Hypertensive nephropathy pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
 
(24 intermediate revisions by 5 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Hypertensive nephropathy}}
{{Hypertensive nephropathy}}
{{CMG}} {{AE}} {{AN}}
{{CMG}} {{AE}} {{AN}} {{NN}}


==Overview==
==Pathophysiology==
The [[kidney]]s may be damaged by or cause hypertension. Evidence from studies on renal transplant recipients and familial studies suggests a genetic component in occurrence of hypertensive nephropathy and nephrosclerosis.
*Hypertension can involve any compartment of the kidney <ref name="SecciaCaroccia2017">{{cite journal|last1=Seccia|first1=Teresa M.|last2=Caroccia|first2=Brasilina|last3=Calò|first3=Lorenzo A.|title=Hypertensive nephropathy. Moving from classic to emerging pathogenetic mechanisms|journal=Journal of Hypertension|volume=35|issue=2|year=2017|pages=205–212|issn=0263-6352|doi=10.1097/HJH.0000000000001170}}</ref> :
**'''Vessels'''
*** Intimal thickening of small arterioles due to migration of myofibroblasts from media into intimal layer and secretion of collagen which leads to narrowing of the afferent arterioles.
*** thining of media layer and [[hyalinosis]] of the afferent arteriole due to loss of smooth muscle cells, which have been changed into myofibroblasts, leads to a reduction in glomerular filtration rate ([[GFR]]).
**'''Glomerules'''
***Constriction of intraglomerular capillaries due to [[hyalinosis]] causes glomerular ischemia and reduced filtration which enhances the accumulation of Extracellular Matrix ([[ECM]]) in the periglomerular region resulting focal segmental glomerulosclerosis ([[FSGS]]) or Global glomerulosclerosis.
***Hypertrophy of the remaining healthy glomerules maintains filtration but increases intra-glomerular pressure and developing microalbuminuria.
***Podocyte loss due to hyperfiltration and glomerulosclerosis leads to destroying the filtration barrier and developing proteinuria.
**'''Tubulointerestitium'''
***Dilatation, flattening and loss of epithelial tubular cells
****Overexpression of fibrogenic and angiogenic factors such as transforming growth factor b1 ([[TGF-b1]]), Endothelin 1 (ET-1), and vascular endothelial growth factor ([[VEGF]]) results in disruption of tubular cells junction, transition of epithelial into mesenchymal cells, production of metalloproteinases, cell migration, production of [[collagen]] by myofibroblasts in the interstitial and subsequent tubulointerstitial fibrosis.
***Activation of [[Renin]] - [[Angiotensin]] - [[Aldosterone]] system further contributes to vasoconstriction, cell proliferation, reactive oxygen species production,inducing inflammation and ECM production.
****Angiotensin II induces differentiation of fibroblasts into myofibroblasts, which synthesize collagen in the periglomerular and peritubular regions.
 
 
 
{| class="wikitable"
! colspan=4 style="background: #4479BA; color: #FFFFFF; " align="center"|Changes of kidney compartments induced by Hypertension
|-
!style="background: #4479BA; color: #FFFFFF; " align="center" |Compartment
!style="background: #4479BA; color: #FFFFFF; " align="center" |Changes
!style="background: #4479BA; color: #FFFFFF; " align="center" |Final effects
|-
|style="background: #DCDCDC; |'''Vessels'''
|Myofibroblasts migration from media into intimal layer
Collagen secretion by myofibroblasts 
 
Smooth muscle cells loss in the media layer
 
|Intimal thickening of small arterioles
Arteriolar narrowing
 
Thining of media layer
 
Arteriolar hyalinosis
|-
|style="background: #DCDCDC; |'''Glomerules'''
|Intraglomerular capillaries constriction
Glomerular ischemia
 
Reduced GFR
 
Remained glomerules hypertrophy
 
Podocyte loss
 
|ECM accumulation
Glomerulosclerosis, FSGS
 
Increased Intraglomerular pressure
 
Microalbuminuria
 
 
 
|-
|style="background: #DCDCDC; |'''Tubulointerestitium'''
|Transition of epithelial into mesenchymal cells
Dilatation and loss of epithelial tubular cells
 
Collagen secretion by myofibroblasts
 
RAAS activation
|Tubulointerstitial fibrosis
 
 
Vasoconstriction
 
Inflammation induction
 
ECM accumulation
|-
 
|}
 
 
 
 
 
