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					Anatomy and Anomalies of the Stomach and Duodenum

Anatomy of the Stomach
• J-shaped dilatation of the alimentary canal continuous with the esophagus proximally & the duodenum distally • Primary function: - reservoir to store large quantities of recently ingested food - to initiate the digestive process - to release its contents in a controlled fashion

Anatomy of the Stomach
• Stomach volume- 30 ml in neonates 1.5 – 2 L in adults • R vagus nerve – post. wall • L vagus nerve – ant. wall • GEJ – lies to the L of T10, 1-2 cm below the diaphragmatic hiatus • gastroduodenal junction – lies at L1, to the R of the midline in the recumbent fasted individual

Anatomy of the Stomach
• Greater curvature – forms the L lower border • Lesser curvature – forms the R upper border • Boundaries: Posterior – pancreas, transverse colon, diaphragm, spleen & apex of the L kidney and suprarenal gland

Anatomy of the Stomach
• Boundaries: *anterior- liver *anterior L lower aspect – inner aspect of the anterior abdominal wall • anatomic or histologic landmarks: 1. Cardia 4. Incisura angularis 2. Fundus 5. antrum 3. Body or corpus 6. Pylorus/pyloric channel

Vascular Supply
• Arterial supply – derived from the branches of the CELIAC ARTERY ( common hepatic, L gastric and splenic arteries) • Blood supply of the lesser curvature: *above- L gastric artery *below- R gastric artery, a branch of the common hepatic artery or gastroduodenal artery

Vascular Supply
• Blood supply of the greater curvature: *above- L gastroepiploic artery ( a branch of splenic artery) *below- R gastroepiploic artery ( a branch of the gastroduodenal artery)

Venous Drainage
• Accompanies the arterial supply & empty into the: 1. Portal vein or 2. Splenic or 3. Superior mesenteric vein

Venous Drainage
• Lesser curvature of the stomach – right and left gastric veins • Inferior aspect and a portion of the greater curvature of the stomach – right and left gastroepiploic veins

Lymphatic Drainage
• Most of the lymphatic drainage eventually reaches the CELIAC NODES after passage through intermediate LN • Inferior gastric region – drains into subpyloric & omental nodes -- hepatic nodes—celiac nodes

Lymphatic Drainage
• Splenic or superior aspect of the greater curvature – pancreaticosplenic nodes – celiac nodes • Superior gastric or lesser curvature – L and R gastric nodes –celiac nodes • Hepatic or pyloric portion of the lesser curvature – drains into the suprapyloric nodes – hepatic nodes – celiac nodes

Gastric Innervation
• Sympathetic innervation – derived from the preganglionic fibers arising predominantly from T 6- T8 spinal nerves, w/c synapse within the bilateral celiac ganglia • Parasympathetic innervation – via the R and L vagus nerves w/c give rise to posterior and anterior vagal trunks near the gastric cardia

Tissue Layers
• 4 layers of the gastric wall: 1. Mucosa 2. Submucosa 3. Muscularis propia 4. Serosa

Microscopic Anatomy
• The gastric mucosal surface is composed primarily of a simple layer of columnar epithelial cells • The cells secrete mucus whose 1º role, along with HCO3, is luminal cytoprotection from ―the elements‖: acid, pepsin, ingested substances, and pathogens

Microscopic Anatomy
• Cellular renewal time for a surface mucus cell is approx. 72 hours • Gastric cardia – cardiac glands populated by mucous, endocrine and undifferentiated cells • Gastric fundus and body – contains the oxyntic ( or parietal or fundic) glands

Microscopic Anatomy
• Antrum and pylorus – contains the pyloric glands composed of endocrine, mucous and gastrin cells • oxyntic glands - the most numerous and distinctive gastric glands - responsible for secretion of acid, intrinsic factor, & the bulk of gastric enzymes

Microscopic Anatomy
• Parietal cell – the principal cell type of the oxyntic gland - responsible for the oxyntic mucosal secretion of H+ ions at a final concentration of 150-160 mmol of HCl per liter

Anatomy of the Duodenum
• Most proximal portion of the small intestine, continuous proximally with the pylorus and distally with the jejunum • Forms a C-shaped loop that is molded around the head of the pancreas • Adult duodenum – 30 cm or 12 inches long

