Chronic hypertension pathophysiology: Difference between revisions

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__NOTOC__
__NOTOC__
{{Template:Hypertension}}
{{Chronic hypertension}}
{{CMG}}; '''Assistant Editor-In-Chief:'''[[User:YazanDaaboul|Yazan Daaboul]], [[User:Sergekorjian|Serge Korjian]], [[User:Rim Halaby|Rim Halaby]]
{{CMG}}; '''Assistant Editor-In-Chief:'''[[User:YazanDaaboul|Yazan Daaboul]], [[User:Sergekorjian|Serge Korjian]]
==Overview==
==Overview==
Although the pathophysiology of secondary [[hypertension]] is known, there is still much debate about the true pathogenesis of primary (essential) hypertension. It is now conceded that hypertension is caused by multiple [[genetic]] and environmental factors with varying roles between individuals.<ref name="pmid16512265">{{cite journal| author=Cuddy ML| title=Treatment of hypertension: guidelines from JNC 7 (the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 1). | journal=J Pract Nurs | year= 2005 | volume= 55 | issue= 4 | pages= 17-21; quiz 22-3 | pmid=16512265 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16512265  }} </ref>
Although the pathophysiology of secondary [[hypertension]] has been outlined, there is still much debate about the true pathogenesis of primary (essential) hypertension. It is now conceded that hypertension is caused by multiple [[genetic]] and environmental factors with varying roles between individuals.<ref name="pmid16512265">{{cite journal| author=Cuddy ML| title=Treatment of hypertension: guidelines from JNC 7 (the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 1). | journal=J Pract Nurs | year= 2005 | volume= 55 | issue= 4 | pages= 17-21; quiz 22-3 | pmid=16512265 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16512265  }} </ref>


==Pathophysiology==
==Pathophysiology==
Below is a figure summarizing the pathophysiology of essential hypertension:
[[Image:Pathophysiology_of_hypertension.png|700px|center]]


===Genetics===
===Genetics===
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*The prevalence of hypertension in patients with family history is almost double than those with no family history.
*The prevalence of hypertension in patients with family history is almost double than those with no family history.
*Examples of [[genetic]] hypertension where specific genetic mutations were identified include, but are not limited to, some forms of primary [[hyperaldosteronism]], [[pseudohyperaldosteronism]], Liddle Syndrome, and syndrome of apparent mineralocorticoid excess.<ref name="pmid16512265">{{cite journal| author=Cuddy ML| title=Treatment of hypertension: guidelines from JNC 7 (the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 1). | journal=J Pract Nurs | year= 2005 | volume= 55 | issue= 4 | pages= 17-21; quiz 22-3 |pmid=16512265 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16512265 }} </ref>
*Examples of [[genetic]] hypertension where specific genetic mutations were identified include, but are not limited to, some forms of primary [[hyperaldosteronism]], [[pseudohyperaldosteronism]], Liddle Syndrome, and syndrome of apparent mineralocorticoid excess.<ref name="pmid16512265">{{cite journal| author=Cuddy ML| title=Treatment of hypertension: guidelines from JNC 7 (the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 1). | journal=J Pract Nurs | year= 2005 | volume= 55 | issue= 4 | pages= 17-21; quiz 22-3 |pmid=16512265 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16512265 }} </ref>
*Inherited cardiovascular risk factors must not be overlooked in the pathogenesis of hypertension.<ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA|title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 |pages= 761-76 | pmid=14597461 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>
*[[Gene therapy]] may be a promising novel therapeutic approach to treat hypertension.<ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 |pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>
*[[Gene therapy]] may be a promising novel therapeutic approach to treat hypertension. <ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 |pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>


===Cardiac Output and Peripheral Vascular Resistance===<ref name="pmid11302910">{{cite journal|author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension.| journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= |pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref>  
===Peripheral Vascular Resistance <span style="font-size:70%"><ref name="pmid11302910">{{cite journal|author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension.| journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= |pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref></span>===
*[[Arterioles]] are known for their relative increase in wall thickness determined basically by the [[smooth muscle cells]]. Patients with hypertension usually have an increased peripheral vascular resistance, which is determined largely by the arterioles.  
*Patients with hypertension usually have an increased peripheral vascular resistance, which is determined largely by the [[arterioles]] with an associated increase in the thickness of [[smooth muscle cells]].  
*Intracellular [[calcium]] concentrations are increased, contributing to [[vasoconstriction]].
*Intracellular [[calcium]] concentrations are increased, contributing to [[vasoconstriction]].
*This vasoconstriction is multifactorial, but is ultimately linked to continuous increase in intracellular [[calcium]].
*This vasoconstriction is multifactorial, but the final common pathway is ultimately linked to a sustained increase in intracellular [[calcium]].
*Prolonged constriction leads to the overall structural damage to [[arterioles]] and consequential elevation in [[blood pressure]].
*Prolonged constriction leads to a structural damage to [[arterioles]] consequently an elevation in [[blood pressure]].
 
