14B. Peptic Ulcer Disease and Helicobacter pylori

Ulcer Diagnosis

Labs -may see nothing, may see slow microscopic oozing of blood (anemic) Radiology Endoscopy

Risk Factors for PUD (Western countries)

Looking at what causes ulcer disease in west Great majority due to HP Some to NSAIDs Over ¾ by HP More with duodenal ZES- is gastrin secreting tumor (uncommon as cause of ulcer disease)

EROSION definition

break in the surface epithelium that does not have perceptible depth

What about those ulcerations not caused by H pylori or NSAIDs?

-Crohn disease -Malignancy - confirm healing (more in stomach than duodenum) -Gastrinoma (+/- Multiple Endocrine Neoplasia) ; dysregulation of gastrin -Systemic Mastocytosis

Role of Endoscopy with ulcers

-Diagnosis of the etiology of bleeding -Administration of specific therapy -Assessment of the risk/likelihood of rebleeding -Guidance of other aspects of patient management, including: --need for hospitalization --need for ICU --pharmacotherapy --angiography --surgery

Things up/down regulating proton pump

Ach, gastrin and histamine activate D cell down regulate (somatostatin) PPIs will shut down pump irrespective of what turning it on (unlike H2R blockers)

Normal Gastric Acid Production

Acid Production -2.5 L/day -isotonic HCl solution -pH < 1 -produced by parietal cells -increase in 10-20% of H pylori-infected patients Mucus Production -produced by mucus neck cells --also produce bicarbonate -becomes trapped in mucus layer -increased pH gradient across mucus layer -can be destroyed by EtOH/NSAIDs ____________ Alcohol and NSAIDs decrease that mucus layer; more susceptible to acid irritation -NSAIDs leading more to ulcers, whil alcohol gastritis

PUD-RELATED COMPLICATIONS

GI bleeding - 15% (more often in those age >60) Perforation Penetration - a form of perforation in which the ulcer bed tunnels into an adjacent organ (pancreatitis) Gastric outlet obstruction - least common

Medications for PUD

Gastric pH>4 renders pepsin inactive and inhibits fibrinolysis Gastric pH>6 allows for platelet aggregation PPI > H2RA > antacids > placebo PPI and clopidogrel interaction?? __________ PPIs do this better than H2R blockers

Risk Factors - PUD

Helicobacter pylori infection -70% of duodenal ulcers in Western countries are related to infection with Helicobacter pylori -eradication prevents recurrence of PUD Aspirin and NSAIDs -Regular use increases odds of GI bleeding 5-6 fold -Serious ulcer complications occur in 1-4% of NSAID users -ASA 325>161>81>ECASA 81>COX2s -No clear dosage or frequency cutoff for NSAID and ASA risk Cocaine and methamphetamines (mucosal ischemia) Steroids, EtOH, and stress (not ICU stress) are NOT independent risk factors for PUD; tobacco is ??? -Glucocorticoids are a risk factor only in presence of NSAIDs -Stress being re-examined -New data suggesting that SSRIs are risk factors

PUD - Epidemiology

Incidence has declined in parallel with the decline in H pylori infection -improved sanitary conditions -safety of food and water supply Prevalence in population studies -4.1% in Danish population -2.9% in a prospective Danish cohort -3.6% in Shanghai Significant decline in mortality from PUD in all groups except older adults

In whom do we need to confirm eradication?

MALT lymphoma Family history of gastric cancer Personal history of gastric cancer Complicated peptic-ulcer disease Maybe in low-risk groups (everyone) now? ___________ Currently only testing if have symptoms/ diseases associated with HP Someone with GERD- not checking HP -either not doing anything for it or even helping it

H pylori - the good, the bad, and the ugly

May be protective against: -Reflux symptoms -Barrett esophagus -Atopic diseases (eczema, asthma, allergic rhinitis/conjunctivitis) Definite risk factor for: -Gastric cancer -Atrophic gastritis -Peptic ulcer disease Association with immune thrombocytopenia purpura and iron deficiency anemia? _______ Why not screen whole world and get rid of it? Some protective -protective against distal esophageal acid exposure Sometimes if treat get reflex acidity

