Possible casues of long term edema after the most common causes have been ruled out?

[Chanasky]

If a patient has long term generalized edema (w/pitting in the legs), what are the other possible diagnostic alternatives, after heart, kidney, liver and protein abnormalities have been ruled out? I've been struggling with this edema nonsense for several years, unremitting, and yet my docs are stumped when it come to diagnosis. I also have some GI motility and hormone stuff happening but they claim there's no connection between the two. However, I do notice that when the gastric system seems to be working, the fluid is much less pronounced and I wind up having a day where I urinate much more often, eliminating much of the excess. But it soon returns again, often within a day or two

I'm 45 yr old male, no diabetes, thyroid usually normal range but flagged as very mildly hyper on a few occasions, and low BP. I was very thin prior to the fluid retention, which averages between 20-30 pounds, by my estimation. I was also otherwise healthy and active prior to these symptoms, but since becoming ill, I am often very fatigued and sleepy most days.

I'm posting in heart forum because I realize that this type of fluid retention is often associated with heart failure, specifically right side failure. As far as I'm aware, though, based on echo, stress test and labs, I'm okay in that dept. Not sure where to turn for help at this point and am very confused

[achillea]

Shock:  By definition, shock is a medical emergency.  It causes an immediate and dangerous fall of blood pressure, and then a racing heart as the body attempts to keep oxygenated blood going to vital areas.

A sudden, wholesale leaking of blood vessels could cause shock, depleting blood volume catastrophically, but general, low-grade leakiness does not have this effect..

So, no, there is no mild form of shock, but you do have a grip on the basic concept.

You ask if a gut inflammation can cause a widespread systemic inflammatory response.   I’ve never heard of that, but the reverse—a widespread inflammatory response that can affect the gut--does happen.  Regarding that, I have sent you a medhelp message.

[Chanasky]

That description almost sounds like sepsis or some form of shock. Would it even be possible for me to still be walking around for years like this, if my body was constantly stressed to that degree and in some form of low grade shock? I do feel awful most days.

Also, the edema/dryness never truly resolves and returns to normal. But there are some days when it's slightly improved, and on those days, the dryness and fluid imbalance seem to even out a bit. Dried out looking hands and skin and the dehydrated mucus membranes seem as though they rehydrate, albeit only temporarily. It's a wonderfully relieving sensation that is often short lived, sad to say. I feel like a wilted plant that finally gets hosed down with some much needed water.

Aside from these fleeting moments of balance, though, it seems like the condition is fairly chronic condition.

In terms of that inflammatory response, is it possible, in theory, for a severe chronic gastric inflammation to cause a widespread systemic inflammatory reaction? When my gastro took a look inside my stomach, he was alarmed by the degree of inflammation going on in there. It was fairly severe according to him. I had a small isolated patch of inflamed colon too, but not ulcerative colitis or anything like that. It seems that my GI system, in general, is very inflamed and irritated

[achillea]

Though I’ve studied anatomy and physiology, I don’t have a specialist’s detailed knowledge, but a simplified explanation is that an inflammatory response to a pathogen or to an allergen, for example, causes white cells to become activated.  Part of their defense is the release of inflammatory mediator substances like histamine, which causes vasodilation.  Vasodilation makes the walls of blood vessels become leaky, and fluid (water and proteins) oozes from them into the tissue spaces; this fluid makes it easier for disease-fighting white cells to get around to do their job.   If the infection or inflammation is very widespread, fluid may leak into tissues everywhere, causing general instead of local edema.

However, the presence of protein and other substances in the tissue spaces is in a sense ‘attractive’ to water, and the more protein and inflammatory material there is in the tissue spaces, the more water is drawn out from the now-leaky blood vessels and surrounding tissues.

In the case of a general, inflammatory condition, much-needed water may be drawn out of local body tissues by this osmotic attraction, leaving them in a sense high and dry, surrounded by edematous fluid they cannot use to rehydrate.

