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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. [email protected] Dec 24, 2013, 13:15-14:00 综合楼 20 9 , 2012 级生物医学专业. Overview – Functions of the Kidney. Regulation of body fluid osmolality Production of hormones : - PowerPoint PPT Presentation
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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
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
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
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
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
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
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
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