Diseases of the stomach
Dr. Székely Hajnal
2nd Department of Internal Medicine
2015/16-I
Stomach - functions
Food reservoir - regulated delivery to small
intestine
Mixing of food, initiation of digestion of
nutrients
Defence against ingested bacteria, toxins
Mucosal barrier: mucus, tight intercellular
junctions, gastric blood flow, high rate of gastric
mucosal turnover, prostaglandins
– Defence against auto-digestion
Role in vitamin B12 absorption: intrinsic factor
Classification of disease by etiology
Gastritis
Gastric ulcer
Non-ulcer dyspepsia
Gastric polyps
Gastroparesis
Gastric cancer
Zollinger-Ellison sy.
Symptoms
Epigastric pain
Nausea, vomiting
Haematemesis
Bloating, belching
Indigestion
progressive weakness, loss of body weight,
anaemia
Diagnostical tools
Upper GI endoscopy
Biopsy
Upper GI series
Endoscopis ultrasound (EUS)
Motility studies
Acute gastritis
Depletion in mucosal protection system
Acid/enzyme injury to gastric mucosa
Inflammation, erosions
– Etiol.:alcohol, Aspirin, NSAID’s,
corticosteroids,
– Helicobacter pylori, bile.
– Diet - spicy food
- Systemic infection: salmonellosis
– Environmental factors - radiation
Endoscopy
Normal antrum
Acute gastritis
Acute gastritis
Acute gastric stress ulcers
Erosive & Hemorrhagic Gastritis
Etiologies: ETOH, NSAIDS; stress from underlying
severe medical/surgical disease (common in ICU
patients).
Symptoms: Often asymptomatic; anorexia, N&V,
“dyspepsia”; initial presentation may be GI bleeding.
Dg- endoscopy:
DDx: bleeding peptic ulcer, esophageal varices,
Mallory-Weiss tear.
Th. PPI (sucralfat) – 4 week course
Stress ulcers
acute ill patients/ ICU
trauma, sepsis, shock, hypotension, resp. Failure
/ mech. ventilation, coagulopathies, ARF, CNS
injury.
extensive burns (Curling’s ulcer)
Neurological disease (Cushing’s ulcer)
Superficial erosions common, develop quickly.
Bleeding in up to 6% with  associated mortality.
Pathophys: gastric mucosal blood flow.
Chronic gastritis
Type I: Autoimmune gastritis
Progressive immune destruction of GPC
– Terminology
Chronic superficial gastritis
Chronic atrophic gastritis
Gastric atrophy
Pernicious anaemia
Anti-gastric parietal cell antibodies
Auto-immune gastritis
Circulating auto-antibodies (anti-GPC)
Inflammation and atrophy involving
fundus/corpus
Low secretion of acid +/- enzymes
Compensatory high serum gastrin levels
Associated with other auto-immune
diseases/HLA
Secretion of intrinsic factor decreased
Associated with low serum B12/
megaloblastic anaemia
Chronic gastritis
– Type II:
Not auto-immune in origin
Different distribution: antral-predominant
Acid secretion increased (some normal)
Serum gastrin normal (some increased)
Concept crystallised with discovery of the role of...
Chronic gastritis
Type II: Helicobacter pylori gastritis
– evidence for role of H. pylori in gastritis/ulcer
epidemiology
– 90% of patients with duodenal ulcer
– 70% with gastritis/gastric ulcer (80-90% if not
taking NSAIDs)
treatment effect
– Hp clearance leads to ulcer healing
– High recurrence after ulcer healing without Hp
clearance
Helicobacter pylori
Gram negative, curved/spiral organism
Motile, flagellate organism
> 20 different species
Adapted to niche of life in the stomach
Colonisation
motility: flagellae
urease enzyme activity
acute infection causes transient hypochlorhydria
Adherence
bacterial adhesins (BabA)
Tissue Injury
lipopolysaccharide, cagA, vacA, others
Pathogenesis
Factors permitting colonisation:
(i) Spiral shape and flagellate – motility within
this mucous layer.
(ii) Urease activity – generates ammonium ions
that buffer gastric activity
(iii) Micro-aerophilism – survival within the
mucous gel
(iv) Attachment to epithelial cells
(v) Evasion of immune response
Acute Helicobacter infection
- Bacterial factors: cagA, (?others) - induce IL-8
secretion by the gastric epithelial cells (+IL-6, IL-7,
IL-15)
- IL8: chemotactic, activates neutrophils
-IL-6, IL-7, IL-15: activate antigen-specific response
-Bacterial lipopolysaccharide:
directly chemotactic
Acute neutrophilic response
Chronic active infection
However H. pylori remains intra-luminal, so
- Neutrophil response fails to clear bacterium
- Bacterial persistence sets up T-cell dependent
response: lymphocytes, plasma cells
- Neutrophil response persists
Chronic
active
Gastritis
Transmission (?)
I,P.: cohors effect
Natural History of Helicobacter pylori Infection.
Different possible outcomes
Gastric ulcer - symptoms
Epigastric pain; burning, gnawing, aching, “hungerlike”.
