Acidosis can change mitochondria

” Acidosis initiates a rapid and reversible homeostatic programme that restructures mitochondria, by regulating mitochondrial dynamics and cristae architecture, to reconfigure mitochondrial efficiency, maintain mitochondrial function and cell survival.” Khacho, M., Tarabay, M., Patten, D. et al. Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survivalNat Commun 5, 3550 (2014). https://doi.org/10.1038/ncomms4550

Respiratory Acidosis [from respiratory pump failure] is one cause of encephalopathy. .

I am interested in the hypothesis that the stress in bipolar attacks is one of respiratory acidosis type 2,  from failure of the respiratory muscle pump complex.

Kraepelin observed too slow breathing at rest in his depressive bipolar patients- thousands of them during his career [and of some of his colleagues]. The patients did not sense their trouble breathing but did complain of the consequences –  anguish and distress- more commonly experienced in the polio era.  A metabolic switch occurred to increase breathing rate at rest but became too fast with apneas…again unknown to the patient and if not carefully measured- not known to the doctor.

This is why Kraepelin thought that these reversible attacks of altered mental status were attacks of retaining of acids [PCO2] in the blood causing a range of symptoms- altered mood, intoxication [euphoria], altered locomotor activity- and altered mental status.  Today we know more about metabolic dysfunction, they are common and all cause nonspecific symptoms.
My friend Paula discovered in a first aid course that her breathing rate was 3-5 breaths per minute. Her doctors were not at all comfortable with this but tests show her to be perfectly healthy.  They have forgotten Dr JS Haldane’s work showing a very wide range of breathing rates at rest in healthy people.

Paula did have an attack of bipolar depression after a series of illness and infection. 

We think now that it may be possible that she [and Kraepelin’s unmedicated depressive patients] had injuries affecting the function of the respiratory pump system AND changing the way her mitochondria work during periods of worsening acidosis.

” Acidosis initiates a rapid and reversible homeostatic programme that restructures mitochondria, by regulating mitochondrial dynamics and cristae architecture, to reconfigure mitochondrial efficiency, maintain mitochondrial function and cell survival.”Khacho, M., Tarabay, M., Patten, D. et al. Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival. Nat Commun 5, 3550 (2014). https://doi.org/10.1038/ncomms4550

Paula was anoxic at birth and was resuscitated and transfused and then was fine [except for that long period of illness].

Kraepelin’s work and now the current work on the plasticity of the mitochondria and the very existence of a Paula suggests a need for a more scientific clinical approach to the diagnosis and treatment of [unmedicated] depression, mania, psychosis, loss of working memory, encephalopathy and insanity, chronic locomotor patterns of delirium and dementia [potentially treatable].

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