Intestinal Disorders Flashcards

Question 1

Q

Small Intestine

Characteristics

Answer

A

Three portions: duodenum, jejunum and ileum
Four wall layers: mucosa, submucosa, muscularis propria, serosa
- Villous:Crypt ratio ranges 3:1 to 5:1
Cell types:
- Enterocyte (columnar absorptive cell)
- Goblet cell
- Endocrine cell
- Paneth cell
- Undifferentiated crypt cell
Function:
- Terminal digestion and absorption of food
- Secretion of IgA
- Uptake of macromolecules (e.g., B12)

Question 2

Q

Large Intestine

Characteristics

Answer

A

Regions: Cecum, ascending, transverse, descending, sigmoid colon (100-150cm), rectum (15-18cm)
Diameter: Cecum 8cm, sigmoid 2-3cm
Four wall layers: mucosa, submucosa, muscularis propria, serosa
Gross Appearance: test tube shaped pits
Cell types:
- Colonocyte (absorptive cell)
- Paneth cell (R colon)
- Goblet cell
- Endocrine cell
- Undifferentiated crypt cell
Function: Fluid absorption, fecal storage, defecation

Question 3

Q

Intestinal

Congenital Abnormalities

Answer

A

Atresia/stenosis
- Most common in duodenum
- Appears as string-like segment or diaphragm
- Pathogenesis: failure to develop, in utero vascular accident or intussception
- Imperforate anus: failure of cloacogenic diaphragm to rupture
Heterotopia: Presence of tissue that belongs elsewhere
- Pancreatic
- Gastric
Other: Duplication, malrotation, omphalocele, gastroschisis

Question 4

Q

Meconium Ileus

Answer

A

Failure to pass meconium during the neonatal period
Obstructive sx
Associated w/ Cystic Fibrosis
Meconium seen as brown material inspissated in the colon

Question 5

Q

Meckel’s Diverticulum

Answer

A

Etiology: failure of involution of omphalo-mesenteric (vitelline) duct
- Connects gut to yolk sac in utero
Located in small intestine on anti-mesenteric side within 30 cm of ileocecal valve
Contains all wall layers (true diverticulum)
May contain gastric or pancreatic heterotopia (50%)
Complications: ulceration, intussception, incarceration, perforation
Incidence: 2% of population, more in males
- 4% will be symptomatic, usually before age 2
- Most common small intestine congenital anomaly

Question 6

Q

Hirschsprung Disease

Pathogenesis

Answer

A

Congenital Aganglionic Megacolon

Abnormality: Absence of ganglion cells in myenteric plexus (Meissner & Auerbach plexus)
- Due to either premature arrest of normal migration of neural crest cells from cecum to rectum or premature death of ganglion cells
- Always involves rectum w/ variable proximal extension (results in distal obstruction)
Associations: Down’s syndrome (10%), other neurologic problems (5%)
- Some genetic component (4% of siblings affected)
- Majority of familial and 15% of sporadic cases show heterozygous loss-of-function mutations in receptor tyrosine kinase RET

Question 7

Q

Hirschsprung Disease

Clinical Characteristics

Answer

A

Incidence: 1/5-8k live births
- M:F 4:1
Presentation: fail to pass meconium, constipation to life threatening obstruction depending on length of agalionic segment
Treatment: resect aganglionic segment
Diagnosis: intra-operative frozen section analysis to confirm presence of ganglion cells @ anastomotic margin, gross ID of aganglionosis difficult
Complication: progressive dilation of proximal innervated colon (megacolon), may eventually rupture

Question 8

Q

Acquired Megacolon

Etiologies

Answer

A

Chagas disease: Trypanosoma cruzi infection (protozoan transmitted by triatomids “kissing bugs”) ⇒ destruction of enteric plexus
Obstruction: tumor, stricture, adhesions
Toxic Megacolon: seen in ulcerative colitis
- Inflammatory mediators ⇒ damage muscularis propria ⇒ disturb neuromuscular function
- Results in colonic dilation and toxic megacolon, which can perforate
Functional psychosomatic disorder

Question 9

Q

Malabsorption

Overview

Answer

A

Definition: Suboptimal absorption of foodstuff
Signs and sx: abnormal stools (steatorrhea), weight loss, ↑ bowel sounds, vitamin deficiencies
Disorder in one of the following:
- Intraluminal digestion
- Terminal digestion
- Transepithelial transport (sometimes due to epithelial injury)
- Lymphatic transport
Etiologies: non-infectious and infectious

Question 10

Q

Malabsorption

Intraluminal Digestion Defects

Answer

A

Gastric disease: absence of normal acid output and intrinsic factor
Pancreatic disease: absence of pancreatic enzymes and hormones
Bacterial overgrowth in blind loop
Enterohepatic circulation problem: ↓ or absent bile salts due to liver, biliary tree or intestinal problem
Histology: small intestine biopsy w/ non-specific changes: mild villous blunting, chronic inflammation

Question 11

Q

Malabsorption

Terminal Digestion Defect

Answer

A

Lactose deficiency

Congenital (rare): AR mutation in lactase gene
Acquired: African-American > White; elderly > young
Defect: inability to break lactose → glucose and galactose
Results in osmotic diarrhea due to lactose
Diagnostic test: ↑ breath hydrogen (d/t ↑ bacterial fermentation in the gut)
Treatment: lactose free diet
Histology: non-specific

Question 12

Q

Malabsorption

Transepithelial Transport Defect

Answer

A

Caused by epithelial injury

Celiac Sprue
Tropical Sprue (uncertain etiology)
Whipple’s disease (infectious): actually due to defective lymphatic transport
Abetalipoproteinemia
Cystic Fibrosis
Inflammatory bowel disease

Question 13

Q

Celiac Sprue

Overview & Pathogenesis

Answer

A

“Gluten sensitive enteropathy, Non-tropical sprue”

