11-8 (1,2) Non-Neoplastic Gastric

Front 1

Stomach Gross anatamy

Back 1

Top to bottom:
-Cardia
-Fundus
-Body
-Antrum
-Pyloris
folds = Rugae

Front 2

Stomach Epithelium

Back 2

-same in all compartments
-tall simple columnar w/ deep pits:
Superficial Part-Foveolar compartment
Deep part-Glandular compartment w/ gastric glands

Front 3

Stomach Glands

Back 3

Vary by part:
Cardia - Mucous
Fundus/Body - Parietal(acid), Chief(pepsin)
Antrium/Pylorus - mucous, G cells(gastrin)

Front 4

Helicobacter Pylori Basics

Back 4

Gram(-) spiral Rod
Seen on Silver Stain

Front 5

H Pylori, where it lives

Back 5

lives in layer of mucus on GASTRIC FOVEOLAR cells only
-concentrates at intracell jxns(more urea)
Adaptation to gastric:
1.bind to foveolar epithelial cells and gastric mucin
2.synthesize urease → degrade urea → ammonia → buffers local pH

Front 6

H pylori pathogenesis

Back 6

make these injurious molecules:
1.Proteases->degrades mucous barrier->indirect epithelial cell injury
2.ammonia-> direct epithelial cell injury
3.cytotoxins-> direct epithelial cell injury

Front 7

H Pylori Natural History

Back 7

epithelial cell injury →:
1.acute inflammation → acute gastritis
2.chronic inflammation → chronic gastritis
3.necrosis → peptic ulcer disease
4.chronic inflammation → gastric lymphomas, ?(gastric adenoCA)

Front 8

Gastritis (def/etiology)

Back 8

Inflammation associated with mucosal injury
Etiology:
-infection
-autoimmune processes
-hypersensitivity

Front 9

Gastropathy (def/etiology)

Back 9

Epithelial cell damage and regeneration without associated inflammation
Etiology:
-irritants
-bile reflux
-hypovolemia
-congestion

Front 10

Gastric injury presentation

Back 10

-Dyspepsia “Stomach ache”
-Nausea and vomiting
-Weight loss
-Hypertrophic gastropathy(diarrhea, severe protein loss)

Front 11

Gastric injury Tests

Back 11

endoscopy w/ Biopsy is ultimate
Others:
-Serum anti-parietal and anti-intrinsic factor antibodies(autoimmune)
-Vitamin B12 level
-Serum gastrin
-Helicobacter pylori testing(serology, rapid urease test)

Front 12

Acute Gastritis Definition

Back 12

Acute inflammation of mucosa (PMNs)
can →:
-necrosis (erosion)
-hemorrhage

Front 13

Acute Gastritis Etiology

Back 13

Lots:
-Drugs(NSAIDs, CA chemo.)
-Complication of other diseases(uremia, infections)
- Mucosal hypoxia (shock, trauma, burns, surgery) = ‘Stress’

Front 14

Acute Gastritis Pathogenesis

Back 14

Causative agents:
1. Directly injure gastric mucosa
2. (and/or) interfere with normal gastric protective mechanisms(e.g. mucus prod., prostaglandin level, epithelial repair, intramural pH)
->Gastric contents injure unprotected gastric mucosa
->Acute inflammatory response

Front 15

Acute Gastritis Gross/histopathology

Back 15

-Acute inflammation(neutrophils)
-Patchy mucosal necrosis (erosions)
-Petechial hemorrhage

(Rarely confirmed by biopsy since profuse hemorrhage may occur at the biopsy site.)

Front 16

Chronic Gastritis Etiology

Back 16

1.Infectious : Helicobacter pylori
2.Autoimmune
3.Other (gastric surgery)

Front 17

Chronic Gastritis Pathogenesis

Back 17

Etiology (X)
->chronic inflammatory cells(lymphocytes, plasma cells, macs)
->cell and humoral mediated immune responses(T-cells)
->epithelial cell necrosis:
can → atrophy(glands and eventually mucosa)
can → intestinal metaplasia(which can progress to dysplasia → cancer)

Front 18

Chronic Gastritis Gross

Back 18

thin, atrophic gastric wall

Front 19

Chronic Gastritis Histopath

Back 19

chronic inflammation
+/- gastric gland and mucosal atrophy
+/- intestinal metaplasia(Goblet cells & brush border

