Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement), pp.

15S-29S

'The Pathophysiology of Peptic Ulcer

Disease
F.P. BROOKS, MD

Heterogeneity is the most important consideration in the pathophysiology o f peptic ulcer

disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or
perforation. I f they heal there is no predictable recurrence. Factors concerned with
mucosal defense are relatively more important than aggressive factors such as acid and
pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at
least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced
ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the
muscularis mucosae) usually present with abdominal pain. Many duodenal Ulcer patients
report that the pain occurs when the stomach is empty or is relieved by food, and follows
a pattern o f relatively long periods o f freedom from symptoms between recurrences.
Approximately 50% of patients experience a recurrence within a year if anti-ulcer
medication is stopped. In most western countries recurrent duodenal ulcer is more
common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent
evidence indicates genetic and familial factors in duodenal ulcer and increased acidpepsin secretion in response to a variety of stimuli. However, it is also becoming clear that
of all the abnormal functions noted, f e w are present in all subjects and many are clustered
in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such
as duodenogastric reflux and atrophic gastritis, seem to be more important than
aggressive factors. Nevertheless, antisecretory medications accelerate the healing o f
such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric
mucosal blood flow are impaired in chronic ulcer disease.

In this article, I will provide an overview of the

pathophysiology of the three main categories of
peptic ulcer: acute ulcers and erosions, chronic and
recurrent gastric ulcer, and chronic and recurrent
duodenal ulcer. There are sufficient differences in
the pathophysiology of these three categories of
ulcer to warrant considering them separately. Indeed, as we shall see, there are important subcategories within the three main groups.
Pathophysiology is the knowledge of how normal
physiological processes are altered in disease. It is
not a substitute for etiology, but in diseases where a
University of Pennsylvania, Philadelphia, Pennsylvania.
Address correspondence to: Professor F.P. Brooks, Professor
of Medicine and Physiology, University of Pennsylvania, 3400
Spruce Street, Philadelphia, Pennsylvania 19104.

cause has not been found, the features of pathophysiology may provide clues leading to the identification of causes, and may also offer guidance in
the development of new methods of treatment.
Methods of reducing acid-pepsin secretion have
been a less successful approach to the prevention of
acute ulcers and erosions or in accelerating their
healing. Yet once healed, these lesions seldom
become chronic or recurrent. It is in this group of
peptic ulcers where improving local defense properties form a most attractive new approach to
treatment.
Treatment with either antisecretory or acid neutralizing agents or substances which appear to affect
only local defense mechanisms has been remarkably effective in accelerating the healing of chronic

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

0163-2116/85/1100-015S$04.50/09 1,985PlenumPublishingCorporation

t5S

BROOKS
TABLE 1. PEPTIC ULCERS. AFTER }]ROOKSFP (1)
A c u t e Ulcers: Often superficial and characterized clinically by

bleeding: recurrence rate is low once the ulcer heals.

Acute ulcers in patients with extensive burns: Curling's
ulcer
Acute ulcers in patients with lesions in the central nervous
system: Cushing's ulcer
Acute ulcers in patients exposed to aspirin and other drugs,
acute alcoholic binges, or bile reflux
Acute ulcers in patients subjected to non-specific stress
Acute ulcers in patients at the extremes of age: neonates,
children, and the elderly
Acute ulcers in patients who eventually follow the clinical
course of chronic or recurrent ulcer
Chronic a n d R e c u r r e n t Ulcers

Gastric ulcers
Corpus or fundUs ulcer
Antral or prepyloric ulcers
Pyloric channel ulcers
Combination of gastric and duodenal ulcers
Ulcers resistant to healing under treatment
Duodenal ulcers
Uncomplicated duodenal ulcers
Bleeding duodenal ulcers
Perforated duodenal ulcers
Gastric outlet obstruction due to duodenal ulcer
Ulcers resistant to healing under treatment
Recurrent ulcers after surgery
Anastomotic ulcers
Recurrent duodenal ulcer
Hormonally-induced ulcers
Zollinger-EUison syndrome--gastrinoma
Retained antrum
G-cell hyperplasia
Esophageal ulcers
Ulcer adjacent to Meckel's diverticulum

recurrent gastric and duodenal ulcers. Prevention of

recurrence is also possibl e in these patients. However there remain a significant number of patients
who do not respond, identification of factors leading to failure of response is needed in order to
devise better methods of treatment.
Peptic ulcers are classified in Table 1 (1). The
morphological distinctions between erosions, acute
and chronic ulcers are shown in Figure 1 (2).
ACUTE EROSIONS AND ULCERS
The clinical hallmark of acute erosions and ulcers
in the stomach and duodenum is upper gastrointestinal hemorrhage manifested as hematemesis or
melena. The relative incidence of acute erosions
and gastric and duodenal ulcers in recently reported
studies is shown in Table 2 (1). In general there has
been a decrease in the percentage of patients bleeding from acute gastric erosions (3).
There are five general concepts which account for
a breakdown in normal defense mechanisms in the

16S

gastric mucosa: (i) the breaking of the gastric

mucosal barrier with resulting back diffusion of H
into the mucosa; (ii) failure of normal cellular metabolism to buffer H + entering the surface epithelial
cells; (iii) local mucosal ischemia; (iv) failure of the
normal secretion of bicarbonate and mucus; and (v)
accelerated shedding of cells or decreased rates of
cell renewal.
The gastric mucosal barrier as originally proposed by Davenport (4a) was the sum of anatomical
factors which determined the relative impermeability of the gastric mucosa to H +, CI-, K +, protein
and water. Injury to the barrier was apparent by
loss of H + from the lumen of the stomach and
increases in [Na+], [CI-], and [K in gastric content.
Figure 2 shows the proposed consequences of back
diffusion of H + release of histamine from mast cells,
cholinergic nerve stimulation of acid and pepsin secretion, vasodilation, increased permeability of capillaries with edema and loss of plasma proteins into the
lumen, and finally bleeding into the lumen (4). The
'barrier-breakers' first identified were aspirin, alcohol, and bile acids. Protein loss into the lumen was
shown to occur coincident with dilated intercellular
spaces and leakiness of the tight junctions (5). Acetylcholine and histamine cause vasodilation and increased vascular permeability respectively (6, 7).
The agents shown to break the barrier were
themselves also able to reduce the electrical potential across the gastric mucosa (8). Figure 3 shows
the effects of sodium acetylsalicylate, acetylsalicylic acid (aspirin), and the combination of aspirin
and ethanol on the gastric mucosal potential difference in human subjects (9). The exact mechanism of
the changes in potential difference is still unknown
but recent experiments in rat stomach showed that
a fall in mucoSal potential difference was the most
sensitive marker of mucosal injury (10).
The back diffusion of H and the increased
entrance of sodium and potassium into the stomach
are more difficult to demonstrate in human subjects

Erosion

Acute ulcer

Chronic ulcer

u_a

Submucosa
Muscularis
Se rosa

-t/,~llW,',~
Sclerosis

Fig 1. Diagramatic illustrations of acute and chronic gastric

rnucosal lesions. Modified from Sava G (2); Fr Med 30:274, 1967.

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

PATHOPHYSIOLOGY OF PEPTIC ULCER DISEASE

TABLE 2. PEPTIC EROSIONS AND ULCERS AND ACUTE UPPER GASTROINTESTINALHEMORRHAGE;AFTER BROOKS FP (1)

Year of
publication

Hospital

Hospital of the University

of Pennsylvania (HUP)
Kaiser Permanente
Metropolitan., NYC
Ben Taub, Houston
Portland, Oregon Veterans
Administration Hospital
Southampton, U.K,

Total no.
of patients

1975

60

13 (22%)

1975
1976

400
150

74 (18.5%)
56 (37%)

1978
1973

221
100

15 (7%)
9 (9%)

1975

150

7 (5%)

than in dogs. New techniques have made it possible

to introduce electrodes into the wall of the rabbit
stomach and record intramural pH. Figure 4 shows
a close correlation between net hydrogen flux out of
the stomach lumen and the intramural pH (! 1).
The second concept, the cellular metabolic theory of mucosal defense, arose partly as a result of a
failure to identify the anatomical barrier postulated
by some workers. Generally, morphological evidence of injury was greater in intracellular organelies than in the cell membrane and tight junctions.
Measures which maintain the buffering capacity
within cells, such as acid secretion at high bicarbonate concentrations in the plasma, increase the
resistance to injury of the mucosa, while systemic
acidosis and the administration of inhibitors of
carbonic anhydrase promote injury (12-15).
In the model of shock-induced ulcers in rabbits,
the fall in mucosal ATP levels correlated with

P e p s i n o g e n ~ Pepsin

/~
H+ ~ . .
~ ~.

'-'t,
[
--

Acute gastric
erosions

Acute duodenal
erosions

13 (9%)

Gastric
ulcers

Duodenal

18 (30%)

5 (8%)

15 (6%)
17 (11%)
5 acute
45 (20%)
15 (15%)
3 acute
29 (19%)

?
25 (17%)
13 acute
71 (32%)
26 (26%)

ulcers

54 (36%)

ulceration in the body of the stomach. The antrum

was less vulnerable to ulceration and the ATP levels
were less depressed (16). Figure 5 shows a scheme
for the pathophysiology of stress-induced acute
erosions and ulcers (17).
The third concept is the role of gastric mucosal
blood flow. Focal ischemia was the initial lesion
seen by endoscopy in the stomach of burn patients.
It was proposed that this subsequently evolves into
erosions and ulcers (18). Gastric mucosal blood
content was reduced focally in patients with head
injuries (19). Nevertheless in some experimental
ulcers ischemia does not appear to be of critical
importance (20).
The fourth concept is concerned with the failure
of normal secretion of bicarbonate and mucus. Both
of these are secreted by the surface epithelial cells
of the gastric mucosa. The principal evidence for a
role of these secretions in local defense tnechanisms
is that they are stimulated by prostaglandins of the

Modified

uJ~rplfialtsimale
~
Histamine
|

4
.

