CHAPTER 7 - DISCUSSION

It has become evident that a great deal of illness is of emotional origin and that all illness has its emotional component. 

The hyperventilation syndrome is one of the ways in which emotional stress becomes manifest. An attempt has been made to study, not only the clinical manifestations but also some of the physiological mechanisms invoked by overbreathing. It is felt that an understanding of the physiological background of an emotionally engendered illness will lead to a much clearer conception of the, at present, vaguely understood entity of "psychosomatic medicine". 

Hyperventilation results from a stimulus to the respiratory center. The manner in which this stimulation is brought about is not precisely known but it is in some way connected with stress. 

The purpose of the hyperventilation is a preparation for motor activity. Symptoms result when this motor activity is restrained by the inbuilt social and cultural inhibitions of the individual. The remarks of Russel (1952) on experimental neuroses are pertinent here. He says: "The precipitating factor is conflict, but another essential factor present in all the successful experimental techniques, is restraint of voluntary movements, either by a harness or by the subject's own learned patterns of movement". 

It is interesting that most patients in this series found that they were unable to keep still during hyperventilation and that even purposeless movements relieved their symptoms to some extent. But, in the absence of coordinated motor activity, the main effect of the overbreathing was turned back on the body, causing a physical disturbance. This physical dysfunction was manifested in all systems of the body, but neurogenic dysfunction gives the hyperventilation syndrome its specific stamp. 

Most of the patients were aware of respiratory dysfunction, but not that they were hyperventilating. The commonest complaint was that of not being able to get a satisfactory breath and this referred particularly to the depth of the breath. This respiratory difficulty is characteristically unrelated to exertion. 

Once hyperventilation was established, the commonest group of symptoms were those of central nervous system disturbance. These comprised cerebral disturbances which, though rarely gross enough to result in loss of consciousness, were nevertheless distressing to the patient. They comprised dizziness, visual disturbance, feelings of unreality, etc. They may be associated with electroencephalographic changes. There is a reduction in cerebral blood flow of about 30%. 

Peripheral nerve involvement was manifested by paresthesia, starting in hands and feet and later becoming generalized. A few cases progressed to tetanic spasm. 

The commonest gastrointestinal disturbance was distension of the stomach which resulted from air-swallowing during overbreathing.

Circulatory disturbances comprised precordial pain, palpitation, and coldness of the extremities. Two patients complained of diuresis. Fatigue was a common symptom.

The signs and symptoms were enhanced if the patient was emotionally disturbed, in fact if stress was present.

At least three separate physiological mechanisms are invoked as a direct result of overbreathing.

These are:

1. The increased alkalinity of the blood which results from loss of CO2 during hyperventilation is of primary importance. Patients who overbreathe a CO2-rich mixture do not develop the characteristic symptoms of neurogenic dysfunction. Conversely, many of the symptoms of this syndrome are rapidly relieved by re-breathing CO2. It is the alkalosis that:

(a) Increases neuromuscular irritability to the point where tetany may develop.

(b) Causes cerebral blood vessels to constrict. This conserves their low CO2 content.

(c) Renders hemoglobin reluctant to part with its oxygen thereby interfering further with the nutrition of the tissues and especially of nerve tissue.

2. Reflex peripheral vasoconstriction is an integral part of hyperventilation syndrome.

It accounts for the cold extremities, the seating, and the pallor. To Henderson (1909) these features were so striking that he described at length the “shock-like" state seen after prolonged overbreathing.

It has been shown that the motor route for this reflex is along the sympathetic nerve fibers. The afferent path is not precisely known but seems to be connected in some way with the expansion of the chest or lungs. The vasoconstriction after several minutes of overbreathing persists for many minutes and tends to persist longer in hyperventilators. This can be only partially explained by the type of respiration after hyperventilation in these subjects, and an additional factor, which is a less easy adaptability of their vasomotor tone, has been suggested.

If hyperventilation is assumed to be part of the physiological preparation for flight or attack, what is the significance of the reflex peripheral vasoconstriction? It seems reasonable to assume that, like the effect of adrenaline, it is part of a general vascular shift to supply the skeletal muscles with additional blood. Limb plethysmography is notoriously difficult to interpret, as so many tissues are included in the plethysmograph that it becomes difficult to assign to any one tissue any specific change in blood supply. With the digital plethysmograph, one is, for all practical purposes, dealing only with skin. Eichna and Wilkins (1941) studied the changes in the volume of the forearm and calf after various stimuli which are known to produce skin vasoconstriction, e.g. deep breath, noise, mental activity, etc. By far the commonest response was a moderate decrease in limb volume. Occasionally the limb increased in volume, either moderately or markedly.

We know that with one deep breath a marked skin vasoconstriction is produced. If the limb as a whole usually shows only a moderate decrease in volume and occasionally even an increase in volume, it seems reasonable to assume that the relatively large quantity of blood being diverted from the skin is being accommodated elsewhere in the limb and that it is probably muscle tissue which is receiving the extra blood.

