Stress response

The stress response, commonly known as the fight-or-flight reaction, is the first part of so-called General Adaptation Syndrome (GAS). It's a short lasting physical reaction of the body (or organism) towards the real (or even any imagined) threat. This response can be seen from multiple of levels - molecular, cellular, anatomic or atomic. It can be defined by physical or/and chemical processes which are triggered by it, or by any physical symptoms on the perception level. Or by some other means.

Three phases of GAS are:

1. stress response (fight-or-flight reaction)
2. resistance
3. exhaustion

So in the hypothetical situation where your life is in danger and you are forced to run away, the first part is very explosive and effective accumulation of energy at your disposal. If the threat persists, the next phase called resistance, is much longer sustainable state of increased level of disposable energy, but decreasing with time. After a while, depending on physical condition of that particular person, the third phase called exhaustion will follow. This is the state where the most of the energy is already spent, and the body is no longer in a position to fight or flight anymore. 

But from those three phases the first one is by far most interesting, so let's go deeper into particular physiological and chemical changes that are triggered by the stress response. It's all happening in real time, so the stress response is occurring on the observable level (to a certain degree of course). The consequences of the stress response could be put into two broad categories:

a) short-term consequences

b) long-term consequences

and those two differ substantially, so let's elaborate both of them.

SHORT-TERM

In the short-term, the stress response can be useful and helpful by presenting some information (a lesson learned), the impulse for the body to improve, or get stronger. In the short-term, it can be even perceived as a pleasurable event, providing it's happening within well-known boundaries (like for example in adrenalin sports). But it can be harmful in the case when the impulse is too strong to handle, and it slips the person into any negative experience of stress. And in the big proportions we talk about trauma (on mental level) or the injury (on physical level).

The principle behind the stress response in the short-term is to provide the organism the opportunity to improve, or strengthen itself in some way. Providing there is the sufficient and quality recovery time, and handling the stress is still manageable (to the comfortable level), the result should be the improvement of the body in dealing with that particular type of stress or condition.

The analogy could be used of learning how to drive the car. The frustration and stress associated with handling new circumstances evoke the stress response on the number of occasions. But if handled, it leads into the ability of driving the car, which in turn becomes a very useful skill in life.

LONG-TERM

By the long-term consequences of stress response I don't mean cyclical and continual short-term stress response with recovery time on day-to-day basis. But mainly it means some degree of continual residue of stress, which hasn't been handled within the manageable (or comfortable) level. Or, in the case when there isn't sufficient recovery time provided to the organism, even if the impulse itself is handled well. This stress is not really used for an improvement of the organism, but instead it builds up as some form of toxic substances within the body, or it can manifest as the lack of useful (energy) substances in the body.

Now here, we really talk about quite negative consequences of the stress response. Those can be recognizable on physical level, as well as on the perception level. It's roughly summarized in the flow diagram bellow:

Noise, heat, infection, isolation, aggression, and many more other factors persisting in the experience of the individual, can lead into some sort of negative long-term consequences of the stress response. Concrete physical symptoms then follow, for example the memory loss, the rapid (unhealthy) weight loss, ulcers, heart diseases, loss of sexual function, and many many others.

DISSECTION OF STRESS RESPONSE:

Once we have cleared the function of it, and the differences between long-term and short-term, we can now go deeper into many particular changes within the body. For easier grasping of so many processes, I created a simple list of direct physical and/or chemical processes that follow immediate stress response. In brackets, I present the particular hormone, which is responsible for that particular physical response - even if only in those cases (of course) where it can be determined. So simply put, the stress response causes:

- increased heart rate (adrenalin)
- increased blood pressure (noradrenalin)
- decreased pain sensitivity (endorphines)
- stopped/slowed down the activity of digestive system (cortisol)
- stopped/slowed down the activity of reproductive system (cortisol)
- alerted mind (adrenalin)
- enriched blood with:
    a) glucose  (glucagon)
    b) fatty acids (cortisol)
- started up/kicked in of the immune system (ACTH)
- started up the proliferation (building up) of T-cells
- inhibited production of GH (growth hormone)
- stimulated release of CRH from hypothalamus into blood
- stimulated anterior pituitary to release ACTH
- stimulated cortisol synthesizing from cholesterol in adrenal cortex
- increased carbohydrate metabolism (glucagon, cortisol)
- stopped/slowed down the tissue repair (less GH)
- increased rate of blood circulation (adrenalin+noradrenalin)
- enhanced memory formation (adrenalin)
- increased signalling of sympathetic part of nervous system
- suppressed signalling of parasympathetic part of nervous system
- prepared body to deal with challenges (adrenalin)
- inhibited inflammatory response (cortisol)
- suppressed stomach activity
- reduced secretion of digestive acids
- decreased blood flow to the walls of the stomach
- slowed down epithelial cell replacement in the gut
- reduced thickness of mucous membrane in the gut
- reduced production of reproductive hormones
- loss of sexual desire (less testosterone)
- disruption of sexual performance (less testosterone)
- enhanced brain activity - agility - learning
- more relaxed lung muscles - prepared for more oxygen getting in
- increased volume of lungs / their effectiveness