Plasma
proteins

. x~-t

-//-%r,e,.
.

Drug
instilled
~ -r 3r ~
I .~T~,..--'~I"~[- v

4~

Blood

4c

"l~r .t

-r Sodium
~ Z~acetyisalicylate
J.(Z28mg)

~,...____~

A,pJrin (300 rag)

]~( ~--"-~"---~--~Ed;2a-/tl--~nterstit'--~'~al
Potential
difference

(-mY) 30

Fig 2. Pathophysiological consequences of the back-diffusion of

acid through the broken gastric mucosal barrier. After Davenport HW (4); reproduced with permission from N Engl J Med
276:1312, 1967.

I ~r-,y~l.

25

~.

"

20

i .....

-]-

15

Cholinergicstimulation

J-

T
T .[Ethanol

T...-;""t " ' I (15+/~w/v)

1" ~"" ~Aspirin
.t.,"L 1.
{600 rag)

i i , , , , T I i u I ~ I ,
6
12
18
24
30
36
42
Time (3 min. intervals)

Fig 3. Effect of sodium acetylsalicylate, acetylsalicylic .acid

(aspirin), and ethanol plus acetylsalicylic acid on gastric
transmucosal potential difference in man. After Murray HS,
Strottman S, Cooke AR (9); reproduced with permission from Br
Med J 1:20, 1974.

Digestive Diseases and Sciences, Vol, 30, No. 11 (November 1985 Supplement)

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BROOKS
8.0-

Net back diffusion

Net secretion

Intramural7'57.0
pH

6.5

r= 0720 (p<.001)
N~23

I
J
i
J
-1500 -1000 -500
0
500
Net H+ flux ~Eq/30 min)

J
1000

Fig 4. Relationship between the intramural pH and the rate of net

H flux in fundic pouches after exposure to luminal acid for 60
minutes. After Silen W, Schiessel R, Kivilaakso E (11): reproduced with permission from Brain Res Bull 5(Suppl I):4, 1980.

E series. Inhibition of prostaglandin synthesis by

agents such as indomethacin reduces the capacity
to form prostaglandins of the E2 series and promotes mucosal injury (21). Prostaglandins are produced by rabbit fetal gastric surface epithelial cells
in mucosal culture. However the correlation between prostaglandin levels in the tissue and
mucosal damage is weak (22). The fifth concept is
the role of cell renewal rates in the defense of the
mucosa. Decreases in cell turnover can be the result
of decreased production of cells or slower rates of
shedding. Some agents which accelerate healing of
gastric mucosal lesions have been reported to slow
the rate of cell turnover. However, Hollander
showed that the shedding of cells was increased by
the topical application of irritants to the mucosa
(23). Later workers found that aspirin increased cell
shedding and that the increase in shedding was
prevented by prostaglandin E2 (24).
Later the ability of mild irritants to protect
against gross injury of the mucosa in rodents was
defined as cytoprotection (25). The observation that
inhibitors of the synthesis of prostacyclin prevented
the protective action of irritants while exogenous
prostaglandins had protective effects, supported a
role for prostaglandins in mediating the protective
action of irritants. The subject has been complicated by the fact that large doses of prostaglandins
inhibit acid secretion.
More recent studies indicate that only the subsurface mucosa is protected so that gastric mucosal
cytoprotection must be more specifically defined
18S

(26). The rapid repair of the surface mucosa after

injury is a property of the mucosal cells independent of prostaglandins. This response has been
called gastric mucosal restitution. Only the hemorrhage and hyperemia in the submucosa are reduced
by prostaglandins (27).
The term cytoprotection is also inaccurate in that
it implies that protection occurs within the cell and
therefore excludes the protective role of secretions
such as bicarbonate and mucus. Nevertheless the
observation that the protective properties of prostaglandins can be differentiated from their antisecretory effects is an important one (28).
The phenomenon of early reconstitution of the
surface epithelium of the gastric mucosa after injury
with ethanol or hypertonic saline appears to be
uninfluenced by prostaglandins in frog mucosa in
vitro or the rat stomach in vivo (29, 30). The
characteristic gross red streaks are related to deep
necrosis but may disappear earlier (31). It remains
to be determined which of the experimentally produced lesions, if either, more closely resembles
acute mucosal erosions and ulcers in man.
Acute Ulcers in Burn Patients

Two observations stand out. (i) The incidence of

ulcers was directly correlated with the proportion of
the body surface burned, reaching nearly 40% at
70% of the body surface (Figure 6) (32). (ii) Twelve
hour nocturnal gastric acid output declined as the
severity of the burn increased. The basal serum
gastrin was not elevated (1). Control of sepsis and
Trauma
Stress
Peritonitis
Myocardial Infarction

Shock

Ischemia and acidosis ]

I of gastric muc0sa I

Reduced
availability of
HCO~ to
neutralize
incoming H+

Reduced
acid secretion
with lowered
alkaline tide
and available
HC03

Reduced J
mucosal blood I
flow to
I
sweep away
influx ng H+

Reduced
availability
of ATP that
may be
required to
neutralize

luminal H+

I
9

r Acute stress ulcer I

Fig 5. Scheme for the pathophysiology of stress ulcers detailing

factors and mechanisms. After Silen W (17): reproduced with
permission from Hosp Pract, March 1980 pp 99.

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

PATHOPHYSIOLOGY OF PEPTIC ULCER DISEASE

40.

30.
% Patients
with
Curling's
ulcer 20

10

20

30

40
50
60
70
% Body surface burned

80

90

1(}O

Fig 6. Incidence of Curling's ulcer as related to burn size in

patients at the Army Burn Center 1967-1969. After Pruitt BA,
Foley FD, Moncrief JA (32): reproduced with permission from
Ann Surg 172:529, 1970.

prophylactic treatment with antacids or H2-antagonists has virtually eliminated this lesion.
Acute Ulcers in Patients with Injury to the Central
Nervous System

This lesion too, has become much less common,

coincident with prophylactic treatment with antacids and H2-antagonists. Some investigators have
reported a high incidence of gastric acid hypersecretion and basal hypergastrinemia in these patients
but others have not. It has been difficult to equate
the extent of injury and to consider observations
over periods of time (33). As in burn patients,
localized ischemia has been demonstrated early in
the evolution of the ulcers. In a controlled study
cimetidine failed to reduce the incidence of ulceration or hemorrhage in patients with acute injury to
the spinal cord (34).
Drug-Induced Erosions and Ulcers

In man aspirin acts topically to damage surface

epithelial cells. In an acid milieu it enters the cells
and inhibits mitochondrial oxidative phosphorylation with a resulting increase in cell permeability
and a decrease in the secretion of mucus and
bicarbonate. The formation of prostaglandins of the
E2 series is reduced and the transmucosal potential
difference falls. The surface cells slough exposing
erosions which may enlarge and rupture superficial
blood vessels. The rate of cell shedding is proportional to the dose of aspirin. In spite of damage to
cell organelles, the tight junctions remain relatively
intact. On endoscopic examination after repeated

ingestion of aspirin, multiple gastric hemorrhages

appear in the fundus and antrum. After 48 hours of
aspirin, erosions can be seen in the stomach in all
subjects and in the duodenum in 50% of subjects.
Most gastric erosions are found in the antrum
(35-37).
In patients with rheumatic diseases receiving
chronic treatment with aspirin, both true gastric
ulcers and erosions can be found in nearly a third of
patients (38).
The incidence of gastric erosions and bleeding
can be reduced by neutralizing gastric acidity or
inhibiting acid secretion (39). The ability of prostaglandins, at doses lower than those inhibiting acid
secretion, to prevent erosions detected endoscopically is controversial (40, 41), but higher doses did
reduce bleeding (42-44). There is also evidence that
doses continued for seven days lead to adaptive
protective mechanisms which reduce the level of
damage (45). In eight of 12 patients sucralfate
pretreatment prevented endoscopically-detected
erosions in response to aspirin (46). These results
emphasize the importance of gastric acidity in aspirin-induced gastric erosions but also raise the possibility that mucosal defense mechanisms can be
strengthened to resist damage.
Other Agents Which Damage the Mucosa

Alcohol can produce mucosal damage to the

stomach in man with increased loss of protein into
the lumen (47, 48). Bile salts have similar injurious
properties (49, 50). A PGE2 substance prevented
the fall in transmural potential in the duodenum but
not in the stomach in response to taurocholate (51).
Acute Erosions and Ulcers Associated with
Non-Specific Stress

These lesions are manifested clinically by

hematemesis and melena. They are seen most commonly in intensive care units in critically ill patients. Shock and sepsis are common preceding
events. A syndrome of respiratory failure, hypotension, sepsis and jaundice has been described with
lethal hemorrhage from acute stress ulceration of
the stomach (52). Unlike aspirin-associated ulcers
these lesions occur predominantly in the body of
the stomach and are often multiple.
The nature of gastric acid secretion in patients
with stress ulcers is controversial, with hyper- or
hyposecretion or normal secretion reported. However, back diffusion of H + occurred in 12 of 26
patients on a respiratory-surgical intensive care unit

