Fom 4.1.docx

Peptic Ulcer Disease Anatomy: 1. Describe the gross anatomy and histology of the stomach and duodenum. Describe the different anatomical structures associated with the stomach and duodenum. STOMACH 4 regions:

>Cardia: narrow transitional zone bet. esophagus and stomach. Mucus production >Pylorus: opens to small intestine. Mucus production >Fundus and Body: Site of gastric glands in gastric pits ~Rugae: Longitudinal folds that flatten when stomach fills with food 4 layers of stomach in all the regions: >Mucosa: contains gastric pits that secrete mucous layer rich in HCO3-.In the fundus and body, gastric glands contain mucous neck cells, chief cells (contains pepsinogen that activates in acidic environment of stomach), enteroendocrine cells (secretes serotonin; in pylorus it secretes gastrin) parietal cells (which secretes HCl and intrinsic factor, a glycoprotein uptake for Vit. B12 in small intestine). Parietal cell activity is stimulated by parasympha and paracrine release of histamine and gastrin from enteroendocrine cells. Cardiac and pyloric glands lack parietal and chief cells secretes only mucus. >Submucosa: Connective tissue with large blood and lymph vessels, mast cells >Muscularis: smooth muscle layer; outer longitudinal, middle circular, inner oblique. Contraction mix chyme with HCl and enzymes. At pylorus middle layer thickened to form pyloric sphincter >Serosa: outer covering

DUODENUM: >Mucosa: with villi which contains enterocytes (absorptive cells covered by glycocalyx with microvilli) with interspersed goblet cells (secrete mucin). Paneth cells (innate immunity) secrete defensins thst break membrane of bacterial cell walls. >Submucosa: with Meissner nerve plexus. Proximal part of duodenum contains Brunner glands (alkaline mucus) for optimum pH of pancreatic enzyme. >Muscularis: Myenteric nerve plexus which produce peristalsis 2 Describe the components of the three (3) levels of the gastroduodenal mucosal defense system or barrier. 1 line of defense: mucus-bicarbonate-phospholipid layer st

 

thick layer of mucus gel into which bicarbonate is secreted by the underlying epithelial cells. sustains a pH gradient between the lumen and cell surface such that epithelial cells are maintained at pH 7 to 8, despite the presence of intraluminal acid 2 line of defense: surface epithelial cells nd





this mechanism may be important in maintaining mucosal integrity (since the pH gradient may be overwhelmed by physiologic concentrations of intraluminal acid) The physical properties of the apical cell membrane and intercellular junctions and the presence of surface-active phospholipids on the membrane may be responsible for preventing hydrogen ions (H+) from diffusing into the mucosa by providing a physical barrier to their movement 3 line of defense: Continuous cell renewal from mucosal progenitor cells rd

  

maintains structural integrity of the mucosa. a thick layer of mucus containing sloughed epithelial cells together with passive movement of bicarbonate-rich fluid from the damaged mucosa. this may prevent exposure of undamaged cell nests to acid and thus aid re-epithelialization

Physiology and Biochemistry: 1. Discuss the functions of the three (3) levels of the gastroduodenal mucosal defense. Discuss the different factors that affect the function of each of these levels. 1. Mucus-bicarbonate -phospholipid layer (Preepithelial)  Physicochemical barrier to multiple molecules, including hydrogen ions  Mucous gel - functions as a non-stirred water layer impeding diffustion of ions and molecules such as pepsin  dissipation of this layer by ulcerogenic substances (such as aspirin and bile salts) leads to both acid back-diffusion and mucosal injury  The efficacy of protective properties of the mucus barrier depends on the gel structure and on the amount or thickness of the layer  between epithelium and lumen 2. Surface epithelial cells  Secretes mucus and bicarbonate  main role: o maintain a selective exchange of different substances (secretions, nutrients, etc.) between these lumen & internal compartments,

o

assure the protection of the organism against the penetration of micro-organisms and other exogenous antigens

