Mast Cells & HISTAMINE WHAT and WHY

Welcome to Medicine Health with Dr. Anderson. I'm, I'm Dr. A. Today we're doing a series on mast cell activation syndrome, mastocytosis, and mast cells behaving badly. This section I want to talk about the one of the key players chemically because it's the most well-known and probably the easiest to understand overall. But we want to keep in mind that this key player gets a lot of attention, but we want to also remember it has other characters that go with it. So if we go back to the idea that mast cell problems are on a spectrum, you could have mast cell activation syndrome, MCAS, as one spectrum, which is a syndrome, which means it covers a broad range. There's a lot of different things that go on. And then there's a disease, a pathology called mastocytosis, That also has a spectrum that goes from non-cancerous mastocytosis to to cancerous mastocytosis. But the mast cells are granular cells. You can go back to the first section, look at that. But when they release the granules, there's chemicals in the granules. And so histamine is kind of the number one chemical. But there's other things in there as well that are chemicals that can cause inflammation and opening of blood vessels and attraction of other immune cells and other stuff that. if we need them for an immune response are great, but if we don't need them and the mast cell just goes, you know, crazy and releases these chemicals, we get symptoms from them. So because histamine is kind of central to this problem, it's again not the only thing, but it's central to the problem. I just want to remind us about histamine. So the first thing we think about histamine is allergies, because you've got allergies, you take an antihistamine. Well, that must be doing something with the histamine. And indeed what it's doing is it doesn't stop this, histamine from being released, but it blocks the histamine when it gets to your cells so that you can't, that you don't enjoy as much of the inflammatory, the allergic reaction. Now that could be at a low level, you could get itching and redness and swelling, you could get wheezing, you trigger an asthma attack, all sorts of other things, your joints can swell, or it can be a very high level where you have a type 1 reaction which leads to anaphylactic shock, and you not only then need, you know, intravenous antihistamines, you need epinephrine and other drugs to save your life if that's— histamine is a big deal. Well, imagine, and if you're one of us who has mast cell release problems anywhere in that spectrum from mast cell activation syndrome to mastocytosis, You're getting histamine and other chemicals released when it's inappropriate. So what does histamine do when it gets out? Well, histamine, if you just had to remember one word about histamine, is it is an inflammation driver. It's inflammatory. So one word would be inflammatory, 2 words would be it's an inflammation driver, kind of saying the same thing. Now, why would I want inflammation? Well, if I'm having an immune response, that's a great time to do some inflammatory activity. So I get more blood in the area, maybe get more mucus if it's mucous membrane, uh, I get opening of capillaries so that the big white cells can get in and out and do, do their business. If I don't need any of that, and again allergy response, which is a piece of mast cell stuff but it's not the whole thing, but the allergy response and the histamine, uh, that comes along is an inappropriate use, an inappropriate application of histamine. So in mast cell, whether it's mast cell activation syndrome or mastocytosis, what we see is we get this big inappropriate release or dumping of histamine and its other collateral characters that come out that are all pretty inflammatory. And so we wind up having often body-wide symptoms. Now, what can histamine, you know, on its own, if the levels are too high, what can that do to me? Well, one of the things that histamine does, in addition to this sort of local inflammation or mucous membrane inflammation like we see in allergy response, the rest of your body can become inflamed. So histamine is involved in, for example, the production of stomach acid. There are, there are different histamine receptors. And so like histamine type 1 receptors are found in many places, but a lot in your mucous membranes. So if you're having an allergic response in the mucous membranes, that's largely a histamine type 1. And then if it's in your GI tract and it's making hydrochloric acid, it's a histamine type 2. But what we want to remember is that these things are not just for those 2 purposes. So histamine type 2 and 1 together can be very pro-inflammatory. If you've ever had a bad histamine reaction, you go to the emergency room, they will often give you 2 kinds of blocking drugs, antihistamine, uh, H1 and H2 receptor blockers. Now there are also histamine receptors of type 1 and 2 and 3 and 4 in our brain. And so people who are having huge histamine dumps can have all sorts of neurological and neuropsychiatric symptoms that are not because they have an organic problem with their brain. It's just their brain is participating in all this extra histamine and it's getting overstimulated. If you had no histamine in your brain, your brain would quit working appropriately and might quit working altogether. Histamine's a big counter-regulatory neurotransmitter in your brain. And that's why your brain has histamine-type receptors of just about all flavors. Well, if you got a whole bunch of histamine going up to