Gastric and Small Bowel Motility: Gastroparesis

0:00Welcome to Board Pearls. This is episode one of two of the Gastric and Small Bowel Motility chapter, in the Stomach and Small Bowel Disorders module. This episode is gastroparesis from mechanism through treatment, and the whole disease sits on one idea: emptying the stomach takes three systems working together, and gastroparesis is what happens when any one of them fails.

0:22Here are the three. The upper stomach is a reservoir, and its job is to relax and accommodate a meal, driven by vagal nerve signals, so the pressure doesn't spike and you don't feel full too soon. The lower stomach is the pump, a grinder that breaks solids into particles small enough to pass the pylorus and pushes them through with coordinated contractions. And underneath both sits an electrical pacemaker, the interstitial cells of Cajal, which fire a slow wave a few times a minute that sets the rhythm and direction of the contractions; the wave is the metronome, and separate spike activity is what actually fires each contraction.

0:56So there are three places this can break, and the differential is just figuring out which one failed: you need an intact vagus for accommodation and coordination, intact pacemaker cells for the rhythm, and intact smooth muscle for the force. Lose any one and the stomach empties slowly. Gastroparesis is that common endpoint.

1:14Diabetes is the most tested cause and the most instructive, because it hits two of the three at once: long-standing high blood sugar damages the vagus, blunting accommodation and uncoupling the coordinated contractions, and it independently injures and depletes the pacemaker cells. And there's a wrinkle that matters for the workup: acute high blood sugar itself slows emptying, so a glucose over two hundred at the time of testing can falsify the study, which is why controlling glucose is part of both the diagnosis and the treatment, and why you confirm it's under two hundred before the test. It's also worth knowing that a good fraction of diabetics have measurably delayed emptying but no symptoms, which is the first hint of a theme: the emptying number and the symptoms don't track each other cleanly.

1:59Idiopathic gastroparesis is the other big category, a diagnosis of exclusion, classically a young to middle-aged woman with nausea, fullness, early satiety, bloating, and upper abdominal pain, with no diabetes, surgery, or drug cause. A subset is post-infectious, where a viral or bacterial gastroenteritis precedes persistent dysmotility by weeks to months, and recognizing that post-viral history is what spares the patient a deeper workup for a disease they don't have. Post-surgical gastroparesis follows any operation that injures the vagus or distorts the anatomy, from the old ulcer vagotomies to fundoplication, sleeve gastrectomy, and esophagectomy, so the surgical history has to be asked about directly or it's missed.

2:43Then the drug causes, which are the most modern testing target. Opioids slow the whole gut through their receptors on enteric neurons. Anticholinergics directly inhibit the antral contractions. And the GLP-1 agonists are now the dominant confounder: semaglutide, liraglutide, tirzepatide, and the others all delay solid emptying by slowing the antrum and modulating satiety, so they'll produce a delayed study in someone with no intrinsic gastroparesis at all. The favored vignette is a patient who started semaglutide weeks ago, developed new nausea and early satiety, and now has an abnormal emptying study, and the patient's age is a distractor, because gastric motility doesn't meaningfully decline with age and there are no age-adjusted normals. The retention is real, the drug is the cause, and the right move is to stop the GLP-1 before any more testing; if the symptoms resolve, you're done. Cannabinoids are a related curveball, with chronic THC slowing emptying and tying into the hyperemesis syndrome in the next episode.

3:46The secondary causes fill out the differential: Parkinson disease, where the gastroparesis often comes before the movement disorder; systemic sclerosis, the prototype connective tissue disease, where most patients have measurable upper-gut dysmotility through a neuropathic-then-myopathic course; amyloid infiltrating the wall as a muscle problem; hypothyroidism, which you screen for in every new workup; and paraneoplastic dysmotility, which lives in the next episode. The unifying lesson is that same three-part frame: vagal injury covers diabetes, surgery, and Parkinson; pacemaker loss covers idiopathic, diabetic, and scleroderma; muscle failure covers the infiltrative and post-surgical cases. Recognizing which one failed is what lets the workup and treatment follow.

