• LecturehallRelationship Between AVL Systems and Pathophysiology of Phlebolymphedema
  • Lecture Transcript
  • Female Speaker: Wonderful. Well, first I just like to thank everybody here in the audience for attending this session and thank you to Pamela for inviting me and a big thank you to 3M and E-Present for hosting this session as well. So I see some familiar faces out there. It's great to see all of you. I'm very excited to see such a large audience for a topic like this. It's very near and dear to my heart. As Pamela said we've got to tear down those silos, but what I'm hoping to do today is present with you some information to show you this interrelated connectedness between these different systems. So with that, I'm going to start and looking at this list -- this is quite an extensive list, right? Starting with lymphedema going all the way -- even peritonitis, cancer, organ transplantation, a lot of the autoimmune diseases, burns and hemorrhagic shock. This list goes on and on. Metabolic disease, diabetes. What is this all have in common, any ideas? There is a commonality with all of these different conditions and we're learning more and more about this every single day. Somebody said it inflammation, what system mediates inflammation? The lymphatic system. Yeah, so what's interesting, these all have a common lymphatic dysfunction, inflammation and altered immunity. So what's ironic is as Pamela just said in medical schools here in United States, they look to Germany and they look to the UK or it might have been Japan. They found that on average, we're teaching our physicians 9.2 hours of wound care education in medical school. When look at the lymphatic system, we're teaching 20 minutes and it's usually nested within the cardiovascular system. So we have a lot of work to do as Pamela had pointed out, but the good news is we're getting much more awareness and as more research is starting to come out linking all these conditions to this underlying common theme of lymphatic dysfunction, we're going to see a very good change, a positive change, I think with respect to education but a better understanding of how this system really impacts our patients. So A.T. Still who is actually I believe from Arizona, the school is named after him. He says it very well. He says we strike at the source of life and death when we go to the lymphatics and then Mortimer and Roxanne were big in lymphedema, kind of make this analogy here where you see a nice brick wall, right? So this is actually -- see if I can get this work -- your lymphatics really are the mortar of your biological system. We teach in the system at least in physical therapy, there is musculoskeletal, there is neuromuscular, there is cardiopulmonary and then there is the other systems, right? That’s where integ and all the other things go, but really it is critically important to realize the importance of how integral our lymphatics are in all of our systems because when there is dysfunction, there is disruption in every other system. And to add to that, what's interesting is we're now starting to describe the lymphatic system as a nodal centric immunovascular system. So it's kind of a mouthful, but if you think about it, it's a nodal centric because it has all the different regional lymph nodes. Again, you are only born with 700 lymph nodes and we can't replace them. We're starting to do some advanced surgeries, but again we only have 700 and it's an immunovascular system. And I think that’s important because we have to recognize it as a vascular system in and of itself. So when I teach my students about the vascular system, it's not just the arteries and the veins, right? It's also the lymphatic systems. So I talk about the AVL system. And this is kind of an important relationship. So our circulatory system really has three components. We have the open or the close system, the circulatory system of the arteries and veins, which we all understand, right? Centered around the heart and then of course we also have our half open lymphatic system. And the reason why it's half open is that the lymph capillaries, which reside in our dermis kind of hang out in that area in those tissues and pick up all the excess fluid and the proteins and metabolic waste. So it's not contiguous like the cardiovascular system is. But I think it's really important that we talk about the interrelationship because this system is responsible for fluid overload and what I like in particular is this picture. And what you are looking at here is you have an artery here with the A. You have a vein here labeled V and you see all this cobweb like structure, what is that? Your lymphatic capillaries. So again you can start to really appreciate that interconnectedness. And this is important because embryologically your lymphatics develop out of your venous system. So when there is impairment in your venous system for whatever reason, there is impairment in your lymphatic system. When there is impairment in your lymphatic system, there is impairment in your venous system. They are that interrelated and when both of those systems are impaired, it can also impact your arterial system because now that system gets backed up, can't deliver oxygen and nutrients the way it's supposed to.