Definition: Mucosal injury due to ingestion of gluten
- Protein found in cereal grains (wheat, barley, rye, oats)
- Luminal and brush-border enzymes digest gluten → amino acids and other peptides (α-gliadin) ⇒ resistant to protease degradation
Pathogenesis caused by Gliadin-derived peptides
- Interact w/ HLA class II on cell surface ⇒ ⊕ T cells ⇒ mucosal injury
- ⊕ Epithelial cells to express IL-15 ⇒ activation/proliferation of CD8⁺ lymphocytes
- NKG2D ⊕ T-cells attack MIC-A ⊕ enterocytes
- Damage ⇒ ↑ passage of other gliadin peptides into lamina propria
- Deaminated by tissue transglutaminase
- Interact w/ HLA-DQ2 or DQ8 on APCs ⇒ ⊕ CD4⁺ T cells ⇒ cytokines ⇒ tissue damage
Genetic susceptibility: Almost everyone w/ disease carries Class II HLA-DQ2 or HLA-DQ8 allele

Question 14

Q

Celiac Sprue

Appearance

Answer

A

Biopsy 2^nd part of duodenum or jejunum

↑ CD8⁺ T lymphocytes
↑ plasma cells, mast cells and eosinophils
↑ epithelial turnover
Villous atrophy
Crypt hyperplasia
Loss of mucosal and brush-border surface area

Question 15

Q

Celiac Sprue

Clinical Characteristics

Answer

A

Serology:
- IgA anti-tissue transglutaminase Ab
- IgA anti-endomysial Ab
Presentation: ± GI symptoms, ± Anemia
Associations: IDDM, Autoimmune Disease, Down’s syndrome, lymphocytic gastritis, IgA deficiency, Dermatitis herpetiformis
↑ risk of many malignancies including:
- T-cell lymphoma (10x)
- Small intestine adenocarcinoma (otherwise uncommon)

Question 16

Q

Tropical Sprue

Answer

A

“Environmental Enteropathy”

Clinical: malabsorption, malnutrition, stunted growth, defective intestinal mucosal immune function
Proposed pathogenesis: defective intestinal barrier function, chronic exposure to fecal pathogens, diarrhea during first 2-3 years of life
- No one organism definitively linked
Histology: villous atrophy, crypt hyperplasia
High Incidence areas: Sub-Saharan Africa, Caribbean, Far East, India

Question 17

Q

Whipple Disease

Answer

A

Defective lymphatic transport
Infectious disease w/ ongoing injury in susceptible host
Pathogen: Tropheryma whippelii (gram ⊕ actinomycete)
Epidemiology: Caucasians; 4-5th decade; M:F 10:1
Symptoms: diarrhea, weight loss, arthralgia; ± polyarthritis, neuropsychiatric sx, lymphadenopathy
Pathology:
- MΦ containing PASD ⊕ granules
- Lysosomes stuffed w/ partly digested bacteria
- MΦ can accumulate in many sites
- Mucosal plaques ⇒ represents lymphatic dilatation and mucosal lipid deposition
Differential diagnosis:
- Whipple disease (AFB ⊖)
- Other fungal infection (e.g., Histoplasmosis)
- Macroglobulinemia (deposition of IgM in mucosa in pts w/ hematopoietic dyscrasia)

Question 18

Q

Mycobacterium Avium Intracellulare (MAI)

Infectious disease

Answer

A

Atypical Mycobacteria
Most commonly occurring in AIDS pts
Pathology: MΦ containing rod shaped organisms, ⊕ PASD, ⊕ acid-fast stain

Question 19

Q

Abetalipoproteinemia

Answer

A

Malabsorption d/t transepithelial transport defect
- Autosomal recessive
Pathogenesis: Inability to synthesize apoprotein B
- Protein needed to form chylomicrons for effective fat transport from epithelial cells
- Lipids (triglycerides) accumulate intracellularly
- Absence of circulating apoprotein B containing lipoproteins: chylomicrons, VLDL, LDL
Burr cells (acanthocytic erythrocytes) on blood smear

Question 20

Q

Cystic Fibrosis

Answer

A

Malabsorption d/t transepithelial transport defect

Absent or reduced amount of epithelial Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
- Defect in intestinal chloride ion secretion
- Interferes w/ bicarb, sodium and water secretion ⇒ ↓ water in luminal secretions
Leads to duct obstruction in pancreas ⇒ injury, inflammation, and fibrosis ⇒ exocrine pancreatic insufficiency

Question 21

Q

Malabsorption

Mechanical Causes

Answer

A

Gastrectomy (complete or partial)
Intestinal surgery:
- Bypass w/ blind loop and bacterial overgrowth
- Loss of critical mass
- Loss of critical functional area
Lymphatic or luminal obstruction due to tumors, adhesions, fistula

Question 22

Q

Infectious Gastroenteritis

Overview

Answer

A

Bacterial, viral, mycobacterial, fungal, parasitic, protozoa etiologies
Some organisms can be visualized and identified based on morphologic and staining characteristics
Histology varies: no visible disease, non-specific changes, granulomatous disease, ulceration
Diagnosis (multimodal approach):
- Serology
- Stool exam for ova and parasites
- Biopsy

Question 23

Q

Bacterial Enterocolitis

Answer

A

Organisms:
- Vibrio cholera, Shigella, Campylobacter jejuni, Yersinia, Salmonella, E. coli
- Clostridium difficile
Mechanisms of disease:
- Ingestion
  - Preformed toxin
  - Toxin producing organism
- Adherence to epithelium w/ interference of function
- Invasion and destruction of epithelium and mucosal integrity
- Spread elsewhere in the body w/ extraintestinal manifestations and/or carrier state

Question 24

Q

Pseudomembranous Colitis

Answer

A

“Antibiotic-Associated Colitis”

