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1、第三节 肾脏泌尿功能的调节 Regulation of urine formation of the kidney,中山医学院生理学教研室 王庭槐,尿生成的调节 regulation of urine formation,肾血流量的调节 神经体液调节regulation of renal blood flow nervous and humoral control(对滤过的调节) (对重吸收和分泌)自身 神经 体液调节 调节 调节 ADH 醛固酮 甲状旁腺素Aldosterone parathyroid hormone,一、抗利尿激素 antidiuretic hormone, ADH,合成部
2、位:视上核(supraoptic nucleus)、室旁核(paraventricular nucleus)合成ADH 运输: 丘脑垂体束 贮存释放:神经垂体(贮存于膨大神经末梢中)前激素 ADH 九肽蛋白水解酶 靶器官:远曲小管 集合管The hypothalamus contains two types of neurons that synthesize ADH in the supraoptic nucleus and paraventricular nucleus.once ADH is synthesized,it is transported down the axons of
3、the neurons to their tips,terminating in the posterior pituitary gland.,作用:1.提高远曲小管和集合管上皮细胞对水的通透性,促进水的重吸收尿液浓缩、尿量减少(抗利尿)主要作用。The most important renal action of ADH is to increase the water permeability of the distal tubule,collecting tubule.This effect helps the body to conserve water in circumstance
4、s such as dehydration.2.增加内髓部集合管对尿素的通透性并减少肾髓质的血流量。ADH increases the urea permeability of collecting tubule in inner zone and decreases the blood flow in medulla.3.促进髓绊升支粗段对NaCl的重吸收,使直小血管收缩。ADH increases the reabsorption of NaCl in thick segment of ascending limb and so leads to constriction of vasa
5、recta.,(一)作用机理: ADH与远曲小管、集合管上皮细胞管周膜上受体结合 激活膜内的腺苷酸环化酶 上皮细胞中cAMP 管腔膜 中蛋白激酶激活 膜蛋白磷酸化 膜构型改变 水通 道开放管腔膜对水通透性 。 ADH ,水通道小泡内移, 对水通透性 。,当抗利尿激素缺乏时,管腔膜上的水 通道可在细胞膜的衣被凹陷处集中,后者形成吞饮小泡进入胞浆,称为内移(internalization)。,ADH combines with the receptor in basolateral membrane and activated the adenylate cyclase,it produces c
6、yclic adenosine monophosphate,which leads to activation of protein kinase in basolateral membrane,then the membrane protein is phosphorylated,so the configuration of membrane changes,this process increases the permeability to water by the open of water channel.,(二)ADH分泌的调节(the regulation of ADH secr
7、etion)血浆晶体渗透压的改变 (the change of crystal osmotic pressure)有效刺激因素(effective stimuli)循环血量的改变(the change of effective blood volume),1、血浆晶体渗透压的改变 特点:敏感,晶体渗透压改变 12%时即有反应。电解质有效 尿素无效 感受器:位于视上核及其附近区域。大量出汗、腹泻、失水 血浆晶体渗透压 视上核 及其周围区域渗透压感受器(+) 神经垂体 膨大神经 末梢去极化 释放ADH 远曲小管、集合管对水通 透性 对水重吸收 ,尿液浓缩 尿量减少。 The precise way
8、 that the osmotic concentration of the extracellular fluids controls ADH secretion is not clear.Yet somewhere in or near the hypothalamus are modified neuron receptors called osmoreceptors.when the extracellular fluid becomes too concentrated,fluid is pulled by osmosis out of the osmoreceptor cell,i
9、nitiating appropriate nerve signals in the hypothalamus to cause additional ADH secretion.,水利尿water diuresis 大量饮清水 尿量 饮1000ml清水,隔30分钟 尿量 (1小时末达高峰,23小时恢复) 饮1000ml NS,隔30分钟 变化不大,2、循环血量的改变(容量感受器途径) 过度输液,血量过多(+) 左心房内膜下容量感受器(+)迷走N,传入冲动中枢,间接抑制下丘脑垂体后叶系统 释放ADH 远曲小管集合管对水通透性 对水重 吸收 尿量 。 When blood volume incr
10、eases because of excess transfuse, the volume receptor in endometrium of left atrium sends impulse through Vagus nerve to center and inhibit the release of ADH by Hypothalami- Pituitary posterior lobe system,so the water permeability in distal tubule and collecting tubule decreases,therefore the rea
11、borption of water decreases and the urine volume increases.,3、其它因素 AP (+) 颈动脉窦压力感受器 窦N ADH反射性释放 尿量 痛刺激、情绪紧张 ADH 尿量 弱冷刺激 ADH 尿量 下丘脑病变累及视上核、室旁核 ADH合成释放障碍 尿崩症(diabetes insipidus)。 When arterial pressure increases, pressorecepto in carotid sinus sends signals to hypothalamic nuclei through sinus nerve t
12、hat decreases ADH secretion.ADH secretion can also be controlled by other stimuli such as pain and nervous mood.,二、醛固酮的作用(Aldosterone),分泌部位:肾上腺皮质球状带 靶器官:远曲小管、集合管 作用:促进对Na+的主动重吸收,同时促进K+的排出保Na+排K+作用。 Aldosterone, secreted by the zona glomerulose cells of the adrenal cortex,is an important regulator of
13、 sodium reabsorption and potassium secretion by the renal tubules.The primary site of aldosterone action is on the principal cells of the cortical collecting tubule.the mechanism by which aldosterone increase sodium reabsorption while at the same time increasing potassium secretion is stimulating th
14、e sodium-potassium ATPase pump on the basolateral side of the cortical collecting tubule membrane.,(一)作用机制: 醛固酮进入远曲小管集合管的上皮细胞后 与胞浆受体结合 形成激素胞浆受体复合物 通过核膜 与核中受体结合 激素核受体复合物 调节mRNA转录,合成多种醛固酮促进小管上皮细胞Na+ 泵运转 诱导蛋白 促进生化氧化提供ATP 促进加强Na+增加管腔膜对Na+ 通透性 的主动重吸收(保Na+) 造成小管腔内负电位 K+被分泌到 小管液(排K+) Aldosterone diffuses r
15、eadily to the interior of the tubulaar epithelial cells and combines with a highly specific cytoplasmic receptor protein,then the aldosterone-receptor complex diffuses into the nucleus where it may undergo further alterations,finally inducing one or more specific portions of the DNA to form one or more types of messenger RNA related to the process of sodium and potassium transport.,