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Small and Large intestines
• Meckel Diverticulum
-failure of the vitelline duct ,which connects the lumen of
the developing gut to the Yolk sac produce a Meckel
Diverticulum
-is a true diverticulum
-heterotopic rests of gastric mucosa (or pancreatic tissue)
are found in about 50%
-occur in 2% of the population but most remain
asymptomatic
-when peptic ulceration occurs in the small intestinal
mucosa adjacent to the gastric mucosa bleeding occur
Small and Large intestines.pptx
Congenital aganglionic Megacolon
(Hirschsprung disease)
• Characterized by the absence of ganglionic
cells in large bowel leading to functional
obstruction and colonic dilation proximal to
the affected segment
• Histologically there is absence of ganglionic
cells in the muscle wall(Auerbach plexus) and
submucosa (Meissner plexus)
• Most cases involve the rectum and sigmoid only
• Proximal to the aganglionic segment , the colon
undergoes progressive dilation and hypertrophy
• Dilation may achieve large sizes
Clinical features
• More common in males but tend to be more
severe in female
• 10% occur in children with Down syndrome
• Usually manifest in the immediate neonatal
period by failure to pass meconium followed
by obstructive constipation
DIARRHEAL DISEASE
Diarrhea is defined as an increase in stool mass, frequency, or
fluidity, typically to amounts greater than 200 grams per
day
• The principal mechanisms of diarrhoea are
– Secretory diarrhoea – intestinal fluid secretion
– Osmotic diarrhoea – osmotic forces exerted by luminal solutes
leads to diarrhoea
– Exudative diseases – mucosal destruction leads to output of
purulent bloody stool
– Malabsorption – improper absorption of gut nutrients produce
voluminous bulky stool
• Painful, bloody, small-volume diarrhea is known as
dysentery
Malabsorption syndrome
• Malabsorption is characterized by suboptimal
absorption of fats, fat-soluble and other
vitamins ,proteins ,carbohydrates ,electrolytes
minerals and water
• Results from disturbance of
– Intraluminal digestion
– Terminal digestion
– Transepithelial transport
Small and Large intestines.pptx
Consequences of malabsorption affect many organ
systems
• Alimentary tract –diarrhea , flatus, abdominal pain,
weight loss. . .
• Hematopoetic system – anemia from ,pyridoxine
,folate, VB12 ,deficiency , bleeding from v.k deficiency
• Musculoekeletal system – osteopenia and tetany from
calcium, Mg . . .deficiency
• Epidermis – purpura and petechiae from vitamin K
deficiency, edema from protein , dermatitis from vit. A,
Zink deficiency
• Nervous system – peripheral neuropathy from
vitamin A and B12 deficiency
Features
• Steatorrhea –passage of abnormally bulky,
frothy , greasy stool is a prominent feature
• Other features are wt loss, abdominal
distension.
Celiac sprue
• Rare chronic disease
• is an immune-mediated enteropathy triggered by the ingestion of
gluten-containing grains.
• The malabsorptive diarrhea in celiac disease is due to loss of
• brush border surface area, including villous atrophy, and,
• possibly, deficient enterocyte maturation as a result of
• immune-mediated epithelial damage
• Characteristic mucosal lesion of the small intestine and impaired
absorption which improves on withdrawal of wheat gliadins and
related grains
• A.k.a. glutein sensitive enteropathy , non-tropical sprue
• Mucosa appears flat or scalloped or may be visually normal
• Biopsy show diffuse enteritis with marked
atrophy or total loss ov villi
• Clinical manifestations include diarrhea ,
flatulence ,wt. loss and fatigue
• There is a long term risk of malignant disease
(more than half of these are intestinal
lymphomas)
Tropical Sprue(enviromental sprue)
• Occurs almost exclusively in people living in or
visiting the tropics #
• is a disorder prevalent in areas and populations
with poor sanitation and hygiene, such as those
in developing countries
• May occur in endemic form and epidemic
outbreaks have occurred
• No specific causal agent has been associated but
bacterial overgrowth by enterotoxigenic is
implicated
• Intestinal changes are extremely variable
ranging from near normal to severe diffuse
enteritis
• Clinically malabsorption becomes apparent
within days or a week of an acute enteric
infection in visitors to endemic locales
• Mainstay of treatment is broad-spectrum
antibiotics
Abetalipoproteinemia
• is an autosomal recessive disease characterized by an
inability to secrete triglyceride-rich lipoproteins.
• Mutation in the microsomal triglyceride transfer
protein renders enterocytes unable to export
lipoproteins and free fatty acids
• It manifests in infancy, and the clinical picture is
dominated by failure to thrive, diarrhoea, and
steatorrhea.
• Failure to absorb essential fatty acids leads to
deficiencies of fat soluble vitamins and lipid defects in
plasma membranes
Disaccharidase(Lactase ) deficiency
• causes an osmotic diarrhea due to the
• inability to break down or absorb lactose.