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

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BROOKS
using polyethylene glycol as an unabsorbable reference compound (53). Recently calculation of intramural pH from the pH of gastric juice and arterial
pCO2 identified a pH < 7.24 in all seven patients
among 103 on intensive care units who developed
massive gastrointestinal bleeding (54).
Gastrocamera studies and endoscopic photographs in patients at risk for stress ulcer, showed
the initial lesion to be one of focal ischemia in the
acid-secreting mucosa progressing to petechiae and
erosions (55).
The results of medical treatment of acute gastrointestinal bleeding have been disappointing (54).
Laser treatment and now possibly heater probe
coagulation seem to be effective in stopping bleeding in a small group of patients identified as being at
high risk for rebleeding, based upon visible vessels
and spurting vessels (1). These results do not contribute much to our understanding of pathophysiology. A single anecdotal report of control of bleeding
from 'hemorrhagic' gastritis with PGE2 after all
other treatments had failed points to the need for
controlled trials (56). Surgical procedures also have
a variable record of success.
Prevention of gastrointestinal bleeding has been
more successful. Both cimetidine and antacids have
reduced the incidence of bleeding in intensive care
units, although in some, antacids titrated to maintain a pH > 3.5-4 have been more effective.
In summary acid-pepsin seems to be an important
permissive factor in stress ulcers, and back diffusion of H into the mucosa an important factor in
denuding the mucosa and exposing blood vessels.
However, once bleeding has occurred, among nonsurgical procedures only methods of coagulating the
vessels appear to significantly alter the course of the
injury.

TABLE 3. RECURRENCERATE FOR GASTRIC ULCERS. AFTER

BROOKS FP (1)

Authors

Smith & Jordan,

1948
Flood & Henning,
1950
Smith et al, 1953
VA, 1971
Halse et al, 1977
Piper et al, 1978
Miyake et al, 1980
Wright et ai, 1981
Gertler et al, 1983
Jensen et al, 1979
Alstead et al, 1983
Barr et al, 1983
Hentschel et al,
1983

Recurrence
rate (%)

Duration o f
follow-up
(years)

Ref.
no.

No. o f
patients

(57)

111

46.8

>5

(58)

101

98.0

>1 (mean 5.6)

(59)

697#

27.0

(60)
(61)
(62)
(63)
(64)
(65)
(66)
(67)
(68)
(69)

377
54
83
84
66
59
9
16
25
42

41.9
43.0*
40.0
34.5*
39.0*
39.0*
44.0*
70.0*
48.0*
55.0*
(5/23)

5 (or to
surgery)
2
1
2
1
>3
6-9 months
1
1
I
1

*verified by endoscopy.
t380 resected surgically.

divides gastric ulcers into three groups: those in the

body of the stomach (Type I), those associated with
duodenal ulcers (Type II), and those in the antrum
or prepyloric area (Type III). In general, Type I
ulcers are associated with normal or subnormal
secretion. Type III ulcers tend to occur in hypersecretors and resemble duodenal ulcers in their secretory pattern (71).
Clinical features which differentiate gastric ulcer
patients from duodenal ulcer patients include
greater age and a higher frequency of associated
diseases. Genetic factors are also important since
children of parents with gastric ulcer have a greater
risk of developing gastric ulcer but not duodenal
ulcer.

Pathology
CHRONIC AND RECURRENT GASTRIC ULCER
The characteristic clinical feature of chronic gastric ulcer is its tendency to recur as shown in Table
3 (1, 57-69). In three recent controlled trials H2antagonists in maintenance doses significantly reduced the rate of recurrence. This suggests a primary role for gastric acid secretion in leading to
recurrence. In a four-year study in Aberdeen, Scotland, about half the gastric ulcer patients in the
community remained symptom-free whether they
were treated by medical or surgical methods (70).
As with other peptic ulcers, heterogeneity exists
among gastric ulcers. One popular classification

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Type I gastric ulcers are surrounded by areas of

chronic gastritis which persist after healing of the
ulcer. Japanese workers found that most gastric
ulcers occurred on the distal side of the boundary
between the fundus and the areas of mucosa containing pyloric glands (71a).
Aspirin plays an important role in gastric ulcer,
acting as a local irritant. An increased incidence of
gastric ulcer was reported in women in Australia
after the Second World War which proved to be
associated with a heavy aspirin intake. The ulcers
usually occurred in the antrum and the surrounding
mucosa was free of gastritis.

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

PATHOPHYSIOLOGY OF PEPTIC ULCER DISEASE

TABLE 4. ABNORMALITIESIN PATIENTSWITH GASTRICULCER
1N THE CORPUS. AFTERBROOKSFP (1)
Hyposecretion of gastric HC1 and pepsin
Basal acid output
12-hour night secretion
Maximal or peak acid output (decreased parietal cell mass)
Response to a meal
Fasting and postprandial hypergastrinemia (G-34)
Decreased gastric antral gastrin content
Decreased release of pancreatic polypeptide in response to a
meal
Decreased mucosal prostaglandin content
Increased bile reflux
Incompetent pylorus
Reduced amplitude of gastric antral contractions
Delayed gastric emptying
Decreased gastric mucosal blood flow

Abnormal Function in Patients with Gastric Ulcer

The functional abnormalities associated with

chronic Type I gastric ulcers are listed in Table 4
(1). Hyposecretion of hydrochloric acid can be
demonstrated in basal secretion, peak acid output,
and acid secretion in response to a meal. Figure 7
presents typical results in gastric ulcer (72). Increased back diffusion of H through the bed of the
ulcer cannot account for the hyposecretion (73).
A recent report found that although patients with
py!oric and duodenal ulcers showed a similar tendency to hypersecretion, those with prepyloric ulcers had significantly lower peak acid outputs (74).
The gastrin content of the antrum is reduced in
patients with gastric ulcer but the fasting serum
level in Type I ulcers is higher than normal. After a
protein meal the serum gastrin rises to higher levels
110

Gastric
cancer

Normal
subjects

Duodenal
ulcer

Gastric
ulcer

54
50
Men Women

237
35
43
30
22
7
Men Women Men Women Men Women

10(2

80

Acid output 60
mEq/hr,

40

20

9 ~

~176176

,
.

,m

~176
. . ,
0

...d

Achlorh~ dria - -

Fig 7. Distribution of values of acid output during intravenous

infusion of histamine diphosphate in normal subjects, and patients with duodenal ulcer, gastric ulcer, and gastric cancer.
After Kirkpatrick JR, Lawrie JH, Forrest APM, Campbell H:
reproduced with permission from Gut 10:761, 1969.

than in normal subjects. Fractionation of the gastrin

shows that the increase in fasting levels is due to an
increase in G-34.
Less pancreatic polypeptide is released into the
circulation after a meal in patients with gastric ulcer.
Mucosal biopsies show lower than normal concentrations of prostaglandins in patients with gastric ulcer.
With healing, values returned to normal (75-77).
A number of investigators have found evidence of
reduced antral contractile activity and delayed gastric emptying in patients with gastric ulcers. The
frequency and amplitude of phasic contractions in
the antrum were reduced (78). The emptying of
solids but not liquids was delayed (79). Other workers have found that the pylorus was incompetent,
permitting duodenogastric reflux (80). Still others
have found duodenogastric reflux to be similar in
patients with gastric ulcers and controls (81). The
presence of bile in gastric contents has been found
more frequently in gastric ulcer patients by some
investigators but not by others (82, 83).
New methods for detecting blood in gastric
mucosa have shown reduced blood flow in the
center and margin of gastric ulcers. With healing,
blood flow increased (84, 85).
Efforts to identify behavioral abnormalities in
patients with gastric ulcer or to link the ulcer to life
events have largely failed with conspicuous individual exceptions (86, 87).
Lessons from the Healing of Gastric Ulcers

Accelerated healing of all types of gastric ulcer

has now been demonstrated with cimetidine (88). In
smaller numbers of patients ranitidine and cimetidine were found to be equally effective (89, 90).
Agents such as sucralfate, carbenoxolone and tripotassium bismuthate which had no antisecretory
action also accelerated the healing of gastric ulcers
(91-93). Unfortunately, the mechanism of action of
these agents is poorly understood. Sucralfate and
bismuthate bind to the ulcerated surface. Presumably, sucralfate binding occurs because polymerized octosulfate molecules become negatively
charged below pH 7 and bind to positively charged,
denatured or degraded proteins in the base of the
ulcer. Sucralfate also inhibits the action of pepsin
and bile salts (94).
Colloidal bismuth chelates with proteins and
forms a protective coating over ulcers. It is not as
active as an antacid but can bind to pepsin (95).
Small numbers of patients with gastric ulcers have
been treated with prostaglandin E2 and with

