Patho Exam 2 Upper GI

• Gastric Acid
• H. pylori
• NSAIDS
• Pepsin

• Prostaglandins
• Mucus
• Bicarbonate
• Blood flow to mucosa

Group of upper GI tract ulcerative disorders that develop whne GI tract is exposed to acid and pepsin secretions

• Imbalance in aggressive and protective factors
• - Increased gastric acidity (Oversecretion)
• - Decreased prostaglandin production (NSAIDS)
• - Interference with mucous layer (H. pylori infection)

Increased histamine secretion

Released in response to damage done to organ wall

• Increased pepsin and acid secretion (causing injury)
• Local vasodilation (increasing capillary permeability- resulting in mucosal edema)

Produces urea-splitting enzyme called urease, which breaks up urea into ammonia and bicarbonate forming a cloud

• Peptic ulcer
• Chronic gastritis
• some Stomach cancers

• H. pylori secretes protease
• Breaks through mucosal gel barrier
• Colonizes mucosa
• Triggers inflammatory response
• Activation of inflammatory mediators

Resulting in: Inflammation-based Damage

Inflammation response

• Advanced age r/t higher does longer
• Higher doses of NSAIDS
• Concomitant use of corticosteroids and anticoagulants (harm GI tract)
• Serious systemic disorders (chronic comorbidities)
• H. pylori infection

Enzyme responsible for production of important biological mediators

• Protects the GI tract
• produces gastric prostaglandins- PGE

therefore NSAIDS harm the GI tract inhibiting production of PGE

Proinflammatory- causing pain

therefore NSAIDS inhibit pain and inflammation (why we take them)

Younger

• Age 55 to 70
• High doses of NSAIDS

• Superficial damage to mucosa and submucosa layers
• known as "stress ulcers"

• Penetration into muscle layer
• if it eats through vascular- more bleeding

• Approaching penetration of the wall
• at this point- through the muscular and deep, it hurts

• Asymptomatic until deeper
• N/V, anorexia
• Weight loss r/t not eating from fear of inflammation
• Bleeding (Hematemesis or melena)
• Pain

• Burning, chewing pain
• Located in the epigastric and back
• Gastric- 1 to 2 hrs following meals
• Duodenal- 2 to 4 hrs following meals
• Relief: antacids and sometimes eating (seen as a buffer)

• Hemorrhage
• Obstruction
• Perforation and Peritonitis

• Bleeding granulation tissue (which sweeps away granulation tissue which could heal the ulcer)
• Further erosion

• Edema
• Spasm
• Contraction of scar tissue

Can interfere with passage of GI contents (causing symptoms) (as the scar tissue develops it strinks causing smaller passageways)

Erosion through all layers of tract ex. GI contents through peritoneum causing peritonitis or can attach to other organs causing damage from gastric juices

• Curling ulcer
• Cushing ulcer
• painless upper GI bleed
• Melena

• Cause: physiologic stress- seen in critical care, top priority (must be corrected within 24 hours)
• It is the shunting of blood
• GI tissue becomes ischemia resulting in tissue acidosis

• Cause: Increased intracranial pressure
• More severe than curling ulcer
• Compromised brain causes hypersecretion of gastric acid

• Backflow (reflux) of gastric contents into esophagus
• due to weakened or incompetent valve or physiological (feeding or NG tube)

• Transient relaxation of esophagus
• Reflux (from increased gastric volume and increased gastric/ abdominal pressure)
• Esophageal mucosal exposure to gastric refluxate
• Symptoms of GERD

• Rapid Neutralization
• esophageal peristalsis
• salivary bicarbonate

• Reflux esophagitis
• mucosal injury
• hyperemia (increased blood to organ)
• inflammation

• Increased exposure time
• Highly acidic refluxate

• Metaplasia condition- normal stratified squamous epithelium replaced by abnormal columnar epithelium
• can result in esophageal cancer

• Onset: following meals and while lying down or bending over
• Regurgitation of "sour" material
• Atypical chest pain

Transient gastric mucosal inflammation with the introduction of gastric irritants

• Drugs or chemicals- common irritants (caffeine, NSAIDS, ETOH) and suppressed gastric PGE
• Bacterial endotoxins (food poisoning)
• H. pylori bacteria

• Exposure to Gastric Irritant
• Gastric inflammation caused by ETOH, Histamine, Metabolic disorders, and certain drugs
• Mucosal injury
• Focal or Generalized Erosion of surface epithelium (superficial)

• Anorexia (from not wanting to eat from pain)
• N/V (from pain in stomach)
• Abdominal discomfort
• Hematemesis (vomitting frank blood) and or melena (black tarry stool)

