Diarrhea Flashcards
How is diarrhea defined from a patient’s standpoint?
physicians standpoint?
patient: change in stool # and consistency
physician: quantitative determination of an increase in stool weight greater than 200 grams per 24 hours
9L fluid enter the bowel lumen per day. How do you not get massive diarrhea?
90% H2O is reabsorbed in small intestines, and 90% of the remaining H2O is absorbed by the colon
What’s the difference between H2O transport and electrolyte transport?
H2O transport
• passive transport – no molecular water pumps, rather H2O moves paracellularly or across the membrane down its conc. gradient into the compartment with the higher solute/electrolyte concentration
electrolyte transport
• active transport – creates a gradient to drive the movement of H2O via Na/K ATPase
• passive transport - occurs via paracellular mechanisms or through pores or carrier proteins
Villi proteins and Crypt proteins have different functions (though it should be noted that there is some overlap).
What are the key proteins of each and how do they work?
Villi proteins = absorption
• Na/K ATPase pumps - present on basolateral side - drives Na out of cell and into subepithelial space
• SLGT1 - present on the apical side - takes advantage of the gradient established by the Na/K ATPase pump presence of glucose in the intestinal lumen enhances Na absorption
Crypt proteins = secretion
• Na/K/2Cl - present on the basolateral membrane
• CFTR - present on the apical membrane – ATP-dependent activation allows egress of Cl that drives the water of movement from the subepithelial space -> lumen
What is the basis behind ORT?
the presence of glucose in the intestinal lumen actually enhances Na absorption via SGLT1
What transporter is affected by digoxin (oaubain/digitalis)?
What is it used for?
What happens in the intestines if you OD on digoxin?
inhibits Na/K ATPase (key transporter for absorption!)
digoxin is used for CHF
digoxin toxicity -> diarrhea
What happens in CF patients in terms of gut physiology?
CFTR is normally present on the apical membrane and its ATP-dependent activation allows egress of Cl that drives the water of movement from the subepithelial space -> lumen (think of it as modulating fecal hardness by adding water back into the stool)
Patients with CFTR mutations -> massive constipation!!
What is fluid transport regulated by?
cAMP
- prolongs opening of CFTR -> decreased absorption of Na
- increases # of Na-K-2Cl transporters on the basolateral side -> increased secetion of Cl
• inhibits Na/H transporter -> decreased Na reabsorption
The villi and crypt has different functions. What are they?
What are the 4 broad mechanisms of diarrhea?
Osmotic
Secretory
Inflammatory
Dysmotility
What is osmotic diarrhea?
What are the examples of things that cause an osmotic diarrhea?
What are some clinical/laboratory hallmarks?
Poorly absorbed solute in the gut lumen that causes H2O retention and eventually causes stool loss
- *Examples**
- Sorbitol
- Lactulose ingestion
- Milk of Magnesia (Mg2+)
- Maalox
- acquired/hereditary defects (ie lactase deficiency)
- malabsorption of fat (steatorrhea), intestinal failure/Celiac’s (sprue), pancreatic exocrine insufficiency
Labs:
- INCREASED osmotic gap
- decreased stool electrolyte concentrations bc of unabsorbed solutes in stool replace the normal cations (Na+ and K+) in the lumen
What is the osmotic gap (of stool)?
What is a normal value?
What does abnormal values mean?
osmotic gap = 2*(Nastool+ Kstool) - normal stool
normal osmolality ~290mOsm/kg H2O
- Osomatic gap >100 = osmotic diarrhea
- Osmotic gap < 50 = secretory diarrhea
What is secretory diarrhea?
What are the examples of things that cause a secretory diarrhea?
What are some clinical/laboratory hallmarks?
- NORMAL mechanism of secretion gets commandeered by an endogenous hormone or exogenous toxin, resulting in cumulative secretion of water and electrolytes >> absorptive capacity in small intestine and colon
Examples:
- enterotoxins by Vibrio cholera
- endocrine tumors (VIPoma, gastrinoma, carcinoid tumors secreting 5HIAA)
- bile acid induced diarrhea (normally reabsorbed in the terminal ileum)
- laxatives (senna, phenolphthalein, bisacodyl)
- lubiprostone - activates Cl channels on the apical membrane of the intestinal epithelial cell; FDA approved for treatment of chronic constipation
- Microscopic colitis
labs/Treatment:
- fasting has no effect
- no change in stool osmotic gap
What type of diarrhea does vibrio cholera cause?
