the right of the midline at the level of the upper border of %1 and may be identified on the surface of the stomach by a circular groove !duodenopyloric constriction". The left part of the curvature gives attachment to the gastrosplenic !lineal" ligament, while to its anterior portion are attached the two layers of the greater omentum, separated from each other by the right and left gastroepiploic vessels.
'.'. (urfaces
)nterosuperior surface This surface is covered by peritoneum and lies in contact with the diaphragm, which separates it from the base of the left lung, the pericardium, the seventh–ninth ribs, and the intercostal spaces of the left side. The right half lies in relation to the left and uadrate lobes of the liver together with the anterior abdominal wall. The transverse colon may lie on the front part of thissurface when the stomach is collapsed. *osteroinferior surface This surface is covered by peritoneum, e&cept over a small area close to the cardiac ori.ce) this area is limited by the lines of attachment of the gastrophrenic ligament, and lies in apposition with the diaphragm, and freuently with the upper portion of the left suprarenal gland. -ther relations are to the upper part of the front of the left (idney, the anterior surface of the pancreas, the left colic fle&ure, and the upper layer of the transverse mesocolon. The transverse mesocolon separates the stomach from the duodeno$e$unal fle&ure and smallll intestine. Thus the abdominal cavity is divided into supra and infracolic compartments. The anterior boundary of the lesser sac !omental bursa" is formed by this surface. This potential space can be accessed via an opening on the free border of the lesser omentum, which contains the common hepatic artery, the common bile duct and the portal vein !the foramen of inslow".
*arts of the stomach
The stomach is divided into a pyloric part and body by a plane passing through the incisura angularis on the lesser curvature and the left limit of the opposed dilatation on the greater curvature. The body is further subdivided into the fundus and cardia by a plane passing hori/ontally through the cardiac orifice. *istally a plane passing from the sulcus intermedius at right angles to the long a&is of this portion further subdivides the pyloric portion. To the right of this plane lies the pyloric antrum. #t operations, a slight groove may be seen in the serosal surface at the gastroduodenal $unction. # small, super.cial subserosal vein, lying within this groove and vertically across the front of the gut may be evident. This is the prepyloric vein of ayo" and drains into the right gastric vein. #t operation, palpation of this area reveals the pyloric ring between the thic( walls of the pyloric region and the thin walls of the duodenum..
++ +. Omenta
Lesser omentum This e&tends from the inferior and posterior surfaces of the liver to the stomach and pro&imal .0 cm of the duodenum. The free border of the lesser omentum between the porta hepatis and the duodenum contains the hepatic artery, the portal vein, the common bile duct, lymph glands, lymph vessels and nerves. 'ehind this free edge is the opening into the lesser sac or epiploic foramen !of inslow". The remainder of the lesser omentum, e&tending from the left end of the porta hepatis to the lesser curvature, contains the right and left gastric arteries and the accompanying veins, as well as lymph glands, lymph vessels and branches of the anterior and posterior vagus nerves. Greater omentum This is formed along the greater curvature of the stomach by the union of the peritoneal coats of the anterior and posterior gastric surfaces. -n its left it shortens into the gastrosplenic omentum, containing the short gastric branches of the splenic artery between its two layers. -n the right it is continued for .0 cm along the lower border of the .rst part of the duodenum. 2rom its origin the greater omentum hangs down in front of the intestines as a loose apron, e&tending as far as the transverse colon, where its two layers separate to enclose that part of the colon. The upper part of the greater omentum contains the greater part of the right and left gastroepiploic arteries and their accompanying veins, lymph vessels, lymph glands, nerve filaments, fat and areolar tissue.
,lood (upply
1. )rterial (upply The coeliac artery, the artery of the foregut, supplies the stomach by its three branches. It arises from the front of the aorta between the crura of the diaphragm and is a short wide trun(, surrounded by the coeliac lymph nodes and flan(ed by the coeliac ganglia of the sympathetic system. The main branches are the left gastric artery, the hepatic artery and the splenic artery.
