Introduction
 
We will now describe the concept of stress and its diverse aristae, also including here answering mechanisms to stress whether acute or chronic, and making a reference to the Adrenal Pituitary Hypothalamus Axis. We will be interested in analyzing marathoners as opposed to sedentary men during exercising situations in order to describe adaptation mechanisms.
We will analyze exercising from an adult point of view. However, we have to understand that in women there will exist some different characteristics (particularly hormonal) related to the muscle mass. Women have a smaller water percentage because, due to hormones, they possess a higher proportion of fat.  Masculine hormones are androgens, and the feminine ones are the estrogens and progesterone.   There are masculine hormones in women and feminine ones in men. Hormones are produced by sexual glands (testicle and ovary) and inside the suprarenal gland (mainly androgens). Thus, women with high androgens will have lots of facial hair, acne, high muscular mass, oldstronger factions.   In general, this is not due to androgen production in the ovaries, but in the suprarenal glands. Feminine hormones will provoke a major level of adipose tissue than in men. Testosterone, on the other hand, is related to muscular mass and aggression.  Maximum contractile strength is the same in men and women and this is considered as the maximum strength produced per square centimeter of muscle surface. Maximum contractile strength is of 3 to 4 kg per sq. centimeter. Women, however, have two thirds of a man’s muscular mass. A lower muscular mass will provoke a lower performance in strength tests. This phenomenon does not repeat in exercises related with liquid retention (hydro saline equilibrium) such as: diving, swimming, sub aquatic activities.  The Mancha Canal swimming record is held by a woman. This is related to her pregnancy preparation and to women’s ablest respiratory capacities.
 

Response and Adaptation: two different concepts

If we climb a stair we will agitate ourselves. There will be a response which will end as soon as the exercise finishes. This is what we call response to exercise.  Adaptation, instead, is a long term process which will be the result of prolonged and frequent training. In order to analyze adaptation what interests us the most is to focalize in a marathoner’s physiological characteristics and compare them with normal values of sedentary individuals.  There is always a doubt in physiology books.  Is there a genetic base by which these individuals are always predisposed to exercise or, on the contrary, are changes produced because they exercise?   That is the question. Moreover if we take into account there are two types of muscular fiber.
 
   
 
Analysis of a “marathoner”
 
In a marathoner the volume minute is 90% superior to any sedentary man.
Lung volume (current volume times respiratory frequency, which means the air quantity that enters the lung as opposed to alveolar volume which is the one that will perform gaseous exchange) will be 65% superior to that of a sedentary man.
If a marathoner is making a high performance exercise, he has a 35% margin in order to reach maximum capacity. His margin in alveolar volume is only of 10%. This means that the capacity of rising the volume minute which will be his top cardiac capacity is lower, since the heart is functioning at his maximum level. In aerobic exercise (isotonic contraction) the most important limiting system is the cardiac one, the heart. If I raised my lung volume some more, that oxygen which I would add to my body will not be able to diffuse in order to generate a better performance, a greater energy, since the volume minute (blood going from the heart to the tissues transporting that oxygen) reached his maximum point.  
The cardiovascular apparatus will be the limiting one since it is working at a capacity of 90%. Therefore, a marathoner best physiological advantage is his cardiovascular capacity not his respiratory one.  So, this is what a marathoner is interested in working the most: his cardiovascular capacity (not his respiratory) since this will be the one that might limit his exercise.

Respiratory capacity will mainly influence resistance exercises, aerobic exercises in marathons and not the speed races (100 plain meters). A marathon runner will have as a main advantage a raise in the lung diffusion of oxygen. A sedentary individual doing exercise will transport 68 ml/min of gases through this membrane, whereas a marathoner will transport 80.

As for the cardiovascular system a marathoner will have a left heart hypertrophy. It is important to comprehend that in this case “dose makes the poison”. An excessive hypertrophy is counterproductive, reduces cardiac capacity through diminishing the volume minute. In this case a marathoner will show a “sane” hypertrophy which will raise the volume minute.  The same stimulus will produce contradictory actions depending on the dose.   Thus, a marathoner while doing exercise will show a 270% higher volume minute that during his rest. He selectively raised his capacity to pump blood towards tissues in exercise, reaching a 40% improvement over a sedentary man. During rest, this figure (5.5 liters) will be the same in both individuals.
A higher cardiac raise and a lower respiratory possibility show why during exercise, the cardiac factor will be the limit.
Why do these adaptations take place?
 
