Small & Large Bowel IBS/IBD/Diverticular Flashcards
Clinical Features of MalabsorptionGeneral Symptoms/Signs
steatorrhea weight loss anorexia abdominal distention borborygmi muscle wasting
Clinical Features of MalabsorptionEffect on Specific Organ Systems
Alimentary tract: diarrhea, flatus, distension
Hematopoietic system: anemia from loss of Fe, folate, B6 or B12; bleeding from vit K def
Musculoskeletal system: osteopenia, hypocalcemia, and hypomagnesemia
Endocrine: amenorrhea, impotence, and infertility
Nervous system: neuropathy from vitamin deficiencies
Celiac Disease
Inflammatory disease of small bowel that results from gluten ingestion.
Genetic predisposition:strong association with certain HLA types (HLA-DQ2 and DQ8)
T-cell (inflammatory) response:
- gliadin is deamidated by tissue transglutaminase (tTG)
- resulting peptides high-affinity ligands for HLA-DQ2/DQ8
- altered peptides are presented to CD4+ T cells in mucosa, leading to a increase in CD8+ intraepithelial lymphocytes
Celiac Disease - Clinical
Adults usually present age 30 – 60 yr, M=F, but detected F>M 2:1
Children classically 6 – 24 mo.
May be silent or latent
Diarrhea with steatorrhea
Various systemic effects of malabsorption, including anemia, osteoporosis, infertility, myopathy and neuropathy
Symptoms may be subtle or even absent in many patients
Skin disease, Dermatitis herpetiformis, is associated in 10%
lymphocytic gastritis and colitis
Increased risk for T-cell lymphoma of the small intestine, small intestinal adenocarcinoma and esophageal squamous cell carcinoma
Celiac Disease: Diagnosis
- clinical malabsorption, documented
- HLA-DQ2 or HLA-DQ8
[if negative, high negative predictive value] - serological tests:
IgA Anti-Transglutaminase Antibody (tTG),
IgA Anti-Endomysial Antibody (EMA),
IgA/G Anti-Gliadin Antibody (AGA),
IgA Anti-Reticulin Antibody (ARA)
positive results are titered; positive endomysial antibody=mucosal disease and indicates need for biopsy. - small bowel biopsy (THE GOLD STANDARD) - distal duodenum/jejunum; endoscopic biopsy
- response to gluten-free diet
Celiac Disease, Dermatitis herpetiformis
Subepidermal blistering skin disease
Biopsy shows separation of epidermis from
dermis at dermal papilla with neutrophilic infiltrate
granular IgA deposits
Is characterized by intensely itchy, chronic papulovesicular eruptions, usually distributed symmetrically on extensor surfaces
Tropical Sprue (Environmental Enteropathy)
Celiac-like disease that occurs in people living in developing countries… the “tropics”
- poor sanitation, hygiene….150 million children worldwide
Occurs in both endemic and epidemic forms
Cause: unknown
- bacterial overgrowth by enterotoxigenic organisms such as Cyclospora, E coli and Hemophilis have been implicated as possible causes
Can result in significant physical and neurological deficits
Treat with a broad-spectrum antibiotic, usually unsuccessful
Autoimmune Enteropathy
X-linked disorder
Severe persistent diarrhea and autoimmune disease, most often in young children
IPEX = severe familial form (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked)…..due to mutation of FOXP3 gene (on X chromosome)
- leads to defective CD4+ T cells
Treat with immunosuppression drugs…sometimes bone marrow/stem cell transplant
Disaccharidase (Lactase) Deficiency
Congenital lactase deficiency is a rare autosomal recessive disorder, caused by a mutation in the gene encoding lactase
Acquired lactase deficiency is common, and sometimes associated with enteric viral or bacterial infections
Lactase is in the apical brush-border membrane of the villus absorptive epithelial cells
Mutation in the MCM6 gene that keeps the LCT gene turned on Because the defect is biochemical, biopsy histology is generally unremarkable.
Incomplete breakdown of lactose leads to osmotic diarrhea from unabsorbed lactose
Abdominal fullness, diarrhea, and flatulence
Abetalipoproteinemia
Rare autosomal recessive, presents in infancy and the clinical picture is dominated by failure to thrive, diarrhea, and steatorrhea
“Mutation in the microsomal triglyceride transfer protein (MTP) in enterocytes which are unable to secrete triglyceride-rich lipoproteins.”
Malabsorption is a failure of transepithelial transport of lipids
Lipid vacuolization of small intestinal epithelial cells
Complete absence of all plasma lipoproteins containing apolipoprotein B & deficiencies of fat-soluble vitamins
Acanthocytic red cells (burr cells) in peripheral blood smears
Treatment normally consists of rigorous dieting, involving massive amounts of vitamin E. Vitamin E helps the body restore and produce lipoproteins, which people with abetalipoprotenimia usually lack. Vitamin E also helps keep skin and eyes health
Irritable Bowel Syndrome (IBS)
“Characterized by chronic, relapsing abdominal pain, bloating, and changes in bowel habits”
Normal GI evaluation
Clinical diagnosis
- abdominal pain or discomfort at least 3 days per month over 3 months
- improvement with defecation
- change in stool frequency or form
Inflammatory Bowel Disease (IBD)
Two inflammatory bowel diseases (Crohn disease and ulcerative colitis) “resulting from inappropriate and persistent activation of the mucosal immune system, probably driven by presence of normal intraluminal flora
“IBD results from unregulated and exaggerated local immune responses to commensal microbes in the gut, in genetically susceptible individuals.
Abnormal T-cell response…
”Prime Culprit CD4+ T-cells (T H17 T cells)
Diagnosis of Ulcerative Colitis and Crohn Disease
pANCA (perinuclear Anti-Neutrophilic Cytoplasmic Antibody) positive in 75% UC, only 11% CD
ASCA (Anti-Saccharomyces Cerevisiae Antibody) positive in some patients with CD, rare in UC
Crohn Disease
Sharply demarcated areas of involvement with intervening Unaffected “skip” areas
sharply delimited and typically transmural involvement with linear mucosal ulcers
Noncaseating granulomas (35%)
Presence of fissuring with formation of fistulae
Creeping fat
Pattern of bowel involvement of Crohn disease
40% small bowel only
30% small bowel and colon
30% colon only
rarely may involve duodenum, stomach, esophagus, mouth