3. Cell renewal  Cell renewal from mucosal progenitor cells is stimulated by growth factors 2. Discuss what gastric acid (HCl) is and how is it produced. Discuss how its production is controlled or regulated. HCl is the main component produced by parietal cells. It is necessary to activate pepsinogens into pepsins which also activates when it comes into contact with previous pepsin. It is stimulated by gastrin (via vagus nerve that signals gastrin cells in antral mucosa), histamine (a cofactor where whenever ACh and gastrin stimulate parietal cells together, histamine enhances secretion). Inhibition is due to excess acid in the stomach (when it falls pH < 3; (a) high acidity releases somatostatin which depresses gastrin secretion by G cells and (b) acid causes an inhibitory nervous reflex that inhibits gastric secretion). Secretin also inhibits it as well as enterogastric reflex (presence of food in small intestine signals enteric nervous system and thru sympathetic and vagus nerves). INFORMATION REGARDING PEPTIC ULCER DISEASE Normal Physiology of the Stomach: The degree of protection of G.I. tract from gastric juices is afforded by: First defense: Gastroduodenal Mucosal Barrier All areas normally exposed to gastric juice are well supplied with mucous glands: Supplier of Mucus: G.I. Part Supplied: Compound Mucus GlandsLower Esophagus Mucous Cell-Coating of Stomach MucosaStomach Mucous neck cells of Gastric GlandsStomach Deep Pyloric GlandsStomach Glands of BrunnerUpper Duodenum (secrete highly alkaline mucus) Second defense: Neutralization of the gastric acid by duodenal juices Duodenum is protected by: 1. Pancreatic secretions (contains a high amount of sodium bicarbonate) >Neutralizes HCl from stomach >Inactivates pepsin thus preventing the digestion of the mucosa 2. Brunner Glands (first few cm of duodenum)- also secretes bicarbonate ions 3. Bile from liver *other protective factors prostaglandins, mucosal blood flow, and growth factors

Two feedback control mechanisms normally ensure that this neutralization of gastric juices is complete, as follows:

1. Excess acid in duodenum→ Inhibit stomach gastric secretion and peristalsis via nervous reflexes and hormonal feedback of duodenum→ Decrease gastric emptying rate 2. Excess acid in small intestine→ Liberate secretin from intestinal mucosa→Stimulates pancreas to release pancreatic juice→acid neutralization Peptic Ulcer is a lesion of the gastric or duodenal mucosa ■Sites: (*= frequent) >Few cm of plylorus* >lesser curvature of the antral end of stomach* >Lower end of esophagus (where stomach juices frequently reflux) ■   can occur when there is loss of the protective mucous barrier (of mucus and HCO3−) and/or excessive secretion of H+ and pepsin. ■   Damaging factors are H+, pepsin, Helicobacter pylori (H. pylori), nonsteroidal antiinflammatory drugs (NSAIDs), stress, smoking, and alcohol.

Causes of Peptic Ulcer: Basic Cause of Ulceration: Imbalance between rate of secretion of gastric juice, and degree of protection afforded by o gastroduodenal mucosal barrier and o neutralization of gastric acid by duodenal juices Main cause: Helicobacter pylori infection > Burrows thru mucosal barrier→ releases ammonium→ liquefies the barrier→ stimulates HCl secretion→ strong acidic digestive juices of the stomach secretions penetrate into the underlying epithelium→ digest the gastrointestinal wall→ peptic ulceration

Other Causes of Ulceration: (1) smoking→ increased nervous stimulation of the stomach secretory glands (2) alcohol→ break down the mucosal barrier

(3) NSAIDs→ strong propensity for breaking down barrier (4) Severe chronic anxiety→ High gastric secretion rates than normal Treatment of Peptic Ulcers. (1) use of antibiotics along with other agents to kill infectious bacteria (2) Discontinue NSAIDS and smoking may interfere with healing (2) administration Drugs that block gastric H+ secretion (acid suppression) a. Atropine    blocks H+ secretion by inhibiting cholinergic muscarinic receptors on parietal cells, thereby inhibiting ACh stimulation of H+ secretion. b. Cimetidine/Ranitidine    blocks H2 receptors and thereby inhibits histamine stimulation of H+ secretion.   is particularly effective in reducing H+ secretion because it not only blocks the histamine stimulation of H+ secretion but also blocks histamine's potentiation of ACh effects. c. Omeprazole  is a proton pump inhibitor.   directly inhibits H+, K+-AT

