The most important pathophysiologic aspects of chronic and acute obstructive pulmonary disease involve disturbances in ventilation with resulting derangement of gas exchange in the lung. There is considerable variability in the type of abnormality, the time of its appearance in relationship to the history of the disease, and in the progression of the abnormality in blood gases

Baker, James P.

O\u27Donohue, Walter J., Jr.

Patterson, John L.

VCU Scholars Compass

The Pathophysiology of Respiratory Failure Chronic Obstructive Pulmonary Disease* . 1n JOHN L. PATTERSON, JR., M.D. Research Professor of Medicine, Director Cardiopulmonary Laboratories and Research, Medical College of Virginia, Health Sciences Division of Virginia Commonwealth University, Richmond, Virginia JAMES P. BAKER, M.D. Associate Professor of Medicine, Medical College of Virginia, Health Sciences Division of Virginia Commonwealth University, Richmond, Virginia WALTER J. O'DONOHUE, JR., M.D. Assistant Professor of Medicine, Medical College of Virginia, Health Sciences Division of Virginia Commonwealth University, Richmond, Virginia The most important pathophysiologic aspects of chronic and acute obstructive pulmonary dis-ease involve disturbances in ventilation with re-sulting derangement of gas exchange in the lung. There is considerable variability in the type of abnormality, the time of its appearance in rela-tionship to the history of the disease, and in the progression of the abnormality in blood gases. The usual sequence, however, is the following: 1 ) In the earliest stages there is no blood gas abnormality at rest or with exercise, 2) With fur-ther progression of the disease the blood gas ten-sions are normal at rest but on exercise there is a significant decrease in arterial blood P o,, 3) In a more advanced stage there may be minimal re-* Presented by Dr. Patterson at the Symposium on Respiratory Failure, May 25, 1972, at Richmond, Virginia. 126 duction in arterial blood P o, at rest, while on exercise hypoxemia is accentuated and arterial blood Pco, rises, 4) In advanced COPD there is decrease in arterial blood P0 , and increase in arterial blood P co, at rest, with moderate or marked worsening of these changes on exercise. Hypoxemia results from one or more of the following factors: disturbance in ventilation/ per-fusion relationships of lung, hypoventilation, and, to a degree, impaired diffusion. Hypercapnia re-sults from alveolar hypoventilation. Ventilation/ perfusion disturbances of the lung may occur be-cause obstruction of bronchi and bronchioles is uneven, resulting in portions of the lung being hypoventilated and other parts being hyperventi-lated. The mechanism of obstruction can involve several of the following factors, all of which may be unevenly distributed in different areas of the MCV QUARTERLY 9(2): 126-129, 1973 PATTERSON, ET AL: PATHOPHYSIOLOGY OF RESPIRATORY FAILURE 127 lung: tenacious exudate in the bronchi and bron-chioles; edema of the bronchial wall and bronchial or bronchiolar wall and mucosa; bronchiolar spasm; loss of the normal radial (outward) traction on the wall of the bronchi and bronchioles, owing to loss of the normal pattern of the pulmonary stroma through departitioning of the ' lung; and, finally, varying degrees of fibrotic obstruction of the airways. The loss of radial traction from de-partitioning of the lung, owing to breakdown of alveolar septae, is perhaps the least appreciated of these common mechanisms of obstruction. Dur-ing expiration, the airways are normally held open, in part, by the outward pull of the various elements in the pulmonary stroma. When this outward pull is diminished or lost, and particularly when the other factors producing obstruction are operative, including loss of integrity of the bronchial and bronchiolar walls, some collapse or closure of the airways after the early phase of expiration is inevitable. As the chest becomes barreled and assumes the position of hyperinflation, the radial traction may be maintained to a greater degree than if the chest had retained its normal contour, although a price is paid in the form of a less ef-ficient performance of the muscles of respiration, including the diaphragm. The accessory muscles of respiration, particularly the scalenes and less importantly the sternomastoids, the upper tra-pezius, and the pectoral muscles, assume increasing importance in the maintenance of ventilation, particularly in the upright position. Blood leaving the alveolus, which is under-ventilated in relation to the amount of blood flow, tpus. has a low ventilation/ perfusion ratio (low V A/ Qc), both in the oxygen and carbon dioxide ex-change. Blood leaving this alveolus will have a lowered oxygen tension and content and an ele-vated carbon dioxide tension and content. In con-trast, certain alveoli are overventilated, since their airways are less obstructed and they feel the ef-fects of the increased respiratory efforts which the patient commonly makes to overcome the overall increase in airway resistance. Blood leav-ing the hyperventilated alveolus with a high ven-tilation/ perfusion ratio (high V A/ Qc ratio) will have an oxygen tension slightly above normal. Owing to the fact that the oxygen dissociation curve is very flat