    So it's really important to appreciate that AVL system. We're not just talking about dysfunction in the venous system or dysfunction in the arterial system or just lymphatic dysfunction. It affects everything and that’s a very important concept. Sorry, I'm not very good with the clicker, okay. So again looking at these slides, the lymphatic structures are critically important and the only places that they are not located because your lymphatics are found everywhere in the body, you will not find them in your cornea. They are not located in striated muscle. They are not in bone marrow. They are not in cartilage and they are not in your hair, your nails or your teeth, but they are everywhere else. And the ones that we directly impact not just your deep lymphatics, but our superficial lymphatics and again those are the lymphatic capillaries that are housed in our dermis, which is only 3 mm below the surface of our skin. This is why our approach to managing lymphedema or lymphatic failure is a very different approach. It's not massage, it's a manual technique employed to really to stretch and open those very thin lymphatic capillaries. So it's a pretty unique system in and of itself. Okay, so the purpose of the lymphatics system, again I think it's important just to kind of review. So fluid or in addition to immune defense, the basic purpose of the lymphatic system is to really drain all those substances that collect in the interstitial tissues and that’s normal. We get some ultrafiltration coming out of the arterial and the venous systems and we get some resorption back into the venous system, but the main responsibility for all that extra fluid is the lymphatic system. So fluid in the interstitial spaces is constantly circulating. And as plasma and plasma proteins escape those small blood vessels, they are picked up by the lymphatic systems. So, we have to remember when proteins end up in their interstitial spaces, they can't re-enter the venous system. They have to be picked up by the lymphatic system because they are just too big to go back in, and that’s critically important and that’s one of the underlying telltale things behind lymphedema is that it's a protein-rich edema and protein loves water, right? So the more protein in those interstitial spaces, the more it's going to attract water and you end up getting this vicious cycle of an enlarging limb. This is why it tends to be pretty progressive. So the lymphatic system resorbs and transport substances that the venous system cannot. Again, based off a Starling equilibrium, there is some new contestation that Starling might have been a little off, but that’s still emerging, so I won't go into that today. But other than just dead cells, bacterial, endotoxins, enzymes, things like MMPs, that’s all what the lymphatic system picks up. And I tell my students to like how many people -- you don't have to raise your hand, but I do this to my students. How many people have tattoos? Usually, some people raise their hand. Tattoo ink is actually part of a lymphatic load and what happens is that’s even picked up. So regional lymph nodes wherever the tattoo is located will be the color of that tattoo. This is how we know how important this system is because it picks up anything that doesn't belong within the venous system. That is its job. The other interesting things are skin absorb 60% of what we put on it. Where does it go? The lymphatic system, right? So it's really important that we think about what we're using, what we're putting on our patients, what we're putting on ourselves. My rule of thumb, if I can't pronounce it, I don't use it, okay. [Laughing]. Another component that the lymphatic system does, it acts as a safety valve for fluid overload and helps to keep edema from forming. This is critically important. So interstitial fluid pressure can increase, which causes an increase in the lymphatics ability to pick up its flow or its ability to pump and circulate the lymphatic fluid a little bit more efficiently. The local lymph system can be overwhelmed by a sudden increase in the interstitial fluid and you will end up with pitting edema. So if any of you who flew here, you might notice that if you take your shoes off on flight, you get some pitting edema. Your system temporarily is overwhelmed, but it can manage. So it's just overwhelmed at this time, but our patients with true lymphedema, it's overwhelmed all the time and it can't manage that additional fluid burden. This can end up being problematic. Another thing our system does is it helps to maintain the homeostasis of the extracellular environment. It removes excess protein molecules and waste from the interstitial fluid and again it's going to bring it back through the venous angles. That’s where it's going to dump it back into the venous angles where it re-enters the venous circulation. So on any given day, an average person returns about 4 L of lymphatic fluid back into their venous system. It's a significant amount of fluid. Another important component is the lymphatic system also cleanses the interstitial fluid and provides a blockade to the spread of infection or malignant cells in the lymphatic system. And I love this picture because this is actually a lymphocyte attacking a cancer cell and you can almost see its arm or its hand or whatever you want to call that, right? Reaching out and just kind of getting ready to absorb and attack that cancer cell. And at any given day -- you know we have malignant cells in our tissues and circulating through our body.


