Small and Large Intestine Pathology Flashcards
Meckel Diverticulum Rule of 2s
2% of population 2 ft from the ileocecal valve 2 in long 2x male incidence by the age of 2 (only 4% are ever symptomatic)
Hirschsprung Disease
- Megacolon
- 10% cases assc w/ Down Syndrome
- Presents w/ failure to pass meconium -> distension of bowel
- Treatment is surgical resection of the aganglionic segment
GI Obstruction
ntusseception, volvulus, hernia and ahesions
-Multiple air fluid levels in intestines on X-ray
Intussusception
- Telescoping of bowel segment into distal segment -> obstruction, ischemia
- common cause; 5-9 mos age
- most idiopathic
- assc w/ viral illness and rotavirus vaccine
- common lead point is Meckel’s diverticulum
Volvulus
- radiographic “coffee bean” sign
- most common in adults; equally small & large intestine
- children only small intestine
External inguinal hernia
- hernia sac -> prolonged -> ischemia, obstruction and danger of perforation
- acquired forms typically occur anteriorly, via the inguinal and femoral canals
- small bowel loops typically involved
Adhesions
- fibrous bridges create closed loops which other loops can slide through and become entraped -> internal hernia
- most common cause in US due to postoperative, inflammation and endometriosis
Lower GI boundary
distal to ligament of Treitz
Lower GI bleeding
- most common in 7th decade
- chronic, low-grade invisible bleeding -> iron deficiency anemia
- commonly caused by diverticulosis, angiodysplasia, ischemia of watershed zones (> 70 yo) and cancer
Angiodysplasia
- non-neoplastic vascular lesion usually around cecum or proximal right colon
- presents with tortuous dilation of malformed submucosal and mucosal blood vessels
Ischemic Bowel Disease
- acute mesenteric ischemia
- presents w/ abdominal pain and hematochezia
- Elder pts often experience little or no pain
Watershed areas
Splenic flexure
Recto-sigmoid junction
Lower GI ischemia caused by aterial insufficiency (85-95%)
- Non-occlusive (25%): systemic hypotension, shock, hypoxemia, dehydration
- Occlusive (70%): obstruction to arterial blood flow to include primary atheromatous emboli (50%) and thrombus (10%)
- outcome determined by degree of collateral circulation
Lower GI ischemia caused by venous insufficiency (10%)
Younger patients complaining of:
- abdominal pain
- havinge xternal venous compression (mechanical)
- mesenteric venous thrombosis
- hypercoag state
Ischemic bowel disease
Acute compromise of any major vessel -> infarction of several meters of intestine
Superficial mucosal infartction: no deeper than mucularis mucosae
Transmural: all 3 wall layers
Pathogenesis of ischemic bowel disease
- Hypoxic injury
2. Reperfusion injury: leakage of lipopolysaccharide, free radical production and neutrophil infiltration
Diarrhea
- normally absorption > secretion
- caused by disruption of epithelial electrolyte transport or reg sys by toxins, drugs, hormones and cytokines
Diarrhea classification
- Watery: secretory or osmotic
- Fatty: defective absorption of fat and thus nutrients
- Inflammatory: disease or neoplasm (purulent or blood stools)
Secretory diarrhea
- persists during fasting
- usually infectious: viral or enterotoxin
Osmotic diarrhea
- abates w/ fasting
- classically lactase deficiency
Exudative diarrhea
- mucosal damage -> purulent, blood stools
- persists during fasting
- usually bacterial or IBD
Infectious enterocolitis
- most self-limited
- related to ingestion of fecal contaminated water or food, and to foreign travel
- result of interaction of host factors and microbial virulence factors
Enterocolitis symtoms
- diarrhea
- N/V
- dehydration
- fever
- abdominal pain
Bacteria that produce preformed toxins
S. aureus, B. cereus, C. botulinum, C. perfringens
Bacteria that secrete toxins
Enterotoxigenic E. coli, V. cholerae, C. jejuni
Bacteria that intracellularly invade
Shigella, Salmonella
Bacteria that enter the blood stream via the intestinal tract
Salmonella typhi, Listeria monocytogenes
Staphylococcus aureus
- gram(+)
- preformed enterotixins while multipling in food
- fast onset diarrhea
Vibrio cholerae
- severe disease leads to dehydration, hypotension shock and death w/i 24 hrs
- produces multiple toxins -> increase Na and Cl ions in lumen
- attach to brush border of epithelial cells in lumen
MOA cholera toxin
toxin causes increased adenylate cyclase activity -> increased cAMP -> loss of nutrients (Na, H20, Cl, K, Bicarb) -> diarrhea
Enterotoxigenic E. coli (ETEC)
- non-invasive, produces secretory toxins
- non-bloody, watery, non-inflammatory diarrhea
- traveler’s diarrhea
Enteropathogenic E. coli (EPEC)
- non-invasive, attaches to effacing mucosal lesions
- non-bloody diarrhea