ADH negative feedback

And just as I promised to you in my last post, I'm bringing here nice flow diagram that very nicely explains how the body regulates the amount of water in the blood and therefore the body itself. It comes from GCSE book on Human biology (Letts, 1994).  The diagram is pretty much self explanatory, so I don't have to say very much about it.

Maybe only that on the most left and most right sides of the picture the text says: "Norm with just the right amount of water". It's the same text on both sides. Just wanted to make sure that you know, because it came out a bit blurry on sides. Otherwise, the picture describe so-called negative feedback loop. It's called negative because it negates any too big alteration from the constant norm level of certain molecule or hormone in the blood. If it goes too up, something happen to make it go down, and vice versa.

In this case, ADH goes up when body's reserves of water are going short, and no new water is getting into system. ADH means anti-diuretic hormone, which could be translated that it goes against of(anti) the loss of water in the urine (diuretic). That happens the way that kidney increases the process of reabsorbtion to the level that is needed, in order to save the water that is already in the system (or in this case in the blood). When ADH goes down, kidney decrease reabsorbtion of water, so more of the water in the blood end up in the urine.

The content of water in the body is controlled by Hypothalamus. This very small part of the brain regulates the content of the water by measuring the osmolarity of the blood. Osmolarity could be simply described as the amount of dissolved particles in the water. It can be solid particles or gases. To give you a clearer picture, imagine two pint glasses of water. One would be filled by pure water and in the other, there will be a lots of salt, sugar, or some other stuff in it. So the difference between those two pints would be the amount of empty space between water molecules, despite of the same volume, or even the mass of the content in the pint glass.

Now, once the Hypothalamus detect the change in the osmolarity in the blood (up or down), it signals the pituitary gland to secret more or less of ADH hormone. This hormone then travels by blood into kidneys, and those interpret it as the signal to reabsorb more or less water, respectively. The mechanism by which this is done, is the inserting the special proteins called aquaporins into the cell membranes. Those proteins work as a channel for the water to be able to cross the membrane, as the name itself suggest - the pore for the water. The more aquaporins, the more water is reabsorbed. So the less ADH hormone means less aquaporins, which means less water reabsorbed and let go into the urine. Simple as that. 

3-tier system of hormones

In this post, I will get into closer examination of endocrine or hormonal system. It's called 3-tier, because the secretion of hormones comes in three sort of "waves". The first one comes from hypothalamus, which release so-called relasing hormones, or in some older literature you can see it by the name releasing factors. Apart of those, there are release-inhibiting factors, which are hormones that act as having an opposite effect to releasing hormones.

 

Hypothalamus releases hormones into two ways. Either through the pituitary stalk into anterior pituitary lobe, or straight into posterior pituitary lobe. And those two lobes are already second wave or tier, from which series of another hormones are secreted. That would be ADH and oxytocin from posterior pituitary lobe and TSH, FSH, LH, PrL, GH, ACTH, beta-lipotropin, and beta-endorphin enkephalins from anterior pituitary lobe. All those hormones are directed towards gland or other organs, which become third tier in the system, and react to the signal by further secreting of another set of hormones.  

 

Those glands and organs could be thyroid gland or mammary gland, or liver, or nerves. For better illustration of what I have just written,  here is a picture I took from Open University course book on Human biology.  It summarizes all pathways I mentioned in nicely color flow diagram. In this case another proper example of human body flow diagram.

 

 

 

So let's start nicely to explain main hormones.

ADH is anti-diuretic hormone, which gives signal to kidney to start reabsorbing more water. When the level of water in the body is adequte, ADH will stop coming to kidney, because hypothalamus will stop releasing first set of hormones. I'll bring nice flow diagram in some future post, as this particular negative feedback deserves more attention in a separate post.

 

TSH stands for thyroid-stimulating hormone, which clearly means that thyroid gland will become stimulated for prodution and secretion its hormones thyroxin and tri-iodothyronine. Those than go out and have the effect on their target cells.

