《基础医学各论2》资料：10泌尿系统生理学

1、Kidney Physiology,Overview Functions of the Kidney,Regulation of body fluid osmolality Production of hormones: Erythropoietin, Kinins and Renin, Prostaglandins，1,25-dihydroxycholecalciferol Regulation of electrolyte and water Excretion of waste products Regulation of acid and base,Structure of the K

2、idney,8-1 肾单位和肾血管的示意图,处于肾皮质不同部位的肾单位和肾血管的结构显著不同,Nephron,Renal corpuscle - Glomerulus - Bowmans capsule Renal tubular system Proximal convoluted tubule Loop of Henle - Decending limb - Ascending thin limb - Ascending thick limb Distal convoluted tubule Collecting duct system,Types of the Nephron,Corti

3、cal nephron 皮质肾单位 Juxtamedullary nephron 近髓肾单位,Differences between the Nephrons,8-2 肾小球、肾小囊微穿刺和球旁器示意图,Juxtaglomerular Apparatus 近球小体,Juxtaglomerular cells 近球细胞 Renin-producing granular cells Macula densa 致密斑 Extraglomerular mesangial cells (Mesangial cell) 间质细胞,Blood Supply of the Kidney 肾脏的血液供应,120

4、0 ml/min, 20 % of the cardiac output Cortex: 94 % Outer medulla: 5-6 % Inner medulla: 1 %,8-3 滤过膜示意图,Tunule micropunctre in mice,Stop Flow Pressure Technique,Autoregulation of Renal Blood Flow肾脏血液供应的自身调节,Range of regulation BP: 80 170 mmHg Mechanisms Myogenic mechanism Flow dependent mechanism (Tubu

5、loglomerular feedback),8-4 不同的分子有效半径和带不同电荷右旋糖酐的滤过能力,滤过能力的值为1.0，表示能自由滤过；0 则不能滤过,Myogenic mechanism 肌源学说,Arterial blood pressure contraction of the vascular smooth muscle constriction of the blood vessel the blood flow relatively constant,8-5 有效滤过压示意图,Tubuloglomerular feedback 管球反馈,Renal blood flow gl

6、omerular filtration Na+ content in the renal filtrate detection by the macula densa a signal sent to the renal arterial system restoration of the renal blood flow and glomerular filtration rate to normal,Neural Regulation of Renal Blood Flow肾脏血流的神经调节,Activation of the renal sympathetic nerves constr

7、iction of the renal arterioles renal blood flow and glomerular filtration rate (GFR) ,Humoral Regulation of Renal Blood Flow肾脏血流的体液调节,Norepinephrine, Epinephrine, and Endothelin To Constrict renal blood vessel and GFR Angiotensin II To Constrict efferent arterioles Nitric Oxide renal vascular resist

8、ance and GFR Prostaglandins and Bradykinin Tend to increase GFR,Urine Formation 尿液的生成,Glomerular Filtration 肾小球的滤过作用,Glomerular filtration rate (GFR) 肾小球滤过率 The quantity of the glomerular ultrafiltrate formed each minute in all nephrons of the both kidneys Normal value: 125 ml / min Filtration fract

9、ion (FF) 滤过分数 FF = GFR / Renal plasma flow,Composition in the Filtration Fluid滤过液的成分,Structure of the Filtration Membrane滤过膜的结构,Permeability of the Filtration Membrane滤过膜的通透性,Capillary endothelium Fenestrae 窗孔: 70 90 nm Basement membrane Meshwork of collagen & proteoglycan fibrillae: 2 8 nm Epitheli

10、al cells of the visceral layer of the renal capsule Slit pore 裂孔: 6 11 nm,Electrostatic Barrier of the Filtration Membrane 滤过膜的电学屏障作用,Negatively charged glycoproteins (糖蛋白) in the endothelial cells & basement membrane,Net Filtration Pressure (NFP)有效滤过压,NFP = Hydrostatic pressure in the glomerulus (C

11、olloid osmotic pressure of plasma + Bowmans capsule pressure),Glomerular Capillary Filtration Coefficient (Kf) 滤过系数,Definition The product of the hydraulic conductivity and surface area of the glomerular capillaries Kf = GFR / Net filtration pressure,Factors Affecting Filtration影响肾小球滤过的因素,1) Glomeru

12、lar hydrostatic pressure 2) Colloid osmotic pressure of plasma 3) Bowmans capsule pressure,Factors Affecting Filtration影响肾小球滤过的因素,4) Renal plasma flow 5) Filtration area 6) Permeability of the filtration membrane,Reabsorption and Secretion by the Renal Tubules 肾小管的重吸收和分泌,Rapid modification of origin

