How Emotional Stress Can Kill You
By Lewis S. Coleman, MD, FAIS
*This is an article from the Winter 2021 -2022 issue of Contentment Magazine.
As American Institute of Stress members know, fear and anxiety are harmful to health, but how this happens has remained unknown. Now, for the first time, the mammalian stress mechanism explains how emotional adversity promotes disease and death. However, emotional adversity seldom acts alone. It synergizes with other environmental stressors including pollution, pathogens, radiation, toxic chemicals, surgery, and trauma to induce stress mechanism hyperactivity that causes disease.
The Mammalian Stress Mechanism
The mammalian stress mechanism is ubiquitous throughout the body. It consists of the following elements:
- The interaction of blood enzyme factors VII, VIII, IX, and X with tissue factor in extravascular tissues.
- The vascular endothelium, which is a delicate layer of specialized cells that lines the inner surface of all blood vessels and isolates tissue factor from the blood enzymes. Endothelial damage exposes tissue factor to blood enzymes and elevates stress mechanism activity.
- The autonomic nervous system, which releases hormones from the vascular endothelium to regulate stress mechanism activity.
This diagram of the stress mechanism illustrates its various elements, relationships, and effects:
The subtleties of the stress mechanism challenge book limitations, but the diagram at least illustrates the rudimentary associations of emotional activity with blood enzymes and their consequences for the purpose of this essay. Please refer to the diagram as you proceed through this presentation. Emotional adversity is harmful because it generates nervous activity that hyperactivates the stress mechanism via the “Cognitive Pathway” that is portrayed in red in the upper left-hand portion of the diagram. Tissue disruption that hyperactivates the stress mechanism is portrayed in blue on the right-hand side of the diagram.
The Stress Mechanism and Disease
The stress mechanism operates continuously, efficiently, and unobtrusively to repair tissues and regulate physiology, but like any mechanism, it has limitations. When its limits are exceeded, it wastes and depletes its substrates, generates harmful or defective excesses of its products, and produces a bewildering blizzard of destructive disease effects that disrupt physiology and damage organs and tissues, and variously manifest as fever, fatigue, malaise, inflammation, immune activity, cell proliferation, tissue edema, pus, exudates, rashes, pustules, hypercoagulability of blood, organ dysfunction, dementia, delirium, sclerosis, infarction, accelerated capillary senescence, atherosclerosis, and amyloidosis.
Greek physicians understood that disparate stressors acting in concert produce nondescript disease:
Illnesses do not come upon us out of the blue. They are developed from small daily sins against Nature. When enough sins have accumulated, illnesses will suddenly appear. — Hippocrates
Certain stressors, especially bacteria and viruses, produce distinctive stress mechanism reactions that enable their diagnosis, and this, combined with germ theory and cell theory, has fostered the notion that each disease is a separate entity unto itself that must be diagnosed and cured using specialized treatments. This viewpoint fails to explain the commonality of disease manifestations (e.g., fever, fatigue, malaise, inflammation, edema, rashes etc.) and the associations of seemingly unrelated diseases. For example, diabetes, hypertension, obesity, and cancer are closely associated. Stress theory explains these observations. It indicates that disease usually results from combinations of environmental stresses, and that universal treatments that restore normal stress mechanism activity and organ function are beneficial in all forms of disease.
The nature of consciousness remains one of the great mysteries of biology. It is generated by the cerebral cortex, and it continuously interprets all forms of sensory information and combines this with memory to produce a computer-like conceptual comprehension of environmental circumstances. It interprets optic information as sight, olfactory information as smell, tactile information as touch, auditory information as sound, and nociception as pain.
Nociception is nervous activity generated by tissue disruption sensors located in organs and peripheral tissues called “nociceptors.” Nociception is conducted via sensory nerves to specialized spinal cord nociception pathways that convey nociception to the cerebral cortex.
The spinal cord nociception pathways also communicate nociception to sympathetic ganglia located in the neck, chest, and abdomen. These ganglia release von Willebrand Factor (VWF) from the vascular endothelium into flowing blood, which accelerates thrombin generation to produce insoluble fibrin that enables coagulation and capillary hemostasis to stem blood loss in the event of trauma.
