Submitted by Pheophyting t3_yi3t9o in askscience
To my very dumbed down knowledge, the hypothalamus pulls some regulatory stuff to get pyrogens like IL-1 to circulate in the body which somehow adjusts the body's "thermostat" to default to a higher temperature.
My question is, how does this actually generate a fever? Where is the increased heat/thermal energy actually coming from?
The 3 phases of fever
Fever is your body’s way of letting you know something is wrong. In a way, the fever is helping to fight off your infection.
This happens in 3 phases.
Your body reacts and heats up
Your blood and lymphatic system make white blood cells, which fight infection. When you have an infection, you make lots of these cells. They work faster to try and fight off the infection.
The increase in these white blood cells affects your hypothalamus. This makes your body heat up, causing a fever.
In the early stages of a fever, you often feel cold and start to shiver. This is your body’s response to a rising temperature. The blood vessels in your skin tighten up (constrict), forcing blood from the outer layer of your skin to inside your body where it is easier to keep the heat in.
The outer skin layer then becomes cool and your muscles start to contract. This makes you shiver. Shivering produces more heat and raises your temperature even more.
The fever levels off
In the second phase of a fever, the amount of heat you make and lose is the same. So the shivering stops and your body remains at its new high temperature.
Cooling down
Your body starts to try and cool down so that your temperature can return to normal. The blood vessels in the skin open again, so blood moves back to these areas. You sweat which helps to cool the skin, this helps to cool down the body.
This phase of a fever may or may not happen naturally. You may need to have some medication to start it off, as well as treating the underlying cause of the fever.
You also shiver a bunch. First you feel “cold” because your body has reset the desired temp to something higher than usual, this then signals your muscles to shiver thus generating heat. Same deal if you are simply outside in the cold and start to shiver.
You are right, it is surprisingly difficulty to find the type of information you are asking about when you include the word "fever" in your search.
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Our body heat is regulated by our body's ability to balance of how much heat we generate and how much heat we lose to the environment.
Here are some examples of heat production (notice how many are simply the result of normal metabolims):
-Basal metabolism
-Muscle activity, by shivering and muscle contractions
-Extra metabolism caused by the effect of sympathetic stimulation and norepinephrine, -epinephrine on the cells
-Extra metabolism caused by increased chemical activity in the cells, especially when the cell -temperature increases
-Extra metabolism caused by thyroid hormone and, to a lesser extent, testosterone and -growth hormone on the cells
-Extra metabolism needed for digestion, absorption, and storage of food
-Most of the heat produced in the body is generated in the liver, brain, heart, and skeletal -0--muscles during exercise.
And we balance that by also regulating mechanisms of heat Loss which is determined almost entirely by:
-How rapidly heat transfers from the skin to the surroundings
-How rapidly heat is conducted from where it is produced in the body core to the skin
https://www.ncbi.nlm.nih.gov/books/NBK499843/
A fever triggers an adjustment of where that balance is, so as metabolic processes are triggered to run hotter, our circulatory system is triggered to allow less heat loss through our skin, and we don't sweat.
The term "a fever broke" is referring to a person who after a fever has begun to sweat to allow for the rapid loss of all that heat.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/
Fever induction and signal transmission
Yesterday I had such a fever (unfortunately there wasn't any thermometer to measure it), that I had terrible shivers, first time so strong that all my muscles literally ached after 15 minutes. And my lips became purple, and fingertips. First time I've seen something like that.
I took paracetamol to fight it and went to bed early, slept under the blanket in uniform (soldier here) and was rather cold anyway until med kicked in and I've almost drowned in my own sweat.
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If you are asking about cellular mechanism in the hypothalamus, see below.
From: https://www.ncbi.nlm.nih.gov/books/NBK562334/
Milton and Wendlandt demonstrated that fever is mediated by the pyrogenic activity of prostaglandins (PGs), specifically PGE2. The synthesis of PGE2 begins with membrane phospholipids being converted to arachidonic acid (AA) by phospholipase A2 (PLA2). AA is then converted to PGH2 via cyclooxygenase (COX), after which PGH2 undergoes isomerization to PGE2 by PGE synthase. PGE2 acts via the EP3 receptor to affect specific neurons within the hypothalamus that aid in thermoregulation. Medications that inhibit COX are a mainstay of treatment for fevers, as it halts the conversion of AA into PGE2 and, thus, other prostanoids that can lead to fever.