- infants
Enterohemorrhagic E. coli (EHEC); O157:H7 and non-O157:H7
- Shiga-like toxin
- bloody diarrhea
- hemorrhagic colitis
- antibiotics inc risk of HUS
- undercooked meat
Enteroinvasive E. coli (EIEC)
- invade epithelial cells
- no toxins
- dystentery and bacterermia
- young children in developing countries
Enteroaggregative E. coli (EAEC)
- chronic non-bloody diarrhea and wasting
- children and in AIDS patients
Campylobacter jejuni
- gram(-) curved bacillus (“gull-winged”)
- most common in developed world
- invasive, toxins
- associated w/ reactive arthritis in patients with HLA-B27 and GBS
Shigella
- bloody diarrhea
- toxin inhibits eukaryotic protein synthesis
- apthous-appearing ulcers
- highly transmissible fecal-oral route or contaminated water
- children < 5 yo
- 75% diarrheal deaths
Salmonella enteritidis
- non-specific features
- acute self-limited colitis (weeks)
- food poisoning
- antibiotic therapy not recommended; can prolong carrier state and does not shorten diarrhea
Salmonella typhi
- typhoid fever
- reative lymphoid hyperplasia in Peyer patches and lymphoid tissues throughout body
Yersinia enterocolitica
- diarrhea
- post-infectious complications: reactive arthritis w/ urethritis and conjunctivitis, myocarditis, erythema nodosum, kidney disease
Yersinia pseudotuberculosis
-fever and abdominal pain mimicking appendicitis
Bacteria with pseudomembranous histological pattern
C. difficile
Shigella
Enterohemorrhagic E. coli
Bacteria with granulomatous histological pattern
Yersinia spp.
Mycobacterium
Parasites and fungi
Bacteria with macrophage histological pattern
Whipple disease-Tropheryma whippelii
Pseudomembranous colitis
- formation of adherent layer of inflammatory cells and debris overlying sites of mucosal injury
- C. difficile overgrowth and toxin (antibiotic-associated colitis)
- Dx by C. difficile cytotoxin in stool
Norovirus
- most common cause of acute gastroenteritis
- second to rotavirus for cause of severe diarrhea in infants/young children
- large group outbreaks due to contaminated food/water
Rotavirus
- common cause of severe childhood diarrhea and mortality worldwide
- selectively destroys mature enterocytes
Adenovirus
- major cause of childhood diarrhea
- important cause of diarrhea in immunocompromised patients
- Associated with intussusception in children
GI pathogens associated with AIDS diarrhea
MAV (foamy macrophage), shigella, salmonella, EAEC, C. Diff
CMS, HSV
Candida, aspergillus
Cryptosporidium, toxoplasma, giardia, entameba histolytica
Strongyloides
Cryptosporidium spp.
- diarrhea
- contaminated drinking water
- AIDS or immunosuppressed patients
- most concentrated in terminal ileum and right colon
Parasitic enterocolitis
Ascaris, most common nematode Pinworm, Whipworm Entamoeba histolytica Giardia lamlia Cryptosporidium spp.
Giardia
- leading GI protozoal disease in US
- 35% prevalence in daycare centers
- endoscopic exam unremarkable; no tissue invasion
- cyst (resistant) and trophozoite forms
Entamoeba histolytica
- dystentery
- AIDS patients
- invade colonic crypts -> flask-shaped ulcer
- embolization to liver and abscesses up to 10 cm
Malabsorption
- defective absorption
- steatorrhea
- pancreatic insufficiency, celiac disease and Chron’s disease most common in US
- disturbance of intraluminal digestion, terminal digestion and/or transepithelial transport or transport into lymphatics
Whipple disease
- blocks nutrient transport into lymphatics
- diarrhea, steatorrhea, malabsorption
- characterized by weight loss, diarrhea and polyarthritis
- caused by infection of Tropheryma whippeli (gram+)
- treat w/ antibiotics
Celiac disease
- inflammatory disease of small bowel in genetically susceptible individuals:
1. strong association w/ HLA-DQ2 and DQ8
2. exposure to gluten (gliadin)
3. T-cell inflammatory response - increased risk for enteropathy-associated T-cell lymphoma and small intestine adenocarcinoma
Celiac disease population
- adults 30-60 yo
- children 6-24 mo
Celiac disease features
- silent (positive serology and villous atrophy w/o sxs) or latent (positive serology and no villous atrophy, may have sxs)
- malaborption, 10-15% dermatitis herpetiformis, vague abdominal discomfort/bloating
Celiac disease typical clinical presentation
diarrhea, steatorrhea, weight loss and nutritional deficiences
More common atypical celiac disease clinical presentation
anemia, fatigue, abdominal bloating/discomfort, osteoporosis, infertility
Celiac disease diagnosis
- IgA Tissue Transglutaminase
- Response to gluten-free diet
- Confirmed by biopsy
Tropical spure
- areas w/ poor sanitation and hygiene
- unknown etiology
- chronic diarrhea, soreness of tongue, weight loss, steatorrhea
Autoimmune enteropathy