The left gastric artery This runs to the left, gives off an ascending oesophageal branch, and supplies the upper part of the stomach. 3owever, it may arise directly from the aorta !5–4.6", and may provide one or both of the inferior phrenic arteries or a common trun( for the two. The left gastric artery turns downwards between the layers of the lesser omentum and runs to the right along the lesser curvature. 3aving divided into two parallel branches, these divide further supplying the anterior and posterior gastric walls. These vessels anastomose freely with arteries from the greater curvature. #round the incisura angularis, the two main branches then anastomose with the two branches of the right gastric artery. The hepatic artery may arise directly from the left gastric. The hepatic artery This is the second branch of the coeliac trun( and passes downwards as far as the first part of the duodenum. #t the opening into right border of the lesser sac it turns forwards !epiploic foramen" and curves upwards between the two layers of the lesser omentum towards the porta hepatis, to supply the liver. The gastroduodenal and right gastric arteries are given off as it turns into the lesser omentum. The right gastric artery passes to the left between the two layers of the lesser omentum, and runs along the lesser curvature of the stomach before dividing into two branches that anastomose with the branches of the left gastric artery. It also gives off branches to the anterior and posterior gastric walls, anastomosing with branches
from the right gastroepiploic artery. The gastroduodenal artery descends behind the first part of the duodenum, which it supplies by multiple small branches. The terminal divisions are the superior pancreaticoduodenal artery, supplying the second part of the duodenum and head of the pancreas, and the right gastroepiploic artery. The right gastroepiploic artery passes along the greater curvature of the stomach between the layers of the greater omentum and gives off branches to the anterior and posterior gastric walls before anastomosing with the left gastroepiploic artery. The splenic artery This passes to the left along the upper border of the pancreas, behind the peritoneum and the stomach, to supply the spleen. *ivision into the terminal branches close to the spleen is called a magistral splenic !71–+ cm from the hilum", but earlier division is called a distributing splenic. *uring its course it gives off branches to the pancreas) $ust before entering the splenic hilum it gives off the short gastric arteries supplying the gastric forni&, and the left gastroepiploic artery. The latter passes downwards and to the right along the greater curvature of the stomach, between the two layers of the greater omentum, to anastomose with the right gastroepiploic artery at the midportion of the greater curvature. It gives off branches to the anterior and posterior gastric walls, which anastomose with branches of the gastric arteries along the lesser curvature.
!. The $enous rainage The gastric veins are similar in position to that of the arteries along the lesser and greater curvatures. These veins drain either directly or indirectly into the portal system .
Left gastric "ein This runs to the left along the lesser curvature, receiving the oesophageal veins below the oesophageal hiatus in the diaphragm. It usually drains directly into the portal vein at the superior border of the pancreas. Right gastric "ein This runs along the lesser curvature to the right towards the pylorus. 8osterior to the first part of the duodenum it $oins the portal vein. It also receives the prepyloric vein which receives the veins from the first + cm of the duodenum. Left gastroepiploic "ein This passes to the left along the greater curvature and with the short gastric veins drains into the splenic vein or its tributaries. The splenic vein is $oined with tributaries from the pancreas as well as the inferior mesenteric vein) these ultimately form the portal vein with the superior mesenteric vein. Right gastroepiploic "ein This runs to the right as far as the head of the pan creas. 9sually it $oins the superior mesenteric vein and thus drains into the portal vein. 3owever, considerable variations may occur and the right gastroepiploic may enter the portal vein directly, or it may $oin the splenic vein. There is no gastroduodenal vein.
'. Lymphatic rainage The lymphatics of the stomach can be divided into three systems: ntramural This consists of three networ(s) submucosal, intermuscular and subserosal. ntermediary This consists of numerous small channels between the subserosal networ( and the e&tramural collecting systems.
E/tramural This consists of four ma$or /ones of lymphatic drainage, corresponding to the arterial supply of the stomach. 9ltimately all /ones drain into the coeliac nodes around the coeliac arterial trun( on the anterior aspect of the aorta.
The lymphatic drainage of the stomach can be divided into four /ones :
0one 1 This comprises the upper twothirds of the lesser curvature and a large part of the body of the stomach. These drain into the left gastric nodes lying along the left gastric artery. These nodes are $oined by lymphatics coming down from the lower part of the oesophagus, and their efferents proceed to the coeliac nodes. 0one ! This is from the distal part of the lesser curvature, including the lesser curvature of the pyloric region, to the suprapyloric nodes along the right gastric artery. ;fferent channels from the suprapyloric nodes drain to the hepatic and ultimately to the coeliac and aortic nodes. 0one ' This /one includes the pyloric part of the stomach as well as the right half of the greater curvature. The lymphatics from these areas drain into the right gastroepiploic nodes in the gastrocolic ligament, lying along the right gastroepiploic vessels, and into the pyloric nodes on the anterior surface of the head of the pancreas. The direction of lymph flow is from above downwards, towards the pylorus and the nodes between the head of the pancreas and second part of the duodenum. 2rom these groups, collectively called the subpyloric glands !which also drain the .rst part of the duodenum", efferent vessels pass along the gastroduodenal artery to the hepatic nodes along the hepatic artery, and thence to the coeliac nodes. 0one + This comprises the left half of the greater curvature and the gastric forni&. The lymph vessels from here pass to the left gastroepiploic nodes, lying along the left gastroepiploic artery. These drain to the pancreaticolienal nodes along the splenic artery, before terminating in the coeliac nodes.
