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乳牛の壊疽性乳房炎の乳房の病理学的研究
https://az.repo.nii.ac.jp/records/3802
https://az.repo.nii.ac.jp/records/3802f6525400-6c00-4b92-bcaf-1c9d7b7b5410
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
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公開日 | 2013-10-01 | |||||||||
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タイトル | 乳牛の壊疽性乳房炎の乳房の病理学的研究 | |||||||||
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タイトル | Pathologic study on the udder of gangrenous mastitis of the cow | |||||||||
言語 | en | |||||||||
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言語 | jpn | |||||||||
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資源タイプ | thesis | |||||||||
著者 |
有田, 忠義
× 有田, 忠義
× Arita, Tadayoshi
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内容記述タイプ | Abstract | |||||||||
内容記述 | 乳牛のいわゆる壊疽性乳房炎は近年多発の傾向にあるが、依然見るべき対策はなされておらず、また無治療で廃用され、酪農家の被害と恐怖は大きい。従って本病の病性を探究すると共に診断、予防、治療の方策を確立することは急務である。本病の概要については吉田らの編集になる家畜診療指針に記載されているが、その他の報告でも細菌や病理組織像等については、例数も少なく深く究明されたものは見当らない。 現在本症発生機序に関する考え方には、細菌の毒素を主とするものと、それに他の要因が加わったとする考え方との二つがあるが、なお十分解明されたとはいい難い。著者は本症の研究を続けて約10年になるが、その成績でも細菌毒のみで説明できないいくつかの現象を感じている。このようなことから著者は本症の究明は、細菌学のみならず、免疫学、病理学及び生化学等人畜を通ずる基礎理論が必要であると考えている。なお、本症の臨床的所見として、発生時期は分娩後3日以内が81%であり、重篤な臨床症状と乳房、乳汁の変化を主徴とし、症例のほとんどのものに食欲廃絶、起立不能、呼吸促迫または困難、皮温の不整または冷感がみられた。眼球は陥没したものが多く、体温は高低区々であるが重症、瀕死のものには低いものも多い。下痢もしばしばみられ暗褐色軟泥状、水様及びタール様便等であった。しかし少数例のやや軽度のものは起立していたり少量の生草を食した。 罹患分房は腫脹硬結し、紫斑の見えるものが多く、暗赤色のものもあり、また疼痛や冷感がみられた。乳質は血乳のものが多く、黄褐色や漿液状のものもあり、少数例には変化の少ないものもあった。乳房にガスのあるものは13例であった。いずれにせよ広範な研究が必要であるが今回は本症の乳房を特に病理学的に倹索し、通常の急性乳房炎と異なる本症の病理学的特徴を明らかにした。 1. 材料及び方法 研究対象とした乳牛は、徳島県内の家畜共済廃用牛のうち主治医に著者が立会し、壊疽性乳房炎と診断した42例の病牛で、その罹患乳房を採取し、同時に細菌の検索も行なった。発生時期は分娩後3日以内が81%で、重篤な臨床症状と乳房及び乳汁の変化を主徴としていた。 病理学的検索方法は、罹患乳房の暗赤色または紫赤色を呈した部分数箇所を採取し、病理組織学的研究においては腺胞、間質、血管、乳管及び膿瘍等に重点を指向し、これをさらに細別して15の所見を観察した。病変の程度は変化の強いもの[トリプルプラス]、より弱いもの(+)、ごく軽いもの(±)、変化の認められないものは(-)の記号を用いて比較検討した。 2. 病理組織学的所見 壊疽性乳房炎の乳房の病理組織学的所見のうちで、病変の強い[ダブルプラス]以上のものを、多いものから列挙すると42例中腺胞上皮の変性、壊死35例(83.3%)、間質の浮腫31例(73.8%)、充血、うっ血31例(73.8%)、血栓形成29例(69.0%)、fibrinの析出28例(66.7%)、血管のfibrinoid壊死(以下ENと略)21例(50%)、間質の出血17例(40.5%)、腺胞内の細胞浸潤16例(38.1%)、腺胞上皮の脱落16例(38.1%)の順であり、乳管壁の変化は腺胞上皮の変化におおむね似ていた。また間質の浮腫とfibrin析出との間の相関は最も緊密で〔γ=0.756 (p<0.01)〕あり、この所見は間質の浮腫が線維素性浮腫であることを裏付けするものと考えられた。 そこでこのような所見をもつ壊疽性乳房炎の病変が日常診療における非壊疽性の急性乳房炎の組織像に比べ、どのような差異や特徴を持つかを究明するため、6例の急性乳房炎を対照牛とし、発病当日のものをパイオプシーにより調べた。通常の急性乳房炎の組織像は腺胞内や間質の細胞浸潤と、これに伴う腺胞上皮の脱落や空胞変性が主体で浮腫は軽く、fibrinの析出や間質の出血、血栓形成のようなものは、ほとんどのものに欠いていた。すなわち壊疽性乳房炎にみるような強度の血管反応系の病変はなく、実質の変性、壊死も軽かった。従って壊疽性乳房炎の病理組織学的特徴は、前に列挙した強い病変のものより、腺胞内の細胞浸潤や上皮の脱落を除いたもの、すなわち血管の充血、うっ血、間質の線維素性浮腫、出血、血栓形成、血管のFNのような強い血管反応系の病変で、それに伴って腺胞上皮の変性、壊死が強いことであると認められた。 膿瘍のみられたものは42例中16例(38.1%)で、強いものは僅か5例よりなく、これを炎症病巣の拡りと比較すると限局性のものが多かった。また膿瘍ができていて、それに感作されて発病したと考えられる所見もあったが、むしろ多くの膿瘍は本症の特徴的所見である出血性、壊死性病変の進展とともに、白血球浸潤の強度の病巣として発生したと考えられるものに多かった。 菌のコロニーは約半数のものにみられたが、1標本で1~3箇の少ないものがほとんどで、これと近傍組織との関係は、コロニーを中心に出血、血栓、壊死等強い炎症像を認めるものもあったが、多くの症例はコロニーに関係なく全体に強い変化が確認された。 また、慢性乳房炎がすでにあったと考えられる線維化の部分と、出血、血栓形成など炎症のさかんなところが一標本で共存する姿もみられた。このことは慢性乳房炎も分娩等発症しやすい機会を得れば本症に転化しうることを示唆するもので、本症の予防上考慮すべき問題と考えられた。 血栓形成は40例、血管のFNは35例で、その程度は線維素性浮腫の主要成分であるfibrin析出の強弱と相互関係〔それぞれγ=0.557 及び 0.564 (いずれもP<0.01)〕がみられた。 3. 腺胞上皮の変牲、壊死と密接な関係にある病変 上皮の変化に関係のある病変は、間質の線維素性浮腫、血栓形成及び血管のFNなどで、これら3者の病変の強弱と上皮の変化の程度との間には有意(P<0.01)の相関関係(それぞれγ=0.478、 0.450、 0.564)が認められ、間質の出血でもその程度に応じて上皮の変性、壊死の強いものが多かった。 しかし腺胞内の細胞浸潤や上皮の脱落ではこのような比例関係はみられず、むしろ逆の現象を示し密接な関係はみられなかった。また膿瘍や菌のコロニーに影響せられたと考えられた所見は例数も少なく局所的な変化であったこと等の現象は、変性、壊死の原因の大きなfactorが強い血管反応による循環障害と考えられた。 4. 病変と臨床症状の関係 壊疽性乳房炎の臨床症状の特徴的所見と考えられている血乳は、腺胞内に出血がみられた30例のうち18例(60%)にみられたが、他の12例には肉眼で血乳とは判断されなかった。このような場合、腺胞内や乳管内に血漿や浸潤細胞、脱落上皮、少量の乳汁等の混在がみられたので、乳汁の性状はこれら滲出物の多少によって左右されるものと考えられた。 また本症における全身症状は、本症乳房の特徴的所見の程度に比例して強かった。 5. 細菌の種類と病変 感染細菌の種類はStaphylococcus aureus 〔Staphylococcus I (越智)〕6例、Staphylococcus epidermidis 〔Staphylococcus II (越智)〕2例、Streptococcus 4例、Escherichia coli 13例、棹菌を含む混合感染14例、球菌のみの混合感染1例、その他2例であった。 病変の特徴はStaphylococcus I は細胞浸潤と膿瘍の形成が強いが、Staphylococcus II はこの傾向が弱い。Streptococcusは細胞浸潤の程度がStaphylococcus I とよく似ているが膿瘍の形成は弱い。Escherichia coliは細胞浸潤、膿瘍の形成は弱いが、充血、出血にはじまり、血管壁のfibrinoid壊死にまでいたる血管反応は最も強かった。混合感染で棹菌を含むものは、細胞浸潤、膿瘍形成がE. coliのものよりやや多いが、血管反応のようなものはよく似ていた。球菌のみの混合感染は1例であるが、間質の細胞浸潤、膿瘍の形成は強かった。このように菌の種類により病変の出かたに多少の差がみられ、これらを大別すれば球菌は細胞浸潤を主とする型で、棹菌は血管反応を主とする型ということになる。しかし、いずれの菌種の場合でも壊疽性乳房炎の特徴である強度の充血に始まる一連の血管反応が統一所見としてみられ、そのうちE. coliは代表的所見を示した。 6. 感染試験 菌の毒力を試すため、壊疽性乳房炎の罹患乳汁を分娩期と離れた時期の他の牛の健康乳房に注入し臨床症状やその組織像を調べたところ、いずれも壊疽性乳房炎にみるような重篤な症状は起らず、組織像も通常の急性乳房炎のものによく似ていた。 7. 発生機序に関連して 壊疽性乳房炎の組織像は血管反応系の病変が主体で、膿瘍や菌のコロニ一は従の関係にあり、実質の変化も強い血管反応による循環障害が主役と考えられたが、このような所見は菌の種類にかかわらず統一所見としてみられたこと、感染試験で本症が再現できなかった事実から考えると菌の毒力の直接的な影響を疑う材料が多い。またこのような組織像特に血管のFNはなんらかの感作反応を示唆しているように考えられた。そしてその形態像はArthus現象またはshwartzman現象の組織像によく似ていた。 本症の発生がこのような現象に加えて分娩期に多いことは、感染細菌の毒素とその時の母体の変調や条件、乳房の状態等が相関連し炎症を激化させると考えられないこともないが、同時にこのような特殊事情にある母体の条件に感作反応が誘発されて加わったとも考えられ、その感作反応は、Arthus現象またはshwartzman現象であるということも十分考えられる。 以上述べてきたことから本症の治療は早期の抗生物質その他の薬物の投与のみならず、同時に母体の調整や血管反応抑制方策等も必要であることが示唆されるようである。 |
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Abstract | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | Gist of this investigation Gangrenous mastitis of the cow has recently a tendency of high incidence, but nevertheless no noteworthy countermeasure has yet been taken, the abandonment of the cow without treatment gives daiary farmers large economical loss and fear. Therefore, it is an urgent need to establish every measures of diagnosis, prophylaxis and treatment together with the investigation of the nature of the disease. The outline of the disease is described in "The Cattle Treatment Guide Book" compiled by Yoshida et al., however, in the other reports, there are very few cases described on bacteriological and histopathological features and no profoundly investigated reports can be found. For the time being, there are two ways of thinking of the pathogenic mechanism of the disease, that is, one based principally on the toxin of bacteria, and the other added other factors to the former, but it has not yet been sufficiently clarified. Although the author has been studying this disease for about 8 years, even with the results, still he feels that there are several phenomena which can not be accounted only for the toxin of bacteria. From this viewpoint, the author thinks it necessary to establish a fondamental theory being common to human and cattle-such as not only bacteriological, but also immunological, pathological, biochemistrical and so forth, but this time, particularly by pathological investigation. of the udder of this disease, the characteristics of the disease discriminated from ordinary acute mastitis has been made clear. 1. Materials and methods The test animals of this study were 42 cows which were chosen among the abandoned and slaughted cows of the Daiary Farmer's Mutual Aid Association of Tokushima prefecture, and were diagnosed as gangrenous mastitis by a home veterinarian, beeng present at the field by the author. The sich udders were collected and the same time the bacteriological examination was carried out. As regards the methods of pathological investigation, several sections were collected out of the parts which showed dark red or violet red colour at autopsy to make preparates, which were roughly divided, into the alveolus, interstice, blood vessel, milk duct, abscess and so forth, which were further subdivided to observe 15 findings. The grade of macroscopical changes was noted by using such sign in order from the strongest to no change as ( +++ ), ( ++ ), ( + ) and ( - ) to provide fundamental data for every examinations. 