Oxygen tension varies from tissue to tissue and is maintained in a dynamic equilibrium between oxygen delivery and oxygen uptake. Both of these factors may vary from time to time, and if P02 is measured at a particular point over a period of some hours, slow fluctuations will be observed in most tissues, often with more rapid fluctuations superimposed. A mean level is, however, normally maintained but differs even within a single tissue from place to place. Oxygen uptake reflects local energy requirements and may change relatively slowly in organs such as liver or skin or very rapidly in muscle and brain tissue. To maintain an adequate supply of oxygen to structures with varying requirements there must be an accurate feedback mechanism coupling the need to the delivery system. Local vascular control mechanisms show features characteristic of autoregulation which require a sensor,
{"title":"Local factors in tissue oxygenation.","authors":"I A Silver","doi":"10.1136/jcp.s3-11.1.7","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.7","url":null,"abstract":"Oxygen tension varies from tissue to tissue and is maintained in a dynamic equilibrium between oxygen delivery and oxygen uptake. Both of these factors may vary from time to time, and if P02 is measured at a particular point over a period of some hours, slow fluctuations will be observed in most tissues, often with more rapid fluctuations superimposed. A mean level is, however, normally maintained but differs even within a single tissue from place to place. Oxygen uptake reflects local energy requirements and may change relatively slowly in organs such as liver or skin or very rapidly in muscle and brain tissue. To maintain an adequate supply of oxygen to structures with varying requirements there must be an accurate feedback mechanism coupling the need to the delivery system. Local vascular control mechanisms show features characteristic of autoregulation which require a sensor,","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"7-13"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11483334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The various phases of energy production have been described. These include glycolysis which is unique in its ability to produce ATP anaerobically, the tricarboxylic acid cycle with its major contribution to ATP production coming through the generation of NADH, and the cytochrome system at which reducing equivalents are converted to water, the released energy being incorporated into high-energy phosphates. The regulation of these pathways has been briefly described and the importance of the small amount of ATP generated anaerobically emphasized. The adaptation of muscle to periods of hypoxia through the presence of myoglobin, creatine phosphate and large amounts of glycogen is then discussed. The role of pH in limiting anaerobic glycolysis in muscle and the importance of the circulation in providing oxygen for exercising muscle are outlined. The effects of hypoxia on certain other tissues such as liver and brain have been detailed and finally methods for assessment of tissue hypoxia in man such as the measurement of the lactate:pyruvate ratio in blood are presented.
{"title":"The biochemical consequences of hypoxia.","authors":"K G Alberti","doi":"10.1136/jcp.s3-11.1.14","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.14","url":null,"abstract":"<p><p>The various phases of energy production have been described. These include glycolysis which is unique in its ability to produce ATP anaerobically, the tricarboxylic acid cycle with its major contribution to ATP production coming through the generation of NADH, and the cytochrome system at which reducing equivalents are converted to water, the released energy being incorporated into high-energy phosphates. The regulation of these pathways has been briefly described and the importance of the small amount of ATP generated anaerobically emphasized. The adaptation of muscle to periods of hypoxia through the presence of myoglobin, creatine phosphate and large amounts of glycogen is then discussed. The role of pH in limiting anaerobic glycolysis in muscle and the importance of the circulation in providing oxygen for exercising muscle are outlined. The effects of hypoxia on certain other tissues such as liver and brain have been detailed and finally methods for assessment of tissue hypoxia in man such as the measurement of the lactate:pyruvate ratio in blood are presented.</p>","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"14-20"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11414382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cells in tumours become hypoxic in either or both of two ways. First, the form of tumour growth may result in some cells lying so far from the capillaries that constitute their immediate source of oxygen that it is almost used up by the metabolism of the intervening cells. Secondly, the vascular system of the growing tumours may fail to deliver enough oxygen both because of inadequacies in the vessels themselves and in the quantity of blood that flows through them. The presence of hypoxic cells in tumours is of importance because it may affect the outcome of treatment by radiotherapy. Some two and a half to three times the dose of x radiation is needed to destroy the ability of cells to proliferate in the absence of oxygen as in its abundance (Alper and Howard Flanders, 1956). These three topics will be discussed, though a fourth, not pursued, should be associated with them: this is that the vascular system of a tumour is the pathway by which cytotoxic drugs used in therapy reach their site of action, and a degree of failure in transport may diminish their effectiveness in treatment.