The action of PGE2 begins when exogenous pyrogens (e.g., bacteria, viruses) stimulate endogenous pyrogens such as IL-1, IL-6, tumor necrosis factor (TNF), and interferon (IFN) to alter the hypothalamic set point via the organum vasculosum of the lamina terminalis (OVLT) and raise the core body temperature. Endogenous pyrogens also act to trigger an immune and inflammatory response. The immune response includes leukocytosis, T cell activation, B cell proliferation, NK cell killing, and increased white blood cell adhesion. The inflammatory response includes increased acute phase reactants, increased muscle protein breakdown, and increased synthesis of collagen.[4]
So if the body is heating up to fight an infection are we not working against it by taking antipyretics?
The fundamental understanding is hard to find, but simple: our metabolism is broken, badly, as a baseline, and we make it worse to have a fever.
It doesn't cost anything near what we pay to run a body of our size. We know this because everything with "cold blood" does so for literally 10% of the cost (normalized for body weight and temperature).
Where do the other 90% of our baseline calories go? Heat. Specifically, we poke holes in the membranes of our mitochondria (via uncoupling proteins) to make them less efficient. This means we burn more energy to get the same ATP (cellular energy molecule), the rest of which is heat. This, in turn, heats our body and lets us be "warm blooded", at tremendous metabolic cost. To get warmer, we simply increase the number of these proteins. There's also diet drugs that do this, but they're incredibly dangerous because you can't plug the holes once they're made, you just have to wait for the proteins to break down.
Incidentally "cold blooded" species can get fevers too - pyrogens prompt them to bask more and get to hotter temperatures, a sort of "behavioral fever".
For pendants, note the quotes around "warm blooded" and "cold blooded".
Yes, that's correct. If I don't have anything pressing to do, I usually don't take fever reducing meds unless my fever is over 38°. low grade fevers aren't hurting me, but they are hurting whatever infection I may have.
Our immune system is a bit outdated. Typically, we can treat the ailment better ourselves with proper medications and procedures. Back when our immune system developed, we didn't have any of these things. A fever damages your body, your brain, and your immune system wreaks a lot of collateral damage. In our early stages of life, a little collateral damage is better than dead. Nowadays, we don't need that collateral damage because we can just treat it ourselves.
Our immune systems are not perfect, but it's better than nothing.
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Here you go.
Uncoupling proteins and/or thermogenin usually generate heat. I actually have a mild fever now…
The link below should hopefully lead you to some of the answers you’re looking for.
I did a brief literature review:
White blood cells The core cause of the fever starts with white-blood cells (specifically mononuclear phagocytes) that produce endogenous pyrogenic cytokines when they encounter a foreign agent (e.g. bacteria, virus, etc...) that is/produces pyrogen(s) TL;DR: Immune cells release a signal
Through unknown mechanisms they communicate to the brain which increases production of additional factors (likely prostaglandin E2) that then act on thermoregulatory neurons. TL;DR The signal communicates with the brain telling it to allow an increase in temperature (think of it as the brain telling the rest of the body the normal temperature is now 100 degrees).
The major changes are thought to be derived from:
TL;DR: Mainly the heat is from an increased metabolism in brown adipose tissue
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/ https://pubmed.ncbi.nlm.nih.gov/223485/
Basically, yes. Fevers are functional in that the higher body temperature begins to denature the proteins in infectious agents, or otherwise makes it inhospitable for them to reproduce, which allows the immune system to finish mopping up. We should let fevers do their thing unless the person is suffering a lot of discomfort (with the understanding that being sick in itself is going to be uncomfortable, and the fever will make them achy and weak. Which is a good signal to rest and let the immune system work.)
If the fever starts getting really out of control (like 105F/40C or higher) it runs the risk of cooking our own proteins as well, causing brain damage, or causing cells that we should probably hold onto to go into apoptosis. That's when we should step in and be like "dude, back the hell off" and try to lower body temperature or encourage the fever to break before it busts something it wasn't supposed to.
Very informative and easy to understand, but the OP's question was entirely about this sentence, which you just glossed over without explanation: "This makes your body heat up, causing a fever."
What makes your body heat up? What mechanism is the hypothalamus controlling? Is is muscular contractions (shivering) or some other thermal process?
"Heat/thermal energy" is simply a measure of how fast tiny little particles are moving; the more work (energy) being done, the faster (hotter) the particles are moving. There are lots of reasons that cause the heat to go up (as outlined by another commenter here). Our bodies are doing A LOT of work; our bodies are constantly generating heat. This is why we sweat; heat transfers to the sweat and the sweat evaporates into the atmosphere, thus cooling us off. You can think of sweat like a biomechanical liquid cooling system. Under Armor clothes for sports works by absorbing the sweat into the material, which increases the surface area in which the atmosphere can evaporate it, cooling us off even faster. To raise our body temperature, all our body has to do is regulate how much energy is being lost to the atmosphere versus how much energy is staying in the system (our body); which it can do in all sorts of ways.
