Potential Long-term Consequences of

H. pylori Infection
H. pylori infection

Weeks-moths

Chronic superficial
gastritis

Years-decades

Peptic ulcer Chronic superficial Lymphoproliferative Chronic atrophic

disease gastritis disease gastritis

Gastric
adenocarcinoma
 Risk Factors for NSAIDs Induced
Gastroduodenal Ulceration

Established Possible
Advanced age Concomitant infection with
History of ulcer H. pylori
Concomitant use of glucocorticoids Cigarette smoking
High-dose NSAIDs Alcohol consumption
Multiple NSAIDs
Concomitant use of anticoagulants
Serious or multisystem disease
 Disorders Associated with Peptic
Ulcer Disease

Strong association Possible association

Syatemic mastocytosis
Chronic pulmonary disease
Chronic renal failure
Cirrhosis
Nephrolithiasis
 Antitrypsin deficiency
Hyperparathyroidism
Coronary artery disease
Polycythemia vera
Chronic pancreatitis
 Reported Pathophysiologic Abnormalities
in Patients with Duodenal Ulcers

Abnormality Approximate Frequency, %

 Nocturnal acid secretion 70
 Duodenal HCO3 secretion 70
 Duodenal acid load 65
 Daytime acid secretion 50
 Pentagastrin-stimulated MAO 40
 Gastrin sensitivity 35-40
 Basal gastrin 35-40
 Gastric emptying 30
 pH inhibition of gastrin release 25
 postprandial gastrin release 25

NOTE : MAO, maximal acid output

 RISK FACTORS FOR H. pylori
INFECTION

Birth or residence in developing country

Low socioeconomic status
Domestic crowding
Unsanitary living conditions
Unclean food or water
Exposure to gastric contents of infected individual
 REGULATION OF GASTRIC ACID
SECRETION AT THE CELLULAR LEVEL
Parietal cell FUNDUS
Vagus

Acetylcholine
Cannaliculus
Histamine
 
H, K ATPase ECL cell
 Tubulovesicles
Histamine –
 – –
ECL cell Somatostatin
Somatostatin
Gastrin D cell


Blood vessel ANTRUM

Gastrin
G cell
D cell –
Somatostatin
SCHEMATIC REPRESENTATION OF THE STEPS INVOLVED
IN SYNTHESIS OF PROSTAGLANDIN E2(PGE2) AND
PROSTACYCLIN (PGI2)
Membrane phospholipids

Phospholipase A2

Arachidonic acid

Stomach Macrophages
Kidney COX-1 COX-2 Leukocytes
Platelets housekeeping inflammation Fibroblasts
Endhothelium Endothelium

TXA2, PGI2, PGE2 PGI2, PGE2

Gastrointestinal mucosal integrity Inflammation
Platelet aggregation Mitogenesis
Renal function Bone formation
Other functions?
 H. pylori-induced inflammation
and inflammatory cytokine IL-8
H. pylori
Epithelial cell
LAP
NAP Tissue injury

Oxygen radicals
IL-1
TNF IL-8 Activation
Macrophage Neutrophil
Chemotaxis

Transmigration

Adhesion

Venule
 CONDITIONS ASSOCIATED WITH
PEPTIC ULCER

None known None known

NSAID ZE, other ZE, other
use NSAID
use

H. pylori H. pylori
infection infection

Duodenal Gastric
 Physiologic Functions of Gastric
Exocrine Secretions
PRODUCT FUNCTION
Hydrochloric acid Provides optimal pH for pepsin and gastric lipase
(see below)
Facilitates duodenal inorganic iron absorption
Negative feedback of gastrin release
Stimulation of pancreatic HCO3- secretion
Supression of ingested microorganisms
Pepsins Early hydrolysis of dietary proteins
Liberation of vitamin B12 from dietary protein
Gastric lipase Early hydrolysis of dietary triglyceride
Intrinsic factor Binding of vitamin B12 for subsequentileal ab-
sorption
Mucin/HCO3- Protection against noxious agents
 Exocrine Cells within Gastric Glands and
Their Secretory Products*,†
GLAND EXOCRINE
AREA CELLS
% OF ANATOMIC WITHIN SECRETORY
TOTAL COUNTERPART GLANDS PRODUCTS
Cardiac Proximal stomach Mucus neck Mucin, PGII
(<5%) just below esoph-
agogastric junc-
tion
Oxyntic Fundus and body Mucus neck Mucin, PGI and
(75%) PGII‡
Chief PGI and PGII, ‡
leptin
Parietal HCI, intrinsic
factor§
Pyloric Antrum and pylorus Mucus neck Mucin, PGII

*Pepsinogen I (PGI), includes Pg 1-5; PGII includes Pg6 and Pg7.

†Endocrine cells are also present within glands
‡PGI and PGII are colocalized in zymogen granules and are secreted concurectly
§Some intrinsic factor may also be produced in chief cells and endocrine cells