==Chronic hypoxia hypothesis==
*Chronic [[hypoxia]] hypothesis by Fine et al. in 1998 revealed that hypertension-associated-changes in postglomerular peritubular capillaries cause decrease in blood flow and tubulointerstitial [[hypoxia]], which induce inflammation and epithelial to mesenchymal differentiation. Proximal tubular epithelial cells that are more sensitive to oxygen deficiency than distal cells, are converted into myofibroblasts which produce collagens and inhibit degradation of ECM leading to tubulointerstitial fibrosis. <ref name="pmid9551436">{{cite journal| author=Fine LG, Orphanides C, Norman JT| title=Progressive renal disease: the chronic hypoxia hypothesis. | journal=Kidney Int Suppl | year= 1998 | volume= 65 | issue=  | pages= S74-8 | pmid=9551436 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9551436  }} </ref><ref name="pmid18633339">{{cite journal| author=Fine LG, Norman JT| title=Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. | journal=Kidney Int | year= 2008 | volume= 74 | issue= 7 | pages= 867-72 | pmid=18633339 | doi=10.1038/ki.2008.350 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18633339  }} </ref>
*[[hypoxia]] also causes up-regulation of fibrogenic and angiogenic factors, which play a major role in fibrosis formation.
 
 
 
 
==Benign versus Malignant Nephrosclerosis==
*Kidney injury from benign and malignant hypertension results in benign and malignant [[nephrosclerosis]], respectively.
 
===Gross Pathology===
*Benign Nephrosclerosis:
** The size of the [[kidney]]s is reduced or shrunken with loss of [[Renal cortex|cortical mass]] and fine granularity.
*Malignant nephrosclerosis:
** [[Hemorrhage]]s from surface capillaries gives the kidney a "flea-bitten" appearance.
 
===Microscopic Pathology===
*Benign nephrosclerosis:
** [[Afferent arteriole]]s have eosinophilic [[fibrin]] deposits in the wall, causing [[Arteriosclerosis|hyaline arteriosclerosis]]
*Malignant nephrosclerosis:
** [[Fibrinoid necrosis]] in [[afferent arteriole]]
** [[Arteriosclerosis|Hyperplastic arteriosclerosis]] in inter-lobar arterioles
** [[Sclerosis]] in glomeruli and renal tubules
 
 
 
 
 
[[File:Fibrous_intimal_thickening_in_hypertensive_nephropathy.jpg|300px|center]]                                                                       
'''Figure 1'''. Fibrous intimal thickening in hypertensive nephropathy                          
 
 
 
 
[[File:Histopathology_of_hypertensive_glomerular_lesion_of_hypertensive_nephropathy.jpg|400px|center]]
'''Figure 2'''. Global glomerular collapse and filling of Bowman’s space with a lightly staining collagenous material
 
 
==References==
{{reflist|2}}


==Pathophysiology==
{{WH}}
*Two pathophysiological mechanisms have been postulated for development of nephrosclerosis and [[chronic kidney disease]] in patients with [[hypertension]].
{{WS}}
*One mechanism suggests that glomerular [[ischemia]] results from [[Afferent arteriole|afferent arteriolar]] constriction, with a consequent reduction in [[glomerular filtration rate]].
 
*Another theory postulates that systemic [[hypertension]] causes injury to the nephrons. As a result, the remaining healthy nephrons undergo hyperfiltration and increase in intra-glomerular pressure from [[vasodilatation]] of afferent renal arterioles. This results in progressive glomerulosclerosis.
[[Category:Disease]]
*In patients with primary [[hypertension]], intra-glomerular hemodynamic studies show a reduction in renal blood flow.
[[Category:Emergency medicine]]
*The reduction in glomerular pressure from afferent arteriolar constriction was thought to reduce ongoing damage to the nephrons. But, with time, [[sclerosis]] or scarring of afferent vessels slowly progresses, thereby further reducing the renal blood flow.
[[Category:Kidney diseases]]
*The [[GFR]] is maintained from constriction of [[Efferent arterioles|efferent renal arterioles]] and [[systemic hypertension]]. Eventually, glomerular and tubular [[ischemia]] progresses and causes sclerosis.
[[Category:Cardiology]]
*This suggests that hypertension accelerates the arteriolar changes and injury to the [[nephrons]].
[[Category:Nephrology]]

Latest revision as of 22:32, 18 June 2020

Hypertensive nephropathy Microchapters

Home

Patient Information

Overview

Classification

Pathophysiology

Differentiating Hypertensive Nephropathy from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Abdominal X Ray

CT

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Hypertensive nephropathy pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Hypertensive nephropathy pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Hypertensive nephropathy pathophysiology

CDC on Hypertensive nephropathy pathophysiology

Hypertensive nephropathy pathophysiology in the news

Blogs on Hypertensive nephropathy pathophysiology

Directions to Hospitals Treating Hypertensive nephropathy

Risk calculators and risk factors for Hypertensive nephropathy pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2] Nasrin Nikravangolsefid, MD-MPH [3]

