Diseases of the Stomach

Non-neoplastic pathology of the Stomach

A. Congenital

diaphragmatic hernias pyloric stenosis

B. Miscellaneous

gastric diverticula gastric dilataion gastric rupture

C. Acquired

inflammation gastritis peptic ulcer

Pyloric Stenosis

A. Congenital

Congenital hypertrophic pyloric stenosis

familial, multifactorial inheritance ♂ : ♀ = 4 : 1 hypertrophy of circular muscle of the muscularis propria projectile vomitting visible peristalsis

B. Miscellaneous

post-inflammatory (gastritis, ulcers) └> fibrosis giving rise to stricture

neoplasia

Gastritis

inflammation of the gastric mucosaAcute gastritis : neutrophil infiltration

Chronic gastritis : lymphocytes, plasma cells +/- intestinal metaplasia and atrophy

Special forms of Gastritis

eosinophilic gastritis : may co-exist in eosinophilic enteritis lymphocytic gastritis : intraepithelial CD8+ T suppressor lymphocytes granulomatous gastritis : idiopathic (extremely rare)

Acute Gastritis

an acute mucosal inflammatory process, usually of a transient nature

congestion – hemorrhage – erosions pathogenesis

↑ acid secretion with back diffusion↓ bicarbonate buffer production↓ blood flowdisruption of the adherent mucous layerdirect damage to the epitheliumregurgitation of bile acids

Gross

- many small spots of bleeding- patients can die of shock (uncontrollable hemorrhage)

acute gastritisacute erosive gastritisacute ulcers

Causes of Acute Erosive Gastropathy

a. Drugs

- NSAIDs (aspirin, ibuprofen)- corticosteroids- cigarette smoking (contributory factor)

b. Direct-acting luminal chemicals

- ethyl alcohol- bile reflux (in postgastrectomy pts)- corrosive ingestion

c. Stress

- severe burns (Cushing’s ulcer)- intracranial lesions (Cushing’s ulcer)- post myocardial infarction

d. Ischemia

- shock- portal hypertension- gastric antral vascular ectasia (GAVE)

e. Chemotherapy

Esp hepatic arterial infusion

Chronic Gastritis

the presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia. The latter may become dysplastic and constitute a background for the development of carcinoma.

Aetiology

- H.pylori associated chronic gastritis- immunologic (autoimmune) : pernicious anemia- toxic : alcohol, cigarettes- postsurgical : bile reflux- motor(?) and mechanical causes- radiation- granulomatous conditions- miscellaneous : graft-vs-host disease

Helicobacter pylori

motile (flagella) urease (ammonium from endogenous urea to buffer acid) adhesion (bind to epithelial cells) toxins (proinflammatory) spiral organisms located in the mucous layer covering the mucosa normally doesn’t cross/penetrate tissueso most important ateiologic factor in chronic gastritiso present in 90% of pts with CG affecting the antrumo colonization rates ↑ with ageo most infected pts are asymptomatico diseases associated with H pylori :

chronic gastritispeptic ulcergastric carcinomagastric lymphoma

Mechanisms Contributing to Peptic Ulceration

urease which generates free ammonia protease which breaks down glycoprotein in the gastric mucosa phospholipases which damage epithelial cells any may release

bioactive leukotrienes neutrophils attracted by H pylori release myeloperoxidase H pylori colonization damages epithelial and endothelial cells thrombotic occlusion of capillaries promoted by a bacterial platelet-

activating factor other antigens recruit inflammatory cells to the mucosa. The

chronically inflamed mucosa is > susceptible to acid injury▪▪

▪

Microscopy (?)

active inflammation : neutrophils, lymphocytes, plasma cells and lymphoid aggregates

regenerative changes : mitoses in epithelium, < mucous vacuoles metaplasia : internalization of gastric epithelium atrophy : loss in glandular structures and specialized cells hyperplasia : gastrin-producing G cells in antrum dysplasia L cytologic atypia carcinoma-in-situ : frank carcinoma

