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

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

[email protected] 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

MechanismsMyogenic 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 tubuleNa+: 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 HCO3- 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

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

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, Pi and HCO3

-

Glucose, amino acids, Pi and HCO3

- 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?