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” danger response, spurs the heart to beat faster in order to pump blood around the body more rapidly and causes anxiety & sweating.

ME/CFS & Three Different Kinds of Shock

ME/CFS intersects with shock in several interesting ways.

The first is that ME/CFS looks rather like sepsis. Sepsis is a inflammatory disorder of blood vessels that impedes blood flow to tissues. At a some point after the onset of sepsis, we say that the patient has septic shock, which means that their blood flow to tissues has taken an obvious hit.

If ME/CFS looks like “slow, chronic sepsis,” as suggested by Dr. David Bell, one of our longtime ME/CFS physicians, does it also look like slow, chronic septic shock?

A second connection to shock is that ME/CFS patients have chronic low blood volume and low blood pressure. My blood pressure is often at a level you would find in septic shock.

Hypovolemic shock is kind of shock that arises after a substantial loss of blood volume.  The loss of blood can be through hemorrhage after an injury or can be from various sources of dehydration. Without enough blood to fill blood vessels, blood pressure can drop dramatically.

Having a less than normal amount of blood in circulation leads to shock because without enough blood you can’t  maintain blood pressure and without enough blood pressure you can’t keep blood vessels open and flowing and tissues fully supplied with blood.

A third connection is the overlap of Mast Cell Activation Syndrome (MCAS) and ME/CFS. When I first got sick, I suddenly developed MCAS. MCAS is a condition in which a strange little immune cell called a mast cell constantly overreacts.  A lot of us with ME/CFS also have MCAS. It makes us feel quite ill and can cause symptoms like becoming allergic to numerous foods.

When mast cells activate suddenly and in an overwhelming way, they can trigger anaphylaxis, which can then lead to anaphylactic shock.  During anaphylaxis, mast cells release agents that cause water to be leaked from the blood resulting in lower blood volume and cause blood vessels to become floppy so that the body has trouble pushing the remaining blood out to tissues. Cells starve for blood in a way that is similar to hypovolemic shock.

When an ME/CFS patient has MCAS, does their condition also resemble a slow, chronic anaphylactic shock?

If during the early stages of my illness I experienced a drop in blood volume and blood pressure from a condition resembling sepsis or anaphylaxis or another unknown cause, might it have triggered a nervous system response that resulted in sweating, palor, anxiety, and rapid heart rate? Might I have felt weak because I was in shock anyone in shock would feel similarly weak? Was the adrenaline release the reason why I stopped sleeping almost entirely?

Most ME/CFS patients have poor sleep. Anecdotally, saline IVs that restore blood volume can allow ME/CFS patients to sleep soundly.  Is this because body no longer needs to release adrenaline to ensure that blood reaches the brain?

My blood pressure is often at 84/54 and seldom a great deal higher. This is a level of blood pressure that you might expect to find in patients with shock. It has been this way since I got very sick at sixteen.

I propose that this level of blood pressure itself may cause slow, chronic shock.

Shock, Blood Flow & HIF-1

What’s the problem with shock? It may have everything to do with the metabolic switch that seems to occur in our illness. It may explain why we suddenly fall off the edge of something. So many of us were normal and then suddenly were not. We were normal and then suddenly we are exhausted all the time, forever.

Shock, that state of not having enough blood flow to the tissues of the body, triggers the increase of a very particular molecule called hypoxia inducible factor -1 (HIF-1). HIF-1 increases whenever there is a problem with blood flow to and oxygenation of tissues. It is the master regulator of the response to low oxygen levels in the body. HIF-1 is not a regulator among many regulators. It is the master regulator of the body’s orchestrated response to low oxygen levels.

HIF-1 reduces mitochondrial function as part of a coordinated response to protect cells from low oxygen levels.  Reducing energy production via the mitochondrial pathway reduces the explosion of oxidative stress that would occur in mitochondria if they were to continue to produce energy without enough oxygen around.

To accomplish mitochondrial shut down, HIF-1 decreases the function of an enzyme called pyruvate dehydrogenase (PDH). Blocking PDH function denies materials to mitochondria that they use produce energy.

Øystein Fluge and Olla Mella are our Norwegian researchers who patented agents that increase nitric oxide as potential treatments. Fluge and Mella ran an experiment that tested the metabolisms of 200 ME/CFS patients and pinpointed PDH inhibition as the point where metabolism breaks down for us.

In a separate study, Dr. Wang at Stanford University found that the metabolism found in the cells of ME/CFS patients is most like the metabolism found in cancer patients. In cancer patients, a type of energy production called glycolysis is ratcheted up to astronomical levels. This is called the Warburg effect.

HIF-1 increases glycolysis and is strongly implicated in the Warburg effect in cancer.

In other studies, Ron Davis at Stanford and Fluge and Mella have suggested that the factor causing energy production problems is found in the serum, the clear portion of the blood, and whatever it is, it is large at over 100 kilodaltons in size.

HIF-1 is actually made up of two molecules: HIF-1α and HIF-1b. HIF-1b is found at steady levels inside cells.  It is the HIF-1α part of HIF-1 that increases in low oxygen conditions and then joins with HIF-1b to make fully functional HIF-1. HIF-1α is found in the serum under pathological conditions and is over 100 kilodaltons in size.