Pathology of Diarrhea

Question 1

What is diarrhea?

Answer 1

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

Question 2

So most of what our gut deals with is what we produce, not food!

Answer 2

notice how most is absorbed by the small intestine

Question 3

What drives fluid uptake from the GI tube?

Answer 3

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

Question 4

What are the two main categories of causes of diarrhea?

Answer 4

1) increased intraluminal fluid (from decreased absorption or increased secretion)
2) Rapid GI transit

Question 5

What is the main cause of decreased absorption leading to diarrhea?

Answer 5

it is an osmotically driven event caused by ingestion of unabsorbable solutes that lead to a subsequent lack of absorption of fluids

Question 6

What is the main cause of increased secretion leading to diarrhea?

Answer 6

this is a secretory mechanism that causes fluid to follow and leads to an electrolyte heavy stool

Question 7

Question 8

Most inflammatory diarrheas involve pathology of the ______

Answer 8

colon

Question 9

What are some causes of Osmotic Diarrhea?

Answer 9

•Non-absorbable carbohydrates

–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

Question 10

The key to all secretory diarrheas is excessive ___ secretion into the gut

Answer 10

Cl- (secreted throuh apical CFTR channels)

Question 11

How does vibrio cholerae cause a secretory diarrhea?

Answer 11

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

Question 12

How is cholera induced diarrhea tx?

Answer 12

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.

Question 13

What are some other causes of secretory diarrhea that work through increased cAMP?

Answer 13

Heat labile and stable E. Coli enterotoxins

VIP (neurohumoral agent)

histamine and prostaglandins

Question 14

What are some other causes of secretory diarrhea that work through increased Ca2+?

Answer 14

Yersinia toxin

Ach and Serotonin

Question 15

What are some other causes of secretory diarrhea?

Question 16

What tumors are associated with secretory diarrhea?

Answer 16

VIPoma

carcinoid

medullary carcinoma of the thyroid

Question 17

Answer 17

Question 18

Question 19

What are some pathologies that cause direct cell death leading to diarrhea?

Answer 19

Ameba, Shigella, Rotavirus

Giardia, Cryptosporidium

Question 20

What are some pathologies that cause cell death via immune-mediated mechanisms (complement, cytokines, cytotoxic T-cells, mastcells, neutrophils, etc) leading to diarrhea?

Answer 20

Crohn’s disease, ulcerative colitis, Whipple’s disease, Salmonella, Campylobacter

Question 21

What is acute diarrhea?

Answer 21

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

Question 22

T or F. Cholera causes damage to the intestinal mucosa

Answer 22

F. It will not kill us any other way then by promoting dehydration

Question 23

Viruses no matter where you are, are the most common cause!

Question 24

described as Falling leaves. Giardia is seasonal!

Typically presents as a dyspepsia

Answer 24

Question 25

Question 26

Question 27

Most likely secretory diarrhea

Answer 27

Question 28

How would acute, non-bloody, no dehydrating diarrhea be treated?

Answer 28

–**likely viral or toxin mediated**, self-limited –p.o. fluids, +/- Peptobismol

Question 29

How would acute, bloody (dysentery), non-dehydrating diarrhea be treated?

Answer 29

–likely bacterial (salmonella, shigella, campylobacter), often self limited –obtain stool for culture, O&P –p.o. fluids, Peptobismol

Question 30

How would acute dehydrating (with or without blood) diarrhea be treated?

Answer 30

-likely cholera ## Footnote –obtain stool for culture, O&P –IV fluids vs. oral WHO rehydration solution –anti-diarrheal agent

Question 31

How would acute dehydrating, bloody, 'septic' diarrhea be treated?

Answer 31

–obtain stool for culture and O&P –hospitalization, IV fluids –IV fluoroquinolone (cipro); avoid with EHEC

Question 32

What are some risk factors for iatrogenic C. diff colitis?

Answer 32

–Antibiotic usage –Extremes of age –Hospitalization or institutionalization

Question 33

What causes C. diff colitis?

Answer 33

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

Question 34

How is C. diff colitis diagnosed?

Answer 34

–pseudomembraneous colitis on rectal endoscopy (below) –Stool assay for Toxin A (+/- B)

Question 35

How is C. diff colitis treated?

Answer 35

–stop the offending antibiotic (if possible) –metronidazole or vancomycin po –cholestyramine to bind toxins

Question 36

C. diff is highly infectious!

Question 37

Question 38

What are some causes of chronic diarrhea with NO mucosal injury?

Answer 38

•Maldigestion and Malabsorption Syndromes –Disaccharidase deficiencies, Bacterial overgrowth, Pancreatic insufficiency, Short bowel syndrome (after surgery/congenital) •Hypermotility –Irritable Bowel Syndrome, Hyperthyroidism, Diabetic neuropathy, Alcoholism •Neuroendocrine Malignancies –VIPoma, carcinoid •Factitious –Laxative abuse

Question 39

How does lactase deficiency present?

Answer 39

An osmotic diarrhea, with flatulence and acidic stool pH

Question 40

bacteria should not be in the small bowel!

Answer 40

Unconjugate bile acids cause a secretory diarrhea when they reach the colon. Take ABX to clean out the small bowel

Question 41

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

Question 42

How is IBS treated?

Answer 42

–anti-cholinergic medications (diarrhea) –5-HT receptor antagonists (constipation) –reassurance

Question 43

What are some causes of chronic diarrhea WITH mucosal injury?

Answer 43

•Chronic Infections –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 •Malignancies –Colon cancer –Lymphoma

Question 44

Question 45

UC is only in the colon with CD can be in the colon or the small bowel or both

Question 46

What is microscopic colitis?

Answer 46

•Two Types (Lymphocytic and Collagenous colitis) marked by a chronic watery, non-bloody diarrhea in adults

Question 47

How is microscopic colitis tx?

Answer 47

–Bismuth –Aminosalisylates –steroids

Question 48

Answer 48

Question 49

Notice the nocturnal diarrhea!

Answer 49

Question 50

Answer 50