• Slow, progressive disorder (initally asymptomatic)
• Begins with superficial inflammation
• Gradually leads to destroyed functional cells

Stomach can atrophy and take on a diff appearance

Elderly

• Type A (Atrophic Gastritis)- autoimmune
• Type B (H. pylori)- slow destruction

Progressive Gastric Mucosa Degeneration from autoimmune disorder

• Loss of chief cells- decrease in pepsin (breakdown protein)
• Loss of parietal cells- decreased HCL and intrensic factor (needed to absorb B12- resulting in pernicious anemia) and increase in Gastrin

• Disappearance of gastric folds (causing smooth pale non-functional stomach)
• Visualization of submucosal blood vessels
• Total or partial loss of mucosal lining

• Chronic inflammation
• Cause: Thinning and atrophy of mucosal layer
• Resulting in decreased protection from autodigestive substances

• Asymptomatic until advanced disease
• Vague gastric distress
• Ulcer-like symptoms
• Pain from erosion
• Type A: sx of anemia, sx of vit B12 deficiency

Portion of upper stomach slips up or passes (herinates) through hiatus and into chest

• Structural Defect
• Cause: Larger than normal esophageal hiatus
• Permanent shortening of esophagus
• Abnormally loose attachment of esophagus to diaphragm

• Asymptomatic then...
• GERD-like
• Worsens with certain activities (like lying down after eating)

Combination therapy with 2 antibiotics for 2 weeks

• Increasing protective factors- antacids, sucralfate, Misoprostol
• Decresing aggressive factors- Histamine 2 blockers, proton pump inhibitor, protectants, Cholingergic-Blockers

The two drugs do the same thing, but balance out the others side effects

• Reduce acid indigestion
• Relief of Sx (heartburn, gastric distress)
• Help protect mucosal layer

Neutralizes acid through a chemical reaction in which the end product is water instead of acid

Promote gastric mucosal defense mechanisms by increasing production of protective secretions (mucous and prostaglandins)

• Acid-Base Imbalance
• Diarrhea or constipation
• Rebound hypersensitivity (symptomatic when therapy stopped)
• Chelation (binds to other drug to prevent absorption)
• Altered stomach pH (other drug cannot break up)
• Metabolic alkalosis

• Seaweed base makes it hydrophobic
• Physical buffer
• Floats on top of chyme as a protectant when backflow present

• MOA: alters when exposed to gastric acid, becomes sticky thick gel and adheres to ulcer crater as a protective barrier
• Therefore is a mucosal protectant and promotes healing

• PO- tablet or suspension
• No major SE- works locally on active ulcer
• Decreases other drugs absorption, take 2 hours apart

• PGE replacement that is lost with NSAIDS (through stimulating COX 1)
• Increases mucosal protective factors through being a synthetic PGE

Approved for gastric ulcer secondary to NSAID therapy

• Diarrhea
• Abdominal discomfort
• Contraindicated in Pregnancy (stimulates contractions)

• Histamine
• Acetylcholine (ACh)
• Gastrin
• (body preparing acids for food)

• Cimetidine (Tagamet)
• look for "-idine" endings

• Block H2 receptors
• Reduces gastric acid secretions (blocks 90% of acids being formed)

• SE: well tolerated
• Slight increased risk for pneumonia in elderly (acids are in the stomach to fight bacteria, if chyme is aspirated without acids there is a risk for bacterial infection)
• Interactions: smoking

• Proton pump
• H+ is a proton
• If the pump is stopped then histamine and other acids are blocked from releasing

• omeprazole (Prilosec)
• look for "-prazole" suffix

• Prodrug
• Blocks final production step
• PPI binds to H+/K+ ATPase
• Prevents release of HCl
• highly effective (targets exiting cells, not entering)

• Safe when taken short term
• Slight increased risk for pnemonia when aspirated gastric contents by elderly resulting in bacterial infections
• Interaction: Other PO drugs require acid pH to break down

• Limit use to 2 weeks- not permanent
• Drug of choice when H2RA (Tagament) not effective
• More expensive therefore insurance companies require proof of H2RA failure

• Prokinetic agent, antiemetic
• MOA: Stimulates gastric muscle contraction, and relaxation of pyloric and duodenal segments (helps peristalsis in the stomach)
• Does not increase secretions

• Drug effects: promotion of movement of substances through GI tract (temporarily move GI tract)
• SE: many! Sedation or restlessness, Extrapyramidal reactions (involuntar limb, facial, or eye movements)

• Short term therapy
• Check pt drug regimen therapy before initiating
• Teach regaring possible side effects