Malabsoprtion And Infectious Enterocolitis Flashcards
Definition of diarrhea and dysentery
Diarrhea = increase in stool mass/frequency/fluidity typically over 200g of feces a day
- **accounts for >700,000 deaths of children <5yrs of age (2nd leading cause of death in this age group)
Dysentery = painful bloody small-volume diarrhea
What are the 4 major categories of diarrhea?
1) malabsorptive diarrhea
- inadequate nutrient absorption associated with steatorrhea
- relieved by fasting
2) osmotic diarrhea
- due to osmotic forces exerted by unabsorbed luminal solutes
- *example = lactase deficiency
3) secretory diarrhea
- due to isotonic stools
- NOT relieved by fasting
4) exudative diarrhea
- inflammatory disease with Purulent bloody stools
- NOT relieved by fasting
Malabsorption diarrhea
“Chronic diarrhea”
Defective absorption of fats, fat and water soluble vitamins, proteins, carbs, electrolytes, minerals and water
Symptoms:
- weight loss
- anorexia
- abdominal distention and pain
- muscle wasting
- borborygmi (rumbling noises in intestines)
***hall mark = steatorrhea
Most commonly associated with
- pancreatic insufficiency
- celiac disease
- Crohn’s disease
What are the 4 phases of nutrient absorption that could cause malabsorptive diarrhea
1) intraluminal digestion
- proteins/carbs/fats are broken down into absorbed forms
2) terminal digestion
- hydrolysis of carbs/peptides/disaccharides and peptidases (brush border)
3) transepithelial transport
- transportation of nutrients/fluid/electrolytes across small-intestinal epithelium
4) lymphatic transport of lipids
**note: only one of these needs to be affected to produce malabsorption
Cystic fibrosis review
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)
- interferes with bicarbonate/sodium and water secretion which results in luminal dehydration
pancreas ducts are plugged by thick mucus which leads to chronic auto digestion of the pancreas (>80% sees pancreatic insufficiency)
Celiac disease
“Celiac sprue/ gluten sensitive enteropathy”
Immune-mediated enteropathy which is triggered by the presence of gluten In sensative patients
- prevalence = 0.5-1%
- more common in white people
Needs histological and serologic finds for specific diagnosis of celiac disease
What is the pathogenesis of celiac disease
1) gluten is digested by luminal brush border -> AA’s and peptides
- *this includes gliadin peptide (doesnt get degraded any further)
2) in susceptible individuals, gliadin is delaminates by tissue transglutaminase and then binds to HLA-DQ2/8 antigens on APCs that are presented to CD4-Tcells
3) autoreactive T-cells in lamina propria then produce cytokines that contribute to inflammation and leads to antibody production against tissue transglutaminase and gliadin
4) although not confirmed, is believed that deamidated gliadin peptides induce epithelial cells to produce IL-15 and proliferation of autoreactive CD8+ cells
What is the morphology of celiac disease?
usually best seen in the transverse duodenum or proximal duodenum
Shows:
- high levels of T-lymphocytes
- intraepithelial lymphocytosis
- crypt hyperplasia
- villous atrophy
Clinical features of pediatric celiac disease
Usually between 6-24 months of age
Classic symptoms:
- irritability
- abdominal distention
- anorexia
- diarrhea
- failure to thrive
- weight loss/muscle wasting
Nonclassic symptoms: (usually only seen in 10 yrs+)
- abdominal pain
- nausea/vomiting
- bloating
- constipation
Clincial features of adult celiac disease
Usually seen between ages 30-60 years of age
Symptoms:
- anemia (iron or Vit. B12/B6 deficiencies)
- diarrhea
- bloating
- fatigue
- dermatitis herpetiformis (looks like herpes on extremities) (only seen in 10% thou)
What are serologic tests of celiac disease
Most sensitive = presence of IgA antibodies to tissue transglutaminase
2nd most sensative = IgA/IgG antibodies to deamidated gliadin
What are the cancers associated to celiac disease
Most common = Enteropathy-associated T-cell lymphoma
2nd most common = small-intestine adenocarcinoma
- **often times will present with uncommon symptoms of celiac disease despite gluten free diet
Environmental enteropathy
Syndrome of - stunted growth - impaired intestinal function - repeated bouts of diarrhea within 2-3 years of life Most common in developing countries
is believed to be caused by malnutrition, however refeeding and/or vitamin supplements DONT fix this disorder
Lactase deficiency
“Lactose intolerance”
Gives rise to osmotic diarrhea in the presence of lactose in the intestinal lumen
- biopsies usually cant be used to determine deficiency
There are 2 types:
1) congenital = autosomal recessive disorder with mutations in the lactase gene.