13、al filtrate,Mechanisms of tubular transport肾小管物质转运的机制,Passive transport 被动转运 Simple diffusion Osmosis 渗透 Facilitated diffusion 易化扩散 Uniport 单一转运 Solvent drag 溶剂拖曳,Mechanisms of tubular transport肾小管物质转运的机制,Active transport 主动转运 Primary active transport Against an electrochemical gradient Directly req

14、uires metabolic energy,Mechanisms of tubular transport肾小管物质转运的机制,Secondary active transport Two or more substances interact with one specific carrier in the cell membrane and are translocated across the membrane Types Co-transport 同向转运 Counter-transport 逆向转运,Characteristics of Secondary Active Trans

15、port,Carrier occupied by both substances (or unoccupied) to be mobile in the membrane Saturable (has a Vmax) To be specificity and affinity of carrier for substance transported “Uphill” transport occurs without direct input of metabolic energy,Mechanisms of tubular transport肾小管物质转运的机制,Pinocytosis 吞饮

16、 For particles too large to diffuse through the cell membrane E.g.: Reabsorption of filtered proteins in the proximal tubules,Pathway of Reabsorption 重吸收的途径,Paracellular transport Passive diffusion only 5-10% of water Some ions & large non-polar solutes Transcellular pathway All active transport Pas

17、sive diffusion also 90-95% of water,Reabsorption of Na+ & Cl,In the proximal tubule Na+: 65 70% Co-transport: Na+ glucose Na+amino acids Counter-transport: Na+ H+ Cl: 55% passively,Changes of Concentration of Solutes in the Proximal Tubule,Cl- goes up because Na+ is reabsorbed with glucose, amino ac

18、ids, Pi and HCO3-,Glucose, amino acids, Pi and HCO3- go down due to reabsorption with Na+,Unchanged due to isosmotic reabsorption,Reabsorption of Na+ & Cl,In the Loop of Henle: 20% Na+-Cl-K+ symportor in the thick ascending limb,Reabsorption of Na+ & Cl,In the distal tubule and collecting tubule Co-

19、transport: Na+ Cl Principal cell: Na+ K+ ATPase pump,Reabsorption of Water,Isosmotic trasporting mechanism In the proximal tubule: 6570 % In the thin descending limb ADH-dependent mechanism In the distal tubule and collecting duct,Water channel: aquaporin,Isosmotic Trasporting Mechanism,Reabsorption

20、 of HCO3-,99% reabsorbed Proximal tubule: 80 90% Key element: exchange of H+ for Na+,Reabsorption of Potassium,Proximal tubule: 6570% Loop of Henle: 20%,Renal Clearance 肾血浆清除率,Defined as the volume of plasma required to supply the amount of a substance X to be excreted in urine per unit time,Inulin

21、(菊糖) clearance as a measure of glomerular filtration,Use of Clearance Methods to Quantify Kidney Function,Use of Clearance Methods to Quantify Kidney Function,Clearance of para-aminohippuric acid (对氨基马尿酸) as a measure of renal plasma flow Para-aminohippuric acid (PAH) freely through the glomerulus A

22、lmost all the remaining PAH in the plasma is secreted into the tubule,Use of Clearance Methods to Quantify Kidney Function,Renal clearance as a calculation of tubular reabsorption or secretion By comparison of inulin clearance with clearances of different solutes,8-6 肾小球毛细血管血压，胶体渗透压和囊内压对肾小球滤过率的影响,8-

23、7 近端小管重吸收NaCl的示意图,近端小管的前半段 X 代表葡萄糖、氨基酸、磷酸盐和Cl-等 B. 近端小管的后半段的细胞旁途径转运,8-8 髓袢升支粗段继发性主动重吸收Na+、K+、和Cl-的示意图,8-9 远端小管和集合管重吸收NaCl、分泌K+和H+的示意图,A.远曲小管初段 B.远曲小管后段和集合管,8-10 近端小管重吸HCO3-的细胞机制,8-11 肾小管各段小管液渗透压和流量的变化,图中数字系两肾全部肾小管与集合管各段每分钟的小管液流量,8-12 肾髓质渗透梯度示意图,线条越密，表示渗透浓度越高,8-13 逆流倍增作用模型,甲管内液体向下流，乙管内液体向上流 ，丙管内液体向下流

24、。M1膜能将液体中 Na+由乙管泵入甲管，且对水不易通透， M2膜对水易通透,8-14 尿浓缩机制示意图,粗箭头表示升支粗段主动重吸收Na+和Cl-。髓袢升支粗段和远曲小管前段对水不通透。 Xs表示未被重吸收的溶质,8-15 血管升压素的作用机制示意图,Reabsorption of Calcium,Mechanism for Calcium Reabsorption,In the proximal tubule,Mechanism for Calcium Reabsorption,In the thick ascending limb,Mechanism for Calcium Reabso

