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Update on the pathologicalclassification of gastritis
Hala El-Zimaity, M.D.M.S. Epidemiology
McMaster UniversityHamilton, Ontario
Canada
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CLASSIFICATION
GASTRITIS GASTROPATHY
Chemical gastropathy(NSAID/Bile reflux)
1.Acute2.Chronic
3.Uncommon Forms
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92%92%
58%58%
8%8%
Gastric UlcerGastric Ulcer
00
%%
99%99%
3030
%%
Duodenal UlcerDuodenal Ulcer
PercentPercent
ofof
GroupGroup
CAUSES OF PEPTIC ULCERCAUSES OF PEPTIC ULCER
100 Consecutive DU and 154 GU PATIENTS100 Consecutive DU and 154 GU PATIENTSVAMC, Houston
Hp POSITIVEHp POSITIVE
NSAID USERNSAID USER
NSAID ONLYNSAID ONLY
El-Zimaity HMT
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Case 1: 45 year old with dyspepsia
El-Zimaity HMT
Gastropathy= no acuteinflammation(unless thereis an erosion)
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Q: Should we care?
1. OTC analgesics including NSAID are widely
used, frequently taken inappropriately, andusers are generally unaware of potential foradverse side effects.
2. Can cause serious side effects includingdyspepsia, peptic ulcer, hemorrhage, and even
result in death.
El-Zimaity HMT
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Q1: HOW OFTEN DO YOU SEE
THE TRIAD?
Triad is only seen in 30 % ofchronic NSAID users.
Triad is most seen at incisura(less marked at other regions ofthe stomach).
Remaining 70%: edema
foveolar hyperplasia only
Fibrosis
FH only or SMF-H only
Incisura
El-Zimaity et al Hum Pathol 1996; 27(12): 1348-54El-Zimaity HMT
Chemical gastropathy is common; you willnot always see the triad; suggest it whensuspected
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CLASSIFICATION
GASTRITIS
1.Acute2.Chronic
3.Uncommon Forms
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GASTRITIS
ACUTE
H. pylori Other
Other bacteria
(Heilmanni,mycobacteria)
Syphilitic
Viral Parasitic
Fungal
Chronic
H. pylori(chronicatrophic gastritis)
Autoimmune (body
predominant)
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GASTRITIS
ACUTE
H. pylori Other
Other bacteria
(Heilmanni,mycobacteria)
Syphilitic
Viral Parasitic
Fungal
Chronic
H. pylori(chronicatrophic gastritis)
Autoimmune (body
predominant)
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Anatomy of The Stomach
WHAT IS NORMAL?
El-Zimaity HMT
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corpus
antrum
El-Zimaity HMT
Anatomy of The Stomach
Acid
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Anatomy of The CORPUS
corpus
antrum
Antrum-corpus junction
G cells
D cells
Parietal cells
ECL
Chief
ECL
corpus
Mucous
El-Zimaity HMT
acid
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NORMAL CORPUS
Chief
ECL
El-Zimaity HMT
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Anatomy of The ANTRUM
corpus
antrum
Mucous
Antrum-corpus junction
G cells
D cells
Parietal cells
ECL
antrum
El-Zimaity HMT
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Acid Secretion Pathophysiology
G cell Gastrin
Parietal cellFood
ACIDACID
El-Zimaity HMT
ECL
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Should you care?
If you speak Arabic you have H. pylori! Yes, you should care.
N b t i lik t h id
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corpus
antrum
El-Zimaity HMT
No bacteria likes too much acid
including H. pylori
Acid
H. pyloristarts its life in theantrum where it is less acidic
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No bacteria likes acidStarts in the antrum
H. pylorisurrounds itself with a bicarbonate cloud tocounter gastric acidity
(it produces urease which converts urea (abundant in saliva &
gastric juices) to ammonia and bicarbonate)C=0(NH2)2 + H+ +2H20 --urease--> HCO3- + 2(NH4)
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Acid Secretion Pathophysiology
G cell Gastrin
Parietal cell
Food/H. pylori
ACIDACID
El-Zimaity HMT
ECL
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Duodenal
Ulcer
G cell Gastrin
Parietal cell
Acid
ACIDACID
100 G cells
100 Parietal cells
El-Zimaity HMT
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Inflammation Depth-Duodenal Ulcer
MNC
PMN
H. pylori ACIDACID
Zone
1
2
3
Body
Zone
1
32
AntrumEl-Zimaity HMT
Inflammation in antrum only
I fl i D h D d l Ul
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Inflammation Depth-Duodenal Ulcer
MNC
PMN
H. pylori
Zone
1
3
2
Antrum
El-Zimaity HMT
H. pylori
toxins
Cytokines
Massive inflammatory response
Destroy stomach
A id S i
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Acid Secretion
G cell Gastrin
Parietal cell
ACIDACID
El-Zimaity HMT
ECL
Parietal cell
GASTRIC ATROPHYDestroyed corpus = no acid = bacteria moves proximal
Food/H. pylori
I fl i D h G i Ul
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Inflammation Depth-Gastric Ulcer
MNC
PMN
H. pylori
Zone
1
32
Antrum
ACIDACID
Zone
1
2
3
BodyEl-Zimaity HMT
Inflammation in both antrum and corpus
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Why is this important?