How does it do this?
How do you treat it?
secretory
affects cAMP (adenylate cyclase)
ORT – provides Na/glucose to counterbalance the ongoing secretion that results from the bad transporters since that transporter is still functional!!
What is inflammatory diarrhea?
What are the examples of things that cause an inflammatory diarrhea?
What are some clinical/laboratory hallmarks?
mucosal ulceration and inflammation leads to exudation of blood, lymph and mucus into the bowel lumen -> destruction of the epithelial cells that control absorption and secretion
- inflammatory bowel disease, Crohns
- bacterial agents secreting cytotoxins, ie EHEC (O157:H7), and Clostridia difficile
- Invasive organisms: Shigella, Campylobacter, Salmonella, Yersinia
Clinical/Laboratory Hallmarks
- Bloody mucoid stool
- fever
- increase in fecal leukocytes
- osmotic gap – more towards normal; but not really measured because it’ll be obvious what the diagnosis is, whereas its more relevant to measure in osmotic diarrhea
What is dysmotility diarrhea?
What are the examples of things that cause an dysmotility diarrhea?
What are some clinical/laboratory hallmarks?
- abnormal intestinal transit time leads to diarrhea
Causes
- Surgeries: pyloroplasty, vagotomy, gastrectomy and antrectomy) -> “dumping syndrome”
- anything that decrease intestinal transit with subsequent increase bacterial growth
- Diseases associated with disordered motility (e.g. scleroderma or diabetes)
Clinical:
- PMH + Past surgical hx
What is the dumping syndrome?
How is it managed?
rapid entry of hypertonic chyme into duodenum - causes an osmotic stimulus and rapid distension of small bowel
• release vasoactive substances that can contribute to secretory diarrhea
• stimulation of intestinal motility and decreases transit time
mgmt: smaller, frequent meals; separate liquids and solids
How does dysmotility affect bile acid stores in the body?
decreased intestinal transit causes subsequent increased bacterial growth -> deconjugates bile acids & prevents proper bile acid reabsorption and function -> leads to steatorrhea
(remember colonic bacteria converts bile acids to something else so that it can further be reabsorbed in the colon)
What is the likely etiology of someone with acute diarrhea?
chronic diarrhea?
acute <3 weeks
- think infectious etiology, mostly viral (norovirus = adults, rotavirus = children)
chronic >3 weeks
- think IBS, incontinence, drugs (digoxin, antacids/Mg, sweetners), habits (caffeine, OH, gum chewing/sorbitol)
rapid association
someone who comes with with acute diarrhea with recent travel to mexico/south america is likely to be infected with this bug:
ETEC
rapid association
someone who comes with with acute diarrhea with recent travel to Asia is likely to be infected with these bugs:
Salmonella
Shigella
Campylobacter
rapid association
someone who comes with with acute diarrhea with recent camping trip is likely to be infected with this bug:
Giardia
rapid association
someone who comes with with acute diarrhea with in the hospital is likely to be infected with these bugs:
C. diff
(strongly with antibiotic use - clindamycin, penicillin, cephalosporin)
Why is anti-diarrheal agents not highly recommended for treatment of acute diarrhea?
can worsen if inflammatory in nature because if you’re slowing transit time, you’re increasing contact time with the bacteria/viral with the intestinal mucosa, which can be bad!
What are two chronic diseases that cause diarrhea?
What are they caused by?
How are the diagnoses established for both?
- *Celiac** (top)
- disease of small bowel as a result of gluten sensitivity
- serum tissue transglutaminase, small bowel bx
- *Microscopic colitis “collagenous colitis”** (bottom)
- abnormal collagen metabolism (either native or caused by something else) that results in thick collagen bands; causes chronic watery (secretory) diarrhea without bleeding
- Biopsy - colon appears normal by colonoscopy or barium enema, but Bx reveals colitis w/o mucosal ulcerations