Acute colitis w/ adherent yellow-green fibrinopurulent exudate
Organism: Clostridium difficile
- Normal gut commensal
- Setting of abx use due to overgrowth
- Exotoxins (A and B)
  - Disaggregation of actin microfilaments
  - Intestinal secretion and acute inflammation
- C. difficile is prevalent in hospitals
- Up to 30% of hospitalized pts colonized w/ C. difficile but most don’t have disease
Other causes: any form of severe mucosal injury
Diarrhea can be very severe
Can lead to dehydration, hypoalbuminemia, even death

Question 25

Q

Giardia Lamblia

Answer

A

Most common pathogenic parasitic infection
Transmission: fecal contaminated water or food
- Present in unfiltered public water supplies, rural streams
- Worse in immunocompromised
Pear shape trophozoite on duodenal biopsy
No obvious invasion ⇒ nl intestinal morphology by LM
Mechanism: organisms adhere to surface, ↓ expression of brush-border enzymes (including lactase) and damage microvilli
Clinical: acute or chronic diarrhea, malabsorption, and wt loss
- Dx infection by finding cysts in stool samples
- Oral abx effective but recurrence is common

Question 26

Q

Entamoeba histolytica

Answer

A

Parasitic causes of enterocolitis
Etiologic agent of amebiasis
Transmission: Fecal-oral
- Cyst form:
  - Infectious form
  - Form identified in colon and feces
Pathogenesis:
- Penetrates mucosa
- ± Deep ulceration
- ± Portal system spread w/ systemic dissemination and formation of liver, lung, and brain abscesses

Question 27

Q

Non-infectious Enterocolitis

Etiologies

Answer

A

Drug Induced
Treatment related: chemotherapy, radiation
Neutropenic colitis (typhlitis)
Obstruction related
Diversion colitis
Diverticular disease related
Graft vs Host disease

Question 28

Q

Mechanical Bowel Obstruction

Etiologies

Answer

A

Hernia
Adhesions
Intussusception
Volvulus
Tumors and strictures (some due to Crohn Disease)

Question 29

Q

Hernia

Answer

A

Protrusion of a portion of the peritoneal sac through a defect in the wall of the peritoneal cavity

# 1 cause of intestinal obstruction world-wide; #3 cause US
Incarcerated: Hernia contains entrapped bowel
Strangulated: Infarction of trapped bowel due to compromise of blood flow

Question 30

Q

Adhesions

Answer

A

Fibrosis between bowel loops or bowel to other structure

#1 cause of intestinal obstruction in US
Etiology: surgery, inflammatory bowel disease, endometriosis, peritonitis (common denominator)
Complication: ‘internal herniation’, obstruction, infarction

Question 31

Q

Intussusception

Answer

A

Segment of small intestine becomes ‘telescoped’ into the more distal intestine, peristalsis propels the segment distally

Children: w/ or without lesion

Adult: w/ lesion (intraluminal mass as ‘lead point’)

Question 32

Q

Volvulus

Answer

A

Twisting of a loop of bowel about its mesenteric base of attachment

Question 33

Q

Ischemic Bowel Disease

Overview

Answer

A

↓ Blood supply ⇒ hypoxia, accumulation of metabolic byproducts, bacterial overgrowth ⇒ necrosis
Extent:
- Mucosal: mucosa only
- Mural: mucosa and submucosa (may be due to non-occlusive flow problem)
- Transmural: necrosis of all layers (vessel is often mechanically obstructed)
  - Sharply defined border w/ normal
  - Infarcted bowel intensely congested (dusky to purple red)
  - Wall edema w/ coagulative necrosis of muscularis propria 1-4 days after onset
Chronic ischemic colitis may mimic Idiopathic IBD

Question 34

Q

Ischemic Bowel Disease

Etiologies

Answer

A

Arterial occlusion (30-50%)
- Thrombus: Usually proximal and w/ plaque
- Embolus: Cardiac vegetations, procedures, aortic plaque
- Dissecting aortic aneurysm
- Other: iatrogenic, vasculitis, hypercoagulable states
Nonocclusive Ischemia (30-50%)
- Splanchnic vasoconstriction: associated w/ myocardial infarction, congestive failure, shock, trauma, hypovolemia, drugs
Mesenteric venous thrombosis (10-15%)
- Hypercoagulable states: oral contraceptives, invasive neoplasms
- Cirrhosis
- Sepsis
Miscellaneous
- Radiation injury
- Mechanical causes of obstruction

Question 35

Q

Ischemic Bowel Disease

Pathogenesis

Answer

A

Intestinal response to ischemia has 2 phases:
- Hypoxic injury
  - At onset of vascular compromise
  - Epithelial cells are relatively resistant to transient hypoxia
- Reperfusion injury
  - More damaging
  - May trigger multiorgan failure
  - May be due to leakage of gut lumen bacterial products into systemic circulation, free radical production, neutrophil infiltration
Variables:
- Severity of vascular compromise
- Time frame of development
- Vessels affected

Question 36

Q

GI Malignant Lymphoma

Overview

Answer

A

GI tract = most common site of extranodal lymphoma
1-4% of GI malignancies
> 95% are B cell type
Sites: stomach (55-60%) > small intestine (25-30%) > colon (10-15%)
Prognosis is dependent on: stage, lymphoma type
- If disease limited to mucosa or submucosa, 10 yr survival ~ 85%

Question 37

Q

Primary GI Malignant Lymphomas

Types

Answer

A

B Cell
- MALT (Mucosal Associated Lymphoid Tissue) type
  - Low grade and High grade
- Mediterranean Lymphoma
  - Pts have underlying chronic diffuse mucosal plasmacytosis
  - Cells make abnormal IgA, often preceded by malabsorption
- Mantle Cell Lymphoma
- Burkitt and Burkitt-like Lymphoma
- EBV-Associated Lymphoproliferative Disease
- Other types as seen in lymph nodes
T Cell
- EATL (Enteropathy Associated T-cell Lymphoma)
- Other

Question 38

Q

Primary GI Malignant Lymphomas

Risk Factors

Answer

A

Helicobacter gastritis
Natives of Mediterranean region
Immunodeficiencies
- Congenital
- HIV
- Immunosuppressed
- EBV related
Celiac sprue