Helicobacter pylori

Most common cause of ulcers in this country Over 50% of the world's population is infected Genetic sequence analysis indicates that humans have been infected as far back as 58,000 years ago when migrating from Africa More common acquisition at a young age and in developing countries In US - more common in blacks than in whites

Conditions arising from infection of HP

Most common presentation is asymptomatic Non-ulcer dyspepsia Gastritis Peptic ulcer disease Gastric adenocarcinoma Lymphoma of gastric mucosa-associated lymphoid tissue (MALT)

Cross section of gastric gland

Mucous cells in the gastric pits secrete mucus Parietal cells secrete hydrochloric acid G cells, which are present predominantly in the antrum of the stomach, secrete gastrin ECL cells secrete histamine Chief cells secrete pepsinogen

Regulation of gastric acid secretion at the cellular level

Parietal cell is biggest driver of acid secretion in stomach -biggest driver of ulcer disease 3 major stimuli to turn on pump 1. Histamine (ECL cells) 2. Gastrin (from G cell of antrum; direct or via ECL cell to secrete histamine) 3. Neural/vagal Ach D cell down regulates via somatostatin

HP Diagnosis

Serologies - IgG (? IgA) -phased out Urea breath test (blow into machine and detect urease bacteria) Stool antigen Biopsy (histology or CLO test) Latter 3 for active infection and can be used to confirm eradication

components involved in providing gastroduodenal mucosal defense and repair

Several factors helping/ preventing ulcers Mucus and bicarb, phospholipids Epithelial protective mechanisms -growth factors and prostaglandins; turning over cells keeps from over exposure Blood flow- bringing nutrients Role of immune system; WBCs repairing damage ________ Protective: Bicarbonate Mucus Blood flow Growth factors Cell renewal Prostaglandins Harmful: H+ Pepsins Smoking Ischemia NSAIDs H pylori

Trends in Peptic Ulcer Disease

Sharp decline in ulcer disease Gastric and duodenal ulcers -treated the same basically; don't have to differentiate that much Sharp decrease in duodenal ulcers (more associated with HP), less so in gastric ulcers Rise in reflux disease -HP potentially protective for reflux

Endoscopic Therapy

Treating PUD endoscopically -epinephrine/alcohol -electrocautery coagulation (thermal) -hemoclip ligation (mechanical)

ULCER definition

break in the lining of the mucosa with appreciable depth at endoscopy or histologic evidence of involvement of the submucosa

Colonization and virulence factors for HP

Urease helps the organism adapt to the gastric milieu, as it retains optimal function at two different pH values (usually pH 7.2 and pH 3) H pylori shows a strict tropism for the gastric mucosa or intestinal sites in which there is gastric metaplasia Lewis (Le) antigens expressed by host cells serve as a receptor for bacterial binding _______ pH in stomach is usually 2 or 3; sometimes 1 How does it survive? -makes urease; hydrolysis of urea- microenvironment that is more alkaline -bubble of pH around 7 Strictly in gastric mucosa- not colon/ intestine

Ways H pilori can cause disease

Ways H pilori can cause disease More than half the world exposed or has HP In west mostly antral predominant insolvent -effecting G & D cells (more down regulation of D cells) --increased gastrin relatively --more HCl from parietal cells, more acidic -> ulcers In far East- body predominant gastritis -inflammation of parietal cells; decreased acidity -> can lead to intestinal metaplasia (dysplasia and cancer) -also have less intrinsic factor, B12 deficiency (associated with these gastric cancers) Can also have nonatrophic affecting whole stomach -generally asymptomatic -can lead to lymphoma- example of a cancer correlated with infection -can treat the cancer by treating the HP

Surgical therapy for ulcers

peptic ulcer disease -vagotomy -pyloroplasty -antrectomy gastric outlet obstruction -vagotomy --with pyloroplasty --with gastrojejunostomy gastrinoma -removal (usually pancreaticoduodenectomy)

PEPTIC ULCER DISEASE definition

used broadly to include ulcerations and erosions in the stomach and duodenum from a number of causes -pepsin, which is proteolytic in acidic solution, plays a major role in causing mucosal breaks regardless of the inciting agent -Helicobacter pylori, aspirin, and nonsteroidal anti-inflammatory drugs (NSAIDs) ___________ Ulcers & erosions -both have break in epithelium -more depth with ulcers -both under PUD Much more driven by acid than pepsin