+. Ner"es The autonomic nervous system consists of two components, cholinergic – mostly parasympathetic, and adrenergic – mostly sympathetic nerves. 3owever, a third component of the autonomic system, which is neither cholinergic nor adrenergic, has been recognised within the gastrointestinal tract – the peptidergic system.
*arasympathetic Ner"e (upply The anterior and posterior vagal trun(s and their branches form the parasympathetic nerve supply to the stomach. #fferent fibres are also present in the vagi. 1. )nterior "agus This is derived mainly from the left vagus nerve but also includes .bres from the right vagus and also some sympathetic fibres from the splanchnic nerves. It enters the abdominal cavity through the oesophageal hiatus in the diaphragm. It is usually single but may be divided into multiple trun(s. 3aving given off several fine branches to the lower end of the oesophagus and cardiac part of the stomach, the anterior trun( brea(s up into its main branches. %atar$et divided the nerves of the anterior vagus into two distinct functional divisions. The first division, consisting of the direct branches, supplies the forni& and body, i.e. the
5 (ympathetic Ner"e (upply This is derived almost entirely derived from the coeliac ple&us. The gastric branches of the coeliac ple&us accompany the vessels supplying the stomach – the left gastric, hepatic and phrenic arteries. *eptidergic (ystem 8eptidergic cells are derived embryologically from neuroectoderm and are referred to as #89* cells because they synthesi/e monoamines through a process of amine precursor upta(e and decarbo&ylation !#89*". They are also referred to as neuroendocrine cells. # large number of biologically active peptides have been detected in these #89* cells within the gut. These peptides include gastrin, vasoactive intestinal peptide !>I8", somatostatin, en(ephalin, neurotensin and substance 8. Microscopic anatomy The wall of the stomach and the pro&imal .0 cm of the duodenum are composed of four coats. 2rom without inwards these are the serous, muscular, submucous and mucous coats. The mucous coat is separated from theluminal contents by a layer of gastric mucus. (erous Coat #)d"entitia) This is formed by the peritoneum, which is a thin layer of loose connective tissue covered with mesothelium. It is attached to the muscular coat, e&cept at the greater and lesser curvatures, where it is continuous with the greater and lesser omentum respectively . %uscularis e/terna The muscularis e&terna is composed of smooth, unstriped or involuntary fibres and is made up of three layers: an e&ternal longitudinal, middle circular, and an inner obliue layer . (umucous coat This is a layer of loose areolar tissue with some elastic .bres that lies between the muscularis mucosae and the muscularis e&terna. It is rich in mast cells, macrophages, lymphocytes, eosinophilic leucocytes and plasma cells.ithin this layer the vessels and nerves divide before entering the mucous membrane. It contains arteries, veins, lymphatics and eissner?s nerve ple&uses. %ucosa This consists of three components: the muscularis mucosae, the lamina propria, and the epithelial lining. 4 %ucosal 2ones The mucous membrane of the entire stomach is lined by glands that open into the gastric pits. The gastric mucosa can be divided into three /ones, based on the predominant cell types within the glands : Cardiac 2one These glands secrete mucus *yloric 2one These glands secrete mucus. They also produce endocrine, paracrine or neurocrine regulatory peptides by virtue of the #89* cells contained in their glands. O/yntic 2one These glands produce nearly all the en/ymes and hydrochloric acid secreted in the stomach as well as producing mucus. 3 The secretory epithelial cells and their roles 2our ma$or types of secretory epithelial cells cover the surface of the stomach and e&tend down into gastric pits and glands: • %ucous cells - secrete al(aline mucus that prote&ts the epithelium against shear stress and acid • *arietal cells - secrete hydrochloric acid • Chief cells - secrete pepsin, a proteolytic en/yme • G cells 3 secrete the hormone gastrin *hysiology Gastric secretions • %ucus secretion The cells of the gastric glands secrete about +500 ml of gastric $uice daily. This contains a variety of substances and gastric en/ymes, whose role is to (ill ingested bacteria, aid protein digestion, stimulate the flow of bilary and pancreatic $uices and provide the necessary p3 for pepsin to begin protein degradation. The most abundant epithelial cells are mucussecreting columnar cells, which cover the entire luminal surface and e&tend down into the glands as by the presence of gastric acid into the active protease pepsin. This is an endopeptidase that is largely responsible for the initiation of protein digestion into smaller peptides and polypeptides. It acts at p3 1.5–+.5 and above p3 5. is inactivated. It is released mainly by vagal stimulation but also by histamine gastrin secretion, alcohol, cortisol, caffeine and aceta/olamide. 