Your observation about having skin or mucous membranes feel ‘dry’ yet capable of rapid rehydration is a worthwhile one.  Hang onto it, and when you see a thoughtful diagnostician, don’t be shy about mentioning it.  Your body seems to have the ability (at least now and then) to rapidly shift liquid from one space or compartment to another.  I do not have a ready explanation for this, because it does not fit well with the idea of general inflammation.

There are pituitary hormones, however, that can have quite a rapid effect on water movement, and since it sounds as though you may have secondary hypogonadism, I think that an investigation of your pituitary function is warranted.

Sadly, your doctors’ inability or unwillingness to relate your symptoms and lab work is probably a sign of the times:  Not enough time and not enough money to do a really thoughtful assessment of a patient whose life is not obviously in danger.  You need an extraordinary diagnostician, someone capable of looking at the whole picture, because in my opinion, the likelihood that all your symptoms are *unrelated* is pretty small.

[Chanasky]

One more thing, achillea. Would you mind going into a bit more detail about the possible causes behind the "inflammatory response" you describe, the one that causes cellular dehydration and leaky vessels?

When this edema is out of control and raging, I feel incredibly dried out (that's the only way I can describe it). I'm not exactly thirsty, per se, but my mouth and mucus membranes are bone dry to an uncomfortable degree. Initially, when I first stated experiencing this dryness, especially in the mouth, I thought I was dehydrated and so I tried to drink more water, despite the lack of thirst. But eventually I realized that extra water wasn't doing the trick and that actual dehydration wasn't my problem.

It's more of a drying effect. The skin on the back of my hands, for example, looks like I have aged 30 yrs and I often develop temporary body rashes/itching due to the generalized dryness. The moment the edema/inflammation improves, however, this generalized dryness improves markedly and all the wrinkled looking skin and dry patches fill out and smooth over.

I've tried to explain this phenomena to my docs but they just shoot me quizzical looks, so these days, I barely mention it when I'm at an appointment for fear of sounding kooky. Truth be told, though, this symptom was one of the first I recognized years ago. I just blew it off at the time thinking it was just a benign oddity or perhaps mild dehydration.  Little did I know.....  

[Chanasky]

Actually, I have had many CBC differential tests performed over the years and the Monocytes and Neutrophils are always elevated, in addition to the overall WBC count that I mentioned. In fact, of the 15 or so lab reports I have on hand from these past few years, not a single case of WBC or subtypes within proper/normal range. They're always elevated. In isolation, I guess a case could be made for minor infection or something along those lines, but after years of consistent abnormalities like this, I too believe that it offers a clue to my problem, especially when considered alongside the edema and other symptoms.

When I first began exhibiting the symptoms, my total WBC count was over 20,000 and the docs suspected possible leukemia, so I was sent to a hematologist who performed a more detailed study. But as has been the case with most abnormalities that they've found, the blood cell issue was never considered alongside the other symptoms (edema, weight fluctuation, hormone, GI inflammation, etc) and soon forgotten, put into the background to focus on some other abnormality.

The most recent CBC I had four months ago once again flagged total WBC as high (13,000) with flagged neutros and monos. Same exact pattern but different report. The seeming inability of the docs to consider the symptoms and abnormalities together, as a whole, and follow through to a diagnosis has been a problems for me from get go. They seem to chase after the latest symptom and then drop the ball when a new one emerges or is discovered or sometimes they backtrack and chase after individual lab abnormalities from the past, which is quite maddening to me, as a patient. I don't need to have extensive medical training to know that such an approach is doomed to failure from the start. This is what led me to consider a teaching hospital

Thanks, again, for your input. It's extremely helpful

[achillea]

After reading your last post, I very much doubt that your edema is caused by or even related to a sedentary lifestyle.

You mention a couple of important things:

One is that your white cell count runs 13K-15K, which is indeed high, not astronomically high, but considerably outside the normal range.  That is meaningful, because white cells increase in number for a reason.  It’s not random.