{"title":"Hypoxia and tumours.","authors":"R H Thomlinson","doi":"10.1136/jcp.s3-11.1.105","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.105","url":null,"abstract":"Cells in tumours become hypoxic in either or both of two ways. First, the form of tumour growth may result in some cells lying so far from the capillaries that constitute their immediate source of oxygen that it is almost used up by the metabolism of the intervening cells. Secondly, the vascular system of the growing tumours may fail to deliver enough oxygen both because of inadequacies in the vessels themselves and in the quantity of blood that flows through them. The presence of hypoxic cells in tumours is of importance because it may affect the outcome of treatment by radiotherapy. Some two and a half to three times the dose of x radiation is needed to destroy the ability of cells to proliferate in the absence of oxygen as in its abundance (Alper and Howard Flanders, 1956). These three topics will be discussed, though a fourth, not pursued, should be associated with them: this is that the vascular system of a tumour is the pathway by which cytotoxic drugs used in therapy reach their site of action, and a degree of failure in transport may diminish their effectiveness in treatment.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"105-13"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11483325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Renal necrosis.","authors":"J F Smith","doi":"10.1136/jcp.s3-11.1.125","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.125","url":null,"abstract":"","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"125-6"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11483327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years bone necrosis has become of increasing significance and has stimulated much interest amongst clinicians, radiologists and pathologists. It is now an important cause of disability because it commonly complicates intracapsular femoral neck fracture which is frequent in aging populations (Barnes et al, 1976; Graham and Wood, 1976). It is a hazard not only to tunnellers working in compressed air(MRCDecompression SicknessPanel Report, 1971) but also to divers whose numbers and activities are ever expanding with the exploitation of North Sea oil (Lancet, 1974; Davidson, 1976). It gives rise to articular symptoms in some patients receiving therapeutic steroids (Fisher and Bickel, 1971; Park, 1976) and particularly in those on the high dosages and prolonged administration associated with immunosuppression following organ transplant. In addition to necrosis associated with these and other well accepted causes, so-called idiopathic or spontaneous necrosis may occur, especially in the femoral head (table I). The predisposing causes of such 'idiopathic' necrosis are currently the subject of intensive investigation (Zinn, 1971a and b) (table II). Unfortunately the clinical diagnosis ofbone necrosis is not easy. There are usually no signs to indicate an ischaemic episode until many months have elapsed and necrotic bone shows no radiological change unless the part is immobilized, then the dead bone may appear denser than the adjacent viable, porotic bone. A true increase in radiological density may result from laying down of new bone during repair, from compaction of trabeculae or from calcification within living or dead tissue (Johnson, 1964). Diagnosis may thus be difficult and caution is required in inferring underlying tissue changes even from well recognized radiological patterns. The widespread use of prosthetic replacement of bone and joints has provided the pathologist with the opportunity of studying more rewarding material than the small biopsy or the end-stage necropsy specimen, and there is now fairly general agreement on the pattern of morphological changes following necrosis (Catto, 1976): the sequence of events which brought these changes about is, however, open to more than one interpretation. In many conditions the pathogenesis of necrosis is controversial and is not always accepted as being primarily vascular (table I). Many questions remain unanswered, including one of major clinical importance; why is revascularization so often arrested and incomplete? The purpose of this paper is to indicate how bone necrosis may be recognized, to describe in a general way the main morphological features, and to point out areas of difficulty and controversy. Many topics, and particularly the osteochondritides of childhood, are omitted since it is rare for the pathologist to obtain material from them.