your brain, Uh, histamine of the H1 variety and some of the other histamine reception in the brain is very excitatory. So it is possible, and I've seen this actually happen with people with mast cell problems, where they suddenly get a trigger. Like, let's say they're allergic to, um, you know, a particular type of food, uh, and they get exposed at a— the one I'm thinking of, they got exposed like at a picnic and they didn't see all of the stuff that was there. And instead of having like asthma attack or something, they actually had a psychotic break, which was very, very unfortunate, uh, and it had to be treated, etc. But it was not because they were psychotic, it was because they had mast cell activation syndrome, and suddenly their body dumped even more histamine out. So it's a faster dumping, and so their, their brain, uh, participated in a psychotic episode because extra histamine. There are many other things that can happen. I've also seen people where they don't have any brain symptoms that really they know of, but I've seen where their joints will swell up. So they're, you know, we had one time a person with mast cell activation syndrome, and they had come from their allergist, and the allergist had increased their allergy desensitizing injections, which is a way to desensitize you to stuff you're allergic to. But when you increase the dose on on the desensitizing, you can trigger a mast cell response. And this person, about 30 minutes later, came back and we were observing them and they suddenly couldn't move. And it was because their ankles and their knees and their hip joints were swelling and it was progressing up their body. We actually had to give that person intravenous histamine blockers. So histamine is that potent. if it can make you have a psychotic break, if it can make your joints swell, if it can derange your digestive function, it can make your muscles hurt, it can do all kinds of stuff. As a central character in mast cell activation problems, histamine becomes a very, very big, uh, important thing to watch but also to target. Okay. So one of the things, because it is such an inflammatory chemical, And again, we need it for immune response and brain regulation and stuff. We just don't need all this extra that happens when we have mast cell activation or mastocytosis. So whenever we're thinking about this, and histamine's a good model for this, we have a releasing cell like a mast cell that degranulates and the chemicals come off, histamine being a big one. So there's the release part. Then there is the binding at your cell receptors. So you have receptors in your brain, you have them all over your body, mucous membranes, gut, all over. If you put histamine in and it binds to these receptors, you get super inflamed, and then wherever it binds, you have an inflammatory response. So we talked about, you know, neurological, neuropsychiatric things all the way through psychotic breaks. It can also just cause agitation. It can cause you to not sleep well. It can cause you to wake up all night long. It can cause you to have disordered thoughts, many, many things there. It can cause, as I said, your digestive tract to not operate correctly, joint swelling, pain, you know, all of those things are very common when it binds. Then the histamine, either before it binds or after it binds, has to be metabolized away because anytime we make something in the body that is important for function, we have to have ways, enzymes, to metabolize it. So histamine has a metabolic pathway that helps to reduce it and remove it. Well, another problem— it's sort of a double problem for people with mastocytosis or mast cell activation syndrome, either one— is that we got extra production. And then the other part of the double whammy is that sometimes we have genetically slow elimination pathways. So when we're dealing with mast cell activation, we're always dealing with these compartments and trying to look at them holistically and trying to have the body have less reasons to have the mast cells become active. Now, a difference between mastocytosis and mast cell activation syndrome is very likely— now, we don't know everything, but very likely, based on signs and symptoms and, and the biology we know. Then in the mastocytosis spectrum, which has cancer-type mastocytosis and non-cancerous, they're all very bad, high level. There are other chemicals that go really high, and the mast cells are even more aggressive to be releasing histamine and other chemistry. In mast cell activation syndrome, there are more roads in seemingly to triggering the mast cells to do this dirty work with histamine as one of the central players. All right, so we're about out of time for this one, but remember histamine is not the only chemical player in mast cell release, but it's a big one. It's very inflammatory, and there are a number of ways to try and either block it or metabolize it away or slow it down— its release— that have to be done medically to deal with mast cell problems. Thank you so much, all you subscribers. Please like, share, subscribe. We're on all the pod burners, CTR Radio Live, and YouTube, just go to D-R-A-N-O-W, dranow.com. Like, share, subscribe, whatever platform you like to use, and do notifications because sometimes the old algorithm shoves us over to the side and nobody sees us. So the notifications will help you a lot there. Otherwise, it's been wonderful talking about histamine, and now we're going to move on to some other topics in the world of mast cell issues. So thank you very much.