There are five different types of white cell, each with different functions.  Some attack infectious agents like bacteria and fungi: some go after viruses or cancers; some are there in response to allergy; some are involved in inflammatory or autoimmune conditions; and some do ‘cleanup’ duty.

A differential count would let your doctors know which white cells were outside the normal range, and their relative numbers--and ages--would give even more specific info about the likely causes for the increase.

Personally, I would not rest until this white cell question was fully addressed--and addressed by a specialist.

Inflammation causes cells to become leaky:  water seeps out into the tissues.  You can see this on a small scale whenever you get a skin infection or an allergic reaction, but it’s possible to have it on a large scale, too.  It can cause cellular dehydration, which might be involved in the thirst you describe.

There are medical conditions, some of them pretty tricky to diagnose, that can cause a much more generalized inflammatory response.  Among these are lupus, sarcoidosis, and histiocytosis.

For these reasons, I think your lab work should include a test for something called c-Reactive Protein, which looks for markers of inflammation.  It is a more discerning test than the Sedimentation Rate.

Testosterone levels that are extremely low for one’s age (probably ‘secondary hypogonadism’  in your case, unless you have had cancer/cancer treatment) also usually have an identifiable cause and can result from pituitary disorders and *some inflammatory diseases,* including several that I mentioned.

All in all, if you can swing it financially, I believe it would be worth it to go to a serious medical center to get yourself really checked out.  If I were in the same situation, it’s what I would do.

[Chanasky]

Thanks for your very comprehensive response.

My albumin levels are normal, as well as the overall protein. I actually increased my dietary protein intake after the edema started because I knew about the connection between the two. I'm aware of nephrotic syndrome but I'm assuming I don't have it based on normal metabolic panel and 24 urine collection that showed no extra protein losses. I could be wrong about this, though, as I'm obviously not a doctor

Yes, ticker has been checked, I'm assuming quite thoroughly, by cardiology team with echo, EKG, lipids, etc and all seem perfectly normal, although I do have evidence of very mild MVP with trace regurgitation. I don't experience any breathing issues or episodes of breathlessness, aside from the diaphragmatic pressure caused by this extra fluid, and I definitely don't experience any breathing problems during the evening, while lying down. My abdomen these days looks quite distended thanks to the extra fluid/weight, but it does deflate occasionally, on the rare day when I release fluid through urination

In regards to your questions about the edema during the evening, while sleeping: yes, the edema does, in fact, decrease to some extent, during the evening, but it never resolves to any appreciable degree. I still awaken weighing around the same as I did when I hit the sheets. If anything, the edema seems to redistribute itself more evenly during sleep, with less prominence in the lower legs. I notice too that I get up several times during the evening to relieve myself, as the fluid appears to reenter my circulatory system when I lay flat, during sleep. Even if I just lay down horizontally, while awake, I'll tend to urinate more often than if I am standing or sitting vertical. Prior to the edema, a few yrs ago, I was an extremely sound sleeper and can't remember even a single instance during adulthood, whereby I got up during the evening to urinate.

According to my GP, who I tend to trust, my edema is of the "third spacing" type in that it's fluid leaked from the vascular system into subcutaneous layers beneath the skin, where it remains "trapped". My edema is generalized throughout my entire body, not just the legs, although the lower legs are the only location where it "pits"/intends after pressure is applied. When the water retention is at it's worst, I am often paradoxically very dried out and feeling very dehydrated (mucus membranes, no sweat, dry lips mouth, less urinary output, etc). Blood pressure is often very low, as well, somewhere around 110/60 and lower.

The other health issues that began at the same time as the edema are hormone problems (extremely low free and total testosterone level), chronically elevated white blood cells (usually within 13-15,000 range- never lower) and lots of gastrointestinal issues. My gastro doc found possible evidence of gastroparesis/leftover food in my gut, during an endoscope, as well as severe inflammation in my stomach/erosive gastritis, despite testing negative for H Pylori. These days, I probably consume half the calories than I did when I was well, due to lack of appetite.

