Lecture 82-83: diseases and pathology of the large intestine

Question 1

what diseases comprise Inflammatory Bowel Disease

Answer 1

UC
CD
(Microscopic colitis)

Question 2

Etiology of IBD?

Answer 2

idiopathic:
○ Not just one etiology
§ Environmental: NSAIDs, Tobacco
§ Luminal Antigens: triggering immune system (nonpathogenic and pathogenic bacteria)
§ Genetics – the strongest evidence (chromosome 5, 10 )

hygiene hypothesis

Question 3

• Ulcerative Colitis:

– where does this disease manifest?

Answer 3

Colonic involvement
continous
can have rectal involvement

Question 4

Intestinal manifestatins of UC?

Answer 4

Blood diarrhea

Tenesmus

Acute toxic Presentation – fevers, abd pain, sepsis like

toxic Megacolon

Question 5

what is seen on endoscopy of Ulcerative Colitis ?

Answer 5

§ Loss of vascular markings

§ Friable, edematous, inflamed mucosa

§ White Patches – ulcers and mucus

§ Pseudo-polyps: lesions due to constant cell turn over in the setting of constant colitis; not a sign of active disease

Question 6

Micropathology of UC?

• what is indicative colitis?
  what is indicative of IBD?
  what is indicative of UC?

Answer 6

limited to mucosal involvement

Indicative of Colitis: Active Inflammation – Neutrophils involving the crypts (Crypitis); Crypt Abscesses -

Indicative of IBD: Architectural abnormality
Feature of chronic injury; regenerative; weird crypt shapes

Indicative of UC: – continuous lesions confined to the mucosa

No Granulomas

Question 7

what is the risk of CRC in UC patients?

Answer 7

8% by 20 years;

increased risk the longer you have UC

Question 8

• Crohn’s Disease

– where does this disease manifest?

• what is spared?

Answer 8

• may be multi focal but can involve the entire GI tract

classically the terminal ileum and colon

Rectal sparing

Question 9

Gross morphology of Crohn’s

some buzzwords

Answer 9

Skip lesions – (non continuous involvement)
Longitudinal ulcers,
“cobblestoning”

Transmural Invlvement: Strictures and fistulas

Question 10

micropathologyof crohn’s

• • what’s indicative of colitis?
• -what’s indicative of IBD?
• • what’s specific to Crohn’s ?

Answer 10

□ Skip lesions – areas of sparing and areas of involvement — macro and micro
□ Granulomas

Transmural Inflammation

Question 11

Complications (colonic) of IBD

Answer 11

§ Malabsorption, weight loss, etc.

Transmural inflammation (CD) — scarring, stricture, perforation, fistula

Crohn’s – Perianal involvement

CRC – due to chronic inflammatory processes

Question 12

extra manifestations of IBD

Answer 12

• peripheral arthritis
• Erythema Nodosom (CD)
• Pyoderma Gangrenosum (UC)
• Eye: Uveitis; Episcleritis
• PSC (UC)

Question 13

Treatment of IBD

Answer 13

Drugs:
CD: Corticosteroids, abx, infliximab, adalimumab

UC: Amino-ASA; 6 MP; Infliximab

Surgery for management of complications;

Question 14

IBD

induce remission?

Maintain remission ?

Answer 14

○ Induce remission: steroids; aminosalicylates, abx, immunomodulators

Maintain Remission: immunomodulators, aminosalicylates, abx

Question 15

Microscopic Colitis -

what is it? 
what is a possible etiology? 
how does it present? 
endoscopy findings? 
what are the two types? 
prognosis 
Treatment?

Answer 15

Idiopathic inflammation of the colon

possible etiology: NSAIDs

watery non bloody diarrhea; normal endoscopy

Collaenous vs Lymphocytic Collitis

Benign course
Treat: Symptomatic; reassurance

Question 16

Collaenous Microscopic Colitis - male to female ratio?

- histo features?

Answer 16

females > males)
□ Increased intra-epithelial lymphocytes

Sub epithelial collagen table Markedly increased in thickness

Question 17

Lymphocytic Colitis

male to female ratio?
- histo features?

Answer 17

(Females = Males)

Increased Intraepithelial lymphocytes

Preserved architecture

Question 18

Infectious Colitis: C. Diff

• microbio
• best assay for dectecion
• risk factors;

Answer 18

anearobic, gram postive, spore forming bacillus

Assay of Choice : PCR

Risk: #1 Nosicomial GI Infection — usually older patients who have finished an course of anitbiotics

Question 19

C. Diff Colitis

• presentation?

Micropathology?

Answer 19

Non bloody, watery diarrhea, fever, leukocytosis, abd cramping

path: Pseudo-membranes; volcanoe lesions

Question 20

C. Diff Colitis

treatment

Answer 20

○ Metronidazole
○ Vancomycin

If relapse – retreat or change meds

2nd replase: probiotics; Fecal Transplant

Severe - colectomy;

Question 21

HIV/AIDs Colitis

• what is to be assumed when an HIV patient has diarrhea?

Answer 21

§ Diarrhea in 1/3 –> 2/3s of patients with HIV

§ Sometimes secondary infection can be indentified (syphilis, crypto, spirocheosis)

§ Assume HIV patinet with diarrhea is an opportunisitic infection until proven otherwise

§ HIV Enteropathy when no secondary infection is identified

Question 22

Ischemic Colitis

• • what is it?
• • classically involves what side and why?
• • presentation?

