Lecture 5.2 - Controls of Blood Pressure PDF

Compensation mechanisms - Baroreceptors: ◦Blood pressure is tightly controlled (Normal: 120/80mmHg) to ensure adequate blood flow to organs throughout the body ◦This is accomplished by negative feedback systems incorporating pressure sensors (i.e. baroreceptors) that sense the...

Compensation mechanisms - Baroreceptors: ◦Blood pressure is tightly controlled (Normal: 120/80mmHg) to ensure adequate blood flow to organs throughout the body ◦This is accomplished by negative feedback systems incorporating pressure sensors (i.e. baroreceptors) that sense the arterial pressure Righttommon ‣ Pressure is highest in the aortic arch as this is the closest pressure to the heart's actual pressure. Right Ey Baroreceptors subclavian ◦Arterial baroreceptors are located in the carotid sinus (at the bifurcation of external and internal Brachiocephalic continton carotids) and in the aortic arch artery acarotid ◦If arterial pressure suddenly rises, the walls of these vessels passively expand, which increases the artery firing frequency of action potentials generated by the receptors Subclavi ◦If arterial blood pressure suddenly falls, decreased stretch of the arterial walls leads to a decrease Baroreceptors in receptor firing. Hypotension: ◦Baroreceptors in carotid and aortic sinus sense the low blood pressure (or change in blood pressure) ◦Aortic sinus has sensory afferent fibers of CN X - sends signals to medulla in brain ◦Carotid sinus has sensory afferent fibers of CN IX - sends signals to medulla in brain ◦Information from CN X and CN IX -> Nucleus of tractus solitarius (NTS) in medulla ◦NTS has control over cardiac acceleratory centre and inhibitory centre Hypotension - compensation mechanisms: ◦BP = CO x TPR ◦When BP is low, compensation mechanisms act to increase CO or TPR, which would increase BP ‣ CO can be increased by increasing stroke volume and heart rate ◦Nucleus of tractus solitarius in medulla -> stimulate cardiac acceleratory centre and inhibit the inhibitory centre ‣ Cardiac acceleratory centre activates the sympathetic branch of nervous system. Hypotension - short term compensation: ◦Sympathetic fibres -> norepinephrine -> binds to beta-1 adrenoceptors (nodal cells) -> increase heart rate -> increase CO -> increase BP ◦Sympathetic fibres -> norepinephrine -> binds to Beta-1 adrenoceptors (contractile cells) -> increase contractility -> increase CO -> increase BP ◦Sympathetic fibers -> norepinephrine -> binds to alpha-1 adrenoceptors (SMC of blood vessels) -> vasoconstriction -> increase total peripheral resistance -> increase BP ◦Sympathetic fibres -> chromaffin cells in adrenal medulla -> release epinephrine (80%) and norepinephrine (20%) -> acts to increase heart rate (SA node/AV node), increase contractility (contractile cardiomyocytes) and increase total peripheral resistance (vasoconstriction) Hypotension - long term compensation: ◦Kidneys get involved ◦Low BP detected by juxtaglomerular (JG) cells in kidneys ◦The epinephrine released activates JG cells by binding to beta-1 adrenoceptors ◦In response, JG cells release renin into circulation ◦Liver produces angiotensinogen (inactive protein) ◦Renin cleaves angiotensinogen and converts it to angiotensin I (Ang I)  ◦Ang I (via circulation) reaches pulmonary capillaries in lung ◦Lungs produce an enzyme called angiotensin converting enzyme (ACE) ◦ACE converts Angiotensin I to Angiotensin II (Ang II) Angiotensin II: ◦Ang II stimulates zona glomerulosa cells in adrenal cortex ◦Zona glomerulosa cells -> release Aldosterone ◦Ang II -> stimulates hypothalamic thirst centres -> increased desire to drink -> increased fluid absorption -> increased blood volume -> increased