- shows explosive diarrhea with watery stools and ab distention
2) acquired = down regulation of lactase gene usually after enteric viral or bacterial infections
- most common in natives, blacks and Chinese populations
Abetalipoproteinemia
Autosomal recessive disease which results in an inability to secrete triglyceride rich lipoproteins
- mutations in the MTTP protien causes enterocytes to be unable to export lipoproteins and free FAs through walls
Symptoms manifest in infancy:
- failure to thrive
- diarrhea
- steatorrhea
- **acanthocytic red blood cells “spur cells” are seen in blood smears
Microscopic colitis
Idiopathic diseases that manifest with chronic non bloody watery diarrhea without weight loss
Two subtypes:
1) collagenous colitis: (seen primarily in middle aged women)
- presence of dense subepithelial collagen layer.
- increased number of lymphocytes
- mixed inflammatory infiltrates in lamina propria
2) lymphocytic colitis: (no preference)
- increases intraepithelial T-lymphocytes
- associated with celiac disease/autoimmune disease
Infectious enterocolitis
responsible for 1 million deaths per year
Enterocolitis caused by numerous bacterial infections
Symptoms: (varies hard based on pathogen)
- diarrhea
- abdominal pain
- urgency
- perianal discomfort
- incontinence
- hemorrhages
Vibrio cholerae
Comma-shaped, gram (-) primarily transmitted by contaminated drinking water especially warm water.
Pathogenesis:
- noninvasive disease that uses cholera toxin to interact with ADP ribosylation factors to ribosylate and activates Gsq = overstimulates adenylate Cyclase and over production of cholride ions into the lumen = diarrhea
Mortality rate for severe = 50-70% with hydration therapy
Campylobacter jejuni
Gram (-), S-shaped bacteria pathogen
- Causes travelers diarrhea and is associated with poor cooking techniques, and contaminated water, milk
Pathogenesis:
- *is associated with reactive arthritis (HLA-B27 susceptible patients only)
- is poorly understood but dose induce net fluid loss and inflammation
Symptoms
- watery diarrhea
- flu-like symptoms
- **15-50% of patients can develop dysentery
Tx = self limiting. Rehydration therapy for all and antibiotic therapy for dysentery or immunocompromised patients
Shigella
Gram (-) bacilli that are non motile, non capsules.
- one of the most common causes of bloody diarrhea and seen in poor sanitized water and food
usually seen in children under 5 yrs since it is only really spread fecal-oral transmission weather directly or indirectly via water
Symptoms: (needs 1-7 day incubation)
- fever
- watery diarrhea (all)
- bloody diarrhea (50-60%)
- ab pain
Tx: self limiting, can use antibiotics if needed
- DONT use anti-diarrhea meds since they can prolong symptoms due to in ability to clear bacteria
Complications of shigellosis
Reactive arthritis
HUS
Salmonella
Gram (-) bacilli
- non typhi = enterocolitis/gastroenteritis
- typhi = enteric/typhoid fever
Infections are most common in young children and elderly
- highest in summer and fall
- transmission = contaminated foos, raw/undercooked meat and poultry/eggs/milk
Typhoid fever
Only seen in salmonella typhi/paratyphi pathogens
Infects 30 million/yr worldwide
Initial phase Symptoms:
- anorexia
- abdominal pain
- bloating
- N/V
- bloody diarrhea
- “rose spots”
- splenomegaly
Chronic phase symptoms:
- all above
- bacteremia
- flulike symtpoms
- typhoidal fever (slowly increasing fever for 2 weeks that gets super high (>104))
Diagnosis = blood cultures
Pseudomembranous colitis
“Anti-biotic associated colitis”
Caused by D. Diff infections that often precedes widespread antibiotic use (since it kills good bacteria and lets C. Diff run unchecked)
Toxins released by C. Diff causes ribosylation of small GTPases (Rho) and leads to:
- disruption of epithelial cytoskeleton
- tight junction barrier loss
- cytokine release
- apoptosis
Other factors that increase risk of C. Diff:
- elderly
- hospitalizations
- immunosupression
Symptoms:
- abdominal cramping
- watery diarrhea
- fever
- leukocytosis
- shows fecal leukocytes
Tx= metronidazole or vancomycin antibiotic use