Clarke (1952) claimed that during moderate over-ventilation (20 per minute for 3 minutes at maximum depth) there is a two-fold increase in blood flow to the forearm. He attributed this to vasodilatation in the muscles and thought that it resulted from the hypocapnia.

The next question that arises is whether this assumed redistribution of blood in the limbs during overbreathing plays any part in the genesis of the peripheral neurological symptoms and signs of the hyperventilation syndrome? Evidence that it plays some part is the fact that procedures designed to interfere with the normal reflex distribution of blood with overbreathing can alter the speed of development and the intensity of the manifestations of peripheral nerve irritability.

Cooling a hand or elevating a limb, especially the leg, usually accelerates the onset of paresthesia, whereas sympathectomizing a limb has the opposite effect.

Cooling a hand presumably increased the intensity of the reflex peripheral vasoconstriction. The effect of elevating a limb is more complicated as shown by Gootz in 1950. He demonstrated striking alterations in the vascular supply to a limb during elevation.

These are: 

(1) An increase in the systolic elevation and a decrease in the dicrotic wave of the pulse. 

(2) An accentuation of the changes in digital volume resulting from extrinsic stimuli, e.g. noise, deep breath, etc. 

(3) A delayed response to reflex body heating. 

(4) A drop in skin temperature. 

These changes were attributed to an acceleration of the venous return from the limb. They are more marked in the lags because the venous return from the legs is considerable. 

The acceleration of the onset of paresthesia with elevation is probably due to the fact that all the tissues in the limb have a less effective blood supply during elevation because of the rapidity of the venous return.

Removal of the sympathetic supply to a limb abolishes the reflex peripheral vasoconstriction of deep breathing. In two cases of upper limb sympathectomy, the paraesthesia of hyperventilation was tardy in appearing and much less intense once the sympathectomy had become established. This effect was strikingly illustrated in one case where the opportunity arose of recording the patient's response to overbreathing pre-operatively. 

The next question and this can only be dealt with very speculatively, is how precisely this vascular factor works. 

We know that a reflex peripheral vasoconstriction of the skin occurs. This will interfere with the vascular supply of the nerve terminal. But the crucial question appears to be whether there is a change in vascular supply to the peripheral nerve itself. This is not known at present, but if the general vascular shift in the limb is to supply the skeletal muscles, then the peripheral nerve may suffer with the skin in depletion of its blood supply. 

Ischemia itself is a potent agent in increasing the irritability of peripheral nerves. Lewis, Pickering, and Rothschild (1933) demonstrated this, and the generally accepted explanation of the Trousseau phenomenon is that it activates the nerve through ischemia. (Lewis, 1942). Neuromuscular tissue functions less well when cold, e.g. myotonic spasm is often precipitated by cold. 

It is the alkalosis that is of primary importance in the pathogenesis of the peripheral nerve irritability. This is emphasized by the fact that after 2 minutes of overbreathing, although the vasoconstriction persists for about 3 minutes, the paresthesias disappear in about a minute. Nevertheless, these investigations indicate that the peripheral vasoconstriction does in some way lower the threshold of nerve irritability, and so contributes to the manifestations of the hyperventilation syndrome. The factor of ischemia may also be of importance, in the genesis of the tetany of hypocalcemic patients. One case of this (resulting from steatorrhoea) was seen and she spontaneously remarked that cold precipitated many of her attacks and she could often avert an impending attack by warming her limbs. 

3. The effect of overbreathing purely as a form of muscular exercise is another factor of importance. This has only been touched on. All patients who overbreathed for 2 minutes developed an increase of heart rate ranging from 6 to 30 beats per minute. This lasted for about 1 minute after the cessation of overbreathing. One patient in the series, who presented with "palpitations'' as her major complaint, regularly produced a pulse rate of 120 beats per minute after a few minutes of overbreathing. This tachycardia also occurs in sympathectomized patients after hyperventilation and explains the diminution in pulse volume which develops despite the absence of reflex peripheral vasoconstriction. 

A fourth factor that must receive mention because of the role of stress in the hyperventilation syndrome is the factor of adrenaline release. Although its direct study is outside the scope of this thesis it must be considered as a possible background factor because of its action as a respiratory stimulant; its effect in causing skin vasoconstriction and muscle vasodilatation and its influence in upsetting the ionic equilibrium. Although adrenaline release does not appear to alter the symptoms and signs of the hyperventilation syndrome in a qualitative sense; it probably plays a part in enhancing or maintaining the physiological effects of the other 3 factors. 

Although the factors of alkalosis, reflex peripheral vasoconstriction, and circulatory effects from muscular effort and adrenaline release are separate and distinct they are intricately interwoven to produce a highly specific clinical picture which we recognize as the hyperventilation syndrome. 

CHAPTER 8 - SUMMARY AND CONCLUSIONS

1. A study has been made of the hyperventilation syndrome, the name given to a group of symptoms and signs which result from overbreathing. 

In this thesis, the viewpoint has been taken that the hyperventilation is a physiological preparation for fight or flight. Certainly, emotional stress is responsible for most cases of the syndrome. Physical function rises because the patient, physiologically prepared for some form of motor activity, is inhibited by social or cultural traditions from carrying his emotional response over into a motor response. 