    With the healthy lymphatic systems, we're able to accommodate for that and to render them insignificant. Okay. So I want to talk a little bit about how our lymphatic system is our body’s drainage system. And I love analogy, so I hope you bear with me on this a little bit, but it makes things a little bit more understandable. So I would like to look at this as a water processing plant. Okay and I'm going to show you a little schematic of a breakdown of the cross section of the skin and here we're going to start with these. These are your lymphatic capillaries. They look a lot like trees and these are what are located in that dermis. And they are just hanging out there. They are one-cell layer thick. They have these anchoring filaments, which is attached to the connective tissue and when those are stretched, they open this one cell layer capillary open to allow fluid to come in. So these to me -- I want you to envision a neighborhood. Maybe it's your neighborhood where you live and all the houses have bathrooms, right ? Because we're talking about recycling system. So your lymphatic capillaries are kind of like the bathrooms in the home. They are going to collect all the waste products for lack of better term. Then you have your pre-collectors. So these look like kind of tree trunks. So these come straight down, kind of like perforators and bring it down to the deep collectors, which are these dark green structures here, which run with the deep vascular system. So your lymphatic capillaries again cover the entire surface of the skin. We're only talking about 3 mm and they pick up those lymphatic loads. So those are your bathrooms. Then you have your pre-collectors, which are really the sewer pipes or sewage pipes from each home leading into the neighborhood sewage collection system. And then you have your collectors. Again these big structures here these are valves, so they permit a one-way flow and these are actually taking all that waste products to neighborhood drainage systems that are connected to the city sewage system. And ultimately they are going to be taking them to these water filtration pots, which are akin to our lymph nodes, our regional lymph nodes, where the goal is purification. So it's kind of that same process, but I think it's important just to appreciate the anatomy because the sealing here would be our lymph capillaries. We have our pre-collectors coming down and then along the floor, we have our collectors. And it's very important because whatever we do to the skin is going to impact the deeper tissue structures as well, but I think it helps people appreciate how that system works. So simple or uncomplicated lymphedema really results from a mechanical failure of the lymphatic system. We basically consider this a low output failure. This means that some pathological processes have reduced the transport capacity of the lymphatic system. So if you look here, which has a bigger transport capacity, right? The truck or the little smart car? So when you have a reduced transport capacity, it's not able to take as much fluid from those interstitial spaces and clear it as it's supposed to. So we get a buildup or backup of that fluid. What also starts to happen is when it's stagnating, we end up with -- instead of a nice clean flowing river of lymph fluid, we end up with a very stagnant river and that stagnant river is what leads ultimately to a lot of those fibrotic changes because it's not picking up those substances and those substances are not supposed to be hanging out in interstitial spaces. When they do, they start to break down and that that leads to fibrosis. So we don't want this and we don't really want this. We want this, this combination. Another important concept is regarding the pathophysiology of phlebolymphedema and one thing -- if there is one thing I want you to take home today is that really all edema is a component of lymphatic failure. We will explain why that is. But the lymphatic system is organized into a one way drainage system to again allow recirculation of tissue fluid, macromolecules and immunologically active cells back into the vascular compartment. That’s really its job. That’s what it's supposed to do. If there is excessive demand on the lymphatics or there is a congenital problem or acquired problem like surgery or trauma, there is a loss of tissue fluid homeostasis and we see this clinically all the time. We may not understand it exactly, but we see this all the time. This is what allows that edema to develop, which can be recognized clinically as a feature of severe chronic venous insufficiency. We see these patients all the time, but what's really important is don't just think of it as a chronic venous insufficiency, think of it as phlebolymphedema because again you can't separate these systems. When there is chronic venous insufficiency, you have lymphatic failure. So we're really talking about phlebolymphedema in all of these patients. Now, this slide, I think, is important because this is going to show you how these systems are interrelated.


