Gastrointestinal Tract

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Gastrointestinal Tract
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Small Large Intestines
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• Small intestine
• Duodenum, Jejunum Ileum
• Villi microvilli increase surface area of the
  mucosa
• crypts of Lieberkuhn Between the bases of the
  villi are pits
• Normal villus crypt height ratio 41.
• Digestive enzymes (brush border enzymes) are
  located in the membranes of microvilli.
• Duodenum
• common bile duct (CBD) pancreatic duct empty
  into 2nd part
• Brunners glands
• Ileum
• Payers patches
• Large intestine
• Cecum ( its appendix) colon (ascending,
  transverse, descending sigmoid) rectum anal
  canal.
• lacks villi Micovilli
• Has numerous goblet cells in the mucosa.
• Absorption of fluids, electrolytes secretion
  of mucous

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• Small Large intestine Normal
• Arterial supply
• up to hepatic flexure of the colon by superior
  mesenteric A.
• Remainder up to rectum- by inferior mesenteric
  A.
• arterial interconnections - mesenteric arcades
• upper rectum - superior hemorrhoidal A ( from
  inferior mesenteric A)
• lower rectum hemorrhoidal A (from internal iliac
  or internal pudendal artery)
• venous drainage
• same distribution
• anastomotic capillary bed between superior and
  inferior hemorrhoidal veins forming portal and
  systemic connections
• Ascending and Descending colon
• retroperitoneal
• Accessory Blood supply and lymphatic drainage
  from posterior abdominal wall
• Lymphatics
• Run as parallel vessels but without arcades

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• Small Large intestine Normal
• Immune System
• lymphoid tissue (MALT)
• ileum - Payer patches (Grossly visible )
• M (membranous) cells
• Transport Ag to APC in SI LI lymphoid sites
• Neuromuscular Function
• Peristalsis
• Small intestinal peristalsis- anterograde and
  retrograde
• mediated by intrinsic (Myenteric plexus) and
  extrinsic (autonomic innervation) neural control
• Myenteric plexus
• Meissner plexus (in submucosa)
• Auerbach plexus (in muscle wall layers)
• Function

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Small intestine Normal
V
Villus Crypt
LM
C
EM
What are these glands?
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Intestines
lacks villi presence of numerous goblet cells
SI
LI
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• Intestines- Pathology
• Symptoms
• General
• Anorexia, nausea, vomiting, flatulence, bloating,
  abdominal discomfort, weight loss, malaise.
• Specific
• Esophageal - Dysphagia (difficulty in
  swallowing), odynophagia (painful swallowing),
  heartburn, regurgitation, retrosternal pain.
• Gastric - early satiety, hematemesis, upper
  abdominal pain/discomfort.
• Small Intestinal - diarrhea, steatorrhea
  (malabsorption), anemia, abdominal colic.
• Large Intestinal - diarrhea, constipation, blood
  and mucus per rectum, tenesmus, proctalgia, anemia

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Intestines - Pathology
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• Intestines- Congenital Anomalies
• Atresia ? complete obstruction
• MC site -duodenum
• Cause of neonatal intestinal obstruction
• jejunum and ileum - equally involved
• colon - never involved
• Stenosis ? incomplete obstruction
• less common
• Imperforate Anus? failure of cloacal diaphragm to
  rupture
• ? neonatal intestinal obstruction
• Meckels Diverticulum ? True Diverticulum
• 2 rule (2 feet from the iliocecal valve, seen in
  2 of people, 2 in size)
• asymptomatic.
• May contain gastric or pancreatic tissues (
  peptic ulcers, diverticulitis, intestinal
  obstruction ,intussusception), ...
• Persistent segment of the vitelline duct (h
  connects the yolk sac gut lumen)