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

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BROOKS
trimipramine, a combination of the tricyclic antidepressant imipramine and levomepromogine, but the
results are inconclusive (96-98). Cholestyramine,
an effective binder of bile salts, was without benefit
in healing gastric ulcers as evaluated radiologically.
Carbenoxolone was one of the first agents shown to
accelerate the healing of gastric ulcer. Carbenoxolone has been reported to increase the secretion of
mucus, decrease the rate of cell turnover, and to
impair the catabolism of prostaglandins (99). A
general criticism of such studies is that the quantitative importance in improving mucosal resistance
due to any one action is unknown.
These results suggest that both acid-pepsin secretion as an aggressive factor, and improved local
defense mechanisms can accelerate the healing of
gastric ulcers. However, this still leaves unanswered the question of a role for deficient endogenous mucosal defense mechanisms.
The good results of surgical treatment, usually
involving excision of the ulcer and removal of either
gastrin or acid-secreting mucosa, also support the
importance of acid-pepsin aggressive factors.
Factors influencing favorable responses to healing of gastric ulcers include hospitalization and
stopping smoking, while salicylates, smoking and
large ulcer size reduce the percentage which heal
(100-102). These observations suggest that salicylates can contribute to chronic gastric ulceration,
possibly through damage to the mucosal barrier.
Once gastric ulcers have healed, H:-antagonists
have been shown to prevent recurrences, at least
during a year of administration (68). Controlled
trials with agents acting through local mucosal
defense mechanisms, e.g. sucralfate and prostaglandins, are still in progress. These results emphasize the importance of acid-pepsin secretion in
initiating recurrent gastric ulcers.
One of the most glaring gaps in our knowledge is
the lack of understanding of the mechanism of pain
in gastric ulcer. Spraying ulcers with 0.2N HCI for
fifteen minutes through an esophagoscope failed to
elicit pain in four subjects (103). This may explain in
part the relative lack of difference between placebo
and ulcer-healing promoting drugs with regard to
relief of pain.
The development of gastric ulcers following truncal vagotomy for duodenal ulcer, and its prevention
by a pyloroplasty, is compatible with a role for
gastric stasis in the pathophysiology of gastric ulcer, rather than meal-induced hypergastrinemia and
hypersecretion as proposed by Dragstedt (1).

22S

CHRONIC AND RECURRENT

DUODENAL ULCER

The pathophysiology of duodenal ulcer patients

differs from that of gastric ulcer patients in a number of ways. A variable proportion of patients are
hypersecretors of HC1 both in the basal state and
after stimulation. The maximal acid output correlates directly with the number of parietal or oxyntic
cells. Gastritis of the fundic gastric mucosa is rare
but that of antral mucosa is common. Increased
levels of group I serum pepsinogens in the blood
identify a subset of patients with gastric acid hypersecretion with an increased risk of developing duodenal ulcer. The male predominance in duodenal
ulcer exceeds that of gastric ulcer. Members of
blood group O and those who are non-blood group
secretors as well as those with H L A - B-12 are also
at increased risk. Patients with duodenal ulcer tend
to be younger than those with gastric ulcer. As with
gastric ulcer, the tendency of children of patients
with duodenal ulcer to develop peptic ulcer is
specific for the same location. There is a clinical
impression that after 10-15 years of recurrent duodenal ulcer, the severity of the disease lessens.
The local defense mechanisms in the duodenum
differ from those in the stomach. Bicarbonate secretion is contributed by the pancreas and liver as
well as by the duodenal mucosa. Brunner's glands
are another potential source of bicarbonate. Duodenal ulcers characteristically occur in the first
portion of the duodenum or the duodenal bulb.
Abnormalities of Function in Duodenal
Ulcer Patients

Table 5 lists the abnormalities in function seen in

some patients with duodenal ulcer (1). It has become quite clear that duodenal ulcer is a heterogeneous syndrome. We should not expect all patients
to exhibit the same abnormalities in function.
Acid Secretion

Figure 7 shows that many patients with duodenal

ulcer have an increased capacity to secrete HCI as
well as an increased rate of basal secretion. The
peak acid output of duodenal ulcer patients declines
with increasing age.
The maximal or peak acid output is a function of
the number of parietal cells. Hypersecretors have
an increased parietal cell mass. However both
vagotomy and antrectomy as separate procedures
reduce the peak acid output by at least 50%, with-

Digestive Diseases and Sciences, Vol, 30, No. ll (November 1985 Supplement)

PATHOPHYSIOLOGY OF PEPTIC ULCER DISEASE

TABLE 5. ABNORMALITIESIN PATIENTSWITH DUODENAL
ULCER. AFTERBROOKSFP (1)
Hypersection of gastric HCI
Basal acid[ output
12-hour night secretion
Maximal or peak acid output to histamine or pentagastrin
(increased parietal cell mass)
Increased response to stimulation
Sham feeding
Insulin hypoglycemia
Gastric distention
Intestinal phase of secretion
Response to a meal
Other secretory abnormalities
Excessive vagal stimulation
Excessive: duodenal acid load
Qualitatively abnormal mucus
Hypersecretion (exocrine and endocrine) of pepsinogens
Failure of' inhibition of gastric acid secretion
Increased sensitivity of secretory processes: response to
gastrin and calcium
Abnormal histamine metabolism
Endocrine abnormalities and disorders of regulation
Inappropriate release of gastrin
Impaired negative feedback: effect of gastric HCI or
inhibition of gastric release
Impaired control of somatostatin release
Abnormalities in mucosal defense mechanisms
Decreased mucin secretion
Decreased availability of prostaglandins
Decreased salivary secretion
Abnormalities in blood flow
Abnormalities in gastric motor function
Increased phasic antral contractility
Accelerated gastric emptying
Abnormal psychodynamics
Genetic factors: HLA-B12 antigens, blood group O, and nonsecretor status present in excessive numbers compared
to general population

out changing significantly the number of parietal

cells, thus the sensitivity of parietal cells plays an
important role in the intact patient.
The mechanism of basal acid hypersecretion is
unknown. Two observations have recently been
made which support a role of increased vagal activity in some patients: (i) Basal acid output correlates
with the concentration of pancreatic polypeptide in
the blood of patients with duodenal ulcer. (ii) Sham
feeding does not increase acid output above the
basal level in patients, but did increase acid output
in response to submaximal doses of pentagastrin
(104; 105). Replotting earlier data showed that 20%
of duodenal ulcer patients failed to show an increase of sham feeding-induced acid Output above
basal levels (100).
Twelve-hour night collections of gastric content
show increased acid outputs in patients with duodenal ulcer and these fall to subnormal values after
vagotomy. Recently single bedtime doses of H2-

antagonists accelerated the healing of duodenal

ulcers and markedly reduced acid output, suggesting that reduction of nocturnal acid output was of
major importance in accelerating the healing of
duodenal ulcers (106, 107).
In response to a variety of stimuli, patients with
duodenal ulcer secrete more acid than do normal
subjects. These stimuli include sham feeding, insulin hypoglycemia, gastric distention, the intestinal
phase of gastric secretion and the response to a
meal. The increased response to sham feeding is
due primarily to an increased basal acid output.
Vagotomy abolishes the acid secretory response to
sham feeding and to insulin. The serum gastrin also
rises to a variable extent after sham feeding and
insulin, and appears to contribute to the increase in
acid output after sham feeding. In other studies the
rise in gastrin played only a permissive role. Two
years after vagotomy the volume :of gastric secretion in response to insulin was reduced more than
that in response to histamine. The increased acid
secretory response to antral distention is thought to
be mediated by a pyloro-oxyntic reflex independent
of gastrin.
The gastric acid output in response to a meal can
be assessed by intragastric titration or by dual
marker perfusions of the stomach and duodenum.
The first technique, which artificially fixes the acidity
of the gastric contents to pH 5.5, showed increased
acid outputs in patients with duodenal ulcer and a
decre~.se in buffering capacity of gastric contents
two hours after a steak meal. The second method
showed an abnormally prolonged period of secretion and a more rapid delivery of acid to the
duodenum. Recently a five-hour study of antral and
intraduodenal pH in patients with duodenal ulcer
and control subjects, before and after a standard
liquid-solid meal, showed lower mean pH levels and
increased acidity to pH < 4.0 for a greater percentage of time in patients with duodenal ulcer. Cimetidine virtually eliminated pH < 4.0 in the duodenum
(108). In duodenal ulcer patients, the acid load
delivered to the duodenum after a meal was 4-5
times that in normal subjects (Figure 8) (I09).
A number of investigators have reported qualitative abnormalities of gastric mucus in patients with
duodenal ulcer using histochemical techniques
(I 10), or biochemical methods based upon analysis
of the sugar moieties in mucus.
Hypersecretion of pepsinogen I occurs in about
68% of patients with duodenal ulcers. Failure of
normal inhibitory secretory mechanisms has not yet

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

23S

BROOKS
2.2
1.8
H + activity

Meal

1.4

entering
duodenum,
(mEq/10min)1.0

o.~
0.20
-1

U patients
.'~,..
(n= 12)
."l.[ ~'v
.("'[~ I f"lr; Healthy subjects
is
--i.i.ti (n=81

~
l..