Anatomy of the Duodenum
• 1. 2. 3. 4. • 4 parts of the duodenum First part – 5 cm long Second part – 7-10 cm long Third part – 10 cm long Fourth part – 5 cm long The junction between the duodenum and jejunum is fixed posteriorly by the ligament of Treitz

Anatomy of the Duodenum
• Duodenal wall – composed of outer longitudinal and inner circular muscle layers • Luminal surface is lined with mucosa forming numerous circular folds known as plicae circulares or valvulae conniventes. * An exception is the duodenal bulbdistinguished radiographically and endoscopically by its smooth featureless mucosa

Vascular Supply
• Arterial supply: * proximal duodenum – branches of the celiac trunk *distal duodenum – branches of the superior mesenteric artery

Venous Drainage
• Corresponds to the arterial supply • Superior pancreaticoduodenal veins coursing between the duodenum and pancreatic head to enter the portal vein • Anterior and posterior inferior pancreaticoduodenal veins empty into either a jejunal vein or directly into the superior mesenteric vein

Lymphatic Drainage
• Corresponds to the vascular supply • Small anterior and posterior duodenal lymph channels drain into the pancreaticoduodenal nodes • Superior – hepatic nodes • Inferior – superior mesenteric nodes

Duodenal Innervation
• Preganglionic sympathetic nerves course through the celiac and superior mesenteric ganglia • Parasympathetic fibers, provided by the hepatic branch of the anterior vagus nerve and the mesenteric nerves, synapse with Meissner’s and Auerbach’s plexuses in the duodenal wall

Microscopic Anatomy
• Mucosa lined with villi surrounded by crypts of Lieberkuhn an submucosa with characteristic Brunner’s glands • Deep to the epithelial layer are absorptive cells – Paneth cells- w/c secrete lysozyme and other host defense factors • Brunner’s glands secrete an alkaline & clear mucus containing HCO3, EGF, Pepsinogen II – most numerous in the proximal duodenum

Gastric Secretion: Normal and Abnormal

• The human stomach secretes: 1. water and electrolytes - H+, Na+, K+, Cl-, HCO32. Enzymes - pepsins and gastric lipase 3. Glycoproteins - intrinsic factor and mucin

Physiologic Functions of Gastric Exocrine Secretions
• Initiation of pepsin hydrolysis of dietary proteins (H+, pepsin) • Initiation of hydrolysis of dietary TGL (gastric lipase) • Liberation of vitamin B12 from dietary protein (H+, pepsin) • Binding of vitamin B12 for subsequent ileal uptake (intrinsic factor) • Facilitation of duodenal inorganic iron absorption (H+)

Physiologic Functions of Gastric Exocrine Secretions
• Stimulation of pancreatic HCO3- secretion via secretin release (H+) • Suppression of antral gastrin release (H+) • Killing or suppression of growth of ingested microorganisms (H+) • Protection against noxious agents (mucin, NaHCO3-, water:components of the mucus gel)

Regulation of Gastric Acid Secretion
• Stimulants of Acid Secretion: Parietal and ECL cells – histamine, acetylcholine, gastrin • Inhibitors of Acid Secretion: Cholecystokinin Prostaglandins Secretin from intestinal S cells Others – peptides (glucagon-like peptide-1 amide, gastric inhibitory peptide), VIP

Gastric Acid Secretion in Humans
• 3 mechanisms contribute to stimulation of acid secretion after a meal: 1. Cephalovagal stimulation – smell, sight, thought of appetizing food, taste 2. Gastric distention – stimulates acid secretion by activating long vagovagal reflexes and short intragastric reflexes 3. Chemical reactions of food with gastrointestinal mucosa - protein - fats - carbohydrates -coffee

Gastric Acid Secretion in Disease
• Increased gastric acid secretion 1. Duodenal ulcer 2. Zollinger-Ellison Syndrome (gastrinoma) 3. Retained Antrum Syndrome 4. Others – hyperparathyroidism (MEN I) extensive small bowel resection antral G cell hyperplasia increased ICP foregut carcinoid tumors with histamine overproduction

