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1、第三节 肾脏泌尿功能的调节 Regulation of urine formation of the kidney,中山大学基础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 humonal 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
2、, ADH,合成部位：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 th
3、e axons of 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
4、 circumstances 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 cons
5、triction of vasa 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 。,ADH combines with the receptor in basolateral membrane and activated the adenylate cyclase,it produces cyclic adenosine monophosphate,which leads to activa
6、tion 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 secretion) 血浆晶体渗透压的改变 (the change of crystal osmotic pr
7、essure) 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 that the osmotic concentration of the ex
8、tracellular 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,initiating appropriate nerve signals in th
9、e 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 increases because of excess transfuse, the vo
10、lume 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 reaborption of water decreases and the urine
11、 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 that decreases ADH secretion.ADH secretion
12、 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 sodium reabsorption and potassium secreti
13、on 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 the sodium-potassium ATPase pump on the baso
14、lateral 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 促进mRNA的合成 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 readily to the interior of the tubulaar epit
15、helial 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 p
16、rocess of sodium and potassium transport.,（心房利尿肽ANP）28个氨基酸残基 集合管对Na+重吸 收(-)，使出入球 小动脉舒张 心钠素（Cardionatrin）(-) aldosterone 释放 ADH 肾素分泌 作用：促进肾脏排钠排水 The function of cardionatrin is to promote the secretion of sodium and water by kidney .the cardionatrin can reduce the release of aldosterone、ADH and renin
17、.,（二）醛固酮分泌的调节：肾素血管紧张素醛固酮系统、血K+、血Na+浓度 促肾上腺皮质激素（ACTH）对醛固酮分泌的日常调节不起重要作用 Potassium ion concentration and the renin- angiotensin system are by far the most potent in regulating aldosterone secretion.,1. 肾素血管紧张素醛固酮系统 （renin-angiotensin-aldosterone system, RAAS） RAA系统的 活性取决于血 浆中肾素浓 度，故凡能影 响肾素分泌的 因素均可间 接影响
18、醛固 酮的分泌。,肝硬化 继发性醛固酮增多症 水肿、腹水 组织液 循环血量 肾素 醛固酮 cirrhosis of liver secondary aldosteronism Edema、Hydroperitonia tissue fluid blood volume renin aldosterone,2.血K+和血Na+浓度 血K+ Na+ 直接刺激肾上腺皮质球状带 醛固酮分泌 保Na+排K+ 血K+ Na+ 醛固酮分泌 保Na+排K+功能减弱 醛固酮的分泌对K+浓度改变较敏感，K+仅增加0.51.0 mmol/L 醛固酮 （敏感度K+ Na+） Increased potassium i
19、on concentration in the extracellular fluid greatly increases aldosterone secretion.a small percentage increase in potassium concentration can cause a severalfold increase in aldosterone secretion.,三、甲状旁腺激素(parathyroid hormone,PTH) 的作用,分泌部位：甲状旁腺 作用：1.促进远球小管和集合管对Ca2+的重吸收，减少尿Ca2+排出 量； 2.抑制近球小管对磷酸盐的重吸收
20、，增加尿中磷酸盐的排出量； 3.抑制近球小管对Na+、K+、HCO3-和氨基酸的重吸收。 PTH is secrected by parathyroid glands.PTH provides a powerful mechanism for controlling extracellular calcium and phosphate concentrations by regulating intestinal reabsorption,renal excretion,and exchange between the extracellular fluid and bone of thes
21、e ions.PTH decreases calcium excretion and increases phosphate excretion by the kidneys.moreover,it increases the rate of reabsorption of magnesium ions and hydrogen ions while it decreases the reabsorption of sodium,potassium,and amino acid ions.,第四节 血浆清除率plasma clearance,肾功能测量方法(use of clearance m