• The autosomal recessive form is rare and severe;
the acquired form usually presents in adulthood
and is common
• The acquired one is more common
• Incomplete breakdown of the disacchride lactose
into glucose and galactose leads to osmotic
diarrhea
Infectious enterocolitis
Viral gastroenteritis
• Rota virus is the most common cause
• Clinically has incubation period of about 2 days followed by
vomiting and diarrhoea for days
• Mostly in children
• Norwalk virus cause the majority of cases of non-bacterial
food-borne epidemic gastroenteritis in older children and
adults
• It has incubation period of 1-2days followed by 12-60hrs of
nausea vomiting watery diarrhoea and abdominal pain
Bacterial enterocolitis
Pathogenetic mechanisms
– Ingestion of preformed toxin present in
contaminated food (S.aureus, Vibrios,
C.perfringens)
– Infection by toxigenic organisms which proliferate
within the gut lumen and elaborate an enterotoxin
– Infection by enteroinvasive organisms which
proliferate invade and destroy mucosal epithelial
cells
• In case of infection key bacterial properties are
1. Ability to adhere
2. Ability to elaborate enterotoxins
3. The capacity to invade
• Adherence is usually mediated by adhesins
• Enterotoxins are polypeptides that cause
diarrhoea e.g. V.cholerae
• Invasion e.g. enteroinvasive E.coli and shigella
possess a virulence plasmid that confers
capacity for invasion
Morphology
• Most bacterial infections exhibit a general non
specific pattern of damage to the surface
epithelium
– Decrease epithelial cell maturation
– Increased mitotic rate (regenerative changes)
– Hyperemia and edema of lamina propria
– Neutrophilic infiltration
Clinical features
• Ingestion of preformed bacterial toxins –
symptoms develop within hours ,explosive
diarrhoea, acute abdominal distress . . .
• Infection with enteric pathogens : after
incubation period of several hours to days
diarrhoea , dehydration . ..
• Insideous infection : e.g. yersinia and
mycobacterium
Antibiotic associated colitis (pseudomembraneous
colitis)
• Acute colitis characterized by formation of an adherent
inflammatory exudate (pseudomembrane) overlying
site of mucosal injury
• Usually caused by two protein exotoxins (A&B) of
C.difficile ,a normal gut comensal
• Disease occurs in patients with a background of chronic
enteric disease after a course of broad spectrum
antibiotic therapy
• Thought to result due to the flourish of toxin forming
strains after alteration of normal intestinal flora
Small and Large intestines.pptx
Whipple disease
• Systemic disease which may involve any organ of the body
but principally affects the intestine ,CNS and joints
• Cause is gram-positive actinomycete Tropheryma Whippeli
• Hallmark of Whipple disease is organism-laden
macrophages accumulate within the small intestinal lamina
propria and mesenteric lymph nodes, causing lymphatic
obstruction.
• Thus, the malabsorptive diarrhoea of Whipple disease is
due to impaired lymphatic transport
• The macrophages contain PAS positive granule
and rod-shaped bacilli by electron microscopy
• More common in whites and male in their thirties
to fourties
• Usually present with diarrhea and wt loss
sometimes of years duration
• The clinical presentation of Whipple disease is
usually a triad of diarrhea, weight loss, and
arthralgia
Parasites and protozoa
– E.histolytica
– G.lamblia
• AIDS
-diarrheal illness occur in 30-60% of HIV infected
pts
-most cases are due to microorganisms
-AIDS enteropathy is thought to represent some
proportion
Small and Large intestines.pptx
INFLAMMATORY BOWEL DISEASE
• is a chronic condition resulting from
inappropriate mucosal immune activation
Crohn disease and ulcerative colitis
• Are chronic, relapsing inflammatory disorders
of obscure origin
• Infections cause
Etiology and pathogenesis
• Genetic predisposition
• most investigators believe that IBD results from
the combined effects of
• alterations in host interactions with
• intestinal microbiota, intestinal epithelial
dysfunction,aberrant mucosal immune
responses, and altered composition of the gut
microbiome
• Inflammation as the final common pathway
CROHN DISEASE
• a.k.a terminal ileitis ,regional enteritis ,
granulomatous colitis
- When fully developed it is characterized
pathologically by
1. sharply delimited and typically transmural
involvement of the bowel by an inflammatory
process
2. the presence of non caseating granuloma
3. fissuring with formation of fistulas
Small and Large intestines.pptx
Epidemiology
• occurs at any age, but peak is teens and twenties
with a minor peak in fifties and sixties
• Females are slightly more affected
• Smoking is a strong exogenous risk factor
Morphology
• Small intestine alone -40%
• Small intestine + colon -30%
• Colon alone -30%
• may involve duodenum, stomach, esophagus
and even mouth but very rarely
• the intestinal wall is rubbery and thick the
result of edema inflammation fibrosis and
hypertrophy
• classic feature is the sharp demarcation of
diseased bowel segments from adjacent
uninvolved bowel
• When multiple bowel segments are involved
the intervening bowel is essentially normal (
skip lesions) and the mucosa acquires a
coarsely textured cobblestone appearance
• linear ulcers develop
• narrow fissures develop between the folds of
the mucosa often penetrating deeply leading
to fistula or sinus tract formation
