Gastroparesis and Functional Dyspepsia Part 1: 2 Disorders, I Spectrum?

In this podcast, gastroenterologists Brian Lacy, MD, David Cangemi, MD, and Kenneth Koch, MD, begin their in-depth discussion of how functional dyspepsia and gastroparesis differ, and whether they are different conditions on belong on a spectrum.

Brian Lacy, MD, is a professor of medicine from the Mayo Clinic in Jacksonville, Florida, and Section Editor for Stomach and Small Bowel Diseases and Disorders for the Gastroenterology Learning Network. Kenneth Koch, MD, is a professor of medicine from Wake Forest University Medical School in Winston-Salem, North Carolina. David Cangemi, MD, is an assistant professor of medicine from the Mayo Clinic in Jacksonville, Florida.

TRANSCRIPT:

Dr. Lacy:  Welcome to this Gastroenterology Learning Network podcast. My name is Brian Lacy. I'm a professor of medicine at the Mayo Clinic in Jacksonville, Florida. I'm delighted to be speaking today to Dr. Ken Koch, professor of medicine in the Division of Gastroenterology at Wake Forest.

Dr. Koch:   Hello, everybody. It's good to be here. Thank you for inviting me to this session.

Dr. Lacy:  Welcome. We're so glad you're here. Also, in this kind of point-counterpoint conversation today, we're delighted to have Dr. David Cangemi, assistant professor of medicine at Mayo Clinic Jacksonville.

Dr. David Cangemi:  Thank you for having me. I'm excited to participate in this exciting, important podcast.

Dr. Lacy:  This is great, David. Thank you for doing this. Our topic today is one that affects everybody who practices in gastroenterology and also internists as well. That's the overlap of gastroparesis and functional dyspepsia. Let's jump right on in.

Ken, again, thank you so much for joining this podcast today. Let's begin with you. How do you define gastroparesis and how common is it?

Dr. Koch:  We have to have a collection of symptoms. The symptoms are going to be unexplained nausea, early satiety. There may be vomiting, and even some bloating. Then patients may have discomfort and even pain. It's those very nonspecific collection of symptoms that in addition we have a delay in the rate of emptying of a standard test meal.

The standard one is an Egg Beaters meal. If that meal is delayed in the absence of a mechanical obstruction to the stomach, then that combination, we will say that makes the diagnosis of gastroparesis in a patient. That's pretty standard over the last number of years.

Gee whiz, when you say, "How common is it? What is the incidence?" This still remains a problem actually in my mind. Some of the community-based...Mayo did a very nice drive in Rochester looking at the incidence. It's quite low there.

Brian, my analogy might be my own practice. Every gastro who's listening probably has their own experience. And I see a lot of patients with unexplained nausea. My clinic is full of unexplained nausea patients. If I have 10 patients who have the symptoms that I mentioned, and a normal endoscopy -- we'll talk about this later -- 2 or 3 will have delayed emptying. It's really hard to say, we know diabetics have it more commonly. The key is it 20%? Is it 30% of them? Is it type 1s more than type 2s?" There's a little more data there.

But in the idiopathics and postsurgicals, it's a tough question. That's about as far as I can take it. Maybe, you have a better idea about that. I would wonder what the gastros, that are listening, what they would come up with. That's my practical, how common is it.

Dr. Lacy:  No, that's a great answer. Just to add on to that, part of the problem is that many of these patients with these symptoms never undergo gastric emptying scans to get the definitive diagnosis. Some studies have shown maybe 2 to 5 million US adult Americans, so pretty common.

David, let's shift gears. How do you define functional dyspepsia, and how common do you think it is?

Dr. Cangemi:  First of all, functional dyspepsia is quite common, I would say, much more than gastroparesis. Most would estimate that functional dyspepsia occurs in about 10% of the population, maybe 6% to 10%. There are some studies that uninvestigated dyspepsia can occur globally as high as 20%. It's a pretty common disorder.

As far as diagnosis goes, many of our listeners would know that we use the Rome criteria to diagnose functional GI disorders or disorders of brain-gut interaction, as functional dyspepsia clearly a functional GI disorder. According to the Rome IV criteria, it is defined as one or more of the following symptoms — bothersome, postprandial fullness; early satiety; epigastric pain; or burning —either one of those symptoms, or multiple even all those symptoms, and with all functional GI disorders, there can be no evidence of any organic, underlying cause.

There has to be some chronicity too. The symptoms have to be present for on-set of 6 months at least, and then present for the last 3 months.

Just to take a little bit further, we know there are 2 subtypes of functional dyspepsia. One is the postcranial distress syndrome subtype, which is characterized by meal-related fullness or satiety. These symptoms have to be present technically at least 3 days per week.

Then, there's the epigastric pain syndrome, which is characterized by epigastric pain or burning. These symptoms have to be present, technically, at least 1 day per week. Not everyone fits nicely into 1 of those 2 categories, and some people have a mixed subtype. Sometimes, categorizing patients into 2 subtypes can help when deciding treatment options.