{"title":"Ischaemia of bone.","authors":"M Catto","doi":"10.1136/jcp.s3-11.1.78","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.78","url":null,"abstract":"In recent years bone necrosis has become of increasing significance and has stimulated much interest amongst clinicians, radiologists and pathologists. It is now an important cause of disability because it commonly complicates intracapsular femoral neck fracture which is frequent in aging populations (Barnes et al, 1976; Graham and Wood, 1976). It is a hazard not only to tunnellers working in compressed air(MRCDecompression SicknessPanel Report, 1971) but also to divers whose numbers and activities are ever expanding with the exploitation of North Sea oil (Lancet, 1974; Davidson, 1976). It gives rise to articular symptoms in some patients receiving therapeutic steroids (Fisher and Bickel, 1971; Park, 1976) and particularly in those on the high dosages and prolonged administration associated with immunosuppression following organ transplant. In addition to necrosis associated with these and other well accepted causes, so-called idiopathic or spontaneous necrosis may occur, especially in the femoral head (table I). The predisposing causes of such 'idiopathic' necrosis are currently the subject of intensive investigation (Zinn, 1971a and b) (table II). Unfortunately the clinical diagnosis ofbone necrosis is not easy. There are usually no signs to indicate an ischaemic episode until many months have elapsed and necrotic bone shows no radiological change unless the part is immobilized, then the dead bone may appear denser than the adjacent viable, porotic bone. A true increase in radiological density may result from laying down of new bone during repair, from compaction of trabeculae or from calcification within living or dead tissue (Johnson, 1964). Diagnosis may thus be difficult and caution is required in inferring underlying tissue changes even from well recognized radiological patterns. The widespread use of prosthetic replacement of bone and joints has provided the pathologist with the opportunity of studying more rewarding material than the small biopsy or the end-stage necropsy specimen, and there is now fairly general agreement on the pattern of morphological changes following necrosis (Catto, 1976): the sequence of events which brought these changes about is, however, open to more than one interpretation. In many conditions the pathogenesis of necrosis is controversial and is not always accepted as being primarily vascular (table I). Many questions remain unanswered, including one of major clinical importance; why is revascularization so often arrested and incomplete? The purpose of this paper is to indicate how bone necrosis may be recognized, to describe in a general way the main morphological features, and to point out areas of difficulty and controversy. Many topics, and particularly the osteochondritides of childhood, are omitted since it is rare for the pathologist to obtain material from them.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"78-93"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.78","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11483335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The majority of hypoxic episodes that result in histologically proven damage in the human brain cannot be adequately defined in physiological terms. They are usually accidents so that basic information such as the precise duration of a cardiac arrest or the blood pressure and heart rate during a period of severe hypotension is very rarely available. In such cases, neuropathological descriptions, however exhaustive, may well explain the final neuropsychiatric status of the patient but can at best indicate only tentatively the nature of the episode itself. The experimental approach is justified if it can indicate whether damage of a particular type in neurones and in white matter is or is not a direct consequence ofa particular hypoxic stress adequately delineated in physiological terms. At the outset it must be recalled that the energy for the normal functioning of the central nervous system is derived from the oxidative metabolism of glucose. A deficiency of oxygen or glucose will impair function and if severe and protracted enough will lead to irreversible brain damage. Interruption of the oxygen supply produces the most rapid impairment of brain function. Thus consciousness is lost about 10 sec after circulatory arrest. Abrupt anoxia exemplified by inhalation of an inert gas or sudden decompression to an altitude above 50 000 ft leads to loss of consciousnessafter aslightlylonger interval (17-20 sec). This rapid loss of consciousness in instances of profound hypoxia may well be responsible for the widely held view that enduring brain damage may begin soon after consciousness is lost.