• Mucosal inflammation
• Chronic mucosal damage
• Ulceration
• Trans mural inflammation affecting all layers
• Non caseating granulomas
Clinical features
• Variable but disease usually begins with intermittent
attacks of mild diarrhea fever and abdominal pain
• In some patients the onset is more abrupt with acute
right lower quadrant pain fever and diarrhea
Small and Large intestines.pptx
• Complications include strictures, fistulas,
malabsorption
• Extra intestinal manifestations include
migratory poly arthritis, sacroilitis ,ankylosing
spondylitis, erythema nodosum, uveitis
• There is an increased incidence of cancer of
the Gl tract ,but is considerably less than
ulcerative colitis
ULCERATIVE COLITIS
• an ulceroinflammatory disease limited to the
colon and affecting only the mucosa and
submucosa except in the most severe cases
• incidence is slightly greater than Crohn disease
• onset peaks between 20 and 25 years
• UC involves the rectum and extends proximally in
a retrograde fashion to involve the entire colon in
the more severe cases
• It is a disease of continuity and skip lesions
like crohn disease are not found
• In10% of patients the distal ileum may
develop mild mucosal inflammation (
backwash ileitis)
• Isolated islands of regenerating mucosa bulge
upward to create pseudopolyps
• Mural thickening does not occur in UC and the
serosal surface is usually completely normal
Small and Large intestines.pptx
Clinical features
• present as a relapsing disorder marked by
attacks of bloody mucoid diarrhea that may
persist for days weeks or months, then
subside & recur
• abdominal pain and in minority constipation
• the most feared long term complication of UC
is cancer
Small and Large intestines.pptx
Small and Large intestines.pptx
Hemorrhoids
• variceal dilations of the anal and perianal venous
plexuses
• common problems which develop secondary to
persistently elevated venous pressure within the
hemorrhoidal plexus
• most frequent predisposing influences are
constipation with straining at stool and the
venous stasis of pregnancy
• much more importantly but rarely develop as
result of portal hypertension
• they may develop in the inferior hemorrhoidal
plexus located below anorectal line –external
hemorrhoid
• they may also develop in the superior hemorroial
plexus and produce internal hemorroids
• commonly both are affected
• secondary effects include thrombosis ,ulceration
,fissure formation and infarction with
strangulation
INTESTINAL OBSTRUCTION
• may occur at any level
• patients present with abdominal pain and distension
vomiting failure to pass flatus…
• Major causes of intestinal obstruction
Mechanical obstruction
• Adhesions
• Hernias
• Volvulus
• Intussusception
• Tumors
• Inflammatory strictures
• Obstructive gall stones, fecalith, ,foreign body
• Congenital strictures, atresias
• Bands
• Imperforate anus
Pseudo-obstruction
• Paralytic ileus
• Vascular-bowel infarction
• Myopathies and neuropathies ( eg Hirschsprung)
• Abdominal hernias may occur through any weakness or
• defect in the wall of the peritoneal cavity, including inguinal and
femoral canals, the umbilicus, and sites of surgical scars.
• ■ Intussusception occurs when a segment of intestine telescopes
into the immediately distal segment.
• It is the most common cause of intestinal obstruction in children
younger than 2 years of age.
• Volvulus
• Twisting of a loop of bowel about its mesenteric point of
• attachment is termed volvulus; it results in both luminal
• and vascular compromise.
• Thus, volvulus presents with features of both obstruction and
infarction
Small and Large intestines.pptx
Small intestine tumors
Adenomas
• most occur in the region of the ampulla of Vater
• patients with familial polyposis coli are particularly
prone
Adenocarcinoma
• majority occur in the duodenum and jejunum
• grow as napkin ring encircling pattern or as polypoid
fungating mass
• those involving ampulla of Vater may present with
obstructive jaundice
• at time of diagnosis most tumors have locally spread
Tumors of the colon and Rectum
Non neoplastic polyps
• non neoplastic polyps ( mostly hyperplastic )
represent about 90% of all epithelial polyps in
large bowel
• inflammatory ( pseudo) polyps represent
islands of inflamed regenerating mucosa
surrounded by ulceration are seen in patients
with longstanding IBD
Hyperplastic polyps
• small epithelial polyps
• often multiple and more than half are
found in the rectosigmoid
• histologically they are composed of well
formed glands and crypts lined by non
neoplastic epithelium
• the usual small hyperplastic polyp has
virtually no malignant potential
Juvenile polyps
• focal hamartomatous malformations of the mucosal
elements
• most frequently occur in the rectum
• mainly sporadic lesions ,majority occurring in children
younger than 5
• in adults they are referred to as retention polyps
• tends to be large ( 1 to 3cm)
• Histology show abundant cystically dilated glands
• Generally occur singly and have no malignant potential
• A rare autosomal dominant juvenile polyposis syndrome
does carry a risk of adenomas and hence adenocarcinoma
Small and Large intestines.pptx
Peutz- Jeghers polyp
• autosomal dominant syndrome characterized
by multiple hamartomatous polyps scattered
throughout the entire GIT and melanotic
mucosal and cutaneous pigmentation around
oral mucosa face genitalia palms .
