Why stress matters (and the importance of being hot)

Tissue swelling, for instance, is a consequence of a decline in vitality, where ATP depletion leads to a disruption of salt linkages between molecules, causing cells to rapidly take up water thereafter (Ling, 1981).

The depletion of ATP also causes membrane pumps – whose function is to maintain gradients of ions across the plasma membrane – to falter.  In doing so, certain ions, namely sodium and calcium, accumulate inside cells, via the sodium-potassium ATPase and then, the sodium-calcium antiport exchanger.  Famously known to cause various cardiovascular pathologies, calcium overloading induces electrical and mechanical abnormalities in the heart (Vassalle & Lin, 2004).

It’s interesting and should be noted that any kind of stress can initiate the aforementioned processes – the final effect being determined by both the intensity and duration in which the stress in question is exerted.

Take for instance the physiological effects of something seemingly as innocuous as loud sounds.  Shown in Han Selye’s experiments, in which rats were exposed to sounds of over 100 decibels for various lengths of time, as little as 5 seconds of exposure produced a 10-fold rise in adrenalin, and over time, the rats developed enlarged adrenal glands and higher-than-normal levels of cortisol. 

Cortisol was the slower responding hormone of the two, but persisted in the blood longer than adrenalin, which was sensitive to even subtle changes in sound levels.  Thus adrenalin initiates the stress response, whereas cortisol sustains it.

Because stress depletes blood calcium, parathyroid hormone (PTH) is necessarily secreted; along with adrenalin, PTH permits calcium loading.  The intensity with which the PTH is secreted is directly proportional to the drop in blood calcium levels. 

The uptake of calcium, intensified during stress, can ultimately converge on the mitochondrion, wherein it induces oxidative stress, inflammation, and opening of mitochondrial transition pores.

Released in response to falling sodium and glucose levels, adrenalin can also increase the cell membrane’s permeability and, via its receptors, adrenalin can raise cyclic AMP levels (thereby activating the enzyme, phospholipase C).  Through these alternate routes, adrenalin reinforces the increase in calcium levels inside cells (Singal, Matsukubo, & Dhalla, 1979).

Stimulation- or injury-induced calcium uptake then stimulates the mobilization of fatty acids.  In Selye’s rats exposed to loud sounds, almost instantly, a rise in NEFA, cholesterol and triglycerides was seen – these are derangements produced by the action of adrenalin.

Certain unsaturated fatty acids, on liberation, activate peroxisome proliferator activated receptors (PPAR) – a type of transcription factor that regulates fat and carbohydrate metabolism, mostly in fat cells.  Overexpression of PPAR favors fat uptake and oxidation, resulting in the accumulation of lipid metabolites inside cells (Finck et al., 2002); on the other hand, inhibition of PPAR expression promotes the use of glucose and restores insulin sensitivity (Campbell et al., 2002).

Prolonged stress decreases thyroid hormone output and increases cortisol output, the hormone that sustains the stress response.  Sustained levels of cortisol leads to the suppression of the immune system, rendering us susceptible to infections and cancer.  In this way, prolonged stress is comparable to exhaustive exercise.

Energetically, fat oxidation is inefficient and produces a greater mitochondrial membrane potential as compared to glucose oxidation; as a result, electrons are likely to get jammed in the mitochondrial electron transport chain, leading to reverse electron flow and massive free radical production, further inhibiting glucose use (Hoehn et al., 2009).

Stress leads to excessive fat oxidation, and by way of providing large amounts of reducing equivalents and depleting oxaloacetate – which comes from sugar and is needed to metabolize glucose oxidatively – impairs insulin signaling (Koves et al., 2008).  Thus excessive – rather than deficient – fat oxidation leads to insulin resistance (Kelley, Goodpaster, Wing, & Simoneau, 1999). 

Free radical generation (e.g., superoxide) increases on the preferential uptake and oxidation of fatty acids (Fabris et al., 1988).  Intracellular antioxidants can curtail the damages therefrom, but extra thyroid hormone, sugar, antioxidants (e.g., quercetin), muscle-building exercise (e.g., not-too-strenuous isomeric contractions where no work but heat is produced), salt, and calcium can help maintain cellular redox balance, and for this reason, keep oxidative stress in check (Ioku et al., 2001).  Starchy vegetables actually have the opposite effect (Deopurkar et al., 2010; Ghanim et al., 2007, 2009).

Because of the presence of activated methylene groups, unsaturated fatty acids are particularly susceptible to free radical attack.   These reactive fats accumulate in membranes with age, and so lipid decomposition products become important factors in the aging process (Hegner, 1980; Nohl & Hegner, 1978).  The increase in fluidity of membranes also leads to a progressive slowing of oxidative metabolism (Gabbita, Butterfield, Hensley, Shaw, & Carney, 1997).

Heart disease is a prominent symptom of hypothyroidism; on the surface this seems very obvious, as strong blood flow, energy generation, tissue oxygenation are indispensable for good cardiovascular health (Ertaş, Kaya, & Soydinç, 2012).  Indeed, being hot and having a not-so-subtle pinkish-red glow are not only aesthetically pleasing.  A high rate of metabolism implies a high rate of carbon dioxide production, too, and this allows efficient unloading of oxygen from red blood cells to tissues throughout the body (Bohr effect) and blood flow (via vasodilatation).  

Because blood flow tends to decline beyond the years of 50 to 55 years of age, older individuals manifest some degree of shock, whereby metabolic needs of vital tissues are inadequately met due to poor circulation – the foremost causes stemming from diseases of the coronary arteries and valvular heart abnormalities.  Low oxygen delivery (and thus low thyroid) accelerates and worsens these pathologies of the heart by furthering the development of atherosclerosis and weakening the heart’s contractility.

Hypothyroidism is one (often overlooked) cause of anemia, again, by compromising blood flow and delivery of oxygen to tissues, as well as by impairing the absorption of nutrients from the digestive tract (Leavell, Thorup, & McClellan, 1957).  Nonetheless, the return of warmth and strength are good guides as to whether there is optimal blood flowing to tissues.  But since adaptive mechanisms can create a false perception of normality, other indicators, such as blood pressure, can also be measured as at-the-moment diagnostic tools of sorts.

In conclusion, we can experience stress from really anything, such as a divorce, death of a family member or spouse, loss of a job, or a shocking mental experience.  Stress can come from even commonplace sources, such as feeling uncertainty, fear, or frustration.

I think the physiological effects of stress are most dramatically illustrated by cholesterol fed rabbits.  Cholesterol is particularly toxic to rabbits but if they are petted, held, and talked to on a regular basis, a significant reduction in atherosclerotic lesions is seen in comparison to rabbits that are ignored. 

The amount of control that we perceive having over a stressful situation governs the severity of it.  This is clear, but what’s also becoming clear is the connection between chronic stress and diseases – from ulcers and migraine headaches to cancer, atherosclerosis, and autoimmunity.  Patients with rheumatoid arthritis for instance have been described as being overly self-conscious and self-sacrificing; they also tend to deny themselves of outlets for emotional expression. 

What has helped me the most with regard to coping with stress is adopting a self-disclosing attitude in my personal relationships.  Staying hot has helped me cope, too, and this is dependent on good thyroid functioning and glucose use, as well as the avoidance of excessive fat oxidation and its attendant consequences.