# 坏死（Necrosis）

- 器官 / 系统：肝 / 肝胆系统（liver / hepatobiliary-system）
- NTP 数据编号：ntp-0401
- 规范 URL：https://www.labsmart.cn/ntp/liver-necrosis.html
- 中文图谱总页锚点：https://www.labsmart.cn/ntp-atlas.html#liver-necrosis
- 原始出处：https://ntp.niehs.nih.gov/atlas/nnl/hepatobiliary-system/liver/Necrosis
- 授权：美国联邦政府作品，公有领域；引用请标注 NTP Nonneoplastic Lesion Atlas
- 适用说明：仅供科研使用，不用于临床诊断

## 一句话结论
肝细胞坏死（hepatocellular necrosis）的范围、模式及形态学特征取决于肝毒性外源化学物（hepatotoxic xenobiotics）的代谢活化程度、宿主对毒物的反应、外源化学物暴露的剂量与持续时间，以及给药后肝样本评估的时间。

## 病变描述（中文）
肝细胞坏死（hepatocellular necrosis）的范围、模式及形态学特征取决于肝毒性外源化学物（hepatotoxic xenobiotics）的代谢活化程度、宿主对毒物的反应、外源化学物暴露的剂量与持续时间，以及给药后肝样本评估的时间。经典凝固性坏死（coagulation necrosis）通常由缺血或梗死引起，由于负责蛋白水解的溶酶体酶变性失活，组织结构在一定程度上得以保持。另一种坏死形式——液化性坏死（liquefaction necrosis）——可导致细胞溶解和细胞学结构丧失。可能伴随坏死出现的变化包括出血、脂肪变（fatty change）、细胞质空泡化、细胞学退变及炎性细胞浸润。Figure 1、Figure 2 代表边界清晰的小叶中央性坏死，伴肝细胞细胞学细节丧失。Figure 3、Figure 4 代表不规则的斑片状凝固性坏死区域，伴早期炎性细胞浸润。该坏死无明显的肝小叶模式。Figure 5、Figure 6 代表以肝细胞丧失并被红细胞替代为特征的坏死示例。这是出血性坏死（hemorrhagic necrosis）的一个例子。Figure 7、Figure 8 代表与脂肪变相关的 局灶性（focal） 坏死。坏死斑片（见 Figure 8 ，底部中央）呈强嗜酸性（hypereosinophilic），脂肪变为小叶中央性并明显延伸至小叶中部区域。Figure 9、Figure 10 代表肝细胞坏死伴肝细胞退变、微泡性脂肪变（microvesicular fatty change）、核固缩（nuclear pyknosis）及炎症的诊断。“退变”（degeneration）一词常用于表示可逆的细胞或组织损伤，被认为是坏死的前驱阶段。由于炎症反应广泛存在，为更准确地反映持续进行的病变过程，附加炎症（细胞浸润）的诊断可能是适当的。

## 诊断与分级建议（NTP 共识，中文）
坏死不应根据类型进行细分，单细胞坏死（single-cell necrosis）除外。对于给定的外源化学物，剂量和动物反应的个体差异可影响肝细胞坏死为全小叶性还是小叶中央性，以及为 局灶性（focal） 还是呈广泛不规则斑片状分布。若基本过程相同，病变应简单地记录为坏死并赋予严重程度分级。肝细胞坏死的模式及其他特征应在病理学描述（pathology narrative）中描述。将诊断拆分得过细会导致发生率表格复杂化，并可能妨碍对任何诱导性毒性的恰当解释。当伴随变化如脂肪变或炎症足够广泛时，可能需要单独诊断，并进行严重程度分级及在病理学描述中讨论。由于退变被认为是坏死过程所涉及变化连续体的一部分，当与坏死同时存在时不应单独诊断。然而，无坏死的退变可发生在低于引起坏死的剂量水平的暴露下，因此可能值得单独诊断。在某些情况下，肝细胞坏死可在肝实质内形成海绵状、充满血液的腔隙。这些充满血液的腔隙不应诊断为出血，因为它们是坏死的继发改变。

## 英文原文 · Comment
The extent, pattern, and morphologic features of hepatocellular necrosis depend on the degree of metabolic activation of hepatotoxic xenobiotics, host response to the toxicant, dose and duration of xenobiotic exposure, and timing of liver sample evaluation after dosing. Classical coagulation necrosis is typically caused by ischemia or infarction, and tissue architecture is somewhat maintained because lysosomal enzymes responsible for proteolysis are denatured. Another form of necrosis, liquefaction necrosis, may result in cellular dissolution and loss of cytologic architecture. Changes that may accompany necrosis include hemorrhage, fatty change, cytoplasmic vacuolization, cytologic degeneration, and inflammatory cell infiltration. Figure 1 and Figure 2 represent sharply demarcated centrilobular necrosis with loss of hepatocyte cytologic detail. Figure 3 and Figure 4 represent irregular patchy areas of coagulation necrosis with early infiltration of inflammatory cells. There is no distinctive lobular pattern to this necrosis. Figure 5 and Figure 6 represent an example of necrosis characterized by loss of hepatocytes and replacement with erythrocytes. This is an example of hemorrhagic necrosis. Figure 7 and Figure 8 represent focal necrosis associated with fatty change. The patches of necrosis (see Figure 8 , bottom center) are hypereosinophilic, and the fatty change is centrilobular with extension well into midlobular areas. Figure 9 and Figure 10 represent a diagnosis of hepatocyte necrosis accompanied by hepatocyte degeneration, microvesicular fatty change, nuclear pyknosis, and inflammation. “Degeneration” is a term often used to indicate reversible cell or tissue damage and is considered to be a precursor to necrosis. Because the presence of the inflammatory response is extensive, an additional diagnosis of inflammation (cellular infiltrate) to capture the ongoing process with more fidelity may be appropriate.

## 英文原文 · Recommendation
Necrosis should not be subclassified based on type, with the exception of single-cell necrosis. For a given xenobiotic, dose and animal variability in response can influence whether hepatocellular necrosis is panlobular or centrilobular and whether it is focal or occurs in extensive irregular patches. If the fundamental process is the same, the lesion(s) should be recorded simply as necrosis and assigned a severity grade. The pattern and other features of the hepatocellular necrosis should be described in the pathology narrative. Splitting out diagnoses too finely will result in complicated incidence tables and may compromise appropriate interpretation of any induced toxicity. When accompanying changes such as fatty change or inflammation are sufficiently extensive, separate diagnoses may be warranted with severity grading and discussion in the pathology narrative. Since degeneration is considered part of the continuum of changes involved in the necrotic process, it should not be diagnosed separately when present with necrosis. However, degeneration without necrosis may occur at exposure levels below doses that cause necrosis and thus may warrant a separate diagnosis. In some cases, hepatocellular necrosis can result in cavernous, blood-filled spaces within the hepatic parenchyma. These blood-filled spaces should not be diagnosed as hemorrhage because they are secondary to necrosis.

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