Types of Peptic Ulcer: 1. Gastric ulcer (GU) ■Location: Stomach ■Principal Cause: H. pylori ■Other causes: NSAIDs/Chronic salicylate (irritant; account for 15-30% of GU) ■Gastric H+ secretroty rates: Normal or reduced because secreted H+ leaks back through the damaged gastric mucosa

■Gastrin levels: increased because decreased H+ secretion stimulates gastrin secretion. ■ H. pylori colonizes the gastric mucus and releases cytotoxins that damage the gastric mucosa. Contains urease, which converts urea to NH3, thus alkalinizing the local environment and permitting H. pylori to survive in the otherwise acidic gastric lumen. ■Clinical Features: > Burning epigastric pain made worse by or unrelated to food > Anorexia > Food aversion > Weight loss (in 40%). Similar symptoms in nonulcer dyspepsia

■Diagnosis: >Drinking a solution of 13C-urea, which is converted to 13CO2 by urease and measured in the expired air (Urea Breath Test) >Upper endoscopy preferable to exclude possibility that ulcer is malignant(brush cytology, ≥6 pinch biopsies of ulcer margin) >Radiographic features (if there’s air it may suggest ulcer) suggesting malignancy >ulcer within a mass, folds that do not radiate from ulcer margin, a large ulcer (>2.5–3 cm). ■Gastritis due to reflux of duodenal contents (including bile) may play a role. ■Pagkakaintindi ko: ‘Di gusto kumain kasi kapag kumain stomach will secrete HCl and pepsin na mas lalong sisira sa mucosa sa stomach na may ulcer so more pain pag kumain so mas gugustuhin na di kumain 2. Duodenal Ulcer (DU) ■Location: Duodenal bulb (initial portion) ■Principal Cause: H. pylori, inhibits somatostatin secretion (thus stimulating gastric H+ secretion) and inhibits intestinal HCO3− secretion (so there is insufficient HCO3− to neutralize the H+ load from the stomach). ■Other causes: glucocorticoids, NSAIDs, chronic renal failure cirrhosis, chronic lung disease ■Gastric H+ secretroty rates: Mild gastric acid hypersecretion (2x as normal), excess H+ is delivered to the duodenum, damaging the duodenal mucosa. ■Gastrin level: Baseline is normal; increases in response to a meal ■Clinical Features: >Burning epigastric pain 90 min to 3 h after meals > Nocturnal (11 pm-2 am) > Relieved by alkali or food ■Diagnosis: >Upper endoscopy or upper GI barium radiography ■Mild gastric acid hypersecretion resulting from: (1) increased release of gastrin (stimulates acid secretion) >due to H. plyori infection (gram-negative) which causes: (a) stimulation of antral G cells by cytokines released by inflammatory cells (b) diminished production of somatostatin (inhibits acid secretion by D cells

(2) Exaggerated acid response to gastrin due to an increased parietal cell mass (parietal cell secretes HCl) resulting from gastrin stimulation. ■Pagkakaintindi ko: Since nasira na ‘yong mucosa ng duodenum so ‘di masyadong makakaabsorb ng nutrients hence after 3 hrs gutom ka kaagad so pagkarating ng food sa duodenum magkakaroon ng hypersecretion dahil nga sa H. pylori so mas lalong masisira yung mucosa ng duodenum lalong di makakaabsorb ng nutrients. Complications of BOTH types: >Bleeding (if it erodes gastric arteries) and perforation (increased risk in GU due to NSAID) >Obstruction >Penetration causing acute pancreatitis >Intractability