During the shock phase of the alarm reaction the medulla of the adrenal gland secretes epinephrine. Some of the symptoms concomitant with this phase, such as the increase in pulse rate, increase in rate of blood clotting, and temporary rise of the blood pressure and the blood sugar, may be in part due to the effects of epinephrine.
The ability of the organism to withstand shock depends, however, upon an intact hypophysis and the cortex of the adrenal gland. If either one of these is damaged, the organism shows less capacity to resist stress situations. During the shock reaction the cortex of the adrenal gland enlarges, and this hypertrophy of the cortex may persist to a less marked extent during the period of resistance. Structural changes have also been reported in the hypophysis.
The reason why the hypophysis must be intact to combat the physiological effects of stress is because it secretes a hormone (corticotropin) which stimulates the cortex of the adrenal gland to a greater output of its hormones. If corticotropin is absent, the cortex of the adrenal will not be stimulated to hypersecretion. It is the hormones of the cortex (cortin) which either directly or in conjunction with corticotropin are responsible for the internal adjustments which occur in resisting the effects of the alarm reaction.
The general hypothesis has been advanced that, if the anterior lobe of the hypophysis is stimulated to an overproduction of corticotropin, then its ability to produce other hormones is diminished. The decrease in the elaboration of the growth hormone, the sexstimulating hormone (gonadotropins), and the hormone producing lactation (prolactin) would decelerate growth, decrease gonadal activity, and stop lactation.
The hormones of the cortex of the adrenal gland have a wide effect on the general metabolism of the body and will produce atrophy of the thymus and other lymphatic tissues. They are important in the carbohydrate or sugar metabolism of the body. Animals treated with cortical extracts will show an increase in the blood-sugar level and the glycogen stores of the liver. These sugars are formed at the expense of the proteins of the body, so that protein metabolism is also affected. At this time a greater amount of nonprotein nitrogen will be excreted in the urine. The hormones also affect the distribution of the blood between the body cells on the one hand and the extracellular structures such as the blood stream on the other. Cortical extracts will shift the body fluids from the cells into the extracellular structures. Sodium and potassium balance will be disturbed under such conditions, since potassium is the principal ion found in the cells and sodium is the principal ion found in the extracellular fluid. The effects described thus far are produced by injecting either normal animals or animals with their adrenals removed with the cortical hormones. Adrenalectomy without replacement therapy produces many physiological changes of a pathological nature, which are due to cortical deficiency. In such organisms the physiological states described above are reversed. The lymph glands, the thymus, and the spleen are enlarged. An insufficiency of blood sugar or hypoglycemia is present. The blood plasma becomes depleted and concentrated. The sodium chloride content of the blood falls but the potassium content is increased. There is a rise in the nonprotein nitrogen of the blood, consisting of urea, uric acid, and creatinine. Hemorrhages and ulcerations may occur in the digestive system. There is a loss of appetite and a general wasting of the body. Any of these conditions or a combination of them will eventually result in death.
The physiological disturbances of the alarm reaction and the whole homeostatic syndrome are extremely complex and have not been worked out completely. At the present time no one theory can explain all the changes that occur. The following factors which have been emphasized by different individuals, especially in explaining the changes occurring during the alarm reaction: impaired circulation, dehydration and hemoconcentration, endogenous intoxication with various metabolites, nervous disturbance, disturbed regulation of body temperature, decrease of chlorides, and deficiency in some important metabolite. From these suggestions one may conclude that the homeostatic syndrome is a response of the body interdependent on a very intricate physiological reaction occurring as a whole. One may consider these responses as those concomitant with an emotion of excitement.
The importance of corticotropin through its action on the adrenal cortex in initiating and maintaining many of the changes of the alarm reaction and the period of resistance indicates the importance of neural factors. The hypophysis has intimate hypothalamic connections, so that this energizing center is directly involved in the whole response. The hypothalamus is also under the control of the cerebral cortex. In this way cortical activity from the higher centers is also involved, especially in exogenous traumatic stimulus situations. Furthermore, the sympathetic nervous system is capable of producing all the disturbances present during an emotion of excitement, so that sympathetic stimulation, also under cortical and hypothalamic control, plays a part in the reaction.
The whole mechanism of the homeostatic syndrome starting with either exogenous or endogenous stress situations is outlined diagrammatically. As already stated, part of the sympathetic consists of symptoms produced by stimulation of the sympathetic system and by epinephrine secreted by the adrenal medulla, but the main effects are due to the hypophyseal-adrenal-cortical relationships.