Histology

atrophy of fundus glands no parietal cells lymphoid aggregates intestinal metaplasia dysplasia carcinoma

Autoimmune Gastritis (Pernicious Anemia)

Vit B12 deficiency megaloblastic anemia atrophic gastritis with failure of intrinsic factor (IF) production by parietal

cells IF-Vit B12 complex is normally transported to the ileum where it adheres

to IF-specific receptors on the ileal cells; hence impaired absorption immunologic destruction of parietal cells by antibodies

Type I : blocking Abs (75%) blocks binding of B12 to IFType II : prevents binding of complex to ileal receptorsType III : parietal canalicular Ab (90%) are localized in the microvilli

and directed against the gastric proton pump

Peptic Ulcer

they are chronic, most often solitary lesions that occur in any portion of the GIT, exposed to the aggressive action of acid-peptic ulcer

a breach in the mucosa usually <4cm in diameter penetrates the muscularis mucosa and deeper – may perforate frequently recurrent; may heal

Sites of Peptic Ulcers

Site Comment

Duodenum (1st part) 75% of peptic ulcers

Stomach 20% of peptic ulcers, mainly in lesser curvature and pyloric antrum

Lower esophagus associated with acid reflux

Stomach (marginal) ulcer at the stoma of a gastrectomy

Meckel’s diverticulum assoc with the presence of heterotropic gastric mucosa

Distal duodenum, in addition to gastric and 1st part of duodenal jejunum (MCQ!) ulcers, in pts with Zollinger-Ellison syndrome

Ileum, colon v.rare; assoc with presence of heterotopic gastricmucosa

Differences Between Duodenal & Gastric Ulcers

Duodenal Gastric

♂ : ♀ 3 : 1 2 : 1Age peak 35-45 yrs ↑s with ageEnvironment stress ?Genetics 1st degree relatives no role

Blood grp O Non-secretion of bld grp substances HLA-B5 antigen

Conditions Associated with Peptic Ulcers

Precipitating Factors

- analgesics- anti-inflammatory drugs- alcohol- smoking- psychologic stress- H pylori infection

Pathophysiology of Gastric Ulcer Disease

Impaired mucosal defenses

1. Motility defect

reflux of duodenal contents through incompetent pyloric sphincters

bile acids act as dilutant : ↓ mucosal barrier vs acid and pepsin

delayed gastric emptying including reflux material delayed gastric emptying and reflux

2. Ischemia

3. Inflammation

attenuates the barrier coated by the epithelial cells with the

mucus and bicarbonate they secrete

Pathophysiology of Duodenal Ulcer

↑ acid-pepsin secretion ↓ mucosal defenses

1. ↑ acid and peptic secretory capacity2. .3. .

Macroscopic Appearance

round to oval, sharply demarcated punched out defect the mucosal margin may overhang the base slightly variable depth base is smooth and clean scarring and puckering of the wall

Microscopic Appearance

4 recognisable layers :

1. surface zone of fibrinopurulent exudates2. acidophilic layer of necrotic tissue3. zone of granulation tissue4. zone of dense scar tissue

Other features :

5. interruption of the muscularis propria6. proximation of the muscularis propria and mucosae7. endarteritis obliterans

bv erodes, thromboses

Complications of Peptic Ulcer Disease

Bleeding

in 25-30% of patientsmost frequent complication; may be massiveaccounts for about 25% of ulcer deathsmay be first indication of presence of ulcer

Perforation

in 5% of patientsaccounts for 2/3 of all ulcer deaths

obstruction from edema or scarring of pyloric canal/duodenum

duodenumcrampy abdominal pain and vomiting

intractable pain

Complications of Chronic Peptic Ulcer Disease

Gastric adenocarcinoma

antrum related to associated chronic antral gastritis proximal stomach (stump) following antral resection 1 digit %

Adenocarcinoma

large irregular ulcer overhanging edges dirty necrotic tissue invasion of wall lymph node enlargement

Surgical

recurrent stomal ulcer retained antrum postgastrectomy gastritis (reflux?) dumping syndrome afferent loop syndrome

Diagnosis

Mucosal Biopsy

gastric ulcer duodenal ulcer

Final Diagnosis (%)

duodenal ulcer 24.3%

gastric erosions 23.4%gastric ulcer 21.3%varices 10.3%Mallory-Weiss tear 7.2%

Non-neoplastic Conditions of the Small and Large Intestines

Congenital

Meckel diverticulum congenital aganglionic megacolon – Hirschsprung

Acquired

vascular disorders enterocolitis malabsorption syndromes idiopathic inflammatory bowel disease diverticular disease intestinal obstruction

Ischemic Bowel Disease

small/large intestine or both particular bv affected – site, size, end-arteries arterial and/or venous system acute/insidious occlusion cause of ischemia infarction may be transmural, mural or mucosal

diagram : sup and inf mesenteric

Predisposing Conditions for Ischemia

arterial thrombosis

atherosclerosis, vasculitis, hypercoagulable states

arterial embolism

cardiac vegetation, aortic atheroembolism

venous thrombosis

hypercoagulable states, oral contraceptives, sepsis

non occlusive ischemia

CCF, shock, dehydration, vasoconstrictive drugs

miscellaneous

radiation, volvulus, herniation, adhesions

Hernia

a) Effects

▪ Functional Obstruction

- vomiting- distention

▪ ischemia of muscle

- pain after meals (abd angina)

▪ mucosal necrosis

- exudation and hemorrhage into lumen- bloody diarrhea

▪ necrosis of muscle

- absence of peristalsis

▪ transmural necrosis▪ Gram negative sepsis

b) Complications

▪ constriction of bv in mesentery produces ischemia & infarction by strangulation▪ constriction of bowel lumen produces intestinal obstruction

Microbial Causes of Diarrheal Disease

Bacterial Viral

o E coli - HSVo salmonella - CMVo Shigellao mycobacteriao vibrio cholerae

Fungal Protozoal

o candida - entamoeba histolyticao asperigillus - giardia lambliao mucormycosis - crytosporidiao histoplasma

Helminths

o Ascaris

o Trichuriso Schistosma

n.b. may be fatal for immunocompromised patients (diabetes, HIV)

Acute Appendicitis

Obstruction of lumen

fecalith (v.hard, stone-like stools) lymphoid hyperplasia

multiplication of luminal bacteria

invasion of mucosa and wall inflammation

Perforated Acute Appendicitis

rapid involvement of full thickness of the wall perforation generalized peritonitis pelvic abscesses subphrenic abscesses

Acute Appendicitis

edema and turgidity congestion and hemorrhage fibrinopurulent exudates ulceration

Interstitial Tuberculosis

primary or secondary involvement ileocecal region is the commonest site circumferential ulcers, thickening of wall, strictures regional lymphadenopathy miliary spread caseasting granulomas mycobacterium tuberculosis : acid fast bacteria in Ziehl-Neelsen stain

Amorbiasis

Entamoeba histolytica (protozoa) colorectum esp cecum bloody diarrhea

ingested cysts release trophozoites (amoeboid form) which invade the colonic epithelium

amoebic proteins aid tissue invasion (proteinases, lectin, amoebapore)

diffuse colitis, ulcers, “amoeboma” flask-shaped ulcers with shaggy edges, napkin-like constrictive mass

(granulation tissue) liver abscesses (40%) via portal circulation

Microscopy

Entamoeba histolytica trophozoites with round dense nucleus and ingested rbc uinicellular

Giardiasis

Giardis lamblia (protozoa) asymptomatic or mild indigestion/diarrhea or malabsorption ingested cysts release trophozoites in duodenum pear-shaped and binucleate (“ghost-like”) biopsy : normal to villous atrophy with inflammatory cells in LP

Pseudomembranous Colitis (Antibiotic-associated colitis)

acute colitis characterized by formation of an adherent inflammatory exudates (pseudomembrane) overlying sites of mucosal injury

acute/chronic diarrheal illness broad-spectrum antibiotic therapy toxin-forming stains of the commensal (Clostridium difficile) flourish after

alteration of the intestinal flora 2 exotoxins A and B L bind to receptors on epithelial cells and cause

damage diagnosis L detection of C.difficile exotoxin in the stools

- fibrin - mucus- WBCs

MCQ : know the antibiotics that cause pseudomembranous colitis

Inflammatory Bowel Disease (IBD)

a large group of diseases of the small and large intestines in which inflammation has a pathogenic role

infectious agents, ischemia, radiation, toxic materials etc

idiopathic IBD, viz ulcerative colitis(UC) and Crohn Disease Ulcerative Colitis and Crohn Disease

- clinical, biochemical, radiographic and oathologic correlation- diagnosis of exclusion

Aetiology and Pathogenesis of IBD

o Genetic Predisposition : familial aggregations, HLA studieso Infectious Causes : Mycobacterium paratuberculosis etco abnormal host immunoreactivity

(host mucosal immunity is stimulated and then fails to downregulate; marked improvement with corticosteroids)

o inflammation of the final common pathway(borne out by clinical manifestations and diagnostic pathologic factors)

Crohn Disease (Regional Enteritis)

A recurrent granulomatous, fibrosing inflammatory disorder that usually affects the terminal ileum or colon but may occur at anl level of the GIT +/- other systemic manifestations.

Systemic Manifestations :

1. Skin

erythema nodosum, pyoderma gangrenosum

2. Joints

migratory polyarthritis, sacrolitis, ankylosing spondylitis

3. Eye

uveitis, conjunctivitis

4. Liver

sclerosing cholangitis, chronic active hepatitis(thus imprt to check liver function)

Salient Features in Rectal Biopsy

Active Phase

a. irregular mucosal surface with luminal pusb. loss of epithelium with ulcerationc. increased chronic inflammatory cell content of lamina

propria

d. focal polymorph infiltration with crypt abcesses and edemae. vascular congestionf. mucin depletion of goblet cells

Complications

1. nutritional2. toxic megacolon (will have to resect, dilated [uncommon but recognized]

v.bad, no haustrations)3. malignancy

may be multifocal carcinoma from glandular epithelium usually undifferentiated (thus usually try to look for dysplasia : early sign of cancer) prophylactic proctocolectomy (anus) ileostomy : outlet through anterior abdominal wall. fluid fecal

material. continuous outflow into bag. empty periodically.

Diverticular Disease

Pathogenesis

1. Foci of muscular weakness in colonic wall2. herniation of mucosal submucosa3. ? disordered motility ↑ intraluminal pressure

e.g. Meckel’s diverticulum (true) all layers (congenital) (false) excluding muscular layer

Complications

acquired outpouchings of mucosa and submucosa focal weakness in colonic wall increased intraluminal pressure

Obstructive Lesions of the Gastroinestinal Tract

1. Mechanial Obstruction

strictures, congenital and acquired atresis (absence or closure of a natural passage) meconium in mucoviscidosis (cystic fibrosis) imperforate anus obstructive gallstones, faecoliths, foreign bodies adhesive bands or kinks

hernias vovulus intussusception neurogenic paralytic ileus tumours

2. vascular obstruction

bowel infarction

Megacolon (Hirschsprung disease)

A. Congenital

failure during embryogenesis of development of Meissner’s and Auerbach’s plexuses

absence of ganglion cells (rectum, sigmoid) obstructive constipation fluid/electrolyte imbalance perforation meconium peritonitis