at the arterial end of its normal range, very little additional oxygen content is gained by this increase in oxygen tension. Further-more, oxygen is relatively insoluble, with only about 0.3 ml of oxygen normally dissolved in 100 ml of arterial blood. The gain in dissolved oxygen from the small increase in oxygen tension is almost negligible. On the other hand, much more carbon dioxide is in solution in the plasma and can be more readily moved under a given diffusion gradient. The C02 dissociation curve is steeper than the oxygen dissociation curve. As a result, the blood leaving the hyperventilated al-veolus has lost much more carbon dioxide than it has gained oxygen. When these two blood streams, one from an underventilated alveolus and the other from an overventilated alveolus, are united, the stream with low oxygen content, mixing with the stream containing a minimally increased oxy-gen content, results in blood which has a reduced oxygen content and tension. On the other hand, the mixing of a stream with an elevated C02 con-tent with one having a reduced C02 content can readily result in blood with normal or near nor-mal carbon dioxide content and tension. There-fore, we commonly observe arterial hypoxia, first during exercise and later at rest, as the initial blood gas abnormality during the progression of chronic obstructive pulmonary disease. The eleva-tion of carbon dioxide tension occurs later as alveolar hypoventilation becomes widespread with further deterioration of respiratory function. Impairment of diffusion (the third major type of respiratory insufficiency) is usually not marked in COPD unless there is concomitant fibrosis of the lung. In the centrilobular type of emphysema, however, owing to dilatation of terminal airways, diffusion may be impaired because of the longer diffusion path ("distance barrier"). The heart is frequently secondarily involved in emphysema. This introduces another abnormal-ity in the oxygen delivery system. Impairment of cardiac function results primarily from pulmonary hypertension which eventually leads to chronic cor pulmonale. The pulmonary hypertension is due to increased pulmonary vascular resistance which in turn is due to the following factors: 1) loss of vascular bed as a result of destruction of vascular channels, 2) increased intra-alveolar pressure compressing the blood vessels in the lung, 3) vasoconstriction due to the reduced P0 , of the blood, primarily when acidosis is present. This last factor is at present thought to be an important reason for the development of pulmonary hyper-128 PATTERSON, ET AL: PATHOPHYSIOLOGY OF RESPIRATORY FAILURE tension in emphysema, but operates primarily when there is respiratory acidosis. Hypoxic con-striction of pulmonary arteries and arterioles is relatively weak when the blood pH is normal. Cardiac function in emphysema may be further impaired as a result of direct harmful effects of the low P 0 , and high P c o , on cardiac muscle and also as a result of increased work of the heart in the high cardiac output stage of the disease. Impairment of cardiac function in emphysema may be more severe if there is associated coronary disease. Chronic hypoxia of a severe degree in the later stages of chronic obstructive pulmonary dis-ease brings about a deterioration of function of most organs of the body. A patient in late em-physema commonly loses weight, is depressed and often confused, and has little or no tolerance for exertion. Reduction of cardiac output with failure of the right heart further increases tissue hypoxia. The hypoxia does, however, stimulate two types of tissue rather late in the disease: the chemoreceptors of the aortic and carotid bodies ( the function of the glomus pulmonale at the bifurcation of the pul-monary artery is still unclear), and the bone mar-row. The chemoreceptor stimulation is important in offsetting the narcotic effects of high arterial carbon dioxide tension on the respiratory center complex in the brain stem. Therefore, too rapid or too large a reduction of the hypoxia without adequate re-spiratory assistance can reduce the drive to respira-tion and rapidly worsen the elevation of arterial CO~ tension (hypercapnia). Physiological Patient Management. In the ap-plication of physiology to patient care we seek to use previously accumulated knowledge of physi-ological processes and mechanisms to plan our therapy, with the aim of shifting abnormal pro-cesses and disease toward the normal. We also util-ize the physiological approach in evaluating the effect of management in a given patient on a day to day, hour by hour, and, at times, moment to moment basis, as well as in evaluating our past performances so as to plan more effective thera-peutic strategies for the future . The application of cardiovascular and respi-ratory physiology to the management of a specific patient rests upon the adequacy of quantitative knowledge of physiological responses and mech-anisms. If the information is not quantitative, ef-fective "physiological" management may not be possible. A difficult and ever present problem is the effective application of knowledge of physi-ological processes and mechanisms obtained from studies on other human beings and animals, both normal and ill, to the