22、ethods to quantify kidney function)： 1.尿浓缩和稀释试验(Urine concentration test and Urine dilution test )反映肾小管功能 2.酚红排泄试验(excretion test of phenolsulfonphthalein)反映肾小管功能 3.血浆清除率试验(plasma clearance test)反映肾小球滤过率、肾血流量,尿浓缩试验主要测定肾小管对水重吸收功能 正常浓缩功能 尿比重可达1.030 Urine concentration test mainly quantifies the reabso
23、rption to water of renal tubule. 尿稀释试验测定多水情况下尿液变淡程度 正常成人短时间内饮水11.5L，尿比重可1.003 Urine dilution test mainly quantifies the dilution degree of urine . 酚红排泄试验反映肾小管的分泌排泄功能 0. 6%酚红1ml静脉注射15分钟 排泄出注入量25%以上 2小时 排泄出注入量60%以上 病理：15分钟 12% 2小时 40%,血浆清除率的概念和意义 概念：血浆清除率（plasma clearance. C）指肾脏在单位时间内（通常用每分钟）能将多少毫升血浆中
24、所含的某物质完全清除出去，这个被完全清除了的某物质的血浆毫升数，这叫该物质的血浆清除率（ml /min），它反映肾脏对不同物质的清除能力。 UV U：尿中某物质的浓度 C = V：每分钟尿量 P P：血浆中某物质的浓度 意义：用血浆清除率可衡量肾脏生理活动情况。 The plasma clearance of a substance is the volume of plasma that is completely cleared of the substance by the kidneys per unit time.this provides a useful way of quant
25、itating the effectiveness with which the kidneys excrete various substances.,1.肾小球滤过率的测定：菊粉清除率、内生肌酐清除率 菊粉inulin滤过后，既不被重吸收也不被分泌，故测定菊粉的血浆清除率可代表肾小球滤过率。 UV 1ml /min125mg /100ml C菊粉= = =125ml /min P 1mg /100ml Inulin clearance can bu used to estimate GFR.inulin is freely filtered and is not reabsorbed or
26、 secreted by the renal tubules,the rate at which that inulin is excreted in the urine(U*V) is equal to the filtration rate of the substance by the kidneys(GFR*p),the GFR,therefore,can be calculated as the clearance of the inulin.,2.肾血流量的测定(estimation of renal plasma flow) 碘锐特diodrast、对氨基马尿酸（PAH）静脉注射
27、后，经肾循环一周后可完全清除掉（通过滤过和分泌）。 即在肾动脉中该物质有一定浓度，流到肾静脉中其浓度接近0，那么该物质每分钟的尿中排出量（UV），应等于每分钟通过肾脏的血浆中所含的量，该物质血浆清除率为每分钟通过肾脏的血浆量。 Theorectically,if a substance is completely cleared from the lasma,the clearance rate of that substance is equal to the total renal plasma flow,in other words,the amount of the substance
28、 delivered to the kidneys in the blood would be equal to the amount excreted in the urine.Thus,renal plasma flow could be calculated as RPF=U*V/p.,UV = XP X：每分钟通过肾脏的血流量 UV X = = C P 此时，可测定C来代表每分钟肾血浆流量，再估计出肾血流量。 注意此时C = 肾血浆流量肾血流量 血浆量： 肾血浆流量 全血的55%，肾血流量= 100 55,3.对肾小管功能的推测 一种物质C 125ml/min 提示肾小管必定有分泌排泄
29、 If plasma clearance of a substance is more than 125ml/min,it must be secreted by the renal tubule.,第五节 尿的排放(micturition),一、输尿管(ureter)的运动 输尿管连接肾盂(pelvis)处平滑肌细胞有自律性(autorhythmicity)，兴奋下传产生蠕动波3次/min，其推进速度23cm/s。 肾盂中尿量越多，内压越大，自动节律性 频率越高，蠕动增强，反之亦然。尿因输 尿管蠕动，一阵阵被推入膀胱(bladder)。,二、膀胱和尿道的神经支配,盆N pelvic nerv
30、es 传入传出 副交感N S24 三对N 腹下N Hypogastric nerves 传入传出 交感N L15 阴部N pudendal nerve 传入传出 躯体N S24受 意识控制,三、排尿反射(micturition reflex),膀胱内压当尿量400ml才明显提高 当尿量达到700ml时，内压为35cmH2O，逼尿肌(detrusor muscles)产 生节律收缩，排尿欲增高。 内压达到70 cmH2O时 产生痛感，不得不排尿 Intravesical pressure evidently increases when the urine volume is more than
31、 400 millilitre.,排尿反射micturition reflex： 脑干、皮层高位中枢 膀胱尿量 膀胱壁牵 骶髓排尿反射 盆N 膀胱逼尿肌收缩 400500ml 张感受器 初级中枢 内括约肌松弛 尿液入后尿道 排尿 When urine volume in bladder is more than 400500 millilitre,it leads to a stretch reflex initiated by sensory stretch receptors in the bladder wall,especially by the receptors in the po
32、sterior urethra when this area begins to fill with urine at the higher bladder pressures.sensory signal from the bladder stretch receptors are pelvic nerves and the reflexively back again to the bladder through the parasympathetic nerve fibers by way of these same nerves,so the detrusor muscles contracts and the intersphincter relaxes.,腰骶部脊髓损伤injury of Lumbosacral spinal cord 麻醉anesthesia 肿瘤tumor 尿潴留retention of 大结石big Calculus urine 脊髓受损(初级中枢与高级中枢失去功能联系) 尿失禁 Urinary incontinence 高位中枢对初级中枢控制能力弱 夜间遗尿enuresis during nighttime,