Intestinal Pathology 2 Flashcards
Malabsorption
Hallmark of malabsorption is * steatorrhea
Defective absorption of fats, fat- and water-soluble vitamins, proteins, carbohydrates, electrolytes and minerals, and loss of water.
Malabsorptive disorders most commonly encountered in the * United States are pancreatic insufficiency, celiac disease and Crohn disease
Malabsorption results from disturbance in at least one of the phases of nutrient absorption
Intraluminal digestion
- Pancreatic insufficiency
(Chronic pancreatitis, Cystic fibrosis)
Terminal digestion and/or transepithelial transport
- Celiac disease
- Disaccharidase deficency
- Crohns disease
- Abetalipoproteinemia
Transport into lymphatics
- Whipple disease
- Intestinal lymphangiectasia
Whipple Disease
Blocks Nutrient Transport into Lymphatics
Chronic, relapsing multisystem illness involving the GI tract (diarrhea, steatorrhea, malabsorption) and distant sites (arthritis, lymphadenopathy)
Disease characterized by * weight loss, diarrhea, and polyarthritis;* occur together at presentation in 75% of cases
Infection of the small intestinal mucosa by the gram positive bacillus Tropheryma whipplei
Usually white males ages 30-49 years (10:1 male predominance)
Treat successfully with antibiotics
histology of whipple disease
foamy macrophages
Distended foamy macrophages in lamina propria contain Tropheryma whippeli, a gram positive intracellular actinomycete
PAS-D+ organisms
Celiac Disease
Celiac disease is an inflammatory disease of small bowel in * genetically susceptible individuals
Genetic predisposition:* strong association with certain HLA types (HLA-DQ2 and DQ8)
Inciting agent exposure: * gluten (actually, the alcohol-soluble * gliadin) from wheat, barley, oat, rye
T-cell (inflammatory) response:
Altered peptides are presented to CD4+ T cells in mucosa, leading to an increase in CD8+ intraepithelial lymphocytes that produce proinflammatory cytokines
Celiac Disease presentation
Adults present usually between the ages of 30-60
Children present usually between the ages of 6 and 24 months.
Can be silent (positive serology and villous atrophy without symptoms)
Can be latent (positive serology and no villous atrophy, may have symptoms)
Systemic effects of malabsorption
10-15% of patients will have dermatitis herpetiformis
Vague abdominal discomfort and especially abdominal bloating can lead to a mistaken diagnosis of irritable bowel syndrome
celiac disease risk associations
Increased risk for enteropathy-associated T-cell lymphoma
Increased risk for small intestine adenocarcinoma
new developments in celiac disease
In the past,* typical celiac disease denoted a clinical presentation with diarrhea, steatorrhea, weight loss, and nutritional deficiencies.
In contrast, presentations previously described asatypical celiac disease
(e.g., anemia, fatigue, abdominal bloating and discomfort, osteoporosis, or infertility) are now * more common
Celiac Disease: Diagnosis
Malabsorption
- Immunoglobulin A Tissue Transglutaminase
Small bowel biopsy distal duodenum/jejunum
- Response to gluten-free diet
HLA-DQ2 or HLA-DQ8
(high negative predictor)
Dermatitis herpetiformis
a chronic blistering intensely itchy skin condition, characterised by blisters filled with a watery fluid
Celiac Disease–> 15-25% develop dermatitis herpetiformis
Deposition of immunoglobulin A (IgA) in upper papillary dermis
Environmental Enteropathy
“Tropical Sprue”
Disorder prevalent in areas and populations with poor sanitation and hygiene
Etiology of tropical sprue remains unknown
Typically affects adults
Typical presentation is with chronic diarrhea, soreness of the tongue
(Vitamin B deficiency), and weight loss
Steatorrhea
Autoimmune Enteropathy
Rare
- Intractable diarrhea and * malabsorption associated with circulating gut autoantibodies and a predisposition to autoimmunity
Affects infants, young children and (rarely) adults
Evidence * suggests a hyperactive immune state due to a defect in regulatory T-cells
Autoimmune enteropathy diagnostic criteria:
Presence of chronic diarrhea and malabsorption
Partial or complete villus blunting, deep crypt lymphocytosis, increased crypt apoptotic bodies, and minimal intraepithelial lymphocytosis
Presence of anti-enterocyte antibodies and anti-goblet cell antibodies
- Absence of antibodies does not exclude the diagnosis
Disaccharidase (Lactase) Deficiency
Congenital lactase deficiency is a rare autosomal recessive disorder
Acquired lactase deficiency is common, particularly among Native-Americans and African Americans
Incomplete breakdown of lactose leads to osmotic diarrhea from unabsorbed lactose
May resolve over time
Abetalipoproteinemia
Abetalipoproteinemia is a rare, autosomal recessive disorder, characterized by fat malabsorption.
Mutation in the microsomal triglyceride transfer protein (MTP)
** -Failure to assemble and export lipoproteins
Malabsorption
Dietary modification and replacement of fat soluble vitamins
Irritable Bowel Syndrome
IBS is characterized by the presence of chronic abdominal discomfort or pain associated with changes in bowel habits.
In GI practices one third of patients have functional GI disorders, IBS being the most common diagnosis.
The diagnosis of IBS rests on a careful history and physical examination.