• patients with the syndrome have an increased
risk of developing carcinomas of the pancreas
breast lung ovary and uterus
Small and Large intestines.pptx
Adenomas
• Intraepithelial neoplasms that range from small, often
pedunculated to large that are sessile
• occur in 20-30% before40,rising to 40-50% after age 60
• there is well defined familial predisposition
Three subtypes
• Tubular adenomas-Tubular glands
• Villous adenomas- villous projections
• Tubulovillous adenoma-a mixture of the two
• adenomatous lesions arise as the result of epithelial
proliferative dysplasia, which may range from mild to so
severe as to constitute carcinoma in situ
• most tubular adenomas are small and
pedunculated :
• villous adenomas tend to be large and sessile and
sessile polyps usually exhibit villous features
• the malignant risk with an adenomatous polyp is
correlated with three independent features
– polyp size ,
– histologic architecture and
– severity of epithelial dysplasia
Small and Large intestines.pptx
• cancer is rare in tubular adenomas smaller
than 1cm
• the risk of cancer is high ( ~40%) in sessile
villous adenomas greater than 4cm
Clinical features
• may be asymptomatic ,but many are
discovered during evaluation of anemia or
occult bleeding
Small and Large intestines.pptx
Familial syndromes
• Uncommon autosomal dominant disorders
Familial adenomatous polyposis (FAP)
• genetic defect is in the APC gene on 5q21
• patients typically develop 500-2500 colonic adenomas
• multiple adenomas may also be present elsewhere in
the alimentary tract
• the majority are tubular
• progression to colon adenocarcinoma approach 100%
• cancer-preventive measures include prophylactic
colectomy
Small and Large intestines.pptx
Gardner syndrome
• also autosomal dominant
• patients exhibit intestinal polyps identical to those in
FAP combined with multiple osteomas, epidermal cysts
and fibromatosis
Turcot syndrome is a rare variant marked by the
combination of adenomatous colonic polyposis and
tumors of CNS
Hereditary non polyposis colorectal cancer(HNPCC)
• Is characterized by an increased risk of colorectal
cancer and extraintestinal cancer particularly of the
endometrium in women
Colorectal carcinoma
• 98% of all cancers in the large intestine are
adenocarcinoma
• Peak incidence is 60 to 79 years
• If found in young person preexisting ulcerative
colitis or one of the polyposis syndromes must
be suspected
• Dietary factors like excess calorie intake, low
unabsorbable vegetable fiber, intake of red
meat and decreased intake of protective
micronutrients
Small and Large intestines.pptx
• about 1-3% occur in patients with familial
syndromes
• tumors in the proximal colon tend to grow
as polypoid exophytic masses and
obstruction is uncommon
• carcinomas in the distal colon tend to be annular
encircling lesions
• microscopically all are adenocarcinomas
• when symptomatic produce anemia fatigue
weakness bowel habit change…
• spread by direct extension into adjacent
structures and by metastasis through the
lymphatics and blood vessels
• the most important prognostic indicator of
colorectal carcinoma is the extent of tumor at
time of diagnosis
Small and Large intestines.pptx
Small and Large intestines.pptx
Small and Large intestines.pptx
Carcinoid Tumors
• tumors of neuroendocrine cells
• arise in the pancreas or peripancreatic tissue
lungs, biliary tree, liver and mainly in GIT
• constitute less than 2% of colorectal
malignancies but almost half of small intestinal
malignant tumors
• tendency for aggressive behavior correlates
with the site of origin, depth of local
penetration and size
• appendiceal and rectal carcinoids infrequently
metastasize, by contrast ileal ,gastric and colonic
carcinoids have higher chance of spread
especially those that have penetrated halfway
through the muscle wall and >2cm
• depending on the predominant product they can
be called gastrinoma, somatostatinoma ,
insulinoma . . .
• appendix is the most common site of gut
followed by small intestine ,rectum, stomach and
colon
• clinically may produce local symptoms owing to
angulation or obstruction of the small intestine
• may produce Zollinger-Ellison syndrome, Cushing
syndrome ,hyperinsulinism
• some neoplasms are associated with a distinctive
carcinoid syndrome( occurs in 1% of patients with
carcinoids and in 20% of those with widespread
metastasis)
• most manifestations are thought to arise from
serotonin
• manifestations include cutaneous flushes, diarrhea
tramps nausea,cough wheezing…
Gastrointestinal lymphoma
• 1-4% of all GI malignancies
• Primary GI lymphomas sometimes arise as sporadic but
occur more frequently in certain populations
1. patients with Helicobacter gastritis
2. Natives of the Mediterranean region
3. patients with congenital immunodeficiency states
4. HIV- infected individuals
5. individuals undergoing immunosuppressive therapy
6. patients with sprue
• sporadic lymphomas are the most common
form in western hemisphere
• arise from the B cells of the mucosa
associated lymphoid tissue ( MALT)
Appendix
Acute appendicitis
• usually ( 50-80%) associated with obstruction
( fecalith , less commonly gall stone, tumor, or
ball of worms ( oxyuriasis vermicularis )
• Obstruction can cause ischemic injury which
favors bacterial proliferation with additional
inflammatory exudate and edema
• Nevertheless a significant minority of inflamed
appendices have no demonstrable luminal
obstruction
Morphology
• initially serosa will be transformed to dull
granular red membrane
• later fibrinopurulent exudate covers the serosa
• abscess formation leads to acute suppurative
appendicitis
Small and Large intestines.pptx
• further progress leads to acute gangrenous
appendicitis
• histologic criterion for the diagnosis of acute
appendicitis is neutrophilic infiltration of the
muscularis
• clinical features include
– abdominal pain
– nausea
– vomiting
– tenderness
– Fever…
Tumors of the appendix
Carcinoids
Mucocele and pseudomyxoma peritonei
Mucocele is globular enlargement of the
appendix by inspissated mucus usually the
result of obstruction
Small and Large intestines.pptx
Mucinous cystadenoma is the most common
mucinous neoplasm
Malignant mucinous cystadenocarcinoma
penetration of the appendiceal wall by
invasive cells and spread beyond the appendix
in the form of localized or disseminated
implants produce cellular proliferation and
mucin secretion pseudomyxoma peritonei
Small and Large intestines.pptx
Peritoneum
Inflammation
• may result from bacterial invasion or chemical irritation the
most common causes are
sterile peritonitis
– –from mild leakage of bile or pancreatic enzymes
– perforation or rupture of the biliary system
– hemorrhagic poncreatitis, with leadkage of pancreatic enzymes
and digestion of adipose tissue to produce fatty acids
– surgical procedures, reaction to surgically introduced foreign
material such as talk, abrasion of serosal surfaces
– Gynecologic conditions eg. Endometriosis
Infection
• the most common disorders leading to such
bacterial dissemination are appendicitis,
ruptured peptic ulcer ,cholecystitis, diverticulitis,
strangulation of bowel, acute salpingitis,
abdominal trauma…
• A wide variety of bacterial organisms are
implicated in peritonitis
• spontaneous bacterial peritonitis is an
uncommon condition which occurs in the
absence of an obvious source of contamination
• in generalized peritonitis an exudate may
accumulate under and above the liver to form
subhepatic ,subdiaphragmatic abscess.