===Cardiac Output===
*Notably, the [[cardiac output]] in hypertensive patients is generally normal. With age, the decreased compliance of central arteries predominates, causing systolic hypertension in the elderly.
*Notably, the [[cardiac output]] in hypertensive patients is generally normal. With age, the decreased compliance of central arteries predominates, causing systolic hypertension in the elderly.


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*Furthermore, [[aldosterone]] has a non-genomic effect in increasing fibrosis, collagen deposition, inflammation, and cardiovascular remodeling.<ref name="pmid20448074">{{cite journal| author=Schrier RW, Masoumi A, Elhassan E| title=Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome. | journal=Clin J Am Soc Nephrol | year= 2010 | volume= 5 | issue= 6 | pages= 1132-40 | pmid=20448074 | doi=10.2215/CJN.01410210 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20448074  }} </ref>
*Furthermore, [[aldosterone]] has a non-genomic effect in increasing fibrosis, collagen deposition, inflammation, and cardiovascular remodeling.<ref name="pmid20448074">{{cite journal| author=Schrier RW, Masoumi A, Elhassan E| title=Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome. | journal=Clin J Am Soc Nephrol | year= 2010 | volume= 5 | issue= 6 | pages= 1132-40 | pmid=20448074 | doi=10.2215/CJN.01410210 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20448074  }} </ref>


===Autonomic Nervous System<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref>===  
===Autonomic Nervous System <span style="font-size:70%"><ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref></span>===  
*The exact role of [[sympathetic nervous system]] in hypertension remains controversial.
*The role of [[sympathetic nervous system]] in hypertension remains controversial.
*The effect of beta blockers and alpha blockers as anti-hypertensive agents validates that [[sympathetic nervous system]] is, at least partially, involved in hypertension.
*The effectiveness of [[beta blockers]] and [[alpha blockers]] as anti-hypertensive agents validates that [[sympathetic nervous system]] is, at least partially, involved in hypertension.
*There is ample evidence that [[norepinephrine]] concentration and rate of norepinephrine spillover from sympathetic nerve terminals are markedly elevated in patients with essential hypertension.<ref name="pmid10489093">{{cite journal| author=Rahn KH, Barenbrock M, Hausberg M| title=The sympathetic nervous system in the pathogenesis of hypertension. | journal=J Hypertens Suppl | year= 1999 | volume= 17 | issue= 3 | pages= S11-4 | pmid=10489093 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10489093  }} </ref>
*There is ample evidence that [[norepinephrine]] concentration and rate of norepinephrine spillover from sympathetic nerve terminals are markedly elevated in patients with essential hypertension.<ref name="pmid10489093">{{cite journal| author=Rahn KH, Barenbrock M, Hausberg M| title=The sympathetic nervous system in the pathogenesis of hypertension. | journal=J Hypertens Suppl | year= 1999 | volume= 17 | issue= 3 | pages= S11-4 | pmid=10489093 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10489093  }} </ref>
* Humoral, metabolic, reflex, and central mechanisms of adrenergic activation are all contributory to characterizing hypertension.<ref name="pmid10523349">{{cite journal| author=Mancia G, Grassi G, Giannattasio C, Seravalle G| title=Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. | journal=Hypertension | year= 1999 | volume= 34 | issue= 4 Pt 2 | pages= 724-8 | pmid=10523349 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10523349  }} </ref>
* Humoral, metabolic, reflex, and central mechanisms of [[adrenergic]] activation are all contributory to characterizing hypertension.<ref name="pmid10523349">{{cite journal| author=Mancia G, Grassi G, Giannattasio C, Seravalle G| title=Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. | journal=Hypertension | year= 1999 | volume= 34 | issue= 4 Pt 2 | pages= 724-8 | pmid=10523349 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10523349  }} </ref>


