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{{Template:Hypertension}}
{{Chronic hypertension}}
{{CMG}}; '''Assistant Editor-In-Chief:'''[[User:YazanDaaboul|Yazan Daaboul]], [[User:Sergekorjian|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.<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>


{{CMG}}; '''Assistant Editor-In-Chief:''' Taylor Palmieri
==Pathophysiology==
 
Below is a figure summarizing the pathophysiology of essential hypertension:
==Overview==
While the mechanisms underlying secondary hypertension are well understood, the mechanisms underlying primary or essential hypertension are poorly understood.  It has been postulated that polygenic influences, increased arterial collagen with aging, salt consumption and sensitivity, [[hyperinsulinemia]] as part of the [[metabolic syndrome]] and renin may all play a role in the pathophysiology of essential hypertension.


==Time Dependence of Pathophysiology==
[[Image:Pathophysiology_of_hypertension.png|700px|center]]
*[[Cardiac output]] is raised early in the disease course, while [[total peripheral resistance]] (TPR) is normal.
* Over time [[cardiac output]] drops to normal levels but TPR is increased. Three theories have been proposed to explain this:
:# Inability of the kidneys to excrete sodium, resulting in [[natriuretic]] factors such as [[Atrial Natriuretic Factor]] being secreted to promote salt excretion with the side-effect of raising total peripheral resistance.
:# An overactive [[renin / angiotension system]] leads to [[vasoconstriction]] and retention of sodium and water. The increase in blood volume leads to hypertension.
:# An overactive [[sympathetic nervous system]], leading to increased stress responses.


==Genetics==
===Genetics===
Genetics account for approximately 30% of the expression of the disorder.  Hypertension is heritable and [[polygenic]] (caused by more than one gene) and a few candidate [[genes]] have been identified.<ref name="polymorphism">{{cite journal |author= Sagnella GA, Swift PA |journal=Current Pharmaceutical Design |title=The Renal Epithelial Sodium Channel: Genetic Heterogeneity and Implications for the Treatment of High Blood Pressure |year = 2006 |month = June |volume = 12 |issue = 14 |pages = 2221-2234 |id = PMID 16787251}}</ref><ref name="polymorphism2">{{cite journal |author= Johnson JA, Turner ST |journal=Current Opinion in Molecular Therapy |title=Hypertension pharmacogenomics: current status and future directions. |year = 2005 |month = June |volume = 7 |issue = 3 |pages = 218-225 |id = PMID 15977418}}</ref><ref name="polymorphism3">{{cite journal|author= Hideo Izawa; Yoshiji Yamada et al |journal=Hypertension |title=Prediction of Genetic Risk for Hypertension |year = 2003 |month = May |volume = 41 |issue = 5 |pages = 1035-1040 |id = PMID 12654703 | url=http://hyper.ahajournals.org/cgi/content/short/01.HYP.0000065618.56368.24v1}}</ref>
*Epidemiological studies suggest that [[genetic]] factors account for 30% of blood pressure variations in populations.<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="pmid12747893">{{cite journal| author=Staessen JA, Wang J, Bianchi G, Birkenhäger WH|title=Essential hypertension. | journal=Lancet | year= 2003 | volume= 361 | issue= 9369 | pages= 1629-41 | pmid=12747893 | doi=10.1016/S0140-6736(03)13302-8 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12747893 }} </ref>
*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>
*[[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>


== Salt Sensitivity and Diet==
===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>===
[[Salt#Health effects|Sodium]] is the environmental factor that has received the greatest attention. Approximately 60% of the essential hypertension population is responsive to sodium intake. This is due to the fact that increasing amounts of salt in a person's bloodstream causes the body to draw in more water, increasing the pressure on the blood vessel walls.  In addition to sodium, choride plays an important role as it causes volume expansion thereby increasing blood pressure.  It is notable that sodium, when combined with other anions, does not increase blood pressure.  It is only when sodium is combined with chloride does the blood pressure rise. <ref>{{cite journal |author=Kurtz TW, Al-Bander HA, Morris RC |title="Salt-sensitive" essential hypertension in men. Is the sodium ion alone important? |journal=[[N. Engl. J. Med.]] |volume=317 |issue=17 |pages=1043–8 |year=1987 |month=October |pmid=3309653 |doi= |url=}}</ref> Salt sensitivity itself is associated with increasing age, obesity, African american race, and the [[metabolic syndrome]].<ref>{{cite journal |author=Obarzanek E, Proschan MA, Vollmer WM, ''et al.'' |title=Individual blood pressure responses to changes in salt intake: results from the DASH-Sodium trial |journal=[[Hypertension]] |volume=42 |issue=4 |pages=459–67 |year=2003 |month=October |pmid=12953018 |doi=10.1161/01.HYP.0000091267.39066.72 |url=http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=12953018}}</ref>
*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]].


