Strategies for the Brain to Regulate Cellular CO2,

– in the face of inadequate breathing and rising acid in the blood].

My guess is that Paula’s body adapted to a lower breathing rate than normal by reducing the rate of CO2 production per minute so that to maintain her blood acidity in the normal range.  Our Lung Doctor/Physiology Professor Consultant

No one really knows how something as complex as metabolism is adjusted by the brain under emergency situations.

A first step would be to understand how cellular metabolism is regulated in healthy people without respiratory defects.

Regulation of cellular respiration

Apparently cellular respiration can be sped up or slowed down. This involves regulating key enzymes and feedback inhibition [and temperature]. Please look at this link to understand further. https://www.khanacademy.org/science/biology/cellular-respiration-and-fermentation/variations-on-cellular-respiration/a/regulation-of-cellular-respiration

[Thank you, Khan Academy, for explaining it so simply. And please donate to their site because they are amazing at teaching very complicated processes.]

It seems that when Paula’s breathing rate couldn’t respond to rising carbon dioxide levels in the blood, the obvious reflex response of the brain and periphery was be to lower carbon dioxide by reducing the rate of cellular respiration like our consultant suggested. This would reduce the carbon dioxide produced by at least some cells and that would lower PCO2 .

Too slow ventilation at rest and difficulty responding to rising acid levels in the body at rest has to produce graded levels of endogenous poisoning, a slowly developing emergency. The body is very practiced when it comes to carbon dioxide, since it is being produced by cellular respiration all the time. along with heat, water and ATP. One can imagine that the brain has a lot of experience managing too high or too low CO2, especially if it develops gradually.

Let us examine this hypothesis further.

During Paula’s attack of bipolar depression, her body temperature was lower than normal. Cellular metabolism is very sensitive to body temperature. …Perhaps Paula was unable to retain body heat/loss balance because of her too slow breathing. What does internal body heat have to do with not breathing enough? I don’t think anyone knows but it seems to make sense.

Hypothermia, defined as a core temperature of < 35.0 °C, may present with shivering, respiratory depressioncardiac dysrythmias, impaired mental function, mydriasis, hypotension, and muscle dysfunction. Paula experienced the signs highlighted in bold. Management includes warming measures, hydration, and cardiovascular support. Review Thermoregulatory disorders and illness related to heat and cold stress William P.CheshireJr. Autonomic Neuroscience, Volume 196, April 2016, Pages 91-104

If the ventilatory system cannot do its job properly, it might be harder to defend adequate body heat and body temperature might drop. Keeping up basal body temperature (BBT) is one of the most costly processes in the body. Lowering thyroid hormones to lower the metabolism and the utilization of energy, also seems part of the domino effect that occurs with ineffective breathing. . Oddly enough, this intricate domino effect might actually be protective. An internal state of mild hypothermia and hypothyroidism would definitely shut down certain enzymes involved in cellular respiration. Energy utilization would be adapted to internal conditions. This would result in a lower CO2 production overall , affecting ATP production as well, unfortunately.

Paula did not move much, most of the time, or would pace in distress. Perhaps, she was also unconsciously conserving energy as is normal when experiencing an energy shortage.

Secondly, Paula stopped feeling hungry or thirsty [because, in my opinion, she was quietly delirious and lost awareness of these sensations]. It is possible that airway defences were disturbed, making eating and drinking dangerous and secretions more difficult to clear. I am guessing that having less food and water for digestion of fuel would further reduce production of carbon dioxide [and ultimately ATP] in the blood.

Thirdly, only some parts of organs seemed to have full function [due to the lowered cellular metabolism]. Kraepelin and Paula describe it well; during depressive attacks – heart function became disturbed, arrhythmia and murmurs were present, heart rate increased, as well as blood pressure. Water and feces were retained and urination and defecation stopped. Dehydration followed., as did accidental malnutrition with involuntary weight loss and muscle wasting. Thyroid function declined, further adjusting metabolism to lower energy availability. And of course, inhibition of intellect and memory as well as organization of behaviour.

This reflex process of lowering cellular metabolism in an internal medical emergency might extend a person’s life under conditions of fixed too slow ventilation at rest, but not their quality of life or their sensory experience of life. The sensation of an unspoken internal medical emergency is unbearable…..especially in the quiet depressive delirium stage; a gradual physiological adaptation to mild asphyxiation.

These physiological and hormonal reactions may have been reflex responses to bring down carbon dioxide through other means beside stimulation of breathing.

Months later, stimulation of breathing rate did occur, but seemed possible only with excessive locomotor activity. When it did occur [in the same person who couldn’t stimulate their breathing before], ventilation was too chaotic, too fast and occurred with hyper-speed locomotor activity. Feeding and speech returned with a vengeance, with the person eating and speaking in a desperate, rushed and chaotic manner. Cognitive function was worse than before, with retroactive amnesia and confabulation. The heart began to fail. Heart rate would drop erratically and sporadically. Mood was completely abnormal -euphoric, labile, irritable and at times combative. Mania as a form of wild hyperactive delirium patterned on unseen underlying too fast chaotic ventilation, replete with hidden occasional apneas. Mania and delirium as brain stem central pattern regulation of ventilation rate and locomotor activity run amok. The brain stem trying to keep the organism alive during biochemical emergencies of cellular respiration.

Paula and I think that thyroid function increased a lot during mania [eyes look wild and popped out] and we have very little understanding what is happening biologically, but we know that the hidden breathing difficulty is too dangerous to risk sleep and that the muscles of the legs and tummy are probably helping to pump air in and out because that is the only way the person can survive. With the surge in sexual hormones and involuntary sexual activity we think that perhaps the system is trying to build back muscle before it is too late. This pattern of activity is in service of the brain stem and the autonomic nervous system and has little to do with reason. This is fight or flight in service of surviving “mild-moderate” internal suffocation and it only makes sense metabolically in this light.

We need scientists to figure out how the circulatory system is working during attacks of depression [prolonged quiet-inhibited delirium] and mania [prolonged unmasked delirium] and we need to know the minute volume and the arterial blood gas results in both stages of the illness to understand what is happening biologically.

Subtle damage to nerve fibres, muscles and bones of the respiratory pump will affect the motor functions crucial for remaining alive, for the entirety of one’s life…..especially when ill or when exposed to a large load of allergens or interior CO2 levels. The patient cannot know what is going on in their body, they are not even aware of their structural defect.

We must figure it out using our knowledge of biology and biochemistry. Then we can help resuscitate them and support their breathing in order to bring back their mind and soul. The “mind” needs adequate circulation of air .

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