The alarm system response to hypercapnia AND to perceived threat.

So, it seems that both HYPERCAPNIA and perceived threats will engage the same systems of the brain and body. This makes it hard to tease them apart. The broader ” Locus Coeruleus-Norepinephrine System” [LC-NE ] governs an ‘alarm system’ response to stress (Lanius et al., 2017) across species.

This makes things complicated.

How can we tell if the patient is experiencing hypercapnia or a perceived threat psychological response?

The first step is to realize that both will result in a “stress response”.

The patient themselves will not be able to tell you , for the same reason they do not know their own vital signs. 1] Vital signs need to be measured. 2] So does the level of the partial pressure of carbon dioxide [PCO2] in their blood. Since this involves getting an invasive arterial blood gas test, it is easier to measure the minute ventilation as a first step.

Yet neither of these are ever measured in order to tease these two causes of the stress response apart. So no one knows to what extent hypercapnia is the main culprit.

Why don’t doctors measure minute ventilation and if it is abnormal, order an arterial blood gas test?

The main reason involves a misconception on the part of doctors, ; namely that psychological factors only are responsible for the stress response. The patient may believe this as well. Neither the psychiatrists or the patients know any better. The other doctors do not know any better either. Why not? Because it is only since the 1960’s that we have been able to measure the partial pressure of carbon dioxide in the blood. . Biochemistry is hard to understand and we have not had the tools to measure PCO2 in the blood for that long – in animals or in humans. The psychological explanation is traditional. I do not think it applies to bipolar illness, delirium or even dementia. We have a lot to learn about blood gases and their effects on the mind and the body. We have a lot to learn about epigenetic changes affecting metabolism, blood gas and the respiratory muscle system moving waste gases out of the body.

Hypercapnia research may well supplant our current opinions about causes of ongoing stress in serious mental illness. I hope so. Psychiatrists are wrong to think only of psychological effects, they are wrong to depend on outdated theories that , in the case of serious mental illness, are failing patients. Psychiatrists are generally ignorant of biochemistry and the underpinnings of gaseous exchanges and homeostasis. They have probably never heard that hypercapnia can trigger the body’s internal alarm.

The brain controls respiratory rate in order to maintain normal acid base of the blood as much as possible. . The brain tracks the carbon dioxide of the blood very carefully. Our cell produce CO2 and water as a byproduct of producing energy. Carbon dioxide is a cerebral vasodilator which must be carefully controlled.

Chronic hypercapnia may have no signs or symptoms if the person is healthy. For these patients, exposure to environments with heightened CO2 [poorly ventilated crowded indoor spaces, indoor use of wood stoves, gas ovens, indoor mold growth] might trigger the stress alarm response but not affect others. Physical illness like viruses, stomach flu, etc..causing poor body condition and fatigue, might trigger the stress alarm response in people with chronic hypercapnia and not have the same consequence in others. Injury, planned surgery and blood loss may also trigger the stress alarm response in those who are more susceptible [ due to unknown chronic hypercapnia] .

For acute on chronic attacks of hypercapnia triggering the stress alarm response, supportive medical care and avoiding internal environments or internal heating sources with high CO2 emissions, will be necessary. Psychological treatment will be useless in these patients.

Oxygen levels and HCO3 levels and other blood tests may be normal in these patients.

Measuring PCO2 is the only way to tell the difference.

It is time to bring the study of hypercapnia into the study of stress, as Dr Kraepelin’s research and Paula’s case [echoing his work] shows us.

The arterial blood gas test is an invasive painful test, but it is the definitive test of PCO2. Few doctors would do this test for even chronic disabling anxiety.

A good first step would be to count a patients breathing rate. This takes one minute of mindful counting and a stopwatch. You can tell the patient what you are doing. Respiratory rate at rest is involuntary, set by the brain stem in responses to gases in the blood.

If the respiratory rate is lower than 10 or higher than 20, then it would be necessary to obtain the tidal volume or the depth of breathing. For this, a spirometry test is necessary [this will probably require a referral to a lung function lab].

If you multiply the respiratory rate times the tidal volume you will get the minute ventilation or the amount of air exchanged every minute at rest when awake.

Paula had this done and found out-to everyone’s surprise- that she exchanges 1.5 litres of air every minute instead of the normal 5-8 litres. Since the cells of the body produce carbon dioxide as it burns food for energy, this suggests that Paula most likely has chronically raised PCO2 of the blood.

Dr Kraepelin also found “too slow breathing rates” in his bipolar depressed patients [in the days before medication]. He understood that this explained their metabolic dysfunction and altered mental status and an unbearable state of “ANGUISH” [a form of dyspnea] . Kraepelin understood that these patients had a form of respiratory failure. Scientists were aware of such things even then. [over 100+ years ago].

No one wants to think that generalized anxiety, bipolar depression, and mania [and perhaps dementia] are manifestations of different degrees of respiratory failure, but there you are.

Discovering more effective treatments for these syndromes depend on knowledge not how we feel about this knowledge.

And doctors [even psychiatrists ] feel horror when I tell them this, because we do not really understand much about states of hypercapnia.

Hypercapnia is reversible [even in its worse outcome- coma].

Hypercapnia is strangely protective. Bipolar patients get extremely sick and extremely mental dull or seemingly intoxicated [euphoria], but most did not die, and they do not tend to suffer permanent brain damage [unlike…say Parkinson’s or tertiary Syphilis ]. Theirs is a remitting/relapsing course. [without medications]. Back in Kraepelin’s day, these patients were the only ones to leave the asylums when they spontaneously recovered, even after decades of being insane [a type of chronic delirium].

The stress response is far more sophisticated than imagined.

As Paula and I and hopefully you, are beginning to discover.

We think that more research into fixed abnormal respiratory rate at rest when awake is needed, especially in the neurological and neuropsychiatric population. Medical treatments can help to lower states of hypercapnia, reduce anxiety and restore baseline mental status……Paula can attest to that!


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