Front 20

Autoimmune Chronic Gastritis Inheritance

Back 20

Autosomal Dominant

Front 21

Autoimmune Chronic Gastritis basic pathogenesis

Back 21

autoAb to Parietal Cell proteins(IF, etc) (BODY/FUNDUS)
->cell-mediated destruction of Parietal Cells(lymphocytes, cytotox Tcells)
->loss of Parietal Cells:
can → atrophy of glands/mucosa, ↓ HCl, ↓ IF (intrinsic factor)

Front 22

Autoimmune Chronic Gastritis pathogenesis-results of less parietal cells:

Back 22

1: ↓ Acid production(hypochlorhidria or achlorhidria)
->Loss of negative feedback on G cells in antrum
->Hyperplasia of antral G(G cells are neuroendocrine cells which secrete gastrin)
2:Atrophy of gastric glands(body, fundus)
3:↓Intrinsic factor
->↓ B12 absorption
->Anemia(When anemia is present, disease is re-named Pernicious anemia)

Front 23

Ulcer Definition

Back 23

A defect in the mucosal surface penetrating through the muscularis mucosa

Front 24

Ulcer Epidemiology

Back 24

-mortality goes up over age 65
-Hospitilazations for Gastric Ulcers has gone up with more incedence of bleeding(from more NSAID use)

Front 25

Ulcer pathophysiology

Back 25

-Balance b/w aggressive and Defensive factors
-H. pylori
-NSAIDs
-Hypersecretory states
-Genetic & environmental

Front 26

Ulcer Aggressive Factors

Back 26

H. pylori
NSAIDs
Radiation
Gastric acid/Bile
Alcohol
Smoking

Front 27

Ulcer Defensive Factors

Back 27

Mucus barrier
Cellular resistance
Mucosal blood flow
HCO3 secretion
Prostaglandins

Front 28

Mucus Barrier

Back 28

-Secreted by superficial mucus cells
-Stomach and duodenum
-15% Glycoprotein and 85% water
-Relatively impermeable to pepsin
-Hydrogen ions flow relatively freely
-pH=2 out of mucus, =7 at cells in mucus

Front 29

Mucus Barrier Stim/Inhib

Back 29

Stimulants:
-Cephalic-vagal stage
-Cholinergic agonists
-Prostaglandins
-Bacterial Toxins

Inhibitors:
-Anticholinergics
-NSAIDs

Front 30

Cellular Resistance

Back 30

Mucosal restitution(rapid migration of mucus cells to cover:
-Minutes
-No cell division required
-Maintain intracellular pH

Regeneration(new epith cells:
-Days
-Requires cell division

Front 31

Mucosal blood flow

Back 31

-Delivers oxygen, nutrients, & bicarbonate
-Removes back diffused acid
-If reduced by more than 50%, mucosa is vulnerable

Front 32

Bicarbonate Secretion

Back 32

-Secreted by surface mucus cells
-Maintains pH gradient
(1-2 in lumen, 6-7 at epithelial surface)
-Pepsin is inactive at pH 5

Front 33

Prostaglandins

Back 33

-Stimulate mucous and bicarb secretion
-Increase mucosal blood flow
-Inhibit acid secretion

Cyclooxygenase
-Rate limiting catalytic step in arachadonic acid to prostaglandins conversion
-COX 1--constitutively expressed
-COX 2-- inducible

Front 34

Peptic Ulcer Disease Definition

Back 34

Chronic ulcers (necrosis extending below mucosa) in GI tract regions exposed to pepsin-acid lumenal contents (stomach, duodenum > other areas)

Front 35

PUD Etiology

Back 35

-H. pylori
-NSAIDs
-↑ gastric acid (including Zollinger-Ellison)

Front 36

PUD Pathogenesis

Back 36

H. pylori or ↑ gastric acid or NSAIDs
->epithelial cell necrosis

Front 37

PUD Gross Pathology

Back 37

-Single (usually)
-‘Punched out', 'cookie cutter' i.e. clean/smooth base and perpendicular/overhanging sides, flat margins
-Stomach : lesser curvature of antrum, prepylorus
-Duodenum : proximal