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Meckels Diverticulum
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• Aganglionic Megacolon (Hirschsprungs Disease)
• Caused by Arrested migration of nerve elements
  into distal part of gut
• Absence of ganglion cells in the large bowel
  (Aurbachs Meissners plexus)
• 50 of familial 15 of sporadic cases are due
  to mutations in the RET gene
• RET- promote survival and growth of neurite
  direction to migrating neural crest cells
• Characterized by Aganglionic (aperistaltic)
  segment? narrow
• unaffected proximal colon ? dilatation and
  hypertrophy (megacolon)
• Clinically ?risk with Down syndrome
• Affects 1 in 8000 live births, M F 4 1
• Presents as meconium ileus, abdominal distension,
  constipation, diarrhea (Enterocolitis)
  perforation (rare).
• Diagnosis Histological demonstration of absence
  of ganglion cells in intestinal submucosa
• stained for acetyl cholinesterase.
• Differential Diagnosis any Acquired megacolon
• Chagas disease
• Obstruction( neoplastic) or inflammatory
  stricture of the bowel
• Toxic megacolon - ulcerative colitis or Crohn
  disease
• functional causes

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Intestines - Pathology
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• Diarrhea frequent passage of loose watery
  stools.
• Secretory Diarrhea passage of gt500 ml/day
  watery stools, isotonic with plasma (intestinal
  secretion).
• Osmotic Diarrhea gt500 ml/d stools, the
  osmolality of which exceeds that of plasma by gt50
  mOsm.
• Exudative Diarrhea frequent passage of loose,
  purulent, bloody stools.
• Dysentery painful bloody diarrhea (tenesmus)
• Malabsorption bulky stools with excess fat
  (floats on water) increased osmolality

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Types of Diarrhea
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Intestines - Pathology Enterocolitis (EC)
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Intestines - PathologyEnterocolitis (EC)
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• Acute, self-limited infectious diarrhea
• major cause of morbidity among children
• MCC - enteric viruses
• Viral EC
• Characterized by
• Food water infections ? Damage of small
  intestinal epithelium with shortening of villi
• Diarrhea for 1-7 days.
• MCC are
• Rotavirus (Group A) ? outbreaks in children
  6-24months
• selectively infects and destroys mature
  enterocytes in the small intestine, without
  infecting crypt cells
• Norwalk viruses ? food-borne nonbacterial
  outbreaks in school children adults
• Adenoviruses ? outbreaks in infants

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• Bacterial EC
• Morphologic changes depend upon the causative
  agent
• Pathogenic mechanisms
• Ingestion of preformed toxins present in
  contaminated food by
• Staph. aureus, Clost. Perfringens, Vibrios
• Infection by toxigenic organisms
• Proliferate within the gut lumen and elaborate an
  enterotoxin
• Enteroinvasive organisms (E. coli, Shigella,
  Salmonella)
• Proliferate, invade, and destroy mucosal
  epithelial cells
• Enterotoxins are either
• Secretagogues (cholera toxin)
• Cytotoxins (Shiga toxin)
• Clinical features
• Ingestion of preformed toxins
• Develop within a matter of hours
• Explosive diarrhea
• Acute abdominal distress
• Passes in a day or so
• Infection with enteric pathogen

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• Bacterial EC
• Complications
• Massive fluid loss or destruction of intestinal
  mucosal barrier
• Include dehydration, sepsis, and perforation
• Feces contaminated beef and chicken
• major sources of Salmonella in USA
• improperly cooked chicken
• Campylobacter jejuni ( Common than Shigella
  Salmonella)
• Cholera toxin
• Causes secretory diarrhea by
• 1. Permanently activate GTP ? persistent
  activation of adenylate cyclase ? high levels of
  intracellular cAMP ? stimulates secretion of
  chloride and bicarbonate
• 2. Chloride and sodium Resorption - inhibited

