From Stress to Inflammation to Chronic Disease…?

This is part 3 of a series of blog posts discussing the ins and outs of stress: what it is, when it’s helpful and when is it harmful, how to optimize your stress response, and some strategies for living with a caveman nervous system in a modern, stressed-out world.

The Importance of Understanding Stress

Understanding Stress

If you’re just joining us now, this is part 3 of an ongoing series all about stress. You might want to check out part 1 and part 2 to get up to speed, because we are going to jump right into discussing what happens when our bodies spend too much time in sympathetic mode, and not enough time in parasympathetic. This will set the stage for understanding how chronic stress can “kill”, and with a firm understanding of how our stress response system works, we will be better able to train our stress response to work for us, instead of against us.

Sources of StressAs previously discussed, stress defines the body’s reaction to life’s inevitable challenges, or stressors. These stressors can be physical (i.e. illness, injury, pain, etc.) or psychological (strong emotions such as fear and worry), and they can be real or imagined. In any case, all stressors elicit a similar response from the body, termed sympathetic or ‘fight or flight.’ Stressors are quantified by their ability to throw your body out of allostasis (homeostasis), and while all stressors activate our ‘fight or flight’ response, some do so more than others. In particular, the more a person fears a particular stressor, the stronger the stress-response elicited when exposed to that stressor. The stressors which we believe to be the most harmful, end up eliciting the strongest stress-response in our bodies.

You don’t need to be a neuroscientist to understand the stress response. However, after teaching anatomy and physiology for over a decade, I’ve observed that people who understand the basics of what’s happening on the cellular level when they are “stressed out” or sick, are more successful at re-training their nervous systems to break free from sympathetic dominance and associated diseases. So hang in there, because we’re about to take a little trip down psychoneuroimmunology lane.

The Stress Response is a Neuroendocrine Response

Endocrine system anatomy

Endocrinology refers to the study of hormones, so whenever you see the word ‘endocrine’, you can just think ‘hormones’. In my last post I talked about the nervous system’s role in the stress response, specifically the sympathetic nervous system’s role in the fight or flight response. The stress response is more accurately described as a neuroendocrine response because it involves both the nervous system and the endocrine system sending chemical and electrical signals back and forth, resulting in the release of hormones which mediate the stress response at the cellular level. The stress hormones that are largely responsible for the physiological changes observed during fight or flight (i.e. increased heart and breathing rate, decreased digestion and healing, etc.) are epinephrine (adrenaline), norepinephrine (noradrenalin), and cortisol.

The hypothalamus is the region of the brain that links the nervous system to the endocrine system via the pituitary gland. The hypothalamus is a major part of the limbic system (also called the paleomammalian brain), which plays important roles in the stress response, as well as in emotion and memory. The adrenal glands sit atop each kidney, and are subdivided into an inner region (the adrenal medulla) and a surrounding outer region (the adrenal cortex). The adrenal glands release epinephrine and norepinephrine from the inner adrenal medulla, and they release steroid hormones (like cortisol) from the outer adrenal cortex. The HPA axis is a complex negative feedback loop relationship between the hypothalamus, the pituitary gland, and the adrenal glands, which work synchronistically to mediate the neuroendocrine stress response. The HPA axis also plays a significant role in the ongoing, chronic stress response.

Acute Stress

As discussed in part one of this blog series, stress can be either acute (short-term) or chronic (long-term). Our bodies are fully equipped to handle acute stress, which is essential for our survival. Chronic stress, on the other hand, is what the saying “stress kills” is referring to, and its basically an acute sympathetic stress response that won’t turn off. Chronic stress (not acute stress) has been correlated with a host of different stress-related diseases and symptoms. Chronic stress and sustained psychological stress are relatively new innovations, evolutionarily speaking, and our primitive stress response systems are simply not evolved enough to deal with them effectively. As it turns out, there’s a bit of a problem when we spend too much time with our sympathetic nervous system stuck in ‘fight or flight.’

Adrenal gland anatomyDuring the acute stress response, the sympathetic nervous system (SNS) and HPA axis are active, and we are said to be in ‘fight or flight’. In response to an acute stressor, the adrenal medulla starts pumping out epinephrine (adrenaline) and norepinephrine, and neurons in the hypothalamus initiate a complex cascade of hormones that ultimately result in the release of cortisol from the adrenal cortex. Cortisol is a powerful natural steroid that plays a major role in the stress response by mobilizing glucose into the bloodstream in preparation for intense exercise. Akin to the other corticosteroids, cortisol suppresses immune system function and is anti-inflammatory by nature. The end result of acute stress hormone production is a temporary increase in available energy, which the body can then utilize to quickly ‘fight or flight’. This, of course, comes at the expense of bodily processes that are not required for immediate survival. When the stressor is removed, the body returns back to its baseline (homeostasis).

