Chronic renal failure pathophysiology: Difference between revisions
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===Hyperfiltration=== | ===Hyperfiltration=== | ||
The landmark works of Brenner et al were the first to propose the maladaptive changes that occur after renal injury. The team showed that after significant loss of nephron mass, major alterations in glomerular hemodynamics occur. The changes lead to glomerular hypertension with an increase in single nephron glomerular filtration rate termed hyperfiltration. Hyperfiltration is a direct result of the increase in glomerular plasma flow and hydrostatic pressure in response to a decrease in preglomerular arteriolar resistance more than the decrease in postglomerular resistance with a net vasocontrictive effect on the efferent arteriole. | |||
The observed alterations occur due to the activation of the RAAS system. Initially, the juxtaglomerular apparatus increases the release of renin in response to the decreased perfusion pressure and solute delivery to the macula densa. Renin converts angiotensinogen to angiotensin I which is then converted to angiotensin II is then produced by angiotensin converting enzyme (ACE). Angiotensin II has been shown to be the main perpetrator in the maladaptation of the kidney to significant damage. | |||
[[Image:Hyperfiltration.jpg|650px]] | |||
Most animal models exploring glomerular hypertension and hyperfiltration show progressive glomerular sclerosis and eventual proteinuria that usually occurs at a linear rate compared to the extent of nephron loss. Furthermore, studies examining the prevention or reduction of glomerular hypertension and single nephron GFR have almost invariably shown a reduction in the rate of progression of renal disease. Among the proposed interventions include dietary protein restriction, ACE inhibitors, and angiotensin receptor blockers (ARBs). | |||
===Inflammation=== | ===Inflammation=== | ||
Revision as of 22:14, 26 October 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Overview
Pathophysiology
The pathophysiologic mechanisms leading to chronic kidney disease stem from the underlying etiologies responsible for the primary renal damage. The initial insult is responsible for a decrease in the number of functional nephrons. However; beyond that initial insult, a form of maladaptive systemic and renal response arises that maintains and perpetuates the existing renal disease. With the activation of the renin-angiotensin-aldosterone system, a combination of mechanisms herald a progressive loss of nephrons. Broadly, 3 main mechanisms exist related in part to the activation of the RAAS: hyperfiltration, inflammation, and accelerated fibrosis.
Hyperfiltration
The landmark works of Brenner et al were the first to propose the maladaptive changes that occur after renal injury. The team showed that after significant loss of nephron mass, major alterations in glomerular hemodynamics occur. The changes lead to glomerular hypertension with an increase in single nephron glomerular filtration rate termed hyperfiltration. Hyperfiltration is a direct result of the increase in glomerular plasma flow and hydrostatic pressure in response to a decrease in preglomerular arteriolar resistance more than the decrease in postglomerular resistance with a net vasocontrictive effect on the efferent arteriole.
The observed alterations occur due to the activation of the RAAS system. Initially, the juxtaglomerular apparatus increases the release of renin in response to the decreased perfusion pressure and solute delivery to the macula densa. Renin converts angiotensinogen to angiotensin I which is then converted to angiotensin II is then produced by angiotensin converting enzyme (ACE). Angiotensin II has been shown to be the main perpetrator in the maladaptation of the kidney to significant damage.
Most animal models exploring glomerular hypertension and hyperfiltration show progressive glomerular sclerosis and eventual proteinuria that usually occurs at a linear rate compared to the extent of nephron loss. Furthermore, studies examining the prevention or reduction of glomerular hypertension and single nephron GFR have almost invariably shown a reduction in the rate of progression of renal disease. Among the proposed interventions include dietary protein restriction, ACE inhibitors, and angiotensin receptor blockers (ARBs).