Hypertension: Pathophysiology
Mean arterial pressure is determined by cardiac output and total peripheral resistance (aka, systemic vascular pressure).
Thus,
hypertension, which is elevated blood pressure, is the result of increased cardiac output and/or increased total peripheral resistance.
Cardiac output is the product of heart rate and stroke volume.
Stroke volume is determined by preload and contractility.
Blood volume contributes to
preload, by way of increased venous return.
The degree of sodium and water retention in the
kidneys contributes to blood volume.
Degree of vasoconstriction, particularly of the small arteries and arterioles, is a significant determinant of total peripheral
resistance.
Key mediators of blood pressure implicated in primary and/or secondary hypertension:
Notice that many of these mediators effect both cardiac output and total peripheral resistance, but be aware that some effects may be more significant in hypertension development than others.
Posterior pituitary secretes
antidiuretic hormone (aka, vasopressin),
Vasoconstrictor that also increases sodium and water retention in the kidneys.
Increased sodium and water retention results in increased blood volume, and, therefore, increased cardiac output.
Aldosterone is secreted by the adrenal cortex and has similar effects.
Angiotensin II, which is a product of the renin-angiotensin-aldosterone system, has direct and indirect effects on blood pressure:
Like antidiuretic hormone and aldosterone, it triggers vasoconstriction and increases sodium and water retention.
Angiotensin II also stimulates the release of norepinephrine, antidiuretic hormone, and aldosterone, further enhancing vasoconstriction and sodium/water retention.
Multiple antihypertensive drugs work against the effects angiotensin II.
Norepinephrine is a vasoconstrictor that also increases heart rate and contractility.
Vascular remodeling: hypertension produces damage and inflammation that leads to vascular remodeling, which alters local mediators.
Endothelin, which is a key vasoconstrictor, is elevated in remodeled vessels.
Secretion of local vasodilators, such as nitric oxide, is reduced.
Vasodiators:
Nitric oxide, prostaglandins, histamine, and bradykinin.
- Bradykinin is broken down by angiotensin II; thus, angiotensin II not only induces vasoconstriction, it removes a vasodilator.
The relationship between angiotensin II and bradykinin contributes to the effectiveness of drugs that inhibit angiotensin-converting-enzyme – when circulating levels of angiotensin II are reduced, bradykinin levels can rise.
Genetic and epigenetic factors, diet, physical activity levels, and other environmental or biological factors can affect blood pressure by acting on the various components of this diagram.
– For example, we can now understand how individuals who are salt-sensitive or have aldosterone-secreting tumors develop hypertension via elevated blood volume and preload.
Hypertensive crisis occurs when blood pressure is dangerously high, typically exceeding 180/120mmHg.
Hypertensive urgency: no end-organ damage
Hypertensive emergency: end-organ damage has occurred
Symptoms of hypertensive emergency include severe headache with confusion and impaired vision, chest pain and shortness of breath, nausea/vomiting, anxiety, and seizures.