If patient is H. pyloripositive
Receives acid suppressor therapy withouttreating the infection (e.g. GERD patient andH. pyloriinfection missed)
You will help him develop gastric atrophy
El-Zimaity HMT
A id S ti
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Acid Secretion
G cell Gastrin
Parietal cell
Food/H. pylori
ACIDACID
El-Zimaity HMT
ECL
Parietal cell
G cell Gastrin
ECL
G cell Gastrin
ECL
HYPERGASTRINAEMIA
ECL HYPERPLASIA
PPI treatment = high pH
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ANTRAL MUCOSA
Before After PPIEl-Zimaity HMT
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CORPUS MUCOSA
Before After PPIEl-Zimaity HMT
VAMC, Houston
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Corpus gastritis Pan-atrophicAntral Predom.
Gastritis Stages
El-Zimaity HMT
G t iti St
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El-Zimaity et al Am J Gastro 2001;96:666-672
Gastritis Stages
B
A
B
A
B
A
A
B
A
A
Corpus atrophy
Normal corpus
Normal antrum
Atrophic border (antral corpus
junction) moves proximally andtowards greater curve with disease
progression.
El-Zimaity HMT
Endoscopic Recognition of the Atrophic Border
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Endoscopic Recognition of the Atrophic Border
Kimura and Takemoto 1969
Endoscopy 1969;1:87-97
Eastern (Japanese) beliefs
El-Zimaity HMT
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El-Zimaity HMT
Lesser curvature
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Greater curvature
Lesser curvature
Advancing atrophic borderEl-Zimaity HMT
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3 questions to answer if youalready decided it is H. pylori
1. Is it in the antrum only or antrum andcorpus?
2. If in the corpus, is inflammationsuperficial or deep?
3. Is there corpus atrophy?
El-Zimaity HMT
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Gastric atrophy
Absence of what is normally there:
Simple absence of glands (reduced thickness,increased fibrosis)
Replacement of what is normally there (with intestinal
metaplasia or pseudopyloric metaplasia)
Phenotypic corpus
Atrophy in Gastric cancer
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Tumor
Intestinal metaplasia I & II
Intestinal metaplasia III
Phenotypic antrum
12 %n = 2
Atrophy in Gastric cancer
(Intestinal type)(a) advancing atrophic border
(b) total atrophy of antrum
advancing atrophic bordertotal atrophy of the antrum
88 %n = 14
El-Zimaity HMT
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Isolated intestinal metaplasia = not importantEl-Zimaity HMT
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Continuous sheets of atrophy (IM and/PPM) is ominous
irrespective of IM subtypeEl-Zimaity HMT
Continuous sheets of atrophy (IM and/PPM) is
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PGI in Pseudopyloric metaplasiaEl-Zimaity HMT
ominous
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We know how to recognize intestinal
metaplasia How do we recognize pseudo-pyloric
metaplasia?
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El-Zimaity HMT
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Pepsinogen I (PG I) Anatomic Corpus
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Pepsinogen I (PG I) Anatomic Corpus
(pseudopyloric metaplasia)
ANATOMIC CORPUS
PGI
PGI
El-Zimaity HMT
GASTRIC ANTRUM
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GASTRIC ANTRUM
PEPSINOGEN I GASTRIN
El-Zimaity HMT
Pepsinogen I (PG I) Anatomic Corpus
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Pepsinogen I (PG I) Anatomic Corpus
(pseudopyloric metaplasia)
ANATOMIC CORPUS Gastrin
El-Zimaity HMT
PSEUDO-PYLORIC METAPLASIA
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PPM starts as early as 9 years old.
Atrophy always starts at antral corpus junctionand moves proximally and towards the greater
curve.