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• Pseudo-membranous colitis Antibiotic-associated
  colitis (EC)
• acute colitis
• Caused by Enterotoxins of Clostridium dificile
• Due to toxins A B ?cytokine production? cell
  apoptosis
• Characterized by The formation of an adherent
  necrotic membrane (pseudomembrane) overlying
  extensive mucosal inflammation
• Pseudo membrane is composed of mucus, fibrin
  inflammatory debris
• Similar fibrino-purulent necrotic pseudomembrane
  forms in enteroinvasive infections in ischemic
  EC
• Clinical features Presents as an acute diarrhea
  while on antibiotic therapy
• toxin detectable in stools.
• Responds to appropriate antibiotics
• Bacterial Overgrowth Syndrome
• Cause Surgical procedures -decreasing the time
  for exposure of ingested bacteria to gastric acid
• bacterial overgrowth in the small intestine
• Clinicallypresent with chronic diarrhea,
  abdominal pain, Malabsorption, and weight loss
• DiagnosisBreath tests for volatile bacterial
  byproducts
• clinical history
• demonstration of bacteria in the proximal small
  intestine by direct culture

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• Parasitic EC
• Nematodes
• 1. Ascaris lumbricoides- MC
• obstruct the intestine or biliary tree
• pneumonitis
• hepatic abscess
• Diagnosis -detection of the eggs in the feces
• 2. Strongyloides
• pulmonary infiltrates with eosinophilia
• Autoinfection in immunosuppressed
• 3. Hookworm (Necator duodenale and Ancylostoma
  duodenale)
• intestinal mucosa -erosions, focal hemorrhage
• Long-term infection lead to IDA
• 4. Enterobius vermicularis (pinworms)
• perineal pruritus worms migrate to the anal
  orifice deposits eggs
• Diagnosis -perianal skin tape
• 5. Trichuris trichiura (whipworm)
• Heavy infections - cause bloody diarrhea and
  rectal prolapse
• in young children

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• Cestodes
• never invade beyond the intestinal mucosa
• No eosinophilia
• Diphyllobothrium latum (fish tapeworm)
• Taenia solium (pork tapeworm)
• Hymenolepsis nana (dwarf tapeworm)
• Protozoa
• Amebiasis (Entamoeba histolytica )
• Giardiasis

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Amebiasis vs. Giardiasis

• Amebiasis
• L I (cecum A. colon)
• Dysentery
• flask-shaped ulcer
• trophozoites have one nucleus
• No flagella

• Giardiasis
• SI (duodenum )
• Diarrhea
• No Ulcers
• trophozoites have two nuclei
• Flagellated

Rx Same for both
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• Necrotizing Enterocolitis
• MC acquired gastrointestinal emergency of
  neonates
• Particularly premature or LBW Babies
• Characterized by Necrotizing inflammation of the
  small and large intestine
• Due to Immaturity of gut immune system
• Initiation of oral feeding ? elicits release of
  cytokines (PAF) ? inflammatory response
• Gut colonization with bacteria
• Mucosal injury
• Morphology Primarily affects terminal ileum and
  ascending colon( Gas in intestinal walls -
  radiology)
• Clinical Features Mild gastrointestinal
  disturbance or as a fulminant illness with
  intestinal gangrene, perforation, sepsis, and
  shock
• Collagen Lymphocytic EC
• Collagen EC patches of band like collagen
  deposits under the surface epithelium, common in
  middle-aged and older women (WgtM)
• Lymphocytic EC intraepithelial infiltrate
  (MF11)
• In Both the conditions
• Endoscopy -normal
• Radiology - unremarkable
• Clinically - characterized by chronic watery
  diarrhea
• Clinical course - benign in nature

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• Miscellaneous EC
• Neutropenic Colitis (Typhlitis) acute
  inflammatory destruction of the mucosa
• compromised blood flow
• Commonly at cecal region
• Pathogenesis impaired mucosal immunity
• life-threatening
• Solitary Rectal Ulcer Syndrome
• Inflammation of the rectum
• impaired relaxation sharp angulation of the
  anterior rectal shelf
• inflammatory polyp
• Characteristic triad
• rectal bleeding
• mucus discharge from the anus
• superficial ulceration of the anterior rectal
  wall