Not sensitive/specific enough to serve as dg.
tool
Pain relief with eating (50%), antacids, with
subsequent return in 2-4 hrs.
Nocturnal awakening with pain common.
Physical exam more often unremarkable;
rectal for occult blood is important.
H. pylori eradication
10-14 day course:
– PPI 2x daily
– Clarithromycin* 500 mg 2x daily
– Amoxicillin 1 gram 2x daily
Alternative : metronidazole*, tetracycline.
*Resistant strains common.
1xPPI - Gastric ulcer– additional 4-6 wks
H pylori reinfection rates are very low
(<.5%/year).
Sequential th.
22
NSAID ulcers
Selective Cox-2 vs. non-selective (N-S) NSAIDs.
Treatment: PPI 4-8 wks, plus stoping NSAID; rapid vs
delayed healing if NSAID continued.
H. pylori not a cofactor but often present- must
eradicate if present.
NSAID –gastritis
Very common - most unrecognized (no symptoms).
Dyspepsia in 25% of patients with NSAID gastritis.
If symptoms present – stop NSAID’s + PPI for 2 wks.
Persistent or worsening symptoms endoscopy
(EGD) PPI 2-4 wks.
Chemical gastritis – type III
• Commonly seen with
bile reflux (toxic to cells)
• Prominent hyperplastic
response (inflammatory
cells scanty)
• With time – intestinal
metaplasia
Hypertrophic gastropathy
Thickened stomach wall, thickened folds
Menetrier’s disease
– expansion of foveolae, increased mucin
– can lead to protein loss into lumen
Hypertrophic-hypersecretory gastropathy
– increased fundic glands
Hyperplasia of glands secondary to
Zollinger-Ellison syndrome
– gastrinoma -> hyperacidity -> ulcers
Zollinger-Ellison Syndrome
Hypersecretory state - gastrin secreting tumor
(gastrinoma).
Tu. in pancreas, duodenum, lymph nodes;
2/3 malignant, metastasize to liver; slow growth.
Excess acid secretion leads to recurrent or refractory
duodenal ulcers.
Can lead to malabsorbtion, weight loss.
Testing: Increased serum gastrin (often >500 pg/ml)
levels (nl< 100pg/ml), + document gastric pH <3 (to r/o
hypochlorhydria which can also raise gastrin levels)
Special imaging - to find primary tumor and/or met.:
somatostatin receptor scintigraphy
endoscopic ultrasonography
26
Treatment of Z-E
If isolated primary tumor: PPI + resection.
If metastasis: PPI in high dose to decrease
basal acid output.
Prognosis: good for isolated tumor.
27
Gastric polyps
Hypeprlastic
Adenoma
Inflammatory
GIST
Carcinoid
Neuroendocrine tumors
Dg.:endoscopy + biopsy
Th.: polypectomy
Gastroparesis
Sy.:early satiety, postprandial bloating,
nausea, vomiting, loss of weight
Dg.: gastroscopy, gastric emptying
study
Causes: DM, vagotomy, scleroderma,
amyloidosis, hypothyreoidism,
idiopathic
Th.:prokinetics, Erythromycin,
Tegaserod (5HT4 antagonit), gastric
pacemaker, jejunostomy for feeding.
Diseases of the pancreas
Pancreas- anatomy
Pancreas –
enzyme
secretion
Pancreas- enzyme secretion
Acute pancreatitis - patophysiology
Acute Severe Pancreatitis
Pathophysiology
Injury or disruption of pancreatic ducts leakage of
active pancreatic enzymes  autodigestion
Breakdown of cell membranes  edema 
vascular
damage, hemorrhage, necrosis  inflammatory mediators
 Shock, MODS, …..
37
Tests
Trypsinogen
Trypsinogen activation peptide (TAP) I
Trypsin
Inflammatory cascade (IL6, IL-8, TNF-)
II
C - reactive protein
Pancreatic injury
III
Amylase, Lipase, Trypsinogen
IV
Blood tests
Amylase and lipase
Lipase-organ specific
Amylase - starts to rise 2-6 hr after onset of pain,
peaks @ 24 hours, return to normal @ 72 hr
Lipase - rises later than amylase (48 hours)
return to normal 5-7 days.
NO CORRELATION WITH
DISEASE SEVERITY!
 WBC’s, CRP
 glucose
 lipids
 calcium
 magnesium
C-reactive protein (CRP)
Severity –inl. Markers (TNF-alfa, IL-8)
Acute phase reactant, synthesis by the
hepatocytes
Peak in serum is three days after the onset
of pain
Most popular single test severity marker
used today
Gold standard for the prediction of the
necrotizing course of the disease
Accuracy of 86%
Readily available
Abdominal Ultrasound (US)
Little part in the diagnosis.
Role in biliary pancreatitis
– Stones in gallbladder
– Common Bile Duct dilation
US findings should be examined in all
patients with possible acute pancreatitis on
admission.
Contrast enhanced abdominal CT
Not necessary for dg.
