Transcript PATHOLOGY OF THE GASTROINTESTINAL TRACT

DIARRHEAL DISEASE
MALABSORPTION SYNDROMES
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Suboptimal absorption of different nutrients,
electrolytes &/or water as a result of disturbance in
intraluminal digestion, absorption, terminal (brush
border) digestion &/or transepithelial transport.
Digestion of food occurs mostly in stomach & small
intestine, while absorption occurs mostly in
duodenum & jejunum
Malabsorption may be caused by a variety of diseases
Small intestinal biopsy is an important diagnostic
tool: may show characteristic findings, normal or
nonspecific changes
c/o weight loss, anorexia, abdominal distension,
muscle wasting and passage of abnormally bulky,
frothy, greasy, yellow or gray stools (steatorrhea)
CONSEQUENCES OF
MALABSORPTION SYNDROMES
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Anemia: iron, pyridoxine, folate or vit. B12 deficiency
Bleeding: vitamin K deficiency
Osteopenia & tetany: Ca, Mg, vitamin D deficiency
Amenorrhea, impotence, infertitlity: generalized
malnutrition
Hyperparathyroidism: Ca & vitamin D deficiency
Purpura & petechiae: vitamin D deficiency
Edema: protein deficiency
Dermatitis & hyperkeratosis: vit A, Zn, eFA, niacin
Mucositis: vitamin deficiencies
Peripheral neuropathy: vit A & B12 deficiency
CLASSIFICATION OF
MALABSORPTION SYNDROMES
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Defective intraluminal digestion: pancreatic
insufficiency; Z-E syndrome; defective bile
secretion due to biliary obstruction, hepatic or
ileal dysfunction; bacterial overgrowth
Mucosal cell abnormalities: lactose intolerence,
bacterial overgrowth, abetalipoproteinemia
Reduced small intestine surface: Celiac sprue,
Crohn’s ,short –gut syndrome
Lymphatic obstruction: lymphoma, tuberculosis
Infection: enteritis, tropical sprue, Whipple’s
disease
Iatrogenic: surgeries, drug induced
MALABSORPTION SYNDROMES
PANCREATIC INSUFFICIENCY
Major cause of defective intraluminal
digestion
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– Chronic pancreatitis
– Cystic fibrosis
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Osmotic diarrhea, steatorrhea
MALABSORPTION SYNDROMES
BACTERIAL OVERGROWTH
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Pathologic colonization of jejunal lumen by an
abnormally large population of both anaerobic
and aerobic organisms qualitatively similar to
those present in the colon
Impairs intraluminal digestion & can damage
mucosal epithelium in proximal small intestine
Occurs in patients with:
– Intestinal luminal stasis: strictures, fistula,
blind loops or pouches
– Post-operative states associated with
inadequate gastric acidity
– Immunologic deficiencies
– Mucosal disease of small intestine
MALABSORPTION SYNDROMES
LACTOSE INTOLERANCE
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Deficiency of lactase is mostly acquired
Lactose cannot be broken down to glucose &
galactose; unabsorbed lactose exerts an osmotic
pull leading to watery diarrhea & malabsorption
Familial inborn error of metabolism: presents at
birth with initiation of milk feeding with explosive
watery frothy stools & abdominal distension
In adults, occurs with bacterial and viral
gastroenteritis & other GIT disorders
Dx: intestinal biopsy is normal; breath hydrogen
testing by gas chromatography
MALABSORPTION SYNDROMES
CELIAC SPRUE
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aka: Gluten-sensitive enteropathy
Sensitivity to gluten, the component of wheat &
related grains (oat, barley & rye) that contain
water insoluble gliadin peptides
Pathology: when exposed to gluten , the proximal
small intestinal mucosa accumulates large
numbers of B cells & plasma cells, resulting in
epithelial damage & total flattening of villi
Patients: 1:2000-3000 in white Europeans; familial
& viral links
Presentation range from infancy to midadulthood; diarrhea and malnutrition
Rx: Gluten-free diet
Px: Increased risk of developing malignancies
MALABSORPTION SYNDROMES
TROPICAL SPRUE
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Celiac-like disease occurring almost exclusively
in the tropics
An infectious etiology is implicated. No definite
microorganism has been identified.
c/o malabsorption symptoms following an acute
diarrheal infection
Pathology: minimal to severe diffuse enteritis with
villous flattening
Rx: Broad-spectrum antibiotics
MALABSORPTION SYNDROMES
WHIPPLE’S DISEASE
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Rare systemic infection, mainly in intestine, CNS
& joints
Pathology: small intestinal mucosa is full of
macrophages in lamina propria, with minimal
inflammation
Macrophages contain Tropheryma whipelii
(Gram + actinomycete).
