What is diarrhea?
Clinically: an increase in the frequency, volume, or urgency of defecation with or w/out change in consistency (normal stool frequency is defined from 3BM/week up to 3 BM/day)
Physiologically: 200+ gm stool/day
So most of what our gut deals with is what we produce, not food!
notice how most is absorbed by the small intestine
What drives fluid uptake from the GI tube?
It follows Na+ absorption via Na/glucose co-transporters and NHEs in the small intestine villi and ENaC (epithelial channels) in the large intestine crypts
What are the two main categories of causes of diarrhea?
1) increased intraluminal fluid (from decreased absorption or increased secretion)
2) Rapid GI transit
What is the main cause of decreased absorption leading to diarrhea?
it is an osmotically driven event caused by ingestion of unabsorbable solutes that lead to a subsequent lack of absorption of fluids
What is the main cause of increased secretion leading to diarrhea?
this is a secretory mechanism that causes fluid to follow and leads to an electrolyte heavy stool
Most inflammatory diarrheas involve pathology of the ______
What are some causes of Osmotic Diarrhea?
–lactose (milk, yogurt, cheese, etc.)
–sorbitol, mannitol (diet soda, gum, candy)
–lactulose (Rx for hepatic encephalopathy)
•Non-absorbable electrolytes (laxatives)
–Mg2+ compounds (MOM, Maalox, Epsom salts)
–Golytely (PEG) prep for colonoscopy
–Fleets phosphosoda prep
•Miscellaneous malabsorption syndromes
The key to all secretory diarrheas is excessive ___ secretion into the gut
Cl- (secreted throuh apical CFTR channels)
How does vibrio cholerae cause a secretory diarrhea?
It produces a toxin that activates the basolateral adenylate cyclase to increase cAMP which causes:
1) hyperactivity of the apical CFTR channel
2) inhibition of apical Na/H+ exchangers and Cl/HCO3 exchangers
How is cholera induced diarrhea tx?
The WHO’s oral rehydration formula for the treatment of cholera and other secretory diarrheas is based on exploitation of the Na/glucose co-transporter. By including glucose in a high salt drink, Na+ absorption can continue despite cAMP inhibition of Na+ absorption by NHE.
What are some other causes of secretory diarrhea that work through increased cAMP?
Heat labile and stable E. Coli enterotoxins
VIP (neurohumoral agent)
histamine and prostaglandins
What are some other causes of secretory diarrhea that work through increased Ca2+?
Ach and Serotonin
What are some other causes of secretory diarrhea?
What tumors are associated with secretory diarrhea?
medullary carcinoma of the thyroid
What are some pathologies that cause direct cell death leading to diarrhea?
Ameba, Shigella, Rotavirus
What are some pathologies that cause cell death via immune-mediated mechanisms (complement, cytokines, cytotoxic T-cells, mastcells, neutrophils, etc) leading to diarrhea?
Crohn’s disease, ulcerative colitis, Whipple’s disease, Salmonella, Campylobacter
What is acute diarrhea?
this is defined as diarrhea lasting less than 3 weeks that is almost exclusively caused by infection, causing a self-limited secretory or inflammatory diarrhea that can be treated with supportive (fluids) measures alone typically
T or F. Cholera causes damage to the intestinal mucosa
F. It will not kill us any other way then by promoting dehydration
Viruses no matter where you are, are the most common cause!
described as Falling leaves. Giardia is seasonal!
Typically presents as a dyspepsia
Most likely secretory diarrhea
How would acute, non-bloody, no dehydrating diarrhea be treated?
–likely viral or toxin mediated, self-limited
–p.o. fluids, +/- Peptobismol
How would acute, bloody (dysentery), non-dehydrating diarrhea be treated?
–likely bacterial (salmonella, shigella, campylobacter), often self limited
–obtain stool for culture, O&P
–p.o. fluids, Peptobismol
How would acute dehydrating (with or without blood) diarrhea be treated?
–obtain stool for culture, O&P
–IV fluids vs. oral WHO rehydration solution
How would acute dehydrating, bloody, 'septic' diarrhea be treated?
–obtain stool for culture and O&P
–hospitalization, IV fluids
–IV fluoroquinolone (cipro); avoid with EHEC
What are some risk factors for iatrogenic C. diff colitis?
–Extremes of age
–Hospitalization or institutionalization
What causes C. diff colitis?
C. diff is commensal so ABX allow it to flourish and produce cytoxins A and B which destroy intestinal mucosa and promote formation of pseudomembranes
How is C. diff colitis diagnosed?
–pseudomembraneous colitis on rectal endoscopy (below)
–Stool assay for Toxin A (+/- B)
How is C. diff colitis treated?
–stop the offending antibiotic (if possible)
–metronidazole or vancomycin po
–cholestyramine to bind toxins
C. diff is highly infectious!
What are some causes of chronic diarrhea with NO mucosal injury?
•Maldigestion and Malabsorption Syndromes
–Disaccharidase deficiencies, Bacterial overgrowth, Pancreatic insufficiency, Short bowel syndrome (after surgery/congenital)
–Irritable Bowel Syndrome, Hyperthyroidism, Diabetic neuropathy, Alcoholism
How does lactase deficiency present?
An osmotic diarrhea, with flatulence and acidic stool pH
bacteria should not be in the small bowel!
Unconjugate bile acids cause a secretory diarrhea when they reach the colon. Take ABX to clean out the small bowel
Basically the diagnosis would be if you had abdominal pain (have to have pain/bloating for diagnosis)/bloating with either the constipation or diarrhea and relief of those symptoms when bowel function returns to normal
There isnt anything functional with the bowels in IBS
How is IBS treated?
–anti-cholinergic medications (diarrhea)
–5-HT receptor antagonists (constipation)
What are some causes of chronic diarrhea WITH mucosal injury?
–HIV, Parasites / worms (Strongyloides, etc.), Tropical sprue and Whipple’s disease
•Allergic / Immune-mediated
–Food allergy (milk, soy, etc.), Celiac sprue,Inflammatory Bowel Disease (Crohn’s and Ulcerative Colitis), Eosinophilic gastroenteritis
–Microscopic (lymphocytic and collagenous) colitis
UC is only in the colon with CD can be in the colon or the small bowel or both
What is microscopic colitis?
•Two Types (Lymphocytic and Collagenous colitis) marked by a chronic watery, non-bloody diarrhea in adults
How is microscopic colitis tx?
Notice the nocturnal diarrhea!