Follow @beeheron Shock, Hypoxia & ME/CFS: Part II Summary Numerous lines of evidence implicate problems with blood flow or oxygen delivery in ME/CFS. HIF-1 is the master regulator of the body's response to diminished oxygen delivery and is upregulated under low oxygen conditions. HIF-1 downregulates mitochondrial energy production and upregulates glycolysis in an effort to protect cells from the adverse effects of oxygen deficit. In a chronic low oxygen state, chronically elevated HIF-1 could account for a low metabolic state resembling hibernation, could account for “deconditioning” and could account for post-exertional malaise (PEM). We will take a look at models of chronically elevated HIF-1 as well as genetically reduced levels of HIF-1. In addition, chronically elevated HIF-1 could potentially be related to increased rates of cancer and autoimmunity in ME/CFS. Ron Tompkins, HIF-1 and Trauma Dr. Ron Tompkins, MD, ScD, is one of our researchers on the scientific advisory board of the Open Medicine Foundation (OMF). He is chief of the Trauma, Burns and Surgical Critical Care Service at the Massachusetts General Hospital, chief of staff at the Shriners Hospitals for Children in Boston and a professor of surgery at Harvard Medical School.  We are so incredibly blessed to have people like Dr. Tompkins working to find answers for ME/CFS patients. Dr. Tompkins specializes in finding new ways to treat patients who have suffered burns and major injuries. These critical injuries are collectively known as trauma. Interestingly, he thinks there may be a connection between trauma and ME/CFS. On his OMF page, it says: “There seems to be a relationship between trauma and ME/CFS, possibly being triggered by or putting the body into a constant state of trauma.” This is an interesting statement because trauma involves bodily injury, but also involves circulation problems [...]

Follow @beeheron Shock, Hypoxia & ME/CFS: Part I When I first got sick with ME/CFS, I was a teenager. I was quite baffled when I suddenly became too exhausted to make it to classes, stopped sleeping almost entirely and started sweating profusely. I sweat raindrops: huge drops of sweat rolled down my sides constantly. No antiperspirant was a match for the sheer quantity of sweat I suddenly began producing. I became pale and weak and developed extreme anxiety, a rapid heartbeat and a feeling that I needed to breathe more. These are weird symptoms and I want to talk about how much they look like a condition called shock, especially given the similarities between ME/CFS and sepsis that we have talked about in recent blog posts. What Is Shock? According to Wikipedia, “Shock is the state of not enough blood flow to the tissues of the body as a result of problems with the circulatory system.” Symptoms of shock include palor, fast heart rate, fast breathing, weakness, anxiety, sweating increased thirst and confusion. This encompasses a lot of how I felt when I first became very ill. The lack of blood flow to the body causes the body to orchestrate an emergency response to try to get blood flow restored at least to the most vital areas of the body. The symptoms of shock arise from a combination of the blood delivery problem itself and our physiological response to that problem. In shock, adrenaline and other stress hormones are released to close off blood flow to less important areas of the body, like the skin and muscles, and redirect it to the heart and the brain, the most important parts. Adrenaline is our hormone of panic. Adrenaline stimulates the body’s “fight or flight” [...]

Follow @beeheron Part II: ME/CFS, Sepsis and Glycocalyx Summary To recap from the previous blog post "Part I: Blood Flow in Sepsis & ME/CFS", ME/CFS looks like a lot like sepsis and sepsis is an inflammatory illness of blood vessels. The blood vessel problems in sepsis interfere with oxygen delivery to cells.   The particular kind of blood flow problem that you find in sepsis is often described as “heterogeneous perfusion.” In heterogeneous perfusion, blood flow is normal through some capillaries, but in neighboring capillaries, blood flow might be slowed or stopped. In both ME/CFS and sepsis, we say that there is a problem with “oxygen extraction.” Cells have trouble accessing and using oxygen from the blood to make energy. Heterogeneous perfusion is known to cause problems with oxygen extraction. Glycocalyx, an important material that lines the inside of blood vessels, is destroyed during sepsis and destruction of glycocalyx leads to heterogeneous perfusion. The loss of glycocalyx might unite seemingly disparate aspects of chronic fatigue syndrome, like the fact that the illness seems to have so many different causes. There may also be an intersection between mast cell activation syndrome and glycocalyx. Glycocalyx loss could shed light on the connection between low blood volume and ME/CFS. Go To > Part I: Blood Flow In Sepsis & ME/CFS Glycocalyx A material called glycocalyx that lines the interior of blood vessels is extremely important for preventing heterogeneous perfusion. Glycocalyx is lost because of inflammation during sepsis and its loss is directly related to problems with capillary function that you find in sepsis. Glycocalyx is a fuzzy, loose, jelly-like substance. For a long time, until imaging techniques improved, we had no idea that glycocalyx took up so much space inside blood vessels. When we saw how much [...]

