Hypertension

Abstract

There are both primary and secondary causes of hypertension. Primary is idiopathic in nature. Some secondary causes include renovascular disease and Conn’s syndrome.
Blood pressure in the short term is controlled by baroreceptors which send out signals to the ANS to change the BP back to normal.
Blood pressure is controlled in the long term by RAAS, the SNS, ADH and by ANP. RAAS, the SNS and ADH all act to increase BP while ANP acts to decrease BP.
Dopamine and prostaglandins both act to prevent the BP becoming too high by buffering the mechanisms that act to increase BP.

Core

Hypertension is a sustained increase in blood pressure, defined as a BP of >140/90 mmHg.

In the UK, hypertension is the second biggest risk factor for premature death (with smoking being the first). Over a quarter of adults in the UK have hypertension, and the prevalence greatly increases with age.

Causes

In primary hypertension the cause is unknown. The majority of patients with hypertension will have primary hypertension.

Secondary hypertension is when there is a clear, identifiable cause for hypertension in a patient. E.g.

Renovascular disease – renal artery stenosis. This decreases kidney perfusion which activates the renin-angiotensin-aldosterone system.
Renal parenchymal disease – sodium and water retention due to inadequate glomerular filtration.
Phaeochromocytoma – secretes catecholamines causing increased sympathetic drive, resulting in increased fluid retention through inappropriate renin-angiotensin-aldosterone system (RAAS) activation.
Hyperaldosteronism/Conn’s syndrome – have excessive aldosterone production which stimulates increased fluid retention.
Cushing’s syndrome – excessive cortisol concentration acts on aldosterone receptors to cause increased fluid retention. (NB don’t confuse with Cushing’s disease which is a cortisol secreting tumour. Cushing’s syndrome refers to the symptoms of excess cortisol regardless of the cause).

Stages of Hypertension

The degree of hypertension can be split into three stage.

Stage 1 Hypertension – ≥140/90 in clinic or a home BP ≥135/85
Stage 2 Hypertension – ≥160/100 in clinic or a home BP ≥150/95
Severe hypertension – ≥180 systolic or ≥110 diastolic

The blood pressure of a patient at a clinic may be higher than normal due to the White Coat Effect. This is thought to be caused by patients becoming nervous or anxious around doctors, causing their blood pressure to rise.

The treatment of hypertension can be found in the article on CVS drugs.

Regulation of Blood Pressure

Short term regulation of blood pressure is via baroreceptors which are found in the carotid sinus and the aortic arch. They respond to short changes in BP and act to quickly change the BP back to normal. They do this by:

Altering autonomic inputs to the heart to change cardiac output.
Altering the total peripheral resistance by affecting the sympathetic inputs to the blood vessels.

Long term regulation of BP is via a number of mechanisms which relate to the sodium concentration within the blood. Generally speaking, water follows sodium when it is transported e.g. when sodium is reabsorbed in the kidney, water passively follows it. Therefore by changing the sodium concentration, the volume of fluid in the blood changes. Simply put - as the concentration of plasma sodium increases, the circulating volume increases. The mechanisms responsible for this balance are:

Renin-Angiotensin-Aldosterone-System (RAAS)
Sympathetic Nervous System
Antidiuretic Hormone (ADH) – also known as Vasopressin
Atrial Natriuretic Peptide

Renin Angiotensin Aldosterone System (RAAS)

Renin is released from granular cells of the juxtaglomerular apparatus (JGA) which are found next to the glomerulus. Renin is key in the RAAS due to its action on angiotensinogen. Renin release is stimulated by:

Reduced NaCl delivery to the distal convoluted tubule.
Reduced kidney perfusion – this is detected by baroreceptors in the afferent arteriole of the kidney.
- Reduced kidney perfusion can occur due to renal artery stenosis or reduced circulating volume.
Sympathetic stimulation of the JGA in the kidneys.

Angiotensinogen produced by the liver circulates in the blood and is converted to angiotensin I by renin. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE) in the lung endothelial cells.

Angiotensin II acts on both angiotensin receptor 1 and 2 (AT1/2), though it mainly acts via AT1. Angiotensin II causes:

Vasoconstriction of arterioles.
Kidneys to reabsorb more sodium.
Aldosterone release from adrenal cortex. Aldosterone acts on the principal cells of the collecting ducts in the kidney to cause:
- Increased sodium and water reabsorption by increased expression of the Na/K ATPase in the basolateral wall of the collecting duct cells, and by activation of epithelial sodium channels (ENaC).
- Upregulation of apical potassium channels which work to secrete the excess potassium brought into the cell by the Na/K-ATPase.
Increased sympathetic nervous system activation (see effects later).
Hypothalamus to increase the thirst sensation and to increase ADH release.

ACE also breaks down bradykinin, so when ACE inhibitors are used to treat heart conditions like hypertension, they prevent the breakdown of bradykinin. This can cause a dry cough.

Diagram - The Renin Angiotensin Aldosterone System

Creative commons source by OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], Connexions [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)]

Sympathetic Nervous System

The sympathetic nervous system is stimulated by a decrease in BP and by the RAAS directly.

High levels of sympathetic stimulation:

Decreases the renal blood flow by causing vasoconstriction of the afferent arterioles. This decreases the glomerular filtration rate which increases sodium retention and hence fluid retention raising BP.
Activates the apical Na/H Exchanger and the basolateral Na/K ATPase in the tubules to increase sodium reabsorption.
Stimulates renin release from the JGA cells to increase the RAAS activation.

Antidiuretic Hormone (ADH)

Antidiuretic hormone is released from the posterior pituitary in response to increased plasma osmolality and hypovolaemia.

ADH increases water reabsorption by causing the insertion of aquaporin channels into the collecting duct cells. This causes concentrated urine formation by increasing the water reabsorption from the kidney.

ADH also stimulates vasoconstriction of blood vessels to help raise the BP.

Atrial Natriuretic Peptide

Atrial natriuretic peptide (ANP) is synthesised and stored in atrial myocytes which detect stretch in the atria. ANP is released in response to stretch. Reduced filling of the heart caused by a low BP/volume leads to decreased stretching of the heart and this inhibits the release of ANP.

ANP causes increased excretion of sodium and water to lower the BP by:

Inhibiting sodium reabsorption in the kidney.
Stimulating vasodilation of afferent arterioles to increase the blood flow to the glomerulus and to increase the glomerular filtration rate.

Other Substances

Prostaglandins cause vasodilation which enhances glomerular filtration and by reduces sodium reabsorption. Prostaglandins act as a buffer to excessive vasoconstriction caused by the SNS or RAAS.

Dopamine acts to buffer against excessive sodium reabsorption. Dopamine is formed in the kidney from L-DOPA. Receptors are found on renal blood vessels and cells of the proximal convoluted tubule (PCT) and the thick ascending limb (TAL) of the Loop of Henle.

Dopamine causes vasodilation of blood vessels supplying the kidney to increase renal blood flow.
Dopamine also reduces the NaCl reabsorption by inhibiting the Na/H Exchanger and Na/K ATPase on the cells of the PCT and TAL.

Edited by: Dr. Ben Appleby

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