【高血压精品英文课件】hypertension and the kidney

Hypertension and the Kidney Chong Myung Kang, M.D. Department of Internal Medicine Hanyang University Hospital Hypertension and the Kidney A. The Role of the Kidney in Hypertension B. Hypertension as a Cause of Renal Disease C. Hypertension as a Risk Factor for the Progression of Renal Disease D. Hypertension as a Consequence of Renal Disease Role of Kidney in Hypertension 1. Pressure-Volume Regulation 2. Congenital Oligonephropathy 3. Renal Transplantation Studies 4. Salt and Hypertension Pressure-natriuresis(1) lEffect of elevated B.P. to raise Na excretion (Feedback system to stabilize B.P. resetting of pressure-natriuresis at higher blood pressure Fig. 1. Predicted long-term effects of a hypertensive stimulus, caused by increased total peripheral resistance, with no change in the renal pressure natriuresis mechanism. Blood pressure is initially elevated(from point A to point B), but hypertension cannot be sustained because sodium excretion exceed intake, thereby reducing extracellular fluid volume until blood pressure return to normal and intake and output of sodium are balanced Fig. 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. 3. Proposed mechanism of pressure natriuresis Pressure-natriuresis(2) (Medullary Blood Flow) lMedullary blood flow(MBF) comprise only 1% of RBF, but important effect on pressure-natriuresis lEndocrine sympathetic N stimulation, CO inhibition, kinin antagonist, NO synthase inhibition, Ang II, AVP- raise BP lIncrease MBF; ANP, prostaglandin, bradykinin, acetylcholine, CEI, Ca blocker-lowering BP Pressure-natriuresis(3) Abnormal pressure-natriuresis in essential hypertension 1. Increased preglomerular resistance widespread vasoconstriction of preglomerular vessels(arteriosclerosis, vasoconstrictors) relieved with Ca blockers 2. Increased tubular reabsorption excessive mineralocorticoid, Ang II (Salt-sensitive; depend on salt intake) Pressure-natriuresis(4) 3. Decreased glomerular capillary filtration coefficient(Kf) Essential HP with subtle dysfunction in glomerular capillary membrane, glomerulonephritis 4. Reduced number of functioning nephrons Hyperfiltratiohglomerulosclerosis Fig. 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. Congenital Oligonephropathy lLow birth weight baby-higher incidence of hypertension in maturity lFewer nephrons, smaller kidney to body size (Japanese, African-American; adapted to less salt 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 IDDM Renal Transplantation Studies lHypertension can travel with kidney lF1 hybrids(F1H) from WKY After bilateral nephrectomy, CEI treated SHR decreased capacity to excrete dietary Na lThus, intrinsic renal mechanism play a major role in manifestation of primary hypertension Fig. 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. 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. Salt and Hypertension(1) lAberrant response of tubuloglomerular feedback (TGF) to salt load is responsible for essential HP lAfferent 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 intakedec. afferent arteriolar resistance aberrant TGF to salt loadvery low salt intake; no HP(Yanomamo, Xingu, Papua New Guinea, KenyaNo hypertension) lHuman body system ; adapted to salt depletion of terrestrial environment ; excessive salt intake in civilizationessential hypertension lSlow genetic change vs rapid environmental change Hypertension as a Cause of Renal Disease(1) lMechanism of HP induced renal damage 1. Glomerular ischemia more effective than Ca antagonist in antiproteinuric reduce preglomeru