8epsinogen release may also occur during periods of hypoglycaemia and prolonged increased intracranial pressure. • 4ormone secretion The principal hormone secreted from the gastric epithelium is gastrin, a peptide that is important in control of acid secretion and gastric motility. Intrinsic factor, a glycoprotein secreted by parietal cells, is necessary for intestinal absorption of vitamin '1+. It acts by combining with the vitamin '1+ and is necessary for its attachment to receptors in the terminal ileum. %ac( of intrinsic factor due to reduction in parietal cell mass following gastric surgery, or the production of antibodies to the cells, called pernicious anaemia, leads to megaloblastic anaemia. Becretion of intrinsic factor occurs following vagal, gastrin or histamine stimulation of the parietal cells. The 5ormation and (ecretion of Gastric )cid Btimulation of the parietal cells results in acid secretion. These cells contain multiple tubulovesicular structures within their cytoplasm that on stimulation move to the mucosal membrane and fuse with it, producing a microvillous appearance that increases the surface area. This results in the presence of the 3@D@ #T8ase that transports the 3@ onto the luminal surface. This secretion is isotonic with other .uids and its p3 is E1. The 3@ is obtained from the ionisation of water, which is then actively transported into the gastric lumen in e&change for D@ that has been recycled from the membrane. Fhloride ions are also actively transported into the gastric lumen. The resulting -3– ion is neutralised by the carbonic acid buffer system to form a bicarbonate ion that diffuses into the interstitium to be replaced by a further Fl– ion. There is a 3F-––Fl– e&change mechanism within the interstitium, but Fl– also enters the cell with Aa@. The carbonic acid is replenished by the hydration of F-+, which is produced by cellular metabolism from the abundance of carbonic anhydrase within the mucosa. #fter a meal this results in the development of a negative respiratory uotient) thus arterial F-+ is higher than venous and the gastric venous return is al(aline with a high 3F-– content. Gastric hormones • Gastrin The highest density of gastrinproducing C cells occurs in the distal .0 cm of the stomach, where the concentration of gastrin is 500 times higher than in the body of the stomach. The first part of the duodenum also contains a signi.cant level of C cells. These cells originate from neuroectoderm together with other cells of the #89* series. There are two main types of gastrin, gastrin I and gastrin II, produced predominantly by the C cells of the pyloric mucosal /one. -ther sources are the duodenal C cells, * cells in the islands of %angerhans in the pancreas, and isolated C cells in the pro&imalacidproducing region of the forni& and body of the stomach. Castrin 1 !1 amino acids" is the predominant form in the pyloric antrum, and is further subdivided into a nonsulphated gastrin I and a sulphated gastrin II form. There is also a H The physiological and pharmacological effects of gastrin 6 • 8arietal cells to stimulate acid secretion • 8epsin and intrinsic factor secretion • Increased mitotic activity in the stomach and small bowel mucosa • Fontraction of the lower oesophageal sphincter • The release of insulin, glucagon and calcitonin • 8ancreatic stimulation and bile flow • Bmall bowel secretion • Castric and small bowel motility to increase • The gastrocolic refle& • (omatostatin It has been identified in the central nervous system, the gastrointestinal tract and other organs, with the highest concentration being found in the pancreas. In the stomach it is found in the pyloric and o&yntic mucosal /ones but not in the cardiac /one. ithin the pancreas it is isolated from the islet * cells. It suppresses the release of thyroidstimulating hormone by the pituitary, the release of glucagon, insulin and e&ocrine secretions by the pancreas, the secretion of cholecysto(inin, motilin and secretin by the intestine, and the secretion of gastrin, gastric acid and pepsin by the stomach. Bomatostatin suppresses gastric acid secretion by direct action on the parietal cells of the cardiac and o&yntic mucosal /ones. Thus by lowering the p3, it also inhibits the secretion of gastrin through a feedbac( loop of low p3 suppressing. • $asoacti"e ntestinal *eptide #$*& >asoactive intestinal peptide !>I8" is a polypeptide with strong vascular effects isolated from small intestine. Its actions include vasodilatation, thus lowering blood pressure, increased cardiac output, glycogenolysis and rela&ation of smooth muscle. In the stomach there is significant inhibition of gastric secretion associated with >I8 release. • (ustance * In the stomach substance 8 is found in the o&yntic /one in a few, thin .bres only and in fibres interconnecting in the pyloric antrum. In the duodenum substance 8 !and >I8" is present in nerve networ(s in the villi as well as in the muscularis mucosae and around blood vessels. It has been found to cause contraction of the muscularis mucosae. Control of Gastric )cid (ecretion #cid secretion may be divided into two phases interprandial, when acid secretion is 1–5 mmolh, and stimulated where acid secretion is ma&imally +0–5 mmolh. This is further subdivided into cephalic, gastric and intestinal phase. Aormal sub$ects ma&imally secrete 0.5 mmolh(g body weight". 1. nterprandial Jesting secretion occurs in the absence of all intestinal stimulation. 