****1"**
2

Hours

I****

*I
4

*P<O.05

Fig 8. D u o d e n a l h y d r o g e n load after meals in patients with

duodenal ulcer (DU) and healthyvolunteers. *Significantdifferences (P< 0.05) at each 10-minuteinterval. After Malagelada
JR, LongstrethGF, Deering TB, et al. (109); reproduced with
permission from Gastroenterology73:992, i977.

been conclusig~Jy demonstrated in duodenal ulcer

patients (i11, 112).
The presence of increased sensitivity of parietal
cells to gastrin stimulation in duodenal ulcer patients is controversial. In one study where the
patients were matched for acid output with controls, there was no increase in sensitivity to exogenous pentagastrin. Increased sensitivity to endogenous gastiin released by a peptone meal has been
reported in duodenal ulcer patients. Increased sensitivity of acid secretion to exogenous calcium was
reported as ffell (113).
The Success of H2-antagohists in the treatment of
duodenal ulcer has renewed interest in the possible
role of histamine in pathophysio!ogy. The gastric
fundic mucosal histamine content has been found to
be reduced in pat~l~fits with duodenal ulcer, along
with a decrease in the activity of histamine methyltransferase, an enzyme involved in the catabolism
of histamine. Successful treatments such as cimetidine therapy or Vagotomy result in an increase in
mucosal histamine. The increase in acid output
after pentagastrin in patients with duodenal ulcers
Was paralleled by an increased output of histamine
in gastric juice but a fall in mucosal histamine.
Figtlre 9 shows a scheme for the role of histamine in
gastric acid secretion (114).
Endocrine Abnormalities in Duodenal Ulcer
No definite abnormality in the antral content of
gastrin has been demonstrated in the great majority
of patients with duodenal ulcer. Increased numbers
of gastrin-containing cells in the antrum have been
reported in a few patients with increased gastrin
secretion in response to a protein meal (antral
G-cell hyperplasia). Fasting serum gastrin concen-

24S

trations are normal in patients with duodenal ulcer.

However, considering the pH of antral contents,
the serum gastrin is inappropriately high. The acidity must be raised to pH <~ 2.5 to inhibit gastrin
release in duodenal ulcer patients, while in normal
controls pH 3.5 is sufficient. Plasma gastrin levels
rise to a higher concentration after a meal due to an
increase in G-34. They rise to even higher levels
after atropine.
There is no good evidence for a decrease in
sensitivity of acid output or gastrin release to somatostatin in duodenal ulcer patients (108). However,
reduced levels of somatostatin in the antrum and
lowered numbers of somatostatin-containing cells
in the antrum have been reported in patients with
duodenal ulcer.
Abnormalities in Mucosal Defense Mechanisms
Little information is available on the response of
mucosal defense mechanisms in patients with duodenal ulcer. Simultaneous recordings of antral and
duodenal pH showed that although the duodenal pH
was lower in patients with duodenal ulcer after a
standard meal, the peak output of alkali was the
same as that in controls (115).
Prostagiandins of the E2 series were synthesized
at an increased rate in the duodenal mucosa of
duodenal ulcer patients. Conversely, aspirin re-

Acetylcholine

N1N~-DMH ~

[O

plexus

N1-MH--"X,

II
Parietalcell

I HistamineI
~
~

O)

",, o!(o!:Mff,
r
":,*'/
~
/ Antr~lm+
"1 s
j~--~'(~----intestine

Fig 9. A concept of the interrelationship b e t w e e n m u c o s a l

m e c h a n i s m s for the stimulation of gastric acid secretion. A R =
acetylcholine receptor, H2-R = H2 receptor, G R = gastrin
receptor, N~N1DMH = NaN" = m e t h y l h i s t a m i n e , N I M H =
N - m e t h y l histamine, S A M = S - a d e n o s y l - L - m e t h i o n i n e , S A H =
S - a d e n o s y l - L - h o m o c y s t e i n e , I(r)-MH = r - m e t h y l h i s t a m i n e ,
H M T = histamine m e t h y l t r a n s f e r a s e , --~ = acting a s a n agonist

or releaser, 9.......b- = actingas an inhibitor, -.....~ = actingas an

activator or inhibitor, dependingupon conditionspresent. After
Lorenz W, Troidl H, Barth H et al.; (114); reproduced with
permissionfrom StimulusSecretionCouplingin the Gastrointestinal Tract, MTP Press, Lancaster, England, p 177 1975.

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

PATHOPHYSIOLOGY OF PEPTIC ULCER DISEASE

duced PGE2 content to lower levels in duodenal
ulcer patients than in normals. Less prostanoid
(PGE2, 6-keto PGF, and thromboxane B2) accumulated in antral biopsies in organ culture from patients with duodenal ulcer than from controls.
There were no significant differences in the duodenal mucosa in organ culture. Cimetidine treatment
increased prostanoid accumulation by cultured gastric mucosa (116).
Gastric mucosal blood flow in relation to gastric
acid secretion was found to be similar in duodenal
ulcer patients and controls (l16a).
Gastric Contractile Activity and Emptying
Some patients with duodenal ulcer empty solid
foods at an accelerated rate. The migrating motor
complexes in patients with duodenal ulcer have been
reported to be prolonged and irregular, while the
frequency and amplitude of antral contractions were
increased.
Psychodynamics and Duodenal Ulcer
Despite intensive studies no consistent pattern has
been established in patients with duodenal ulcer.
Attempts have been made to subclassify patients
with duodenal ulcer. Lam has proposed a primary
classification based upon the age of onset (117).
Those with an onset before age 30 have a positive
family history of ulcer dyspepsia in about 50% of
subjects, more acid hypersecretion, more male predominance and more gastrointestinal bleeding. Late
onset patients (after age 30) have an increased
prevalence of blood group O, an increased tendency
to perforate, to develop gastric outlet obstruction,
to have severe exacerbations and to have large or
multiple ulcers (117).

failure of ulcer healing is smoking. Failure to suppress nocturnal acid secretion, the male sex, old
patients, large deep irregular ulcers, peak acid outputs >30 mM/h are associated with failure to heal.
Smoking has been shown to decrease the effectiveness of Hz-antagonists as antisecretory agents.
These results point to the major role of acid
secretion in the healing of duodenal ulcer. However
a number of other agents which have no significant
gastric acid antisecretory effect also accelerate the
healing of duodenal ulcer at rates not significantly
different from Hz-antagonists. These include colloidal bismuth and sucralfate. The failure rate is nearly
the same (119).
The latest addition to the medical armamentarium
is omeprazole. This agent healed 93% of duodenal
ulcers in two weeks at a dose of 40 mg daily (120).
After seven days of treatment of healthy subjects
with omeprazole 30 or 60 mg per day, basal acid
output and peak acid output to pentagastrin were
nearly totally suppressed (121). There was no significant effect of omeprazole on pepsin. This agent
functions as an inhibitor of the parietal cell H +K+-ATPase. It enters the cell and remains there
after 16 hours despite a rapid disappearance from
the plasma. Figure 10 shows a diagramatic representation of the parietal cell and the role of the
H+-K+-ATPase (122).
HCl

Apical /

"

Lessons from the Treatment of Duodenal Ulcer

The striking success of Hz-antagonists in accelerating the healing of duodenal ulcers and in the
prevention of recurrence attests to the importance
of acid-pepsin secretion in the pathophysiology of
duodenal ulcer. However 20-30% of patients do not
heal within four weeks and nearly the same percentage have recurrences despite maintenance treatment.
The percentage of patients whose ulcers healed during
placebo treatment is about 40%. The recurrence rate
on placebo after healing varies from 43-100%, while
in patients given cimetidine 400 mg at bedtime, cimetidine 400 mg twice-daily, or ranitidine 150 mg at night,
the recurrence rate was 9-65% (118).
In most studies the factor which predisposes to

+1\CaM

\,,..~./

Ca++ I

~ oAyP

",:v: Na+

ReceptA:hI " Kt!, +

',:',~,:~7 1

'"" ~

c,- ,. /%..
F!O

....... .~

......

NaKelz

Ionpathways
Basal
Fig 10. Schematic model of the parietal cell s h o w i n g the receptor
s y s t e m s and ion p a t h w a y s in the basal-lateral m e m b r a n e , and the
apical m e m b r a n e transition from a resting to a stimulated state.
G = gastrin; A c h = acetylcholine; H = histamine; C a M =
calmodulin; sc = secretory canaliculus; tv = tubulovesicles; m f
= microfilaments. After M a l i n o w s k a D H and Sachs G: (126);
reproduced with permission from Clin Gastroenterol 13:322, 1984.

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

25S

BROOKS

Other new agents shown to accelerate the healing

of duodenal ulcer include the anticholinergic M2receptor antagonist pirenzepine and a prostaglandin
E1 analog, misoprostol, at doses with antisecretory
effects.
One approach to the problem of drug resistant
duodenal ulcers is to shift to another class of drug
(123). Colloidal bismuth healed 10 of 12 ulcers
refractory to cimetidine, whileiarge doses of cimetidine healed 5 of 13 ulcers (124). Alternatively, One
can increase the dose of the same drug. In another
study performed over three years, 18 patients were
refractory to cimetidinr during the first month of
treatment at a dose of 1.2 ~day.' Increasing the dose
of cimetidine up to 3 g/day eventually healed 29 of
41 patients (125).
The treatment results in duodenal ulcer therefore
support the importance of both acid aggression and
mucosal defense in healing dtiodenal ulcers.
REFERENCES
1. Brooks FP: The pathophysiology of peptic ulcer: An overview. In Peptic Ulcer, New York, Churchill Livingstone, in
press, pp 51=60
2. Sava G: Ulcrrations et ulc~re aigus de l'estomac. France
Medicale 30:274, 1967
3. Hunt PS, Korman MG, Hansky J, Schmidt GT, Hillman
HS; Acute gastric ulceration: A prospec.tive study of incidence a n d r e s u l t s of management. Aust NZ J Med
10(3):305-308, 1980
4. DavenPort HW: Salicylate damage to the gastric mucosal
barrier. N Engl J Med 276:130721312, 1967
4a.Davenport HW: Gastric mucos~ injury by fatty acid and
acety!salicylic acids. Gastroenterology 46:245-253, 1965
5. Munro DR: Route of protein loss during a mode! proteinlosing gastropathy in dogs. Gastroenterology 66:960-972,