In the absence of trauma, sympathetic nervous activity generates insoluble fibrin to enable a “capillary gate mechanism” that regulates microvascular flow resistance. This determines cardiac output, cardiac efficiency, tissue perfusion, tissue oxygenation, and organ function in accord with autonomic balance. This is normal stress mechanism operation. However, when sympathetic nervous activity is prolonged and excessive, it invites infarction, systemic inflammation, and amyloidosis that causes chronic illnesses.
The Emotional Mechanism
Unlike the stress mechanism, which maintains and repairs the body, the emotional mechanism is an “emergency mechanism” which enables “fight or flight” that preserves life and prevents injury in life-threatening circumstances, such as being chased by a predator. The emotional mechanism consists of a memory mechanism and a dreaming mechanism. These two mechanisms work together to facilitate “fight or flight.”
The Memory Mechanism
The memory mechanism automatically retains a detailed audiovisual “movie” of all waking moments from infancy to the end of life. This was accidentally discovered by Dr. Wilder Penfield, a neurosurgeon who sought to control epilepsy by surgically excising damaged brain tissue. He inserted tiny electrodes to stimulate various portions of the brain in conscious patients and his electrodes elicited childhood memories. Years later a patient named Jill Price sought the help of memory experts at UC Irvine because her distracting memories disrupted her ability to function.1 The UC professors confirmed her condition and called it “Hyperthymestic memory.”2 Since then, several other patients have been discovered. Milder cases manifest as “photographic memory.” The actress Marilu Henner of “Taxi Driver” fame enjoys this condition, because it enables her to effortlessly memorize acting scripts.
The Dreaming Mechanism
Sleep abnormalities reveal the nature of the dreaming mechanism, which automatically reviews and re-evaluates accumulating memory records during “REM” (rapid eye movement) sleep to identify dangerous environmental circumstances. During REM sleep, the brain normally halts nervous motor innervation of skeletal muscles to prevent violent movements during its review of retained memories. Persons awakened during REM sleep sometimes perceive paralysis and become aware of their dreams before they regain full consciousness. Inadequate motor suppression during the dreaming process sometimes manifests as sleepwalking or violent movements as affected patients subconsciously re-enact their dreams.
The Necessity of Sleep
Prolonged sleep deprivation is lethal in most people, but there are those who don’t require sleep or dreaming.
Prolonged sleep deprivation is lethal in most people, but there are those who don’t require sleep or dreaming. They remain awake through the night reading books or otherwise entertaining themselves and enjoy normal longevity. Thus, the emotional mechanism appears to serve little purpose in humans, whose superior intelligence enables them to avoid the life-or-death circumstances that bedevil wild animals.
How Consciousness Regulates Nociception
The specialized spinal cord nociception pathways conduct nociception to the brain as well as sympathetic ganglia. Consciousness interprets nociception as pain. Here things get complicated. Consciousness works closely with emotional mechanisms to generate “corticofugal” (descending) nervous signals to the spinal cord that continuously inhibit the spinal cord nociception pathways. The emotional mechanism modulates these inhibitory signals to regulate spinal cord nociception activity. This enables the emotional mechanism to regulate pain perception, and thereby prevent distracting pain during “fight or flight.”3 The classical example is a soldier who is wounded in battle but doesn’t notice the pain and continues to fight. When the combat subsides, he suddenly becomes aware of incapacitating pain on account of his injury.
Spinal cord damage in the neck around the level of T4 abolishes both ascending nociception from the spinal cord to the brain and descending inhibition of nociception from the brain to the spinal cord. This creates a dangerous condition called “autonomic dysreflexia” in which the victim can no longer perceive nociception as pain in tissues below the level of the injury, but stimulation of those tissues can harmfully increase sympathetic nervous activity that threatens organ damage or even death. This predicament afflicted the actor Christopher Reeves when he was flung off a horse, broke his neck, and became quadriplegic. Unsurprisingly, he survived for only ten years after the accident, and died prematurely at the age of 52.
Fight or Flight
The emotional mechanism works closely with consciousness to pre-emptively detect dangerous environmental circumstances, whereupon it generates fear and anxiety, and reduces the inhibition of spinal cord nociception pathways. The increased nociception activity releases HPA hormones (epinephrine, norepinephrine, glucagon, cortisol, etc.) and VWF to increase blood coagulability, elevate blood glucose, and restrict blood flow to non-essential organs and tissues. The increased blood coagulability limits blood loss in the event of injury. The elevated glucose levels provide cell energy and divert blood perfusion to facilitate fight or flight and thereby enhance survival. However, these emergency measures are inherently wasteful of energy reserves and stress mechanism substrates, and they cause harmful stress mechanism hyperactivity that generates excessive or defective stress mechanism products. This explains why chronic fear and anxiety promotes disease.