===Role of Pressure Natriuresis and Renal Damage<ref name="pmid10523349">{{cite journal|author=Mancia G, Grassi G, Giannattasio C, Seravalle G| title=Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. | journal=Hypertension | year= 1999 |volume= 34 | issue= 4 Pt 2 | pages= 724-8 | pmid=10523349 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10523349 }} </ref>===  
===Role of Pressure Natriuresis and Renal Damage <span style="font-size:70%"><ref name="pmid10523349">{{cite journal|author=Mancia G, Grassi G, Giannattasio C, Seravalle G| title=Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. | journal=Hypertension | year= 1999 |volume= 34 | issue= 4 Pt 2 | pages= 724-8 | pmid=10523349 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10523349 }} </ref></span>===  
*Pressure [[natriuresis]] is the effect of arterial pressure on sodium excretion. Experimental evidence has shown that pressure natriuresis is impaired in hypertension even without significant variations in renal blood flow or changes in [[glomerular filtration rate]] (GFR).
*Pressure [[natriuresis]] is the impact of the arterial pressure head on sodium excretion. Experimental evidence has shown that pressure natriuresis is impaired in hypertension even without significant variations in renal blood flow or changes in [[glomerular filtration rate]] (GFR).
*In non-hypertensive patients, the increased blood pressure is countered by activation of the renal pressure natriuresis to allow maintenance of normal sodium balance and [[blood pressure]]. In hypertensive patients, however, pressure [[natriuresis]] seems to be permanently set at a higher BP threshold, whereby an inappropriately normal sodium excretion rate is maintained despite the high blood pressure values.
*In non-hypertensive patients, the increased blood pressure is countered by activation of the renal pressure natriuresis to allow maintenance of normal sodium balance and [[blood pressure]]. In hypertensive patients, however, pressure [[natriuresis]] seems to be permanently set at a higher BP threshold, whereby an inappropriately normal sodium excretion rate is maintained despite the high blood pressure values.
*Renal damage follows via loss of [[nephron]] function leading to a vicious circle of further impairment of pressure natriuresis and elevated BP.
*Renal damage follows via loss of [[nephron]] function leading to a vicious circle of further impairment of pressure natriuresis and elevated BP.


===Endothelial Dysfunction<sup><ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref></sup>===  
===Endothelial Dysfunction <span style="font-size:70%"><ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref></span>===  
*The vascular [[endothelium]] plays an important vasoactive role via release of vasoactive substances, such as [[nitric oxide]] and [[endothelin]].
*The vascular [[endothelium]] plays an important role in releasing [[vasodilators]] such as [[nitric oxide]] and [[endothelin]].
*The cross-talk between the [[endothelium]] and the media is an important determinant of the function of the latter.
*Endothelial cell dysfunction and permanent endothelial structural changes may play a role at least in part in the irreversible changes of the vascular bed in chronic hypertension.
*Endothelial dysfunction and permanent endothelial structural changes seem to be responsible for irreversible changes of the vascular bed and of chronic hypertension.
* Furthermore, [[renal microvascular disease]] is currently hypothesized as an important factor leading to the development of [[hypertension]].<ref name="pmid20282156">{{cite journal| author=GOLDBLATT H| title=The renal origin of hypertension. | journal=Physiol Rev | year= 1947 | volume= 27 | issue= 1 | pages= 120-65 | pmid=20282156 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20282156  }} </ref>
* Furthermore, [[renal microvascular disease]] is currently hypothesized as an important factor leading to the development of [[hypertension]]<ref name="pmid20282156">{{cite journal| author=GOLDBLATT H| title=The renal origin of hypertension. | journal=Physiol Rev | year= 1947 | volume= 27 | issue= 1 | pages= 120-65 | pmid=20282156 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20282156  }} </ref><ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910  }} </ref>.
**'''Increased role of vasoconstrive substances:'''
====Role of Vasoactive Substances====
***[[Endothelin]]: Potent local vasoactive peptide with vasoconstrictor properties. Development of [[endothelin receptor antagonist]] for the treatment of systemic hypertension has been discontinued because of [[teratogenicity]], [[testicular atrophy]] and [[hepatotoxicity]].<ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 | pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>
*'''Increased role of vasoconstrive substances:'''
***[[Ouabain]]: Steroid-like substance that plays a role in [[sodium]] and [[calcium]] transport.<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 |volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref>
**[[''Endothelin'']]: Potent local vasoactive peptide with vasoconstrictor properties. Development of [[endothelin receptor antagonist]] for the treatment of systemic hypertension has been discontinued because of [[teratogenicity]], [[testicular atrophy]] and [[hepatotoxicity]].<ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 | pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>
**'''Defect in vasodilatory substances:'''
**[[''Ouabain'']]: Steroid-like substance that plays a role in [[sodium]] and [[calcium]] transport.<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 |volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref>
***[[Nitric oxide]]: Potent [[vasodilator]], whose role is diminished in hypertension.<ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 |pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>
 
