Chronic Diarrhea and Malabsorption: Chronic Diarrhea and Malabsorption: First Workup

0:00Welcome to Board Pearls. This is episode one of two of the Chronic Diarrhea and Malabsorption chapter, in the Stomach and Small Bowel Disorders module. This episode is the first evaluation of chronic diarrhea, then secretory diarrhea. A woman with three months of watery stools shows why small problems cause big diarrhea, which parts of the history matter most, why the medication list is the most productive part of the visit, which first labs and stool tests to send, and how the stool osmotic gap places diarrhea into one of four types. A man with large-volume watery diarrhea and low potassium shows how to prove diarrhea is secretory, which common causes come first, when to send a neuroendocrine panel, and how a hormone-secreting tumor is treated. And a young woman with a normal workup shows the self-inflicted cause.

0:49Here's the first patient. A sixty-four-year-old woman has had loose, watery stools four to six times a day for three months. There's no blood. She doesn't wake at night to go, and she hasn't lost weight. She has diabetes and osteoporosis. When asked about medications, she lists metformin, alendronate, and a statin.

1:08She has chronic diarrhea, and the evaluation aims to place it into one of four mechanisms, osmotic, secretory, inflammatory, or fatty, because each has its own tests. One fact explains why so many causes exist: small problems cause big diarrhea. The gut handles nine or ten liters of fluid a day. The small bowel absorbs seven or eight of them, and the colon absorbs nearly all of the remaining one to one and a half liters, leaving a hundred to two hundred grams of stool water. Absorption runs about ninety-nine percent efficient, and a drop to ninety-eight percent shows up as diarrhea, so almost any small insult can cause it.

1:47Her duration already changes the likely causes. Chronic means loose stools for more than four weeks. Acute diarrhea is mostly infection that resolves on its own within a couple of weeks. Chronic diarrhea is mostly structural, inflammatory, malabsorptive, or endocrine, and it needs a workup rather than reassurance. She's at three months.

2:08The history comes first, because it finds the diagnosis in most patients. Continuous diarrhea suggests organic disease, while intermittent diarrhea overlaps with irritable bowel. Nocturnal stools and weight loss point away from irritable bowel, which follows the day-night cycle and rarely causes weight loss. Abrupt onset suggests infection or a post-infectious syndrome, and gradual onset over months suggests inflammatory or neoplastic disease. Diarrhea since infancy points to rare congenital disorders such as chloridorrhea, congenital lactase deficiency, and microvillus inclusion disease. She has continuous diarrhea without nocturnal stools or weight loss, which is reassuring but not a diagnosis.

2:50The medication list is the most productive part of the history, and how it's asked decides what's heard. Over-the-counter products and supplements matter as much as prescriptions, so she's asked specifically about antacids, supplements, vitamins, laxatives, herbal products, and sugar-free foods. When asked, she adds a magnesium supplement she started for leg cramps four months ago and sugar-free candies she eats through the day.

3:13The over-the-counter culprits are a short list. They're magnesium antacids and supplements, sorbitol in sugar-free gum and candies, sugar-free elixirs, herbal products, and laxatives.

3:25The prescription culprits are longer. They're metformin; antibiotics, especially cephalosporins; proton pump inhibitors, PPIs; H2 blockers; selective serotonin reuptake inhibitors, SSRIs; nonsteroidal anti-inflammatory drugs, NSAIDs; five-aminosalicylic acid, five-ASA, drugs; beta-blockers; angiotensin-converting enzyme, ACE, inhibitors and angiotensin receptor blockers; statins; colchicine; and chemotherapy. Olmesartan is the angiotensin receptor blocker that can cause a sprue-like enteropathy with villous atrophy that mimics celiac disease. She now has three candidates: magnesium, sorbitol, and metformin.

4:11The surgical history comes next, because each operation has its own diarrhea. Cholecystectomy raises bile acid diarrhea. Ileal resection raises bile acid or fatty diarrhea, depending on how much was removed. Vagotomy, gastrectomy, and gastric bypass raise dumping and bile acid diarrhea. Sleeve gastrectomy speeds transit. Pancreatic resection causes pancreatic insufficiency. She's had no surgery.