{"title":"Experimental hypoxic brain damage.","authors":"J B Brierley","doi":"10.1136/jcp.s3-11.1.181","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.181","url":null,"abstract":"The majority of hypoxic episodes that result in histologically proven damage in the human brain cannot be adequately defined in physiological terms. They are usually accidents so that basic information such as the precise duration of a cardiac arrest or the blood pressure and heart rate during a period of severe hypotension is very rarely available. In such cases, neuropathological descriptions, however exhaustive, may well explain the final neuropsychiatric status of the patient but can at best indicate only tentatively the nature of the episode itself. The experimental approach is justified if it can indicate whether damage of a particular type in neurones and in white matter is or is not a direct consequence ofa particular hypoxic stress adequately delineated in physiological terms. At the outset it must be recalled that the energy for the normal functioning of the central nervous system is derived from the oxidative metabolism of glucose. A deficiency of oxygen or glucose will impair function and if severe and protracted enough will lead to irreversible brain damage. Interruption of the oxygen supply produces the most rapid impairment of brain function. Thus consciousness is lost about 10 sec after circulatory arrest. Abrupt anoxia exemplified by inhalation of an inert gas or sudden decompression to an altitude above 50 000 ft leads to loss of consciousnessafter aslightlylonger interval (17-20 sec). This rapid loss of consciousness in instances of profound hypoxia may well be responsible for the widely held view that enduring brain damage may begin soon after consciousness is lost.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"181-7"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11544753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A wide variety of neuronal alterations ascribed to the effect of hypoxia of different types has been described in man and in several species of experimental animals (Spielmeyer, 1922; Gildea and Cobb, 1930; Tureen, 1936; Hoff et at, 1945; Morrison, 1946; Grenell and Kabat, 1974; Krogh, 1952; Courville, 1951; Meyer, 1963). In a comprehensive review of the literature, Hoff et al (1945) concluded that the changes were remarkably alike whatever the cause of hypoxia. These changes, probably best seen with the Nissl stain, range from non-specific forms where the cells appear very pale or are undergoing swelling and loss of stainable substance to the classical descriptions given by Spielmeyer (1922). These latter changes, which include 'coagulation necrosis' or 'ischaemic cell change', 'homogenizing cell change' and 'liquefaction necrosis', have been discussed in terms of more modern views by Greenfield and Meyer (1963) and Brierley (1976). Nissl's 'acute cell disease' (Spielmeyer's 'acute swelling') and Nissl's 'chronic cell degeneration' must be added to the above neuronal alterations because they are so often mentioned as evidence of hypoxia and ischaemia. From this wide range of neuronal alterations Spielmeyer's ischaemic cell change, the term originally used to describe the alteration in nerve cells after general or local circulatory arrest, is now recognized as the degenerative response that is common to all types of hypoxia. Thus it is also seen in substrate deficiency (hypoglycaemia), anaemic hypoxia represented by carbon monoxide intoxication, histotoxic hypoxia as exemplified by cyanide poisoning and the complex situation represented by status epilepticus. However, it is important to stress that the patterns of distribution of ischaemic cell change in the brain may differ widely among the categories of hypoxia. The great diversity ofthe morphological alterations in neurones attributed to hypoxia is probably the outcome of postmortem autolytic changes unavoidable in human material, where there is a variable delay between death and necropsy coupled with slow penetration of the fixative, and to the use of immersion-fixation in experimental animals with the inevitable introduction of histological artefacts. Thus Hicks (1968) described diminished staining of Nissl bodies and other eosinophilic changes as the earliest neuronal alterations in anoxic necrosis in human material but considered them to be indistinguishable from postmortem changes. There are two common cytological artefacts encountered in human and experimental animal brains each of which has been interpreted as evidence of hypoxic damage and reported as such. The hyperchromatic neurone or 'dark cell' has been the subject of numerous studies, including those of Scharrer (1938), Wolf and Cowaen (1949), Koenig and Koenig (1952), Cammermeyer (1960, 1961, 1962) and Cohen and Pappas (1969). This artefact is most frequently observed after a fresh neurosurgical biopsy specimen is fixed in formal
{"title":"Structural abnormalities in neurones.","authors":"A W Brown","doi":"10.1136/jcp.s3-11.1.155","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.155","url":null,"abstract":"A wide variety of neuronal alterations ascribed to the effect of hypoxia of different types has been described in man and in several species of experimental animals (Spielmeyer, 1922; Gildea and Cobb, 1930; Tureen, 1936; Hoff et at, 1945; Morrison, 1946; Grenell and Kabat, 1974; Krogh, 1952; Courville, 1951; Meyer, 1963). In a comprehensive review of the literature, Hoff et al (1945) concluded that the changes were remarkably alike whatever the cause of hypoxia. These changes, probably best seen with the Nissl stain, range from non-specific forms where the cells appear very pale or are undergoing swelling and loss of stainable substance to the classical descriptions given by Spielmeyer (1922). These latter changes, which include 'coagulation necrosis' or 'ischaemic cell change', 'homogenizing