2. The literature on the effects of overbreathing in man has been reviewed. 

3. The clinical symptoms of forty patients with this syndrome have been analyzed. Neurogenic dysfunction, both central and peripheral, gives the syndrome its distinctive character but the involvement of other systems, especially the circulatory one, is often prominent. 

4. The criteria for diagnosis, the value of a hyperventilation test, and differential diagnosis have been discussed. 

5. Treatment consists of explaining the mechanism or hyperventilation to the patient, demonstrating the reproduction of symptoms by overbreathing and the relief of symptoms by re-breathing a carbon dioxide-rich atmosphere or by breath-holding. The idea is to break at one point the physiological chain of reactions of the emotional response.

Long-term treatment is aimed at relieving emotional stress by discussions with the patient and by teaching him the technique of progressive relaxation. 

6. The experimental section inquires into the peripheral vasoconstrictor effect of overbreathing. This is an integral part of the syndrome. 

The peripheral vasoconstriction is reflex and mediated through the sympathetic pathway. The afferent path is not precisely known but it is evoked by the act of taking a deep breath, making an obstructed respiratory effort, or by rapid, shallow breathing. It occurs with a carbon dioxide-rich mixture as well as with air or other gases. The reduction in pulse volume is considerable. Digital volume and arterial inflow are also reduced. 

7. Plethysmographic studies of eight normal controls and eight members of the series of cases described show that this reflex peripheral vasoconstriction has the same characters in both groups. 

The only difference between them is that the hyperventilators tend, clinically and plethysmographically, to be cold-handed, so that any vasoconstrictor stimulus will reduce their peripheral blood flow to a lower level than that of a normal subject responding to the same stimulus. 

8. The following changes produced by 2 minutes or overbreathing have been investigated in eight normals and eight hyperventilators. 

(a) Reflex peripheral vasoconstriction. 

In normal subjects, this vasoconstriction persisted for about 3 minutes after termination of 2 minutes of overbreathing. In the hyperventilators, the vasoconstriction persisted for about 5 minutes. The high vasomotor tone of the hyperventilators might be partly responsible for the longer duration of the vasoconstriction. 

(b) An increase in pulse rate. 

This varied markedly in both normal subjects and hyperventilators. The range of increase was from 6 to 30 beats per minute. This increase in pulse rate also occurred in sympathectomized patients. It caused a diminution in their pulse volume after 2 or more minutes of overbreathing. 

(c) Abnormal respiration. 

In six of the eight normal subjects, the respiration after 2 minutes of hyperventilation was characterized by periods of apnoea. In the hyperventilators apnoea occurred in only one case; in four cases the respiration actually increased in depth compared with that before hyperventilation; in one case it was grossly irregular. 

9. Investigations were undertaken to see whether the time of onset and intensity of the symptoms of peripheral nerve irritation was influenced by changes in the vascular supply to the limbs. The maneuvers carried out for this purpose were: 

(a) Cooling one hand and warming the other. 

In seven of ten cases, local cooling accelerated the onset of paresthesia. 

(b) Elevating a limb. 

This accelerated the onset of paresthesia in the leg in eight of ten cases. 

(c) Sympathectomized upper limbs. 

Sympathectomy delayed the onset and diminished the intensity of paresthesia in both the cases investigated. 

10. The syndrome is discussed with particular reference to the mechanisms brought into operation by overbreathing. 

These are: 

(a) An alkalemia produced by the blowing off of CO2. This produces a cerebral vasoconstriction, reducing blood flow in the brain by as much as 30 percent. It causes peripheral nerve irritability which manifests itself as tetany. It also interferes with tissue oxidation. 

(b) A reflex peripheral vasoconstriction which is responsible for the cold hands, sweating, etc. It is considered as part of a general vascular shift to supply the skeletal muscles with more blood. It is assumed that the peripheral nerve, as well as the skin, has its blood supply curtailed. 

Consequently, the peripheral nerve is not only subjected to the exciting influence of the alkalosis but this excitation is enhanced by the ischemia resulting from the reflex peripheral vasoconstriction. 

Maneuvers that accentuate this ischemia, such as local cooling or elevation of a limb, accelerate the onset of symptoms of peripheral nerve irritation. Conversely, sympathectomy, which abolishes the reflex peripheral vasoconstriction, delays the onset of these symptoms. It is pointed out that after several minutes of hyperventilation the peripheral pulse volume in sympathectomized limbs is also ultimately reduced. This diminution in pulse volume is closely correlated with the tachycardia that occurs after overbreathing. 

(c) Circulatory effects produced by the muscular exercise of overbreathing. Most patients get an increase in heart rate after several minutes of overbreathing. This varies widely between 6 and 30 beats per minute. In some patients who get a considerable increase in heart rate, "palpitations" is a major complaint. 

Fatigue, which is a very common complaint, is probably partly caused by the muscular work of overbreathing. 

(d) There may be a background factor of emotional stress which, when present, enhances the symptoms and signs.

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Chapter 9 - Appendix of Case Histories