TUMORS
• virtually all tumors of the peritoneum are
malignant and can be divided into primary
tumors(mesotheliomas) and secondary
tumors
• peritoneal mesotheliomas are associated
with asbestos exposure in at least 80% of
the cases
• secondary tumors are common and can
occur in any form of advanced cancer

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Small and Large intestines.pptx

  • 1. Small and Large intestines
  • 2. • Meckel Diverticulum -failure of the vitelline duct ,which connects the lumen of the developing gut to the Yolk sac produce a Meckel Diverticulum -is a true diverticulum -heterotopic rests of gastric mucosa (or pancreatic tissue) are found in about 50% -occur in 2% of the population but most remain asymptomatic -when peptic ulceration occurs in the small intestinal mucosa adjacent to the gastric mucosa bleeding occur
  • 4. Congenital aganglionic Megacolon (Hirschsprung disease) • Characterized by the absence of ganglionic cells in large bowel leading to functional obstruction and colonic dilation proximal to the affected segment • Histologically there is absence of ganglionic cells in the muscle wall(Auerbach plexus) and submucosa (Meissner plexus)
  • 5. • Most cases involve the rectum and sigmoid only • Proximal to the aganglionic segment , the colon undergoes progressive dilation and hypertrophy • Dilation may achieve large sizes Clinical features • More common in males but tend to be more severe in female • 10% occur in children with Down syndrome
  • 6. • Usually manifest in the immediate neonatal period by failure to pass meconium followed by obstructive constipation
  • 7. DIARRHEAL DISEASE Diarrhea is defined as an increase in stool mass, frequency, or fluidity, typically to amounts greater than 200 grams per day • The principal mechanisms of diarrhoea are – Secretory diarrhoea – intestinal fluid secretion – Osmotic diarrhoea – osmotic forces exerted by luminal solutes leads to diarrhoea – Exudative diseases – mucosal destruction leads to output of purulent bloody stool – Malabsorption – improper absorption of gut nutrients produce voluminous bulky stool • Painful, bloody, small-volume diarrhea is known as dysentery
  • 8. Malabsorption syndrome • Malabsorption is characterized by suboptimal absorption of fats, fat-soluble and other vitamins ,proteins ,carbohydrates ,electrolytes minerals and water • Results from disturbance of – Intraluminal digestion – Terminal digestion – Transepithelial transport
  • 10. Consequences of malabsorption affect many organ systems • Alimentary tract –diarrhea , flatus, abdominal pain, weight loss. . . • Hematopoetic system – anemia from ,pyridoxine ,folate, VB12 ,deficiency , bleeding from v.k deficiency • Musculoekeletal system – osteopenia and tetany from calcium, Mg . . .deficiency • Epidermis – purpura and petechiae from vitamin K deficiency, edema from protein , dermatitis from vit. A, Zink deficiency
  • 11. • Nervous system – peripheral neuropathy from vitamin A and B12 deficiency Features • Steatorrhea –passage of abnormally bulky, frothy , greasy stool is a prominent feature • Other features are wt loss, abdominal distension.
  • 12. Celiac sprue • Rare chronic disease • is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains. • The malabsorptive diarrhea in celiac disease is due to loss of • brush border surface area, including villous atrophy, and, • possibly, deficient enterocyte maturation as a result of • immune-mediated epithelial damage • Characteristic mucosal lesion of the small intestine and impaired absorption which improves on withdrawal of wheat gliadins and related grains • A.k.a. glutein sensitive enteropathy , non-tropical sprue • Mucosa appears flat or scalloped or may be visually normal
  • 13. • Biopsy show diffuse enteritis with marked atrophy or total loss ov villi • Clinical manifestations include diarrhea , flatulence ,wt. loss and fatigue • There is a long term risk of malignant disease (more than half of these are intestinal lymphomas)
  • 14. Tropical Sprue(enviromental sprue) • Occurs almost exclusively in people living in or visiting the tropics # • is a disorder prevalent in areas and populations with poor sanitation and hygiene, such as those in developing countries • May occur in endemic form and epidemic outbreaks have occurred • No specific causal agent has been associated but bacterial overgrowth by enterotoxigenic is implicated
  • 15. • Intestinal changes are extremely variable ranging from near normal to severe diffuse enteritis • Clinically malabsorption becomes apparent within days or a week of an acute enteric infection in visitors to endemic locales • Mainstay of treatment is broad-spectrum antibiotics
  • 16. Abetalipoproteinemia • is an autosomal recessive disease characterized by an inability to secrete triglyceride-rich lipoproteins. • Mutation in the microsomal triglyceride transfer protein renders enterocytes unable to export lipoproteins and free fatty acids • It manifests in infancy, and the clinical picture is dominated by failure to thrive, diarrhoea, and steatorrhea. • Failure to absorb essential fatty acids leads to deficiencies of fat soluble vitamins and lipid defects in plasma membranes
  • 17. Disaccharidase(Lactase ) deficiency • causes an osmotic diarrhea due to the • inability to break down or absorb lactose. • The autosomal recessive form is rare and severe; the acquired form usually presents in adulthood and is common • The acquired one is more common • Incomplete breakdown of the disacchride lactose into glucose and galactose leads to osmotic diarrhea
  • 18. Infectious enterocolitis Viral gastroenteritis • Rota virus is the most common cause • Clinically has incubation period of about 2 days followed by vomiting and diarrhoea for days • Mostly in children • Norwalk virus cause the majority of cases of non-bacterial food-borne epidemic gastroenteritis in older children and adults • It has incubation period of 1-2days followed by 12-60hrs of nausea vomiting watery diarrhoea and abdominal pain