Question 39

Q

Chronic Colitis

Overview

Answer

A

Etiology unknown
Must exclude known causes first
Idiopathic inflammatory bowel disease (IIBD)
- Ulcerative Colitis (UC)
- Crohn Disease (CD)
- Indeterminate Colitis (~10% of IBD pts)
Microscopic colitis
- Collagenous colitis
- Lymphocytic colitis

Question 40

Q

Inflammatory Bowel Disease

Overview

Answer

A

Initially individuals may have a dx of chronic colitis, etiology unknown
Idiopathic inflammatory bowel disease (IIBD)
- Ulcerative Colitis (UC)
- Crohn Disease (CD)
- Indeterminate Colitis
  - ~10% of IBD pts

Question 41

Q

Inflammatory Bowel Disease

Differential Diagnosis

Answer

A

Consider other possibilities when pts present w/ 1^st episode suspicious for IBD
Must r/o other causes:
- Parasitic disease
- Bacterial pathogens (C. difficile, Salmonella, Shigella, E. coli, Campylobacter)
- Diverticulitis
- Ischemia and other potential causes for bleeding, diarrhea, fever, and/or abd pain

Question 42

Q

Inflammatory Bowel Disease

Epidemiology

Answer

A

↑ Worldwide incidence
- Areas adopting a more “Western” lifestyle
More common in Jewish individuals
Less common in African-Americans
Anyone can develop IBD regardless of race/ethnicity
M=F incidence

Question 43

Q

Inflammatory Bowel Disease

Risk Factors

Question 44

Q

Inflammatory Bowel Disease

Etiology and Pathogenesis

Answer

A

Genetics / Fhx
- ~10-15% of lBD pts have an affected 1° family member
- MZ twins: CD ~60% concordance, UC concordance ~15%
Pathogenesis
- Genetic susceptibility, environmental factors, and immune response
- “Trigger” in susceptible host ⇒ abnormal immune response ⇒ inflammation ⇒ tissue injury

Question 45

Q

NOD 2/Card 15

Gene

Answer

A

Susceptibility locus for IBD

NOD2 activates down-stream inflammatory cell signaling
Ass. w/: aggressive disease, fibrostenotic disease, and recurrence post-op
Common in Caucasian population
Up to 20% carry one mutation, 1% carry two
Chance of NOD-2 homozygotes developing CD no greater than 4%

Question 46

Q

Inflammatory Bowel Disease

Serologic Markers

Question 47

Q

IBD

Clinical Comparison

Question 48

Q

Crohn’s Disease

Clinical Characteristics

Answer

A

Location:
- Limited to the ileum (ileitis) (~40%)
- Terminal ileum and colon (ileocolitis) (~40%)
- Only the colon (20%)
Predominant sx: crampy pain, diarrhea, fever, weight loss
Physical exam findings vary w/ location and severity of disease
- ± Aphthous mouth ulcers
- ± TTP over involved bowel (usu. RLQ TTP & thickening)
- ± Perianal disease (fistulas or tender induration)
± Anemia from chronic disease or blood loss
CRP or ESR may be used to monitor inflammation

Question 49

Q

Crohn’s Disease

Gross Pathology

Answer

A

Disease is regional ⇒ skip lesions
Earliest lesion is the aphthous ulcer
Multiple lesions can coalesce into linear ulcers
Some mucosa is spared ⇒ cobblestone appearance
Diseased tissue is depressed
Can develop fissures between mucosal folds
These can extend transmurally to become fistula tract or perforation site
Bowel wall thickens ⇒ fibrotic
Mesenteric fat can extend to cover the serositis ⇒ ‘creeping fat’

Question 50

Q

Crohn’s Disease

Histology

Answer

A

Active Crohn’s disease:
- Cryptitis
  - Neutrophils infiltrate ⇒ damage crypt epithelium
- Crypt abscess
  - Cluster of neutrophils w/in a crypt
- Often associated w/ crypt destruction
- Ulceration
Repeated cycles of crypt destruction and regeneration lead to:
- Distortion of mucosal architecture
  - Crypts w/ bizarre branching shapes and unusual orientations to one another
- Epithelial metaplasia w/ gastric antral-appearing glands (Pseudo-pyloric metaplasia)
- Paneth cell metaplasia
- Mucosal atrophy w/ loss of crypts
- Noncaseating granulomas (~35%)
  - Any layer of intestinal wall or in mesenteric lymph nodes

Question 51

Q

Crohn’s Disease and Neoplasia

Answer

A

6x ↑risk of carcinoma

↑ Risk of EBV-Associated Lymphoma related to therapy

Question 52

Q

Ulcerative Colitis

Clinical Characteristics

Answer

A

Location:
- May involve rectum only (ulcerative proctitis)
- Varying degrees of sigmoid and descending colon (left sided colitis)
- Disease proximal to the splenic flexure (pancolitis)
Dominant feature of UC is bloody diarrhea
Bowel urgency, rectal discomfort, and abdominal cramping
± Systemic complications (ex. fever and weight loss)
- Depends on the extent of colonic involvement
Episodic > continuous disease
Abdominal TTP common (often over left colon)
Labs:
- Anemia from blood loss
- ↑ WBC
- ↑ ESR or CRP

Question 53

Q

Ulcerative Colitis

Gross Pathology

Answer

A

Continuous involvement
Friable surface w/ easy bleeding
Broad-based ulceration
Pseudopolyps
Isolated islands of regenerating mucosa
- Can fuse to create ‘mucosal bridges’
Leather strap appearance
Mucosal atrophy
- Smooth surface w/o folds
Backwash ileitis (10%)
- Mild mucosal inflammation of the distal ileum in severe cases w/ pancolitis
Inflammation may disturb neuromuscular function ⇒ colonic dilation and toxic megacolon ⇒ ± perforation

