Thermoregulation and body temperature

[HTester]

My daughter's extremities are constantly ice cold.

Besides shivering, and brown adipose thermogenesis (BAT), the third major physiological defense against cold is peripheral (mostly skin) sympathetic vasoconstriction. As far as the autonomic nervous system is concerned, the critical thermoregulatory task is to maintain the temperature of the internal organs and the brain near 37 C or 98.6 F. One mechanism that has evolved to ensure this, is to divert blood flow away from the skin when core body temperature is too low and direct blood flow toward the skin when core body temperature is too high. Probably you are all aware of this.

Your daughter's arms, legs, fingers, and toes are cold because her body is trying to protect her brain and her heart from cold. The question I'm trying to get at is why these three physiological mechanisms appear to be operating at the wrong "setpoint" in PWME. My current idea is an extension of the IDO metabolic trap, involving the predicted high brain serotonin. Hypothalamic serotonin, at least in rats, is a known inhibitor of all three of these thermoregulation mechanisms.

There are temperature sensors in skin sensory nerves and also in the brain. They consist of neurons with temperature-sensitive ion channels in their cell membranes. So evolution cares about the temperature of fingers and toes, but naturally, it cares more about the brain and internal organs.

The reason I'm using shivering for an inquiry into thermoregulation is that people know when they are shivering and don't know when brown adipose cells are generating heat. We might use skin vasoconstriction as a measure but it's not as objective or as quantitative as a thermometer.

 

[Rufous McKinney]

The question I'm trying to get at is why these three physiological mechanisms appear to be operating at the wrong "setpoint" in PWME. My current idea is an extension of the IDO metabolic trap, involving the predicted high brain serotonin. Hypothalamic serotonin, at least in rats, is a known inhibitor of all three of these thermoregulation mechanisms.

I think your onto a productive line of inquiry.

Not shivering at the moment, I'm 97.8 degrees...low again. (I don't really have major issues with cold hands and feet).

 

[Fighttolive]

I don’t know my baseline temperature, but I’ve been checking it recently, doesn’t get out of 96 F, that’s really interesting, maybe my thyroid is messed up or..

Viral-mediated hypothalamus damage?

my hands and feed are always cold. Even as a child though.

 

[JadeD]

I’m not sure if the skin vasoconstriction is purely due to a lower core body temperature in PwME. It might also be due to autonomic dysregulation when posture changes. For example my hands are always warm when supine but merely sitting up in bed in the morning makes me have a hot flush and start to sweat. My peripheries then go freezing cold for most of the day despite my normal temperature being 37.2 degrees C.

Peripheral vasoconstriction in this case is probably attempting to push blood from the extremities to the core. Internally I feel very hot but my hands are like ice blocks.

 

[WantedAlive]

Have you thought about how it can be that the temperature threshold for activating BAT is a half degree (C) warmer than the threshold for activating shivering?

I didn't know that. In response I would be inclined to conclude therefore that the thermogenic response in PWME is not cold induced but infection induced. WAT is a known reservoir for chronic infections and lasting thermogenic responses, and also acute infections (such as influenza infection via folate cycle) triggering a thermogenic response that persist long after the virus has cleared. I had an acute onset (acute SIRS - 4/5 SOFA score) from a flu vaccine, possibly preceded by chronic enterovirus infection (8 year symptoms of progressive dyspepsia then recurring gastritis). I guess there could be both (chronic / acute) contributing to thermogenesis in PWME.

UCP-1 expression was not increased

Mmmm, interesting. So UCP1 independent thermogenesis leaves creatine-cycling or more likely calcium-cycling generated thermogenesis. That's moving toward 'malignant hyperthermia' phenotype, which is interesting because exercise can trigger malignant hyperthermia in susceptible individuals, and a mild MH might resemble something similar seen in ME/CFS exercise studies.

So I wonder if UCP1 is impaired in ME/CFS? A study demonstrated mice lacking microbiota have impaired UCP1-dependent thermogenesis [1]. Considering all PWME seem to have altered microbiome perhaps has some influence in this thermogenic adaptation. Pigs don't have UCP1, do they get ME/CFS?!!

I mentioned heme in my earlier post as a contender in sustaining thermogenesis. Ruling out UCP1 might support this more. The red blood cell membrane blebbing seen in PWME, the lack of deformability, the sticky blood, all this has led me to thinking there might be high RBC turnover, and as a result high free heme. Evidently, increased heme oxygenase and bilirubin levels found in PWME might support this theory. Increased heme interacts with the protein MFSD7C which switches mitochondrial ATP synthesis to thermogenesis [2]. Heme also potently inhibits PDH activity [3]. Heme promotes inflammation and vascular dysfunction. I've not managed to find any statistics of free heme tests in PWME to rule this theory in or out.

Thanks for the informative discussion! You've whet my appetite to explore UCP1 independent thermogenesis further.

 

[wigglethemouse]

I mentioned heme in my earlier post as a contender in sustaining thermogenesis. Ruling out UCP1 might support this more. The red blood cell membrane blebbing seen in PWME, the lack of deformability, the sticky blood, all this has led me to thinking there might be high RBC turnover, and as a result high free heme. Evidently, increased heme oxygenase and bilirubin levels found in PWME might support this theory.

This is the Hanson finding on Heme

Prospective Biomarkers from Plasma Metabolomics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Implicate Redox Imbalance in Disease Symptomatology
https://www.mdpi.com/2218-1989/8/4/90/pdf

"Heme, the pigment that gives blood its red color, is one of the most statistically different metabolites, with higher abundance
in patients compared to controls (Figure 1a and Table 2)."

