Mast Cell Disorders - WHAT and WHY

Okay, good day and welcome to Medicine Health with Dr. Paul Anderson. That's me, I'm Dr. Paul, and today we are going to be— today our topic is going to be mast cell problems. Now you may or may not have heard of mast cells or mast cell disorders like mast cell activation syndrome or mastocytosis, the disease, or any flavor in between. But that's what we're talking about in these 4 sections today on the podcast. So the first one I think is always a good question to answer, which is, you know, what are mast cells? Uh, what do they do for us normally? Like, usually if our body has a particular cell type, it's got a job to do, and that's the case with the mast cells. And then what happens when they so-called go wrong? So obviously, if there is a disorder called mast cell activation syndrome, and there's a disease called mastocytosis, which has some variety to it, there can be places where these things sort of, you know, are not working in our favor anymore, at least giving us symptoms. So What I want to start with is there are a group of cells in your body. Many of them are what we would consider immunologic, meaning that they do something with the immune system. That could be in a limited fashion, such as some of the clotting cells. It could be in a broad fashion, such as the, you know, the T and the B cells that we've talked about, and the natural killer cell family. And within all of these cells, there are groups of them of which some of your white blood cells fall into and your platelets fall into and certain other things such as the mast cells that are called granular cells. Now, they're called granular cells because a long time ago when we were using light microscopes and staining things so that we could see them, we noticed that some, for example, white blood cells had no granules in them, little dots, and some had granules in them. So in the white blood cell world, we divide them into the granulocytes and the agranulocytes, or things without granules. Well, there's other things, as I said, like platelets, etc., that have that. Now, mast cells are a specific type of immune cell that falls into the granular category because they have these little granules. So if we fast forward past, you know, the olden days of just light microscopy and, uh, cell biology was very rudimentary, and then we start looking at, you know, culturing cells and taking them out and putting them under stress, doing other stuff, what we saw was, well, these granules have a purpose, right? So the purpose of the granules is that they are holding on to material that are within the cell. And then when that cell is triggered, normally by— we've talked about cytokines, which are chemical signaling agents in the body— a granular cell triggered in the right way will degranulate, meaning it will shoot out these chemicals that are inside these little granule storage areas. So you might think, well, why have the little storage areas? Why not just have, you know, the metabolism make these chemicals on demand? Well, The big reason is, is that if you have an immune reason where you need to degranulate a cell, you may not have time to synthesize all of that chemistry. It's very similar to other more complex chemicals in your body where your body has a proform that's not active yet, but it's ready to go, and on demand when you need it, it's already made and it just turns a switch and gets activated, so to speak. Well, that's kind of what your mast cells are doing now. A normal purpose of these granulocytes, of which the mast cells are one category, is that under immune stimulation, we wind up having them degranulate, and then they release other chemicals that either help us with our direct immune response. maybe help to attract other immune cells to the area, maybe help with access to the tissues such as opening up the capillaries, creating local inflammation, helping big white blood cells move in and out of the capillaries, you know, all manner of things that go on. So, you could see if I have these, you know, granular cells and they're there and then they get triggered by an inciting event, let's say my immune system needs some help, and then they degranulate and they basically shoot all of these chemicals out in the area and then those chemicals help with my immune response, that's going to be a really positive thing, right? I'm going to have a good immune response. So we talked about that in a number of cases, that the initial part of the immune response can be very inflammatory, but we want that. And then later we calm that down after, you know, the cleanup has happened, etc. So then you think, well, okay, these mast cells, which are a type of a granulocyte cell, of which there are many that do immunologic and chemical things, are there, and they've got these stored granules of different chemicals, and they're there for our benefit, for our immune function. Why are there disorders, diseases, etc., that are associated with these mast cells behaving badly? Well, the first thing to keep in mind with the mast cells is that there's a spectrum of— we could go with the idea of bad behavior of mast cells. There's a spectrum of problems. Now, the ones that have mast cell in their name kind of go from mast cell activation syndrome, MCAS it's often called, which has a whole bunch of problems that are physical and chemical in the body. And then there's a continuance over to a pathological triggering of the mast cells called mastocytosis. And long ago, it was kind of thought that maybe there was just mastocytosis and it was super rare. And, you know, if we were seeing these other inflammatory things in people, it probably wasn't mastocytosis. And the reason for that is, is that the testing and assessment on that far end of the pathological spectrum of mastocytosis is not the most specific in the world or sensitive. It's a little tricky to nail down. And the world of mastocytosis actually has a spectrum that goes from non-cancerous mast cell disorder to cancerous mast cell disorder. So for example, one of, uh, there, there are a few, it's not a lot of people, but a handful of people in, uh, the world who