Question 54

Q

Ulcerative Colitis

Histology

Answer

A

Active UC (similar to Crohn’s)
- Inflammatory infiltrates
- Crypt abscesses
- Architectural crypt distortion
- Epithelial metaplasia
- But inflammatory process is diffuse & limited to mucosa and superficial submucosa
Healed disease:
- Submucosal fibrosis
- Mucosal atrophy
- Distorted mucosal architecture
- May also revert to near normal after prolonged remission
Granulomas are not present in UC

Question 55

Q

UC Association w/ Dysplasia/Carcinoma

Answer

A

20-30x ↑ risk for neoplastic transformation of colonic mucosa
Highest risk of dysplasia:
- Disease >10 years duration
- Pancolitis
Inactive disease is not protective
Absolute risk of 35% at 30 yrs of disease

Question 56

Q

Crohn’s Disease vs Ulcerative Colitis

Path Features

Question 57

Q

Inflammatory Bowel Disease

Extra-intestinal Manifestations

Answer

A

Aphthous ulcers in the mouth
Sclerosing cholangitis in UC
- Does not improve w/ tx of the UC
Ankylosing spondylitis
- Is not influenced by tx
Migrating large joint arthritis
- Usually asymmetric
- May precede the onset of IBD
- Usually responds to IBD treatment
Pyoderma gangrenosum
- Ulcerating and undermining skin lesion
- May respond to aggressive IBD therapy
Erythema nodosum
- Painful and hyperemic nodules on the anterior leg
- Usually responds well to IBD therapy
Ocular complications include episcleritis, scleritis, and uveitis

Question 58

Q

Inflammatory Bowel Disease

Complications

Answer

A

Fibrostenosis ⇒ Stricture
Stricture ⇒ proximal dilation and pressure ⇒ abscess and fistula
Penetrating Disease ⇒ Fistula
- Fistulas can form between: Entero-Enteric, Entero-Colonic, Entero-Vesicular, Entero-Vaginal, Entero-Cutaneous
Perianal Disease w/ abscess
Superinfection
- C. difficile is a common offender
Toxic Megacolon
- Leads to intestinal perforation
Short Bowel Syndrome
- Severe malabsorption due to loss of small bowel surface area
Colorectal Neoplasm
- ↑ Colon cancer risk w/ duration of illness and extent of disease
- Guidelines for screening vary on the location / extent of disease
Pts w/ primary sclerosis cholangitis at risk for cholangiocarcinoma

Question 59

Q

Inflammatory Bowel Disease

Treatment

Answer

A

Potential pharm IBD treatments:
- Mesalamine
- Steroids
- Immunomodulators
- Antibiotics
- Anti-TNF agents
Surgical:
- Severe and unresponsive UC may require a colectomy
- Surgery for CD is usually for obstruction and/or abscess in the small bowel and for chronicity in large bowel disease
- Resections performed w/ aim of preserving as much small bowel as possible
- Newer treatment options ⇒ ↓ need for surgery in IBD

Question 60

Q

Microscopic Colitis

Answer

A

Unknown Etiology
No gross abnormality seen
Chronic watery diarrhea
Two forms:
- Collagenous Colitis
- Lymphocytic Colitis

Question 61

Q

Collagenous Colitis

Answer

A

Type of microscopic colitis
Women 40-70 y/o
Focal thickening of subepithelial collagen
↑ intraepithelial lymphocytes
↑ mixed inflammatory cells in lamina propria

Question 62

Q

Lymphocytic Colitis

Answer

A

Type of microscopic colitis
F=M
Marked ↑ intraepithelial lymphocytes
Associations: Celiac sprue, other autoimmune diseases

Question 63

Q

Diverticular Disease

Overview

Answer

A

1° in sigmoid colon (> 95%)
Pseudodiverticulum: mucosa and submucosa herniate through wall in area of muscle interruption
Epidemiology:
- Affects 50% of those > 60 y/o in US
- Rare under age 30
- 80% are clinically silent
Pathogenesis:
- Colonic structure issue
  - Weak areas in muscularis propria where the nerves, arterial vasa recta, and connective tissue sheaths penetrate inner circular muscle coat
  - Colonic external longitudinal layer of muscularis propria gathered into 3 bands (taeniae coli)
  - ↑ Intraluminal pressure from exaggerated peristaltic contractions, w/ spasmodic sequestration of bowel segments
  - Inner layers prolapse through muscle gaps (pseudodiverticula)
  - Enhanced by diets low in fiber (↓ stool bulk)

Question 64

Q

Diverticulosis

Answer

A

Clinician dx: presence of diverticula
Pathological dx: presence of uninflamed diverticula
Pt may experience crampy discomfort, constipation, diarrhea, but most have no sx

Answer 61

A

Diverticulum becomes obstructed ⇒ inflammation ⇒ diverticulitis
Clinical sx: fever, ↑ WBC count, peritoneal signs
Pathologist sees inflamed diverticula
If perforation occurs ⇒ pericolonic abscesses, sinus tracts, peritonitis
Pt can present w/ acute abdomen
Even without perforation, can be left w/ chronic issues ⇒ fibrosis, stricture, etc.