19,74
6. Davenport HW, Kauffman GL Jr: Plasma shedd!ng by the
canine. Oxyntic and pyloric glandular mucosa induced by
top!cal action of acetylcholine. Effect of atropine and
physostymine. Gastroenterology 69:190-197, 1:975
7. Wood J G, Davenpo~ HW: Measurement of canine vascular permeability to plasma proteins in the normal and
protein-losing states. Gastroenterology 82:72.5-733, 1982
8. Geall MG; Phillips SF, Summerskill WHJ: Profile of gastric
potential difference in man: Effects of aspirin, alcohol, bile
and endogenous acid. Gastroenterology 58:437--443, 1970
9. Murray HS, Strottmari MP, Cooke AR: Effect Of several
drugs on gastric potential difference in man. Br Med J
1:1%21, 1974
!0. Morris GP, Wallace JL, Harding PL, Krausse EJ, Lolle SJ:
Correlations between chmiges in indicators of gastric
mucosal barrier. !ntegrity at time of exposure to "Barrier
Breakers" and extent of hemorrhagic erosions one hour
later. Dig Dis Sci 29i6-11, 1984
11. Silen W, Schiessel R, Kiviiaakso E : The gastric mucosal
barrier and ulceration. Brain Res Bull 5(Supp! 1):3--6, 1980

26S

12. Kivilaakso E, Bargilai A, Schiessel R, Fromm D, Silen W:

Experimental ulceration of rabbit antral mucosa. Gastroenterology 80:77-83, 1981
13. O'Brien P, Silen W: Influence of acid secretory state on the
gastric mucosal tolerance to back diffusion of H Gastroenterology 71:760-765, !976
14. Kivilaakso E: High plasma HCO3 protects gastric mucosa
against acute ulceration in the rat. Gastroenterology
81:921-927, 1981
!5. O'Brien P, Bushnell M: R01e of acid-base status in the
responses of the isolated amphibian gastric mucosas to
back diffusion 'of H Gastroenterology 79:439--445, 1980
16. Menguy R: Role of gastric mucosal energy metabolism in
the etiology of stress Ulceration. World J Surg'5:175-179,
1981
17. Silen W: The prevention and management of stress ulcers.
H0sP Pract, March 1980, 15:pp 93-100
18. Czaja A J, McAlhany JC, Pruifl BAJr: Acute gastroduodenal disease after thermal inju{y: An endoscopic evaluation.
N Engl J Med ~91:925-928, i974
19. Kamada T,. Sato N, Kawano S, Fusamoto H, Abe H:
Gastric mucosal dynamics after thermal or head injury: A
clinical application of reflectance spectrophotometry. Gastroenterology 83:535-540, 1982
20. Mersereau WA, Hinchey EJ: Effect of gastric acidity on
gastric ulceration induced by hemorrhage in the rat utilizing
a gastric chamber technique. Gastroenterology 64:11301135, 1973
21. Garner AI Flemstr6m G, Allen A; Heylings JR, McQueen
S: Gastric mucosal protective mechanisms: Roles of epithelial bicarl~onate and mucus secretions. Scand J
Gastroenterol 19(Suppl 101):79-86, 1984
22. Kauffman GL Jr, Lig'umsky M: Role of endogenous prostaglandins in gastric mucosal integrity. In Mechanisms of
Mucosal Protection in the Upper Gastrointestinal Tract, A
Allen, G Flemstrrm, A Garner, W Silen, LA Turnberg
(eds). New York, Raven Press, !984, pp 317-322
23. Hollander F: The tWO-component mucus barrier. Arch
Intern Med 94:107-120, !974
24. Hurst BC, Rees WDW, Garner A: Cell shedding by the
stomach and duodenum. In Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, A Allen, G
Flemstr6m, A Garner, W Silen, LA Turnberg (eds). New
York, Raven Pressl 1984, pp 2!-26
25. Chaudhury TK, Robert A: Prevention by mild irritants of
gastric necrosis produced in rats by sodium taurocholate.
Dig Dis Sci 25:830-836, 1980
26. Robert A: Role of endogenous and exogenous prostaglandins in muc0sal protection. In Mechanisms of Mucosal
Protection in the Upper Gastrointestinal Tract, A Allen, G
Flemstr6m, A Garner, W Si!en, LA Turnberg (eds). New
York, Raven Press, 1984, pp 377-382
27. ItoS, Lacy ER, Rutten MJ, Critchlow J, Silen W: Rapid
repair of injured gastric mucosa. Scand J Gastroenterol
19(Suppl 101):87-95, 1984
28. Robert A: Cytoprotect!on: What it is and what it is not. In
Mechanisms of Muc0sal Protection in the Upper Gastrointestinal Tract, A Allen, G Flemstr6m, A Garner, W Silen,
LA Turnberg (eds). New York, Raven Press, !984, pp
381-382
29. Svanes K, Critchlow J, Takeuchi K, Magee D, Ito S, Silen
W: Factors influencing reconstitution of frog gastric

Digestive Diseases and Sciences, Vol. 30, No, 11 (November 1985 Supplement)

P A T H O P H Y S I O L O G Y OF PEPTIC U L C E R D I S E A S E

30.

31.

32.

33.

34.
35.

36.

37.

38.

39.

40.

41.

42.

mucosa: Role of prostaglandins. In Mechanisms of Mucosal

Protection in the Upper Gastrointestinal Tract, A Allen, G
Flemstrfm, A Garner, W Silen, LA Turnberg, (eds). New
York, Raven Press, 1984, pp 33-39
Lacy ER, Ito S: Ethanol-induced insult to the superficial rat
gastric epithelium: A study of damage and rapid repair. In
Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, A Allen, G Flemstr6m, A Garner, W Silen,
LA Turnberg (eds). New York, Raven Press, 1984, pp
49-63
Ito S, Lacy ER: Characteristics of ethanol-induced lesions
in rat gastric mucosa. In Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, A Allen, G
Flemstr6m, A Garner, W Silen, LA Turnberg (eds). New
York, Raven Press, 1984, pp 57-63
Pruitt BA, Foley FD, Moncrief JA: Curling's ulcer: A
clinical pathology study of 323 cases. Ann Surg 172:
523-539, 1970
Zach GA, Gyr KE, Alvenslebew E, Mills JG, Stalder GA,
Dunn SL, Bloom SA: Double-blind, randomized, controlled study to investigate the efficacy of cimetidine given
in addition to conventional therapy in the prevention of
stress ulceration and hemorrhage in patients with acute
spinal injury. Digestion 29:214-222, 1984
lvey KJ: Drugs, gastritis, and peptic ulcer. J Clin
Gastroenterol 3 (Suppl 2):29-34, 1981
Domschke S, Domschke W: Gastroduodenal damage due
to drugs, alcohol and smoking. Clin Gastroenterol 13:405436, 1984
Rees WDW, Gibbons LC, Warhurst G, Turnberg LA:
Studies of bicarbonate secretion by the normal human
stomach in vivo: Effect of aspirin, sodium taurocholate,
and prostaglandin E2. In Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, A Allen, G
Flemstr6m, A Garner, W Silen, LA Turnberg (eds). New
York, Raven Press, 1984, pp 119-123
Silvoso GR, Ivey KJ, Butt JH, Lockard OD, Holt SD, Sisk
C, Baskin WN, Mackercher PA, Hewett J: Incidence of
gastric lesions in patients with rheumatic disease on chronic
aspirin therapy. Ann Intern Med 91:517-520, 1979
Carlson D, Gerber E, Weinstein W, Grossman MI,
Bluestone R, Guth P: Drug-associated gastroduodenal lesions in rheumatoid arthritis: An endoscopic and histologic
study. Gastroenterology 78:1147, 1980
Welch RW, Bantch HL, Harris SC: Reduction of aspirininduced gastrointestinal bleeding with cimetidine. Gastroenterology 74:459-463, 1978
Muller P, Dammann HG, Simon B, KommereU B: Prostaglandins and human gastric mucosa: Molecular aspects and
protecti~ve properties. In Mechanisms of Mucosal Protection in the Upper Gastrointestinal Tract, A Allen, G
Flemstr6m, A Garner, W Silen, LA Turnberg (eds). New
York, Raven Press, 1984, pp 311-316
Stern AI, Hogan DL, Sandersfield MA, Kahn LH, Isenberg
JI: Do low doses of 15(R) 15 Methyl-PGE2 (MPGE) prevent
aspirin (ASH) induced gastric damage in man? Gastroenterology 84:1325, 1983
Gilbert DA, Surawicz CM, Silverstein FE, Weinberg CR,
Saunders DR, Feld AD, Sanford RL, Bergman D, Washington P: Prevention of acute aspirin-induced gastric
mucosal injury by 15R-15R methyl prostaglandin E~: An
endoscopic study. Gastroenterology 86:339-345, 1984

