浙江大学医学部 赖蒽茵 浙江大学求是特聘教授，浙江省“千人计划”学者，博导

1. Kidney Physiology 浙江大学医学部 赖蒽茵 浙江大学求是特聘教授，浙江省“千人计划”学者，博导 laienyin@zju.edu.cn Dec 24, 2013, 13:15-14:00 综合楼209，2012级生物医学专业

2. 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

3. Structure of the Kidney

4. 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

5. Types of the Nephron Cortical nephron 皮质肾单位 Juxtamedullary nephron 近髓肾单位

6. Nephron Renal corpuscle -Glomerulus - Bowman’s capsule Renal tubular system Proximal convoluted tubule Loop of Henle - Decending limb - Ascending thin limb - Ascending thick limb Distal convoluted tubule Collecting duct system

7. 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

8. Blood Supply of the Kidney肾脏的血液供应 1200 ml/min, 20 % of the cardiac output Cortex: 94 % Outer medulla: 5-6 % Inner medulla: < 1 %

9. 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 (Tubuloglomerular feedback)

10. 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

11. Tubuloglomerular feedback 管球反馈 Renal blood flow → glomerular 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

12. 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 resistance and ↑ GFR • Prostaglandins and Bradykinin Tend to increase GFR

13. Structure of the Filtration Membrane滤过膜的结构

14. 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 Epithelial cells of the visceral layer of the renal capsule Slit pore 裂孔: 6 ~ 11 nm

15. Net Filtration Pressure (NFP)有效滤过压 NFP = Hydrostatic pressure in the glomerulus – (Colloid osmotic pressure of plasma + Bowman’s capsule pressure)

16. Factors Affecting Filtration影响肾小球滤过的因素 1) Glomerular hydrostatic pressure 2) Colloid osmotic pressure of plasma 3) Bowman’s capsule pressure

17. 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 fraction (FF) 滤过分数 FF = GFR / Renal plasma flow

18. Reabsorption and Secretion by the Renal Tubules 肾小管的重吸收和分泌 Rapid modification of original filtrate

19. 肾髓质渗透梯度示意图 线条越密，表示渗透浓度越高

20. 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

21. 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

22. Formation of Concentrated or Dilute Urine浓缩尿和稀释尿的形成 • In the absence of ADH Collecting duct impermeable to water  excretion of a diluted urine • In the presence of ADH Collecting duct permeable to water  excretion of a concentrated urine

23. Urine Formation 尿液的生成

24. 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 increases in Na+ reabsorption

25. 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

26. 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 requires metabolic energy

27. Mechanisms of tubular transport肾小管物质转运的机制 • Pinocytosis吞饮 • For particles too large to diffuse through the cell membrane E.g.: Reabsorption of filtered proteins in the proximal tubules

28. 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 Passive diffusion also 90-95% of water

29. 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

30. Reabsorption of Water • Isosmotic trasporting mechanism • In the proximal tubule: 65~70 % • In the thin descending limb • ADH-dependent mechanism • In the distal tubule and collecting duct

31. Water channel: aquaporin

32. Reabsorption of Potassium Proximal tubule: 65~70% Loop of Henle: 20%

33. 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

34. 髓袢升支粗段继发性主动重吸收Na+、K+、和Cl-的示意图髓袢升支粗段继发性主动重吸收Na+、K+、和Cl-的示意图

35. 远端小管和集合管重吸收NaCl、分泌K+和H+的示意图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

36. 近端小管重吸HCO3-的细胞机制

37. Reabsorption of Calcium

38. Mechanism for Calcium Reabsorption In the proximal tubule

39. Reabsorption of Glucose Totally in the proximal tubule, mainly the early portions Sodium-dependent glucose transporter

40. Reabsorption of Glucose Tm-G: Tubular transport maximum for glucose Renal threshold for glucose 肾糖阈 Critical value of the plasma glucose concentration when the kidney begins to excrete glucose 160-180 mg/dL

41. Reabsorption of Amino Acids In a similar way as glucose but by different carrier

42. 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

43. 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 the tubular fluid 小管液中溶质的浓度

44. Changes of Concentration of Solutes in the Proximal Tubule Cl- goes up because Na+ is reabsorbed with glucose, amino acids, Pi and HCO3- Unchanged due to isosmotic reabsorption Glucose, amino acids, Pi and HCO3- go down due to reabsorption with Na+

45. 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

46. 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  reducing the osmotic gradientin the medulla

47. Humoral Control of Renal Functions Aldosterone 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+

48. 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

49. 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

50. Humoral Control of Renal Functions Atrial natriuretic peptides (ANP) 心房钠尿肽 Synthesis in the cardiac atrial muscle cell Leading to increased excretion of salt & water Its mechanism: