Chronic hypertension pathophysiology
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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]
- 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.[8]
- 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.[4]
- Ouabain: Steroid-like substance that plays a role in sodium and calcium transport.[2]
- Defect in vasodilatory substances:
- Nitric oxide: Potent vasodilator, whose role is diminished in hypertension.[4]
- Bradykinin: Potent vasodilator, inhibited by RAAS in hypertensive patients.[2]
- 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.[2][4]
- Increased role of vasoconstrive substances:
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
- ↑ 1.0 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.
- ↑ 2.0 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.
- ↑ 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.
- ↑ 4.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 7.0 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.
- ↑ GOLDBLATT H (1947). "The renal origin of hypertension". Physiol Rev. 27 (1): 120–65. PMID 20282156.
- ↑ 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). - ↑ Kulkarni S, O'Farrell I, Erasi M, Kochar MS (1998). "Stress and hypertension". WMJ. 97 (11): 34–8. PMID 9894438.
- ↑ 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.