Gastric Acid Secretion in Disease
• Decreased Acid Secretion: 1. Chronic atrophic gastritis 2. Chronic active superficial gastritis 3. Human Immunodeficiency virus infection 4. Other causes – gastric ulcer, polyps, cancer, islet cell tumors, severe hypocalcemia, partial gastric resection &/or vagotomy

Helicobacter pylori

• H pylori – causally linked with 1. Gastritis 2. Peptic ulcer disease 3. Gastric adenocarcinoma 4. Gastric B cell lymphoma 5. Non-ulcer dyspepsia - uncertain

• H. pylori – highly motile, gram-negative spiral organism whose most striking biochemical characteristic is the abundant production of urease • H pylori – trophic for gastric epithelium ( stomach and areas of gastric metaplasia outside the stomach) • H pylori infection elicits robust inflammatory and immune responses that are lifelong unless the infection is cured

Epidemiology
• Infection is typically acquired in childhood • In developing countries, most children are infected by age 10 • In developed countries, there is an age-related increase in prevalence • The major risk factor for infection is the socioeconomic status of the family during childhood • Genetic susceptibility to infection has been confirmed in studies of monozygotic twins

Transmission of Infection
• The bulk of data suggests that the organism is transmitted from person to person • Means of transmission – uncertain • 3 possibilities: 1. Fecal-oral transmission 2. Oral-oral transmission 3. Gastro-oral transmission

Acute Infection
• Severe neutrophilic gastritis • Seroconversion occurred between days 14-74 • Fasting gastric pH was above 7.0 on days 14 and 37 but fell to 2.0 on day 74 • Earliest effect of infection is a transient increase in basal acid secretion • The fall in acid secretion correlated best with the degree of inflammation in the gastric body

Virulence Factors
• Colonization Factors – allow the organism to establish its presence and persist despite the body’s attempts to rid itself of infection 1. Motility 2. Urease 3. Induction of hypochlorhydria 4. Adherence 5. P Type ATPase

Virulence Factors
• Factors that Induce Tissue Injury 1. Lipopolysaccharide (LPS) 2. Leukocyte recruitment and activating factors 3. CagA and VacA proteins 4. Heat shock protein

Chronic Infection
• Although the organism is spontaneously cleared in some individuals, infection in most adults appears to be long term • Antral biopsy reveal focal epithelial cell damage as well as an inflammatory infiltrate in the lamina propia • The severity of the infiltrate correlates with the intensity of H pylori colonization • The infiltrate consists of PMN leukocytes (PMNs), eosinophils, and mononuclear cells

Chronic Infection
• The lymphocytic component of the inflammatory response is referred to s MALT (mucosaassociated lymphoid tissue) • Inflammation in gastric body is less severe than in the antrum • In patients with duodenal ulcer, gastritis is often severe in the antrum but may be absent in the body • Cure of H pylori infection results initially in reduction of PMNs followed by a gradual resolution of the chronic inflammatory cell infiltration

Natural History of Chronic Infection
• Most individuals with chronic H pylori infection remain asymptomatic throughout their lives • PUD develops in about 1 in 6 • Atrophic gastritis, gastric adenocarcinoma and gastric lymphoma are less frequent outcomes of infection

Chronic Atrophic Gastritis
• In some individuals, chronic superficial H pylori gastritis progresses over time to atrophic gastritis • 3 patterns of atrophic gastritis: 1. Body predominant (Type A) 2. Antral predominant (Type B) 3. Gastritis in both body and antrum (Type AB)

Chronic Atrophic Gastritis
• As the degree of atrophy progresses in type A or AB atrophic gastritis, the presence of H pylori decreases – hypochlorhydria creates an uninviting milieu for the organism • Mechanism by which gastric atrophy occurs is unclear – major factor may be environmental

Chronic Atrophic Gastritis
• Type A atrophic gastritis - may be associated with pernicious anemia (PA) - antibodies against the proton pump, pepsinogen and intrinsic factor - loss of secretory function begins with acid, followed by pepsinogen and finally intrinsic factor

Chronic Atrophic Gastritis
- PA is thus a marker for the most severe, end-stage form of type A atrophic gastritis - the antibodies to the secretory elements appear to develop after the atrophic process begins - H pylori-related PA is associated with antral evidence of present or past infection whereas in pure autoimmune PA, the antral mucosa would be normal

