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== Introduction ==

== Introduction ==

Arterial blood pressure is created by the combined forces, and complex interactions, of cardiac output, systemic vascular resistance (resistance produced mainly in the arterioles), and viscosity of the blood.

Arterial blood pressure is created by the combined forces, and complex interactions, of cardiac output, systemic vascular resistance (resistance produced mainly in the arterioles), and viscosity of the blood.

'''Blood Pressure (BP) = Cardiac Output (CO) x Systemic Vascular Resistance (SVR)'''

 

<big><center>'''Blood Pressure (BP) = Cardiac Output (CO) x Systemic Vascular Resistance (SVR)'''</center></big>

 

The arterial blood pressure is the force causing blood to flow through the arteries, into the capillaries, then back to the heart via the veins.

The arterial blood pressure is the force causing blood to flow through the arteries, into the capillaries, then back to the heart via the veins.

3) Hormonal responses

3) Hormonal responses

4) [[Kidney Control of Blood Pressure - Anatomy & Physiology|Kidney]] and fluid balance mechanisms

4) [[Kidney Control of Blood Pressure - Anatomy & Physiology|Kidney and fluid balance mechanisms]]

==Autonomic nervous system (ANS) responses==

==Autonomic nervous system (ANS) responses==

==='''''Response to stimulus'''''===

==='''''Response to stimulus'''''===

Adrenaline released from the adrenal medulla into the circulation, and noradrenaline released at nerve terminals, stimulates cardiac and vascular '''alpha and beta-receptors''', resulting in vasoconstriction of both the arterial and venous side of the circulation (alpha-receptors) and increased contractility of the heart (beta-receptors).

Adrenaline released from the adrenal medulla into the circulation, and noradrenaline released at nerve terminals, stimulate cardiac and vascular '''alpha and beta-receptors''', resulting in vasoconstriction of both the arterial and venous side of the circulation (alpha-receptors) and increased contractility of the heart (beta-receptors).

'''Alpha Effects''' increase arterial blood pressure and protects perfusion of essential vascular beds (cerebral and coronary) but the increased systemic vascular resistance leads to increased afterload and decreased cardiac output, with increased myocardial oxygen demand. It is likely to exacerbate hypoperfusion of non-essential vascular beds.

'''Alpha Effects''' increase arterial blood pressure and protects perfusion of essential vascular beds (cerebral and coronary) but the increased systemic vascular resistance leads to increased afterload and decreased cardiac output, with increased myocardial oxygen demand. It is likely to exacerbate hypoperfusion of non-essential vascular beds.

'''Beta Effects''' stimulate the release of adenylate cyclase, which generates intracellular cyclic AMP. This in turn has many intracellular effects, including increasing the rate and magnitude of the contractions in intracellular calcium fibres. This has positive inotrope (increased myocardial contractility which increases cardiac output), positive chronotrope (increased heart rate), and positive luisitrope (improved diastolic relaxation) effects, and stimulates renin release from the [[Reabsorption_and_Secretion_Along_the_Distal_Tubule_and_Collecting_Duct_- Anatomy & Physiology#Juxtaglomerular_Apparatus|Juxtaglomerular apparatus (JGA)]].

'''Beta Effects''' stimulate the release of adenylate cyclase, which generates intracellular cyclic AMP. This in turn has many intracellular effects, including increasing the rate and magnitude of the contractions in intracellular calcium fibres. This has positive inotrope (increased myocardial contractility which increases cardiac output), positive chronotrope (increased heart rate), and positive luisitrope (improved diastolic relaxation) effects, and stimulates renin release from the [[Reabsorption_and_Secretion_Along_the_Distal_Tubule_and_Collecting_Duct_- Anatomy & Physiology#Juxtaglomerular_Apparatus|Juxtaglomerular apparatus (JGA)]].

These effects lead to an increased rate and strength of cardiac contraction, and improved myocardial relaxation. This process does, however increase myocardial oxygen consumption (increased heart rate and increased work due to inotropic stimulation) and increased intracellular calcium can lead to calcium overload that in turn can result in cardiac rhythm disturbances and cell death. Chronic stimulation leads to down-regulation of the system.