cell change' and 'liquefaction necrosis', have been discussed in terms of more modern views by Greenfield and Meyer (1963) and Brierley (1976). Nissl's 'acute cell disease' (Spielmeyer's 'acute swelling') and Nissl's 'chronic cell degeneration' must be added to the above neuronal alterations because they are so often mentioned as evidence of hypoxia and ischaemia. From this wide range of neuronal alterations Spielmeyer's ischaemic cell change, the term originally used to describe the alteration in nerve cells after general or local circulatory arrest, is now recognized as the degenerative response that is common to all types of hypoxia. Thus it is also seen in substrate deficiency (hypoglycaemia), anaemic hypoxia represented by carbon monoxide intoxication, histotoxic hypoxia as exemplified by cyanide poisoning and the complex situation represented by status epilepticus. However, it is important to stress that the patterns of distribution of ischaemic cell change in the brain may differ widely among the categories of hypoxia. The great diversity ofthe morphological alterations in neurones attributed to hypoxia is probably the outcome of postmortem autolytic changes unavoidable in human material, where there is a variable delay between death and necropsy coupled with slow penetration of the fixative, and to the use of immersion-fixation in experimental animals with the inevitable introduction of histological artefacts. Thus Hicks (1968) described diminished staining of Nissl bodies and other eosinophilic changes as the earliest neuronal alterations in anoxic necrosis in human material but considered them to be indistinguishable from postmortem changes. There are two common cytological artefacts encountered in human and experimental animal brains each of which has been interpreted as evidence of hypoxic damage and reported as such. The hyperchromatic neurone or 'dark cell' has been the subject of numerous studies, including those of Scharrer (1938), Wolf and Cowaen (1949), Koenig and Koenig (1952), Cammermeyer (1960, 1961, 1962) and Cohen and Pappas (1969). This artefact is most frequently observed after a fresh neurosurgical biopsy specimen is fixed in formal","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"155-69"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11617198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although skeletal muscle and peripheral nerves are both resistant to ischaemia there are nevertheless many syndromes in which they are affected, either separately or together. It is frequently difficult to distinguish the effects of arterial ischaemia from those of compression, which may operate through vascular occlusion, or, in the case of peripheral nerve, by mechanical deformation of nerve fibres. A great deal has been learned from experimental models, but not all of it is applicable to the complexity of human neuromuscular ischaemia which requires further study.
{"title":"Ischaemia of peripheral nerve and muscle.","authors":"D G Harriman","doi":"10.1136/jcp.s3-11.1.94","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.94","url":null,"abstract":"<p><p>Although skeletal muscle and peripheral nerves are both resistant to ischaemia there are nevertheless many syndromes in which they are affected, either separately or together. It is frequently difficult to distinguish the effects of arterial ischaemia from those of compression, which may operate through vascular occlusion, or, in the case of peripheral nerve, by mechanical deformation of nerve fibres. A great deal has been learned from experimental models, but not all of it is applicable to the complexity of human neuromuscular ischaemia which requires further study.</p>","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"94-104"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.94","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11483336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Since the publication of the classical studies of Heymans et al (1930) it has been accepted that the carotid body is a chemoreceptor which monitors the oxygen tension of systemic arterial blood, and it has been extensively investigated by physiologists (Biscoe, 1971). Because chronic hypoxia is a major hazard of life at high altitude and ofcardiorespiratory disease at sea level, it might be thought that much is known about the pathology of the carotid body in such situations. This, however, is not the case. It was not until 1969 that Arias-Stella reported enlargement of the cartoid bodies in high-altitude dwellers in the Peruvian Andes and 1970 that Heath et al described such enlargement in sea-level patients with emphysema. Thus until the last decade, the only condition of the carotid body which the general pathologist was aware of was the rare tumour known as the chemodectoma. Since the pioneering observations of Arias-Stella, pathological studies by Heath and Edwards (1971) of the carotid body have been made on human subjects and animals born and living at high altitude, and also on animals living at subatmospheric pressure in hypobaric chambers. These chambers are very convenient for working with small animals in the laboratory without the inconvenience and expense of long journeys to countries with mountain ranges over 3600 metres high. However, a distinction must be made between the examination of animal tissues derived from experiments using hypobaric chambers and the examination of tissues from human subjects and animals born and living for many years at high terrestrial altitude. Hypobaric chambers can accurately reproduce the low atmospheric pressure ofhigh altitude but not the climatic and other environmental features of life in a high mountainous region. This paper briefly reviews the structure and function of the normal carotid body, and then deals with the morphological changes associated with acute and chronic alveolar hypoxia in human subjects and animals.