Diagnosis
• Culture - the least sensitive of the techniques involving mucosal biopsy • Mucosal biopsy and histologic examination of the specimen for the presence of H pylori and/or gastritis - gold standard • The standard HE stain - excellent for histologically determining chronic or chronic active inflammation (gastritis) • A silver stain ( Warthin-Starry) - better at demonstrating the organism if small numbers of bacteria are present

Accuracy of Diagnostic Tests for Helicobacter pylori
Parameter
Chronic inflammation
Acute inflammation

Sens.
100
87

Spec.
66
94 99 100 97 96

PPV
84
96 99 100 95 98

NPV
100
80 89 84 85 84

Warthin-Starry 93 silver stain Rapid urease test Serum IgG antibody Urea breath test 90 91 90

Treatment
• Antibiotics Used in Regimens to Eradicate H. pylori 1. Amoxicillin 2. Tetracyline 3. Metronidazole 4. clarithromycin

Treatment
• Adjunctive Agents Ued in Regiments to Treat H. pylori Infection 1. Bismuth 2. Proton-Pump inhibitors 3. H2 Receptor Antagonists 4. Ranitidine Bismuth Citrate

Treatment
• Therapeutic Regimens to Treat H. pylori Infection 1. One antibiotic plus one adjunctive agent ( dual therapy) - amoxicillin plus omeprazole – 80% cure rate - clarithromycin plus omeprazole – 75% - clarithromycin plys RBC – 80%

Treatment
2. Two antibiotics plus One Adjunctive Agent (Triple Therapy) - metronidazole (250 mg TID), tetracycline (500 mg QID), bismuth (2 tabs QID) – ―traditional‖ bismuth triple therapy – 85-90% cure rate - metronidazole, amoxicillin, ranitidine – 10 days – 89% cure rate - clarithromycin (250 mg BID), tinidazole (500 mg BID), omeprazole )(20 mg OD) – 7 days95% cure rate

Treatment
• 3. Two Antibiotics plus Two Adjunctive Agents (Quadruple Therapy) - traditional bismuth triple therapy plus ranitidine – 14 dyas – 84% curerate - traditional bismuth triple therapy plus omeprazole – 7 days – 95% cure rate

Treatment
• Therapeutic Strategy - the most effective regimens are combination of 2 antibiotics and 1 or 2 adjunctive agents for 7 – 14 days - Europe – triple therapy – 7 days - United States – 14 days - OAC has lower cure rate than OMC unless given for 14 days

Follow-Up After Antimicrobial Therapy
• Uncomplicated ulcer disease – monitor for recurrent symptoms - if asymptomatic – assume cure - if symptoms recur – determine persistence or recurrence of infection • bleeding or perforated ulcer associated with H. pylori – document cure of infection before stopping HRA - endoscopy with mucosal biopsy - urea breath test

Peptic Ulcer and Its Complications

Ulcer Pathogenesis
Exogenous factors: Acid + pepsin

NSAIDS, alcohol

Endogenous factors: bile, lysolecithin

FIRST LINE DEFENSE: Mucus/Bicarbonate Barrier SECOND LINE DEFENSE: Epithelial cell mechanisms Barrier function of apical plasma membrane; intrinsic cell defense; and extrusion of acid THIRD LINE DEFENSE: Blood flow-mediated

Removal of back-diffused H+ and Supply of energy

EPITHELIAL CELL INJURY

Ulcer Pathogenesis
FIRST LINE REPAIR: Restitution SECOND LINE REPAIR: Cell Replication ACUTE WOUND FORMATION

THIRD LINE REPAIR: WOUND HEALING
Formation of granulation tissue Angiogenesis Remodelling of basement membrane

ULCER

Pathology of Peptic Ulcers
• Erosions – superficial mucosal defects • Ulcers – extend through the muscularis mucosa into the submucous or muscularis propia • Chronicity of lesions is important • Acute lesions ( aspirin injury) – multiple, shallow w/ minimal surrounding inflammation or fibrosis