Is that colateral damage only for high fevers or would a 38° fever do some colateral damage?
Thank you! So the hypothalamus induces the fever primarily by reducing heat loss, e.g. by reducing blood flow to the skin surface and cutting off the sweat response, rather than increasing mechanical or chemical thermal generation? Or is it more of "there are lots of processes in the body that contribute to heat generation and heat loss, and the hypothalamus pulls all of them simultaneously?" Or is it that there are so many interrelated processes that it's not clear exactly which levers the hypothalamus is pulling, we just know that heat generation increases and heat dissipation becomes less efficient?
The hypothalamus is responsible for regulating certain metabolic processes and other activities of the autonomic nervous system. It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland. The hypothalamus controls body temperature, hunger, important aspects of parenting and maternal attachment behaviours, thirst,[3] fatigue, sleep, and circadian rhythms.[4]
Mostly high level fevers; but our bodies maintain a "body temperature" for optimal performance for a reason. Low grade fevers are not much to worry about.
We have a pretty good idea of how the immune system works; but we know less about how it works than we do know how it works (as far as we know). It's mostly reducing the amount of thermal energy lost, but doing "more work" does inherently increase thermal energy. So it's probably a balance of all of that.
Here's a good YouTube channel that covers quite a lot of the immune system in a very layman's kind of way.
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If we are allowing less heat loss, why do we feel warm on the forehead?
Pretty sure of you're close to 104 or higher you run the risk of dying. Gotta drop that fever. Or if you have a non productive fever like when you get a vaccine. It's doing nothing to help you in that case
You forgot an important mechanic - perceived body temperature. People with serious fevers often feel cold and actively take steps to warm up (e.g. warmer clothes).
This is the answer. White blood cells causing heat? How do the other posters find that sensical? Energy amounts to raise and sustain body temp in 50 liters of water is IMMENSE. When you start exercising in the cold, it takes minutes to feel the heat.
Brown fat + non shivering skeletal muscles. Makes WAY more sense than white blood cells, a tiny tiny fraction of body mass.
That's part of resetting the internal thermostat, so I didn't include it as one of the biochemical mechanisms for generating the heat, but its a good point.
>There's also diet drugs that do this, but they're incredibly dangerous because you can't plug the holes once they're made, you just have to wait for the proteins to break down.
I always wondered if that were a thing. It always seemed to me like an excellent way to burn calories. I grew up and currently live in Vermont where the winters get very very cold and it's well-known that you have to nearly double your caloric intake if you're going to be outdoors in cold temperatures for extended periods of time. Especially doing a vigorous activity like skiing or snowboarding on a blustery day, it's frankly INCREDIBLE the sheer amount of energy the human body can cough up when it's well-fed and the need arises. I tracked myself as burning like 7k calories in a single day once.
Likewise, just going on a short walk can sap an incredible amount of energy from your body if you're not dressed well in poor weather, and it can take several hours and several good meals to get your energy level back up so it's easy to imagine that a significant amount of your body's energy budget goes to keeping you warm.
>TL;DR: Mainly the heat is from an increased metabolism in brown adipose tissue
Isn't that basically the conclusion that Wim Hof guy came to after being studied by doctors while he submerged himself in icy water? He has some breathing technique that supposedly activates his brown fat tissues and keeps him warm. Dude claims to have hiked Kilimanjaro wearing nothing but a pair of shorts. Not sure how real any of that actually is, but it's a pretty neat though. I wish I could activate my brown fat tissues on purpose sometimes.
Can hypothalamus break down and order cells to boil themselves?
>Typically, we can treat the ailment better ourselves with proper medications and procedures.
What? I object to this immune system slander. We've invented some great medicines, sure. But first off, your immune system is constantly watching out for infections and cancer and kills them before they get out of hand enough for you to even notice them. There's no way you could replace that.
When things do get out of control, we have medicine to help us out, but most of them won't just fix you by themselves, they work in tandem with your immune system. That's why people whose immune systems are wiped out are basically dead men walking. Not to mention the constant arms race with antibiotic-resistant bacteria.
The immune system isn't perfect (I'm well-aware, I have allergies and an autoimmune disease), but it's incredibly sophisticated, to the point that we still don't completely understand it, and our medical technology hasn't gotten close to making it obsolete.
I don't really disagree; it is an incredibly complex, useful, and absolutely necessary system. But with the use of medications, we can prevent a whole host of side effects from the immune system. Why wouldn't you if you could? I don't recall ever saying any of the things you're implying I've said.
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people are full of info based on old wives tales and incomplete understanding
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I always weigh this when I'm sick, because I have three related factors that make fevers much more difficult for me (30F).