** Pathogenesis unknown
Peak prevalence of IBS is between 20 and 40 years of age
Significant female predominance
*** Need to rule out other causes, such as enteric infection or inflammatory bowel disease
2 types of IBD
Inflammatory bowel disease(IBD) is a chronic condition resulting from inappropriate mucosal immune activation.
Crohn disease may involve any area of the GI tract and is frequently transmural.
Ulcerative colitis is limited to the colon and rectum and extends only into the mucosa and submucosa.
Crohn Disease
Diagnosed most often among persons 15 to 30 years of age
Intermittent attacks of diarrhea, fever, and abdominal pain
Most commonly affects *distal ileum and colon, but may involve mouth to anus
Risk of GI * adenocarcinoma is increased
5-6x
Crohn Disease EPIDEMIOLOGY
Primarily Western nations
Incidence 3/100,000 in US, and rising
More common in whites than blacks: Jews than non-Jews
More common in females than males (~2:1)
Disease peaks in 2nd to 3rd decade; minor peak 6th to 7th
Pattern of bowel involvement of Crohn disease
40% small bowel only (Ileum)
30% small bowel and colon
30% colon only
rarely may involve duodenum, stomach, esophagus, mouth
Crohn DiseaseGross Pathologic Features
Non-contiguous mucosal inflammation
- aphthous ulcers
- serpiginous ulcers
- fissures
- cobblestone mucosa
Fibrosing Strictures
Perforation and abscess
Adhesions
Thickened intestinal wall
Fistula
Creeping Fat
Mucosa with Cobblestone Appearance
Crohn Disease Histopathologic Features
Non-necrotizing * granulomas
- Transmural lymphoid aggregates
Frequently transmural inflammation with deep ulcers (*fissures)
Crypt destruction/distortion
Submucosal fibrosis
Mucosal ulcers
[crypt distortion resembling animals]
Aphthous lesions
are small erosions that are associated with a neutrophilic infiltrate
Ulcerative Colitis- epidemiology
Approximately 800,000 people afflicted with ulcerative colitis in the United States
Common symptoms include diarrhea, rectal bleeding, passage of mucus, urgency, and abdominal pain.
Following the initial flare, 40% to 65% of patients have an intermittent course, and * 5% to 10% of patients have a chronic continuous course
Onset of disease peaks from ages 20-25 yrs
Ulcerative colitis is more common among nonsmokers than among current smokers
- Systemic disorder with migratory polyarthritis, ankylosing spondylitis, uveitis and * primary sclerosing cholangitis
Ulcerative Colitis - what we see in tandem
pANCAThis autoantibody is present in 41% to 73% of patients with UC.
Risk of adenocarcinoma of the colon is greatest in those with pancolitis of >10 years duration (20-30-fold increased risk)
Ulcerative Colitis Pathology
Most severe distally and progressively less * severe more proximally
- Initial presentation
45% of patients with UC have disease limited to the rectosigmoid
35% have disease extending beyond the sigmoid
20% of patients have pancolitis.
- Sharp transition between diseased and uninvolved segments of the colon.
- Always involves rectum
- Toxic megacolon occurs in approximately 5% of severe flares of UC
Toxic megacolon
Complete cessation of colon neuromuscular activity leads to massive dilatation of the colon and black-green discoloration signifying gangrene and impending rupture.
Ulcerative Colitis Histopathology
Inflammation in UC characteristically is confined to the mucosa
- Cryptitis/crypt abscess and gland destruction/distortion
Ulcers and * pseudopolyps
Mucosa biopsy uniformly involved by inflammation
- No granuloma
Anti-Saccharomyces cerevisiaeantibodies(ASCAs)
antibodiesagainst antigens presented by thecell wallof the yeastSaccharomyces cerevisiae.
one more time, ulcerative colitis vs crohn’s disease
UC: bloody diarrhea, extends poxially from rectum; no skip lesions. Does not involve ileum. Strictures are rare. Diffuse mucosal inflammation/ ulceration. no granulomas. no serositis/ adhesions. no fisutla.
Crohn’s:
watery diarrhea or constipation, segmental with rectal sparing, frequently involves ileum, strictures are common, focal inflammation and ulceration, granulomas common, serositis/ adhesions. fistula.
Indeterminant Colitis
Because of the extensive pathologic and clinical * overlap between ulcerative colitis and Crohn disease definitive diagnosis is not possible in approximately 10% of IBD patients.
These cases are termed
* Indeterminate colitis
Lymphocytic Colitis
Chronic watery diarrhea for months to years
Middle aged patients
Female to male 3:1
Normal endoscopic appearance
Collagenous Colitis
Chronic watery diarrhea for months to years
Middle aged or older patients
Female to male 8:1
Normal endoscopic appearance
Diversion Colitis
Surgical treatment –> temporary or permanent ostomy and a * blind distal segment of colon
Graft versus Host Disease
Occurs following hematopoietic stem cell transplantation
Donor T cells targeting antigens on the recipient’s GI epithelial cells
Intestinal graft-versus-host disease often presents as a watery diarrhea but may become bloody in severe cases
Diverticular Disease
Refers to acquired pseudo-diverticular outpouchings
Most common in the sigmoid colon
Colonic diverticula are rare under 30 yr
> 80% asymptomatic
Inflammation of diverticula is called diverticulitis(pain, leukocytosis and fever)
Perforation is uncommon but it can result in pericolonic abscesses, sinus tracts, and peritonitis