{"title":"Hypoxia and the carotid body.","authors":"J M Kay, P Laidler","doi":"10.1136/jcp.s3-11.1.30","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.30","url":null,"abstract":"Since the publication of the classical studies of Heymans et al (1930) it has been accepted that the carotid body is a chemoreceptor which monitors the oxygen tension of systemic arterial blood, and it has been extensively investigated by physiologists (Biscoe, 1971). Because chronic hypoxia is a major hazard of life at high altitude and ofcardiorespiratory disease at sea level, it might be thought that much is known about the pathology of the carotid body in such situations. This, however, is not the case. It was not until 1969 that Arias-Stella reported enlargement of the cartoid bodies in high-altitude dwellers in the Peruvian Andes and 1970 that Heath et al described such enlargement in sea-level patients with emphysema. Thus until the last decade, the only condition of the carotid body which the general pathologist was aware of was the rare tumour known as the chemodectoma. Since the pioneering observations of Arias-Stella, pathological studies by Heath and Edwards (1971) of the carotid body have been made on human subjects and animals born and living at high altitude, and also on animals living at subatmospheric pressure in hypobaric chambers. These chambers are very convenient for working with small animals in the laboratory without the inconvenience and expense of long journeys to countries with mountain ranges over 3600 metres high. However, a distinction must be made between the examination of animal tissues derived from experiments using hypobaric chambers and the examination of tissues from human subjects and animals born and living for many years at high terrestrial altitude. Hypobaric chambers can accurately reproduce the low atmospheric pressure ofhigh altitude but not the climatic and other environmental features of life in a high mountainous region. This paper briefly reviews the structure and function of the normal carotid body, and then deals with the morphological changes associated with acute and chronic alveolar hypoxia in human subjects and animals.","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"30-44"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11414383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The relationship between the blood supply of a neurone and its capacity to function and survive remains of fundamental importance in the study of cerebral vascular disease from both the surgical and the medical standpoint. Thus it has been assumed that a matter of only a few minutes is necessary to cause complete and permanent loss of function of key neurones in the primate nervous system (Dennis and Kabat, 1939; Weinberger et al, 1940; Grenell, 1946; Boyd and Connolly, 1962), but everyday clinical experience confirms that dense neurological deficits following soon after a cerebral ischaemic episode may gradually resolve and finally even disappear. It has long been an intriguing clinical question whether such resolution of neurological deficits relates to the recovery of neurones so damaged following the ischaemic episode as to cease functioning, yet subsequently recover, or whether associated areas outwith the zone of immediate ischaemia are capable of assuming the function of structures rendered irreversibly damaged by the ischaemic event. The theory that certain cells probably survive in a state of structural integrity but functional paralysis has seemed to us for some years most likely, while possible explanations for the recovery of neurones have been either improvement in residual circulation with expansion of the collateral vessels from neighbouring cerebrovascular beds, or modification of the neuronal metabolism itself so that function may be resumed at a lower basal level of blood flow. The experimental findings in this paper relate attempts to elucidate the relationship between structure, function and blood supply in the nervous system. They have been stimulated by surgical rather than medical phenomena, since the occlusion of vessels during the excision of basal tumours, or the occlusion of portions of the cerebral circulation in the treatment of intracranial aneurysm, generally gives a human preparation less clouded by incidental vascular disease than occlusion in the course of the development of atherosclerosis with its attendant impairment of function of collateral vessels, and, possibly, disorder reactivity