***[[Bradykinin]]: Potent vasodilator, inhibited by RAAS in hypertensive patients.<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 |volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref>
*Defect in vasodilatory substances:
***[[Atrial natriuretic peptide]] (ANP): Hormone secreted by cardiac atria in response to atrial stretch by increased blood volume. Physiologically, it induces natriuresis to decrease blood volume.<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910  }} </ref><ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 | pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461  }} </ref>
**[[''Nitric oxide'']]: Potent [[vasodilator]], whose role is diminished in hypertension.<ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 |pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461 }} </ref>
**[[''Bradykinin'']]: Potent vasodilator, inhibited by RAAS in hypertensive patients.<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 |volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910 }} </ref>
**[[''Atrial natriuretic peptide'']] (ANP): Hormone secreted by cardiac atria in response to atrial stretch by increased blood volume. Physiologically, it induces natriuresis to decrease blood volume.<ref name="pmid11302910">{{cite journal| author=Beevers G, Lip GY, O'Brien E| title=ABC of hypertension: The pathophysiology of hypertension. | journal=BMJ | year= 2001 | volume= 322 | issue= 7291 | pages= 912-6 | pmid=11302910 | doi= | pmc=PMC1120075 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11302910  }} </ref> <ref name="pmid14597461">{{cite journal| author=Oparil S, Zaman MA, Calhoun DA| title=Pathogenesis of hypertension. | journal=Ann Intern Med | year= 2003 | volume= 139 | issue= 9 | pages= 761-76 | pmid=14597461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14597461  }} </ref>.


===Environmental Factors===
===Environmental Factors===
*[[Obesity]] and [[metabolic syndrome]] play a major indirect role in the pathogenesis of hypertension by increasing [[renal tubular reabsorption]], impairment of pressure [[natriuresis]], and activation of sympathetic and RAAS. <ref name="pmid(Ref: 12623970)">{{cite journal| author=Hall JE| title=The kidney, hypertension, and obesity. | journal=Hypertension | year= 2003 | volume= 41 | issue= 3 Pt 2 | pages= 625-33 | pmid=(Ref: 12623970) | doi=10.1161/01.HYP.0000052314.95497.78 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12623970  }} </ref>
*[[Obesity]] and [[metabolic syndrome]] play a major indirect role in the pathogenesis of hypertension by increasing [[renal tubular reabsorption]], impairment of pressure [[natriuresis]], and activation of sympathetic and [[RAAS]]. <ref name="pmid(Ref: 12623970)">{{cite journal| author=Hall JE| title=The kidney, hypertension, and obesity. | journal=Hypertension | year= 2003 | volume= 41 | issue= 3 Pt 2 | pages= 625-33 | pmid=(Ref: 12623970) | doi=10.1161/01.HYP.0000052314.95497.78 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12623970  }} </ref>
*Emotional stress causes immediate, but transient, increase in [[blood pressure]]. Although stress, per se, has not been shown to cause [[hypertension]], it has been hypothesized that stress contributes to development of hypertension and when risk factors of hypertension are accompanied by environmental stress, the outcome on [[blood pressure]] is worse.<ref name="pmid9894438">{{cite journal| author=Kulkarni S, O'Farrell I, Erasi M, Kochar MS| title=Stress and hypertension. | journal=WMJ | year= 1998 | volume= 97 | issue= 11 | pages= 34-8 | pmid=9894438 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9894438  }} </ref>
*Acute emotional stress can cause an immediate, but transient, increase in [[blood pressure]]. Although chronic stress, per se, has not been shown to cause [[hypertension]], it has been hypothesized that chronic stress may contribute at least in part or may play an additive role in the context of other risk factors.<ref name="pmid9894438">{{cite journal| author=Kulkarni S, O'Farrell I, Erasi M, Kochar MS| title=Stress and hypertension. | journal=WMJ | year= 1998 | volume= 97 | issue= 11 | pages= 34-8 | pmid=9894438 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9894438  }} </ref>
*Similarly, depression seems to negatively affect hypertension, despite scarce scientific evidence. It remains controversial whether depression develops secondary to hypertension or causes it and whether [[antidepressant]] medications are the only etiology of hypertension in depression.<ref name="pmid15962086">{{cite journal| author=Scalco AZ, Scalco MZ, Azul JB, Lotufo Neto F| title=Hypertension and depression. | journal=Clinics (Sao Paulo) | year= 2005 | volume= 60 | issue= 3 | pages= 241-50 | pmid=15962086 | doi=/S1807-59322005000300010 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15962086  }} </ref>
*It remains controversial as to whether depression develops secondary to hypertension or alternatively if it causes hypertension.  It is also unclear if [[antidepressant]] medications contribute to hypertension in depression.<ref name="pmid15962086">{{cite journal| author=Scalco AZ, Scalco MZ, Azul JB, Lotufo Neto F| title=Hypertension and depression. | journal=Clinics (Sao Paulo) | year= 2005 | volume= 60 | issue= 3 | pages= 241-50 | pmid=15962086 | doi=/S1807-59322005000300010 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15962086  }} </ref>
 