  • 19. Bacterial enterocolitis Pathogenetic mechanisms – Ingestion of preformed toxin present in contaminated food (S.aureus, Vibrios, C.perfringens) – Infection by toxigenic organisms which proliferate within the gut lumen and elaborate an enterotoxin – Infection by enteroinvasive organisms which proliferate invade and destroy mucosal epithelial cells
  • 20. • In case of infection key bacterial properties are 1. Ability to adhere 2. Ability to elaborate enterotoxins 3. The capacity to invade • Adherence is usually mediated by adhesins • Enterotoxins are polypeptides that cause diarrhoea e.g. V.cholerae • Invasion e.g. enteroinvasive E.coli and shigella possess a virulence plasmid that confers capacity for invasion
  • 21. Morphology • Most bacterial infections exhibit a general non specific pattern of damage to the surface epithelium – Decrease epithelial cell maturation – Increased mitotic rate (regenerative changes) – Hyperemia and edema of lamina propria – Neutrophilic infiltration
  • 22. Clinical features • Ingestion of preformed bacterial toxins – symptoms develop within hours ,explosive diarrhoea, acute abdominal distress . . . • Infection with enteric pathogens : after incubation period of several hours to days diarrhoea , dehydration . .. • Insideous infection : e.g. yersinia and mycobacterium
  • 23. Antibiotic associated colitis (pseudomembraneous colitis) • Acute colitis characterized by formation of an adherent inflammatory exudate (pseudomembrane) overlying site of mucosal injury • Usually caused by two protein exotoxins (A&B) of C.difficile ,a normal gut comensal • Disease occurs in patients with a background of chronic enteric disease after a course of broad spectrum antibiotic therapy • Thought to result due to the flourish of toxin forming strains after alteration of normal intestinal flora
  • 25. Whipple disease • Systemic disease which may involve any organ of the body but principally affects the intestine ,CNS and joints • Cause is gram-positive actinomycete Tropheryma Whippeli • Hallmark of Whipple disease is organism-laden macrophages accumulate within the small intestinal lamina propria and mesenteric lymph nodes, causing lymphatic obstruction. • Thus, the malabsorptive diarrhoea of Whipple disease is due to impaired lymphatic transport
  • 26. • The macrophages contain PAS positive granule and rod-shaped bacilli by electron microscopy • More common in whites and male in their thirties to fourties • Usually present with diarrhea and wt loss sometimes of years duration • The clinical presentation of Whipple disease is usually a triad of diarrhea, weight loss, and arthralgia
  • 27. Parasites and protozoa – E.histolytica – G.lamblia • AIDS -diarrheal illness occur in 30-60% of HIV infected pts -most cases are due to microorganisms -AIDS enteropathy is thought to represent some proportion
  • 29. INFLAMMATORY BOWEL DISEASE • is a chronic condition resulting from inappropriate mucosal immune activation Crohn disease and ulcerative colitis • Are chronic, relapsing inflammatory disorders of obscure origin • Infections cause
  • 30. Etiology and pathogenesis • Genetic predisposition • most investigators believe that IBD results from the combined effects of • alterations in host interactions with • intestinal microbiota, intestinal epithelial dysfunction,aberrant mucosal immune responses, and altered composition of the gut microbiome • Inflammation as the final common pathway
  • 31. CROHN DISEASE • a.k.a terminal ileitis ,regional enteritis , granulomatous colitis - When fully developed it is characterized pathologically by 1. sharply delimited and typically transmural involvement of the bowel by an inflammatory process 2. the presence of non caseating granuloma 3. fissuring with formation of fistulas
  • 33. Epidemiology • occurs at any age, but peak is teens and twenties with a minor peak in fifties and sixties • Females are slightly more affected • Smoking is a strong exogenous risk factor Morphology • Small intestine alone -40% • Small intestine + colon -30% • Colon alone -30%
  • 34. • may involve duodenum, stomach, esophagus and even mouth but very rarely • the intestinal wall is rubbery and thick the result of edema inflammation fibrosis and hypertrophy • classic feature is the sharp demarcation of diseased bowel segments from adjacent uninvolved bowel
  • 35. • When multiple bowel segments are involved the intervening bowel is essentially normal ( skip lesions) and the mucosa acquires a coarsely textured cobblestone appearance • linear ulcers develop • narrow fissures develop between the folds of the mucosa often penetrating deeply leading to fistula or sinus tract formation • Mucosal inflammation
  • 36. • Chronic mucosal damage • Ulceration • Trans mural inflammation affecting all layers • Non caseating granulomas Clinical features • Variable but disease usually begins with intermittent attacks of mild diarrhea fever and abdominal pain • In some patients the onset is more abrupt with acute right lower quadrant pain fever and diarrhea
  • 38. • Complications include strictures, fistulas, malabsorption • Extra intestinal manifestations include migratory poly arthritis, sacroilitis ,ankylosing spondylitis, erythema nodosum, uveitis • There is an increased incidence of cancer of the Gl tract ,but is considerably less than ulcerative colitis
  • 39. ULCERATIVE COLITIS • an ulceroinflammatory disease limited to the colon and affecting only the mucosa and submucosa except in the most severe cases • incidence is slightly greater than Crohn disease • onset peaks between 20 and 25 years • UC involves the rectum and extends proximally in a retrograde fashion to involve the entire colon in the more severe cases