Pathology of Peptic Ulcers
• Stress ulcers (ICU) – often acute, not generally surrounded by fibrosis • Four histologic zones surrounding chronic peptic ulcers: - superficial layer of fibrin and exudate - successive underlying zones of fibrinoid necrosis, - granulation tissue, - fibrosis

Pathology of Peptic Ulcers
• Chronic ulcers – usually single, although 5-20% may be multiple • Healing ulcers – initially covered with a single layer of undifferentiated epithelial cells, followed by variable resolution of the underlying inflammation

Ulcer Location
• 4 subsets of ulcers: 1. Duodenal ulcer 2. Distal gastric ulcer (distal antral or prepyloric ulcers) 3. Proximal GU – occur freq. on the lesser curvature, near the angularis at the transition of oxyntic and antral mucosa) 4. Ulcers in the gastric cardia or in a hiatal hernia pouch – more inclined to complications

H. Pylori and Peptic Ulcer
• HP causes chronic, active gastritis that involves predominantly the antrum or the entire stomach • HP colonize the human gastric mucosa, induce inflammation without invasion, and persist for a lifetime usually without causing symptoms

Potential Risk Factors and Associations
1. NSAIDS and aspirin 2. Cigarette smoking 3. Alcohol – damages the gastric mucosal barrier to H+ in high conc.and is asso. With acute gastric mucosal lesions char. by mucosal hemorrhages; no evidence that these acute effects cause either gastritis or chronic peptic ulcer - biphasic dose response: stimulation at concentrations between 1-4%, higher concentrations had no effect or inhibited secretion - wine and beer are very effective stimuli of acid secretion

4. Diet - although certain foods, beverages, and spices cause dyspepsia, there’s no convincing data that such food cause, perpetuate or reactivate peptic ulcers - dietary insufficiency of essential fatty acids has been hypothesized to be a pathogenic factor in DU - coffee is a strong stimulant of acid secretion and produces dyspepsia w/c often results from enhanced esophageal reflux - decaffeination does not reduce the effect of coffee - no evidence that coffee consumption is a risk factor for ulcer disease per se

Psychologic Factors in Peptic Disease
• Psychologic stress impacts visceral function and organic disease • no established association between stress and ulcer formation in controlled studies • The individual’s interpretations and reactions to stress are more important than the intensity of the external stress

Genetics of Peptic Ulcer Disease
• Familial aggregation of peptic ulcer: - 20-50% of DU patients have a (+) fam hx of DU - first-degree relatives of DU (GU) patients have 3-fold increase in the prevalence of DU (GU) • ―Genetic‖ markers in peptic ulcer - blood group O have an increased risk of DU

Diseases Associated with Peptic Ulcer
• Reflux esophagitis and Barrett’s esophagus • Chronic pulmonary disease • Cirrhosis • Renal failure

• Atrophic fundic gland gastritis • Gastric cancer - negative association between gastric carcinoma and DU - contradicting earlier studies, it appears that benign GU, but not prepyloric ulcer, is associated with gastric cancer

Disorders Associated with a Decreased Incidence of Peptic Ulcer

Clinical Presentation
• ―acid dyspepsia‖ – classic ulcer symptom - burning epigastric ―hunger‖ pain or discomfort 2-3 hours after meals and at night, between 11 pm to 2 am, when the circadian stimulation of acid secretion is maximal, but rarely before breakfast

Clinical Presentation
• • • • • • • • • • Increased appetite Anorexia Weight loss Nausea Vomiting Heartburn Nondyspeptic symptoms Fatty food intolerance Bloating Belching

Presentation of Ulcer Complications
• Penetrating ulcers – more localized and intense pain that radiates to the back and has lost relief with food or antacids • Perforation – sudden severe, diffuse abdominal pain • Pyloric outlet obstruction – vomiting • Hemorrhage – heralded by nausea, hematemesis, melena, or dizziness

Presentation of NSAID ulcers
• Hallmark of NSAID gastropathy is the dissociation of symptoms and pathology • Presence of symptoms does not reliably predict ulcers nor does the absence of symptoms exclude disease • NSAIDS can induce bleeding, perforation, or gastric outlet obstruction