Front 38

PUD Histopathology

Back 38

Four characteristic zones outter to inner:
-Fibrinopurulent exudate
-Necrotic tissue
-Granulation tissue
-Fibrotic tissue

Front 39

NSAID mechanism of injury

Back 39

can still cause ulcers even if given by IV

Front 40

PUD clinical features

Back 40

-Abdominal pain-60% sensitive finding
•Burning
•Epigastric
•Postprandial and nocturnal
•Relieved or exacerbated with food or medication
-Bleeding
-Perforation
-Obstruction

Front 41

PUD diagnosis

Back 41

-Endoscopy
-radiography (Ba swallowa)

Front 42

PUD treatment

Back 42

-Medical therapy
-Endoscopy for acute bleeding
-Surgery for refractory bleeding and complications

Front 43

PUD medical therapy

Back 43

-Acid Reduction(Proton Pump Inhibitor for 8 weeks)
-Antibiotic Therapy for HPylori positive patients(prevents ulcer recurrence in > 90%)
-Reduce/discontinue NSAIDs
-Smoking cessation

Front 44

Zollinger-Ellison syndrome (ZE) definition

Back 44

Triad:
-severe ulcer disease
-gastric acid hypersecretion
-non-β islet cell tumors of the pancreas

Front 45

Zollinger-Ellison syndrome (ZE) underlying cause

Back 45

-Gastrinoma (often in pancreas) causing ↑ gastric HCl secretion, which leads to severe peptic ulceration.
-uncommon cause of peptic ulcers.

Front 46

PUD complications

Back 46

1.Hemorrhage
-Common
-Ranges from occult to severe

2.Perforation
-Uncommon in stomach (more common in duodenum)
-Causes peritonitis

3.Obstruction
-Especially in pylorus → gastric outlet... obstruction
-Arises from edema, scar contraction, muscle hypertrophy, of nearby ulcer

Front 47

Gastrinomas Epidemiology

Back 47

-True incidence not known
-Responsible for 0.1-1.0% of all DU
-Responsible for 1 in 50 recurrence after surgery
-Sporadic (75%)
-MEN I(mult endocrine neoplasia) (25%)
1.pituitary, parathyroid, pancreas (3P’s)
2.autosomal dominant
3.chromosome 11q

Front 48

Gastrinomas Symptoms

Back 48

-Peptic Ulcer Disease
(multiple, refractory, recurrent)
-Gastroesophageal Reflux
-Diarrhea(malabsorption)

Front 49

Gastrinomas Diagnosis

Back 49

-Basal Acid Output (BAO) > 15 meq/h
-BAO/MAO > 6
-Fasting gastrin >1000 pg/ml
.gastric pH < 3
.No further work up necessary
-Fasting gastrin 100-999 pg/ml
.Secretin Stimulation Test
.Gastrin level increase > 200 pg/ml

Front 50

Gastrinoma Provacotive test

Back 50

Secretin Test:
-Secretin directly activates the secretin receptor expressed on gastrinoma cells
-This receptor is not found on antral G cells
-Secretin is infused IV
-Serum collected for gastrin measurement 10 minutes and 1 minute prior to infusion and at 2, 5, 10, 15, 20 and 30 minutes post infusion
-With gastrinoma see rise within 15 minutes of infusion
-Rise of 200 pg/ml or more positive test

Front 51

Gastrinomas causes of chronic hypergastrinemia

Back 51

Low Gastric Acid:
-pernicious anemia
-chronic atrophic gastritis
-pharmacological

High Gastric Acid:
-ZES
-antral hyperplasia
-chronic renal failure
-short bowel syndrome
-gastric outlet obstruction

Front 52

Gastrinoma location

Back 52

-85% occur in gastrinoma triangle
.medially head and body of pancreas
.inferiorly 2nd and 3rd portion of duodenum
.superiorly junction of cystic duct and common bile duct
-Multiple in more than half
-Size can range from 0.1-20 cm
-Malignant in 50-90%
.mets to lymph nodes and liver
.40% will have metastatic disease at time of dx

Front 53

Gastrinoma Localization

Back 53

-CT scan
-Endoscopic Ultrasound
-Nuclear Scan (SRS)
-Exploratory laparotomy

Front 54

Gastrinoma Treatment

Back 54

-Proton Pump Inhibitors
-Surgery
-Chemotherapy