 
 
 
 
Stress Concept
 
Hans Selye is one of the forefathers of the stress concept. He defined it as an organism non specific response before any sort of demand, before a stimulus. He observed that before a stimulus from aggressive substances of any sort (cold, heat, trauma, psychological), different species’ organisms have a similar response.  He called this response general adaptation syndrome.  There exists a whole group of processes which start within the organism that respond in analogous manners to any sort of stimulus. This response arouses before fasting and exercise.
Stressor stimulus is not necessarily a bad one, it does not necessarily hurt. Playing a soccer game or making love represents a great joy. They are necessary in life. Selye used to say: “once there is no stress there is just death”.
Claude Bernard enounced that any change in the external world will produce an alteration in the organism against that natural ability which live beings possess to set an equilibrium process, towards equilibrium in the internal world and that these modifications will deviate this equilibrium in order to try to reestablish it.  
 
 
Homeostasis: homoios, “similar” in Greek, stasis “place” in that same language.  It is the group of processes which collaborate towards a stable medium against an external or environmental stimulus which tries to destabilize it.
The body will try to keep itself within a status of normality when it faces resting and exercising.  They are different situations. However, they are placed within a normal rank. If stimulus was to disappear, death becomes the major equilibrium level. Stress comes from the Greek and it means provoking tension. It is, in other words, to provoke a change.
Alostasis: Critical levels of stress which will produce perturbations that might stimulate pathological phenomena. This will produce a weakening of the equilibrium process. A stressing stimulus is a signal which will alert about situations which might jeopardize life or produce some change, pushing the body to adopt two basic responses: fleeing or fighting.  Both are linked to a very primitive and instinctive system within our organism.  Physiological processes that we might observe within our organism will prepare us for both processes. SNA and suprarenal gland are intermediaries before these responses. They will mediate as a nexus between the external stimulus and internal physiological processes.  A response to stress is therefore a stereotyped response.  The organism has a previously prepared plan regarding any circumstance. It just requires of the right stimulus to set it up. Stimulus’ perception will much influence the response intensity.  And this changes with each individual. Some of the factors which influence
 
 
 

   
They are: the individuals’ valuation of the resources prepared to face the problem, the novelty of the stimulus, its foreseeable quality and the individual’s personal characteristics.
Stress equals stimulus.
Response to stress
They are internal physiological changes, wide neuronal endocrinal mechanisms. They are no local but systemic. They are short and long term adjustments. We will analyze two of the mechanisms. One is short and the other long term.  In other words they are the adaptation of a stressing stimulus which ensures survival through two responses: fleeing and fighting.
An important concept becomes the inhibition of the processes which are not decisive for survival: digestion, reproduction, growing and inflammation. Whatever is not related with survival is inhibited. These constant stress situations are observed in children that have difficulties with their growth.  Stress will build fleeing and fighting adaptation mechanisms. However, if these are excessive they might become prejudicial and might produce pathological damage thus exacerbating preexistent sicknesses.
 
Afferent ways in response to stress.
 
Ways through which external stimulus will activate SNA or suprarenal gland and it will produce this response.
A hypothetical case: pre-surgery stress. Three different stimuli: perception, tissue damage and loss of extra-cellular liquid.  An incision will take place. Our body will perceive whether submitted to anesthesia or not.  There will be a stress at a tissue level (tissue damage) and there will also be a loss of extra cellular liquid, mainly blood (hemorrhage).
Perception: Our organism will suffer from something defined as anxiety. Anxiety will reach a cortex structure (since we are talking of conscious perception we will have to go to the consciousness structure, brain cortex). It will reach the brain area related with emotions, fear.  This area is known as limbic system. Affection, fear, anxiety and everything related to affective and emotional links is located there. I listen to someone without seeing him and I know who he is.
Tissue damage: It will reach our central system through the nociceptive ways or pain.  Again, when we analyzed the somatic system we reviewed that there was an ascendant way reaching the areas 3, 1, 2 and later area 4 descending in a motor manner.  Some of the afferent ways are nociceptive.
Loss of extra cellular liquid: it will have as an afferent way extra cellular volume receptors called baroreceptors. Baro makes reference to pressure but in a practice was it is related to volume. They will be able to perceive volemia changes, extra cellular liquid changes. If they face a hemorrhage they will perceive a volemia diminution.  At this level there are no mediators except the nervous ones.
 
