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| ==Overview== | | ==Overview== |
| Each [[kidney]] is made of approximately one million [[nephrons]]. In the event of an injury to the [[nephrons]], the remaining healthy [[nephron]]s compensate for the decrease in [[GFR]] by hypertrophying and hyperfiltrating. This innate ability of nephrons allows for continued removal of waste products from the body. Over time, this compensation mechanism becomes maladaptive, and the increased filtration pressure in the healthy nephrons leads to distortion of its structural architecture, causing sclerosis and eventual dropout of these nephrons.
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| ==Pathophysiology== | | ==Pathophysiology== |
| *[[Chronic kidney disease]] (CKD) is the progressive loss of renal function caused by a heterogeneous group of diseases but involving a common final pathophysiological process. [[CKD]] results from irreversible loss of glomeruli by glomerulosclerosis, a process consisting mainly of glomerular scarring.
| | The pathophysiologic mechanisms leading to chronic kidney disease stem from the underlying etiologies responsible for the primary renal damage. However; beyond that initial insult, a form of maladaptive systemic and renal response arises that maintains and perpetuates the existing renal disease. Broadly, 2 main mechanisms exist both related in part to the activation of the renin-angiotensin-aldosterone: hyperfiltration, and inflammation with accelerated fibrosis. |
| *Age related [[glomerulosclerosis]] and progressive decrease in renal function are a manifestation of normal aging. In fact, the [[GFR]] normally decreases by 1 ml/min/year after the age of 40. However, accelerated scarring of [[glomeruli]] and their premature irreversible loss occur in pathological contexts where kidneys undergo glomerulosclerosis secondary to insults.
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| *Some insults on the kidneys lead to the initiation of progressive kidney injury that becomes self perpetuating. These initiating factors are commonly related to systemic vascular diseases, like [[diabetes]], [[hypertension]] or [[atherosclerosis]]. Kidneys are well-vascularized organs consisting of millions of [[glomerulus|glomeruli]], which makes the kidney function highly dependent on the systemic vascular status and susceptible to systemic vascular diseases. Other diseases that contribute to CKD include toxin exposure, immune complex deposition and [[autoimmune diseases]].
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| *Regardless of the type of the primary cause, the pathological sequence of events involved in CKD is almost the same. The initiating factor causes decrease in the number of nephrons leading to structural and functional changes in the remaining surviving nephrons to compensate for the nephrons loss. Hence, adaptive mechanisms initially occur to increase the blood flow to the non sclerosed glomeruli and hence maintain a normal [[GFR]]. This is called hyperfiltration and it is mediated by vasoactive mediators, RAAS, cytokines, [[transforming growth factor β]] (TGF-β) as well as by other growth factors.
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| *This adaptive mechanism leads to increase in the pressure in the remaining glomeruli and cause their accelerated sclerosis leading to further loss of the nephrons number. Further adaptation by hyperfiltration overwhelms the remaining normal nephrons that will be at further risk of sclerosis. Hence, chronic kidney disease progresses in a self perpetuating way.
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| *As the number of nephrons decreases more and more, the [[GFR]] further decreases and renal shrinkage occurs. When the [[GFR]] dramatically decreases, symptoms of uremia start and the patient would be having end stage renal disease.<ref> Louis R. The pathophysiology underlying chronic kidney disease. Prim Care Cardiovasc J 2009; Special Issue: Chronic Kidney Disease: 11–13 </ref>
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| [[Image:Pathophysiology_of_CKD.png|Pathophysiology of chronic kidney disease: a self perpetuating process involving irreversible loss of nephrons|center]]
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| ===Pathophysiology of Cardiovascular Complications=== | | |
| *Cardiovascular risk and mortality is connected with the early stages of renal disease and in patients with [[chronic renal failure]], with its highest relative risk mortality in younger patients.
| | ===Hyperfiltration=== |
| *This high risk for cardiovascular mortality results from hemodynamic and pressure overload, causing [[left ventricular hypertrophy]] and [[cardiomyopathy]]. Accelerated [[atherosclerosis]] and [[arteriosclerosis]] also contribute to the cardiovascular mortality risk.
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| *Damage to and narrowing from [[atherosclerosis]] of the large vessels are major contributing factors for the high incidence of [[congestive cardiac failure]], [[ischemic heart disease]], [[left ventricular hypertrophy]], [[cerebrovascular accidents]], [[peripheral artery disease]] and [[sudden death]].<ref name="pmid12641870">{{cite journal |author=London GM |title=Cardiovascular disease in chronic renal failure: pathophysiologic aspects |journal=Semin Dial |volume=16 |issue=2 |pages=85–94 |year=2003 |pmid=12641870 |doi= |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0894-0959&date=2003&volume=16&issue=2&spage=85}}</ref>
| | ===Inflammation and Accelerated Fibrosis=== |
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| ==References== | | ==References== |
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. However; beyond that initial insult, a form of maladaptive systemic and renal response arises that maintains and perpetuates the existing renal disease. Broadly, 2 main mechanisms exist both related in part to the activation of the renin-angiotensin-aldosterone: hyperfiltration, and inflammation with accelerated fibrosis.
Hyperfiltration
Inflammation and Accelerated Fibrosis
References
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