Patients: males 30-50 yrs; lymphadenopathy,
polyarthritis, CNS symptoms
Rx: antibiotics
MALABSORPTION SYNDROMES
ABETALIPOPROTEINEMIA
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Rare autosomal recessive inborn error of
metabolism, with inability to synthesize
apoproteins required for export of lipoproteins
from mucosal cells
Free fatty acids & monoglycerides enter
absorptive cells and are normally re-esterified but
cannot be synthesized into chylomicrons
Pathology: mucosal cells have vacuolated lipid
inclusions
Severe hypolipidemia (decreased chylomicron,
VLDL, LDL)
c/o: diarrhea, steatorrhea, failure to thrive
Peripheral blood picture: RBCs show
characteristic burr cells (acanthocytosis)
PROTOZOAL ENTEROCOLITIS
Giardia lamblia
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World’s most prevalent pathogenic gut
protozoan
Asymptomatic carrier state is common
Trophozoites live in duodenum & give rise to
infective cysts that are shed into the stools
Spread by fecal contaminated water
Parasite attaches to small intestinal mucosa but
does not invade
Pathology: intestinal villi may be normal or
blunted with a mixed inflammatory cell infiltrate
in lamina propria
Malabsorptive diarrhea
VASCULAR DISORDERS OF INTESTINES
ISCHEMIC BOWEL DISEASE
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aka: mesenteric ischemia
Involves small &/or large intestines depending on
particular vessel(s) involved (celiac, superior & inferior
mesenteric arteries)
Usually elderly patients; may be acute or insidious
Causes:
– Arterial thrombosis: severe atherosclerosis, ...
– Arterial embolism: cardiac vegetations, ...
– Venous thrombosis: hypercoagulable states
– Nonocclusive ischemia: heart failure, shock, ..
– Miscellaneous: radiation, volvulus, herniation, ...
TYPES OF
ISCHEMIC BOWEL DISEASE
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Ischemic bowel disease is divided according to the
severity of injury:
– 1) Mucosal infarction & 2) Mural infarction
(hemorrhagic gastroenteropathy): usually due to
hypoperfusion, damaging only the inner layers of
the GIT; multifocal or continuous lesions;
hemorrhage, edema & ulceration; intact serosa
– 3) Transmural intestinal infarction: dark red
hemorrhagic bowel segment of variable length;
ischemia starts in mucosa and extends outwards,
with edema, hemorrhage, necrosis, mucosal
sloughing followed by gangrene & perforation
CLINICAL FEATURES OF
ISCHEMIC BOWEL DISEASE
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Transmural lesions: sudden abdominal pain,
bloody diarrhea, shock, …
Mural & mucosal: abdominal distension, GI
bleeding, gradual pain or discomfort
Dx: high index of suspicion in the appropriate
setting
Px: mortality rate with transmural infarction is
nearly 90%, largely due to delay in diagnosis;
mural & mucosal infarction may not be fatal if
causes of hypoperfusion are corrected
VASCULAR DISORDERS OF INTESTINES
ANGIODYSPLASIA
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A misnomer; not a pre-malignant lesion
Tortuous dilations of submucosal & mucosal
blood vessels, mostly in cecum & rt. colon,
elderly patients
Blood vessels may rupture & bleed; account for
20% of significant lower GIT bleeding
Difficult to diagnose: -ve Barium enema
radiology; normal gross appearance. Visible by
endoscopy & angiography.
Isolated lesions or part of systemic disorder, e,g.
