Medical Inspection – Health Blog

Several important factors modify hypoxic vasocon­striction (Table 1). While the effects of many of these factors have been repeatedly substantiated, the mech­anisms of action remain largely unexplained.

Although the AHPR is present in the lungs of all mammalian species examined, there is considerable species variation in the magnitude of the response. Pigs and cows have a very vigorous response, while dogs and hamsters have a comparatively mild pressor response to alveolar hypoxia. This variability ex­tends to individuals within a given species and among human subjects where significant differences in the strength of the response suggest the influence of unknown genetic factors. A genetic influence on the magnitude of the response is also apparent in animal studies of the adaptation to high altitude. Strains of cattle susceptible to the development of pulmonary hypertension at high altitude (“brisket disease”) have a larger acute hypoxic pressor response than nonsusceptible cattle. Different strains of rats exhibit differences in the magnitude of the response and in their susceptibility to the development of pulmonary hypertension at high altitude.

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The AH PR is an important adaptive mechanism that diverts blood flow away from hypoxic alveoli. This shift in blood flow from poorly ventilated to better ventilated areas improves the matching of ventilation and perfusion which minimizes arterial hypoxemia. The degree of flow diversion away from the hypoxic site with a localized pathologic process depends on the size of the hypoxic segment; the smaller the hypoxic region, the greater the percentage diversion of blood flow away from that segment.

Flow diversion becomes less effective with wide­spread hypoxia, but still serves the purpose of increasing perfusion of the apices of the lungs via an increase in pulmonary arterial pressure. The apices of the lungs are less well perfused than the bases with a lower pulmonary artery pressure due to the effect of gravity. Increased apical perfusion enhances recruit­ment of alveolar capillaries which can participate in effective gas exchange, thus improving arterial oxygenation. This effect is seen in residents at high altitude who are subject to global alveolar hypoxia and show a more uniform distribution of perfusion com­pared to residents at sea level. This may convey an advantage in living in such a rarified environment by providing a larger effective area for gas exchange.

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The pulmonary circulation responds to acute hypoxia with increases in pulmonary artery pressure and vascular resistance. This acute hypoxic pressor response (AHPR) is a unique physiologic feature distinguishing the pulmonary from the systemic cir­culation which dilates in response to hypoxia. Since Von Euler and Liljestrand described the phenomenon of acute hypoxic pulmonary vasoconstriction within the feline pulmonary circulation, it has fascinated vascular physiologists and stimulated a substantial number of studies aimed at defining the mechanism of this response.

Airway hypoxia is a consequence of many lung diseases. In addition, abnormalities of the pulmonary vasculature are prominent features of the pathophysi­ology of acute and chronic respiratory failure. In this context, the AH PR occupies a unique position at the interface between the normal and abnormal pulmo­nary circulation in transition from health to disease.

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Generalized tetanus has become very rare in devel­oped countries because of successful active immuni­zation programs. For instance, by September 1986, only 46 cases had been reported to the Centers for Disease Control for 1985 in the United States, infor­mation quite consistent with our incidence of 0.07 cases per 100,000 per year in Geneva between 1968 and 1989. However, С tetani remains ubiquitous in the soil and in the gastrointestinal tract of man and many domesticated animals. Elderly individuals are frequently inadequately protected against tetanus, either because they had never received a full course of immunization or because they had not received booster injections of tetanus toxoid. Our elderly patients with generalized tetanus had a negative history for tetanus vaccination, as did patients in many reported series, which is consistent with the poor protection of many elderly adults against tetanus when assessed by serologic studies.

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According to previous studies showing an increased mortality in elderly patients, we divided the study group according to age (Tables 2 and 3). There was no difference between groups in terms of duration of intubation, hospital stay, and frequency of cardiovas­cular complications. Infectious complications were fairly common in both groups. Two patients died: a 63-year-old woman developed fatal peritonitis due to a perforated duodenal ulcer after 14 days in the intensive care unit; and a 45-year-old woman pre­sented with severe and protracted hypotension that resulted in massive cerebral infarction and death on the 180th day. The eight other patients all experienced uneventful recovery, without any sequelae upon hos­pital discharge.

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Case 3

An 81-year-old female patient was hospitalized on March 28, 1989, for progressive cervical and dorsal muscle contractures, trismus, and swallowing difficulty for eight days before hospitaliza­tion. A superficial wound on the left foot was noted, tetanus was diagnosed, and she was transferred to the medical intensive care unit. She had never been vaccinated against tetanus. An orotracheal tube was inserted, later to be replaced by a tracheostomy on day 20. Mechanical ventilation, sedation (diazepam), and curarization (pancuronium bromide) lasted 45 days. The treatment regimen was similar to that of patients 1 and 2. She presented cardiac dysrhythmia in the form of bradycardia and tachycardia during the first two weeks of mechanical ventilation. The patient was discharged from the intensive care unit on day 47, from the hospital on day 124, and she is now free from any incapacitating problem.

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Case 1

An 85-year-old female patient was hospitalized on July 7, 1984, for an open heal fracture. She had never been vaccinated against tetanus. She received a tetanus Iwoster injection, was operated on, and was put on a regimen of intravenous (IV) penicillin. On the fifth hospital day she experienced difficulty opening her mouth, and by the next day she presented with trismus and diffuse muscular contractures. Tetanus was diagnosed and she was transferred to the medical intensive care unit. Tracheostomy was performed and mechanical ventilation was started along with myorelaxation with a continuous infusion of diazepam and hourly injections of pancuro­nium bromide and sedation with a continuous infusion of a meper­idine (pethidine), promethazine, and chlorpromazine combination. Treatment also included local debridment and lavage, antitetanic 7-globulin, penicillin, parenteral nutrition, gastric protection with ranitidine, heparin prophylaxis, nursing, and early passive mobili­zation. Complications consisted of sympathetic hyperactivity and pneumonia due to Klebsiella pneumoniae. Weaning from mechanical ventilation was successful on day 38, and the patient was transferred to the ward on day 42. The tracheostomy tube was removed on day 55. Progressively active mobilization was undertaken, and she was discharged from the hospital on day 142, free of any invalidating sequelae. Five years later, she was still leading an active and independent life.

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