Lecture 82-83: diseases and pathology of the large intestine Flashcards
what diseases comprise Inflammatory Bowel Disease
UC
CD
(Microscopic colitis)
Etiology of IBD?
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
• Ulcerative Colitis:
– where does this disease manifest?
Colonic involvement
continous
can have rectal involvement
Intestinal manifestatins of UC?
Blood diarrhea
Tenesmus
Acute toxic Presentation – fevers, abd pain, sepsis like
toxic Megacolon
what is seen on endoscopy of Ulcerative Colitis ?
§ 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
Micropathology of UC?
- what is indicative colitis?
what is indicative of IBD?
what is indicative of UC?
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
what is the risk of CRC in UC patients?
8% by 20 years;
increased risk the longer you have UC
• Crohn’s Disease
– where does this disease manifest?
- what is spared?
- may be multi focal but can involve the entire GI tract
classically the terminal ileum and colon
Rectal sparing
Gross morphology of Crohn’s
some buzzwords
Skip lesions – (non continuous involvement)
Longitudinal ulcers,
“cobblestoning”
Transmural Invlvement: Strictures and fistulas
micropathologyof crohn’s
- what’s indicative of colitis?
- -what’s indicative of IBD?
- what’s specific to Crohn’s ?
□ Skip lesions – areas of sparing and areas of involvement — macro and micro
□ Granulomas
Transmural Inflammation
Complications (colonic) of IBD
§ Malabsorption, weight loss, etc.
Transmural inflammation (CD) — scarring, stricture, perforation, fistula
Crohn’s – Perianal involvement
CRC – due to chronic inflammatory processes
extra manifestations of IBD
- peripheral arthritis
- Erythema Nodosom (CD)
- Pyoderma Gangrenosum (UC)
- Eye: Uveitis; Episcleritis
- PSC (UC)
Treatment of IBD
Drugs:
CD: Corticosteroids, abx, infliximab, adalimumab
UC: Amino-ASA; 6 MP; Infliximab
Surgery for management of complications;
IBD
induce remission?
Maintain remission ?
○ Induce remission: steroids; aminosalicylates, abx, immunomodulators
Maintain Remission: immunomodulators, aminosalicylates, abx
Microscopic Colitis -
what is it? what is a possible etiology? how does it present? endoscopy findings? what are the two types? prognosis Treatment?
Idiopathic inflammation of the colon
possible etiology: NSAIDs
watery non bloody diarrhea; normal endoscopy
Collaenous vs Lymphocytic Collitis
Benign course
Treat: Symptomatic; reassurance
Collaenous Microscopic Colitis - male to female ratio?
- histo features?
females > males)
□ Increased intra-epithelial lymphocytes
Sub epithelial collagen table Markedly increased in thickness
Lymphocytic Colitis
male to female ratio?
- histo features?
(Females = Males)
Increased Intraepithelial lymphocytes
Preserved architecture
Infectious Colitis: C. Diff
- microbio
- best assay for dectecion
- risk factors;
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
C. Diff Colitis
- presentation?
Micropathology?
Non bloody, watery diarrhea, fever, leukocytosis, abd cramping
path: Pseudo-membranes; volcanoe lesions
C. Diff Colitis
treatment
○ Metronidazole
○ Vancomycin
If relapse – retreat or change meds
2nd replase: probiotics; Fecal Transplant
Severe - colectomy;
HIV/AIDs Colitis
- what is to be assumed when an HIV patient has diarrhea?
§ 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
Ischemic Colitis
- what is it?
- classically involves what side and why?
- presentation?
– gross pathology?
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
Ischemic Colitis
Acute vs Chronic — micropathology
• Acute: necosis and inflammation
• Chronic: Fibrosis, atrophic crypts, cellular atypia
§ “whithered” glands in the setting of atrophy and diminished supply
Ischemic Colitis
acute vs chronic – causes
Acute – thombosis, trauma, patients at risk for MI
Chronic – § PVD, CVD, “gut angina” — older patients
§ Young patients who are avid runners
Risk factors for ischemic colitis ?
Presenation ?
Embolic disease, Previous Cardiopulmonary bypass, MI, Drugs, Hemodialyiss, thrombotic condtions, venous thrombosis, exercise and long distance running
left sided abd pain; hematochezia
what are the two types of premalignant polyps of colo-rectal cancer ?
– gross morphological differences
Microscopic differences
Adenoma Polyp – usually portruding out of the mucosa;
Picket Fence nuclei
Serrated Polyp – usually flat/sessile
Mucin rich
serrated appearance
No picket fence nuclei
Adenoma Polyp vs Serrated genetic differences?
Adenoma — Chromosomal instability pathway (KRAS, APC, BRAF)
SErrated – CPG island methylator phenotype (gene silencing mutations); Microsatellite instability (MMR genes)
what are the two colon cancer “polyposis” syndromes (malignant)?
what is the genetic mutaiton of each
what is the risk of cancer progression
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
name two colonic polyposis syndromes which are mostly benign?
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
Molecular aspects of Colon cancer: describe three pathways of carcinogenesis
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
why is testing molecular phenotypes of CRCs important?
may direct treatment options
example – KRAS and BRAF mutations are negatively predictive of anti-EGFR therapies
what is the most common CRC?
what are some risk factors for CRC?
Adenocarcinoma
Risk factors: Adematous and Serrated Polyps, family hx, IBD, Tobacco use, diet of high meat and low fiber
Adenoma-Carcinoma Progression:
order of gene events?
APC
KRAS
P53, DCC
Low grade dysplasia –> High grade dysplasia –> invasive carcinoma
In terms of IBD diseases, which has a greater risk for colon cancer ?
UC > CD
Irritable Bowel Syndrome – what is it?
what is the Rome III criteria?
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
Diagnosis?
Etiology?
Treatment ?
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
what is the differnce betwen a false and true diverticulum?
False (majority) – only mucosa and submucosa ooutpouch
true – all 3 walls of the gut outpouch (meckel’s)
Diverticulitis
risk factors:
- classic symptoms:
complication
Risk factors; Age, western diet
LLQ pain, fever, leukocytosis
fistula
Appendicitis
- pathogenesis
presentation –
Treat –
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
Hirschsprung’s Disease
-- what is it? who presents? -- Symptoms? -- Radiology tests pathology? histology? Treatment?
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