Chronic Stress

Fight or Flight organs
When the stress response becomes chronic, the levels of stress hormones in our blood remain continually elevated, never returning to their baseline. High concentrations of cortisol, epinephrine, and norepinephrine in the blood further amplify the symptoms of fight or flight: increased blood pressure, elevated heart rate, increased blood sugar, sharpened senses, decreased immunity, etc. These symptoms are not a problem in the short term, in fact they are a key reason why humans have managed to last this long on planet earth.

When the symptoms of fight or flight become chronic however, they can predispose the body to a wide array of illnesses, in a number of different ways:

  • Excessive demands are placed on the cardiovascular system from chronically elevated blood pressure, which can predispose to heart disease. Elevated cortisol levels also place an undue strain on the cardiovascular system and other organ systems.
  • Increased aldosterone output by the kidneys promotes the retention of salt and water, which also raises blood pressure by increasing fluid volume in the cardiovascular system.
  • Chronically elevated cortisol levels can increase a person’s susceptibility to many types of illnesses by reducing sensitivity of the immune system, and interfering with the natural inflammatory response.
  • Thyroid hormone and growth hormone are increased, which speeds up metabolism…for awhile…
  • Chronic stress lowers production of gonadotropin, a hormone related to growth and reproduction. Stress-related cessation of menstrual periods results from the fall in gonadotropin hormone, which is also responsible for the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Fight or Flight Sympathetic Response
You can see from this partial list, that chronically elevated stress hormones can put a person at risk for a number of health issues, all essentially stemming from an out of control acute fight or flight response! But this isn’t the entire story. While the above-mentioned factors have long been recognized as negative consequences of chronic stress, more recent revelations by scientists have also implicated chronic inflammation as a major cause of several stress-related diseases.

Chronic Inflammation

While the process is more complex than I’m going to make it out to be, the end all effect of chronic stress is chronic inflammation. Chronic inflammation is said to lie at the root of most, if not all diseases of ‘modern civilization’. Now those of you who are still paying attention (insert sound of crickets chirping), you might be asking yourself how chronic stress (characterized by chronically elevated cortisol levels), can lead to chronic inflammation, if cortisol (being a corticosteroid) is anti-inflammatory!? Well that is a very good question, and I am quite impressed that you asked it! More recent research studying the very-long-term effects of chronic stress have revealed that eventually…..(wait for it)……eventually your tissues and cells lose sensitivity to the various stress hormones, much like a mother of three loud and rowdy boys eventually learns to tune them out.

As put by stress researcher Sheldon Cohen: “the prolonged stress alters the effectiveness of cortisol to regulate the inflammatory response because it decreases tissue sensitivity to the hormone. Specifically, immune cells become insensitive to cortisol’s regulatory effect. In turn, runaway inflammation is thought to promote the development and progression of many diseases.” This reminds me of the boy who cried wolf story. Eventually, your tissues become desensitized to the anti-inflammatory effects of cortisol, and inflammation runs amok.

Other researchers have found that chronic stress also causes alterations to our genes, causing our immune system to become overly reactive, even in the absence of any stressors. The truth of the matter is, research is still in its infancy with regards to our understanding of stress, the stress response, and it’s exact role in chronic and inflammatory disease states. Enough empirical evidence exists however to understand the basic issue at hand:

Chronic Stress → Inflammation → Disease → More stress → More inflammation → Worsening of disease → And so on and so forth.

From Chronic Inflammation to Chronic Disease…and Beyond!

As discussed in part one of this series, a very large number of diseases and symptoms have been related to chronic stress and chronic inflammation. It may very well be that inflammation lies at the root of most, if not all, chronic disease. So to put the brakes on our current epidemic of chronic disease, we need to stop the out-of-control inflammatory response in it’s manic tracks.

How do we do this? It’s easy, just don’t be stressed! Haha, just kidding. But in all seriousness, breaking the cycle of chronic stress requires us to re-train our nervous systems, and exercise our stress response into submission. You don’t have to be a monk living in a cave to gain control over your autonomic nervous system, rather steady and regular practice will eventually get you there. In the next post of this series, we will discuss some helpful ways to optimize the stress in your life. Notice how I didn’t say Meditation to retrain stress respponseeliminate the stress, because it’s important to realize that stress is not the enemy here. It’s unreasonable to try and ‘stop stress’, because as we’ve been discussing, we need the stress response for survival! Overcoming chronic stress involves learning how to efficiently recognize life’s many and inevitable stressors, and appropriately modify our behavior. With time, patience, forgiveness, and diligent practice, we learn to not give away our sympathetic energy to anything that isn’t currently threatening our life.

In good health,

Kinsey Jackson, MS, CNS®