3owever, in order to abolish all gastic acid secretions, a bilateral vagotomy !truncal" and e&cision of the pyloric antrum would be necessary. !. (timulated secretion K • The cephalic phase The cephalic phase is initiated by seeing, smelling and anticipating food. These influences act on the limbic system and hypothalamus and these nuclei stimulate the dorsal motor nucleus of the vagus. This stimulus is transmitted thought the vagus nerve to the enteric nervous system, resulting in release of acetylcholine in the vicinity of C cells and parietal cells. 'inding of acetylcholine to its receptor on C cells induces secretion of the hormone gastrin, which, in concert with acetylcholine and histamine, stimulates parietal cells to secrete small amounts of acid. #dditionally, a low level of gastric motility is induced. 1 The release of acetylcholine and bombesin !gastrinreleasing peptide" initiates gastrin release from the C cells. The gastrin passes via the portal circulation to stimulate the parietal cells. It potentiates the effect of vagal stimulation, thus resulting in increased acid secretion. The parietal cells also have 3+ receptors !histamine" stimulated by the release of histamine from mast cells close to the parietal cells. The histamine sensitises the parietal cell to the action of gastrin and acetylcholine. The 3+ receptor bloc(ers !cimetidine and ranitidine" act on these receptors, thus reducing acid secretion. • The gastric phase 7 hen food enters the stomach several additional factors come into play, foremost among them being distension and mucosal irritation. *istension e&cites stretch receptors and irritation activates chemoreceptors in the mucosa. These events are sensed by enteric neurones, which secrete additional acetylcholine, further stimulating both C cells and parietal cells. Castrin from the C cells feeds bac( to the parietal cells, stimulating it even further, mediated by vagovagal refle&es through the dorsal motor nucleus. #dditionally, activation of the enteric nervous system and release of gastrin cause vigorous smooth muscle contractions. The net result is that secretory and motor functions of the stomach are fully turned on – acid and pepsinogen are secreted, pepsinogen is converted into pepsin and vigorous grinding and mi&ing contractions ta(e place. 3owever, acid secretion may be inhibited during the gastric phase by local mechanisms. If the antral p3 falls to 1–1.5, inhibition of gastrin release occurs. This is mediated by two mechanisms – the effect of luminal acid on the microvilli of the C cell and the stimulation of somatostatin from * cells in the antrum, which acts inhibits directly on the C cells and parietal cells by a local paracrine effect. • The intestinal phase This phase of gastric function is dominated by the small intestine sending inhibitory signals to the stomach to slow secretion and motility. Two types of signals are used: nervous and endocrine. *istension of the small intestine, as well as chemical and osmotic irritation of the mucosa, is transduced into gastricinhibitory impulses in the enteric nervous system – this nervous pathway is called the enterogastric re.e&. 2at and carbohydrate in the chyme cause the release of CI8 !gastric inhibiting peptide", which inhibits gastrin secretion. Becondly, enteric hormones such as cholecysto(inin and secretin are released from cells in the small intestine and contribute to suppression of gastric activity. Castrin also causes the release of calcitonin from the F cells of the thyroid gland, which inhibits further release of gastrin via a feedbac( loop. Ethiopathogeny of peptic ulcer The pathophysiology of peptic ulcers, whether gastric or duodenal, is multifactorial. 10 9lcers develop depending on the balance of in$urious factors and host defense mechanisms. ;nvironmental stressors are numerous. #cid secretion is involved in the final common pathway of ulcer formation. In regards to duodenal ulceration, mucosal e&posure of acid is a necessary component of their pathogenesis. In general, patients with duodenal ulcers have an increased capacity for acid secretion. a&imal acid output in normal patients is usually around +0 m;hour but patients with duodenal ulcers may e&ceed 0 m;hr. #dditionally, patients with duodenal ulcer have increased basal acid outputs with normal basal gastrin levels. The role that acid secretion plays with the formation of gastric ulcers is less clear. 3ypersecretion of acid is not associated with all subtypes of gastric ulcers. Castric acid does, however, play a role in the chain of events that leads to ulceration. 5actors 7hich are associated 7ith the de"elopment of peptic ulcers6 • 4elicoacter pylori is a spiral bacterium which specifically coloni/es gastric mucosa. It is able to survive in a near neutral p3 through the production of urease. 3. pylori infection has been correlated with the formation of peptic ulcers. Beveral lines of evidence lin( 3. pylori to peptic ulceration: ;radication of 3. pylori, without the suppression of acid, leads to ulcer healing rates that are similar to those of acid suppression therapy alone) Jelapse of duodenal ulceration after antimicrobial treatment is preceded by reinfection of gastric mucosa. The prevalence of 3. pylori in patients with duodenal ulceration is near 1006. 