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Intestines - Pathology
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• Malabsorption Syndromes
• Characterized by Deficient absorption of fats,
  proteins carbohydrates, as well as
  electrolytes, minerals, fat soluble vitamins
  water. ? vit. Deficiency, tetany
• Caused by Deficient digestion (Biliary-pancreatic
  disease)
• Deficient absorption (small intestinal disease)
• Clinical findings Weight loss, flatulence
  diarrhea with bulky, frothy, greasy stools
• In prolonged cases Anemia, petechiae,
  hemorrhages, dermatitis, bone aches, latent
  tetany, menstrual disturbances, impotence or
  infertility.
• MCC Celiac sprue, chronic Pancreatitis, Crohns
  disease, tropical sprue, Whipples disease,
  bacterial overgrowth, Disaccharidase deficiency
  Abetalipoproteinemia
• 1. Celiac Sprue
• 2) Tropical sprue

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• 3) Whipples disease Rare systemic disease
• involves intestines, joints CNS
• Caused by Gram-positive actinomycetes
  Tropheryma Whippelii (not yet cultured)
• Affects white Males (MF10 1), 30-50 yrs
• Hallmark features distended macrophages in
  lamina propria contain
• PASve granules (tiny rod-shaped bacilli in EM)
• Clinical features malabsorption syndrome, fever,
  joint pains, cardiac neurologic SS
• Wt. Loss MC presenting feature
• Rx- broad-spectrum antibiotic therapy
• 4. Disaccharidase deficiency
• Apical membrane enzyme that cleaves lactose.
• deficiency ?accumulation of lactose in the gut
  lumen exerting an osmotic purgative effect ?
  diarrhea malabsorption.
• Congenital forms infants on exposure to milk or
  milk products.
• acquired form more common affects adults,
  blacks gt whites, (probably related to intestinal
  infections)
• Intestinal mucosa shows no morphologic
  abnormalities

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• 5. Abetalipoproteinemia
• Congenital deficiency of beta lipoprotein ? which
  is required for intestinal transport of
  chylomicrons.
• The inability to synthesize apoprotein (required
  to assemble lipoproteins) by the enterocytes
  leads to accumulation of triglycerides in the
  cells, with lipid Vacuolation.
• Results in marked lowering of serum LDL, VLDL
  chylomicrons ? defective lipid-membranes of
  cells, including red blood cells ? acanthocytic
  erythrocytes (burr cells), and widespread cell
  injury.
• Presents in infancy with malabsorption wasting.
  

Normal
Malabsorption
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Intestines - Pathology
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• Idiopathic Inflammatory Bowel Diseases
• Etiology Pathogenesis
• Characterized by A chronic, relapsing
  inflammatory conditions
• unknown etiology.
• speculations involve Genetic factors, unknown
  infectious agents, special susceptibility
  factors, altered immuno-reactivity to dietary or
  infectious antigens altered regulatory controls
  of the inflammatory responses
• Distinguished into two clinicopathologic
  entities
• Crohns disease (CD)
• Ulcerative colitis (UC)
• Crohns disease (CD)
• Transmural granulomatous inflammation of the
  bowel, with mucosal ulcerations, fissures
  fistulas in Young (20s)whites Females
• Skip lesions (cobble stone app.)
• Ulcerative colitis (UC)
• crypt abscesses, psudopolyps ?risk of carcinoma
  (adenocarcinoma)

