HPA Axis and Cortisol - Part 1

Written by Anil Bajnath, MD
Posted October 15, 2020

Dear Reader,

As Jack walks around the restaurant, he thinks about all the things that could go wrong. The cook could quit. The food could be spoiled upon arrival. The waitresses could be stealing money. The customers could be unsatisfied with their experience.

Jack’s brain processes these imaginary events as reality. It doesn’t completely distinguish between perceived danger and actual danger. As a result of millions of years of human evolution, Jack’s body prepares itself for stress the only way it knows how- activating the HPA axis.

Role of the HPA Axis

The HPA axis is a feedback loop that regulates your reactions to stress. Specifically, it links the hypothalamus, pituitary gland, and adrenals- all vital parts of the neuroendocrine system.

The loop begins when something stressful happens- one of the waitresses at Jack’s restaurant gets ill in the middle of the busiest shift of the week. As soon as Jack hears the news, his sympathetic nervous system is activated. Epinephrine and norepinephrine are released, the hormones responsible for the “fight-or-flight” response we once used to run from saber-toothed tigers.

With these hormones released, Jack’s HPA axis is in full swing. His hypothalamus (a small part of the brain concerned mainly with keeping the body in a state of homeostasis) secretes corticotropin-releasing hormone (CRH) into his bloodstream. In the brain, CRH increases feelings of anxiety and temporarily improves Jack’s memory and selective attention. He’ll need his brain in an attentive state to deal with whatever stressor he’s facing.

CRH is a message to the pituitary gland to secrete adrenocorticotropic hormone (ACTH) which travels to the adrenal cortex like a letter traveling to your mailbox, binding to adrenal receptors, and causing the final section of the loop- the secretion of cortisol, the “stress hormone."

Role of Cortisol

As the night goes on, and more inevitably stressful events occur, Jack’s bloodstream becomes inundated with cortisol as his adrenal cortex pumps out the hormone a little at a time. Cortisol’s main job is to release glucose into the bloodstream to be used as instant fuel for either fighting or running from his problems. Each pump results in about fifteen minutes of sustained cortisol release.

Cortisol also helps shut down secondary functions like sexual desire and urinary urges. You wouldn’t want to have to pee while running for your life or fighting an enemy and Jack is able to cover the waitress’s entire shift without having to use the restroom.

Unfortunately, Jack’s stress does not end after the difficult shift. He carries the weight of the night home with him and wakes up to another day of difficult obstacles. Each event re-actives the HPA axis and starts the whole process over again, inevitably leading to elevated cortisol levels for long periods of time.

Many studies show this kind of chronic stress is not beneficial for longevity and overall well-being:

“It appears that being exposed to stress can cause pathophysiologic changes in the brain, and these changes can be manifested as behavioral, cognitive, and mood disorders (Li et al., 2008). In fact, studies have shown that chronic stress can cause complications such as increased IL-6 and plasma cortisol but decreased amounts of cAMP-responsive element-binding protein and brain-derived neurotrophic factor (BDNF), which is very similar to what is observed in people with depression and mood disorders that exhibit a wide range of cognitive problems.”

Yaribeygi, H., Panahi, Y., Sahraei, H., Johnston, T. P., & Sahebkar, A. (2017). The impact of stress on body function: A review. EXCLI journal16, 1057–1072. https://doi.org/10.17179/excli2017-480

If Jack is constantly bombarded with cortisol, his immune system is constantly suppressed. This leaves him vulnerable to disease and inflammation that can be detrimental to the body over time.

Cortisol also activates the autonomic nervous system, indirectly affecting the cardiovascular system. Jack’s heart rate increases, his muscles tense and contract, and blood flow is diverted from his organs to parts of his body that will help him fight or run. Again, this is all fine for a short period of time, but the organs need blood flow to operate correctly.

In addition, his hippocampus is extremely sensitive to stress and also responsible for the conversion of short to long-term memory. Animal studies show that a chronic state of stress can cause a reduction in the accuracy of spatial memory and negatively affect learning. Temporarily, Jack is sharper and better able to handle his environment. But over time, this kind of attention is not sustainable, and his brain physically begins to change to compensate for the abundance of cortisol.

To your longevity,

Anil Bajnath
CEO/Founder, Institute for Human Optimization
Chief Medical Advisor, Longevity Insider HQ

*This content is provided by the Institute for Human Optimization.