4:40The exam adds volume status and a few specific clues. Orthostasis and a fast heart rate mean volume depletion, and muscle wasting or edema means protein-energy malnutrition. Urticaria pigmentosa or dermatographism suggests mastocytosis. Pinch purpura and an enlarged tongue suggest amyloidosis. Skin darkening suggests Addison disease. A migrating rash in skin folds suggests glucagonoma. Flushing with a right-sided heart murmur and wheeze suggests carcinoid syndrome.

5:12A few more exam findings point to small bowel and endocrine disease. Dermatitis herpetiformis points to celiac disease. Oculomasticatory myorhythmia, rhythmic movements of the eyes and jaw, points to Whipple disease. A thyroid nodule with lymph nodes suggests medullary thyroid cancer. An abdominal bruit suggests mesenteric ischemia.

5:32A rectal exam is always done, because the complaint may not be diarrhea at all. Fecal incontinence is often reported as diarrhea, and it's treated with pelvic floor work and biofeedback, not more stool tests. Her exam, including the rectal exam, is normal.

5:50Her first labs are chosen to catch the common systemic causes cheaply. They're a blood count, metabolic panel, C-reactive protein, CRP, thyroid-stimulating hormone, TSH, and tissue transglutaminase immunoglobulin A, IgA, with total IgA. Iron deficiency suggests celiac disease, inflammatory bowel disease, IBD, or cancer. A macrocytic anemia suggests B12 or folate loss from ileal disease, tropical sprue, or bacterial overgrowth. Leukocytosis or eosinophilia points to specific causes.

6:27The chemistry panel reads the severity. Low potassium, metabolic acidosis, or kidney injury suggest high-volume secretory diarrhea. Low albumin suggests protein-losing enteropathy. The TSH catches hyperthyroidism, which speeds motility. And the celiac antibody goes with a total IgA, because selective IgA deficiency invalidates IgA-based serology in about one in twenty-eight celiac patients.

6:56Stool studies are the second layer, and each answers one question. Fecal calprotectin separates inflammatory from non-inflammatory diarrhea. Under fifty micrograms per gram essentially excludes IBD, fifty to two hundred fifty is indeterminate and may need a repeat, and over about two hundred fifty, or one hundred fifty in some labs, supports inflammation and calls for colonoscopy. Lactoferrin and fecal leukocytes give similar information less precisely.

7:23Fecal elastase tests the pancreas. Under two hundred suggests insufficiency and under one hundred is severe, but it's falsely low in watery stool, so a formed sample is sent when possible.

7:36Infection is tested more broadly than in acute diarrhea. A multiplex polymerase chain reaction, PCR, panel covers the common bacteria, viruses, and protozoa, with culture and ova and parasites for completeness, and Giardia and Cryptosporidium antigens if PCR isn't available. C. difficile toxin testing is included, because chronic diarrhea after antibiotics or in a hospitalized patient is C. difficile until proven otherwise.

8:05The last stool tests look for fat and measure electrolytes. A Sudan stain screens for fat, and a seventy-two-hour fecal fat on a one-hundred-gram fat diet is the reference test. Stool sodium and potassium give the osmotic gap.

8:20Imaging and endoscopy come third, driven by the pattern the first two layers show. Computed tomography, CT, or magnetic resonance, MR, enterography looks for structural small bowel disease: Crohn disease, mesenteric ischemia, lymphoma, a neuroendocrine tumor, or pancreatic disease. Colonoscopy with the ileum and segmental biopsies, including random biopsies of normal-looking mucosa, is for bloody diarrhea, a high calprotectin, red flags, or the secretory workup. Endoscopy with at least four duodenal biopsies plus one or two from the bulb is for steatorrhea or suspected mucosal disease. Capsule endoscopy is kept for the unexplained case.

9:05Her stool electrolytes give the osmotic gap, which separates osmotic from secretory diarrhea. Stool osmolality is assumed to equal serum, about two hundred ninety, because water moves freely across the bowel wall. The sum of stool sodium and potassium is doubled, to account for their anions, and subtracted from it, and what's left is the part of stool osmolality not explained by electrolytes.

9:27The gap is read in three bands. A gap under fifty means the stool water is held by electrolytes, so the diarrhea is secretory. A gap over one hundred means something unmeasured is holding water, a sugar, magnesium, or polyethylene glycol, so the diarrhea is osmotic. Between fifty and one hundred is mixed. A measured stool osmolality far below two hundred ninety means the sample was diluted with water or urine, and far above means it sat at room temperature and fermented, and either way the gap can't be trusted.