  • 40. • It is a disease of continuity and skip lesions like crohn disease are not found • In10% of patients the distal ileum may develop mild mucosal inflammation ( backwash ileitis) • Isolated islands of regenerating mucosa bulge upward to create pseudopolyps • Mural thickening does not occur in UC and the serosal surface is usually completely normal
  • 42. Clinical features • present as a relapsing disorder marked by attacks of bloody mucoid diarrhea that may persist for days weeks or months, then subside & recur • abdominal pain and in minority constipation • the most feared long term complication of UC is cancer
  • 45. Hemorrhoids • variceal dilations of the anal and perianal venous plexuses • common problems which develop secondary to persistently elevated venous pressure within the hemorrhoidal plexus • most frequent predisposing influences are constipation with straining at stool and the venous stasis of pregnancy • much more importantly but rarely develop as result of portal hypertension
  • 46. • they may develop in the inferior hemorrhoidal plexus located below anorectal line –external hemorrhoid • they may also develop in the superior hemorroial plexus and produce internal hemorroids • commonly both are affected • secondary effects include thrombosis ,ulceration ,fissure formation and infarction with strangulation
  • 47. INTESTINAL OBSTRUCTION • may occur at any level • patients present with abdominal pain and distension vomiting failure to pass flatus… • Major causes of intestinal obstruction Mechanical obstruction • Adhesions • Hernias • Volvulus • Intussusception • Tumors
  • 48. • Inflammatory strictures • Obstructive gall stones, fecalith, ,foreign body • Congenital strictures, atresias • Bands • Imperforate anus Pseudo-obstruction • Paralytic ileus • Vascular-bowel infarction • Myopathies and neuropathies ( eg Hirschsprung)
  • 49. • Abdominal hernias may occur through any weakness or • defect in the wall of the peritoneal cavity, including inguinal and femoral canals, the umbilicus, and sites of surgical scars. • ■ Intussusception occurs when a segment of intestine telescopes into the immediately distal segment. • It is the most common cause of intestinal obstruction in children younger than 2 years of age. • Volvulus • Twisting of a loop of bowel about its mesenteric point of • attachment is termed volvulus; it results in both luminal • and vascular compromise. • Thus, volvulus presents with features of both obstruction and infarction
  • 51. Small intestine tumors Adenomas • most occur in the region of the ampulla of Vater • patients with familial polyposis coli are particularly prone Adenocarcinoma • majority occur in the duodenum and jejunum • grow as napkin ring encircling pattern or as polypoid fungating mass • those involving ampulla of Vater may present with obstructive jaundice • at time of diagnosis most tumors have locally spread
  • 52. Tumors of the colon and Rectum Non neoplastic polyps • non neoplastic polyps ( mostly hyperplastic ) represent about 90% of all epithelial polyps in large bowel • inflammatory ( pseudo) polyps represent islands of inflamed regenerating mucosa surrounded by ulceration are seen in patients with longstanding IBD
  • 53. Hyperplastic polyps • small epithelial polyps • often multiple and more than half are found in the rectosigmoid • histologically they are composed of well formed glands and crypts lined by non neoplastic epithelium • the usual small hyperplastic polyp has virtually no malignant potential
  • 54. Juvenile polyps • focal hamartomatous malformations of the mucosal elements • most frequently occur in the rectum • mainly sporadic lesions ,majority occurring in children younger than 5 • in adults they are referred to as retention polyps • tends to be large ( 1 to 3cm) • Histology show abundant cystically dilated glands • Generally occur singly and have no malignant potential • A rare autosomal dominant juvenile polyposis syndrome does carry a risk of adenomas and hence adenocarcinoma
  • 56. Peutz- Jeghers polyp • autosomal dominant syndrome characterized by multiple hamartomatous polyps scattered throughout the entire GIT and melanotic mucosal and cutaneous pigmentation around oral mucosa face genitalia palms . • patients with the syndrome have an increased risk of developing carcinomas of the pancreas breast lung ovary and uterus
  • 58. Adenomas • Intraepithelial neoplasms that range from small, often pedunculated to large that are sessile • occur in 20-30% before40,rising to 40-50% after age 60 • there is well defined familial predisposition Three subtypes • Tubular adenomas-Tubular glands • Villous adenomas- villous projections • Tubulovillous adenoma-a mixture of the two • adenomatous lesions arise as the result of epithelial proliferative dysplasia, which may range from mild to so severe as to constitute carcinoma in situ
  • 59. • most tubular adenomas are small and pedunculated : • villous adenomas tend to be large and sessile and sessile polyps usually exhibit villous features • the malignant risk with an adenomatous polyp is correlated with three independent features – polyp size , – histologic architecture and – severity of epithelial dysplasia
  • 61. • cancer is rare in tubular adenomas smaller than 1cm • the risk of cancer is high ( ~40%) in sessile villous adenomas greater than 4cm Clinical features • may be asymptomatic ,but many are discovered during evaluation of anemia or occult bleeding
  • 63. Familial syndromes • Uncommon autosomal dominant disorders Familial adenomatous polyposis (FAP) • genetic defect is in the APC gene on 5q21 • patients typically develop 500-2500 colonic adenomas • multiple adenomas may also be present elsewhere in the alimentary tract • the majority are tubular • progression to colon adenocarcinoma approach 100% • cancer-preventive measures include prophylactic colectomy