8atients with gastric ulcers have a prevalence of 3. pylori in the range of 40H06.Fomparatively, 3elicobacter coloni/es appro&imately +06 of those without peptic ulcer disease. etection of 4elicoacter pylori Three tests areavailable to assess the presence of 3. pylori: endoscopic biopsy, the breath test, and ;%IB# antibody testing. • ;ndoscopic 'iopsy ucosal biopsy specimens can be e&amined histologically for the presence of bacterium andgastritis. The best use of the biopsy specimen is to perform a urease test, in which the specimen is placed in a solution of urea containing a p3 indicator. If urease is present, ammonia is generated from the urea, causing the solution to turn more al(ali. The urease test is highly specific and sensitive. # biopsy specimen can also be cultured to grow the bacterium. hile highly specific, culture has very low sensitivity. • 'reath Test 9rea labeled with either 1F or 1F is administered with a meal. If 3. pylori infection is present, its urease will cleave the labeled urea, releasing labeled bicarbonate that is then converted into labeled e&pired F-+. The great value of this test is that it can be used serially to assess the efficacy of 3. pylori eradication therapy. • ;%IB# #ntibody Test 3. pylori infection leads to the development of antibodies that can be detected in the blood. The ;%IB# antibody test is not as useful as the breath test to monitor response to 3. pylori eradication because antibody titers in the blood decrease slowly. • Cigarette smo8ing has been associated with peptic ulcer disease in so far as it impairs healing, decreases the effectiveness of therapy, increases recurrence rates, and increases the li(elihood of complications. • Ethanol also has in$urious effects on gastroduodenal mucosa. 11 • N() use has also shown ulcerogenic effects. 9lcer formation is promoted through the systemic effects of cycloo&ygenase inhibition and a direct to&ic effect on mucosal cells. The use of AB#I*B is more strongly associated with gastric ulcers. • )ltered host defense mechanisms play a role in the pathogenesis of peptic ulcer formation. Burface epithelial cells produce bicarbonate and mucus. The generation of these substances allows for the creation of a p3 gradient at the luminal interface such that there is a near neutral environment at the mucosal surface. #dditionally, prostaglandins 8C;+ and 8CI+ have a protective effect on the mucosa through inhibition of acid secretion by the parietal cell. 8atients with peptic ulcer disease have been shown to have decreased bicarbonate secretion and decreased production of mucosal prostaglandins. • %otility disorders can also promote ulcerogenesis presumably through a mechanism of impaired clearance of no&ious substances. Clinical and paraclinical diagnosis Clinical presentation The characteristic ulcer symptom is a *uodenal ulcers are found in the first portion of the duodenum in about K56 of cases. The presence of ulcers in more distal areas of the duodenum is atypical and should arouse clinical suspicion of an underlying gastrinoma. Castric ulcers most commonly occur on the lesser curvature. They are located $ust above the incisura angularis on the lesser curvature in about 406 of cases. #n additional 15 +56 are located distal to the incisura on the lesser curvature and another 106 are located high on the lesser curvature. -nly about 56 are found on the greater curvature of the stomach. The diagnosis of peptic ulcer 1+ The diagnosis of peptic ulcer disease is best verified by upper endoscopy. ;sophagogastroduodenoscopy is greater than K56 sensitive and near 1006 specific in identifying peptic ulcers of both the duodenum and stomach. There are several endoscopic features, additionally, of gastric ulcers that can help to distinguish between peptic ulceration and malignant ulceration. • 'enign ulcers typically appear as round lesions with slightly raised, smooth borders. The surrounding mucosal folds are symmetric and taper evenly toward the edge of the ulcer. In addition, benign ulcers often have a smooth base covered with a fibrous layer. #lthough these characteristics may suggest a benign ulcer the only way to truly distinguish is with multiple biopsies at the ulcer edge. • alignancy must be ruled out with biopsy upon the discovery of a gastric ulcer. ,arium meal The use of the barium meal to diagnose peptic ulcer has declined with advances in fiberoptic endoscopy. # gastric ulcer usually shows as a niche along the lesser curvature, with the barium e&tending outward beyond the stomach. In contrast, the floor of an ulcer crater that is malignant does not e&tend outside the lesser curvature !Farlan?s sign". Jadiating mucosal folds from the ulcer may be apparent when seen en face. In duodenal ulcers, a bariumfilled crater and deformity of the duodenal cap are typical signs. The presence of stenosis or gastric outlet obstruction can also be assessed. (utypes of gastric ulcers6 • Type ulcers occur along the lesser curvature, in the body of the stomach, $ust above the incisura angularis. These ulcers account for about 0506 of gastric ulcers and as such are the most common type of gastric ulcer. Castric acid output