上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）Diuretics Excretion of Water and Electrolytes

图 上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Capillary Diuretics Filtraion Reabsorption Lymph Flow Lymphatic Excretion of Water and Electrolytes G AI JIAO TONG UNIVE

Diuretics Excretion of Water and Electrolytes

上浒充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Introduction 漏 。Diuretics agents that increase the renal excretion of sodium and water classification based on site of action knowledge of the normal renal physiology is important

• Diuretics – agents that increase the renal excretion of sodium and water – classification based on site of action – knowledge of the normal renal physiology is important Introduction

上浒充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Background Primary effect of diuretics is to increase solute excretion,mainly as NaCl Certain disease states may cause blood volume to increase outside of narrowly defined limits Hypertension Congestive heart failure Liver cirrhosis Nephrotic syndrome Renal failure AO TONG Dietary Na restriction often not enough to prevent edema diuretics needed

Background  Primary effect of diuretics is to increase solute excretion, mainly as NaCl  Certain disease states may cause blood volume to increase outside of narrowly defined limits  Hypertension  Congestive heart failure  Liver cirrhosis  Nephrotic syndrome  Renal failure  Dietary Na restriction often not enough to prevent edema  diuretics needed

上浒充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Review of Kidney Structure bowman's Glomerular Filtration capsule glomerulus Tubular Reabsorption collecting duct blood capillaries Tubular Secretion

Review of Kidney Structure Glomerular Filtration Tubular Reabsorption Tubular Secretion

上游充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Background to Mechanisms of Action of Diuretics Movement from tubular fluid through renal epithelial cells and into peritubular capillaries accomplished by three transport mechanisms after cell interior is polarized by Na+/K+pump 1. Channels formed by membrane proteins Allows only sodium to pass through 2. Cotransport Carrier mediated Simultaneously transports both Na+and other solute(Cl-,glucose,etc) from tubular lumen into renal epithelial cell 3. Countertransport Carrier mediated Transports Na in,another solute(H+)out of renal epithelial cell Water moves transcellularly in permeable segments or via tight junctions between renal epithelial cells

Background to Mechanisms of Action of Diuretics Movement from tubular fluid through renal epithelial cells and into peritubular capillaries accomplished by three transport mechanisms after cell interior is polarized by Na+/K+ pump 1. Channels  formed by membrane proteins  Allows only sodium to pass through 2. Cotransport  Carrier mediated  Simultaneously transports both Na+ and other solute (Cl-, glucose, etc) from tubular lumen into renal epithelial cell 3. Countertransport  Carrier mediated  Transports Na in, another solute (H+) out of renal epithelial cell  Water moves transcellularly in permeable segments or via tight junctions between renal epithelial cells

上浒充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Electrolyte Transport Mechanisms Tubular fluid Nat/spump caillary Channel 6 A Na+ Cotransport ⑧ Na ② 3 Na [Na'] Countertrapsport Na+ © Na Lateral intercellular space H2O Tight junction X=glucose,amino acids,phosphate, etc. Net Na +H2O Transport Apical cell Basolateral membrane cell membrane Elsevier 2005.Minneman Wecker:Brody's Human Pharmacology 4e www.studentconsult.com

Electrolyte Transport Mechanisms Channel Cotransport Countertransport Na+/K+ pump X = glucose, amino acids, phosphate, etc

上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Summary of sites of renal reabsorption of filtrate Water filtered at 125 ml/min 8 100 80 70% 60 A 40 20 15% 14% 1% Proximal Loop of Distal and I Excreted Henle collect.duct Sodium filtered at 17.5 mEq/min 100 80 70% 60 B 40 25% 20 4.5% 0.5% Proximal Loop of Distal and Excreted Henle collect.duct O Elsevier 2005.Minneman Wecker:Brody's Human Pharmacology 4e www.studentconsult.com

Summary of sites of renal reabsorption of filtrate

上游充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Diuretic Agents ■Loop diuretics Thiazide and thiazide-like diuretics Potassium-sparing diuretics Carbonic anhydrase inhibitors Osmotic diuretics JIAO TONG UNIVEKS

Diuretic Agents  Loop diuretics  Thiazide and thiazide-like diuretics  Potassium-sparing diuretics  Carbonic anhydrase inhibitors  Osmotic diuretics

7 上游充通大辛 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 eypes and Names of Diuretics Example Sites of Action Osmotic agents Mannitol Proximal tubule Descending loop Collecting duct Carbonic Acetazolamide Proximal tubule anydrase inhib Thiazides Hydrochlorothiaz Distal convoluted ide tubule Loop diuretic Ethacrynic acid Loop of Henle Furosemide K+sparing Spironolactone Collecting tubule Amiloride

Types and Names of Diuretics Osmotic agents Mannitol Proximal tubule Descending loop Collecting duct Carbonic anydrase inhib. Acetazolamide Proximal tubule Thiazides Hydrochlorothiaz ide Distal convoluted tubule Loop diuretic Ethacrynic acid Furosemide Loop of Henle Type Example Sites of Action K+ - sparing Spironolactone Amiloride Collecting tubule

上浒充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Nephron sites of action of diuretics Afferent Distal convoluted arteriole tubule Glomerulus Proximal convoluted tubule Cortical Efferent collecting arteriole tubule Thick ascending Proximal limb straight tubule Medullary collecting tubule Site of diuretic action Carbonic anhydrase inhibitors ☑ Osmotic diuretics Thin descending Loop diuretics limb Thin ascending Thiazide diuretics limb K'-sparing diuretics Elsevier 2005.Minneman Wecker:Brody's Human Pharmacology 4e www.studentconsult.com

Nephron sites of action of diuretics