I was a naturally lean person prior to the edema and most of the weight gain seems to be primarily from fluid (i went from 6ft/180 to today's 220-230 depending on how much fluid I am carrying). I am not diabetic and prior to developing this weird syndrome, I was a very healthy and active person, or at least I felt very healthy

Also, although I do have a "desk job", so to speak (graphic design), I do try to walk quite a bit. But I've lost quite alot of energy and stamina with this illness. If I could, I would probably sleep much longer and take naps during the day to fend off exhaustion. When you mention the idiopathic edema from sedentary lifestyle, are you talking about a generalized edema or just edema in the lower legs from poor vein circulation, similar to problems of obese people?

I must admit that my activity levels have decreased considerably since becoming ill thanks to low energy. I could definitely stand to add some extra physical activity to my daily routine. Unfortunately, however, whenever I've attempted any significant exercise schedule over the past few years, I usually wind up feeling exhausted afterwards and the edema actually increases to some degree. I guess I could try it again, though. I'm a former long distance runner, so exercise routines and training aren't alien concepts to me. I just don't seem to have the extra energy these days

The only med I take is a .25 mg nighty dose of Kolonopin for anxiety and sleep, which have both become a problem since these symptoms manifested

Sorry about my lengthy post, but I'm trying to answer the questions as comprehensively as possible. Again, I really appreciate the feedback. The only people I communicate with about these chronic health problems are the docs and close family members. Most of my friends think that I've simply put on weight and become antisocial, not realizing that I have been struggling w/ an undiagnosed condition for several years now. So far, none of the docs I've seen can offer me any clear answers or explanation, particularity for the edema, which is quite alarming to me. My next step, if all else fails, is a teaching hospital like The Cleveland Clinic

[achillea]

Well, when you see pitting edema, the first things you think of are indeed heart,  kidney, and liver problems.  Apropos of the last two, has your lab work ever turned up 'hypoalbuminemia'?  Has anyone ever mentioned 'nephrotic syndrome' to you?

Your ticker has been checked out thoroughly, right?  If it has been found to be in good shape, the chances are that it IS in good shape, because there's nothing subtle about right heart failure.

I gather you don't have congestive heart failure, either.  It causes not only swollen limbs but difficulty breathing when you're lying down.  You'd notice that.

Here are a few questions that might help clarify what's going on:  Does the pitting in your legs go away during the night when you're lying down, only to return and get worse during the day when you're mostly upright?  Or is it present when you wake in the morning, even before getting out of bed?

You mention 'hormone stuff.'  It might be useful to know what kind of hormone stuff, because some hormones can affect water balance.

Regarding edema, the bottom line is that it is usually caused by too much salt in the body, which causes water retention.  Interestingly, one contributing factor to that can be hypoalbumineria, in which too little protein (albumin) is being kept on board.  There are various causes--one of them being starvation--and you might want to google the term.

When all else fails, there is a catchall diagnosis of 'idiopathic edema,' which is used as a last resort, hopefully after all diagnostic tests have been done.  You can google that term and read up on it, for there is treatment, though it has to be done thoughtfully.

You mention that 'since you became ill,' you are often very fatigued and sleepy.  By 'becoming ill,' are you referring to this tendency to retain water, or do you have some other illness?

I ask this because, in the absence of some definable illness or organ failure, idiopathic edema can be caused by a sedentary lifestyle.  In talking about returning blood from the periphery to the heart, we refer to the 'muscle pump.'  The fact is that veins, which return blood to the heart under low pressure, have no pumping ability themselves.  They've got little 'cup valves' that help prevent pooling, but the real engine for getting that blood uphill is muscular activity.  So if you are not actually sick right now, if you are not anorexic, and if all your other organ systems are OK, it is just possible that increasing your activity level gradually might help mobilize the extra fluid.