These effects lead to an increased rate and strength of cardiac contraction, and improved myocardial relaxation. This process does, however, increase myocardial oxygen consumption (increased heart rate and increased work due to inotropic stimulation) and increased intracellular calcium can lead to calcium overload that in turn can result in cardiac rhythm disturbances and cell death. Chronic stimulation leads to down-regulation of the system.

'''NOTE''' There is a strong correlation between the severity of heart failure and the degree of stimulation of the adrenergic system. Veterinary studies have confirmed greater stimulation of the adrenergic system in patients with more advanced heart disease. Human studies have demonstrated a worse prognosis in those patients with higher levels of circulating noradrenaline.

'''NOTE''' There is a strong correlation between the severity of heart failure and the degree of stimulation of the adrenergic system. Veterinary studies have confirmed greater stimulation of the adrenergic system in patients with more advanced heart disease. Human studies have demonstrated a worse prognosis in those patients with higher levels of circulating noradrenaline.

*decreased chloride delivery to the macula densa is detected by chemoreceptors - a drop in glomerular filtration rate (GFR) detected as a drop in chloride presented at the macula densa leads to increased reabsorption in the proximal convoluted tubule.

*decreased chloride delivery to the macula densa is detected by chemoreceptors - a drop in glomerular filtration rate (GFR) detected as a drop in chloride presented at the macula densa leads to increased reabsorption in the proximal convoluted tubule.

Renin then leads to the [[Renin_Angiotensin_Aldosterone_System#The_System|cleavage]] of circulating Angiotensinogen (produced by the liver) to angiotensin I, and then [[Angiotensin Converting Enzyme|angiontensin converting enzyme (ACE)]] catalyses the production of angiotensin II from angiotensin I - this occurs mainly in the lungs. ACE is bound to endothelial cells throughout the vascular system. Angiotensin II acts as a stimulus to [[Aldosterone|aldosterone]] release from the zona glomerulosa of the [[Adrenal Glands - Anatomy & Physiology|adrenal cortex]], which in turn leads to sodium and water retention in the cortical collecting duct of the renal tubule.

Renin then leads to the cleavage of circulating Angiotensinogen (produced by the liver) to angiotensin I, and then [[Angiotensin Converting Enzyme|angiontensin converting enzyme (ACE)]] catalyses the production of angiotensin II from angiotensin I - this occurs mainly in the lungs. ACE is bound to endothelial cells throughout the vascular system. Angiotensin II acts as a stimulus to [[Aldosterone|aldosterone]] release from the zona glomerulosa of the [[Adrenal Glands - Anatomy & Physiology|adrenal cortex]], which in turn leads to sodium and water retention in the cortical collecting duct of the renal tubule.

'''NOTE''' This system is responsible for the long-term maintenance of blood pressure, but is also activated very rapidly in the presence of hypotension.

'''NOTE''' This system is responsible for the long-term maintenance of blood pressure, but is also activated very rapidly in the presence of hypotension.

===Vascular Hormal Effects===

===Vascular Hormal Effects===

'''Angiotensin II''' is a potent vasoconstrictor  which causes an increase in mean arterial pressure), and the direct stimulation of sodium retention in the proximal convoluted tubule of the kidney via the increased synthesis and release of aldosterone. '''Aldosterone''' stimulates reabsorption of sodium and chloride, and the secretion of potassium and protons. Initially, the effects are advantageous by protecting perfusion to essential vascular beds and expanding the circulation fluid volume, and therefore increasing contractility by the [[Heart_Failure_-_Pathophysiology#Introduction|Starling mechanism]]. As systemic vascular resistance increases, however, there is increased myocardial work and increased myocardial oxygen demand. Expanded circulatory volume ultimately results in congestion of vascular beds once the Starling mechanism is overwhelmed in the failing heart. Angiotensin II and aldosterone also effect genetic expression, which may lead to a progression of the myocardial dysfunction present. They therefore play a role in the progression of hypertrophy and fibrosis.