    Chronic venous insufficiency as you know leads to that venous hypertension, right? We get reflux, we get back flow, we get a lot of congestion and that’s very problematic because this results in a high filtration pressure, which causes increased fluid in the tissues and an increased lymphatic water load. Remember that safety factor. So now it's being asked to work even harder and it really can't often keep up demand over a long period of time. So what happens with that, the lymphatic transport capacity becomes exceeded by that water load and what this does is it causes a state of low protein edema while also causing a lymphatic hypertension because you're adding water load into those interstitial tissues causing pressure on that lymphatic system to work harder and harder than it really can. So constant lymphatic hypertension causes infiltration of that lymphatic load into the perilymphatic tissues leading to fibrosclerosis that hardening that we see in our patients where they start to not pit very well and the tissue becomes a little bit changed and even lymphangitis. Now from this point, protein permeability starts to increase leading to additional lymphatic damage because it now can't keep up with that load. And those proteins being out there when they start to break down and lyse and degrade, it's kind of like rancid butter and that leads to an immune response and inflammatory reaction that we start getting all these fibrosclerosis. So lymphedema again is a high protein edema, which actually becomes the underlying pathophysiology that contributes to the formation of venous stasis ulcers. But remember venous stasis ulcers are just the symptom of the disease, right? The disease is chronic venous insufficiency, which has been basically preceeded by a lymphatic hypertension. Whether lymphatic hypertension happens first leading to CVI or whether CVI happens first leading to venous hypertension doesn't really matter, but the systems are both involved and that is what we end up seeing that lymphedema is that underlying pathology contributing to the formation of venous ulcers and this is that challenge, right? You see these patients and your wound therapist like, I can't do anything about the lymphedema and they won't touch them and then the lymphedema therapist like they look at wounds, they won't touch them and we've got to stop that process because it's all integumentary dysfunction. And we know that once we start complete decongestive therapy, which we will talk about, those wounds resolve very, very quickly because it's just a matter of fluid overload. Okay, I've got to hurry. So what I want to share with you here is just some pictures. You've seen these. These look like all your patients, yeah, pretty much, okay. So [Indecipherable] [0:17:43.1] looked at the morphological changes of dermal blood and lymphatic microcirculation by taking skin biopsies in patients with CVI and venous stasis dermatitis and what he found is that the blood vessels had occluded lumen thickening and reduplication of the basement membrane. And in the dermal lymphatic vessels, what they found was the lumen was collapsed in these small tiny lymphatic capillaries. There were some complex interdigitations between the contiguous endothelial cells and there was a lack of open junctions. And more importantly, there was a derangement of those anchoring filaments. So those structures that are supposed to pull to open up those lymphatic capillaries weren't working anymore. They were like rubber bands that got stretched past their breaking point. So again you can start to appreciate that pathophysiology and interconnection. Sorry, we'll move back here. So what I want to point out here is this is some new emerging technology using ICG, which is indocyanine green with near infrared fluoroscopy and in real time, we can watch the uptake and map the lymphatic system. So here is the patient with classic chronic venous insufficiency. This was just the injection site. So this is not a wound. And you can see the uptake, but what you see here, what does that look like? Is that like proximal flow? That’s dermal back flow. Those lymphatic capillaries are not functional here. And in particular, what you can note is in areas around where this patient had a wound, look at the dermal back flow around that wound. A lot of stagnation, so even in wounds, even wounds that are not really maybe even related to CVI that arterial wounds or pressure injuries, what we're seeing is dermal back flow. That system is overwhelmed but those vessels become deranged and they don't become functional. So this is a great new technique. It's going through FDA approval now, but I think we're going to learn a lot from this because you can see in real time the lymphatic fluid uptake. Now, this is something too that I want you to remember. All edema including chronic venous insufficiency is actually a secondary lymphedema. All of you are familiar with the CEAP-classification, right? So all of your patients that end up at C3, these are really phlebolymphedema patients, again because of that interconnected relationship.