– gross pathology?

Answer 22

reduction of blood flow and insufficient to meet the demands of discrete regions of the colon — leading to necrosis

classically involving the left side of the colon, due to vulnerable vascular supply (less redundancy)

• Gross: Infarcts, Ulcers, pseudomembranes, Colonic edema

Question 23

Ischemic Colitis

Acute vs Chronic — micropathology

Answer 23

• Acute: necosis and inflammation
• Chronic: Fibrosis, atrophic crypts, cellular atypia
§ “whithered” glands in the setting of atrophy and diminished supply

Question 24

Ischemic Colitis

acute vs chronic – causes

Answer 24

Acute – thombosis, trauma, patients at risk for MI

Chronic – § PVD, CVD, “gut angina” — older patients

§ Young patients who are avid runners

Question 25

Risk factors for ischemic colitis ? Presenation ?

Answer 25

Embolic disease, Previous Cardiopulmonary bypass, MI, Drugs, Hemodialyiss, thrombotic condtions, venous thrombosis, exercise and long distance running left sided abd pain; hematochezia

Question 26

what are the two types of premalignant polyps of colo-rectal cancer ? -- gross morphological differences Microscopic differences

Answer 26

Adenoma Polyp -- usually portruding out of the mucosa; Picket Fence nuclei Serrated Polyp -- usually flat/sessile Mucin rich serrated appearance No picket fence nuclei

Question 27

Adenoma Polyp vs Serrated genetic differences?

Answer 27

Adenoma --- Chromosomal instability pathway (KRAS, APC, BRAF) SErrated -- CPG island methylator phenotype (gene silencing mutations); Microsatellite instability (MMR genes)

Question 28

what are the two colon cancer "polyposis" syndromes (malignant)? what is the genetic mutaiton of each what is the risk of cancer progression

Answer 28

FAP -- Familial Adenomatous Polyposis APC mutation -- 100% risk of CRC Treat with prophylactic colectomy ``` Hereditary Non Polyposis Colon Cancer (HNPCC) -- Lynch Syndrome MMR gene (Microsatellite instability) ``` 80% risk of CRC also risk of endometrial and ovarian cancers

Question 29

name two colonic polyposis syndromes which are mostly benign?

Answer 29

Peutz Jeghers: Mostly benign Polyps Colorectal cancer risk present with intussception Juvenile Polyposis: Mostly Benign Poylps Increased cancer risk: GI and Pancreatic cancers Polyps may auto-amputate

Question 30

Molecular aspects of Colon cancer: describe three pathways of carcinogenesis

Answer 30

1) Chromosomal Instability (80%) (APC, KRAS, BRAF, p53) seen in sporadic cancers and FAP 2) Microsatellite Instability Pathway (15%) mutations in MMR genes seen in Lynch and Sporadically 3) CpG islands: Gene silencing via methylation

Question 31

why is testing molecular phenotypes of CRCs important?

Answer 31

may direct treatment options example -- KRAS and BRAF mutations are negatively predictive of anti-EGFR therapies

Question 32

what is the most common CRC? what are some risk factors for CRC?

Answer 32

Adenocarcinoma Risk factors: Adematous and Serrated Polyps, family hx, IBD, Tobacco use, diet of high meat and low fiber

Question 33

Adenoma-Carcinoma Progression: order of gene events?

Answer 33

APC KRAS P53, DCC Low grade dysplasia --> High grade dysplasia --> invasive carcinoma

Question 34

In terms of IBD diseases, which has a greater risk for colon cancer ?

Answer 34

UC > CD

Question 35

Irritable Bowel Syndrome -- what is it? what is the Rome III criteria?

Answer 35

Abn stool frequency and abnormal stool passage (straining, urgnecncy, incomplete evaculation) ROME: at least two of the following 1) Discomfort improved with defecation 2) Onset associated with change in frequency of stool 3) onset associated with change in form of stool

Question 36

Diagnosis? Etiology? Treatment ?

Answer 36

Dx -- more of a diagnosis of exclusion. Do bx to r/o other disease Etiology -- unclear (increased motiligy, CNS/ENS dysregulation) Treatment -- Fiber, anti-diarrheals, antispasmodics, laxatives

Question 37

what is the differnce betwen a false and true diverticulum?

Answer 37

False (majority) -- only mucosa and submucosa ooutpouch true -- all 3 walls of the gut outpouch (meckel's)

Question 38

Diverticulitis risk factors: - classic symptoms: complication

Answer 38

Risk factors; Age, western diet LLQ pain, fever, leukocytosis fistula

Question 39

Appendicitis - pathogenesis presentation -- Treat --

Answer 39

Obstruction of lumen (fecalith, lymphoid hyperplasia) Resulting ischemia and perforation of appendix Classic symptoms: migratory abd pain (umbilicus, mcburney's point), N/V IVF, electrolytes, abx, percutaneous drainage, Surgery

Question 40

Hirschsprung's Disease ``` -- what is it? who presents? -- Symptoms? -- Radiology tests pathology? histology? Treatment? ```

Answer 40

Motility Disorder -- congenital loss of ganglia; leading to loss of peristalsis Symptoms: in infants (neonates); delayed meconium passage; Constipation - but very severe • Radiology: barium enema shows transition zone from normal to abnormal bowel Pathology -- absence of ganglion cells. Hetertrophic nerves with no ganglion cells Treatment: resection of the aganglionic segment