4:33Diagnosis can't be made on symptoms, because nausea, vomiting, early satiety, fullness, bloating, and upper abdominal pain overlap with functional dyspepsia, ulcer disease, outlet obstruction, cyclic vomiting, rumination, eating disorders, and cannabinoid use. So you need to objectively show delayed emptying with no mechanical obstruction, and the workup is sequenced to exclude the alternatives first. Step one is endoscopy to rule out obstruction, because a retained bezoar, food after an adequate fast, or a pyloric stenosis changes everything, so the diabetic with vomiting needs the scope before the emptying study. Cross-sectional imaging or a barium study gets added when malrotation, a hernia, or external compression is in play.

5:17Once obstruction is excluded, the standard test is four-hour gastric emptying scintigraphy, a standardized low-fat egg-white meal labeled with a tracer, imaged over four hours after an overnight fast. The four-hour timepoint is essential, because shorter studies vary too much in the normal range to be diagnostic. More than ten percent of the meal still retained at four hours is diagnostic of delayed emptying, and more than sixty percent retained at two hours corroborates but doesn't stand alone, and the four-hour number grades severity that guides treatment intensity: mild is ten to fifteen percent retained, moderate is fifteen to thirty-five, and severe is over thirty-five.

5:57The pre-test drug management is the highest-yield detail in this whole section, and it follows the logic of not letting a drug fake or mask the result. Prokinetics speed emptying and cause false negatives, so metoclopramide, erythromycin, domperidone, and prucalopride are held for two to three days. Opioids delay emptying and cause false positives, so they're held for a couple of days when possible, as are anticholinergics, cannabinoids, and tobacco. Glucose has to be under two hundred at the start. And the GLP-1 agonists are the modern complication, with the hold matched to the drug's duration, the daily ones often held the day of testing and the weekly ones needing longer, and the favored move when someone with delayed emptying is on one is to stop it, watch for resolution, and only repeat the study if symptoms persist. The wireless motility capsule is the alternative when scintigraphy isn't available or you also want small-bowel and colon transit, measuring pH and pressure as it travels, with a gastric emptying time over five hours consistent with gastroparesis; its advantage is a whole-gut transit map, its downside the risk of getting stuck in a stricture. Adjunctive labs address specific questions: A1c and glucose for diabetes, TSH for thyroid, the connective-tissue and scleroderma antibodies, and a paraneoplastic panel with chest CT when the picture is acute with weight loss or small-bowel involvement.

7:22And one diagnostic principle a stem will test: the link between emptying delay and symptom severity is loose. Someone can have profoundly delayed emptying with few symptoms, or near-normal emptying with severe ones, and gastroparesis gets over-diagnosed when the four-hour test isn't used, the drug holds aren't enforced, and the glucose isn't corrected. That mismatch between the number and the picture is itself the point.

7:49Treatment is a series of steps where the earliest ones are the most powerful, because these patients are typically undertested and overmedicated, so you fix the foundations before reaching for drugs or procedures. The first step is exactly that foundation: correct the fluids, electrolytes, and nutrition, optimize glucose in diabetes, and remove the offending medications, because stopping opioids, anticholinergics, GLP-1 agonists, and cannabinoids alone resolves a meaningful share of cases, many of which were never a disease, just a drug effect. The second step is diet, which is more effective than most clinicians appreciate: small frequent meals are easier for the impaired pump than a few large ones, low fat helps because fat slows emptying through hormonal feedback, and low insoluble fiber matters because indigestible fiber forms bezoars in this stomach. As severity climbs, the diet becomes more liquid, from oral supplements to blenderized foods, and finally jejunal feeding that bypasses the stomach entirely, indicated for significant unintentional weight loss or repeated hospitalizations, often through a tube that both feeds past the stomach and vents it.

