【高血压英文课件】Hypertension-and-the-Kidney

Hypertension and the Kidney Chong Myung Kang,M.D.Department of Internal Medicine Hanyang University HospitalHypertension and the Kidney 1Hypertension and the KidneyA.The Role of the Kidney in HypertensionB.Hypertension as a Cause of Renal Disease C.Hypertension as a Risk Factor for the Progression of Renal DiseaseD.Hypertension as a Consequence of Renal Disease Hypertension and the KidneyA.2Role of Kidney in Hypertension1.Pressure-Volume Regulation2.Congenital Oligonephropathy3.Renal Transplantation Studies4.Salt and HypertensionRole of Kidney in Hypertension3【高血压英文课件】Hypertension-and-the-Kidney4【高血压英文课件】Hypertension-and-the-Kidney5Fig.2.Predicted Long-term effects of a peripheral vasoconstrictor that has a relatively week effect on pressure natriuresis.The normal curve(Solid line)is compared with the vasoconstrictor curve(dash line).Initially,the vasoconstrictor would cause natriuresis,because increased peripheral vascular resistance elevates arterial pressure(from point A to point B)above the set-point for balance between intake and output of sodium due to increased.However,increased arterial pressure would cause a transient natriuresis and a reduction in extracellular fluid volume until arterial pressure eventually stabilized at a level(point C)at witch sodium intake and output are balanced.Fig.2.Predicted Long-term ef6Fig.3.Proposed mechanism of pressure natriuresisFig.3.Proposed mechanism of 7Pressure-natriuresis(2)(Medullary Blood Flow)lMedullary blood flow(MBF)comprise only 1%of RBF,but important effect on pressure-natriuresislEndocrine¶crine factors(renal nerve,Ang II prostaglandin,ANP,NO,kinin,vasopressin modulate RPP&urine excretion by regulation of medullary blood flow lReduce MBF;sympathetic N stimulation,CO inhibition,kinin antagonist,NO synthase inhibition,Ang II,AVP-raise BPlIncrease MBF;ANP,prostaglandin,bradykinin,acetylcholine,CEI,Ca blocker-lowering BPPressure-natriuresis(2)(Medul8Pressure-natriuresis(3)Abnormal pressure-natriuresis in essential hypertension1.Increased preglomerular resistance widespread vasoconstriction of preglomerular vessels(arteriosclerosis,vasoconstrictors)-relieved with Ca blockers2.Increased tubular reabsorption excessive mineralocorticoid,Ang II (Salt-sensitive;depend on salt intake)Pressure-natriuresis(3)Abnorma9Pressure-natriuresis(4)3.Decreased glomerular capillary filtration coefficient(Kf)Essential HP with subtle dysfunction in glomerular capillary membrane,glomerulonephritis4.Reduced number of functioning nephrons Hyperfiltratioh-glomerulosclerosisPressure-natriuresis(4)3.Decr10Fig.4.Steady-state relationships between arterial pressure and urinary sodium ecreation and sodium intake for normal kidney and four types of renal dysfunction that cause hypertension:decreased kidney mass,increased reabsorption in distal and collecting tubules,reduction in glomerular capillary filtration coefficient(Kf),and increased preglomerular resistance.Fig.4.Steady-state relations11Congenital OligonephropathylLow birth weight baby-higher incidence of hypertension in maturitylFewer nephrons,smaller kidney to body size (Japanese,African-American;adapted to less salt&water in tropical area-HP in salt replete state)lNephron number;genetic,conditions in utero (300,000-1,000,0000;low socioeconomic state,rat experiment,SHR)lLow birth weight,short stature;higher incidence of NIDDM,nephropathy in IDDMCongenital OligonephropathyLow12Renal Transplantation StudieslHypertension can travel with kidneylF1 hybrids(F1H)from WKY&SHR;After bilateral nephrectomy,CEI treated SHR&WKY kidney transplanted to F1H Recipient of SHR-HP,recipient of WKY-normal No difference between 2 group in BUN,RBF,GFRlGenetic predisposition for HP in donors is required to elicit post-transplantation HPlSHR;decreased capacity to excrete dietary NalThus,intrinsic renal mechanism play a major role in manifestation of primary hypertensionRenal Transplantation StudiesH13Fig.5.Effects of renal cross-transplantations on systolic blood pressure in five different animal medels of genetic hypertension.A.Normotensive recipients received a kidney from hypertensive donors.B.Hypertensive recipients received a kidney from normotensive donors.Symbols are:()Dahl salt-senstive hypertensive rats;()Milan hypetensive rats and Milan normotensive rats;()Prague hypertensive rats and Prague