  • 65. Gardner syndrome • also autosomal dominant • patients exhibit intestinal polyps identical to those in FAP combined with multiple osteomas, epidermal cysts and fibromatosis Turcot syndrome is a rare variant marked by the combination of adenomatous colonic polyposis and tumors of CNS Hereditary non polyposis colorectal cancer(HNPCC) • Is characterized by an increased risk of colorectal cancer and extraintestinal cancer particularly of the endometrium in women
  • 66. Colorectal carcinoma • 98% of all cancers in the large intestine are adenocarcinoma • Peak incidence is 60 to 79 years • If found in young person preexisting ulcerative colitis or one of the polyposis syndromes must be suspected • Dietary factors like excess calorie intake, low unabsorbable vegetable fiber, intake of red meat and decreased intake of protective micronutrients
  • 68. • about 1-3% occur in patients with familial syndromes • tumors in the proximal colon tend to grow as polypoid exophytic masses and obstruction is uncommon
  • 69. • carcinomas in the distal colon tend to be annular encircling lesions • microscopically all are adenocarcinomas • when symptomatic produce anemia fatigue weakness bowel habit change… • spread by direct extension into adjacent structures and by metastasis through the lymphatics and blood vessels • the most important prognostic indicator of colorectal carcinoma is the extent of tumor at time of diagnosis
  • 73. Carcinoid Tumors • tumors of neuroendocrine cells • arise in the pancreas or peripancreatic tissue lungs, biliary tree, liver and mainly in GIT • constitute less than 2% of colorectal malignancies but almost half of small intestinal malignant tumors • tendency for aggressive behavior correlates with the site of origin, depth of local penetration and size
  • 74. • appendiceal and rectal carcinoids infrequently metastasize, by contrast ileal ,gastric and colonic carcinoids have higher chance of spread especially those that have penetrated halfway through the muscle wall and >2cm • depending on the predominant product they can be called gastrinoma, somatostatinoma , insulinoma . . . • appendix is the most common site of gut followed by small intestine ,rectum, stomach and colon
  • 75. • clinically may produce local symptoms owing to angulation or obstruction of the small intestine • may produce Zollinger-Ellison syndrome, Cushing syndrome ,hyperinsulinism • some neoplasms are associated with a distinctive carcinoid syndrome( occurs in 1% of patients with carcinoids and in 20% of those with widespread metastasis) • most manifestations are thought to arise from serotonin • manifestations include cutaneous flushes, diarrhea tramps nausea,cough wheezing…
  • 76. Gastrointestinal lymphoma • 1-4% of all GI malignancies • Primary GI lymphomas sometimes arise as sporadic but occur more frequently in certain populations 1. patients with Helicobacter gastritis 2. Natives of the Mediterranean region 3. patients with congenital immunodeficiency states 4. HIV- infected individuals 5. individuals undergoing immunosuppressive therapy 6. patients with sprue
  • 77. • sporadic lymphomas are the most common form in western hemisphere • arise from the B cells of the mucosa associated lymphoid tissue ( MALT)
  • 78. Appendix Acute appendicitis • usually ( 50-80%) associated with obstruction ( fecalith , less commonly gall stone, tumor, or ball of worms ( oxyuriasis vermicularis ) • Obstruction can cause ischemic injury which favors bacterial proliferation with additional inflammatory exudate and edema
  • 79. • Nevertheless a significant minority of inflamed appendices have no demonstrable luminal obstruction Morphology • initially serosa will be transformed to dull granular red membrane • later fibrinopurulent exudate covers the serosa • abscess formation leads to acute suppurative appendicitis
  • 81. • further progress leads to acute gangrenous appendicitis • histologic criterion for the diagnosis of acute appendicitis is neutrophilic infiltration of the muscularis • clinical features include – abdominal pain – nausea – vomiting – tenderness – Fever…
  • 82. Tumors of the appendix Carcinoids Mucocele and pseudomyxoma peritonei Mucocele is globular enlargement of the appendix by inspissated mucus usually the result of obstruction
  • 84. Mucinous cystadenoma is the most common mucinous neoplasm Malignant mucinous cystadenocarcinoma penetration of the appendiceal wall by invasive cells and spread beyond the appendix in the form of localized or disseminated implants produce cellular proliferation and mucin secretion pseudomyxoma peritonei
  • 86. Peritoneum Inflammation • may result from bacterial invasion or chemical irritation the most common causes are sterile peritonitis – –from mild leakage of bile or pancreatic enzymes – perforation or rupture of the biliary system – hemorrhagic poncreatitis, with leadkage of pancreatic enzymes and digestion of adipose tissue to produce fatty acids – surgical procedures, reaction to surgically introduced foreign material such as talk, abrasion of serosal surfaces – Gynecologic conditions eg. Endometriosis
  • 87. Infection • the most common disorders leading to such bacterial dissemination are appendicitis, ruptured peptic ulcer ,cholecystitis, diverticulitis, strangulation of bowel, acute salpingitis, abdominal trauma… • A wide variety of bacterial organisms are implicated in peritonitis • spontaneous bacterial peritonitis is an uncommon condition which occurs in the absence of an obvious source of contamination
  • 88. • in generalized peritonitis an exudate may accumulate under and above the liver to form subhepatic ,subdiaphragmatic abscess.
  • 89. TUMORS • virtually all tumors of the peritoneum are malignant and can be divided into primary tumors(mesotheliomas) and secondary tumors • peritoneal mesotheliomas are associated with asbestos exposure in at least 80% of the cases • secondary tumors are common and can occur in any form of advanced cancer