    Now, Hammond way back in 1991 showed that 75% of his patients looked at of extremities with CVI had abnormal lymphoscintigram and [Indecipherable] [0:20:16] in 1998 also showed 79% of the patients he looked at had an abnormal lymphoscintigram and you see that same presentation here. That’s that dermal black flow. So we've known this a long time. We just haven't been calling it phlebolymphedema. I will skip that part for now if it will let me. There we go. So again lymphedema results in chronic inflammation and a very stagnant wound milieu, so that’s a problem. Stagnating high protein edema develops a pathohistological state of chronic inflammation with infiltration of all these different cells and structures leading to fibrosis and fibrosclerosis. Oxidation and degradation of interstitial proteins actually tracks more monocytes to the area that change into macrophages. These hopefully ingest proteins and activate fibroblast that, in turn, form collagen, which result in that connective tissue proliferation, that fibrosclerotic changes we start to have. And another important thing is to remember this also triggers our adipocytes, right? And those are actually hormone producing tissues. So it leads to more fatty tissue proliferation as well in these patients and later, we will talk a little bit about lipedema, which is separate. But I think it's important to remember, all edema indicates an inadequacy or failure of lymphatic drainage and lymphatic failure is responsible for all forms of peripheral edema. That’s a really big paradigm shift and what we're used to saying, but that’s really important thinking point. So I'm going to stop here. We're going to have questions at the end. I have two minutes. Okay, I have two minutes if there are any questions on what we just covered. You can Google or go to YouTube and type in that ICG, near infrared fluoroscopy and you can see some work done by Eva Sevick-Muraca and Rasmussen to actually see that lymphatic uptake in real time, it's very, very interesting, but it's going to help us understand how to route the fluid better and help us get an appreciation of where the congestions are really residing. Yes, Steve, okay, sorry. Thanks for saying something. We will talk about the CEAP classification in a little bit, but it's how we can kind of classify venous pathology. It looks at clinical presentation. It looks at etiology, anatomy and pathophysiology. That’s what the CEAP stands for. What's kind of a new thing that people are starting to appreciate is that when you classify people and they are starting to show edema at that C3 level, that’s really a phlebolymphedema and that’s kind of new change in thought. Great question. How does bouncing on a trampoline effect lymph drainage? Again, it's that rhythmic contraction because the system works off of a siphoning effect. So when you contract muscles in a gentle supported way that’s not really aggressive or causing a lot of rebound, you are actually stimulating lymphatic flow. So I'll give you some tricks because we're going to talk about what do you with these patients when you're not a certified lymphedema therapist, right? I don't have time to get certified. I don't want to get certified, whatever the reason is. We'll give you some take-home points, but what they call the rebounding on those little mini trampolines is a very effective modality. Yes, diaphragmatic breathing. Pilates, yoga, absolutely. Diaphragmatic breathing is probably one of the most important things you can teach your patients how to do. Most people don't know how to breathe, right? We take it for granted. Most people don't know really how to belly breathe. So if you take the time to instruct them on diaphragmatic breathing, they will start to see a reduction in their edema. Might be subtle, but they will start to see a reduction. The reason being is the largest lymphatic vessel, your thoracic duct pierces your diaphragm, and because this system -- the entire lymphatic system works off as suction or siphoning -- when you stimulate that the whole system works faster and more efficiently. So something is basic as diaphragmatic breathing and really making sure they know how to do it properly can make a big difference for your patients. I'm glad you brought that up.