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 Dec 24, 2013, 13:15-14:00 综合楼 209 ， 2012 级生物医学专业 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 Kidney

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

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

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

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 1200 ml/min, 20 % of the cardiac output Cortex: 94 % Outer medulla: 5-6 % Inner medulla: < 1 %

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)

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

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

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

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

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

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

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

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

肾髓质渗透梯度示意图 线条越密，表示渗透浓度越高

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

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

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 Collecting duct impermeable to water  excretion of a diluted urine

Urine Formation 尿液的生成

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

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 requires metabolic energy

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

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

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

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

Water channel: aquaporin

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

近端小管重吸收 NaCl 的示意图 A. 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

髓袢升支粗段继发性主动重吸收 Na + 、 K + 、和 Cl - 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

近端小管重吸 HCO 3 - 的细胞机制

Reabsorption of Calcium

Mechanism for Calcium Reabsorption In the proximal tubule

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

Reabsorption of Glucose  T m-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 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

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

Changes of Concentration of Solutes in the Proximal Tubule Cl - goes up because Na + is reabsorbed with glucose, amino acids, P i and HCO 3 - Glucose, amino acids, P i and HCO 3 - go down due to reabsorption with Na + Unchanged due to isosmotic reabsorption

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

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 gradient in the medulla

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 +

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

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

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:

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 aquaporins in apical membrane

Diabetes Insipidus 尿崩症

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）

General Question What are the change of urine and its mechanism when one is injected intravenously 50% glucose 100 milliliter?