2. Outline of clinical symptoms As for the time of the oncet, those which appeared within 3 days after delivery occupied 81 %, being mainly characterized by severe clinical symptoms and changes in the udder and milk, and in almost all of the cases anorexia, astasia, tachypnea or dyspnea were observed, and thermal ataxia or hypothermy of skin temperature of body were also noted. The eyeballs often sank, body temperature varied either high or low, but many of severe and critically ill cases showed hypothermy. Diarrhea were also often observed showing dark brown soft muddy form, watery and tarry-looking stool. But small number of cases with relatively slight symptoms could stand or sometimes eat small amount of green herbages. The lesion of udders showed swelling and induration, many of them coloured purpura, some of them were dark red, and pain and chill were also observed. As regards the quality of milk, many of them were bloody, some of them were yellowish-brown and serous looking, and there were small number of cases with little changes. 13 cases of the udder contained gases were also recognized. 3. Histopathological findings The histological characteristics of gangrenous mastitis are violent exudative inflammation consisting chiefly of hemorrhage of the interstice, exudation of fibrin, formation of thrombus and so on, necrosis of glandular cells and blood vessels are severe. On the contrary, the exudation of neutrophil ( suppuration ) was rather slight in many cases, and abscesses were scattered. In order to show them accurately, when the number of histological changes stronger than ( ++ ) was counted out of 42 cases, there were 35 cases ( 83.3 % ) of the degeneration and necrosis of the alveolar epithelium, 31 cases ( 73.8 % ) of edema of the interstice, 31 cases ( 73.8 % ) of hyperemia and congestion, 29 cases ( 69.0 % ) of thrombus formation, 28 cases ( 66.7 %) of fibrin exudation, 21 cases ( 50 % ) of fibrinoid necrosis ( hereinafter abbreviated as FN ) of the blood vessel, 17 cases ( 40.5 %) of hemorrhge of the interstice, 16 cases ( 38.1 o ) of cellular exudation in the alveolus, and 16 cases ( 38.1 %) of desquamation of alveolar epithelium, and the change of the milk duct wall was almost similar to the change of the alveolar epithelium. And in the correlation between edema and fibrin exudation, a proportional relationship was observed with a significant difference ( P < 0.01 ), and this fact supported that edema of the interstice was fibrinous. Then, in order to examine what difference and characteristics were to be shown by the histological changes of gangrenous mastitis compared with those of non gangrenous acute mastitis in daily treatment, 6 cases of acute mastitis at the day of onset were set as control cows for biopsy. The histological findings of ordinary acute mastitis chiefly consisted of cellular exudation in the alveolus and interstice accompanied by desquamation of the alveolar epithelium and vacuolar degeneration, edema was slight and almost of them lacked of fibrin exudation and hemorrhage of the interstice, and thrombus formation. That is, there were not so severe changes in blood vessel reaction system as seen in gangrenous mastitis, and the degeneration of the interstice and necrosis were also slight. The histopathological characteristics of gangrenous mastitis were, therefore, noticed to be those in which intracellular infiltration and desquamation of the epithelium were eliminated from such severe histological changes as above-mentioned, that is, to be the severe histological changes in blood vessel system, such as hyperemia and congestion of the blood vessel, fibrinous edema of the interstice, hemorrhage, thrombus formation and FN of the blood vessel, strongly involving the degeneration of the alveolar epithelium and necrosis. The number of the cases in which abscesses were observed was 16 cases ( 38.1 % ) out of 42 cases, there were only 5 severe cases, and compared with the extent of inflammatory focus, many of them were found to be localized. And there were some findings in which it was thought that abscesses previously formed provoked the onset of the disease by sensitization but many of abscesses were found in the cases which were thought to have appeared as intensive focus of leucocyte infiltration along with the progress of hemorrhagic and necrotic lesions which were characteristic findings of this disease. The colonies of bacteria were observed in about half the cases, but almost of them showed few colonies such as 1 - 3 per one preparate, and as for the relationship with the surrounding tissue, the intensive changes in many cases were confirmed as a whole independently of the colonies, although there were also the cases in which intense inflammatory changes such as hemorrhage, thrombus, necrosis and so on were observed in the center of colonies. Coexisting feature of the part of fibrosis which led to think of chronic mastitis already existed, and the part where inflammation such as hemorrhage and thrombus formation were violent, was also observed in a preparate. This fact suggests that chronic mastitis, when obtained on easy chance for onset such as delivery and so on, can also invert to this disease, and it was thought that this problem should be taken into consideration from the prophylactic viewpoint of this disease. Thrombus formation was observed in 40 cases, and FN of the blood vessel was seen in 35 cases, and as regards their grades, parallel relationships to the intensity of fibrin exudation as primary constituent of fibrous edema were observed. 4. The lesion closely related to degeneration, necrosis of the alveolar epithelium The lesion related to the changes of the epithelium were fibrous edema of the interstice, thrombus formation, FN of the blood vessel, hemorrhage of the interstice and so on, and in the relationships between the intensities of lesion in the former three and the grade of the change of the epithelium, proportional relationships were observed with significant differences at ( P < 0.01 ), ( P<0.01 ) and ( P<0.01 ) respectively, and there were many cases of intensive degeneration and necrosis of the epithelium also in the hemorrhage of the interstice responding to the grade. But no such proportional relationship was observed at the cellular infiltration in the alveolus and the desquamation of the epithelium, and no close relationship was observed rather showing inverse phenomena. And the phenomena which were thought to be influenced by abscess and the colonies of bacteria were few and local changes led us to think that the important factor of the cause of degeneration and necrosis was circulatory disorder caused by severe blood vessel reaction. 5. Relationships between morbid changes and clinical symptoms Bloody milk which is thought to be one of the characteristic findings of the clinical symptoms of gangrenous mastitis was observed in 18 cases ( 60 % ) out of 30 cases in which hemorrhage was observed in the alveolus, but in the remaining 12 cases, bloody milk was not judged macroscopically. In such cases, as the admixture in plasma, migrated cell, desqumated epithelium, a small amount of milk and so on was observed in the alveolus and milk duct, it was thought that the description of milk was influenced by the amount of these exudates. And the seriousness of general symptoms in this disease was depending on the grade of the characteristic findings of the udder of this disease. 6. Species of bacteria and lesion Species of infecting bacteria were 6 cases of Staphylococcus aureus 〔 Staphylococcus I ( Ochi )〕, 2 cases of Staphylococcus epidermidis 〔 Staphylococcus II ( Ochi )〕, 4 cases of Streptococcus, 13 cases of Escherichia coli, 14 cases of mixed infection including bacillus, I case of mixed infection consisting of only coccus, and other 2 cases. As regards the characteristics of lesion, Staphylococcus I, showed the intense celluler infiltration and many abscesses were observed, but Staphylococcus II was weak in this tendency. Streptococcus showed a similar grade of cellular infiltration to that of Staphylococcus I, but was weak in abscess formation. Escherichia coli caused weak cellular infiltration and abscess formation, but showed the most severe blood vessel reaction beginning with hyperemia and hemorrhage and resulted to FN of the blood vessel wall. In mixed infection containing bacillus, there were slightly more cellular infiltration and abscess formation than that containing E. coli, but showed similar blood vessel reaction. Mixed infection consisted of coccus only was I case, which showed the sever cellular infiltration of the interstice and abscess formation. These findings show that the appearance of lesion was varied to some extent due to the species of bacteria, and when they were roughly classified, it becomes that coccus shows a type chiefly consisting of cellular infiltration, and bacillus does a type chiefly consisting of blood vessel reaction. But in either case, a series of blood vessel reaction beginning with strong hyperemia characteristic to gangrenous mastitis was observed in common. Among them, E. coli was typical. 7. Infection test To examine the toxicity of bacteria, by infusing the milk infected with gangrenous mastitis to the udder of a healthy cow which was in the time from delivering period, the clinical symptoms and histopathological changes were examined, and it was found that no such serious symptoms as seen in gangrenous mastitis occurred, and the histopathological findings resembled that of ordinary acute mastitis. 8. On the mechanism of occurrence of gangrenous mastitis. It was thought that the pathological histology of gangrenous mastitis chiefly consisted of the lesions based on blood vessel reaction, while abscess and bacterial colonies acted the subordinating roles, therefore the changes in the parenchyma chiefly consisted of circulatory disorder caused by strong blood vessel reaction, however, the fact that such finding was observed in common, independently on the species of bacteria, and this disease could not be reproduced by experimental infection, presented many holds to doubt of the direct influence on the changes with the toxicity of bacteria. Further it was thought that such a histological changes, particularly the FN of the blood vessel seemed to suggest some kind of sensitized reaction. And its morphological picture was very similar to the histological changes of Arthus phenomenon or Shwartzman phenomenon. The fact that the appearance of this disease often occurs at the period of delivery in addition to such phenomena does not negate the thought that the toxicity of infecting bacteria, the disorder of the mother body, the state of the udder were related with each other to intensify the inflammation, but at the same time, it may be also thought that a sensitized reaction was added to the condition of the mother body under such special situations, thus it can be sufficiently thought that this sensitized reaction will be such as Arthus phenomenon or Shwartzman phenomenon. And judging from the above-mentioned facts, it is suggested that the treatment of this disease needs not only early therapy with antibiotics, but also the adjustment of the mother body condition and every measures to suppress the blood vessel reaction. |
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学位名 | ||||||||||
学位名 | 獣医学博士 | |||||||||
学位授与機関 | ||||||||||
学位授与機関名 | 麻布大学 | |||||||||
学位授与年月日 | ||||||||||
学位授与年月日 | 1977-12-19 | |||||||||
学位授与番号 | ||||||||||
学位授与番号 | 乙第121号 | |||||||||
著者版フラグ | ||||||||||
出版タイプ | AM | |||||||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |