SMALL INTESTINE

CELIAC DISEASE
CELIAC DISEASE

 Celiac disease  AKA  celiac sprue or gluten sensitive enteropathy,

 Defination  It is an immune-mediated disorder triggered by the ingestion of gluten-containing foods such as
wheat, rye, or barley in genetically predisposed individuals.
CELIAC DISEASE
 Pathogenesis 
 Enterocytes  induced to express surface
MIC-A  d/t stress
 Gluten  gliadin peptides  epithelial cells
to express IL-15  activation and
proliferation of CD8+ intraepithelial
lymphocytes  express NKG2D (a natural
killer cell marker and receptor for MIC-A) 
l/2 epithelial damage  enhance passage of
gliadin peptides into the lamina propria where
they are deamidated by tissue
transglutaminase  gliadin peptides interact
with HLA-DQ2 or HLA-DQ8  on antigen-
presenting cells  stimulate CD4+ T cells 
produce cytokines  tissue damage.
 Associated with  type 1 diabetes,
thyroiditis, Sjögren syndrome, and IgA
nephropathy
CELIAC DISEASE

 Morphology
 Location  second portion of the duodenum or proximal
jejunum
 characterized by  increased numbers of intraepithelial
CD8+ T lymphocytes, crypt hyperplasia, and villous atrophy
 plasma cells, mast cells, and eosinophils  within lamina
propria.
 The combination of histology and serology is most specific
for diagnosis of celiac disease T lymphocytes, which can be
complete loss of villi,
recognized by their small,
plasma cell infiltrates in densely stained nuclei relative
the lamina propria to larger, pale-staining
epithelial nuclei.
CELIAC DISEASE

 c/f  chronic diarrhea, bloating, or chronic fatigue, anemia,

 Inv most sensitive test is the measurement of IgA antibodies against tissue transglutaminase.
 IgA antiendomysial antibodies
 IgG anti–tissue transglutaminase antibodies
 t/t  gluten free diet
 increased risk of malignancy  enteropathy associated T-cell lymphoma
INFLAMMATORY BOWEL DISEASE (IBD)

 Inflammatory bowel disease (IBD) is a chronic condition resulting from complex interactions between intestinal
microbiota and host immunity in genetically predisposed individuals that leads to inappropriate mucosal immune
activation.
 CROHN’S DISEASE AND ULCERATIVE COLITIS
 Age - teens and early 20s
 IBD are also associated with other autoimmune diseases including diabetes mellitus, rheumatoid arthritis, and
psoriasis.
INFLAMMATORY BOWEL DISEASE (IBD)

 Pathogenesis :-
 Mucosal immunity –
 Polymorphisms in genetic loci that include genes in both proinflammatory, e.g., interferon-γ, and anti-inflammatory (immunoregulatory),
e.g., IL-10 and the IL-10 receptor, signaling are involved.
 Th1 polarization is present in both diseases, although there is also evidence of Th2 activation in ulcerative colitis, perhaps reflecting the
underlying differences in genes associated with disease.
 Th17 signaling is also important to IBD pathogenesis, as both Crohn disease and ulcerative colitis are linked to polymorphisms in the IL-
23 receptor and other molecules involved in Th17 signaling.
INFLAMMATORY BOWEL DISEASE (IBD)

 Pathogenesis :-
 Autophagy and cellular stress responses
 ATG16L1 and IRGM, are involved in autophagosome formation
 Autophagy is a normal homeostatic mechanism that clears damaged organelles and is upregulated in response to cellular stress including
nutrient deprivation and endoplasmic reticulum stress. Autophagy is also a means of clearing sources of reactive oxygen species and
intracellular pathogens
 The ATG16L1 mutation that is linked to Crohn disease promotes ATG16L1 degradation, thereby limiting autophagy.
INFLAMMATORY BOWEL DISEASE (IBD)

 Pathogenesis :-
 Host-microbial interactions
 Specific examples include Clostridia species, which stimulate development of regulatory T cells, and Bifidobacterium, which promote Th17
differentiation
 In addition, multiple species produce butyrate, whose activities include enhancement of mucosal barrier function, increased epithelial
proliferation, and immune regulation.
 Soluble microbial products activate host sensing proteins, including surface TLRs and dectin receptors and intracellular microbial-
associated pattern receptors, e.g., NOD2
 Conversely, the immune system can markedly alter the microbiome by mechanisms that include luminal secretion of antimicrobial
peptides and antibacterial IgA.
 This interplay between microbes and the immune system may contribute to the evolution of dysbiosis, characterized by shifts in microbial
populations and reduced species diversity, in disease.
INFLAMMATORY BOWEL DISEASE (IBD)
 CROHN’S DISEASE
 Location - terminal ileum, ileocecal valve, and cecum
 Gross
 presence of strictures
SERPENTINE ULCERS AND
 aphthous ulcer
STRICTURE COBBLESTONE APPEARANCE

 multiple lesions often coalesce into elongated, serpentine ulcers

oriented along the axis of the bowel
 Ulceration with sparing of interspersed mucosa, a result of the patchy
distribution of Crohn disease, results in an irregular, cobblestone
appearance of the mucosa
 Fissures may extend deeply to become fistula tracts or sites of
perforation
 The intestinal wall is thickened and rubbery as a consequence of transmural
edema, inflammation, submucosal fibrosis, and hypertrophy of the muscularis
propria, all of which contribute to stricture formation
 In cases with extensive transmural disease, mesenteric adipose tissue
frequently extends over the serosal surface (creeping fat)
PERFORATION CREEPING FAT
 Haphazard crypt organization results
from repeated injury and regeneration

INFLAMMATORY BOWEL DISEASE (IBD)