The combined activities of the memory mechanism and the dreaming mechanism explain how animals adapt to changing environmental circumstances. For example, guinea pigs trapped in wire mesh initially exhibit extreme alarm and struggle to escape, but after a few days of such confinement they appear to accept their predicament and cease to struggle. Nevertheless, the unceasing emotional stress reduces their life span. A more natural example was provided by the re-introduction of wolves to Yellowstone National Park. In the absence of wolves, the Yellowstone caribou learned to linger near streams and rivers where water and grass were abundant, and they gradually destroyed the trees where they lingered. The caribou were familiar with harmless coyotes and were not alarmed by their first encounters with wolves, but they soon learned the difference, and preferred open spaces where they could detect and avoid wolf attacks. They exhibited extreme nervousness when obliged to approach water sources surrounded by dense vegetation.
PTSD, Chronic Pain and Fear Syndromes
Emotional memory can mimic reality, especially when the dreaming mechanism dramatizes distressing memories. Such memories are subconsciously re-activated by environmental circumstances, and they can induce panic and sympathetic nervous activity that undermines health in the same manner as the original events. For example, the memory of a traumatic dental experience can be re-activated by the sound of the dentist’s drill, or the sight of an approaching needle. They can be so frightening as to necessitate general anesthesia to enable ordinary dental treatment. Such emotional memories explain the nature of PTSD (post-traumatic stress disorder) where people experience subconscious recall of automobile accidents, combat events, and so forth.4 Sedatives can prevent such troublesome memories, but once established they are notoriously difficult to treat.5-7 Tranquilizers suppress their anxiety, and opioids can mitigate their perception of pain, but the memories persist and re-occur, and invite addiction. Furthermore, tranquilizers and sedatives, including alcoholic beverages, are inherently toxic, and they damage tissues and promote disease with persistent exposure. Stellate ganglion blocks can mitigate the harmful sympathetic nervous activity associated with troublesome memories, but they require special training and entail risks.8 Experimental evidence suggests that drugs can disrupt fearsome memories, but they also invite toxicity.9
The mammalian stress mechanism explains why emotional adversity is a major contributing environmental factor in disease causation. It explains the “placebo effect” wherein sick patients improve when they are assured that they have received effective treatments, even though they have received only sugar pills with no medicinal properties. It likewise explains “Voodoo death” as described by Cannon.10 Whenever possible, patients should be removed from stressful circumstances such as job stress and marital stress. Cancer patients should never be frightened by the news of their dismal prospects, and placing sick patients in clean, comfortable, caring, and pleasant surroundings can promote their recovery from sickness. Surgery patients should be pre-medicated to improve surgical outcome.
- J. Price, The Woman Who Can’t Forget: The Extraordinary Story of Living with the Most Remarkable Memory Known to Science–A Memoir. (Free Press, a division of Simon and Schuster, 2008), pp. 263.
- E. S. Parker, L. Cahill, J. L. McGaugh, A case of unusual autobiographical remembering. Neurocase 12, 35-49 (2006).
- R. Melzack, P. D. Wall, Pain mechanisms: a new theory. Science 150, 971-979 (1965).
- J. B. Rosen, J. Schulkin, From normal fear to pathological anxiety. Psychol Rev 105, 325-350 (1998).
- G. Park, Rescue is stressful. Anesth Analg 95, 263-265 (2002).
- V. Dorges et al., The effect of midazolam on stress levels during simulated emergency medical service transport: a placebo-controlled, dose-response study. Anesth Analg 95, 417-422, table of contents (2002).
- L. W. Crile GW, Anoci-association. (Saunders, Philadelphia, 1914), pp. 223-225.
- K. L. Rae Olmsted et al., Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial. JAMA Psychiatry 77, 130-138 (2020).
- K. Nader, J. E. LeDoux, Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations. Behav Neurosci 113, 891-901 (1999).
- W. B. Cannon, Voodoo death. Psychosom Med 19, 182-190 (1957).