 

[wigglethemouse]

@HTester would like some community members to measure their temperature when they start shivering. See this thread for directions and posting.
https://forums.phoenixrising.me/threads/a-community-thermoregulation-experiment.82096/

 

[WantedAlive]

This is the Hanson finding on Heme

You champion, thanks.

 

[HTester]

I’m not sure if the skin vasoconstriction is purely due to a lower core body temperature in PwME.

I'm sure you are right. What I've been posting about is how the system works normally. Much of autonomic nervous system control is routed through the hypothalamus, so it's reasonable to look for ways in which hypothalamic signaling could go wrong in PwME. One of those signals is serotonin, and since the IDO metabolic trap predicts too high serotonin in brain serotonergic neurons, this seems like a good line of investigation to follow for awhile.

 

[HTester]

For example my hands are always warm when supine but merely sitting up in bed in the morning makes me have a hot flush and start to sweat. My peripheries then go freezing cold for most of the day despite my normal temperature being 37.2 degrees C.

If, after sitting up in the morning and inducing the flush/sweat and the freezing cold hands/feet, you lie down again, do your hands and feet get warm again? Does the sweating stop?

I'm assuming the sweating and flush are happening in your face, not in your arms, for example. Is that true?

 

[Judee]

I don't shiver unless I'm sitting for a long time in a cold car in the middle of winter.

I sleep under two comforters and 3 blankets - one of them electric and set the highest it will go. Sometimes I will fall asleep under all that and still wake up 2 hours later with my legs cold to the touch but I don't shiver. This year I'm even considering adding a 3rd comforter.

Thanks, @HTester. Good to see you again.

 

[JadeD]

If, after sitting up in the morning and inducing the flush/sweat and the freezing cold hands/feet, you lie down again, do your hands and feet get warm again? Does the sweating stop?

I'm assuming the sweating and flush are happening in your face, not in your arms, for example. Is that true?

Lying back down would cause my hands to go warm eventually but once the sweating is triggered it can remain for most of the day. Although some days on occasion I don’t sweat at all so I’m unsure as to what’s driving it.

The hot flush I experience in the morning with a posture change and even something simple like drinking a tea is felt all over. The sweating happens in quite a few places, hands and feet included.

 

[vision blue]

Intersting sets of issues. Is there a poll on this? I'd be curious to know what percent of CFS folk feel like they have a temperature regulation problem.

 

[wigglethemouse]

You champion, thanks.

The supplementary data has the raw values in Excel if you are interested
http://www.mdpi.com/2218-1989/8/4/90/s1

 

[WantedAlive]

My current idea is an extension of the IDO metabolic trap

In context of this and my exploration into the possibility of heme-sustained thermogenesis, I forgot to include in my earlier post that IDO2 has demonstrated to be a negative regulator of IDO1 by competing for heme-binding [1]. There's a lot of unexplored territory here, but it does suggest one possibility of how IDO1 might become 'overwhelmed' in the metabolic trap hypothesis that if in the presence of high heme a defective (mutated) IDO2 might suppress IDO1 expression and allow TRP levels to become too high.

Don't mean to divert this from 'thermoregulation and body temperature' but I just feel sure the thermogenesis subject is why we struggle with thermoregulation.

 

[anni66]

My daughter's extremities are constantly ice cold. The only time this abates a little is during the summer months, or when she is in the sauna she has. Shortly after coming out of this sauna, or warm bath, she is cold again. She does shiver too. There is almost constant temperature dysregulation, and there is no way to stabilise it.

Here in Canada where summer is really only serious in July and August (a bit in September) the challenge is even more difficult. The winter comes early and lasts for a good 6 months, it is hard to keep temperature stable. Indoor heating is dry and leads to its own discomforts, and the houses are often drafty due to severe weather.

There are extra heating pads in her bed and chesterfield, plus extra mobile oil radiators in the house, because the central system just doesn't provide enough ambient heat.

My daughter had less chills in Florida, and generally likes the hot climate.

My daughters limbs are always freezing ( very weirdly her knees are colder than thighs and calves ) , I had put this down more to OI issues than central thermostat.

She often complains that the cold is " inside", in her bones. Even in a warm bath they don't heat up.
I don't kn8w that she shivers, her muscles fo contract involuntarily but she dosnt associate this with cold.

She can't handle too much heat weather wise, though humidity / pressure is more of an issue.
Set points are way off. She gets too hot too.

 

[raghav]

I cant tolerate the summer heat and humidity. I stay in my airconditioned bedroom throughout the 3 months of summer. I come out at around 2 am in the night for some time and sit in the living room.

 

[aquariusgirl]

I had to wear thermal ski clothes in bed including socks for 6 months at my worst. Body Temperatures was 95/96 for years. Never shivered.

 

[HTester]

I cant tolerate the summer heat and humidity.

Do you sweat and/or flush (red face) when very hot?

 

[raghav]

I sweat excessively when I go out in the sun for even a few minutes. I was taking a medication called Deanxit (Flupentixol + Melitracen ) which helped me tolerate the heat. But the medicine was subsequently banned and my body is not able to tolerate the summer heat. I feel like I am going to faint if I stay in the living room for even a few minutes. Once I get into the airconditioned bedroom my energy levels come back. I also get good relief when I take a cold bath.