Dr. Lacy:  David, great, thank you. For our listeners, as you're hearing, Dr. Cangemi's initial explanation of symptoms, a lot of overlap with gastroparesis, and we're going to come back to that in just a second.

Ken, you touched on this and you mentioned 1 or 2 etiologies of gastroparesis. You mentioned diabetes and this large idiopathic group, but kindly tell us some of the other more common causes that would help our listeners.

Dr. Koch:  For so long, you would hear, “My patient can't have gastroparesis because they don't have diabetes.” Now, we know maybe a third -- at least in our gastroparesis consortium, where we collect many of these patients -- of our patients are diabetic type 1 and type 2. Certainly, if you see a diabetic with those symptoms, your radar is certainly up.

Still 40%, 50% are going to be idiopathic. Then the next category is postsurgical. We now tell that fundoplication was the most common surgical cause of gastroparesis probably when maybe the vagus gets inadvertently nicked.

In the idiopathic group, we haven't cracked that nut very well. I still think of postinfectious, maybe collagen vascular diseases get mixed in there if you're looking for a cause. By the way, I should say we always should be looking for a cause. You just don't accept that there's gastroparesis, you say, "Why is there gastroparesis? Why is this happening?"

Then, I say, "Well, you're an elderly person. Maybe, there's some Parkinson's going along." A few people who've had bad pancreatitis in the past. It becomes many different ways to injure the neuromuscular wall of the stomach. Let alone the autonomic nervous system, I should add, I even look for people with POTS. I'm seeing more people with POTS. How is that related?

Once you get into this area, the number of folks with different diagnoses that show up with these symptoms, these nonspecific symptoms, and the late emptying, is an interesting differential diagnosis. You got to think, in my mind pretty broadly, and if it's idiopathic, don't just look for other defense. I always get a TSH. I just want to know, are you hypothyroid? Could there be something slowing your stomach down even from a hormonal cause?

Yeah, the big ones, of course, diabetes, the big category idiopathic and postsurgical. Under that idiopathic, I think it behooves us to think about, can we get a more specific diagnosis?

Dr. Lacy:  Right, that's a great teaching point, not just you have it but why do you have it and do a little bit of investigative work. David, similarly, functional dyspepsia, we think of as a big category, but there are a lot of reasons why it can occur. At least in your experience, what are some of the more common reasons why people develop functional dyspepsia?

Dr. Cangemi:  I would start by saying that our understanding of functional dyspepsia is evolving, and I think we still don't quite understand functional dyspepsia entirely when it comes to an etiology standpoint, it's a complex disorder. It's diverse. Different factors are important for different individuals.

For example, some individuals may have a genetic predisposition. There's more work that needs to be done in that area. For many people, it's probably some sort of an environmental exposure whether that's a medication, an infection being a big category, postinfectious, maybe tobacco use, psychologic stressors.

When you're talking about infection, specifically H. pylori has been identified as a risk factor, most would accept that. H. pylori is important in terms of the diagnostic or the workup and treatment for H. pylori so that's one in particular to keep in mind.

Also, it's worth mentioning how, as a functional GI disorder, again, psychological stressors whether that's anxiety or depression, or somatization can certainly impact how people feel. It can augment symptoms, enhance symptoms and likely plays a role for many patients and in taking them from maybe mild symptoms to more moderate or severe symptoms. It's important to keep in mind when you're seeing dyspeptic patients in clinic.

Dr. Lacy:  All right, David, thank you. Ken, I'm going to come back to you and I wish you were in front of a chalkboard right now because I'd like you to draw out the stomach and the pathophysiology of gastroparesis. Since we can't do that today, could you briefly explain, at least in your mind, some of the most common pathophysiologic processes that can lead to symptoms of gastroparesis and delayed stomach emptying?

Dr. Koch:  Yeah. Thank you, and I love to do this. I'm always sitting around drawing stomachs. Trying to improve on the anatomy. Briefly, I'll tell you, I was giving a grand rounds, and there was an older surgeon in the audience, and I went through what I'm going to visually take you through my view of the stomach neuromuscular function.

It's quite detailed. It's very complex. It's very sophisticated, as gastros know. After my lecture, this surgeon comes up and he says, "Dr. Koch, I really enjoyed your talk. I didn't have any idea the stomach was so neurologically, neuromuscularly connected. We thought it was just a bag."

I said, "Oh, my gosh," in the surgeon’s mind over the years, it was a bag that you could cut on pretty much however you want it. Now erase that vision of a bag from your mind please. All the gastros whose scope and so on, they know all this anatomy.

The pathophysiology — I start with the fundus. The fundus is there to receive our food effortlessly. It relaxes, thanks to nitric oxide. We receive the volume of food that we want to ingest.

Then, the corpus antrum is the workhorse, especially the antrum where we mix and triturate. And then, very carefully, literally in small aliquots, empty the chyme through the pylorus into the duodenum. This requires very sophisticated coordination.

