Peptic Ulcer Disease

Anatomy:
1. Describe the gross anatomy and histology of the stomach and
duodenum. Describe the different anatomical structures associated
with the stomach and duodenum.
STOMACH 4 regions:

>Cardia: narrow transitional zone

bet. esophagus and stomach. Mucus
production
>Pylorus: opens to small intestine.
Mucus production
>Fundus and Body: Site of gastric
glands in gastric pits
~Rugae: Longitudinal folds that
flatten when stomach fills with food

4 layers of stomach in all the regions:

>Mucosa: contains gastric pits that secrete mucous layer rich in HCO3-.In the
fundus and body, gastric glands contain mucous neck cells, chief cells
(contains pepsinogen that activates in acidic environment of stomach),
enteroendocrine cells (secretes serotonin; in pylorus it secretes gastrin)
parietal cells (which secretes HCl and intrinsic factor, a glycoprotein uptake
for Vit. B12 in small intestine). Parietal cell activity is stimulated by
parasympha and paracrine release of histamine and gastrin from
enteroendocrine cells. Cardiac and pyloric glands lack parietal and chief cells
secretes only mucus.
>Submucosa: Connective tissue with large blood and lymph vessels, mast
cells
>Muscularis: smooth muscle layer; outer longitudinal, middle circular, inner
oblique. Contraction mix chyme with HCl and enzymes. At pylorus middle
layer thickened to form pyloric sphincter
>Serosa: outer covering
DUODENUM:
>Mucosa: with villi which contains enterocytes (absorptive cells covered by
glycocalyx with microvilli) with interspersed goblet cells (secrete mucin).
Paneth cells (innate immunity) secrete defensins thst break membrane of
bacterial cell walls.
>Submucosa: with Meissner nerve plexus. Proximal part of duodenum
contains Brunner glands (alkaline mucus) for optimum pH of pancreatic
enzyme.
>Muscularis: Myenteric nerve plexus which produce peristalsis

2 Describe the components of the three (3) levels of the gastroduodenal

mucosal defense system or barrier.
1 line of defense: mucus-bicarbonate-phospholipid layer
st

 thick layer of mucus gel into which bicarbonate is secreted by the

underlying epithelial cells.
 sustains a pH gradient between the lumen and cell surface such that
epithelial cells are maintained at pH 7 to 8, despite the presence of
intraluminal acid

2 line of defense: surface epithelial cells

nd

 this mechanism may be important in maintaining mucosal integrity

(since the pH gradient may be overwhelmed by physiologic
concentrations of intraluminal acid)
 The physical properties of the apical cell membrane and intercellular
junctions and the presence of surface-active phospholipids on the
membrane may be responsible for preventing hydrogen ions (H+) from
diffusing into the mucosa by providing a physical barrier to their
movement

3 line of defense: Continuous cell renewal from mucosal

rd

progenitor cells
 maintains structural integrity of the mucosa.
 a thick layer of mucus containing sloughed epithelial cells together with
passive movement of bicarbonate-rich fluid from the damaged mucosa.
 this may prevent exposure of undamaged cell nests to acid and thus
aid re-epithelialization
Physiology and Biochemistry:
1. Discuss the functions of the three (3) levels of the gastroduodenal
mucosal defense. Discuss the different factors that affect the function
of each of these levels.
1. Mucus-bicarbonate -phospholipid layer (Preepithelial)
 Physicochemical barrier to multiple molecules, including
hydrogen ions
 Mucous gel - functions as a non-stirred water layer impeding
diffustion of ions and molecules such as pepsin
 dissipation of this layer by ulcerogenic substances (such as
aspirin and bile salts) leads to both acid back-diffusion and
mucosal injury
 The efficacy of protective properties of the mucus barrier
depends on the gel structure and on the amount or thickness of
the layer
 between epithelium and lumen

2. Surface epithelial cells

 Secretes mucus and bicarbonate
 main role:
o maintain a selective exchange of different substances
(secretions, nutrients, etc.) between these lumen &
internal compartments,
 o assure the protection of the organism against the
penetration of micro-organisms and other exogenous
antigens