Tissue damage: It will pass through the nociceptive fibers and it will use the immune system as mediator. Before pain there exists an immune response and some molecules will function as signal molecules: IL (interleukins): IL-1, IL-6 and TNF (Tumor Necrosis Factor). They will generally be immune response triggers. 
Loss of extra cellular liquid: It will be perceived by volemia receptors and its mediators will be affective introceptive tracts.
Let us analyze each one of these axis.
 
.
Hypothalamus Pituitary Adrenal Axis
AFH: adrenocorticotrofine freeing hormone.
ACTH: adrenocorticotrofine hormone.
A: adrenalin.
NA: noradrenalin.
ME: medium eminence.
ANS: autonomous nervous system.
S: sympathetic.
PVN: Para ventricular nucleus.
Hypothalamus: It is a gland located at a central level, within the encephalon. It has poorly defined limits. At a central level there is an area where we know the hypothalamus is located. We know it is there because of injuries that are produced there (we comprehend normal physiology through pathologies). We call hypothalamus this group of nuclei which will control certain hormones. These hormones will trigger hormonal cascades in the whole body which means that the hypothalamus will regulate most of our body functions. It regulates the dream-awake cycle, reproduction rhythms, hunger and satiety; it regulates the gonad (reproduction) axis, states of mind.  That is way emotional reasons could lead to amenorrhea: both nucleus are one next to the other, and they influence each other. PVN will also be satiety’s center (CRH will also the satiety’s neuronal transmitter).  EM and PVN are two hypothalamus nuclei.
ADH (anti diuretic hormone which will trigger thirst sensation and produce water re-absorption): we can find it within the hypothalamus.
Although the brain constitutes the master of the voluntary, the hypothalamus is regulating, the involuntary, and the primitive master.
Hypofisis: We will hierarchically find it just below the hypothalamus. The hypothalamus will mostly produce hypofisiary hormone liberating factors. Hypofisis usually sends a second hormone, the effectors hormone which will effectively produce the second reaction. Hypothalamus and Hypofisis relate themselves from nervous fibers and a vessel system: the hypothalamus hypofisiary system through which hypothalamus will deposit hormones in those vessels and blood alone will fill the hypofilisis wing.  They are two mechanisms: one of them acts through nervous tracts and the other thorough blood tracts, and that is how these hormones are transported. 
 
 
The hypofisis is also called Pituitary gland.
The suprarenal gland has two portions: one Cx and the other Md.
Cx has three portions. Aldosterone (produces water re-absorption and potassium and hydrogen secretion) is produced by its outermost external layer. It will be liberated due to the angiotensine II stimulus. The second layer will produce cortisol or gluco-corticoids. (a great majority of gluco-corticoids are cortisol). And the internal layer will produce androgens (masculine sexual hormones).  In women, the suprarenal Cx is the main source of androgens. In men, these will not have much importance within the suprarenal since most of androgens will be produced in the testicle. We will find catecholamine (A and NA, mainly A) within de medulla. NA will liberate itself in certain particular states.
 