10:00Her stool sodium is thirty and potassium forty. Two times seventy is one hundred forty, and two hundred ninety minus one hundred forty gives a gap of one hundred fifty, which is osmotic diarrhea. With a sodium of seventy and potassium of sixty, the gap would be thirty, secretory, and stopping her candies wouldn't help. Her calprotectin, celiac serology, TSH, and infection panel are all normal.

10:27Her osmotic result narrows the causes to a short list. Osmotic diarrhea comes from poorly absorbed solutes that hold water in the lumen. The gap is high, and the diarrhea stops when the patient fasts, because the solute has to be eaten. The causes are lactose in lactase deficiency, excess fructose, sorbitol and mannitol, magnesium, phosphate, sulfate, polyethylene glycol, undigested starch in pancreatic insufficiency, and acarbose, which blocks carbohydrate digestion. A stool pH under six suggests fermenting carbohydrate, because colonic bacteria turn it into acids. Most cases are solved by the diet and medication history.

11:07The other three types send the workup elsewhere. Secretory diarrhea comes from failure to absorb, or active secretion of, electrolytes and water. The gap is low, volume is often over a liter a day, it continues during a fast, and it often wakes the patient. Inflammatory diarrhea comes with blood, fever, pain, and a high calprotectin, and its workup is colonoscopy with ileal intubation and biopsies. Microscopic colitis is inflammatory under the microscope but causes watery, not bloody, diarrhea.

11:38Fatty diarrhea is greasy, foul stools with weight loss and fat-soluble vitamin loss, split into pancreatic maldigestion and mucosal malabsorption. A patient can have more than one type at once. Ileal resection can cause bile acid or fatty diarrhea, and microscopic colitis can have osmotic and secretory parts.

11:58Two ingested solutes explain her osmotic diarrhea, the magnesium supplement and the sorbitol candies. She stops both, and the diarrhea resolves within a week. If it hadn't, metformin would have been next.

12:12One warning applies to every patient labeled irritable bowel with diarrhea. Seventy to ninety-five percent of them have a specific, treatable condition. Food intolerance and bile acid malabsorption are the most common, followed by bacterial overgrowth or dysbiosis, microscopic colitis, and celiac disease. So the label isn't accepted until the basic workup is done and those causes have been considered.

12:36The second patient's diarrhea is a different kind, and it's dangerous. A fifty-two-year-old man has had watery diarrhea for four months, now about four liters a day, with no blood. He wakes three times a night to go. He's weak, with leg cramps, and he's lost twenty pounds. His potassium is two point six, and he has a non-anion-gap metabolic acidosis and a rising creatinine. His face and chest flush red at times. He's been admitted twice for dehydration. His celiac serology, TSH, calprotectin, and infection panel are normal.

13:10Large-volume, nocturnal, watery diarrhea with low potassium and acidosis suggests secretory diarrhea, and the first step is to prove it. His stool sodium is ninety and potassium fifty. Twice their sum is two hundred eighty, so the gap is ten, which is secretory.

13:26A supervised fast confirms it at the bedside. If the volume stays high without food for twenty-four to forty-eight hours, the drive isn't something he eats. It's a toxin, a hormone, bile acids, an inflamed colon, or something idiopathic. If the fast stops the diarrhea, an osmotic cause was missed. His diarrhea continues at three liters a day during the fast, and his nighttime stools pointed the same way.

13:52The mechanism explains his labs. Secretory diarrhea happens when second messengers inside the enterocyte, cyclic adenosine monophosphate, AMP, cyclic guanosine monophosphate, GMP, or intracellular calcium, are switched on. They open the cystic fibrosis transmembrane conductance regulator, CFTR, chloride channel, pushing chloride and bicarbonate into the lumen, and they block sodium absorption, and water follows the salt.

14:19The shared pathway is why very different causes look alike. Cholera toxin and the enterotoxins of E. coli and C. difficile use the same pathway, so a toxin, a tumor hormone, or bile acids can all produce identical stool. His bicarbonate loss explains his acidosis, and his potassium loss explains his cramps and weakness.

14:40The causes are worked through from common to rare, because the common ones are found far more often. Microscopic colitis comes first, as the leading cause of chronic watery diarrhea in older adults. It needs colonoscopy with biopsies from both the right and left colon even when the mucosa looks normal, because the changes are denser on the right. Bile acid diarrhea comes second, especially after cholecystectomy, ileal resection, or ileal Crohn disease, and a cholestyramine trial of four grams once to four times a day is both test and treatment.

15:13Drugs and chronic infection come third and fourth. His colonoscopy with right and left colon biopsies is normal, a cholestyramine trial does nothing, his medication list is clean, and repeated infection studies are negative.

15:26Only now is a neuroendocrine panel sent, and only because his picture fits. These tumors are rare. The panel is sent with very high volume, persistence with fasting, severe electrolyte loss, or a syndromic clue such as flushing, ulcers, a thyroid nodule, or a rash. It includes chromogranin A, vasoactive intestinal peptide, gastrin off PPIs for at least a week, calcitonin, somatostatin, glucagon, and a twenty-four-hour urine five-hydroxyindoleacetic acid, five-HIAA.

16:01Two details of the panel and imaging decide whether it's believed. Chromogranin A is a broad marker for neuroendocrine tumors, but PPIs raise it and produce false positives. Pancreatic tumors are imaged with multiphase contrast CT or MR, and gallium sixty-eight DOTATATE positron emission tomography with CT, PET-CT, is the most sensitive somatostatin receptor scan. Endoscopic ultrasound finds small tumors inside the pancreas, such as gastrinomas and insulinomas.

16:34His vasoactive intestinal peptide is one thousand four hundred picograms per milliliter. CT shows a six-centimeter mass in the tail of the pancreas, with several liver lesions.

16:46His tumor is a VIPoma, a tumor secreting vasoactive intestinal peptide, also called pancreatic cholera or Verner-Morrison syndrome. It's summarized as WDHA: watery diarrhea, hypokalemia, and achlorhydria. Vasoactive intestinal peptide, VIP, binds its receptor on enterocytes, raises cyclic AMP, drives chloride and bicarbonate secretion, and blocks sodium absorption. That produces diarrhea often over three liters a day and the potassium loss. It also suppresses gastric acid, causing achlorhydria, and dilates blood vessels, causing flushing of the head and trunk.

17:25His tumor's size and spread are typical. About ninety percent of VIPomas are in the pancreas, mostly the body or tail. They're usually over five centimeters at presentation, and about sixty percent have liver metastases at diagnosis. The diagnosis is a fasting VIP over two hundred picograms per milliliter with large-volume secretory diarrhea, often far higher, plus cross-sectional imaging and somatostatin receptor imaging, such as DOTATATE PET-CT.

17:52His treatment follows from his metastases. His dehydration and potassium are corrected first. A localized tumor is resected. In metastatic disease like his, a somatostatin analog, octreotide or lanreotide, controls the symptoms, and advanced disease gets chemotherapy or lutetium one seventy-seven DOTATATE radionuclide therapy. He starts octreotide, his stool output falls within days, his potassium and kidney function recover, and he's referred to oncology.

18:22Had his clues been different, other tumors would have led. Carcinoid syndrome occurs almost only when a midgut neuroendocrine tumor, from the jejunum, ileum, appendix, or ascending colon, has spread to the liver. Liver metastases release serotonin, histamine, prostaglandins, and tachykinins directly into the circulation, bypassing first-pass clearance. Foregut tumors can produce an atypical picture from histamine, and hindgut tumors are usually nonsecretory.

18:51Carcinoid syndrome has its own triad and complications. The triad is flushing of the face and neck, often triggered by alcohol or food; watery diarrhea; and wheezing. Serotonin scars the right-sided heart valves, causing tricuspid regurgitation and pulmonic stenosis. And the tumor's use of tryptophan to make serotonin depletes the precursor of niacin, which can cause a pellagra-like rash.

19:14Its diagnosis and treatment differ from the VIPoma's. The test is twenty-four-hour urine five-HIAA, the serotonin breakdown product, with chromogranin A and DOTATATE imaging. Treatment is a long-acting somatostatin analog. Telotristat, which blocks serotonin synthesis, is added for refractory diarrhea, and the liver metastases are treated surgically or by intervention.

19:38A gastrinoma causes diarrhea with severe ulcers, and one feature separates it from a VIPoma. The acid load overwhelms duodenal bicarbonate, inactivates lipase, and injures the small bowel, so the diarrhea is both secretory and fatty. Unlike a VIPoma's, it improves with a high-dose PPI. The diagnosis rests on fasting gastrin with gastric pH off PPIs, and a secretin test for intermediate values.