Shown below is an image that summarizes the pathophysiology of hypertension.
[[Image:Pathophysiology_of_HTN.png|centre|600 px| Pathogenesis of Essential Hypertension. Adapted from Oparil S, Zaman MA, Calhoun DA. Pathogenesis of Hypertension. Ann Intern Med. 2003, 139(9):761-76]]


==References==
==References==

Latest revision as of 14:01, 17 May 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Assistant Editor-In-Chief:Yazan Daaboul, Serge Korjian

Overview

Although the pathophysiology of secondary hypertension has been outlined, there is still much debate about the true pathogenesis of primary (essential) hypertension. It is now conceded that hypertension is caused by multiple genetic and environmental factors with varying roles between individuals.[1]

Pathophysiology

Below is a figure summarizing the pathophysiology of essential hypertension:

Genetics

  • Epidemiological studies suggest that genetic factors account for 30% of blood pressure variations in populations.[2][3]
  • The prevalence of hypertension in patients with family history is almost double than those with no family history.
  • Examples of genetic hypertension where specific genetic mutations were identified include, but are not limited to, some forms of primary hyperaldosteronism, pseudohyperaldosteronism, Liddle Syndrome, and syndrome of apparent mineralocorticoid excess.[1]
  • Gene therapy may be a promising novel therapeutic approach to treat hypertension.[4]

Peripheral Vascular Resistance [2]

  • Patients with hypertension usually have an increased peripheral vascular resistance, which is determined largely by the arterioles with an associated increase in the thickness of smooth muscle cells.
  • Intracellular calcium concentrations are increased, contributing to vasoconstriction.
  • This vasoconstriction is multifactorial, but the final common pathway is ultimately linked to a sustained increase in intracellular calcium.
  • Prolonged constriction leads to a structural damage to arterioles consequently an elevation in blood pressure.

Cardiac Output

  • Notably, the cardiac output in hypertensive patients is generally normal. With age, the decreased compliance of central arteries predominates, causing systolic hypertension in the elderly.

Renin-Angiotensin Aldosterone System (RAAS)

  • While the systemic role of RAAS shows little evidence of contribution, local release of renin-angiotensin in the kidneys, heart, and arteries seems to play a much more important role in the pathogenesis of hypertension.[2]
  • Angiotensin II constricts resistance vessels, directly stimulates renal sodium reabsorption, activates aldosterone to increase sodium reabsorption, helps release antidiuretic hormone (ADH), and promotes sympathetic activity of the autonomic nervous system.[4]
  • Aldosterone increases sodium reabsorption by increasing the quantity of open sodium channels in the luminal membrane of the principal cells of the collecting tubules in the kidney.
  • Furthermore, aldosterone has a non-genomic effect in increasing fibrosis, collagen deposition, inflammation, and cardiovascular remodeling.[5]

Autonomic Nervous System [2]