25、rption,In the distal tubule,Reabsorption of Glucose,Totally in the proximal tubule, mainly the early portions Sodium-dependent glucose transporter,Reabsorption of Glucose,Tm-G: Tubular transport maximum for glucose Renal threshold for glucose 肾糖阈 Critical value of the plasma glucose concentration wh

26、en the kidney begins to excrete glucose 160-180 mg/dL,Reabsorption of Amino Acids,In a similar way as glucose but by different carrier,Tubular Secretion of Hydrogen,In the proximal tubule Counter-transport: Na+H+ In the distal tubule & collecting duct: Na+H+ exchange Intercalated cell: H+-ATPase,Tub

27、ular Secretion of Ammonia (NH3),Tubular Secretion of Potassium,In the distal tubule tubule and collecting duct Principal cell 主细胞 Dependent on reabsroption of sodium, under the control of aldosterone In competition with secretion of H+,Tubular Secretion of Other Substances,Para-aminohippuric acid (P

28、AH) Some foreign substances, such as penicillin and phenol red,Factors that affect tubular transport影响物质转运的因素,Osmotic diuresis 渗透性利尿: Increase in solute concentration of the tubular fluid decreases the reabsorption of water, and thus increases the amount of the urine,1) The solute concentration in t

29、he tubular fluid 小管液中溶质的浓度,Factors that affect tubular transport 影响物质转运的因素,2) GFR Glomerulo-tubular balance 球-管平衡: The ratio of reabsorption rate and GFR is relatively constant Related to hydrostatic pressure and oncotic osmotic pressure Due to increased filtered glucose and amino acids, leading to

30、increases in Na+ reabsorption,General Question,What are the change of urine and its mechanism when one is injected intravenously 50% glucose 100 milliliter?,Urinary Concentrating Mechanism尿液浓缩的机制,The Countercurrent Theory Countercurrent Multiplication 逆流倍增,A,C,B,The Countercurrent Theory,Countercurr

31、ent Exchange 逆流交换,8-16 一次饮一升清水（实线）和饮一升等渗盐水（0.9%NaCI溶液）（虚线）后的排尿率（箭头表示饮水时间）,8-11 肾小管各段小管液渗透压和流量的变化,图中数字系两肾全部肾小管与集合管各段每分钟的小管液流量,8-12 肾髓质渗透梯度示意图,线条越密，表示渗透浓度越高,Permeability of the Tubular System,Countercurrent Multiplier in the Kidney肾脏中的逆流倍增器,Loop of Henle,Establishing of Osmotic Gradient of the Renal M

32、edulla 肾髓质渗透梯度的建立,Maintenance of the Osmotic Gradient in the Medulla 髓质渗透梯度的维持,The vasa recta (直小血管): Countercurrent Exchanger,Formation of Concentrated or Dilute Urine浓缩尿和稀释尿的形成,In the presence of ADH Collecting duct permeable to water excretion of a concentrated urine,In the absence of ADH Collect

33、ing duct impermeable to water excretion of a diluted urine,Factors that affect the concentration and dilution of the urine 影响尿液浓缩和稀释的因素,1) Damage of renal medulla Resulting in an impairment of the concentrating ability 2) Loop diuretics such as frusemide, inhibiting the Na+/ K+/ 2Cl- cotransport sys

34、tem in the thick ascending limb,Factors that affect the concentration and dilution of the urine,3) Lack of urea (尿素) in the body such as malnutrition, reducing the osmotic gradient established in the renal medulla 4) Increased velocity of blood flow in the vasa recta carrying away amount of NaCl red

35、ucing the osmotic gradient in the medulla,Humoral Control of Renal Functions,Antidiuretic hormone (ADH) 抗利尿激素 Synthesis in supraoptic and paraventricular nuclei Release from the posterior pituitary,Mechanism of ADH Antidiuresis抗利尿激素作用的机制,Increasing water permeability of collecting duct Insertion of

36、aquaporins in apical membrane,Diabetes Insipidus 尿崩症,Regulation of ADH Release,Plasma osmolality Plasma osmolality hypothalamic osmoreceptors production and release of ADH Blood volume Blood volume baroreceptor reflex & atrial stretch receptors ADH release ,Humoral Control of Renal Functions,Aldoste

37、rone 醛固酮 Secreted by the glomerulosa of the adrenal cortex To increase the reabsorption of Na+ in the distal tubule and early collecting duct, coupled to secretion of K+,Mechanism of Aldosterone Action醛固酮作用的机制,To increase number of Na+ channels To increase number & activity of Na+ pumps,Renin-Angiotensin System,Regulation of Aldosterone Secretion醛固酮分泌的调节,1. Renin-Angiotensin System 肾素-血管紧张素系统,Regulation of Aldosterone Secretion,2. Plasma concentrations of sodium and potassium K+ Aldosterone Secretion Na+ Aldosterone Secretion 3. Adrenocorticotrophin (ACTH) Necessary for Aldosterone Secretio