Follow @beeheron Part I: Blood Flow in Sepsis & ME/CFS Summary A blood flow pattern known as heterogeneous perfusion is found in sepsis. ME/CFS bears a striking resemblance to sepsis. We share peculiar problems with low blood volume, low blood pressure and trouble with pulling oxygen out of the blood to use as energy. Could correcting this pattern of blood flow lead to treatments for ME/CFS patients? ME/CFS looks like a slow, chronic sepsis, says Dr. David Bell, a longtime ME/CFS physician.  He made this observation after decades of treating patients. At this year’s Open Medicine Foundation symposium for ME/CFS patients, carers and researchers, one of the scientists who spoke held up Dr. Bell’s book and indicated that Dr. Bell was really onto something. Sepsis is a dangerous illness that occurs after a huge inflammatory response to a bacterial infection. Forty percent of people with sepsis die.  We ME/CFS patients don’t often die of our illness, but in other respects, we look strangely similar to sepsis patients. Like sepsis patients, we tend to have remarkably low blood volume, which means that the total amount of blood we have in circulation is low.1,2 This is a weird symptom not found in very many illnesses. Along with low blood volume, we also tend to have very low blood pressure, just like sepsis patients. My blood pressure often hovers around 84/54, a level of blood pressure you might find in a septic patient. ME/CFS, like sepsis, often starts with an infection, though this can be bacterial, viral or possibly parasitic. We used to think that people died of sepsis because of the huge inflammatory response.  This is correct, but more specifically, people die of sepsis because this huge inflammatory response causes damage to blood vessels [...]

Follow @beeheron Why Does ME/CFS Look Like Sepsis? Summary ME/CFS looks like sepsis.  Sepsis on the surface is an illness caused by massive inflammation.  At its core, however, sepsis is an illness of blood vessels. In sepsis, inflammation wreaks havoc with the function of our tiniest blood vessels, impeding blood flow and interfering with the delivery of oxygen to tissues. Nitric oxide is a tiny molecule that helps hold small blood vessels open so that blood can flow through them. My ME/CFS and autism symptoms improve with agents that increase nitric oxide. Other patients have also seen improvement. I developed Mast Cell Activation Syndrome at the same time that I developed ME/CFS. Mast cells are located in and around blood vessels and can be activated by changes in blood flow and blood flow deprivation.  Is this the cause of MCAS? Mast cells can cause blood vessel damage that resembles the blood vessel damage in sepsis. Can chronic mast cell activation look like chronic, mild sepsis? At the level of blood vessels, hemorrhage, the sudden loss of blood, causes damage that looks like the damage that sepsis causes. ME/CFS patients have chronic low blood volume. Does having chronic low blood volume cause chronic, mild damage to the blood vessels in a way that could give rise to an illness that looks like chronic, mild sepsis? Glycocalyx is a material that lines the blood vessels.  Glycocalyx helps keep small blood vessels open by releasing small amounts of nitric oxide. Inflammation causes it to dissolve during sepsis, causing the blood vessel problems that you find in sepsis. Glycocalyx can be destroyed by mast cell activation, systemic inflammation, psychological stress, blood volume loss, and major injuries. All of these events have been linked to ME/CFS. ME/CFS and sepsis look like hibernation at a cellular [...]

On Autism & Chronic Fatigue Syndrome When I was in second grade, a little girl started calling me Weird One. I was elated. I felt that I had been knighted with some sort of public identity and it felt wonderful. I felt as though I belonged in some way and I hardly ever felt as though I belonged at all. That same year, classmates pointed out to me that I stood strangely.  I had no idea.  Looking down at myself, I realized that my hands were drawn up as if holding dangling dust rags, poised to begin cleaning the house. Knees bent backward, stomach poking out much more than normal for an eight-year-old, more like a two-year-old. I had no idea my posture was this awkward until another child pointed it out to me. I made a point of monitoring my posture from then onward. The year before, as a first grader, I couldn’t understand the game played the entire year where all the little boys and girls pretended they were boyfriend and girlfriend, a merry-go-round of who was currently “going out” with whom. I took stock of the situation quite seriously and determined that I was not actually romantically attracted to any of the boys.  I decided therefore that I must be gay, barely knowing what gay was, but knowing it had something to do with not being attracted to the opposite sex. It’s not that I was gay; I grew up to marry a man. But I couldn’t naturally understand the games that other kids played any more than I would naturally have been aware of standing abnormally. My parents pushed me to call other children on the phone to arrange play dates, but I was terrified. I was happy enough playing by myself, working on intricate [...]