are expert in this area as far as writing and, you know, things of that nature. One of them is, uh, Dr. Afrin, and, uh, yes, the same name as the over-the-counter drug, but It's not his drug. But Dr. Afrin is an oncologist. He's a hematologist oncologist. And so they were often people who would be sent patients with the obviously cancerous type of mastocytosis. Now, what he and a lot of the rest of us started to see was he would work these people up for the cancer type of mastocytosis and notice that it wasn't that. And they really didn't have the laboratory characteristics of mastocytosis that was non-cancerous, but they certainly had all of the same problem or many of the same problems. They didn't have cancer, obviously. So he started to write about this. Now, there's also another doctor named Dr. Theorides, who is the first expert that I came into contact with a long time ago when I was trying to sort out patients who didn't have cancer but had all these mast cell problems that they were going on. And he was the first expert I started reading, and it helped illuminate my practice. Then Dr. Afrin, and there's many other folks. So the bottom line here is that you don't have to have the disease called mastocytosis to have mast cell problems. The fuzzy part of that is that the non-mastocytosis part called mast cell activation syndrome is much more common in people than mastocytosis is, and you get very similar symptomatic problems. So what happens if I don't need an immunologic response and my mast cells degranulate and send all these chemicals out? Well, we're going to talk a lot about one of the primary chemicals that mast cells send out in their granules when they degranulate, and that is histamine. We've talked a lot about histamine, but most of us understand that histamine does a lot of things in the allergic response. Histamine is also used as a signaling molecule in our digestive tract and other places, and also our brain has a very complex set of histamine receptors that it uses to make our brain work. So histamine's super important, but if we have a bunch of it dumped out of these cells, then suddenly we get histamine responses in our body that we don't need. If we need them, it's great. So we're going to talk specifically about histamine. That'll be the next little subpart that we do. But the point I wanted to make is in this spectrum from mast cell activation syndrome, which is a lot of different things, and then mastocytosis, when these cells degranulate, we get histamine symptoms. But granules contain many, many other chemicals. They contain some chemicals that are neurotransmitters if it's in our brain. Uh, If they're peripheral, like in the— in anywhere else in the body, it's not your brain. We use neurotransmitters for connecting the nerve cells. We also use neurotransmitters for many, many other things as well. So again, if just like with histamine, if I don't need a bunch of this stuff released in the area, I might get symptoms. Now let's say I don't need a granular cell like a mast cell to degranulate and give me all this wonderful chemical business. And let's say it's kind of happening in many parts of my body. How might I feel? So I don't need this to happen, but it's happening. That is the key to either mastocytosis or mast cell activation syndrome. Well, histamine and some of the other chemicals think, well, we're— and I realize chemicals probably don't think, but it's, it It sometimes helps to have a story around these things, so don't, don't pick on that too much. But so histamine, you know, gets released and it looks chemically around, you know, physiologically, and says, well, I'm out, there must be a purpose. And so I and all of my cast of characters that came out of the granule are going to go and we're going to do what we normally do. Now, if what you normally do is cause swelling, and redness and itching and inflammation and opening up of capillaries and production of maybe mucus and other stuff in the area, and I don't need that, then I'm gonna have a problem. Now, what does this sound like? This sounds like a standard allergic reaction, and that is true. That is a piece of the standard allergic reaction can be due to mast cell and other cells degranulating when they are not needed. Now, if we go back to that idea, and again, we're going to spend a whole little section on histamine, so I won't get too personal with histamine at the moment. But if we go back to that idea and we think about, well, I've got all this stuff happening, it's out there, and I don't need it. Why would that happen? Well, it's similar to a pure histamine reaction when I have allergies or atopic conditions where my body is confused and it perceives something like pollen, which really can't hurt me, as an invader, and it tries to attack the pollen. So it gets, it gets a confused response. When you get to mast cell activation, and then certainly in mastocytosis, you have these reactions at a heightened level and at a more broad level, meaning they can happen all over. They can affect all your body systems. They can be a big, big problem. Well, We're just down to the last minute on this section. So I just want to remind us that first, mast cells are these granular cells that have chemicals inside they release from our immune system. Second, we have an over-responsive set of mast cells, and so we get symptoms from them. And then third, it's not one disorder. There is a spectrum of mast cell activation syndrome, and then there's a spectrum of mastocytosis, which is a known disease, but that even has a spectrum with inside of it. So we're ready to wrap up here with this section, and we're going to get into histamine, and then we're going to get into drug treatments and natural treatments and other things to think about. But I just want to remind you, like, share, and subscribe, and please do the notifications if you can. We're loving all the new subscribers, and notifications helps you know even if the algorithm is slowing us down. We're all over the place, but you can check dranow.com and get all of the links. All right, well, we'll take a break for a moment. We'll be back with the next section.