normotensive rats;Normotensive Wistar Kyoto rats(donors),spontaneously hypertensive rats and F1 hybrids(recipients)bred from the first two strains;()normotensive Wistar-Kyoto rats(donors),stroke-prone spontaneously hypertensive rats(donors)and F1 hybrids(recipients)bred from the first two strain.Fig.5.Effects of renal cross14Fig.6.Blood pressure in human renal graft recipients at one year after transplantation.Based on indirect evidence,donors were assumed to have been normotensive()or hypertensive().The differences in blood pressure between recipients of a kidney from normotensive and hypertensive donor occurred despite more vigorous antihypertensive treatment in the latter.Fig.6.Blood pressure in huma15Salt and Hypertension(1)lAberrant response of tubuloglomerular feedback (TGF)to salt load is responsible for essential HPlAfferent arteriole contract or relax in response to inc.or dec.in macula densa Cl-delivery(autoregulation of RBF)lFine tuning of SNGFR through TGF Low salt intake-dec.afferent arteriolar resistance&TGF -maintain GPF&Ang II inc.RE-maintain PGC-SNGFRlInability of kidney to excrete salt load is responsible for development of hypertensionSalt and Hypertension(1)Aberra16Fig.7.Autoregulation of renal plasma flow and glomerular filtration rate.Note afferent arteriolar resistance(RA)is regulated by boyh myogenic response and tubuloglomerular feedback and angiotensin II(AngII)can selectively act on efferent resistance(RE)allowing the maintenance of SNGFR in the face of reduced renal perfusion pressure.Fig.7.Autoregulation of rena17【高血压英文课件】Hypertension-and-the-Kidney18Salt and Hypertension(2)lHP;aberrant TGF to salt load-very low salt intake;no HP(Yanomamo,Xingu,Papua New Guinea,Kenya-No hypertension)lHuman body system;adapted to salt depletion of terrestrial environment;excessive salt intake in civilization-essential hypertensionlSlow genetic change vs rapid environmental changeSalt and Hypertension(2)HP;a19Hypertension as a Cause of Renal Disease(1)lMechanism of HP induced renal damage 1.Glomerular ischemia&hypoperfusion 2.Glomerular capillary HP&hyperperfusion -inc.SNGFR-transglomerular passage of protein-inc.influx of protein¯omolecule into mesangium-proliferation&inc.matrix -GlomerulosclerosisHypertension as a Cause of Re20Hypertension as a Cause of Renal Disease(2)lIncreased protein traffic into urinary space-increased protein reabsorption by proximal tubule-tubulointerstitial damage (NH3 production-C3 activate-trigger inflammatory response in interstitium,stimulate cell growth,hypertrophy,reactive O2 specieslProgression of renal disease correlate best with interstitial damagelLeakage of plasma component across GBM-activate MAC-GEC damage-disrupt normal GBM turnover-GBM damageHypertension as a Cause of Re21Fig.9.Mechanism whereby immune damage to the GBM results in the leakage of complement components to the epithelial side of the membrane.This may facilitate the assembly of the membrane attack complex on the epithelial cell and disrupt the normal GBM turnover.Fig.9.Mechanism whereby immu22Hypertension as a Cause of Renal Disease(3)l“Hypertensive nephrosclerosis”Myointimal hyperplasia,hyaline arteriosclerosis in small arteries&arterioles-progression to ESRD(30%of ESRD in U.S.A.)lHistory of HP at least 5 years,initially normal renal function&urinalysis,proteinuria 1g/daylPrimary renal parenchymal disease;abnormal urinalysis prior to onset of hypertensionlNo hypertensive nephrosclerosis in patients with BP controlled reduce intraglomerular pressure;more effective than Ca antagonist in antiproteinuric&preventing progression of renal diseaselCa antagonist;reduce preglomerular arterial resitance;inc.urinary albumin excretionHypertension as a Risk Factor 24Fig.10.Possible hemodynamic mechanism of renal protection by calcium antagonists and ACE inhibitors.Fig.10.Possible hemodynamic 25Hypertension as a Risk Factor for Progression of Renal Disease(2)lJoint National Committee for Detection,Evaluation,and Treatment for High Blood Pressure;target blood pressure 130/85 mm Hg for patients with renal disease(not 140/90)lMDRD study;target BP depend on proteinuria Proteinuria 0.25 to 1.0 g/D;130/80(mean 98)1.0 g/D;125/75(mean 92)Hypertension as a Risk Factor 26Hypertension and the Kidney“Kidney is a causative organ for hypertension and target organ of hypertensive damage”Hypertension and the Kidney“K27