Date of Award


Document Type


Degree Name

Master of Science (MS)


Environmental Science

First Advisor

Dr. Sherif Karam

Second Advisor

Dr. Mohamed Galal EI-Din

Third Advisor

Dr. Tharek Yousef


Stress ulcer is a common problem in critically ill patients. Recent statistics indicated that bleeding from stress ulcer is a common cause of death in patients admitted to intensive care units. Little is known about the cellular changes that occur in the gastric mucosa during stress ulcer formation. The aim of this study is to define the changes that occur in the mouse stomach during development of stress ulcer by using different microscopy techniques.

The cold-restraint mouse model of stress ulcer was used in this study. Mice of both sexes were restrained and maintained in a cold (4°C) room for 1-4 hours. The stomachs of stressed mice and their weight and sex-matched normal littermates were divided into two parts. One part of the mucosa was processed for multi-label immuno-histochemistry using antibodies specific for the gastric proton pump of the acid-secreting parietal cells, intrinsic factor of the zymogenic cells. Some tissues were processed for lectin histochemistry using tetramethylrhodamine isothiocyanate-labeled Ulex europaeus type 1 agglutinin (UEA-1) and flourescine isothiocyanate-labeled Grifforia simplifolica II (GSII) lectins as markers for pit and neck cells, respectively. Since trefoil factors (TFFs) are known to play a role in the gastric mucosal protection, the expression profiles of trefoil factors in the gastric epithelium was also studied. Antibodies specific for TFF1 (mucus-secreting pit cells), TFF2 (mucus-secreting neck cells) and TFF3 (pepsinogen/intrinsic factor-secreting zymogenic cells) were used. The other part of the stomach was processed for electron microscopy to study the ultrastructural changes that occur in the different cell lineages during stress ulcer formation.

Routine histological examination the stress-induced mouse model used in the present study developed multiple superficial gastric mucosal erosions. None of the animals examined showed any ulcer formation spanning the whole thickness of the mucosa. In addition periodic acid Schiff staining revealed an increase in the amount of mucus produced by pit cells. Lectin histochemistry confirmed that during stress, there is an enhanced mucus production mostly by pit cells lining the luminal surface and the pit regions of the epithelial units throughout the gastric mucosa. The increase in the number of mucous granules in pit cells was then demonstrated by electron microscopy. The presence of multiple granules in exocytosis explained the increased mucus at the luminal surface.

Immunohistochemistry using anti-H, K-ATPase antibody showed an over-expression of the proton pump by parietal cells which was intensified around the areas showing erosions. Electron microscopy showed that these parietal cells are not only producing much H, K-ATPase, but they are in the secretory state where tubulovesicular membranes are fused with apical and canalicular membranes to form extensive intracellular canalicular system with long microvilli. The results also showed an up-regulation in the expression of TFF1 and TFF3 suggesting a feedback mechanism for protection against mucosal injury.

In conclusion, the present study suggests that while mucus, TFF1 and TFF3, produced mainly by pit cells, play a key role in protection during stress ulcer formation, parietal cells play an aggressive role and probably contribute to the stress-induced mucosal damage. Finally, enhancing our understanding to the cellular and molecular changes that occur during stress ulcer formation would hopefully lead to an improvement in designing new therapeutic modalities and preventive strategies against stress ulcer.