patoloji-ders-notlari

Title

Serdar Balcı

Pathology of the Small Intestines, Colon and Appendix

Serdar BALCI, MD

Intestines

Intestines face the “exterior” surface where many “foreign” elements to the body are located
- Food, bacteria
  - Bacteria (beacteriom) outnumber the human cells (genome) by 10x
- Infections, inflamations
  - Incluiding inflamation against foreign elements, allergy
Tubes
- Absence of tube
- Perforation
- Duplication
- Kink formation
Living organs depending on circulation
Subject to systemic disease
Tumors

INTESTINAL OBSTRUCTION

Intestinal Obstruction

May occur at any level
Small intestine is most often involved
- Relatively narrow lumen
Hernias, intestinal adhesions, intussusception, and volvulus account for 80% of mechanical obstructions
Tumors and infarction account others
Abdominal pain, distention, vomiting, and constipation
Surgery is necessary for most cases

Robbins Basic Pathology

Intussusception

Peristalsis propels one segment of bowel and its mesentery into the immediately distal segment

Autopsy Pathology: A Manual and Atlas

Intussusception

telescoped segment of bowel

Autopsy Pathology: A Manual and Atlas

Volvulus

the complete twisting of a loop of bowel about its mesentery

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

HIRSCHSPRUNG DISEASE

Hirschsprung Disease

1 of 5000 live births

Congenital defect in colonic innervation

May be isolated or occur in combination with other developmental abnormalities

Common in males, more severe in females

Siblings of patients have an increased risk of Hirschsprung disease

Neonates with failure to pass meconium in the immediate postnatal period

Obstructive constipation

Enterocolitis, fluid and electrolyte disturbances, perforation, and peritonitis

Surgical resection of the aganglionic segment with anastomosis of the normal colon to the rectum

Hirschsprung diseaseCongenital aganglionic megacolon

Enteric neuronal plexus
Neural crest cells migrate into the bowel wall during embryogenesis
Normal migration of neural crest cells from cecum to rectum is disrupted
No Meissner submucosal plexus and the Auerbach myenteric plexus
Coordinated peristaltic contractions are absent
- Functional obstruction
- Dilation proximal to the affected segment

Robbins Basic Pathology

Heterozygous loss-of-function mutations in the receptor tyrosine kinase RET
- majority of familial cases
- 15% of sporadic cases
Most cases are limited to the rectum and sigmoid colon
- Severe disease can involve the entire colon
- Always affects the rectum
- Length of the additional involved segments varies
Aganglionic region may have a grossly normal or contracted appearance
Normally innervated proximal colon may undergo progressive dilation as a result of the distal obstruction
Diagnosis of Hirschsprung disease requires demonstrating the absence of ganglion cells in the affected segment

ABDOMINAL HERNIA

Abdominal Hernia

Any weakness or defect in the wall of the peritoneal cavity
Protrusion of a serosa-lined pouch of peritoneum
- Hernia sac

Robbins Basic Pathology

Acquired
- Most commonly anterior wall
Congenital
- Bochdalek hernia
  - posterior
- Morgagni hernia
  - anterior, retrosternal

Inguinal and femoral canals

Umbilicus

Sites of surgical scars

Robbins Basic Pathology

External herniation
Visceral protrusion
Inguinal hernias
- Small bowel loops are herniated
- portions of omentum
- large bowel
When organs entrapped → Impaired venous drainage → stasis and edema → increase the bulk of the herniated loop → permanent entrapment, incarceration → arterial and venous compromise, strangulation → infarction

ISCHEMIC BOWEL DISEASE

Ischemic Bowel Disease

Ischemic damage
Mucosal infarction
- Up to muscularis mucosa
Mural infarction
- Mucosa and submucosa
Transmural infarction
- All three layers of the wall