43. Hunt JN, Smith JL, Jiang CL, Kessler L: Effect of synthetic prostaglandin El analog on aspirin-induced bleeding
and secretion. Dig Dis Sci 28:89%902, 1983
44. Konturek SJ, Kwiecien N, Obtulowicz W, Polanski M,
Kopp B, Oleksy J: Comparison of prostaglandin E2 and
ranitidine in prevention of gastric bleeding by aspirin in
man. Gut 24:89-93, 1983
45. Graham DY, Smith JL, Dobbs SM: Gastric adaptation
occurs with aspirin administration in man. Dig Dis Sci
28:1--6, 1983
46. Tesler MA, Lira ES: Protection of gastric mucosa by
sucralfate from aspirin-induced erosions. J Clin Gastroenterol 3(Suppl 2):175-179, 1981
47. Palmer ED: Gastritis: A Revaluation. Medicine 33:
19%280, 1954
48. Brosinne A: Effects of ethanol on plasma protein shedding
in the human stomach. Dig Dis Sci 24:44-47, 1979
49. Ivey KJ, Den Besten L, Clifton JA: Effect of bile salts on
ionic movement across the human gastric mucosa. Gastroenterology 59:683-690, 1970
50. Duane WC, Wiegand DM, Gilberstadt ML: Intragastric
duodenal lipids in the absence of a pyloric sphincter:
Quantitation, physical state, and injurious potential in the
fasting and post prandial states. Gastroenterology 78:
1480-1487, 1980
51. Fimmel CJ, Mfiller-Lissner SA, Blum AL: Acute bile
salt-induced mucosal damage in man: Time course and
effect of misoprostol a PGEl-analogue. In Mechanisms of
Mucosal Protection in the Upper Gastrointestinal Tract, A
Allen, G Flemstr6m, A Garner, W Silen, LA Turnberg
(eds). New York, Raven Press, 1984, pp 341-349
52. Skillman JJ, Bushell LS, Goldman H, Silen W: Respiratory
failure, hypotension, sepsis, and jaundice: A clinical syndrome with lethal hemorrhage from acute stress ulceration
of the stomach. Am J Surg 117:523-530, 1969
53. Skillman JJ, Gould SA, Chung RSK, Silen W: The gastric
mucosal barrier: Clinical and experimental studies in critically ill and normal man and in the rabbit. Ann Surg
172:564-584, 1970
54. Fiddian-Green RJ, McGough E, Pittenger G, Rothman E:
Prediction value of intramural pH and other risk factors for
massive bleeding from stress ulceration. Gastroenterology
85:613-620, 1983
55. Lucas CE, Sugawa C, Friend W, Walt AS: Therapeutic
implications of disturbed gastric physiology in patients with
stress ulceration. Am J Surg 123:25-34, 1972
56. Weiss JB, Peskin GW, Isenberg JI: Treatment of hemorrhagic gastritis with 15(R)-15 methyl prostaglandin E~:
Report of a case. Gastroenterology 82:558-560, 1982
57. Smith FH, Jordan SM: Gastric ulcer: A study of 600 cases.
Gastroenterology 11:575-597, 1948
58. Flood CA, Hennig GC: Recurrence in gastric ulcer under
medical management, Gastroenterology 16:57-72, 1950
59. Smith FH, Boles RS Jr, Jordan SM: Problems of the gastric
ulcer reviewed--Study of one thousand cases. JAMA
153:1505-1508~ 1953
60. The Veterans Administration co-operative study on gastric
ulcer. Gastroenterology 61:561-564, 1971
61. Halse SA, Kristensen E, Moller-Jensen O, Morkbak NK:
Prognosis of medically treated gastric ulcer. Scand J
Gastroenterol 12:489-495, 1977
62. Piper DW, Shinners J, Greig M, Thomas J, Waller SL:

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

27S

BROOKS
Effect of ulcer healing on the prognosis of chronic gastric
ulcer. Gut 19:419-424, 1978
63. Miyake T, Ariyoshi J, Suzaki T, Oishi M, Sakai M, Ueda S:
Endoscopic evaluation of the effect of sucralfate therapy
and other clinical parameters on the recurrence rate of
gastric ulcers. Dig Dis Sci 25:1-7, 1980
64. Wright JP, Kahavovitz C, Marks IN: Gastric ulceration: A
follow-up study. S Afr Med J 60 (16):611-612, 1981
65. Gertler S, Isenberg J, ElashoffJ, Reedy T, Sandersfield M,
Peterson W: Gastric ulcer recurrence following medical
healing. Gastroenterology 84:1164, 1983
66. Jensen KB, Mollman K-M, Rabbek I, Madsen JR, Rune SJ,
Wolff HR: Prophylactic effect of cimetidine in gastric ulcer
patients. Scand J Gastroenterol 14:175-176, 1979
67. Alstead EM, Ryan FP, Holdsworth CD, Ashton MG,
Moore M: Ranitidine in the prevention of gastric and
duodenal ulcer relapse. Gut 24:418-420, 1983
68. Barr GD, Kang JY, Canalese J, Piper DW: A two-year
prospective controlled study of maintenancecimetidine and
gastric ulcer. Gastroenterology 85:100-104, 1983
69. Hentschel E, Schultze K, Weiss W, Rudiger E, Judmaci G,
Reichel W, Kerstan E, Horton J: Effect of cimetidine
treatment in the prevention of gastric ulcer relapse: A one
year double blind multicentre study. Gut 24:853-856, 1983
70. Mowat NAG, Needham CD, Brunt PW: The natural history
of gastric ulcer in a community: A four-year study. Quart J
Med 44:45-56, 1975
71. Johnson HD: The classification and principles of treatment
of gastric ulcers. Lancet 2:518-520, 1957
71a.Oi M, Oshida K, Sugimura S: The location of gastric ulcer.
Gastroenterology 36:45-56, 1959
72. Kirkpatrick JR, Lawrence JH, Forrest APM, Campbell H:
The short pentagastrin test in the investigation of disease.
Gut 10:760-762, 1969
73. Chapman MA, Werther JL, Janowitz HD: Response of the
normal and pathological human gastric mucosa to an instilled acid load. Gastroenterology 55:344-353, 1968
74. Ornsholt J, Amdrup E, Andersen D, Hostrup H: Arhus
county (Denmark) vagotomy trial: Acid secretory patterns
in patients with prepyloric, pyloric and duodenal ulcer.
Digestion 26(3):146-152, 1983
75. Schlegel W, Wenk K, Dollinger HC, Raptis S: Concentrations of prostaglandin A-, E- and F-like substances in
gastric mucosa of normal subjects and of patients with
various gastric diseases. Clin Sci Mol Med 52:255-258, 1977
76. Wright JP, Young GO, Klaff LJ, Weers LA, Price SK,
Marks IN: Gastric mucosal prostaglandin E levels in patients with gastric ulcer disease and carcinoma. Gastroenterology 82:263-267, 1982
77. Kobayashi K, Arakawa T, Nakamura H, Yamamoto S: An
endoscopic study on the mucosal prostaglandin level in
patients with peptic ulcer. World Congress of Gastroenterology, Stockholm, 1982, Abstr. 108
78. Garrett JM, Summerskill WHJ, Code CF: Antral motility in
patients with gastric ulcer. Am J Dig Dis 11:780-789, 1966
79. Miller LS, Malagelada JR, Longstreth GF, Go VLW:
Dysfunction of the stomach with gastric ulceration. Dig Dis
Sci 25:857-864, 1980
80. Fisher RS, Cohen S: Pyloric-sphincter dysfunction in patients with gastric ulcer. N Engl J Med 288:274-276, 1973
81. Mfiller-Lissner SA, Fimmel CJ, Sonnenberg A, Will N,
Midler-Duysing W-M, Heinzel F, Muller R, Blum AL:

28S

82.
83.

84.

85.

86.
87.

88.

89.

90.

91.

92.
93.

94.
95.

96.

97.

98.

99.

