《药理学》课程PPT教学课件（Cardiovascular Sys）23 diuretic

ticAgentsDiuretics are drugs that work on the kidrThey are useful in clinical conditions to re

Diuretic Agents Diuretics are drugs that work on the kidneys to increase urine volume by reducing salt and water reabsorption from the They are useful in clinical conditions to remove edema, hypertension, renal stones hypercalcemia, etc

Abnormalities in fluid volume and electrolytecomposition are common and important clinicalproblems that can become life threatening ifuntreated.Drugsthatblockthetransportfunctionsof therenal tubules areimportantclinical tools in the treatment of these disordersFor the most part, each diuretic agent actsupon a single anatomic segment of the nephron.Because these segments have distinctive transportfunctions,the actions of each diuretic agent can bebest understood in relation to its site of action inthe nephron and the normal physiology of thatsegment

Abnormalities in fluid volume and electrolyte composition are common and important clinical problems that can become life threatening if untreated. Drugs that block the transport functions of the renal tubules are important clinical tools in the treatment of these disorders. For the most part, each diuretic agent acts upon a single anatomic segment of the nephron. Because these segments have distinctive transport functions, the actions of each diuretic agent can be best understood in relation to its site of action in the nephron and the normal physiology of that segment

1NatNatCl-Ca2+Nat H+PTHLGlomerulusCollectingK+DistaltubuleProximalconvolutedCa2+convolutedtubuleLtubuleNatMg?+5=Na+.K+-2CI+aldosteroneCortexOutermedullaNat-K2CI31.AcetazolamideH,02. Osmotic agents+ADHK3. Loop agents6H0H+4. Thiazides25.AldosteroneantagonistsLoop of6.ADH antagonistsHenleTubule transportsystems and sites of action of diuretics

Na+ - K+ - 2CI￾Na+ - K+ -2CI￾Na+ H+ Na+ Na+Cl￾Na+ H2O 1 2 Mg2+ Ca2+ K+ Ca2+ PTH 3 5 4 +aldosterone H2O +ADH H+ K+ Cortex Outer medulla Glomerulus Loop of Henle Proximal convoluted tubule Collecting tubule Distal convoluted 3 tubule 6 2 1. Acetazolamide 2. Osmotic agents 3. Loop agents 4. Thiazides 5. Aldosterone antagonists 6. ADH antagonists Tubule transport systems and sites of action of diuretics

Normal regulation offluidandelectrolytesbythekidneyDespite making up only 1% of total bodyweight,thThe volume of plasma filtered by the kidneys is teriThis means that the filtered fluid is almost entirely reab

Despite making up only 1% of total body weight, the kidneys receive approximately 25% of the cardiac output. The volume of plasma filtered by the kidneys is termed the This means that the filtered fluid is almost entirely reabsorbed. Normal regulation of fluid and electrolytes by the kidney

A.Glomerularfiltration:Approximately 20% of the plasma enteringthe glomerulus isfiltered.Sinceover 99%ofglomerular filtrate is reabsorbedbytubules,drugs that work on the glomerular filtrationshould get less diuretic effects

Approximately 20% of the plasma entering the glomerulus is filtered. Since over 99% of glomerular filtrate is reabsorbed by tubules, drugs that work on the glomerular filtration should get less diuretic effects. A. Glomerular filtration:

B.Tubular function(Reabsorption oftubules and collectivetubes)The tubulars are involved in reabsorptionand secretion.Important components of plasmatend to be reabsorbed more or less completely:99-100%e.g.sodiumandglucose--arereabsorbed.Waste products are only partiallyreabsorbed:e.g.about45%ofisureareabsorbed

The tubulars are involved in reabsorption and secretion. Important components of plasma tend to be reabsorbed more or less completely: e.g. sodium and glucose are 99-100% reabsorbed. Waste products are only partially reabsorbed: e.g. about 45% of urea is reabsorbed. B. Tubular function (Reabsorption of tubules and collective tubes)

I.Renal tubuletransport machanismsProximal tubule1. Sodium bicarbonate, sodium chloride,glucose.amine acids,and other-organicsolute arepreferentially reabsorbed via specific transportsystems in the early proximal tubule.2.Water is reabsorberedpassivelytoSOasofnearly-osmolalitymaintainconstantproximal tubular fluid

I. Renal tubule transport machanisms Proximal tubule 1. Sodium bicarbonate, sodium chloride, glucose, amine acids, and other organic solute are preferentially reabsorbed via specific transport systems in the early proximal tubule. 2. Water is reabsorbered passively so as to maintain nearly constant osmolality of proximal tubular fluid

ProximalconvolutedInterstitiumLumen-urineABtubulebloodNatNatNatNatATPK+K+HCO3-+H+HCO3H+十HCO3H,CO3H,CO3CACA1+1CO, +H,0H,0+CO2The Nat-H+ exchange is related to carbonic anhydraseCarbonic anhydrase catalyzes the reaction of CO,and H,Oleading to H+and HCO3

H2O+CO2 CO2 + H2O H2CO3 H+ + HCO3 - Proximal convoluted tubule Lumen-urine Interstitium￾blood Na+ HCO3 - Na+ CA Na+ H2CO3 HCO3 - + H+ K+ K+ Na+ B A The Na+ -H+ exchange is related to carbonic anhydrase. Carbonic anhydrase catalyzes the reaction of CO2 and H2O leading to H+ and HCO3 - . CA ATP

Loopof henleThe thickascending limb--of-the loop of Henleactively reabsorbesNaCl from thelumen (about35%of thefiltered sodium),but unlikethe proximal tubuleand the thin limb, it is extremely impermeable towater.Salt reabsorption in the thick ascendinglimbtherefore dilutes the tubularfluid,leadingtoitsdesignation as a “diluting segment.Medullaryportionsof thick ascending limbcontribute tomedullary hypertonicity and thereby also play animportantrolein concentration of urine

Loop of henle The thick ascending limb of the loop of Henle actively reabsorbes NaCl from the lumen (about 35% of the filtered sodium), but unlike the proximal tubule and the thin limb, it is extremely impermeable to water. Salt reabsorption in the thick ascending limb therefore dilutes the tubular fluid, leading to its designation as a “diluting segment”. Medullary portions of thick ascending limb contribute to medullary hypertonicity and thereby also play an important role in concentration of urine

ThickascendingInterstitiumLumen-urinelimbbloodCa2+,Mg2+Ca?+,Mg2+Ca?+,Mg2+Potential(+)KK+K+ATPK+NatNatNa+→ Nat2CI2CI→2CI2CIThe NaCl transport system in the luminal membrane ofthe thick ascending limb is aNa+/K+/2Cl-cotransporter

ATP Na+ 2Cl￾Na+ K+ Potential(+) K+ K+ 2Cl￾K+ Na+ 2Cl- 2Cl￾Na+ Ca2+,Mg2+ Ca2+,Mg2+ Lumen-urine Thick ascending limb Interstitium￾blood The NaCl transport system in the luminal membrane of the thick ascending limb is a Na+ /K+ /2Cl- cotransporter. Ca2+,Mg2+