Diagnosis of PUD
• Laboratory evaluation - CBC, LFT, serum creatinine, serum calcium, fasting serum gastrin - H. pylori testing – serology for IgG, UBT, urease test, histology, culture • Upper gastrointestinal radiography - optimal radiography, using double-contrast, compression or hypotonic duodenography – detects 80-90% of ulcers - benign GUs – more freq at lesser curvature at the incisura

Diagnosis of PUD
- larger lesions have a greater likelihood of being cancer - the occurrence of DU along with GU decreases the likelihood of malignancy - signs indicating malignancy: 1. An ulcer within a definitive mass 2. Effaced, interrupted, fused, or nodular mucosal folds as they approach the margin of the crater 3. Negative, irregular filling defects in the ulcer crater

Diagnosis of PUD
- signs suggesting benignancy
1. Radiation of smooth, symmetric mucosal folds to the edge of the ulcer crater or to a smooth mound of edema 2. A smooth translucent band or collar surrounding the ulcer crater, suggesting edema 3. Hampton’s sign – a radiolucent line about 1 mm in width that rims the mouth of the ulcer crater, resulting from undermining of normal mucosa 4. An incisura, an indentation on the opposite wall due to edema and spasm of the circular muscle 5. Extension of a crater outside the gastric lumen

Diagnosis of PUD
• Endoscopy - sensitive, specific and safe method for diagnosing peptic ulcers, allowing direct inspection and biopsy - For GUs, endoscopy correctly predicts the presence or absence of ulcers in more than 95% of cases

• Endoscopy - Benign ulcers have smooth, regular, rounded edges, with a flat, smooth ulcer base often filled with exudate - malignancy is obvious if an ulcerated massprotrudes into the lumen, if the folds surrounding the ulcer crater are nodular, clubbed, fused or stop short of the ulcer margin, or if the margins are overhanging, irregular or thickened - multiple biopsy specimens are necessary - four jumbo specimens of the ulcer margin are equivalent to 6 to 7 regular-sized specimens

Differential Diagnosis
• Functional disorders that overlap with peptic ulcer – GERD, acid dyspepsia, ―dysmotility-like‖ indigestion/dysgastria • Gastric carcinoma • Drug-induced dyspepsia • Infiltrative, granulomatous, neoplastic, and infectious diseases

Recommendations for Evaluation and Follow-up
• Gastric Ulcer - if HP (+), treat - if HP (-), additional testing to firmly exclude HP - multiple biopsy specimens of the ulcer margin are indicated to exclude malignancy - at least 3 specimens are also justified of the antrum for urease testing, and if negative, histology

Recommendations for Evaluation and Follow-up
• HP-negative Ulcers - the most common causes for HP negative ulcers are false-negative testing for HP and undiscovered consumption of NSAIDS

Atypical Ulcers
• • • • Giant ulcers Pyloric Channel ulcers Postbulbar ulcers Multiple ulcers

Natural History of Peptic Ulcer
• 40% of DUs and 30% of GUs heal by 4 weeks • Both DUs and GUs frequently recur until the underlying cause is removed (cure of HP or discontinuation of NSAIDS) • 50-80% recurrence rate during the 6-12 months after initial ulcer healing

Antiulcer Therapy
1. H2RA - inhibit acid secretion by blocking H2 receptors on the parietal cell - hepatic and renal metabolism - toxic effects: hypochlorrhydria bacterial overgrowth hypergastrinemia altered absorption from alkalinization decreased absorption of divalent cations decreased vit B12 absorption

Antiulcer Therapy
• H2RA – side effects:
antiandrogenic cimetidine – central CNS reactions headache immune modulation cardiac conduction abnormalities idiosyncratic hepatic injury immune hypersensitivity reactions thrombocytopenia granulocytopenia

Antiulcer Therapy
2. Proton Pump Inhibitors – inhibit H+-K+ -ATPase - hepatic metabolism and excretion - adverse effects are few hypergastrinemia leydig cell tumors

Antiulcer Therapy
3. Antacids
- Al(OH) binds growth factors, enhances EGF binding to ulcers, possibly serving to deliver GF to injured mucosa - promote angiogenesis in injured mucosa - bind bile acids and inhibit pepsin activity - adverse effects: Mg-containing antacids - diarrhea, hypermagnesemia calcium carbonate – milk-alkali syndrome (hypercalcemia, alkalosis, renal impairment)