It's such an important event, of course, nutrition of the body, of the organism that it's paced. What we know that the stomach has the pacemaker. I tell patients this, and we talk about how delicate this is. Then, they began to appreciate how they have to be careful about what they eat.

The pacemaker we know now is run by the interstitial cells of Cajal. Every fellow here has to know exactly what ICC means. I'm sure all the gastros out there know that pacemaker is run by the interstitial cells of Cajal at a rhythm of 3 cycles per minute. Are you kidding me? Three cycles per minute? We breathe at 16, our hearts run at 60, 70. Everything is on a rhythm. The body is an amazing clock, and the stomach runs at 3 cycles per minute.

I worry about the pylorus a lot in our patients. That is going to regulate the rate of emptying. There has to be an antro-pylorus-duodenal coordination as we empty. Every one of these areas then can misfire, the fundus fails to relax. Sometimes the fundus relaxes too much. Food is retained in the fundus. Food is emptied too fast to the antrum. There's a whole series of dysrhythmias. We'll talk about this later. Loss and depletion of ICCs is now really a higher level of interest. The ICC seems to be more depleted in gastroparesis with lots of dysrhythmias because without the ICCs, you have less than 3 cycles per minute and more dysrhythmia and that occurs on a continuum.

We're now understanding in 2 or 3 papers that people with FD or unexplained chronic nausea have depletion of ICCs that supposedly appears to be not as depleted as in gastroparesis. My discussion is going to go is that these 2 entities are very closely related on the pathophysiology scale and we have a lot to learn, of course, about the spectrum. If you don't have a good rhythmicity then you tend to have weaker contractions, they may not be as coordinated. They may not be as connected to the pylorus. Then, is the pylorus in spasm? Is the pylorus clicking closed prematurely?

The pylorus now is another interest area, as you all know. Do we want to destroy the pylorus with a knife or a sphincterotome, or is there something else we can do? We'll talk about that.

You see, if we appreciate the pathophysiology of these different parts, I think we begin to understand the symptoms. My patients all feel bad after they eat. They're supposed to feel very good.

We have to understand why they feel bad. Is it early on and a combination? Is later on and prolonged fullness and nausea? As we learn more and more about the pathophysiology and the physiology of how the stomach works as this sophisticated, highly-tuned instrument, we can begin to understand our patient's symptoms better.

Dr. Lacy:  That was an amazing visual. For all of our listeners, this exactly explains why we've all learned so much from Dr. Koch over the last 30 years and why he's contributed so much.

As I used to explain to the medical students at Dartmouth, I would give them the extra credit question on their tests. What's the smartest organ in the body? The answer, of course, it's the stomach. Because really, what organ tells you on a second-by-second basis, it's functional status. It's a sensory and motor organ.

David, boy, hard to beat that. What can you layer on to this in terms of the complexity of the pathophysiology of functional dyspepsia?

Dr. Cangemi:  Yeah, maybe a little bit more confusion instead of clarity here, but so much like etiology, I'd say, the pathophysiology of functional dyspepsia remains incompletely understood.

There are a couple important processes that have been identified. Delayed gastric emptying being one. It's been suggested up to 20 to 30% of patients with functional dyspepsia may have delayed gastric emptying. That point, in particular, always confused me as a medical trainee. Wouldn't that be kept until these patients have gastric braces and delayed gastric emptying and symptoms?

Most experts would agree that when we say delayed gastric emptying and talking about dyspeptics, we're talking about mild delays in gastric emptying. This gets into, perhaps, later discussion about the overlap and get the whole idea that functional dyspepsia and gastroparesis may actually be the same gastric motor sensory disorder, and they occur along a spectrum.

Also impaired gastric accommodation, as Dr. Koch mentioned, it's been suggested that this may occur in up to 30% of patients with dyspepsia. We mentioned H. pylori previously as a risk factor. There's been some recent data suggesting that low-grade inflammation in the duodenum, in particular with some studies showing increased eosinophils and mast cells, that this might be implicated in symptom generation.

Again, as a disorder of brain-gut interactions, it's important to mention visceral hypersensitivity, the concept of abnormally sensitive nerve endings in the gastrointestinal tract and the altered communication that can occur between the brain in the gut. That's also very important pathophysiologic mechanism.

Then, finally, within the last year or so, Dr. Bill Chey’s group from Michigan just put out a study in the Red Journal showing evidence of epithelial barrier impairment. The so-called leaky gut or increase intestinal permeability is a small study identifying increased epithelial gap densities and impaired mucosal integrity using confocal laser endomicroscopy, specifically which allowed for very close, high-magnification views of the duodenal epithelium. That's a very exciting area that will likely be studied more in detail but could be a new, unappreciated mechanism.

Dr. Lacy:  David, thank you. I think it points out why research in this area is just taking off and how we're going to learn some really exciting things in the next few years, courtesy of both of you.

In our next podcast, Dr Kenneth Koch, Dr David Cangemi, and I will discuss how the historic distinction between gastroparesis and functional dyspepsia has become blurred.