Pathophysiology

  • Hypertension can involve any compartment of the kidney [1] :
    • Vessels
      • Intimal thickening of small arterioles due to migration of myofibroblasts from media into intimal layer and secretion of collagen which leads to narrowing of the afferent arterioles.
      • thining of media layer and hyalinosis of the afferent arteriole due to loss of smooth muscle cells, which have been changed into myofibroblasts, leads to a reduction in glomerular filtration rate (GFR).
    • Glomerules
      • Constriction of intraglomerular capillaries due to hyalinosis causes glomerular ischemia and reduced filtration which enhances the accumulation of Extracellular Matrix (ECM) in the periglomerular region resulting focal segmental glomerulosclerosis (FSGS) or Global glomerulosclerosis.
      • Hypertrophy of the remaining healthy glomerules maintains filtration but increases intra-glomerular pressure and developing microalbuminuria.
      • Podocyte loss due to hyperfiltration and glomerulosclerosis leads to destroying the filtration barrier and developing proteinuria.
    • Tubulointerestitium
      • Dilatation, flattening and loss of epithelial tubular cells
        • Overexpression of fibrogenic and angiogenic factors such as transforming growth factor b1 (TGF-b1), Endothelin 1 (ET-1), and vascular endothelial growth factor (VEGF) results in disruption of tubular cells junction, transition of epithelial into mesenchymal cells, production of metalloproteinases, cell migration, production of collagen by myofibroblasts in the interstitial and subsequent tubulointerstitial fibrosis.
      • Activation of Renin - Angiotensin - Aldosterone system further contributes to vasoconstriction, cell proliferation, reactive oxygen species production,inducing inflammation and ECM production.
        • Angiotensin II induces differentiation of fibroblasts into myofibroblasts, which synthesize collagen in the periglomerular and peritubular regions.


Changes of kidney compartments induced by Hypertension
Compartment Changes Final effects
Vessels Myofibroblasts migration from media into intimal layer

Collagen secretion by myofibroblasts

Smooth muscle cells loss in the media layer

Intimal thickening of small arterioles

Arteriolar narrowing

Thining of media layer

Arteriolar hyalinosis

Glomerules Intraglomerular capillaries constriction

Glomerular ischemia

Reduced GFR

Remained glomerules hypertrophy

Podocyte loss

ECM accumulation

Glomerulosclerosis, FSGS

Increased Intraglomerular pressure

Microalbuminuria


Tubulointerestitium Transition of epithelial into mesenchymal cells

Dilatation and loss of epithelial tubular cells

Collagen secretion by myofibroblasts

RAAS activation

Tubulointerstitial fibrosis


Vasoconstriction

Inflammation induction

ECM accumulation



Chronic hypoxia hypothesis

  • Chronic hypoxia hypothesis by Fine et al. in 1998 revealed that hypertension-associated-changes in postglomerular peritubular capillaries cause decrease in blood flow and tubulointerstitial hypoxia, which induce inflammation and epithelial to mesenchymal differentiation. Proximal tubular epithelial cells that are more sensitive to oxygen deficiency than distal cells, are converted into myofibroblasts which produce collagens and inhibit degradation of ECM leading to tubulointerstitial fibrosis. [2][3]
  • hypoxia also causes up-regulation of fibrogenic and angiogenic factors, which play a major role in fibrosis formation.



Benign versus Malignant Nephrosclerosis

  • Kidney injury from benign and malignant hypertension results in benign and malignant nephrosclerosis, respectively.

Gross Pathology

  • Benign Nephrosclerosis:
  • Malignant nephrosclerosis:
    • Hemorrhages from surface capillaries gives the kidney a "flea-bitten" appearance.

Microscopic Pathology



Figure 1. Fibrous intimal thickening in hypertensive nephropathy



Figure 2. Global glomerular collapse and filling of Bowman’s space with a lightly staining collagenous material


References

  1. ↑ Seccia, Teresa M.; Caroccia, Brasilina; Calò, Lorenzo A. (2017). "Hypertensive nephropathy. Moving from classic to emerging pathogenetic mechanisms". Journal of Hypertension. 35 (2): 205–212. doi:10.1097/HJH.0000000000001170. ISSN 0263-6352.
  2. ↑ Fine LG, Orphanides C, Norman JT (1998). "Progressive renal disease: the chronic hypoxia hypothesis". Kidney Int Suppl. 65: S74–8. PMID 9551436.
  3. ↑ Fine LG, Norman JT (2008). "Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics". Kidney Int. 74 (7): 867–72. doi:10.1038/ki.2008.350. PMID 18633339.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Hypertensive_nephropathy_pathophysiology&oldid=1614809"