1. Discuss the pathophysiologic effect of the following factors in the causation of this patient's disease.

a. alcohol
 Alcohol concentrations greater than 10% had been shown to affect the barrier, histology, and
permeability of the barrier.
 Chronic alcoholism can cause the ff:
o Gastric metaplasia
o Altered gastric acid secretion
o Acute gastric mucosal injury
o Interference with gastric and intestinal motility
 Several studies have suggested that a decrease in prostaglandins and an increase in the
production of leukotrienes might play a role in the development of alcohol-induced mucosal
injury
 Mucosal injuries can result to chemical inflammation by:
o Macrophages and neutrophils release the cytokine IL-8, which combines with its
receptor in the endotheliocyte, and facilitate further development of the inflammation
and up-regulate the expression of adhesion molecules such as inter-cellular adhesion
molecule 1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1).
o IL-8 may interact with HP0638 to augment the adherence capacity of H. pylori and
increase the colonization density.

b. stress
 The GI system and brain are closely connected via the autonomic nervous system, namely
the brain-gut axis.
 Psychological and physical stress may affect the hypothalamic-pituitary-adrenal axis:
1. Epinephrine stimulates cell groups in the posterior hypothalamus, which stimulation is
relayed to the anterior lobe of the hypophysis.
2. This stimulation causes an increased release of ACTH or corticotrophin which in turn
causes an increased release of cortisone from the cortex of the adrenal glands.
3. Cortisone, the end product of this series of reactions, then is postulated to stimulate
directly the gastric glands, causing a hypersecretion of gastric juice and duodenal ulcer
formation.

c. hypertension
 PHG develops in response to increased resistance to portal blood flow, which occurs in
several diseases that affect the liver and/or portal circulation, and leads to complex
hemodynamic changes in the splanchnic and systemic vascular territory that can ultimately
affect function in the stomach and other organ systems.
 Patients with portal hypertension develop increased blood flow to the stomach:
o Increased cardiac output and heart rate with reduced mean arterial blood pressure
are classic manifestations of the hemodynamic changes that can be detected in
patients with cirrhosis and portal hypertension.
o PHG rarely leads to severe, acute bleeding, and is more often associated with chronic
blood loss, which leads to anemia and the requirement for multiple blood
transfusions that can have a significant and negative effect on a patient’s quality of
life.
 Reduced delivery of oxygen to the gastric mucosa, a phenomenon related to the modified
tissue architecture (vascular congestion) and blood flow regulation of the stomach and lungs
in portal hypertension, has a role in the reduced resistance of gastric mucosa to irritants in
patients with cirrhosis and portal hyper tension.
 There is also reduced basal and stimulated gastric acid secretion, a phenomenon probably
secondary to a compensatory adaptation to cirrhosis and portal hypertension.
d. smoking
 Cigarette smoking is coupled with the initiation and prolongation of gastric ulcers.
 Increased gastric acid secretion is mediated through the stimulation of H2-receptor by
histamine released after mast cell degranulation and due to the increase of the functional
parietal cell volume or secretory capacity in smokers.
 Smoking and nicotine stimulate pepsinogen secretion by increasing chief cell number or with
an enhancement of their secretory capacity. Long-term nicotine treatment in rats also
significantly decreases total mucus neck cell population and neck-cell mucus volume.
 Smoking increases bile salt reflux rate and gastric bile salt concentration thereby increasing
duodenogastric reflux that raises the risk of gastric ulcers.
 Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through
oxidative damage of the mucosa by increasing the generation of reactive oxygen
intermediates (ROI), which is potentiated by nicotine and smoking.
 Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin
level, which plays an aggressive role in the development of gastroduodenal lesions.
 Smoking increases production of platelet activating factor (PAF) and endothelin, which are
potent gastric ulcerogens.
 Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF)
and decrease the secretion of EGF from the salivary gland, which are necessary for gastric
mucosal cell renewal.
 Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby
making the mucosa susceptible to ulceration.
 Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of
nitric oxide synthesis thereby arresting cell renewal process.

e. NSAIDS
 Two ways NSAIDS affect duodenal ulcers: Topical and Systemic

1. TOPICAL
o Aspirin and many other nonsteroidal anti-inflammatory drugs are carboxylic
acids.Their pKa values range from 3.50 (aspirin) to 4.85 (ibuprofen). They are not
ionized at the acidic pH ordinarily found in the gastric lumen and thus can be absorbed
across the gastric mucosa. When these drugs move from the acidic environment of
the gastric lumen into the pH–neutral mucosa, the drugs ionize and are trapped
temporarily in gastric epithelial cells where it may damage these cells (Ion Trapping).
o NSAIDS also affect mitochondrial respiration by uncoupling of oxidative
phosphorylation leading to a depletion of ATP and therefore reduce the ability to
regulate normal cellular functions, such as the maintenance of intracellular pH.
o A third mechanism that could account for the topical irritant properties of NSAIDs is
their ability to decrease the hydrophobicity of the mucus gel layer in the stomach. The
surface of the stomach is hydrophobic and that this hydrophobicity can be reduced by
NSAIDs thru disruption of surface-active phospholipids within the mucus gel layer.

2. SYSTEMIC
o The therapeutic effects of NSAIDs are mediated by their inhibition of prostanoid
biosynthesis. Prostanoid derivatives arise from the conversion of arachidonic acid by
cyclo-oxygenase (COX) isoenzymes following cell injury.
o There are two distinct isoforms of COX. COX-1 is present in the majority of cells
including endothelial cells, gastrointestinal epithelium and platelets, and functions
continuously. COX-2 is present in only a few tissues and is induced by inflammation.
NSAIDs exert their therapeutic anti-inflammatory and analgesic effects by inhibiting
COX-2.
 o Inhibition of COX the gastrointestinal tract leads to a reduction of prostaglandin
secretion and its reduces regulation of mucus and bicarbonate secretion by the gastric
and duodenal epithelium, mucosal blood flow, epithelial cell proliferation, epithelial
restitution and mucosal immunocyte function. This therefore increases the
susceptibility to mucosal injury.

ADDITIONAL LANG HAHAHA:

Asia and Pacific islanders have the highest risk of H. pylori infection compared to all other races.
51-65 year olds have the highest frequency of H. pylori infection.