Cardona et al Journal of Clinical Pathology; 2005;58(11):1189-93.El-Zimaity HMT
Two things to remember
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Two things to remember
1.Look for the Atrophic Front (starts atantral corpus junction)
2.Recognize all forms of atrophy(absence of normal or replacementwith intestinal metaplasia and/or
pseudopyloric metaplasia)El-Zimaity HMT
What about Pernicious Anaemia?
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What about Pernicious Anaemia?
Scandinavian decent
Auto immune gastritis Parietal cell and
Intrinsic Factor
antibodies-megaloblastic anemia
Three to five foldincreased risk ofgastric cancer
El-Zimaity HMT
GASTRITIS PATTERN
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PA
GASTRITIS PATTERN
El-Zimaity HMT
pernicious anaemia
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Big overlap in the literature since most PA
studies were done beforeH. pylori era; some
deny its existence!
El-Zimaity HMT
In any H Pylori Gastritis
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In any H. PyloriGastritis
H. pyloripositive
patient
Use patients serum
as primary antibody Parietal cells stain
dark blue
= autoantibodies in every day H. pylorigastritis
El-Zimaity HMT
PERNICIOUS ANEMIA
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-
+
+
D
ECL
G
PD
Gastric acid
+ +
PERNICIOUS ANEMIA
2. G cells increase in number
1. Parietal cells disappear early
3. ECL cells keep growing
Gas
trin
El-Zimaity HMT
Acid production drops
much faster in PA; so, H.pyloriand associatedinflammation movesproximally much faster.
Parietal cell antibodiesMany folds higher
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Chromogranin GrimeliusEl-Zimaity HMT
PERNICIOUS ANAEMIA
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PERNICIOUS ANAEMIA
Corpus atrophy with
gastric cancer risk (intestinal type)
ECL hyperplasia and
eventually carcinoidsEl-Zimaity HMT
QUESTIONS TO ANSWER IN
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GASTRIC BIOPSIES?
1. Is it normal? Is it a gastritis or agastropathy?
2. Why it looks like H. pyloribut no bacteriafound?
3. Is there atrophy?
Landmark for NORMAL lymphoid
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infiltratesmuscularis mucosae
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Lymphoid infiltrate:
Loose next to muscularis mucosae Normal=
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Lymphoid Follicles in H. pylori
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infection
Pre-treatmentHave marginal zone,
mantle, and follicle center
Post treatmentLymphoid tissue first disappear
from marginal zone, followedby mantle zone.
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If you found this in a 45 year old
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El-Zimaity HMT
y y
with dyspepsia (mucosa looks
Safety Pin Appearance HP
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y pp
El-Zimaity HMT
NOT ALL BACTERIA IN THE
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STOMACH ARE H. pylori With PPI use, the gastric pH increases
which allows other bacteria to survive inthe stomach.
Make sure you are really looking at H.
pylori. Look for squiggle bacteria withsafety pin appearance.
Causes of (apparent) H.pylori
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negative gastritis Proton pump inhibitors (omeprazole etc.)
Recent antibiotics or eradication therapy
Missed organisms - few bugs
Focal chronic active colitis - Crohnsdisease
Other types of gastritis (e.g. lymphocyticgastritis)
GASTRITIS
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1.Acute2.Chronic
3.Uncommon Forms
LymphocyticEosinophilicCrohn's disease
SarcoidosisIsolated granulomatous
Lymphocytic Gastritis
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Protein loss.
Ratio of 25 CD3+ IEL/100 epithelial cells (focal).
Usually accompanied by lamina propriaplasmacytosis
Celiac Disease, Gastric Lymphoma, MenetriersDisease.
H. pylori(low H. pyloricount)
El-Zimaity HMT
Lymphocytic Gastritis
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El-Zimaity HMT
Crohns Gastritis
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Same as any other part of thegastrointestinal tract
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1.Focal enhanced inflammation
2.Granulomas
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Gastritis (acute and chronic) is multifocalEl-Zimaity HMT
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Granulomas in the Stomach
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1. Focally enhanced
gastritis (acute andchronic)
2. Granuloma
H. pylori Granuloma basics:
IBD
T.B. Sarcoid
Foreign body
El-Zimaity HMT
Crohns
Reporting gastritis
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1. Where am I? (Site - Antral, Oxyntic,
Cardiac, Pangastritis, Focal)2. Is it a gastritis or a gastropathy?
3. Are there epithelial/vascular changes(e.g. dysplasia or cancer)?