8:56The third step is prokinetic drugs, and four matter, taught by mechanism because the mechanism predicts who responds and what goes wrong. Metoclopramide is the only approved drug and stays first-line: it blocks dopamine receptors, which improves coordination and gives a central antiemetic effect, and weakly stimulates serotonin receptors to boost acetylcholine, dosed a few times a day before meals. Its defining safety point is the warning for tardive dyskinesia, which caps therapy at about twelve weeks, along with reversible movement side effects in a notable minority and elevated prolactin causing galactorrhea and amenorrhea, which is the favored vignette of secondary amenorrhea in a young woman on chronic metoclopramide, so it's reassessed and stopped when possible at twelve weeks. Domperidone is the peripheral version that doesn't cross into the brain, giving the same benefit without the movement side effects, which makes it the choice when metoclopramide isn't tolerated, but its trade-off is QT prolongation and a sudden-death association, so you get a baseline ECG and only start it below the QTc thresholds of four hundred fifty in men and four hundred seventy in women, with periodic monitoring, and in the US it's available only through a special access pathway, which is itself the testable detail. Erythromycin stimulates the motilin receptor to trigger strong antral contractions, and intravenous erythromycin is the most effective prokinetic for an acute flare, so it's the answer for the hospitalized patient with severe vomiting needing decompression, while the oral form is limited long-term by tachyphylaxis as the receptor downregulates within weeks to months, and it has no antiemetic effect and prolongs the QT. Prucalopride is a selective serotonin-receptor agonist that speeds stomach, small-bowel, and colon transit, approved for chronic constipation and used off-label for gastroparesis especially when constipation coexists, and it's preferred over the older agents in its class that were withdrawn for cardiac concerns, though the recent guidelines actually diverge on whether to use it.

10:56Antiemetics run alongside the prokinetics: the phenothiazines for mild-to-moderate disease, sharing the movement side effects; ondansetron as the main serotonin-blocker for more severe nausea, with a QT caution; and mirtazapine as a useful dual agent that controls nausea and stimulates appetite, which makes it the favored answer for a gastroparesis patient losing weight. And low-dose tricyclics like nortriptyline help when visceral pain or chronic nausea dominate. Refractory disease is severe symptoms despite optimized diet, prokinetics, and antiemetics, and the interventions there have to be matched to the phenotype. Intrapyloric botulinum toxin has not shown durable benefit in controlled trials and is recommended against, which makes it the favored wrong answer for the next step after failed medical therapy. Gastric electrical stimulation, an implanted neurostimulator, reduces nausea and vomiting in selected diabetic patients even though it doesn't pace the stomach or improve emptying, with the favored candidate being a diabetic with severe vomiting and frequent admissions and the poor candidates being nondiabetics with pain-dominant symptoms and patients on opioids. Gastric peroral endoscopic myotomy, cutting the pyloric muscle endoscopically, is the newer and most actively studied refractory option, improving symptoms in a substantial share of selected patients, best in those with significant baseline retention. Surgical pyloroplasty and gastrectomy remain options for the most refractory cases at real cost, and a venting tube with a feeding port handles nutrition and decompression in severe disease.

12:24So the way to think about it: gastroparesis is one phenotype with three failure points, the vagus for accommodation and coordination, the pacemaker cells for the rhythm, and the muscle for the force. Diabetes hits two, surgery hits the vagus, idiopathic disease hits the pacemaker, and drugs mimic the whole thing by slowing the pump. The four-hour scintigraphy with strict drug holds and a controlled glucose is the only test that anchors the diagnosis, and the favored move is often to stop a drug rather than confirm a disease. Treatment climbs from foundation, to diet, to prokinetics, to refractory procedures, each matched to a phenotype: metoclopramide approved and capped at twelve weeks, domperidone QT-limited, erythromycin for the acute admission, prucalopride when constipation coexists, and the endoscopic pyloromyotomy for selected refractory disease with real baseline retention.

13:16The next episode takes this chapter into the episodic and functional presentations: cyclic vomiting with its stereotyped attacks and migraine link versus cannabinoid hyperemesis with its hot-shower relief, intestinal pseudo-obstruction that mimics mechanical obstruction without a blockage, and functional dyspepsia treated by subtype after H. pylori test-and-treat.

13:38For 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 eight, and I'll see you in the next one.