Secondary to acute or chronic hypoperfusion

Acute vascular obstruction

Causes of acute arterial obstruction
- Severe atherosclerosis, at the origin of mesenteric vessels
- Aortic aneurysm
- Hypercoagulable states
- Oral contraceptive use
- Embolization of cardiac vegetations
- Aortic atheromas
Intestinal hypoperfusion
- Cardiac failure
- Shock
- Dehydration
- Vasoconstrictive drugs
- Systemic vasculitides
  - Polyarteritis nodosum
  - Henoch-Schönlein purpura
  - Wegener granulomatosis
- Mesenteric venous thrombosis
- Invasive neoplasms
- Cirrhosis
- Portal hypertension
- Trauma
- Abdominal masses that compress the portal drainage
Initial hypoxic injury occurs at the onset
- some damage occurs, cells are relatively resistant to transient hypoxia
Second phase, reperfusion injury
- Restoration of the blood supply
- Associated with the greatest damage
- May lead to multiorgan failure
- Free radical production, neutrophil infiltration, and release of inflammatory mediators, such as complement proteins and cytokines
Severity of ischemic bowel disease depend on
- Time frame
- Vessels affected
Watershed zones
- Splenic flexure, where the superior and inferior mesenteric arterial circulations terminate
- Sigmoid colon and rectum where inferior mesenteric, pudendal, and iliac arterial circulations end
- Generalized hypotension or hypoxemia cause localized injury, and ischemic disease should be considered in the differential diagnosis for focal colitis of the splenic flexure or rectosigmoid colon

Dark purple serosa of necrotic small intestines

Autopsy Pathology: A Manual and Atlas

distinct demarcation can be seen between the viable and nonviable tissue

Autopsy Pathology: A Manual and Atlas

Multifocal mucosal hemorrhagic infarcts in the small and large bowel

Autopsy Pathology: A Manual and Atlas

Transmural infarct of the cecum

Yellow exudates

Necrotic purple-red mucosa

Autopsy Pathology: A Manual and Atlas

Intestinal capillaries run alongside the glands, from crypt to surface
- Make a hairpin turn at the surface
- Empty into the postcapillary venules
Oxygenated blood to supplied to crypts but leaves the surface epithelium vulnerable to ischemic injury
- Protects the crypts
  - Contain the epithelial stem cells
- Surface epithelial atrophy, necrosis, consequent sloughing
- Normal or hyperproliferative crypts

Increased susceptibility of watershed zones, but may occur anywhere

Segmental and patchy in distribution

Mucosa is hemorrhagic and often ulcerated

Edema that may involve the mucosa or extend into the submucosa and muscularis propria

Extensive mucosal and submucosal hemorrhage and necrosis

Serosal hemorrhage and serositis generally are absent

Damage is more in acute arterial thrombosis and transmural infarction
Blood-tinged mucus or blood accumulates within the lumen
Coagulative necrosis of the muscularis propria occurs within 1 to 4 days
- associated with purulent serositis and perforation
Mesenteric venous thrombosis
- Arterial blood continues to flow for a time
- Less abrupt transition from affected to normal bowel
- Impaired venous drainage eventually prevents entry of oxygenated arterial blood

Atrophy or sloughing of surface epithelium

Crypts may be hyperproliferative

Inflammatory infiltrates initially are absent in acute ischemia

Neutrophils are recruited within hours of reperfusion

Robbins Basic Pathology

Chronic ischemia
- Fibrous scarring of the lamina propria
- Uncommonly, stricture formation

Robbins Basic Pathology

In acute phases of ischemic damage
- Bacterial superinfection
- Enterotoxin release
- Pseudomembrane formation that can resemble Clostridium difficile –associated pseudomembranous colitis
Signs overlap with those of other abdominal emergencies
- Acute appendicitis, perforated ulcer, and acute cholecystitis
- Diagnosis of intestinal infarction may be delayed or missed
As the mucosal barrier breaks down
- Bacteria enter the circulation
- Sepsis can develop
- Mortality rate may exceed 50%
Mucosal and mural infarctions
- by themselves may not be fatal
- may progress to more extensive, transmural infarction if the vascular supply is not restored
Chronic ischemia
- may masquerade as inflammatory bowel disease
CMV infection
- ischemic gastrointestinal disease as a consequence of the viral tropism for and infection of endothelial cells
- can be a complication of immunosuppressive therapy

Radiation enterocolitis

Epithelial damage

Vascular injury may be significant and produce changes that are similar to ischemic disease

Presence of bizarre “radiation fibroblasts” within the stroma

Necrotizing enterocolitis

Acute disorder of the small and large intestines

Transmural necrosis

Most common acquired gastrointestinal emergency of neonates

Premature or of low birth weight

Occurs most often when oral feeding is initiated

Ischemic injury generally is considered to contribute to its pathogenesis

Angiodysplasia

Malformed submucosal and mucosal blood vessels
Cecum or right colon
Presents after the sixth decade of life
Prevalence of angiodysplasia is <1% in the adult population
- but 20% of major episodes of lower intestinal bleeding

DIVERTICULITIS

Diverticulitis

Acquired pseudodiverticular outpouchings of the colonic mucosa and submucosa
Rare <30 years of age
Prevalence approaches 50% in Western adult populations >60 age
Generally multiple, diverticulosis
Much less common in Japan and nonindustrialized countries
- dietary differences
Elevated intraluminal pressure in the sigmoid colon
Nerves, arterial vasa recta, and their connective tissue sheaths penetrate the inner circular muscle coat to create discontinuities in the muscle wall
In other parts of the intestine, these gaps are reinforced by the external longitudinal layer of the muscularis propria
- In the colon, this muscle layer is discontinuous, taeniae coli
High luminal pressures, by exaggerated peristaltic contractions, with spasmodic sequestration of bowel segments

Small, flask-like outpouchings

Usually 0.5 to 1 cm in diameter

Regular distribution in between the taeniae coli

Robbins Basic Pathology

Thin wall composed of

-flattened or atrophic mucosa

-compressed submucosa

-attenuated or absent muscularis propria

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Most common in the sigmoid colon, but other regions of the colon may be affected in severe cases
Compressible, easily emptied of fecal contents, often surrounded by the fat-containing epiploic appendices on the surface of the colon
- May be missed on casual inspection
Hypertrophy of the circular layer of the muscularis propria in the affected bowel segment
Obstruction of diverticula → inflammatory changes → diverticulitis and peridiverticulitis → lead to perforation
With or without perforation, recurrent diverticulitis cause segmental colitis
- fibrotic thickening in and around the colonic wall, or stricture formation
Perforation
- formation of pericolonic abscesses
- development of sinus tracts
- peritonitis

HEMORRHOIDS

Hemorrhoids

5% of the general population
Dilated anal and perianal collateral vessels
Connect the portal and caval venous systems to relieve elevated venous pressure within the hemorrhoid plexus
Constipation and associated straining
- increase intra-abdominal and venous pressures
Venous stasis of pregnancy
Portal hypertension
External hemorrhoids
- Collateral vessels within the inferior hemorrhoidal plexus
- Located below the anorectal line
Internal hemorrhoids
- Superior hemorrhoidal plexus
- Within the distal rectum
Thin-walled, dilated, submucosal vessels
Protrude beneath the anal or rectal mucosa
Subject to trauma, superficial ulceration
Tend to become inflamed, thrombosed, and, in the course of time, recanalized

**Meckel diverticulum **

Autopsy Pathology: A Manual and Atlas

Acute Appendicitis

Most common in adolescents and young adults
- May occur in any age group
- Lifetime risk for appendicitis is 7%
- Males are affected slightly more often than females
May be confused with
- Mesenteric lymphadenitis
  - Yersinia infection or viral enterocolitis
- Acute salpingitis
- Ectopic pregnancy
- Mittelschmerz
- Meckel diverticulitis
Initiated by progressive increases in intraluminal pressure
Compromised venous outflow
50%-80% associated with overt luminal obstruction
- small, stonelike mass of stool, fecalith
- less commonly, a gallstone
- tumor
- mass of worms
Ischemic injury → stasis of luminal contents → bacterial proliferation → inflammatory responses → tissue edema → neutrophilic infiltration of the lumen → muscular wall → periappendiceal soft tissues
Early acute appendicitis
- Subserosal vessels are congested
- Modest perivascular neutrophilic infiltrate within all layers of the wall
- Serosa dull, granular-appearing, erythematous surface
- Mucosal neutrophils and focal superficial ulceration often are present
- Diagnosis of acute appendicitis requires neutrophilic infiltration of the muscularis propria
Severe cases
- Focal abscesses may form within the wall
  - Acute suppurative appendicitis
- Large areas of hemorrhagic ulceration and gangrenous necrosis
  - Acute gangrenous appendicitis
- Rupture and suppurative peritonitis