of the vascular system as a whole. In the experimental analysis of these phenomena the experimental stroke model described elsewhere has been used (Symon et al, 1971; Symon, 1975), in which the middle cerebral artery is occluded either by an intracranial approach along the sphenoidal wing, or by a transorbital approach after removal of the contents of the orbit and dissection through the enlarged superior orbital fissure. Temporary occlusion of the vessel in acute experiments is performed with a small spring clip such as a Scoville clip, while for permanent occlusion the artery is divided between two small 'haemo' clips. The site of occlusion used in this model is the first millimetre of the middle cerebral which, as Shellshear (1921) and Abbie (1934) have indicated, is free from perforating vessels. The intensity of ischaemia i
{"title":"The concepts of thresholds of ischaemia in relation to brain structure and function.","authors":"L Symon, N M Branston, A J Strong, T D Hope","doi":"10.1136/jcp.s3-11.1.149","DOIUrl":"https://doi.org/10.1136/jcp.s3-11.1.149","url":null,"abstract":"The relationship between the blood supply of a neurone and its capacity to function and survive remains of fundamental importance in the study of cerebral vascular disease from both the surgical and the medical standpoint. Thus it has been assumed that a matter of only a few minutes is necessary to cause complete and permanent loss of function of key neurones in the primate nervous system (Dennis and Kabat, 1939; Weinberger et al, 1940; Grenell, 1946; Boyd and Connolly, 1962), but everyday clinical experience confirms that dense neurological deficits following soon after a cerebral ischaemic episode may gradually resolve and finally even disappear. It has long been an intriguing clinical question whether such resolution of neurological deficits relates to the recovery of neurones so damaged following the ischaemic episode as to cease functioning, yet subsequently recover, or whether associated areas outwith the zone of immediate ischaemia are capable of assuming the function of structures rendered irreversibly damaged by the ischaemic event. The theory that certain cells probably survive in a state of structural integrity but functional paralysis has seemed to us for some years most likely, while possible explanations for the recovery of neurones have been either improvement in residual circulation with expansion of the collateral vessels from neighbouring cerebrovascular beds, or modification of the neuronal metabolism itself so that function may be resumed at a lower basal level of blood flow. The experimental findings in this paper relate attempts to elucidate the relationship between structure, function and blood supply in the nervous system. They have been stimulated by surgical rather than medical phenomena, since the occlusion of vessels during the excision of basal tumours, or the occlusion of portions of the cerebral circulation in the treatment of intracranial aneurysm, generally gives a human preparation less clouded by incidental vascular disease than occlusion in the course of the development of atherosclerosis with its attendant impairment of function of collateral vessels, and, possibly, disorder reactivity of the vascular system as a whole. In the experimental analysis of these phenomena the experimental stroke model described elsewhere has been used (Symon et al, 1971; Symon, 1975), in which the middle cerebral artery is occluded either by an intracranial approach along the sphenoidal wing, or by a transorbital approach after removal of the contents of the orbit and dissection through the enlarged superior orbital fissure. Temporary occlusion of the vessel in acute experiments is performed with a small spring clip such as a Scoville clip, while for permanent occlusion the artery is divided between two small 'haemo' clips. The site of occlusion used in this model is the first millimetre of the middle cerebral which, as Shellshear (1921) and Abbie (1934) have indicated, is free from perforating vessels. The intensity of ischaemia i","PeriodicalId":75996,"journal":{"name":"Journal of clinical pathology. Supplement (Royal College of Pathologists)","volume":"11 ","pages":"149-54"},"PeriodicalIF":0.0,"publicationDate":"1977-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s3-11.1.149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11617197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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