20:04The remaining endocrine causes each have a giveaway. Medullary thyroid cancer secretes calcitonin and causes watery diarrhea, with a thyroid nodule and sometimes a family history of multiple endocrine neoplasia type two. Glucagonoma causes the four D's: dermatitis from necrolytic migratory erythema in the skin folds, diabetes, deep vein thrombosis, and depression, with weight loss and a glucagon over five hundred to a thousand. Somatostatinoma causes steatorrhea from suppressed cholecystokinin, gallstones from a sluggish gallbladder, and high sugar from suppressed insulin.

20:40Three non-tumor endocrine and mast cell causes complete the list. Mastocytosis causes flushing, urticaria pigmentosa, a high tryptase, and histamine-driven diarrhea. Addison disease causes diarrhea with skin darkening, low sodium, and high potassium, confirmed with a cosyntropin stimulation test. Hyperthyroidism speeds transit and is caught by the TSH.

21:05The third patient shows that secretory diarrhea can be self-inflicted. A twenty-four-year-old woman who works as a nursing assistant has months of watery diarrhea, low potassium, dehydration, and weight loss, with a completely normal workup. Surreptitious laxative use is the diagnosis to consider, classically in a young woman in health care or with an eating disorder. Urine and stool laxative screens look for bisacodyl, senna-type anthraquinones, and phenolphthalein.

21:34Two other findings support it. Colonoscopy may show melanosis coli, brown-black pigmentation of the lining from anthraquinone-induced cell death and pigment in macrophages. And the stool osmolality gives the method away. Far below two hundred ninety means water was added to the collection to fake volume, while far above, with high magnesium or sulfate, means an ionic laxative.

21:57When everything is excluded, the diagnosis is idiopathic secretory diarrhea. It starts abruptly, causes frequent watery stools, often about ten a day, for weeks to years, with modest weight loss, and eventually resolves on its own. An epidemic form, Brainerd diarrhea, followed drinking raw milk. Antibiotics and bile acid binders don't help, so treatment is supportive.

22:22Here are the traps the boards set in these patients. "No medications" isn't accepted without asking about over-the-counter products and supplements. The rectal exam isn't skipped. The celiac antibody is sent with a total IgA. Fecal elastase isn't sent on watery stool. The gap is two hundred ninety minus twice the sum of sodium and potassium, and it isn't trusted when the measured osmolality is far from two hundred ninety. And nocturnal stools or weight loss point away from irritable bowel.

22:52The secretory diarrhea traps follow. The fast that confirms secretory diarrhea isn't skipped. A neuroendocrine panel doesn't come before microscopic colitis and bile acid diarrhea are excluded. Microscopic colitis is missed when only the left colon is biopsied. And chromogranin A drawn on a PPI isn't trusted.

23:12The tumor and factitious traps close the list. Carcinoid syndrome needs liver metastases. Achlorhydria and hypokalemia are clues to a VIPoma. Gastrinoma diarrhea improves on a PPI, and VIPoma diarrhea doesn't. And laxative abuse is considered in a young patient with hypokalemia and a normal workup.

23:32So, start to finish. Chronic diarrhea is more than four weeks of loose stools. The history finds most diagnoses: medications including supplements, surgery, travel, and diet, with nocturnal stools and weight loss pointing away from irritable bowel. Examine for clues and always do a rectal exam.

23:52Start with a blood count, metabolic panel, CRP, TSH, celiac serology with total IgA, calprotectin, elastase, an infection panel, and stool electrolytes. Then classify. An osmotic gap over one hundred that resolves with fasting is osmotic. A gap under fifty that persists with fasting is secretory. Blood and a high calprotectin are inflammatory. Greasy stools with weight loss are fatty.

24:24For secretory diarrhea, work from common to rare: microscopic colitis, bile acid diarrhea, drugs, chronic infection, then neuroendocrine tumors, laxative abuse, and idiopathic disease. Send the neuroendocrine panel only when the picture fits.

24:40A VIPoma is watery diarrhea, hypokalemia, and achlorhydria from a large pancreatic tail tumor with a VIP over two hundred. It's treated with fluids, potassium, somatostatin analogs, and resection when possible. Carcinoid syndrome needs liver metastases from a midgut tumor and is diagnosed by urine five-HIAA.

25:02Episode two is bile acid diarrhea, microscopic colitis, fatty and bloody diarrhea, and the patient whose workup comes back empty.

25:14For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of two of chapter twelve, and I'll see you in the next one.