Analysis of Stress Response
ANS nuclei are within the encephalic trunk. And the hypothalamus will be close to those nuclei. Through neurotransmitters the hypothalamus will stimulate ANS nuclei, triggering the sympathetic system which uses NA as neurotransmitter. 
First response to stress –short term stress- will be an acute one. It could be an exam, for example. We all get nervous when we face an exam. Thus there will be an acute response to that stress.  Stress will mainly stimulate hypothalamus PVN. The nucleus will liberate a hormone, CRH which will stimulate the EM. This will stimulate the ANS nuclei and through them will start that cascade which activates the sympathetic way that utilizes NA as neurotransmitter.  In turn, NA stimulates the suprarenal medulla, thus producing adrenalin liberation.  Then we reach a point where we have two catecolamines: A and NA.  They will produce a sympathetic response within the organism. This sympathetic response will produce vessel constriction, bronco dilation, stimulation of the five cardiac properties, muscular excitability, midriasis (dilated pupils), muscular, brain and cardiac blood flow rise, diminution of the digestive apparatus blood flow, and of the gonad system. Generally we can speak of a redistribution of the blood flow redirecting it towards activities which might be necessary for survival. Glucemia’s rise will also take place in order to allow an increase of the necessary combustible. This is the sympathetic-adrenal-medullar axis (medulla of the suprarenal grand).

In chronic stress we will receive a response from the suprarenal cortex. In this case, stress is prolonged and a response to this stress continues to take place. Hypothalamus is still stimulated. PVN continues to liberate CRH using blood and not nervous ducts, reaching the hypofisis  and stimulating it through cells which will liberate ACTH, this will stimulate the adrenal cortex so it might free cortisol (glucocorticoid).  Cortisol will produce a long term response to stress. Generally, it is said that costisol response is mime-sympathetic or simile-sympathetic.   This means that it is very similar to the sympathetic one. It will produce these same responses. The main ones are: vessel constriction and glucemia´s rise.  Glococorticoids, however, will be complex hormones which will produce contradictory responses. It is the typical case of “dose makes poison”. In low doses, glucocorticoids stimulate protein synthesis and muscle mass formation.  In supra-physiological conditions (high pharmacologic) will produce muscular proteolysis, or protein destruction, muscular mass destruction.  In normal doses they also produce a glucemia rise and in high doses is able to produce hypo-glucemia conditions. High dosed Glucocorticoids might produce growth delays. It has oldstrong effects on the immune depression.  Glucocorticoids are a very important and widely used drug but it is also a double edged weapon and might be very dangerous too.

Here, however, we are speaking of very low physiological doses triggered by the organism. In turn, cortisol will show this negative feedback through retro alimentation (sending an inhibitory response towards hypofisis in order to inhibit ACTH liberation and also send a response to the hypothalamus to impede CRH liberation).  At this level homeostasis, equilibrium, concept appears.  If it is small, stimulation provokes its secretion; if it is abundant it is inhibited to avoid any excess. This retro alimentation process repeats itself many times at many levels. An acute response to stress usually does not produce any pathology. A chronic response might do so. In normal chronic responses we see that a cortisol rise provokes a diminution of the CRH and ACTH levels due to this negative feedback. Pathological conditions provoke a failure of the negative feedback system, thus simultaneously provoking high cortisol, ACTH and CRH levels. It means that this mechanism it is not able to stop, the duct is exacerbated, and this we call hyper reactivity of the HPA axis.
 
Response in diverse organs and systems
 
Biphasic Response of anti stress hormones
If a stressing stimulus takes place there will be a dysphasic response of certain hormones. This can be observed in the GH (growth hormone), testosterone and pro-lactines (related to maternal milk and reproduction as a whole). This biphasic response is a risen response to a stress which afterwards lowers below basal, normal levels.
Pro-lactines: reacting to a stressing stimulus rises much, but when facing a chronic stress diminishes below basal levels thus producing amenorrhea or anovulatory periods.
GH: rises when facing an acute stress but soon diminishes reaching lower basal levels. Children who undergo stress face retarding growth problems.
Testosterone: acute rise and afterwards, diminution below basal levels. It is similar to pro-lactines. Inhibition of gonad axis during chronic stress. We said that testosterone was related to aggression levels. Fast initial rise is related to high aggression levels.  Both men and women experience this condition.
 