is within the normal range. Burgical therapy consists of a distal gastrectomy with gastro$e$unostomy. >agotomy is not necessary since these ulcers are not associated with acid hypersecretion. In fact, the addition of a vagotomy does not decrease the ulcer recurrence rate, which is about 6. • Type ulcers also occur along the lesser curvature, in the body of the stomach, and again are found $ust above the incisura. These ulcers, however, are associated with the simultaneous presence of a duodenal ulcer. They account for about +56 of gastric ulcers. Type II ulcers are associated with gastric acid hypersecretion. Burgical therapy generally consists of a truncal vagotomy with either antrectomy or pyloroplasty. • Type ulcers are prepyloric ulcers. They account for about +56 of gastric ulcers. These ulcers are also associated with gastric acid hypersecretion. Burgical therapy consists of truncal vagotomy with either antrectomy or pyloroplasty. 8arietal cell vagotomy is associated with higher rates of ulcer recurrence when used for the treatment of type III ulcers. • Type $ ulcers occur high on the lesser curvature, near the C; $unction. They account for less than 106 of gastric ulcers. Type I> ulcers are associated with normal levels of gastric acid secretion. Burgical therapy is more complicated than with the other types of gastric ulcers and depends on the pro&imity of the ulcer to the C; $unction. ;sophagogastrectomy may be necessary for ulcers too close to the distal esophagus to allow for preservation of the C; $unction. *ositi"e and differential diagnosis 1 The diagnosis of gastric or duodenal ulcer is probable when the patient is a young or adult man, who smo(es and has a stressing $ob and who has a sudden digestive haemorrhage, in a state of perfect health or with associated dispeptic problems. *ifferential diagnosis : • ;&tragastric lesion : 1. ;pigastric hernia +. *iafragmatic hernia . Fholecystitis . 8ancreatitis 5. #ppendicitis 4. # disease of transverse colon. • Castritis • 3iatus hernia • *uodenal diverticulum • *uodenal stasis • Castric cancer %edical treatment • 4! receptor antagonists competitively bind histamine receptors on the surface of the gastric parietal cell. Beveral different 3+ bloc(ers are clinically available. 3owever, there is no significant difference among these different 3+ bloc(ers in regards to their efficacy in healing ulcers. #bout 06 of patients are ulcerfree after wee(s of treatment. 9p to K06 of patients will be ulcerfree at the end of H wee(s of treatment. • *roton pump inhiitors bind to membranebound 3@D@#T8ase on parietal cells and in doing so bloc( the intraluminal secretion of hydrogen ion. *irect comparisons between omepra/ole and 3+ bloc(ers have demonstrated that omepra/ole is superior in regards to pain relief and ulcer healing. #bout H06 of patients are ulcerfree after + wee(s of treatment. 9p to K56 are ulcerfree at the end of wee(s of treatment. • (ucralfate is activated at a p3 of E.5 and polymeri/es to form an insoluble gel which binds to proteins on in$ured mucosa. In doing so it forms a barrier between in$ured mucosa and luminal acid to prevent further acidinduced in$ury. Bucralfate also binds free bile salts and pepsin, reducing their ability to cause mucosal damage. #dditionally, it stimulates mucosal production of mucus, bicarbonate, and prostaglandins. #s it does not influence acid secretion, sucralfate does not promote bacterial overgrowth within the stomach. #cid reducing therapy with proton pump inhibitors or 3+ receptor antagonists raise intraluminal gastric p3 and conseuently decrease the efficacy of sucralfate when these medications are used in combination. Bucralfate displays ulcerhealing efficacy similar to that of 3+ bloc(ers. • )ntacids wor( by neutrali/ing gastric acid. They have ulcerhealing efficacy comparable to 3+ bloc(ers. 3owever, effective treatment with antacids reuires freuent daily dosing which negatively influences patient compliance. The antimicrobial treatment of 3elicobacter pylori is an important component of the treatment of peptic ulceration. #s previously mentioned, 3. pylori is associated with duodenal ulceration in nearly 1006 of cases and with gastric ulceration in about 406 of cases. 1 3elicobacter infection should be considered when patients e&perience ulcer recurrence on maintenance medical therapy or when peptic ulcers fail to heal. ultiple medical regimens e&ist consisting of some combination of clarithromycin, metronida/ole, bismuth, andor tetracycline. Triple therapy is becoming more popular with use of a 88I and two antibiotics !i.e., omepra/ole, clarithromycin and metrinida/ole". Jegardless of the e&act regimen used, a 101 day course leads to eradication of 3. pylori in appro&imately K06 of cases. (urgical treatment There are three basic operations for uncomplicated peptic ulceration: parietal cell vagotomy, truncal vagotomy with pyloroplasty, and truncal vagotomy with antrectomy. ith the advent of 3+ receptor antagonists and, more recently, proton pump inhibitors the surgical treatment of peptic ulcer disease has become less common. Burgical treatment is indicated when ulcers fail to heal after months of appropriate medical therapy or when ulcers recur on maintenance