ca.re of one particular patient; the physiological responses may differ in important respects, both qualitative and quantitative, from those described in the literature. As an example of the need for quantitative information, we may cite the pulmonary vascular response to hypoxia. It is not enough to know that pulmonary vessels constrict on the influence of arterial hypoxia and that this constriction is greater during states of acidemia. One needs to know the quantitative relations between hypoxia and acidemia in the studies reported in the litera-ture. From this information, an estimate can then be made of the probable magnitude of the pul-monary vasoconstriction in the patient under treat-ment, given the data on his arterial blood gas ten-sions and pH. Certain additional questions must be answered in order to plan effective therapy: Is the magnitude of this patient's hypoxia and of his acidemia by combined effect sufficient to pro-duce a serious increase in pulmonary vascular resistance and an increase in the work load of the right heart? Are the hypoxia, the hypercapnia ( if present), and the acidemia acting to impair the ability of the right heart to handle the in-creased work load? What other important factors, for example, coronary arterial or pulmonary vas-cular disease, are present and how do they in-teract with the blood gas and pH abnormalities? Is therapeutic intervention needed, and how ur-gently? What are the probable favorable and po-tentially unfavorable physiological effects of the therapeutic options? If only rough and approximate answers to such questions can be given, which is commonly the case, 'then some means of continuous or fre-quent discontinuous monitoring of the physiolog-ical state of the patient must be available. Such monitoring can be instrumental, including bio-chemical, or human. The continuous human mon-itoring of the patient-the nurse at the bedside of a single patient- is becoming less and less common. The development of intensive care units, providing the nurse with physical proximity to more than one patient, makes possible effective visual and auditory monitoring of two, perhaps three, patients by one nurse. The more seriously PATTERSON, ET AL: PATHOPHYSIOLOGY OF RESPIRATORY FAILURE 129 ill the patient, the smaller his physiological re-serves and the greater the need for continuous or frequent discontinuous monitoring of basic func-tions. Such monitoring provides the essential feed-back information required for precise adjustment of therapy to the physiological state of the patient and for the early detection and correction of er-rors in management. A difficult challenge that must be met is the devising of means of continuous and discontinuous measurement of physiological processes in the in-dividual patient that are sufficiently basic yet prac-ticable to provide the data required for effective therapy. At present, variables commonly and read-ily monitored are: intravascular pressures, the electrocardiogram and the heart rate, the tidal volume and respiratory rate ( althoug~ this last presents some problems), and rectal temperature. Continuous body weight recording can be done, but these recording scales are at present expen-sive. Frequent discontinuous information on the blood gas tensions and pH is, of course, readily obtained but continuous recording of these vari-ables still presents problems. Continuous infor-mation on other functions, including cardiac out-put and oxygen delivery to the tissues, is clearly needed in many patients critically ill with cardio-respiratory disorders. The need is particularly great in relation to the often rapidly changing clinical states of re-spiratory failure. This is not to say that in every case sophisticated instrumentation is required, or that it will provide all of the information needed for optimal management. Sensitive clinical obser-vation remains essential. For example, the human face, particularly in the elderly in whom physio-logical reserves are low, is an exceedingly delicate indicator of favorable or unfavorable terms of physiological events. The greatest clinicians of the past, or of today, appear to have an intuitive feel-ing of the pathophysiology in the patient, even though they are not always able to articulate this feeling. The present day clinician should not aban-don efforts to sharpen his own sensitivities toward the subtle summation of physiological processes that result in changes in the appearance of the patient's face, tone of voice, gesture, feel of tissue, in favor of excessive reliance on sophisticated in-strumentation. These methods of study of the pa-tient are complementary, not usually exclusive. One can safely predict that, for example, when continuous recording of arterial blood gas ten-sions, pH, and cardiac output become common-place in the management of critically ill patients, these same measurements will make it possible to sharpen our bedside observations and the conclusions that we .draw from them. 

The Pathophysiology of Respiratory Failure in Chronic Obstructive Pulmonary Disease

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The Pathophysiology of Respiratory Failure in Chronic Obstructive Pulmonary Disease

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