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Different Clinical, Endoscopic, and Radiographic
Features of Crohns Ulcerative Colitis
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Intestines - Pathology Idiopathic Inflammatory
Bowel Diseases
Fissuring Ulcer
noncaseating granulomas
(UC)
(CD)
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Intestines - Pathology
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Types of Ischemic Bowel Diseases
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• Angiodysplasia Tortuous dilated sub mucosal
  veins in the cecum
• May cause massive bleeding.
• Occurs in old age
• Hemorrhoids Dilated varicose veins of the
  perianal plexuses
• Affect 5 of adults
• Due to Chronic constipation, Pregnancy, Liver
  cirrhosis
• two types which may occur singly or together
• External (inferior hemorrhoidal plexus)- painful
• Internal (superior hemorrhoidal plexus)- painless
  
• May cause hemorrhage, inflammation, thrombosis
  fissures
• Diverticular Disease Multiple, flask like
  outpouchings
• gt 60 years.
• Characterized by protruding into the appendices
  epiploicae, in the distal colon.
• They are lined by mucosa but no muscularis
  propria.
• Caused by Focal anatomic defect in the bowel
  wall at the site of penetration of blood vessels.
  
• Increased intraluminal pressure is a contributory
  factor (constipation increased peristalsis).
• Complications are Bleeding, Diverticulitis,
  pericolic abscess, peritonitis

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Intestines - Pathology
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• Intestinal Obstruction
• MC site small intestine ( why?)
• Hernias
• Protrusion of peritoneal hernial sac into a
  defect in the abdominal wall (inguinal, femoral,
  umbilical, surgical scars retroperitoneal
  space).
• Viscera become trapped ? incarceration,
  obstruction, strangulation
• Adhesions
• Twisting of bowel loops around peritoneal fibrous
  bands
• Caused by previous surgery, infection,
  endometriosis or radiation
• Intussusceptions
• A segment of the gut telescopes into the distal
  one
• May be caused by tumors
• Volvulus
• Complete twisting of a bowel loop around its
  mesenteric base
• MC sigmoid colon

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Intestines - PathologyTumors
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• Intestinal Neoplasms
• Small intestine neoplasms are rare
• Benign tumors
• MC Adenoma
• MC site - ampulla of Vater
• Complaints occult blood loss/ rarely-obstruction
  or intussusceptions
• Associated with familial polyposis
• Rx surgical excision difficult
• Clinical Coursepremalignant
• Malignant tumors
• MC Adenocarcinoma
• MC site - duodenum
• clinical -intestinal obstruction
• occult blood loss -only sign
• if involves ampulla of Vater -cause fluctuating
  obstructive jaundice
• risk factors
• most tumors -no identifiable factor
• Crohns, celiac disease, FAP, HNPCC Peutz -
  Jeghers syndrome)

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Intestines - PathologyTumors
Malignant
Benign
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• Intestinal Neoplasms
• Large intestine neoplasms are common
• Benign tumors
• MC Adenoma Polyp
• MC site of GI Polyps Colon
• Types
• Non-neoplastic (Hyperplastic, inflammatory,
  hamartomatous)
• Neoplastic or adenomatous( Tubular, Villous,
  Tubulo-villous)
• Malignant risk of adenomatous polyps correlates
  with
• 1) polyp size ( gt 4cm)
• 2) degree of dysplasia
• 3) extent of villous component (More villous
  more cancerous)

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• Intestinal Neoplasms
• Large intestineNeoplastic or adenomatous(
  Tubular, Villous, Tubulo-villous)
• True neoplasms
• Cause occult bleeding, anemia, protein loss,
  obstruction
• FAP syndrome 100 polyps and 100 malignant risk
• Autosomal dominant inheritance
• innumerable polyps (minimum 100, may be gt1000) in
  the colon other parts of the GIT
• 100 risk of progression to adenocarcinoma in
  10-15 years (indication for prophylactic
  pancolectomy).
• Onset in adolescence (bleeding anemia)
• Gardners syndrome
• FAP syndrome associated with abnormal dentition,
  epidermal cysts, desmoid tumors, osteomas,
  duodenal thyroid cancers
• Turcots syndrome
• FAP syndrome associated with CNS gliomas.