therapy. Burgery is also indicated when malignancy cannot be e&cluded and when complications of disease occur. Fomplications of peptic ulcer disease include perforation, hemorrhage, and obstruction. *arietal cell "agotomy selectively inhibits vagal stimulation of parietal cells and smooth muscle cells of the gastric fundus. It spares the vagal enervation to the antrum, pylorus, small bowel, biliary tract, and pancreas. #cid secretion is diminished by the interruption of vagal stimuli to parietal cells. Bpecifically, basal acid secretion is decreased by about H06 and ma&imal acid secretion is decreased by about 06. There is some rebounding of both basal and ma&imal acid secretion over time but neither rebound to preoperative levels. >agal denervation of the gastric fundus inhibits receptive rela&ation of the fundus. #s a result, gastric emptying of liuids is increased. #s the antrum and pylorus are spared, there is no effect on the emptying of solids. Truncal "agotomy has similar efficacy in regards to the reduction of acid secretion. #s with parietal cell vagotomy, truncal vagotomy decreases receptive rela&ation of the gastric fundus increasing the emptying of liuids. Truncal vagotomy additionally inhibits antral and pyloric motility which results in poor emptying of solids. 8yloroplasty is included to overcome the effect of diminished gastric emptying. It effectively provides a wider gastric outflow tract so that the emptying of solids is increased. )ntrectomy removes the bul( of gastrin producing cells and effectively reduces basal gastrin levels by 506 and postprandial gastrin levels by 46. Jeconstruction of the upper CI tract is via gastroduodenostomy !'illroth I" or loop gastro$e$unostomy !'illroth II". Truncal "agotomy and antrectomy results in the reduction of basal and ma&imal acid secretion by about H56. Inhibited fundic receptive rela&ation again results in the increased emptying of liuids. The emptying of solids is decreased. 'oth forms of reconstruction are similar in regards to operative mortality, morbidity, and rates of recurrence. Electi"e surgical procedures for duodenal ulcer 8 • *ro/imal Gastric $agotomy It is generally agreed that pro&imal gastric vagotomy !8C>"Lalso (nown as highly selective vagotomy !3B>" or parietal cell vagotomy !8F>"L is the elective surgical treatment of choice for duodenal ulcer because it has the lowest operative mortality !E0.16" and few, if any, side effects. The longterm seuelae of vagotomy and gastrectomy !e.g., dumping syndrome, diarrhea, anemia, weight loss, and so on" are not seen with 8C>. -n the other hand, the operation must be performed meticulously 15 by welltrained surgeons. 8C> can be done via laparotomy or laparoscopically. The advantage of the laparoscopic approach is that visibility is improved by magnification, and both hospital stay and postoperative pain are significantly reduced. hether the operation is done Electi"e surgical procedures for gastric ulcer hile vagotomy is the cornerstone of elective surgery for duodenal ulcer, gastric resection is often more appropriate to treat patients with gastric ulcer. Two reasons support this philosophy. 2irst, unli(e duodenal ulcer,where increased or inappropriate acid secretion is invariably a factor, gastric ulcer appears to be associated more with reduced mucosal defense. Becond, although a duodenal ulcer is nearly always benign, a gastric ulcer can be malignant. Jesection provides the best chance for the diagnosis and cure of gastric ulcer. Types of Gastric Ulcer Three types of gastric ulcer have been described : 14 1. Type , the most common type of gastric ulcer, occurs at the lesser curvature and is typically found in the transitional mucosa between the body of the stomach and the antrum. +. Type is a gastric ulcer that coe&ists with a duodenal ulcer. . Type is a prepyloric or pyloric channel ulcer that seems to be associated with gastric acid hypersecretion. Choice of Operation The operation of choice differs for these three types of gastric ulcer. The best surgical procedure for Type I ulcer is conservative distal gastrectomy, which can often be limited to antrectomy. # gastroduodenal anastomosis is associated with fewer long term complications, and so is preferred over a gastro$e$unal anastomosis. 8atients with Type II gastric ulcers are also best treated with conservative distal gastrectomy and gastroduodenal anastomosis. Bome surgeons add truncal vagotomy to this procedure because gastric acid hypersecretion is freuently seen with this type of ulcer.#ny benefits of truncal vagotomy may be outweighed by the longterm seuelae of postvagotomy diarrhea. # large clinical e&perience is now documented to indicate that 8C> as the only operation is inappropriate in this setting because ulcer recurrence in patients approaches 06. 8atients with Type III gastric ulcers are more definitively treated with vagotomy and antrectomy. Ideally, a selective gastric vagotomy should be done to preserve e&tragastric vagal innervation and minimi/e the incidence of postvagotomy diarrhea. Types of Electi"e *eptic Ulcer (urgery Abbreviations: 'I, 'ilroth I gastrectomy) 8C>, pro&imal gastric vagotomy) T>, truncal vagotomy) > M #, vagotomy and antrectomy . 1 1H 1K +0 +1