Answer 62

A

Bleeding
Abscess
Fistula
Stenosis
Rupture
Impaction

Answer 63

A

Variceal dilations of anal and perianal venous plexus due to ↑ venous pressure
Affects 5% of population
Risks include:
- Straining at stool
- Pregnant woman
- Portal HTN
Complications:
- Thrombosis
- Infarction
- Fissure
- Ulceration

Answer 64

A

Malformed mucosal and submucosal vessels
Most often in cecum and right colon, usu. after age 60
Pathogenesis: interference w/ submucosal venous drainage ⇒ retrograde distension, ? loss of vascular integrity
Seen in 1% of adults but accounts for 20% of significant lower GI bleeding
- Chronic, intermittent
- Acute, massive

Answer 65

A

Worm-like structure: 7 cm length, 1 cm diameter
Lined by colonic type mucosa, rich in lymphoid follicles
Fibrous obliteration w/ ↑ age
Function unknown
Disorders:
- Acute appendicitis
- Mucocele
- Tumors (Carcinoid is most common)

Answer 66

A

Clinical features:
- Relatively common
  - Lifetime risk is 7%, M>F
- Primarily young adults
- RLQ/periumbilical pain, N/V, fever
Pathogenesis:
- Luminal obstruction by fecalith or other object (worms, gallstone, tumor, etc) seen in 50-80% of cases
- Compromises venous outflow
- Tissue undergoes ischemic injury
- Stasis of lumen contents ⇒ bacterial proliferation ⇒ inflammatory response (edema, PMN infiltration)
- Can result in perforation and peritonitis if not detected and removed

Answer 67

A

Most common is carcinoid
May also see adenomas or non-mucin-producing adenocarcinomas
Mucocele
- Dilated appendix filled w/ mucin
- Multiple etiologies:
  - Obstructed appendix filled w/ mucin
  - Mucinous cystadenoma
  - Mucinous cystadenocarcinoma
    - May result in pseudomyxoma peritonei: implantation of mucinous carcinoma cells on peritoneum
      - Can do repeated debulking’s but is usu. fatal

Answer 68

A

Arise from neuroendocrine cell of GIT
- Neuroendocrine cell differentiates from gut stem cell
Endocrine and paracrine functions
Can also arise in the lung
Peaks in 6^th decade
Location:
- Appendix > small intestine > rectum > stomach > colon
May present w/ syndrome related to hormone production
Prognosis of GI carcinoids determined by location
- Foregut carcinoids: rare metz, includes stomach
- Midgut carcinoids: often aggressive, in jejunum and ileum, can invade and metastasize
- Hindgut carcinoids: in appendix and colorectum, usually discovered incidentally, worse behavior in prox. colon than in rectum, rarely metastasize
For individual tumors, also consider:
- Depth of penetration
- Size
  - < 1 cm rarely metastasize
  - > 2 cm usually have metz
Overall survival: 90% exclusive of appendiceal

Answer 69

A

Intramural or submucosal lesion w/ overlying mucosa that can ulcerate
Tumors are yellow or tan, and firm
Histology
- Islands or strands of tumor cells w/ ‘salt and pepper’ chromatin
- Stain for NE markers: chromogranin, synaptophysin, NE granules on EM
Histologic examination cannot distinguish benign from malignant tumors

Answer 70

A

Due to excessive serotonin
Can test blood and urine for:
- 5-hydroxy-tryptamine [5HT]
- 5-HIAA (5-hydroxyindoleacetic acid)
Occurs in 1% of carcinoid pts and in 20% of those w/ metastases
Requires bypass of portal circulation
- Metastases w/ GI tumors
- Lung tumors, ovary tumors
Clinical features:
- Vasomotor disturbances: cutaneous flushing, cyanosis
- Intestinal hypermotility: diarrhea, cramps, nausea and vomiting
- Asthmatic bronchoconstrictive attacks: cough, wheezing, dyspnea
- Hepatomegaly: nodular liver
- Systemic fibrosis: endocardial, valvular, retroperitoneal, pelvic

Answer 71

A

Most common in the colon, can see elsewhere
Begin as small mucosal elevations
- Sessile: grow directly from surface w/o stalk
- Pedunculated: have a stalk

Answer 72

A

Non-neoplastic polyps
- Hyperplastic polyps
- Inflammatory polyps
- Hamartomatous polyps (sporadic/syndromatic)
  - Juvenile polyps
  - Peutz Jegher polyps
Neoplastic polyps
- Adenoma (see dysplasia)

Answer 73

A

Non-neoplastic polyp
- Due to delayed shedding of surface epithelial cells
Most common in rectosigmoid
Typically small (< 0.5 cm)
Usually seen in pts in 50s-60s
No known neoplastic potential

Answer 74

A

Ex. solitary rectal ulcer syndrome

Presents w/ rectal bleeding, mucus discharge, inflammatory lesion of anterior rectal wall
Due to impaired relaxation of anorectal sphincter
Creates sharp angle @ anterior rectal shelf ⇒ recurrent abrasions ⇒ ulceration of rectal mucosa ⇒ polyp & ± mucosal prolapse

Answer 75

A

Examples:

Juvenile Polyps
Peutz Jeghers Syndrome
Cowden Syndrome and Bannayan-Ruvalcaba-Riley Syndrome
Cronkhite-Canada Syndrome

Answer 76

A

Majority present as sporadic lesion in rectum
Most common in children < 5 yrs
In adults, sporadic lesion can be present ⇒ retention polyp
- Pedunculated, dilated glands filled w/ mucin and inflammatory debris

Answer 77

A

Autosomal dominant
3-100 polyps throughout GI tract, most in colorectum
Can hemorrhage when ulcerated
Dysplasia in up to 20% of these polyps ⇒ ↑ risk of colon CA
Associated congenital defects: pulmonary AVMs

Answer 78

A

Genetic defect: LOF mutation in LKB1/STK11 in 50% w/ familial syndrome
- Encodes a kinase regulating cell growth and metabolism
- Autosomal dominant
Presents near age 11
Clinical characteristics:
- Melanotic mucosal and cutaneous pigmentation
  - Lips, buccal mucosa, genitalia, palmar surfaces
- Hamartomatous polyps throughout GI tract
  - Most common in small intestine
Associations:
- ↑ Risk of carcinoma
  - Colon, pancreas, breast, lung, ovary, uterus, testes
- In women: ovarian sex cord tumor w/ annular tubules

Answer 79

A

Hamartomatous polyp syndromes
LOF mutation in PTEN
- Tumor suppressor gene
- Autosomal dominant
Cowden
- Microcephaly, hamartomatous polyps in intestine, benign skin tumors, subcutaneous hemangiomas
- ↑ Risk of breast, follicular thyroid and endometrial CA
BRR
- Also mental deficiency, developmental delay
- Less neoplasia than Cowden