'''Angiotensin II''' is a potent vasoconstrictor  which causes an increase in mean arterial pressure, and the direct stimulation of sodium retention in the proximal convoluted tubule of the kidney via the increased synthesis and release of aldosterone. '''Aldosterone''' stimulates reabsorption of sodium and chloride, and the secretion of potassium and protons. Initially, the effects are advantageous by protecting perfusion to essential vascular beds and expanding the circulation fluid volume, and therefore increasing contractility by the [[Heart_Failure_-_Pathophysiology#Introduction|Starling mechanism]]. As systemic vascular resistance increases, however, there is increased myocardial work and increased myocardial oxygen demand. Expanded circulatory volume ultimately results in congestion of vascular beds once the Starling mechanism is overwhelmed in the failing heart. Angiotensin II and aldosterone also effect genetic expression, which may lead to a progression of the myocardial dysfunction present. They therefore play a role in the progression of hypertrophy and fibrosis.

==Kidney and Fluid Balance Mechanisms==

==Kidney and Fluid Balance Mechanisms==

The kidneys help to regulate the blood pressure by increasing (when blood pressure falls) or decreasing (when blood pressure rises) the blood volume, and also by the renin-angiotensin system described above. The kidney-fluid system is the main method of the long-term control of blood pressure. In additiion to the RAAS sytem, renal blood flow is regulated by:

The kidneys help to regulate the blood pressure by increasing (when blood pressure falls) or decreasing (when blood pressure rises) the blood volume, and also by the renin-angiotensin system described above. The kidney-fluid system is the main method of the long-term control of blood pressure. In addition to the RAAS sytem, renal blood flow is regulated by:

*Pressure Diuresis: As arteriolar blood pressure increases, so flow through the kidneys also increases and this increases filtration rate and urinary output

*Pressure Diuresis: As arteriolar blood pressure increases, so flow through the kidneys also increases and this increases filtration rate and urinary output

*Pressure Natriuresis: If renal perfusion pressure is increased then sodium excretion increases i.e. sodium excretion increases when blood pressure increases. If more sodium is excreted less water is reabsorbed therefore the ECF volume decreases and blood pressure decreases. The actual mechanism is not clear but it is thought to involve a direct effect of the pressure on the renal interstitium.

*Pressure Natriuresis: If renal perfusion pressure is increased then sodium excretion increases i.e. sodium excretion increases when blood pressure increases. If more sodium is excreted less water is reabsorbed therefore the ECF volume decreases and blood pressure decreases. The actual mechanism is not clear but it is thought to involve a direct effect of the pressure on the renal interstitium.

== Local Regulators of Blood Flow ==

== Local Regulators of Blood Flow ==

Individual vascular beds have the ability to regulate blood flow according to the demands of the organ being supplied. Alterations in vasculature at this level probably contribute to the pathophysiology of heart failure, but are more difficult to establish because levels of regulators are regionally variable and cannot therefore be assessed systemically. These changes are induced by various vasoregulatory substances:

Individual vascular beds have the ability to regulate blood flow according to the demands of the organ being supplied. Alterations in vasculature at this level probably contribute to the pathophysiology of [[:Category:Heart Failure|heart failure]], but are more difficult to establish because levels of regulators are regionally variable and cannot therefore be assessed systemically. These changes are induced by various vasoregulatory substances:

*Endothelin: A polypeptide factor involved in local regulation of blood flow. Manufactured in the vascular endothelium and active locally.

*Endothelin: A polypeptide factor involved in local regulation of blood flow. Manufactured in the vascular endothelium and active locally.

*Prostaglandin/Prostacyclin: Locally produced vasodilatory substances.

*Prostaglandin/Prostacyclin: Locally produced vasodilatory substances.

[[Category:Vascular System - Anatomy & Physiology]]

[[Category:Vascular System - Anatomy & Physiology]]

[[Category:Blood Pressure]]

[[Category:Blood Pressure]]