Hypertension

1. Causes of Hypertension
2. Stages of Hypertension
3. Regulation of Blood Pressure
4. Renin Angiotensin Aldosterone System (RAAS)
5. Sympathetic Nervous System
6. Antidiuretic Hormone (ADH)
7. Atrial Natriuretic Peptide (ANP)
8. Other Substances
9. Quiz

• There are both primary and secondary causes of hypertension. Primary hypertension is idiopathic (it has no known cause). Some secondary causes include renovascular disease (narrowing of the arteries that supply the kidneys) and Conn’s syndrome (too much aldosterone, a hormone from the adrenal glands).
• Blood pressure in the short term is controlled by baroreceptors (pressure sensors in the artery walls) which send out signals to the ANS (autonomic nervous system) to change the BP back to normal.
• Blood pressure is controlled in the long term by the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP, a hormone released by the heart that makes the kidneys lose sodium and water). 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.

Hypertension is a sustained increase in blood pressure (BP). It is usually diagnosed in two steps. First, the clinic BP is 140/90 mmHg or higher. Then the average BP on ambulatory blood pressure monitoring (ABPM, a cuff worn during normal daily activities that takes regular readings) or home blood pressure monitoring (HBPM, readings taken by the person at home over several days) is 135/85 mmHg or higher.

In the UK, hypertension was the third biggest risk factor for disease in 2015, after smoking and poor diet. Over a quarter of adults in England have hypertension (an estimated 26% in 2017), 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 (narrowing of the artery that supplies a kidney). This decreases kidney perfusion, which activates the renin-angiotensin-aldosterone system.
• Renal parenchymal disease (disease of the working tissue of the kidney) - sodium and water retention due to inadequate glomerular filtration.
• Phaeochromocytoma (a rare tumour that secretes catecholamines, such as adrenaline and noradrenaline) - the catecholamines cause increased sympathetic drive (more activity of the sympathetic nervous system), leading to vasoconstriction and increased cardiac output, which raise blood pressure.
• Hyperaldosteronism/Conn’s syndrome - too much aldosterone is made (aldosterone makes the kidneys keep sodium and water). This causes increased fluid retention.
• Cushing’s syndrome - excess cortisol is present for a long time. Some of it escapes being broken down in the kidney and activates mineralocorticoid receptors (the receptors that aldosterone normally acts on), which causes increased fluid retention. (Note: do not confuse this with Cushing’s disease, which is Cushing’s syndrome caused by a tumour of the pituitary gland that secretes ACTH, a hormone that makes the adrenal glands release cortisol. Cushing’s syndrome refers to the effects of excess cortisol regardless of the cause.)

Stages of Hypertension

The degree of hypertension can be split into three stages.

• Stage 1 Hypertension - clinic BP of 140/90 to 159/99 mmHg and an ABPM daytime average or HBPM average BP of 135/85 to 149/94 mmHg
• Stage 2 Hypertension - clinic BP of 160/100 mmHg or higher (but below 180/120 mmHg) and an ABPM daytime average or HBPM average BP of 150/95 mmHg or higher
• Stage 3 (severe) hypertension - clinic systolic BP of 180 mmHg or higher, or clinic diastolic BP of 120 mmHg or higher

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 cardiovascular system (CVS) drugs.

Regulation of Blood Pressure

Short term regulation of blood pressure is via baroreceptors which are found in the carotid sinus (a small widening of the carotid artery in the neck) and the aortic arch. They respond to short-term 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 (how much the blood vessels resist blood flow) by affecting the sympathetic inputs to the blood vessels.

Long term regulation of BP is via a number of mechanisms which control the amount of sodium in the body. Generally speaking, water follows sodium when sodium is transported, e.g. when sodium is reabsorbed (taken back into the blood) in the kidney, water passively follows it. Therefore by changing the amount of sodium in the body, the volume of fluid in the blood changes. Simply put - the more sodium the body holds on to, the greater the circulating volume. 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 (an enzyme that starts the RAAS) 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 (a protein made by the liver). Renin release is stimulated by:

• Reduced sodium chloride (NaCl) delivery to the distal convoluted tubule (a part of the kidney tubule).
• Reduced kidney perfusion - this is detected by baroreceptors in the afferent arteriole of the kidney (the small artery that carries blood into each glomerulus).
  
  • 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 the adrenal cortex (the outer layer of the adrenal gland). Aldosterone acts on the principal cells of the collecting ducts in the kidney (the last part of the kidney’s tubules) to cause:
  • Increased sodium and water reabsorption by increased expression of the Na/K ATPase (the sodium-potassium pump) in the basolateral wall (the side facing the blood) of the collecting duct cells, and by activation of epithelial sodium channels (ENaC, channels that let sodium into the cell).
  • Upregulation (an increase in the number) of apical potassium channels (on the side of the cell facing the urine), 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 (a peptide that widens blood vessels). ACE inhibitors (drugs that block ACE) are used to treat conditions such as hypertension and heart failure. They prevent the breakdown of bradykinin, which is thought to be one cause of the dry cough that ACE inhibitors can cause.

Diagram - The Renin Angiotensin Aldosterone System

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