Hyper tensor Response
   
 
Stress will be hypo tensor. And response to stress will be hyper tensor. Adrenalectomized animals submitted to stressing stimuli will not be able to respond to these stimuli, they will not be able to give an adaptation response. Thus they will die from hypotension and hypoglycemia. In reality hyper tension and the rise of glucemia are adaptation responses to stress, compensating responses. By itself, stress is hypo tensor and hypo glucemiant. If response to stress does not take place, death does. 
This hyper tensor response can be observed in the cardiovascular system. A rise of the five cardiac properties will take place (volume minute, volemia, vessel tension, hyper tension, they all, will rise). Vessels will constrict and a blood flow rise will take place in the heart, the brain and the muscle. Blood flow will diminish in the digestive, gonad, skin. This happens because of a sympathetic stimulation and the Para sympathetic inhibition. Flow does not only increase in the muscle, contraction-relaxation’s rise will produce muscular vessels contractility.  Venous return (VN) to heart will increase. Pre-charge (how much blood the heart receives), therefore, will rise. The more it receives, the more it will eject. Higher will be the expulsion and the volume minute. Thus, volemia and arterial pressure rise.
Response in the kidney
Sympathetic response in the kidney will be the contraction of the afferent arteriole. Renal plasmatic flow (amount of blood which reaches the glomerular capillary), consequently, will diminish. Glomerular filtration’ volume will then diminish. This is why excretion lowers, volemia rises and so does arterial pressure.  If this response is exacerbated during chronic stress left ventricle’s hypertrophy and arteriosclerosis will take place. Heart stroke, ischemia and death are almost inevitable.


 
Gastrointestinal Response
 
There will be a blood flow and acid secretion (stomach) inhibition. Therefore, hunger will diminish. Motility and transit within the thin intestine also diminish. Inside the colon (thick intestine) will be stimulated and the same will happen with defecation. During acute stress this function might as well be inhibited. And the same happens with urinary activity. This is also an indicator of this type of biphasic response.
 
Immunity
We already know that it is an immune-depressive effect. It is produced by the immune-depressive hormones’ rise (A, NA and cortisol), and a diminution of the immune-stimulating hormones (GH and pro-lactines). These hormones which should be ensuring our defenses are below basal levels. If we are stressed, therefore, we are exposed to immune deficient pathologies.
There exist three important signal molecules in the immune system: IL-1, IL-6 and Tumor Necrosis Factor.
 
Reproduction
In dancers or in athletes undergoing intense exercise, even in individuals who develop intense work, might suffer from gonad axis depression. In women is clearer, there is amenorrhea, anovulatory cycles, puberty delay or even a backward process in maturation (loss in mammary system development or loss of their secondary sexual characteristics with teen age resemblances). Men might suffer infertility.
 
 
Gonad Axis
LHRH: gonad atropine liberating hormone.
LH: luteinizant hormone (gonad atropine)
FSH: follicle-stimulant hormone (gonad atropine)
PRL: pro lactines (gonad axis stimulating hormone)
Hypothalamus regulates the gonad axis (reproductive action). It liberates a LHRH hormone which will stimulate gonad atropine liberation (LH and FSH). Gonad atropines will stimulate gonad tropism (ovary and testicle), they feed them, keep them. These hormones will keep the ovary active. FSH will influence the menstrual cycle first stage where follicles with ovaries will develop. These follicles are stimulated to favor ovulation. Once ovulation appears, the follicle frees that ovule and what is left is called lute or yellow body. This body will produce progesterone and will become the hormonal support for the baby during pregnancy.  LH will appear at a second stage.
Estrogens and progesterone will be produced in the ovary. Androgens, among them testosterone, will be produced in men.  We find these same hormones in men, but they carry on other functions. Ovary is replaced by testicle. The axis is the same, but functions will be different.
Hypothalamus liberates CRH. Hypofisis frees ACTH. Suprerenal Cx liberates cortisol. Cortisol directly inhibits the ovary. It will inhibit LH and FSH receptors. At the same time it inhibits the hypofisis in the nuclei destined to produce pro-lactine which stimulates the gonad axis. CRH will inhibit the hypothalamic nuclei which will free LHRH. Thus, gonad atropines themselves will be inhibited. 
 
Nociseption
There is an analgesic theory of stress. It is linked to the fleeing and fighting response. Mechanisms are polemic. Clearly defined molecules do not exist. It is thought that there could be inhibition in the central level descendent ducts which inhibit the nociceptive ways. However, this is still a theory.  Some signal molecules might exist.  
 
Psychological state
Acute stress is linked with high anxiety levels and chronic stress, with depression.