The proposed mechanism for salt-sensitvity is increased salt intake over a long period of time leads to impaired excretion of salt which causes hypertension.  There may be several other pathways involved in the pathophysiology of salt-sensitivity leading to hypertension.  Salt-sensitive patients are known to have a dysregulated [[renin-angiotensin]] pathway and patients show an abnormal vascular response to [[angiotensin II]]<ref>{{cite journal |author=Chamarthi B, Williams JS, Williams GH |title=A mechanism for salt-sensitive hypertension: abnormal dietary sodium-mediated vascular response to angiotensin-II |journal=[[J. Hypertens.]] |volume=28 |issue=5 |pages=1020–6 |year=2010 |month=May |pmid=20216091 |doi=10.1097/HJH.0b013e3283375974 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0263-6352&volume=28&issue=5&spage=1020}}</ref>.
===Cardiac Output===
Increased sodium re absorption, though not well understood, is mostly related abnormalities across Na-H [[proximal tubule]] channels, Na-K-Cl co-transporter across the [[thick ascending limb]], Na-Cl distal tubule co-transporter and epithelial Na channels.  Dietary deficiency in potassium is also known to trigger increased sodium sensitivity in patients in particular African-Americans, but the mechanism is not well understood.
*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 ==
===Renin-Angiotensin Aldosterone System (RAAS)===
[[Renin]] is a [[hormone]] secreted by the [[juxtaglomerular cell]]s of the kidney and linked with [[aldosterone]] in a negative feedback loop.  The range of renin activity observed in hypertensive subjects tends to be broader than in normotensive individuals. As a consequence, some hypertensive patients have been defined as having low-renin and others as having essential hypertension. Low-renin hypertension is more common in African Americans than Caucasians and may explain why African Americans tend to respond better to diuretic therapy than drugs that interfere with the renin-angiotensin system.
*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.<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>
*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]].<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>
*[[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.<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>


High Renin levels may predispose to hypertension through the following sequence of events:
===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>===
Increased Renin --> Increased Angiotensin II --> Increased Vasoconstriction, Thirst/ADH and Aldosterone --> Increased Sodium Reabsorption in the Kidneys (DCT and CD) --> Increased Blood Pressure.
*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.<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>


== Insulin resistance ==
===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>===  
[[Insulin]] is a polypeptide [[hormone]] secreted by the [[pancreas]]. Its main purpose is to regulate the levels of [[glucose]] in the body antagonistically with [[glucagon]] through negative feedback loops. Insulin also exhibits vasodilatory properties. In normotensive individuals, insulin may stimulate sympathetic activity without elevating mean arterial pressure. However, in more extreme conditions such as that of the [[metabolic syndrome]], the increased sympathetic neural activity may override the vasodilatory effects of insulin. Insulin resistance and/or [[hyperinsulinemia]] have been suggested as being responsible for the increased arterial pressure in some patients with hypertension. This feature is now widely recognized as part of [[metabolic syndrome|syndrome X]], or the [[metabolic syndrome]].
*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.


==Age==
===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>===
As a patient ages, the number of [[collagen]] fibers in artery and arteriole walls increases, making blood vessels stiffer, and blood pressure higher for any given stroke volume.
*The vascular [[endothelium]] plays an important role in releasing [[vasodilators]] such as [[nitric oxide]] and [[endothelin]].
*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.
* 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>
**'''Increased role of vasoconstrive 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>
***[[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>
**'''Defect in vasodilatory substances:'''
***[[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>


==Associated conditions<ref name="pmid12748199">{{cite journal| author=Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al.| title=The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. | journal=JAMA | year= 2003 | volume= 289 | issue= 19 | pages= 2560-72 | pmid=12748199 | doi=10.1001/jama.289.19.2560 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12748199}}</ref>==
===Environmental Factors===
*[[Obesity]]
*[[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>
*Excess alcohol intake
*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>
*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>


==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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