3. Cell renewal
 Cell renewal from mucosal progenitor cells is stimulated by
growth factors

2. Discuss what gastric acid (HCl) is and how is it produced. Discuss how
its production is controlled or regulated.

HCl is the main component produced by parietal cells. It is necessary

to activate pepsinogens into pepsins which also activates when it
comes into contact with previous pepsin. It is stimulated by gastrin (via
vagus nerve that signals gastrin cells in antral mucosa), histamine (a
cofactor where whenever ACh and gastrin stimulate parietal cells
together, histamine enhances secretion). Inhibition is due to excess
acid in the stomach (when it falls pH < 3; (a) high acidity releases
somatostatin which depresses gastrin secretion by G cells and (b) acid
causes an inhibitory nervous reflex that inhibits gastric secretion).
Secretin also inhibits it as well as enterogastric reflex (presence of food
in small intestine signals enteric nervous system and thru sympathetic
and vagus nerves).

INFORMATION REGARDING PEPTIC ULCER DISEASE

Normal Physiology of the Stomach:

The degree of protection of G.I. tract from gastric juices is afforded by:

First defense: Gastroduodenal Mucosal Barrier

All areas normally exposed to gastric juice are well supplied with mucous
glands:
Supplier of Mucus: G.I. Part Supplied:
Compound Mucus Glands- Lower Esophagus
Mucous Cell-Coating of Stomach Mucosa- Stomach
Mucous neck cells of Gastric Glands- Stomach
Deep Pyloric Glands- Stomach
Glands of Brunner- Upper Duodenum
(secrete highly alkaline mucus)

Second defense: Neutralization of the gastric acid by duodenal juices

Duodenum is protected by:
1. Pancreatic secretions (contains a high amount of sodium bicarbonate)
>Neutralizes HCl from stomach
>Inactivates pepsin thus preventing the digestion of the mucosa
2. Brunner Glands (first few cm of duodenum)- also secretes bicarbonate
ions
3. Bile from liver
*other protective factors prostaglandins, mucosal blood flow, and growth factors

Two feedback control mechanisms normally ensure that this neutralization of

gastric juices is complete, as follows:
 1. Excess acid in duodenum→ Inhibit stomach gastric secretion and
peristalsis via nervous reflexes and hormonal feedback of duodenum→
Decrease gastric emptying rate
2. Excess acid in small intestine→ Liberate secretin from intestinal
mucosa→Stimulates pancreas to release pancreatic juice→acid
neutralization

Peptic Ulcer is a lesion of the gastric or duodenal mucosa

■Sites: (*= frequent)
>Few cm of plylorus* >lesser curvature of the antral end of stomach*
>Lower end of esophagus (where stomach juices frequently reflux)
■   can occur when there is loss of the protective mucous barrier (of mucus
and HCO3−) and/or excessive secretion of H+ and pepsin.
■   Damaging factors are H+, pepsin, Helicobacter pylori (H. pylori),
nonsteroidal antiinflammatory drugs (NSAIDs), stress, smoking, and alcohol.

Causes of Peptic Ulcer:

Basic Cause of Ulceration: Imbalance between rate of secretion of gastric
juice, and degree of protection afforded by
o gastroduodenal mucosal barrier and
o neutralization of gastric acid by duodenal juices

Main cause: Helicobacter pylori infection

> Burrows thru mucosal barrier→ releases ammonium→ liquefies the
barrier→ stimulates HCl secretion→ strong acidic digestive juices of the
stomach secretions penetrate into the underlying epithelium→ digest the
gastrointestinal wall→ peptic ulceration

Other Causes of Ulceration:

(1) smoking→ increased nervous stimulation of the stomach secretory glands
(2) alcohol→ break down the mucosal barrier
(3) NSAIDs→ strong propensity for breaking down barrier
(4) Severe chronic anxiety→ High gastric secretion rates than normal

Treatment of Peptic Ulcers.