- rare
- intractable diarrhea and malabsorption
- infants, young children
- defect in regulatory T-cells
Lactase deficiency
- congenital rare, acquired more common
- osmotic diarrhea
- may resolve over time
Abetalipoproteinemia
- autosomal recessive disorder, MTP mutation
- fat malaborption
- treated by diet mod and fat soluble vitamins
Irritable Bowel Syndrome
- chronic abdominal discomfort, changes in bowel habits
- most common diagnosis
- unknown pathogenesis
- female, 20-40 yo
- diagnosis of exclusion
Inflammatory Bowel Disease
-chronic condition resulting from inappropriate mucosal immune activation:
Crohn’s disease: any area of GI tract, transmural
Ulcerative colitis: limited ot colon/rectum, mucosa/submucosa
Crohn Disease
- 15-30 yo, western nations, whites, females
- intermittent diarrhea, fever and abdominal pain
- most commonly distal ileum
- 5-6x risk of adenocarcinoma
- apthous ulcers, cobblestone mucosa, strictures
- granuloma
Ulcerative colitis
- 20-25 yo
- diarrhea, rectal bleeding, passage of mucus, urgency, abdominal pain
- most intermittent course, 5-10% continuous course
- assc w/ primary sclerosing cholangitis
- pANCA
- pancolitis -> 20-30x risk of adenocarcinoma
Ulcerative colitis pathology
- most severe distally, less severe proximally
- sharp transition between diseased and uninvolved segments
- always involves rectum
- toxic megacolon in 5% flares
- psuedopolyps
- no granuloma
Lymphocytic colitis
- chronic, watery diarrhea for months/years
- middle aged patients
- female 3:1
Collagenous colitis
-chronic, water diarrhea for months/years
middle-aged or older
-female 8:1
Diversion colitis
surgical treatment -> temporary or permanent ostomy and a blind distal segment of colon
GVHD
- hemaopoietic stem cell transplate
- donor T cells targeting antigens in GI cells
- watery to bloody diarrhea
Diverticular disease
- acquired outpouchings
- most commonly sigmoid colon
- 80% asymptomatic
- inflammation -> diverticulitis
- perforation -> pericolonic abscesses
Non-neoplastic polyps
- hamartomatous
- inflammatory
- hyperplastic
Neoplastic polyps
- sessile-serrated adenoma
- adenoma
- polyposis syndromes
Hamartomatous polyps
- haphazard arrangement
- Peutz-Jegher syndrome and juvenile polyposis
Peutz-Jegher syndrome
-autosomal dominant, 11 yo
-multiple GI polyps small intestine and mucocutaneous hyperpigmentation
40% lifetime risk of some maglignancy
Juvenile (retention) polyp
- <5 yo
- no malignant potential when solitary
- juvenile polyposis syndrome assc w/ dysplasia (autosomal dominant)
- 30-50% adenocarcinoma by age 45
Inflammatory polyp
- regenerative/healing phases of inflammation
- severe colitis, solitary rectal ulcer syndrome
Hyperplastic polyp
- benign
- 6-7th decade of life
- most common types of polyps (50% of 50+ yo)
Sessile serrated adenoma
- resembles hyperplastic polyp
- right colon
- high rate of DNA methylation and BRAF mutations
- increased risk of adenocarcinoma
Conventional adenoma
- asymptomatic
- premalignant
- 50% population
- > 2 cm increased risk of malignancy
- treatment is to removal via colonoscopy (50+ yo old and more adenomas, more frequent screenings)
Malignancy risk of adenoma
- > 4 cm
- villous > tubular histology
- increased severity of epithelial dysplasia
Risk factors for malignancy
- family history
- adenoma
- familial adenomatous polyposis: defect in APC tumor suppressor gene, thousands adenomas by 20-30 yo
- lynch syndrome: germline mutations, assc other cancers
Colorectal adenocarcinoma
- males more common
- begin as intramucosal epithelial lesions
- 7th decade of life
- matastases are common
- early surgical resection most effective treatment
- apple-core sign
Clinical features of colorectal carcinoma
- grow slowly
- occult blood loss
- microcytic hypochromic anemia
- often misdiagnosed
- lymph node, liver metastasis
Tumors of small intestines
- uncommon
- most ampulla of Vater
- small neuroendocrine (carcinoid) tumors are most common
Carcinoid tumors
- location most important prognostic factor:
good: esophagus, stomach, appendix, rectum
aggressive: jejunum, ileum - most are at least low-grade malignancies
Carcinoid syndrome
- skin flushing
- diarrhea, abdominal cramping
- asthma sxs
- rapid HR, tricuspid valve insufficiency
Anal canal malignant tumors
Upper 1/3: adenocarcinoma
Lower 1/3: SCC (HPV-associated, cloacogenic [SCC w/ basaloid growth pattern])
Acute appendicitis
- periumbilical pain localizing to RLQ (McBurney sign)
- leucocytosis
- CT decreases false positive rate to 3%
Peritonitis
most caused by: foreign material (talc), endometriosis, leakage of bile/pancreatic enzymes
Peritoneal cavity tumors
- mesothelioma is most common primary (asbestos)
- also metastatic