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• Intestinal Neoplasms
• Large intestine Colorectal carcinoma
• Epidemiology
• One of the MC malignancies
• Peak age
• 60 - 70 years for sporadic cases
• 30 - 40 years for FAP syndromes
• Etiology/Pathogenesis
• Arise in preexisting adenomas
• Related to
• Genetic factors
• Diet
• rich in carbohydrates fats and
• low in vegetables Fruits vitamins (A, C E).
• Site distal colon
• All are invasive adenocarcinomas
• Clinical Presentation
• Iron deficiency anemia (occult bleeding),
  abdominal discomfort, progressive bowel
  obstruction, weight loss and liver metastases.
• Prognosis

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Intestines - Pathology L I Tumors
Astler-Coller modification of Dukes staging
system

• A - Limited to mucosa
• B1 - Extending to (not penetrating) muscularis
  propria no LNs
• B2 - Penetrating the muscularis propria, but with
  no LNs
• C1 - Extending to (not penetrating) muscularis
  propria LNs.
• C2 - Penetrating through muscularis propria
  LNs.
• D - Distant metastatic spread.
• Surgery is the only hope for cure.
• Prognosis ( 5-year survival )
• Stage A (100),
• B1 (65), B2 (55),
• C1 (45), C2 (25)

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• Intestinal Neoplasms
• Carcinoid Tumors
• MC site Appendix
• Represent one-half of small intestinal
  malignancies.
• Peak Age sixth decade.
• Arise from Neuroendocrine cells, secrete active
  amines or peptides (gastrin ? Zollinger-Ellison
  syndrome, insulin ? hypoglycemia, ACTH ?
  Cushings syndrome, serotonin ? carcinoid
  syndrome).
• Liver Metastasis what is the clinical
  implication ?
• Appendiceal rectal carcinoids rarely
  metastasize.
• Ileal, gastric colonic carcinoids commonly
  metastasize
• Prognosis5-year survival
• 90 without metastases
• 50 with metastasis

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Case - 1

• A 31-year-old woman has had a 10 year history of
  intermittent, bloody diarrhea. Radiographic
  studies and sigmoidoscopy revealed a friable,
  ulcerated colonic mucosa extending to the splenic
  flexure . The descending colon along with sigmoid
  colon and rectum were resected. The gross
  specimen shown is from another case with even
  more severe disease, in which the ulceration
  extends nearly to the ileocecal valve. Image
  reveals the appearance of the mucosa on closer
  inspection. Microscopic examination reveals the
  appearance.

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1.1
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1.2
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1.3
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1.4
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Case -2

• A 27-year-old man has had recurrent attacks of
  abdominal pain, diarrhea, and low-grade fever for
  several months. He has also developed
  steatorrhea. Colonoscopy revealed erythema and
  erosions of the terminal ileum (image 2.1).
  Radiographic studies demonstrate an enteroenteric
  fistula that bypassed much of the small
  intestine, which was the cause of the
  malabsorption and steatorrhea (image 2.2). He was
  taken to surgery where a portion of small
  intestine was resected. The gross specimen is
  shown in image 2.3. The microscopic appearance is
  seen in images 2.4 and 2.5).

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2.1
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2.2
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2.3
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2.4
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2.5
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Case - 3

• A 43-year-old man came in to the emergency room
  because of intense abdominal pain associated with
  abdominal swelling which had developed over the
  past two days. A plain film radiograph of the
  abdomen showed numerous dilated loops of small
  intestine. A laparotomy was performed. The lower
  ileum was found to have a palpable mass lesion
  involving the muscular wall that obstructed the
  lumen (image 6.1). A segmental resection of ileum
  was performed. The opened bowel specimen from
  surgery shows a segment of buckled small bowel.
  At the apex of the buckle, the mucosa is
  ulcerated. Beneath this can be seen the lesion
  (images 6.2 to 6.3).

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3.1
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3.2
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3.3