 CROHN’S DISEASE
 Mx features 
 abundant neutrophils that infiltrate and damage crypt epithelium.
 Clusters of neutrophils within a crypt are referred to as crypt
abscesses
 Ulceration is common
 Repeated cycles of crypt destruction and regeneration
lead to distortion and disorganzation of mucosal glands;
 Noncaseating granulomas , a hallmark of Crohn disease

Noncaseating granuloma
INFLAMMATORY BOWEL DISEASE (IBD)

 CROHN’S DISEASE
 Mx features 
 Epithelial metaplasia is another consequence of
chronic relapsing injury
 pseudopyloric metaplasia, refers to the presence of
gastric antral-appearing glands
 Paneth cell metaplasia may also occur in the left
colon, where Paneth cells are normally absent

 Mucosal atrophy, with loss of crypts, may also

occur after years of disease Active Crohn disease, with ulceration
and purulent exudate

Transmural Crohn disease with submucosal and serosal

granulomas
INFLAMMATORY BOWEL DISEASE (IBD)
 Clinical Features
 mild diarrhea, fever, and abdominal pain.
 right lower quadrant pain, fever, and bloody diarrhea that may mimic acute appendicitis or bowel perforation
 Iron deficiency anemia due to blood loss
 protein loss sufficient to cause hypoalbuminemia and malabsorption of nutrients, vitamin B12, and bile salts
 Fibrosing strictures, particularly of the
 terminal ileum, are common and require surgical resection
 Fistulae develop between loops of bowel and may also involve the urinary bladder, vagina, and abdominal or perianal skin
 Perforation and peritoneal abscesses are common.
 Extraintestinal manifestations of Crohn disease include cutaneous nodules formed by granulomas, uveitis, migratory
polyarthritis, sacroileitis, ankylosing spondylitis, erythema nodosum, cutaneous granulomas, and clubbing of the fingertips,
 Therapies include anti-inflammatory agents, e.g., salicylates; immunosuppressive drugs, e.g., corticosteroids; and
biologic therapies, e.g., anti-TNF antibodies.
INFLAMMATORY BOWEL DISEASE (IBD)

 ULCERATIVE COLITIS
 Location  intestinal involvement is limited to the colon and rectum
 C/F  Extraintestinal manifestations include migratory polyarthritis, sacroiliitis, ankylosing spondylitis, uveitis, and
skin lesions.
 T/T anti-TNF antibodies, that are effective in Crohn disease are also effective in ulcerative colitis
INFLAMMATORY BOWEL DISEASE (IBD)
 ULCERATIVE COLITIS
 MORPHOLOGY
 Grossly
 involves the rectum and all of the colon  pancolitis Sharp demarcation
pancolitis
 small intestine is normal, although mild mucosal
inflammation of the distal ileum may be seen  backwash
ileitis
 abrupt transition between diseased and uninvolved colon
 Isolated islands of regenerating mucosa often bulge into the
lumen to create pseudopolyps  tips fuse to create
mucosal bridges
 mucosal atrophy ++
 severe cases  inflammation of the muscularis propria and
neuromuscular dysfunction  colonic dilation and toxic
megacolon  risk of perforation.
pseudopolyps Mucosal bridges
INFLAMMATORY BOWEL DISEASE (IBD)

 ULCERATIVE COLITIS
 C/F  attacks of bloody diarrhea with stringy mucoid material, lower abdominal pain, and cramps
 T/t - Colectomy
IBD
CHOLERA

 Background and Epidemiology

 - **Pathogen**: Cholera is caused by *Vibrio cholerae*, a comma-shaped, gram-negative bacterium.
 - **Historical Endemic Area**: Ganges Valley of India and Bangladesh.
 - **Pandemics**: Since 1817, seven pandemics have spread globally but retreated to the Ganges Valley.
 - **Presence in Gulf of Mexico**: Cholera persists but causes rare seafood-associated diseases.
CHOLERA

 Transmission and Outbreaks

 - **Reservoirs**: Shellfish and plankton.
 - **Seasonal Incidence**: Increases in summer due to warm temperatures.
 - **Primary Transmission**: Drinking contaminated water.
 - **Disasters**: Epidemics occur when disasters destroy sewage systems, e.g., 2010 Haitian earthquake (affected
5% of the population, over 50% hospitalized, 1% fatality).
CHOLERA

 Pathogenesis
 - **Noninvasive Nature**: Vibrio organisms remain in the intestinal lumen.
 - **Colonization Factors**: Motility and attachment proteins.
 - **Dissemination**: Hemagglutinin aids in detachment and stool shedding.
 - **Cholera Toxin**: Encoded by a virulence phage, composed of five B subunits and one A subunit.
 - **B Subunits**: Bind to GM1 ganglioside on intestinal epithelial cells.
 - **A Subunit**: Processed and transported to cytosol, activates G protein Gs α, stimulates adenylate cyclase,
increases cAMP, opens CFTR, and causes chloride ion release and massive diarrhea.
CHOLERA

 Pathogenesis
 - **Noninvasive Nature**: Vibrio organisms remain in the intestinal lumen.
 - **Colonization Factors**: Motility and attachment proteins.
 - **Dissemination**: Hemagglutinin aids in detachment and stool shedding.
 - **Cholera Toxin**: Encoded by a virulence phage, composed of five B subunits and one A subunit.
 - **B Subunits**: Bind to GM1 ganglioside on intestinal epithelial cells.
 - **A Subunit**: Processed and transported to cytosol, activates G protein Gs α, stimulates adenylate cyclase,
increases cAMP, opens CFTR, and causes chloride ion release and massive diarrhea.