(1) use of antibiotics along with other agents to kill infectious bacteria
(2) Discontinue NSAIDS and smoking may interfere with healing
(2) administration Drugs that block gastric H+ secretion (acid
suppression)

a. Atropine
   blocks H+ secretion by inhibiting cholinergic muscarinic receptors on
parietal cells, thereby inhibiting ACh stimulation of H+ secretion.

b. Cimetidine/Ranitidine
   blocks H2 receptors and thereby inhibits histamine stimulation of H+
secretion.
  is particularly effective in reducing H+ secretion because it not only
blocks the histamine stimulation of H+ secretion but also blocks
histamine's potentiation of ACh effects.

c. Omeprazole
 is a proton pump inhibitor.
  directly inhibits H+, K+-AT

Types of Peptic Ulcer:

1. Gastric ulcer (GU)
■Location: Stomach
■Principal Cause: H. pylori
■Other causes: NSAIDs/Chronic salicylate (irritant; account for 15-30%
of GU)
■Gastric H+ secretroty rates: Normal or reduced because secreted H+
leaks back through the damaged gastric mucosa
 ■Gastrin levels: increased because decreased H+ secretion stimulates
gastrin secretion.
■ H. pylori colonizes the gastric mucus and releases cytotoxins that
damage the gastric mucosa. Contains urease, which converts urea to
NH3, thus alkalinizing the local environment and permitting H. pylori to
survive in the otherwise acidic gastric lumen.
■Clinical Features:
> Burning epigastric pain made worse by or unrelated to food >
Anorexia > Food aversion > Weight loss (in 40%). Similar symptoms in nonulcer
dyspepsia
■Diagnosis:
>Drinking a solution of 13C-urea, which is converted to 13CO2 by
urease and measured in the expired air (Urea Breath Test)
>Upper endoscopy preferable to exclude possibility that ulcer is
malignant(brush cytology, ≥6 pinch biopsies of ulcer margin)
>Radiographic features (if there’s air it may suggest ulcer) suggesting
malignancy
>ulcer within a mass, folds that do not radiate from ulcer margin, a
large ulcer (>2.5–3 cm).
■Gastritis due to reflux of duodenal contents (including bile) may play a
role.
■Pagkakaintindi ko: ‘Di gusto kumain kasi kapag kumain stomach will
secrete HCl and pepsin na mas lalong sisira sa mucosa sa stomach na
may ulcer so more pain pag kumain so mas gugustuhin na di kumain

2. Duodenal Ulcer (DU)

■Location: Duodenal bulb (initial portion)
■Principal Cause: H. pylori, inhibits somatostatin secretion (thus
stimulating gastric H+ secretion) and inhibits intestinal HCO3−
secretion (so there is insufficient HCO3− to neutralize the H+ load from
the stomach).
■Other causes: glucocorticoids, NSAIDs, chronic renal failure
cirrhosis, chronic lung disease
■Gastric H+ secretroty rates: Mild gastric acid hypersecretion (2x as
normal), excess H+ is delivered to the duodenum, damaging the
duodenal mucosa.
■Gastrin level: Baseline is normal; increases in response to a meal
■Clinical Features:
>Burning epigastric pain 90 min to 3 h after meals > Nocturnal (11
pm-2 am)
> Relieved by alkali or food
■Diagnosis:
>Upper endoscopy or upper GI barium radiography

■Mild gastric acid hypersecretion resulting from:

(1) increased release of gastrin (stimulates acid secretion)
>due to H. plyori infection (gram-negative) which causes:
(a) stimulation of antral G cells by cytokines released by
inflammatory cells
(b) diminished production of somatostatin (inhibits acid
secretion by D cells
 (2) Exaggerated acid response to gastrin due to an increased
parietal cell mass (parietal cell secretes HCl) resulting from
gastrin stimulation.
■Pagkakaintindi ko: Since nasira na ‘yong mucosa ng duodenum so ‘di
masyadong makakaabsorb ng nutrients hence after 3 hrs gutom ka
kaagad so pagkarating ng food sa duodenum magkakaroon ng
hypersecretion dahil nga sa H. pylori so mas lalong masisira yung
mucosa ng duodenum lalong di makakaabsorb ng nutrients.

Complications of BOTH types:

>Bleeding (if it erodes gastric arteries) and perforation (increased risk in GU

due to NSAID)
>Obstruction
>Penetration causing acute pancreatitis
>Intractability