  • The role of sympathetic nervous system in hypertension remains controversial.
  • The effectiveness of beta blockers and alpha blockers as anti-hypertensive agents validates that sympathetic nervous system is, at least partially, involved in hypertension.
  • There is ample evidence that norepinephrine concentration and rate of norepinephrine spillover from sympathetic nerve terminals are markedly elevated in patients with essential hypertension.[6]
  • Humoral, metabolic, reflex, and central mechanisms of adrenergic activation are all contributory to characterizing hypertension.[7]

Role of Pressure Natriuresis and Renal Damage [7]

  • Pressure natriuresis is the impact of the arterial pressure head on sodium excretion. Experimental evidence has shown that pressure natriuresis is impaired in hypertension even without significant variations in renal blood flow or changes in glomerular filtration rate (GFR).
  • In non-hypertensive patients, the increased blood pressure is countered by activation of the renal pressure natriuresis to allow maintenance of normal sodium balance and blood pressure. In hypertensive patients, however, pressure natriuresis seems to be permanently set at a higher BP threshold, whereby an inappropriately normal sodium excretion rate is maintained despite the high blood pressure values.
  • Renal damage follows via loss of nephron function leading to a vicious circle of further impairment of pressure natriuresis and elevated BP.

Endothelial Dysfunction [2]

Environmental Factors

  • Obesity and metabolic syndrome play a major indirect role in the pathogenesis of hypertension by increasing renal tubular reabsorption, impairment of pressure natriuresis, and activation of sympathetic and RAAS. [9]
  • Acute emotional stress can cause an immediate, but transient, increase in blood pressure. Although chronic stress, per se, has not been shown to cause hypertension, it has been hypothesized that chronic stress may contribute at least in part or may play an additive role in the context of other risk factors.[10]
  • It remains controversial as to whether depression develops secondary to hypertension or alternatively if it causes hypertension. It is also unclear if antidepressant medications contribute to hypertension in depression.[11]

References

  1. ↑ 1.0 1.1 Cuddy ML (2005). "Treatment of hypertension: guidelines from JNC 7 (the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 1)". J Pract Nurs. 55 (4): 17–21, quiz 22-3. PMID 16512265.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Beevers G, Lip GY, O'Brien E (2001). "ABC of hypertension: The pathophysiology of hypertension". BMJ. 322 (7291): 912–6. PMC 1120075. PMID 11302910.
  3. ↑ Staessen JA, Wang J, Bianchi G, Birkenhäger WH (2003). "Essential hypertension". Lancet. 361 (9369): 1629–41. doi:10.1016/S0140-6736(03)13302-8. PMID 12747893.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Oparil S, Zaman MA, Calhoun DA (2003). "Pathogenesis of hypertension". Ann Intern Med. 139 (9): 761–76. PMID 14597461.
  5. ↑ Schrier RW, Masoumi A, Elhassan E (2010). "Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome". Clin J Am Soc Nephrol. 5 (6): 1132–40. doi:10.2215/CJN.01410210. PMID 20448074.
  6. ↑ Rahn KH, Barenbrock M, Hausberg M (1999). "The sympathetic nervous system in the pathogenesis of hypertension". J Hypertens Suppl. 17 (3): S11–4. PMID 10489093.
  7. ↑ 7.0 7.1 Mancia G, Grassi G, Giannattasio C, Seravalle G (1999). "Sympathetic activation in the pathogenesis of hypertension and progression of organ damage". Hypertension. 34 (4 Pt 2): 724–8. PMID 10523349.
  8. ↑ GOLDBLATT H (1947). "The renal origin of hypertension". Physiol Rev. 27 (1): 120–65. PMID 20282156.
  9. ↑ Hall JE (2003). "The kidney, hypertension, and obesity". Hypertension. 41 (3 Pt 2): 625–33. doi:10.1161/01.HYP.0000052314.95497.78. PMID 12623970) (Ref: 12623970) Check |pmid= value (help).
  10. ↑ Kulkarni S, O'Farrell I, Erasi M, Kochar MS (1998). "Stress and hypertension". WMJ. 97 (11): 34–8. PMID 9894438.
  11. ↑ Scalco AZ, Scalco MZ, Azul JB, Lotufo Neto F (2005). "Hypertension and depression". Clinics (Sao Paulo). 60 (3): 241–50. doi:/S1807-59322005000300010 Check |doi= value (help). PMID 15962086.

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