 

FSH is follicle-stimulating hormone, which means the follicle in the ovary and testes. Those produce and secrets their own hormones. For testes it's testosterone and for ovary it's progesterone and oestrogen. Those two organs are further stimulated by LH (luteinizing hormone), and ovary also with PrL (prolactin), which affects mammary gland too (for producing a milk).

 

Then we have here a growth hormone (GH), which gives signal to liver that it's time to build some more tissue - hence the growth promotion. Liver reacts by releasing IGF-1 (insulin-like growth factor), which starts the action by bringing more glucose from bloodstream into the cells, where it can be used as energy for building new tissue, or repairing the old one.

 

ACTH stands for adrenocorticotropic hormone, because it stimulates adrenal glands, and it further release the group of hormones called corticosteroids. So that would be all abbreviations from the picture above, but there is still more to come as I didn't mention no examples or releasing hormones yet. So here it is. There are two types of hormones coming from hypothalamus to anterior pituitary lobe, also called neurohormones:

 

Releasing hormones (or factors):

GnRH - gonadotropin-releasing hormone

CRH - adrenocorticotropic hormone-releasing hormone

TRH - thyroid-stimulating hormone-releasing hormone

GRH - growth hormone-releasing hormone

 

and release-inhibiting factors:

SIF - somatostatin - inhibits secretion of GH and TSH

(also known as GIF - growth hormone release-inhibiting factor)

PIF - prolactin release-inhibiting factor

 

So now I hope you have some idea about what hormonal system is. Of course, there is much more to be said about any particular hormnone or pathway, but that would be loads of pages about each one. This post serves for a rough summary, accompanied with nice flow diagram for better imagination of what is being written. Only time will tell if I expand this post in the future, but so far I think that it's deep enough. See you later. 

Level of glucose in the blood

In this post I'm bringing here one of the most typical representative of the flow diagram. This one explains the process of working on the steady level of glucose ( type of simple sugar) in the blood. This is achieved by so-called negative feedback loop. Negative, because it negates any bigger changes from the balance, and restore the level towards the stable position - within the norm. The mechanism is two-fold.

 

The pancreas creates two hormones called the insulin and the glucagon, and they act in antagonistic way, meaning they function in contrast. Insulin takes glucose from bloodstream into the cells that need it, and this way lower the level of glucose in the blood. Glucagon, on the other hand, supress the action of insulin, so the glucose in the blood starts accumulating again. If I may offer an analogy, they work just like the gas pedal and the break pedal in the car.

 

But this is all pretty basic knowledge. I took this picture out of the GCSE book on Human biology (Letts, 1994)  and technically, we talk the language of sixteen years old pupils. So let's go a bit deeper. The healthy blood glucose level is within the range of  4 to 6 mmol/l. Of course, that level fluctuates during the day as the reflection of having meals containg carbohydrates.
 

After such a meal, the level tends to rise, because the food needs to be digested and all micronutrients (results of digestion) go into the bloodstream. This is the signal for pancreas to release the insulin, which takes the glucose molecules across the cell membrane into the cells. Glucose molecule is too big to cross the plasma (cell) membrane by itself, so it needs the insulin to help widen a gap a little bit.

But then, when you don't eat for a while, the level goes down, and this is a signal for pancreas to release the glucagon, which stops the insulin from doing its job. This way the glucose can't get inside anymore, and stays in the blood. By this mechanism, the relatively stable level is achieved, falling in the healthy range of 4-6 mmol/l. This could be translated as 4-6 milimole per litre of blood, in which one milimole (or thousanth of one mole) is 180 mg of glucose.

I know that this is probably really hard to imagine, so I put it into the perspective. Fluctuation during the day within this healthy range is ok, but hit the level of 10 mmol/l, and you'll be diagnosed with hyperglycemia - which basically means having too much of glucose (sugar) in the blood. Or on the other hand, if your level sinks under 3 mmol/l, then you'll be diagnosed with hypoglycemia - which means not enough glucose in the blood.

So why is so important for the body to have always a stable supply of glucose? Well, many reasons, but probably the biggest one is that the glucose is the only food for the brain, and the whole nervous system. And you probably want those parts to work all the time, and properly. Plus the glucose is used as a fuel for movement. Fat is also a fuel, but glucose is much more readily available for immediate actions and reactions. Lipids chips in mostly when you move very slowly, or not at all (holding the position of the body). But all rapid movements, including your fingers, eyes, or ankles, are down to glucose, so without it (or with low level of it), the body would be pretty slow and stiff. That's why.