第三节 良性高血压病
良性高血压病(benign hypertesion,BH),又称良性(相)原发性高血压病(benign phase of essential hypertesion)和慢性高血压病(chronic hypertesion)。本病在人群中有极高的发生率,是一种十分常见的疾病。但在肾活检病例中却并不多见,据我组7 908例肾活检病例的统计,仅为45例,占肾活检病例总数的0.6%。
BH多发生于成年人,尤以40岁以上者为多见,男性多于女性。起病时可无症状,或仅有头晕表现,常在体格检查后发现高血压而求医。病程后期,其症状或体征主要与心力衰竭、冠状动脉狭窄和脑血液循环障碍有关,也可并发眼底动脉硬化和视网膜病变等。累及肾脏时,尿检正常或仅为轻度蛋白尿,如出现显著蛋白尿者则不考虑是原发性高血压病,而常是继发性高血压(系统性疾病或肾小球病)所致。肾功能多为正常,但随着疾病的进展,可因肾血流灌注不足而致肾小球滤过率和肾小管分泌能力降低。患者血浆肾素水平正常或降低,低肾素水平性高血压随年龄增大而增多,60岁以上者所发生的低肾素水平的高血压均是良性高血压病。
【病因和发病机制】
BH真正的病因和发病机制尚未完全阐明,然而大量的研究表明,它是一类由多因素,包括遗传、环境和神经内分泌因素等共同起作用所引起的疾病。遗传因素的作用不仅表现在患者有家族倾向和实验动物的自发性模型,而且近年研究还发现与其发病的相关基因(如肾素-血管紧张素基因、Na+- K+- ATP酶基因等);环境因素中较为确定者有钠盐摄入、工作压力、精神刺激等;在神经内分泌因素中,较为肯定的有肾上腺皮髓质激素、肾球旁器颗粒细胞分泌的肾素等。这些因素的共同作用,可引起体内钠水潴留和外周缩血管物质的大量释放,从而引起血压升高。随着疾病的进展,外周血管随之可发生形态结构的改变,尤其是平滑肌细胞的增生和肥大,内膜增厚,管腔狭窄,可致肾缺血,从而进一步刺激球旁器颗粒细胞分泌肾素,再经过肾素-血管紧张素系统的作用,使血压升高呈慢性和持久性。
【病理改变】
BH肾组织的主要病理改变发生于细小动脉。入球微动脉壁可明显增厚、透明变性,呈均质状嗜伊红性,PAS染色阳性,提示细动脉已发生硬化(图4-29);而小叶间动脉的内膜呈纤维性增厚(图4-30),伴有弹力纤维增生,可呈多层排列,而其管壁中层结构大致正常。肾小球常因肾血流灌注不足而呈缺血状,有数量不等的肾小球呈皱缩状,伴有血管襻的塌陷、管腔闭塞和基膜增厚,最终可致呈灶性分布的肾小球萎缩和硬化,并演变成含有大量胶原积聚的透明变肾小球。硬化肾小球周围的肾小管萎缩、基膜增厚,伴有肾小管蛋白管型,间质灶性纤维化伴有少量单个核细胞浸润。
▲图4-29 良性高血压病(PAS ×200)
肾组织内细动脉壁增厚,呈PAS染色阳性
▲图4-30 良性高血压病(HE ×200)
肾细小动脉壁内膜纤维性增厚,其管腔狭窄或闭塞
免疫荧光检查显示呈现透明变性的细小动脉壁内含有C3、IgM成分,有时它们也可沉积于肾小球系膜区。
电镜检查显示透明变性的细动脉壁,尤其是内膜下可有呈均匀、微细颗粒状、中等密度的电子致密物沉积(图4-31),可伴有细小脂滴和膜性小泡形成,而小动脉壁常显示内膜增厚,由增生的平滑肌细胞、肌内膜细胞(myointimal cells)、纤细胶原纤维和复层弹力纤维组成。
▲图4-31 良性高血压病(EM ×2 250)
细动脉内膜不规则增厚,管腔明显狭窄伴管壁内呈均质状电子致密物沉积
【鉴别诊断】
须与BH鉴别的肾病,包括老年性肾病变、糖尿病肾病等。前者多见于老年人,有时两者可难以区别;后者累及的细动脉,也常包括BH较少累及的出球动脉在内,且其临床表现、肾小球内形成结节状病灶等均与BH明显不同。
【预后】
BH的预后主要取决于心脑血管病的严重性,其中心力衰竭和脑出血是其常见的死亡原因。目前,各种有效的降压药物的应用,已明显降低了它的病死率,并延长了人类的平均寿命。
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