37 terms

Non-neoplastic Disorders 12-3

OM3 - Bernardino - 1hr
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Describe the following type of microscopic colitis:
1. Collagenous colitis
1. Middle aged and older women

Histology:
Dense subepithelial collagen layer
Increased # of intraepithelial lymphocytes
Mixed inflammatory infiltrate within lamina propria
Describe the following type of microscopic colitis:
1. Lymphocytic colitis
1. Middle aged and older men
Strong association with celiac disease
And autoimmune disease

Histology:
Increased # of intraepithelial lymphocytes
Explain the pathogenesis of colonic diverticulae
Result from the unique structure of the colonic muscularis propria & elevated intraluminal pressure in the sigmoid colon -> outpouching of mucosa & submucosa
Explain the cause of diverticulitis
inflammation of diverticula due to obstruction by fecal material
Discuss the embryologic origin of the pathology of Hirschprung
Defective neural crest cell migration -> loss of innervation of colon
Relate the primary pathologic abnormality of Hirschprung to its clinical presentation
Defective neural crest cell migration -> congenital aganglionic megacolon. Since there is a loss of innervation to the muscle -> failure to pass meconium
Describe the putative role of RET gene in the pathogenesis of Hirschprung
Heterozygous loss of function mutation in RET gene in majority of familial cases
- oncogene, but results in loss of function
Describe the clinical presentation of appendicitis
Periumbilical pain that localizes to the RLQ
Nausea, vomiting, fever
Elevated WBC count
Describe the histologic diagnosis of appendicitis
Neutrophilic infiltration of the muscularis propria (ie inner circular & outer longitudinal muscles)
Describe Irritable Bowel Syndrome in terms of:
1. pathogenesis
2. clinical features
3. prognosis
1. poorly defined. interplay between psychological stressors, diet & abnormal GI motility

2. peak prevalence 20-40 y/o females
*Abdominal pain or discomfort at least 3 day per month over 3 months
Improvement with defecation
Change in stool frequency or form*
- fibromyalgia or other chronic pain disorder may be present
-gross & micro evaluation is normal

3. longer duration reduces likelihood of improvement
what is inflammatory bowel disease
idiopathic, chronic condition due to inappropriate mucosal immune activation

- crohn Dz & ulcerative colitis

more common in females in teens-20s
Describe the pathogenesis of IBD
combination of:
-genetics
-microbiota
-epithelial barrier defects
-aberrant mucosal immunity
Describe Crohn Disease in terms of:
1. clinical presentation
2. risk factors for reactivation of symptoms
3. complications
1. intermittent attacks of relatively mild diarrhea, fever and abdominal pain
~ 20% present acutely with RLQ pain, fever and bloody diarrhea
- Periods of active disease are typically interrupted by asymptomatic periods for weeks to months.

may also develop:
Uveitis
Migratory polyarthritis
Sacroilitis
Ankylosing spondylitis
Erythema nodosum
Clubbing of fingertips

2. cigarette smoking associated w/Dz onset, *stress, diet

3. Iron deficiency anemia in those with colonic disease
Hypoalbuminemia
Nutrient malabsorption (B12)
Fibrosing stricture
Fistula may involve the urinary bladder, vagina and abdominal or perianal skin
Describe Crohn Disease in terms of:
1. Gross Morphology
1. May occur in any area of the GI tract
Skip lesions
Strictures are common (A)
Cobblestone appearance (B)
-disease tissue is depressed below the level of normal mucosa
Fissures frequently develop between mucosal folds and may extend deeply -> perforation (C)
Creeping fat (D) - mesenteric fat extends around serosal surface
Describe Crohn Disease in terms of:
1. Histology
active Dz = abundant neutrophils that infiltrate and damage crypt epithelium

Abrupt transition between ulcerated and normal mucosa
Distortion of mucosal architecture; bizarre branching shapes (A)
Non-caseating granuloma (photo B)
Transmural inflammation (photo C)
Describe how the polymorphisms in the NOD2 gene may contribute to Crohn disease
it is gene involved with production of NF-kB which has a role in alpha-Defensin production which has a bactericidal effect.

- polymorphism of NOD2 may cause a loss of bactericidal effect -> Crohn disease
Describe Ulcerative Colitis in terms of:
1. clinical presentation
1. Relapsing disorder characterized by attacks of bloody diarrhea with stringy, mucoid material with lower abdominal pain and cramps temporarily relieved by defecation
- Symptoms may persist for days to month

Infectious enteritis precedes disease onset in some cases; in some patients, smoking may partially relieve symptom

> 50% have clinically mild disease
1/3 require colectomy within 3 years of presentation due to uncontrollable symptoms

Pt may also have:
Migratory polyarthritis
Sacroilitis
Ankylosing spondylitis
Uveitis
Pericholangitis
Primary sclerosing cholangitis
Describe Ulcerative Colitis in terms of:
1. Gross Morphology
1. Involves ONLY the colon and always the rectum
Inflammation limited to mucosa and diffuse
- May involve the entire colon -pancolitis (A) showing active disease, with red, granular mucosa in cecum and smooth atrophic mucosa distally
Pseudopolyps- inflammatory polyps (C)
Describe Ulcerative Colitis in terms of:
1. Histology
1. crypt abscess
pseudopyloric metaplasia
disease limited to mucosa
Describe Crohn Disease in terms of:
1. Region & Distribution of involvement
2. Depth of inflammation
1. any area of GI tract w/skip lesions
2. transmural! -> deep ulcerations, fistula, sinuses, fissures
Describe Ulcerative Colitis in terms of:
1. Region & Distribution of involvement
2. Depth of inflammation
1. colon only! continuous colonic involvement beginning in rectum

2. mucosal only, superficial, broad based ulcers
what is indeterminate colitis?
Features that are not typical of either Crohn disease or ulcerative colitis and defies classification

Serologic studies may be useful
p-ANCA positive in UC (75%) and CD(11%)
Antibodies to S. cerevisiae absent in UC but positive in CD
what factors affect the risk of dysplasia in IBD?
- Primary sclerosing cholangitis- surveillance (regular & extensive mucosal biopsy) starts at time of diagnosis

- Increased after 8-10 yrs of disease initiation- surveillance starts at this time

- Pancolitis has higher risk vs. left-sided only disease
- Severity of active inflammation (presence of neutrophils)
Define:
1. Low-grade dysplasia
2. high-grade dysplasia
1. nuclear stratificaiton, hyperchromasia

2. cribriform architecture, high N/C ratio
- associated w/invasive -> prompts colectomy
Describe Graft vs host Disease
Occurs following allogeneic bone marrow transplantation
- Often presents as watery diarrhea
Small bowel and colon are involved
Secondary to donor T cells targeting antigens on the recipient's GI epithelial cells
Epithelial apoptosis in crypt cells is common histologic finding
what causes graft vs host disease?
donor T cells targeting antigens on the recipient's GI epithelial cells
What is Angiodysplasia?
Characterized by malformed submucosal and mucosal blood vessels
Occurs most often in cecum or right colon after 6th decade of life
Accounts for 20% of major lower intestinal bleeding

histo reveals Ectatic nests of tortuous veins, venules and capillaries
Describe the pathogenesis of Angiodysplasia
Unknown but may be due to mechanical and congenital factors

- Normal distention and contraction may intermittently occlude the submucosal veins that penetrate through the muscularis propria and can lead to focal dilation and tortuosity of overlying submucosal and mucosal vessels.

Cecum having the largest diameter and probably greatest wall tension is affected by the malformation
what are diverticula?
acquired pseudodiverticular outpouchings of the colonic mucosa and submucosa
Describe the pathogenesis of Hemorrhoids
due to persistently elevated venous pressure w/in the hemorrhoidal plexus
describe external hemorrhoids
dilation of a vessel within the inferior hemorrhoidal plexus below the anorectal line
- painful due to pain-sensing nerves in the anus
describe internal hemorrhoids
dilation of a vessel within the superior hemorrhoidal plexus within the distal rectum
- bright red blood; not painful
what is a thrombosed hemorrhoid?
when blood clots inside the vessel
Describe the pathogenesis for acute appendicitis
- initiated by progressive increases in intraluminal pressure that compromise venous outflow -> luminal obstruction by fecalith, tumor or worms (Oxyuriasis vermicularis)
*ischemic injury and stasis of luminal contents favor bacterial proliferation and trigger inflammatory reaction
what can be included on the differential diagnosis for acute appendicitis?
Mesenteric lymphadenitis
Acute salpingitis
Ectopic pregnancy
Mittelschmerz
Meckel Diverticulitis
what complications can occur w/Hirschprung Disease?
enterocolitis
fluid and electrolyte disturbances
perforation
peritonitis
Describe the morphology of Hirschprung megacolon
**Rectum is always affected
Most cases are limited to rectum and sigmoid colon

Barium enema will show constricted aganglionic segment and dilated proximal segment
Aganglionic region may be grossly normal, while the normally innervated proximal segment is dilated