Antiulcer Therapy
4. Sucralfate
- sulfated polysaccharide (sucrose octasulfate) complexed with Al(OH) - binds to ulcer base - prevents acute, chemically induced mucosal damage and heals chronic ulcers without altering gastric acid or pepsin secretion or significantly buffering acid - stimulates angiogenesis and formation of granulation tissue (GF binding) - side effects-aluminum absorption, phosphate depletion

Antiulcer Therapy
5. Bismuth - does not inhibit or neutralize gastric acid - pepsin activity but not pepsin secretion is inhibited by CBS - bind to ulcer craters - increase mucosal prostaglandin production and mucus and bicarbonate secretion - suppression of HP – most dramatic action - adverse effects: bismuth intoxication

Antiulcer Therapy
6. Prostaglandins (E and I group) - inhibit acid secretion by selectively reducing the ability of the parietal cell to generate cAMP in response to histamine - only misoprostol has been approved for use in the US for prevention of NSAID-induced GU - adverse effect: crampy abdominal pain and diarrhea

Factors Influencing Ulcer Healing
1. Smoking - risk factor asso. with the occurrence, persistence, recurrence, and complications of peptic ulcer - smokers are at increased risk for both Dus and GUs - smoking increases the risk of complications and the need for surgery - death rates from ulcer disease are greater in smokers

Factors Influencing Ulcer Healing
- smoking is a risk factor before, not after, eradication of HP - ulcer risk correlates with the quantity of cigarettes smoked - < 10 cigarettes/day – modest risk - >30 cigarettes/day – healing is markedly impaired and recurrences in 3 months can approach 100%

Factors Influencing Ulcer Healing
2. NSAIDS - cause ulcers in the absence of gastritis or HP but also exacerbate an underlying ulcer diathesis due to HP - ulcers generally heal readily on antiulcer therapy if NSAIDS are discontimued

Factors Influencing Ulcer Healing
3. Acid Secretion - meta-analysis had demonstrated a correlation 4. Inpatient Versus Outpatient Ulcers - stress ulcer respond poorly to medical and surgical therapy

Factors Influencing Ulcer Healing
5. Ulcer Size - large and small GUs heal at the same rate on antacids, about 3 mm/week - therefore, larger ulcers will require more time to heal 6. Age and Gender - ulcers in young females may heal more readily that those in young males - ulcers in older patients may heal slowly than in younger patients

Factors Influencing Ulcer Healing
7. Alcohol and Beverage Consumption - alcohol abuse interferes with patient compliance and ulcer healing - wine, beer, coffee, decaffeinated coffee – strong acid secretagogues 8. Diet - no evidence that specific foods alter ulcer healing or recurrences - red and black peppers cause acute, superficial gastric mucosal injury comparable to that produced by aspirin

Factors Influencing Ulcer Healing
8. Diet - frequent feedings may lead instead to more sustained stimulation of acid secretion - bedtime snacks stimulate nocturnal acid secretion - milk – strong secretagogue, largely because of its calcium and protein content - milk stimulates more acid secretion than it buffers and is not an effective antacid

Treatment Options for Refractory Ulcers
1. HP Eradication 2. Conventional Therapy 3. Surgery - it is preferable to initially opt for vigorous attempts to find curable underlying causes and maximal medical therapy before opting for elective surgery

Management of Giant Ulcers
• • • • • PPI – drugs of choice Giant GUs heal slowly 10% chance of being malignant Early surgery Trial of 12 weeks of medical therapy with close monitoring of the patient – effective in the majority

Treatment of NSAID Ulcers
2 critical steps: 1. When possible, discontinue or reduce the NSAID dose 2. Search and cure HP infection - with continued use, most DU and GU will heal with standard, slit-dose H2RA but with moderate delay - healing efficacy of omeprazole – not compromised with continued NSAID use

Risk Factors for NSAID Ulcers
1. Age > 70 years 2. History of prior ulcer disease or complications – major risk factor for ―clinical‖ NSAID ulcers and their complications 3. Co-therapy with corticosteroids or with anticoagulants increases the risk of ulcer complications


				
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