Answer 80

A

a. Trichilemmomas on the nape of the neck
b. Palmar keratoses
c. Perioral papillomatous papules and nasal polyposis
d. Gastric hamartomas

Answer 81

A

Not hereditary
Usually seen over age 50
Clinical:
- Diarrhea, wt loss, abd pain, weakness, nail atrophy and splitting, hair loss, skin hyperpigmentation/hypopigmentation
- Hamartomatous polyps in stomach, small intestine and colorectum
Resemble juvenile polyps but non-polyp mucosa shows similar changes
Cause unknown, no specific therapy, 50% fatal

Answer 82

A

Neoplastic epithelium that remains confined w/in the basement membrane
Can develop in flat areas that look normal
Nuclear hyperchromasia (dark nuclei), elongation, and stratification
± Large nucleoli and fewer goblet cells
Epithelial cells fail to mature as they move toward surface
Show genetic characteristics of neoplastic transformation
Colonoscopic appearance of dysplasia:
Flat mucosa w/ appearance of colitis/normal (sessile)
DALM: Dysplasia associated lesion or mass
Adenoma-like: polypoid projection w/ stalk (peduculated)
- Graded as: Low grade, High grade
- Precursor lesion to adenocarcinoma

Answer 83

A

Benign pedunculated or sessile polypoid lesion composed of dysplastic tissue
Incidence is age related
50% of adults in West have by age 50
Precursor lesion to adenocarcinoma
- Recommend surveillance exam by age 50
- Earlier for those w/ family hx
  - 10 yrs before youngest affected relative was dx
  - 4x risk for family members
Most adenomas won’t progress to adenocarcinoma, but don’t know which ones
No gender predominance
Often asymptomatic, can cause bleeding

Answer 84

A

Tubular: > 75% pit architecture
- Most common adenoma (90%)
- Usually small, pedunculated
Tubulovillous: 25-50% villous architecture
- 5-10% of adenomas
Villous: > 50% villous
- 1% of adenomas
- Usually large and sessile
Sessile serrated:
- Looks like hyperplastic polyps but are premalignant
Carcinoma risk
- Consider size of adenoma, tubular vs villous, pedunculated vs sessile, and amount of dysplasia
- ~40% risk of CA in sessile polyps > 4 cm

Answer 85

A

Dysplastic epithelial cells breach BM → lamina propria or muscularis mucosa
Adenoma → intramucosal carcinoma
- Does not metastasize
Polypectomy is adequate therapy unless:
- Cannot be performed d/t location and/or size
- Lesion on tissue margin
- Intramucosal carcinoma poorly differentiated
- Angiolymphatic invasion present
Next step would be invasion beyond muscularis mucosa
- Now invasive adenoCA ⇒ can spread

Answer 86

A

Most common GI cancer
Preventable cancer
- High impact disease (incidence and death)
- At-risk population (family hx, genetics, elderly etc.)
- Precursor lesions (polyps or adenomas)
- Tests to detect precursor lesions (colonoscopy ⇒ highly sensitive)

Answer 87

A

USA
- Most common GI malignancy, peak age 60-70
- 2nd most common cause of CA death after lung
- 130k new cases/yr; 55k deaths/yr
Worldwide
- 30x difference in incidence rate in developed countries vs India, South America, Africa
- Migration changes risk status
  - Lifestyle and diet changes
  - Low fiber, high carbs and fats associated w/ ↑ risk
  - NSAIDs may have protective effect
    - ⊗ COX -2
    - Highly expressed in colon CA

Answer 88

A

⊕ Risk Factors
- Age
  - ≥ 50 y/o
- Hereditary syndromes
  - Present as early as 10-15 y/o
  - FAP (APC Pathway)
  - HNPCC (Microsatellite instability)
- Family Hx ⇒ even w/o genetic syndromes
- Diet
  - Low dietary fiber, High animal fat, High sugar
- Red meat and smoking
  - Nitrosamines and heterocyclic amines
  - ? APC mutations
  - ? K-ras mutation
- Alcohol
  - Acetaldehyde-DNA damage
- Obesity
  - Insulin Resistance and high Insulin growth factors
- Smoking
- IBD
  - Crohn’s colitis
  - Ulcerative Colitis
⊖ Risk Factors
- Vegetables
  - Antioxidants ⇒ ↓ DNA damage
  - Folate ⇒ ↑ DNA integrity
  - ↓ Growth stimulus
  - ↓ Transit time
- Physical activity/low body mass

Answer 89

A

Typical progression up to 10 yrs

Multifactorial etiology:

Hereditary susceptibility
Diet & environmental factors
Somatic genetic change
- Two distinct genetic pathways
  - Both involve stepwise accumulation of multiple mutations
  - Epigenetic events, e.g. methylation-induced gene silencing, may enhance progression along both
Genetic syndromes ⇒ can accelerate progression to < 3 yrs

Answer 90

A

Adenomatous Polyposis Coli (APC) / B-catenin Pathway
- 80% of sporadic colon CA
- Associated w/ WNT and classic adenoma-carcinoma sequence
- Mutation in KRAS, p53, SMAD 2 and 4 play a role
Microsatellite Instability Pathway
- Associated w/ defects in DNA mismatch repair
- Mutation in MSH2, MLH1, and BRAF play a role
- Common in SSA, mucinous CA, right colon site

Answer 91

A

FAP and variants (mutation in APC gene)
- Familial adenomatous polyposis (FAP)
- Attenuated FAP
  - Delay in polyps, < 100, delayed colon CA
- Gardner syndrome
  - Soft tissue and bone tumors, epidermal cysts, dental issues
- Turcot syndrome (CNS tumors)
  - ⅔ have APC gene mutation ⇒ medulloblastomas
  - ⅓ have DNA repair gene mutation ⇒ glioblastomas
Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome)