I have MS, and that means:
Thankfully, I don't get fevers often, but when I do, they seriously kick my butt. My first dose of COVID vaccine took me 3 days to feel mostly normal and a full week to feel completely normal. I have had 4 doses now, and know to proactively take both naproxen and acetaminophen at their recommended highest dose/interval.
Your body can’t stop dry heat from conducting out. If the blood in the vessels of your brain and head are hotter than normal, then you will feel warmer to the touch. There’s no way for your body to become more insulating except by wearing more layers or a blanket. The amount of heat lost via dry conduction is much less than what would be lost due to sweat. Water carries much more heat than air, and when it evaporates, it also removes more heat by conduction. That’s why if you get sweat on your shirt and then move to a place at room temperature, your shirt will feel uncomfortably cold.
Also when you feel someone’s forehead, your hand is a better heat conductor than air, and your hands and extremities also tend to run colder than your core body temperature, so foreheads feel warm to the touch even at normal temperatures.
I don’t have a background in physiology, but in materials science, so I understand heat conduction. If I made a mistake, someone who knows could chime in
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If you’re a soldier why not seek medical attention?
Offshoot question: how high of a temp. Can a human body get to on it’s own?
according to NPR the record is:
115 degrees: On July 10, 1980, 52-year-old Willie Jones of Atlanta was admitted to the hospital with heatstroke and a temperature of 115 degrees Fahrenheit. He spent 24 days in the hospital and survived. Jones holds the Guinness Book of World Records honor for highest recorded body temperature.
It's a specific situation, where our warship required electrical supervision and there was noone who could replace me anyway.
I took leave of my duties quite early (around 6 PM, where I should be on legs until 10PM), took the med, sweated my butt and woke up 4:30AM in rather good shape and finished supervision. I'm already home, military is specific place where you sometimes grit your teeth to avoid massive inconvenience for a lot of people.
Huh. You’d think with 900Billion spent annually they’d have another solider available.
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While good and interesting info, I feel like that doesn't qualify as on its own. With a heatstroke aren't their external factors raising the body temperature?
for the 95% of the earth's population that don't use cheeseburger units - that's 46 celsius
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Although evaporation dominates as a method of heat loss, there are two biological mechanisms that I am aware of that can additionally decrease dry conduction.
Capillary constriction in the skin reduces blood flow and makes the skin a more efficient insulator.
Piloerection of hair follicles helps trap air against the skin and improve insulation (works better on hirsute people and is mostly redundant in people that wear clothing).
> -growth hormone on the cells
does that mean someone who's growing has a higher body tempature?
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Also, is the Fever caused by using more nutrients to kill the pathogen, (As the liver, as you said, already produces lots of heat)
The rest of the world Profiting off American innovations while complaining. Typical lol
I mean fevers are always in response to some external factor, no? Heat stroke, infection, medications, etc.
What I mean as external heat source, not just a cause of a fever. An infection is not actually hot itself, your body temp is rising in response to it. In the case of a heatstroke, there's literally heat being added to your system, not just your body responding to stimuli.
It's like with hypothermia, your body isn't cooling down on its own, the freezing air/water is doing it.
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Do you happen to know how capillary constriction transmits across other organs? Would it be fair to assume that if the capillaries in our skin constrict, capillaries in other parts of the body are constructing too? E.g. I recently read a summary (layperson here) of a paper suggesting Covid 19 triggers capillary constriction in the brain and am wondering if that triggers manifestations in other organs? Or if the circulatory system is big enough that capillaries in one part of the body don’t have to experience the same fluctuations as another (provided no mechanical separation like a tourniquet or tumour or whatever)?
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40C (104F) is quite normal, specially in children. I believe what they say here is to seek help if you have 40C for more than a few days. Any thing above 41C (~106F) or if you’re in otherwise bad shape and it’s probably a good idea to seek help sooner.
People are different though, some will have 40C and be in fairly good shape, while others can barely walk as soon as they go above 38.5C.
I’m just like you. I never get fever temperatures even if I’m sick. I also get cold in the summer even if it’s hot outside. I can also manually lower my body temperature with some given time and effort and I’m learning how to raise it. Even if I get really really sick I still don’t get a fever.
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A lot of heat is generated during growth and also regeneration in the body (recovering from exercise). It’s often localized in joints and bones and takes time to dissipate, so probably won’t raise temperature much wherever you’re sticking the thermometer.
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Different systems respond to different messages. Brain and muscles increase blood flow, while digestion decreases blood flow under stress.
Not quite answering the question but fever is an adaption to viral and bacterial infections. Many pathogens are adapted to human body temperature and fever can inhibit pathogen replication and even kill some pathogens.
[deleted] t1_iuhm4ni wrote
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