Novel approaches to quantify duodenogastric reflux in

healthy volunteers with type I gastric ulcer. Gut 24: 510518, 1983
Janowitz HD: Bile in the stomach: Gastroenterology
57:356-357, 1969, Editorial comment
Alexander-Williams J, Wolverson RL: Pathogenesis and
pathophysiology of gastric ulcer. Clin Gastroenterol
13:601-619, 1984
Fukutomi H, Yamagata J, Takase Y, Takao S: Endoscopical measurement of gastric blood flow of the patients with
gastric ulcer. World Congress of Gastroenterology, Stockholm, 1982, Abstr. 777
Kamada T, Kawano S, Sato N, Fukuda M, Fusamoto H,
Abe H: Gastric mucosal blood distribution and its changes
in the healing process of gastric ulcer. Gastroenterology
84:1541-1546, 1983
Thomas J, Greig M, Piper DW: Chronic gastric ulcer and
life events. Gastroenterology 78:905-911, 1980
Peters MN, Richardson CT: Stressful life events, acid
hypersecretion and ulcer disease. Gastroenterology
84:114-119, 1983
Isenberg JI, Peterson WL, Elashoff JD, Sandersfield MA,
Reedy TJ, Ippoliti AF, Van Deventer GM, Frankl H,
Longstreth FG, Anderson DS: Healing of benign gastric
ulcer with low-dose antacid or cimetidine: A double-blind,
randomized, placebo-controlled trial. N Engl J Med
308:1319-1323, 1983
Kellow JE, Barr GD, Cowen AE, Ward M, Wood L, Piper
DW: Comparison of ranitidine and cimetidine in the treatment of chronic gastric ulcer. Digestion 27:105-110, 1983
Barbara L, Corinaldesi R, Dobrilla G, Defretis G, Bianchi
Porro G, Parada A, Currata R, Paoluzi P, Mazzacca G,
Sabbatini F, Scuro LA, Civallini G, Verne G, Pera A:
Ranitidine vs cimetidine short term treatment of gastric
ulcer. Hepato-gastroenterology 30:151-153, 1983
La Brooy S, Taylor R, Hunt R, Golding T, Laidlaw J,
Chapman R, Founder R, Vincent S, Colin-Jones D, MiltonThompson G, Misiewicz J: Controlled comparison of cimetidine and carbenoxolone sodium in gastric ulcer. Br
Med J 1:1308-1309, 1979
Sutton DR: Gastric ulcer healing with tripotassium dicitrito
bismuthate and subsequent relapse. Gut 23:621--624, 1982
Morgan AG, McAdam WAF, Pacsoo C, Darnborough A:
Comparison between cimetidine and caved-S in the treatment of gastric ulceration and subsequent maintenance
therapy. Gut 23:545-551, 1982
Nagashima R: Mechanisms of action of sucralfate. J Clin
Gastroenterol 3 (Suppl 2):117-127, 1981
Tytgat GNJ, Hameeteman W, Olffen GH: Sucralfate, bismuth compounds, substituted-benzimidazoles, trimipramine
and pirenzepine in the short- and long-term treatment of
duodenal ulcer. Clin Gastroenterol 13:543-568, 1984
Rybicka J, Gibinski K: Methyl-prostaglandin E2 analogs for
healing of gastro-duodenal ulcers. Scand J Gastroenterol
13:155-160, 1978
Valnes K, Myren J, Ovigstad T: Trimipramine in the
treatment of gastric ulcer. Scand J Gastroenterol 13:
497-500, 1978
Black RB, Rhodes J, Davies GT, Gravelle H, Sweetnam P:
A controlled clinical trial of cholestyramine in the treatment
of gastric ulcer. Gastroenterology 61:821-825, 1971
Kelly KA, Malagelada J-R: Medical and surgical treatment

Digestive Diseases and Sciences, Vol. 30, No. 11 (November 1985 Supplement)

P A T H O P H Y S I O L O G Y OF PEPTIC U L C E R DISEASE
of chronic gastric ulcer. Clin Gastroenterol 13:621-634,
1984
100. Doll R, Pygott F: Factors influencing the rate of healing of
gastric ulcer: Admission to hospital, phenobarbitone and
ascorbic acid. Lancet 1:171-175, 1952
101. Piper DW, Hunt J, Heap TR: The healing rate of chronic
gastric ulcer in patients admitted to hospital. Scand J
Gastroenterol 15:113-117, 1980
102. Herrmann RP, Piper DW: Factors influencing the healing
rate of chronic gastric ulcer. Am J Dig Dis 18:1-6, 1973
103. James O, Kenefick JS: Pain in gastric ulcer. Lancet 1:562,
1974
104. Feldman M: Neural and hormonal factors in peptic ulcer
disease. J Clin Gastroenterol 3 (Suppl 2):51-56, 1981
105. Feldman M, Richardson CT, Fordtran JS: Sham feeding in
DU patients. Letter to editor. Gastroenterology 79:13531354, 1980
106. Lam SK, Lai CL, Lee NW, Fok KH, Ng M, Siv KF, Wong
J: Effective healing of duodenal ulcer with single night time
dose of 9xmetidine: A double-blind controlled study. Gastroenterology 85:1221, 1983
107. Gledhill T, Howard OM, Buck M, Paul A, Hunt RH: Single
nocturnal dose of a n H 2 receptor antagonist for the treatment of duodenal ulcer. Gut 24:904--908, 1983
108. McCloy RF, Greenberg GR, Baron JH: Duodenal pH in
health and duodenal ulcer disease. Gut 25:386-392, 1984
109. Malagelada J-R, Longstreth GF, Deering TB, Summerskill
WHJ, Go VLW: Gastric secretion and emptying after
ordinary meals in duodenal ulcer. Gastroenterology 73:992,
1977
110. Morrissey SM, Ward PM, Jayaraj AP, Tobey FI, Clark CG:
Histochemical changes in mucus in duodenal ulceration.
Gut 24:909-913, 1983
111. Olsen PS, Pedersen JH, Kirkegaard P, Been H, Stadil F,
Fahrenkrug J, Christiansen J: Neurotensin induced inhibition of gastric acid secretion in duodenal ulcer patients
before and after parietal cell vagotomy. Gut 25:481--484,
1984
112. Coluti TJ, Unger RH, Feldman M: Role of circulating
somatostatin in regulation of gastric acid secretion, gastric
release, and islet cell function. Studies in healthy subjects
and duodenal ulcer patients. J Clin Invest 74:417--423, 1984
113. Christiansen J, Kirkegaard P, Olsen PS, Petersen B: Interaction of calcium and gastrin on gastric acid secretion in
duodenal ulcer patients. Gut 25:174-177, 1984
114. Lorenz W, Troidl H, Barth H, Rohoe H, Schulz S, Becker
H, Dormann P, Schmal A, Kusche J, Meyer R: Stimulussecretion coupling in the human and canine stomach: Role
of histamine. In Stimulus Secretion Coupling in the Gastrointestinal Tract, RM Case, H Goebell (eds). Lancaster,
England, MTP Press, 1975, p 177
115. Dubey 17, Kundy S: Simultaneous measurement of gastric
and duodenal alkali secretion by in situ titration in health
and disease. Gut 24:1126-1129, 1983
116. Rachmilewitz D, Branski D, Sharon P, Karmeli F: The
possible role of endogenous prostanoids in the pathogenesis
of peptic ulcer. In Mechanisms of Mucosal Protection in the
Upper Gastrointestinal Tract, A Allen, G Flemstr6m, A
Garner, W Silen, LA Turnberg (eds). New York, Raven
Press, 1984, pp 329-333

116a.Guth PH, Baumann H, Grossman MI, Aures D, Elashoff J:

Measurement of gastric mucosal blood flow in man. Gastroenterology 74:831-834, 1978
117. Lam SK: Pathogenesis and pathophysiology of duodenal
ulcer. Clin Gastroenterol 18:447--472, 1984
118. Thomas JM, Misiewicz G: Histamine Ha receptor antagonists in the short and long-term treatment of duodenal
ulcer. Clin Gastroenterol 13:501-541, 1984
119. Hamilton I, Worsley BW, O'Connor HJ, Axon TR: Effects
of tripotassium dicitrato bismuthate (TDB) tablets or cimetidine in the treatment of duodenal ulcer. Gut 24:1148-1151,
1983
120. Walan A, Bergsaker-Aspoy J, Farup P, Gillberg R,
Halvorsen L, Kilander A, Lind T, Noesdal J, Offergaard S:
Four week study of the rate of duodenal ulcer healing with
omeprazole. Gut 24:A792, 1983
121. Howden CW, Forrest JAH, Reid JL: Effects of single and
repeated doses of omeprazole on gastric acid and pepsin
secretion in man. Gut 25:707-710, 1984
122. Sachs G: Pump blockers and ulcer disease. N Engl J Med
310:785-786, 1984
123. Pounder RE: Duodenal ulcers that will not heal. Gut
25:697-702, 1984
124. Lam SK, Lee NW, Koo J, Hui WM, Fox KH, Ng M:
Randomized crossover trial of tripotassium dicitrato
bismuthate versus high dose cimetidine for duodenal ulcers
resistant to standard dose of cimetidine. Gut 25:703-706,
1984
125. Bardhan KD: Refractory duodenal ulcer. Gut 25:711-715,
1984
126. Malinowska DH, Sachs G: Cellular mechanisms of acid
secretion. Clin Gastroenterol 13:322, 1984
GROUP DISCUSSION
I. Cleator, St P a u l ' s , C a n a d a : G a s t r i c u l c e r c a n be
a s s i g n e d to the f o l l o w i n g c l a s s e s : 1, m a l i g n a n t , 2,
b e n i g n d i v i d e d into A, p r i m a r y u l c e r , B, u l c e r
s e c o n d a r y to d u o d e n a l u l c e r s t e n o s i s , a n d C, drugi n d u c e d ulcer. W o u l d this c l a s s i f i c a t i o n b e h e l p f u l
in d e c i d i n g b e t w e e n m e d i c a l a n d surgical treatment?
F . P . Brooks: I t h i n k the c l a s s i f i c a t i o n is u s e f u l ,
a l t h o u g h I do n o t h a v e a n y e v i d e n c e t h a t r e s u l t s are
i m p r o v e d . I n t e r e s t i n g l y , a s p i r i n - i n d u c e d u l c e r s are
a l m o s t all in the a n t r u m as o p p o s e d to the c o r p u s .
P y l o r i c a n d p o s s i b l y p r e p y l o r i c u l c e r s t e n d to b e
a s s o c i a t e d with h y p e r s e c r e t i o n to t h e s a m e e x t e n t
as are d u o d e n a l u l c e r s . T h e d i s t i n c t i o n b e t w e e n
c o r p u s ulcers a n d a n t r a l u l c e r s goes b a c k a l o n g
time. It is v e r y likely t h a t t h e r e is a p a t h o p h y s i o l o g ical difference w h i c h is reflected in the r e s p o n s e to
treatment. After surgery, recurrences with corpus
ulcers are u n c o m m o n , b u t w i t h d u o d e n a l u l c e r s o n e
w o u l d e x p e c t a high r e c u r r e n c e rate.

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