Answer 92

A

Autosomal dominant
Germline genetic defect:
- Chromosome 5q21
- Adenomatous polyposis coli (APC) gene
APC function:
- Regulation of ß catenin induced signaling
- Regulation of cell adhesion via ß-catenin and E-cadherin
- Regulation of cell migration via microtubule interaction
- Cell cycle block ⇒ ? inhibits cell cycle components

Answer 93

A

Multiple adenomas
- In colorectum: min 100, max > 2k
  - Look like sporadic ones
  - Flat or depressed adenomas and microscopic ones
- In upper GI tract, most commonly around ampulla
- In stomach, may develop adenomas, more commonly see fundic gland polyp
Extra-intestinal signs and symptoms
- Congenital hypertrophy of retinal pigment epithelium
  - Can detect at birth
Virtually all pts develop colorectal carcinoma
- Usually before age 30
Treatment:
- Colectomy
  - Still need to monitor other GI sites

Answer 94

A

“Lynch Syndrome”

Most common type of familial colorectal CA syndrome
Accounts for 1-5% of cases of colorectal cancer
Do not see extensive polyposis but polyps present
Difficult to distinguish from “sporadic” cases
Early onset of colon CA (usually right colon)
And other cancers
- Esp. those in endometrium, urinary tract, stomach and biliary system

Answer 95

A

Germline mutation in a DNA mismatch-repair gene
- MSH2, MLH1, PMS1, PMS2, MSH6
Encode proteins that repair mismatches of nucleotides
- Occur when DNA polymerase inserts the wrong bases in newly made DNA
W/o repair, mistakes persist as unstable tandemly repeated DNA sequences ⇒ microsatellite instability
Also seen in 15% of sporadic cancers

Answer 96

A

Molecular testing
- Demonstrate tumor has microsatellite instability
- Test for germline mutation in DNA mismatch repair gene
Amsterdam Criteria
- ≥ 3 members in at least 2 successive generations must have colorectal CA
- At least one case dx before age of 50 yrs
- One of the affected members should be a first degree relative of the other two
Bethesda Criteria
- Amsterdam criteria individuals
- Individuals w/ two HNPCC- related cancers
- Individuals w/ colorectal CA and 1^st degree relative w/ ≥ 1 of the following:
  - Colorectal CA dx’d under 45 yrs
  - HNPCC-related CA dx’ed under 45 yrs
  - Adenoma dx’ed under 40 yrs
- Individuals < 45 yrs w/ colorectal or endometrial CA
- Individuals w/ proximal cancer of undifferentiated type
- Individuals < 45 yrs w/ signet-ring CA
- Individuals < 40 yrs w/ adenomas

Answer 97

A

Screen everyone between 50-75 y/o
- FHx, genetic syndromes start at lower age
76-85 y/o ⇒ screen if not done before and if relatively healthy
> 85 y/o ⇒ do not screen

Answer 98

A

Precursor lesions (polyps) ⇒ many asymptomatic
- Remains silent for years
Invasive component elicits a strong desmoplastic response ⇒ firm consistency
Clinical presentation: Symptoms insidious
- Right colon (38%)
  - Fatigue, weakness, iron deficiency anemia (d/t occult blood loss)
  - Exophytic, polypoid lesions
    - Protrudes into lumen
- Transverse colon (18%)
- Descending (left) colon (8%)
  - Occult bleeding, change in bowel habit, LLQ discomfort
  - Annular, encircling lesions
    - Constricting, ‘napkin ring’ prone to obstruction
    - Colonic obstruction ⇒ abd pain, vomiting, inability to eat
- Sigmoid colon (35%)
  - In the rectum, sigmoid colon, villous adenoma ⇒ diarrhea
- Multiple sites 1%
- Advanced stages
  - Grossly visible rectal bleeding
Spread:
- Direct extension
- Metastasizes through blood vessels and lymphatics
  - Preferred sites ⇒ LN, liver, lungs, bones
  - When cancer metastatic ⇒ weight loss
Prognosis: most influenced by depth of invasion and whether LN’s are positive

Answer 99

A

T staging:
- Rectal CA: Endoscopic US (EUS) and MRI are equivocal
- Colon CA: EUS can be used, but usu. not needed
N staging:
- Rectal CA: EUS has the best sensitivity, can biopsy, CT
- Colon CA: CT, often better-established post-op (histology)
M staging:
- CT, esp. combo w/ PET
- Brain ⇒ MRI
- Liver ⇒ Dynamic MRI/CT

Answer 100

A

For carcinoma in situ (Tis), intramucosal carcinoma, or high-grade dysplasia
- Polypectomy or endoscopic mucosal resection via colonoscopy
For all other stages
- Tx options depend on disease specifics
  - Ex. depth of tumor invasion in the colon and presence of metastasis
- Includes:
  - Surgery
  - Chemotherapy
  - Radiation therapy

Answer 101

A

Upper ⅓: lined by columnar rectal epithelium
Middle ⅓: transition to stratified squamous
Lower ⅓: stratified squamous

Answer 102

A

1.5% of digestive system CA
In US: 3,400 new cases per year
Can be glandular, squamous, or basaloid (cloacogenic CA)
Pure squamous cell CA often ass. w/ HPV infection
- Also causes precursor lesions: Anal Intraepithelial Neoplasia (AIN), condyloma

Answer 103

A

Rectal bleeding: 45%
- May be mistaken as hemorrhoid
Pain/rectal mass sensation: 30%
No rectal symptoms: 20%
Size of tumor most important prognosticator
- ≤ 2cm: cure 80%
- ≥ 5cm: cure < 50%

Answer 104

A

Strong evidence
- HPV infection
- Receptive anal intercourse
- STI
- > 10 sexual partners
- Hx of cervical, vulvar or vaginal CA
- Immunosuppression after solid organ transplantation
Moderately strong evidence
- HIV infection
- Long-term use of corticosteroids
- Cigarette smoking

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Intestinal Disorders Flashcards

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