EDV -> increased stroke volume -> increased CO -> increase BP ◦Ang II can act on proximal convoluted tubule -> increased reabsorption of Na+ and water ◦Ang II has receptors on tunica media of blood vessels -> vasoconstriction ADH and aldosterone: ◦ADH (vasopressin) acts in collecting duct of nephron -> increase water reabsorption ◦ADH binds to V2 receptors in collecting duct -> G stimulatory protein -> produce aquaporins (Type II) -> increase water reabsorption ◦Increased water reabsorption -> increased blood volume -> increased EDV -> increased SV -> increased CO -> increased BP ◦Adrenal cortex releases Aldosterone, which acts on distal convoluted tubule -> increased reabsorption of Na+ -> increased reabsorption of water, therefore increasing fluid volume ◦Proximal convoluted tubule -> increased reabsorption of water ‣ Vasoconstriction - Increased TPR ◦Oliguria (reduced urine output) Hypertension - compensation mechanisms: ◦BP = CO x TPR ◦When BP is high, compensation mechanisms act to decrease CO and TPR, as well as SV and HR ◦Nucleus of tractus solitarius in medulla -> stimulate cardio inhibitory centre and inhibit the cardio acceleratory centre ‣ Stimulates vagus nerve of the parasympathetic branch of NS Hypertension - inhibition of cardio acceleratory centre: ◦Decreased heart rate due to reduced stimulation of SA node and AV node -> decreased HR -> decreased CO -> decreased BP ◦Reduced contraction of smooth muscles of blood vessels -> leads to vasodilation -> decreased TPR -> decreased CO -> decreased BP ◦Reduced stimulation of adrenal medulla -> reduced epinephrine -> leads to vasodilation -> decreased BP Hypertension - activation of cardio inhibitory centre: ◦Cardio inhibitory centre -> has parasympathetic fibres (Dorsal nucleus of vagus) -> innervate SA node (rught vagus) and AV node (left vagus) ◦No parasympathetic innervation to myocardium ◦Parasympathetic fibres -> acetylcholine -> binds to muscarinic type 2 receptors -> decrease heart rate Hypertension - long term compensation: ◦If there is increased blood pressure -> increase in atrial pressure -> secretes atrial natriuretic peptide (ANP)  ◦ANP has vasodilator effects: ‣ Venodilation (dilation of veins) -> Increased venous compliance -> decrease central venous pressure -> reduce ventricular preload -> reduced CO ‣ Cause arterial vasodilation -> reduced TPR ◦ANP acts as counter regulatory system for renin-angiotensin-aldosterone system (RAAS): ‣ Inhibits renin synthesis ‣ Reduced Ang II synthesis -> Reduced aldosterone and ADH synthesis ‣ Reduce stimulation of hypothalamic thirst centres ‣ Increased glomerular filtration rate (GFR) -> increased Na+ excretion (Natriuresis) and increased fluid (water) excretion (diuresis) Drugs used to manage blood pressure: ◦Sympatholytic drugs - inhibit sympathetic activity e.g. beta blockers ◦Angiotensin inhibitors - inhibits angiotensin e.g. ACE inhibitors ◦Diuretics - removes volume ◦Vasodilators Stages of hypertension: ◦Normal - SBP 120 mmHg and DBP 80 mmHg ◦Elevated BP - SBP 120-129 mmHg and DBP less than 80 mmHg ◦Hypertension stage 1 - SBP 130-139 mmHg or DBP 80-89 mmHg ◦Hypertension stage 2 - SBP greater than or equal to 140 mmHg or DBP greater than or equal to 90 mmHg Classification: ◦Essential hypertension: ‣ No single, reversible cause can be readily identified ‣ ~85-90% of adults with hypertension have primary or essential hypertension ‣ Risk factors - lower levels of physical activity, high sodium intake, high caloric intake ◦Secondary hypertension: ‣ Due to underlying, identifiable cause ‣ Treatment of the underlying cause can potentially reverse hypertension ‣ Common causes - obstructive sleep apnea, renal artery stenosis, primary hyperaldosteronism