Osler-Weber-Rendu syndrome & CREST
syndrome
VASCULAR DISORDERS OF INTESTINES
HEMORRHOIDS
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aka: piles
Dilated varices of anal and perianal submucosal
venous plexuses
Patients: common in adults >50 yrs; setting of
persistently elevated venous pressure within the
hemorrhoidal plexus
Predisposing factors:
– Chronic constipation
– Pregnancy
– Portal hypertension
Pathology: thin-walled dilated blood vessels covered
by anal mucosa
HEMORRHOIDS
CLINICAL FEATURES OF
HEMORRHOIDS
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Types of hemorrhoids:
– 1) Internal: above the dentate line
– 2) External: below the dentate line
Clinical features:
– Usually asymptomatic
– Protrusion & itching
– Ulceration & bleeding
– Thrombosis & pain
– Prolapse: internal hemorrhoids trapped by anal
sphincter, with sudden pain, edema, enlargement or
strangulation
Rx: depends on severity; medical & surgical
PATHOLOGY OF SMALL & LARGE INTESTINE
IDIOPATHIC INFLAMMATORY BOWEL DISEASE
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Crohn’s disease & ulcerative colitis: chronic
relapsing disorders of unknown cause, which are
characterized by extensive bowel inflammation,
tissue injury & mucosal destruction
Intermittent bloody diarrhea; pain; malabsorption
Etiology:
– Genetic predisposition ,IBD 1 on chromosome 16 ,HLA-DR
– Abnormal mucosal structure ,
– Infectious
– Abnormal host immunoreactivity ; IL-2,IL-10,TNF,IL-R
INFLAMMATORY BOWEL DISEASE
ULCERATIVE COLITIS & CROHN’S DISEASE
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Ulcerative colitis and Crohn’s disease have
common features:
– Chronic recurrent inflammation
– No definit cause is identified
– May have extra-intestinal manifestations
Integration of clinical, radiological and
pathological findings are essential for diagnosis of
UC or CD.
Histologic feature may be identical, particularly
with small biopsies
In 10-30% of cases, distinction between the two
diseases cannot be made (indeterminate cases)
INFLAMMATORY BOWEL DISEASE
CROHN’S DISEASE
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aka: terminal ileitis, regional enteritis
Systemic disease with predominant GI involvement
– Any level of GIT may be involved
– Associated immune extra-intestinal manifestations
(iritis, uveitis, polyarthritis, erythema nodosum,
hepatic pericholangitis, sclerosing cholangitis..)
Patients: any age, peaks 2-3rd & 6-7th decades; F>M
Insidious or sudden onset of symptoms which may
remit spontaneously or with therapy, usually followed
by relapses
Marked weight loss & malabsorption
Complications: fistulas,abdominal abscesses &
peritonitis, stricture and obstruction, bleeding
Cancer: Increased risk, but significantly less than UC
INFLAMMATORY BOWEL DISEASE
ULCERATIVE COLITIS
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Ulcero-inflammatory disease of colon, limited to
mucosa & submucosa, except in severe cases
Starts in rectum & extends proximally in a continuous
fashion
Systemic disease, may be associated with
polyarthritis, ankylosing spondylitis (HLA-B27+),
uveitis, liver (pericholangitis & PSC) & skin
involvement
Patients: any age; peak 20-25 yrs.
Chronic relapsing & remitting disease; bloody stools
Complications: severe diarrhea & electrolyte
disturbances, massive hemorrhage, toxic
megacolon, rupture
Cancer: depends on duration & extent of disease
INFLAMMATORY BOWEL DISEASE
CROHN’S DISEASE
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ULCERATIVE COLITIS
Incidence: 1-3/100,000
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Whites, Jews
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Small intestine 40%;
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small & large intestine
30%; large intestine 30%
Skip lesions
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Granulomas 40-60%
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Deep linear ulcers
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Cobble stone appearance 
Strictures: early
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Fissures, sinuses &
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fistulas
Incidence: 4-6/100,000
Whites
Rectum/rectosigmoid
80% extending proximally; pan-colitis 10%
Continuous involvement
No granulomas
Superficial ulcers
Pseudopolyps
Strictures: late/rare
No
MICROSCOPIC FEATURES OF
CROHN’S DISEASE
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ULCERATIVE COLITIS
Inflammation, ulceration & 
chronic mucosal changes
Deep ulcers with transmural
involvement
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Wall thickening
Granulomas +/Marked lymphoid reaction 
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Marked serositis
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Fistulas or sinuses
Moderate-marked fibrosis
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Inflammation,
ulceration & chronic
mucosal changes
Ulcers with mostly
mucosal involvement
Wall is usually thin
No granulomas
Mild lymphoid
reaction
No or mild serositis
No fistulas or sinuses
Mild fibrosis