Diagnostic doubt, atypical presentations
Asymptomatic hyperamylasaemia or hyperlipasemia
Non-visualization of a part of the pancreas
Sensitivity: 90-95%, Specificity – 100%
Ranson-Imrie Score
On admission or dx
Age >55 years
WBC >16K/mm³
BG >200 mg/dl
LDH >400 IU/L
AST >250 IU/L
During first 48 hours
 in HCT by 10%
IV Fluid needed > 6000 ml
Ca < 8 mg/dl
PO2 < 60 mm Hg
BUN > 5 mg/dl after IV’s
albumin < 3.2 gm/dl
Early agressive th.:250-500 ml/ h (except: renal,CV) for 12-24h
goal: decrease BUN, Htc, manintain creat.
Vasoactive drugs – dopamine
 BP via vasoconstriction in high doses
 renal perfusion in lower doses
Controlled fluid replacement
Enteral feeding- stabilizes the gut barrier
function, prevents systemic complications,
improves morb. and mortality.
Safer, less exp. than TPN.
Nutrition - Rationale
Hyper metabolic state
– Total energy expenditure 1.5 x resting energy
requirement
Nutrition depletion
– Starvation
– Preexisting protein-calorie malnutrition &
micronutrient deficiency
Parenteral Nutrition
Rationale against
Pancreatic rest
– Poorly defined
Increased risk of sepsis
– Gut atrophy - increased
bacterial translocation
– Hyperglycemia
Greater costs
Enteral Nutrition –within 48 h. in SAP
Rationale for:
Minimal effect on pancr.
secretions
Prev. of gut mucosal atrophy
Avoid TPN related
complications (line sepsis,
hyperglycemia)
Rationale against
Proximal displacement of the
feeding tube may worsen the
disease outcome
Management – Pain
“Rest” the pancreas & GI tract
– NPO
– NG tube to suction
– parenteral vs. enteral
nutrition
– drug therapy
Manage Pain
– Major analgetics
– NSAID,
spasmolytics
–
PPI’s
Antibiotics
Sepsis - Accounts for > 80% of deaths
Intestinal flora - Gram negative bacteria
Mechanism – translocation of the bacteria across
the gut wall
Early (1 week) Sterile necrosis
– Massive inflammatory response – (SIRS)
Late – Infected necrosis
Appropriate AB - active against in particular gramnegative organisms
as early as possible after the identification of a
severe attack
Management –
biliary pancreatitis
Passage /impaction of a
stone
Women (age of 50-70)
Mortality 6%
Abnormal liver function tests
– ALT elevation of > 3 x normal
Ultrasound
– Gallstone
ERCP:
Gold standard
– Potential serious
complications
Pancreatic necrosis
Sterile necrosis – SIRS(First week)
– Mortality rate of 10-40%
Surgery:
Massive pancreatic necrosis (>50%) with a
deteriorating clinical course (Evidence C)
Patients with progression of organ
dysfunction
No signs of the improvement
Infected necrosis – Sepsis (After 3 weeks)
– Mortality – 20-70%
– CT guided FNA with gram stain and culture is a
confirmatory test
– necrosectomy
Acute Severe Pancreatitis –complications
Pulmonary
Cardiovascular
Coagulation
Renal
Immunological
Management of Acute Pancreatitis
I.
Confirm Acute
I.
Acute Pancreatitis
Pancreatitis
I. Confirm
Confirm Acute
Pancreatitis
Amylase/
Lipase
Amylase/
Lipase
Amylase/ Lipase
Lipase
> Amylase
Lipase
Lipase >
> Amylase
Amylase
Trypsinogen
2
Trypsinogen
Trypsinogen 2
2
CT
scan -- Atypical
cases
CT
CT scan
scan - Atypical
Atypical cases
cases
II.
Initial Management
II.
II. Initial
Initial Management
Management
Pain
control/ Fluid
Pain
Pain control/
control/ Fluid
Fluid
NPO
NPO
NPO
NG
NG Tube
Tube NOT
NOT recommended
recommended
III. Severity Stratification
III.
III. Severity
Severity Stratification
Stratification
APACHE II
APACHE
II
APACHE
II
C-Reactive
Protein
C-Reactive
C-Reactive Protein
Protein
Mild AP
Mild
Mild AP
AP
Severe AP
Severe
Severe AP
AP
Management of Acute Pancreatitis
Mild
MildAP
AP
80%
80%of
ofcases
cases
<<5%
5%of
ofmortality
mortality
Severe
SevereAP
AP
20%
20%of
ofcases
cases
>>95%
95%of
ofmortality
mortality
Recommended
Recommended(All
(Allpts.)
pts.)
Admit
Admitto
togeneral
generalward
ward
Refeed
Refeedwhen
whenpain
painsubsides
subsides
Recommended
Recommended
Admit
Admitto
toICU
ICU
Antibiotics
Antibiotics
CT
CTscan
scan--day
day33
Not
NotRecommended
Recommended
Antibiotics
Antibiotics
CT
CTscan
scan
PPI
PPI
Necrosis
Necrosis
SterileSterile-observe
observe
IfIfinfection
infectionsuspected
suspected--FNA
FNA
Necrosectomy
Necrosectomyin
ininfected
infectednecrosis
necrosis