Blood Pressure and Control Mechanisms PDF

Blood Pressure and Control Mechanisms Look at the following Pressure in CV system Factors involved in blood pressure Peripheral resistance Cardiac output Volume control Homeosta>c control of cardiovascular func>ons Autonomic nervous system , RAAS Endothelial factors...

Blood Pressure and Control Mechanisms Look at the following Pressure in CV system Factors involved in blood pressure Peripheral resistance Cardiac output Volume control Homeosta>c control of cardiovascular func>ons Autonomic nervous system , RAAS Endothelial factors , NO, PGI2 Natriure>c pep>des Blood Pressure Generated by Ventricular Contrac>on Pulsa>le: surges in arteries Systolic and Diastolic pressure E.g. 120mm Hg/ 80 mm Hg (120/80) Elas>c rebound evens & maintains pressure Pulse and Mean Arterial Pressures Role of arteries Factors A6ec7ng Blood Pressure Cardiac Output Peripheral Vascular resistance Volume Mean Arterial Pressure (MAP) 0 MAP = Diastolic + 1/3 Pulse Pressure o (Pulse Pressure = Systolic Pressure – Diastolic Pressure) What is the MAP when BP = 120/80? i  Mean Arterial Pressure (MAP) Important Equa7ons MAP = CO (Cardiac Output) x PVR (Peripheral Vascular Resistance) ooo O Cardiac Output = Stroke Volume x Heart Rate Average CO =70 ml x 70 bpm = approx. 5000 ml/min  Col Factors aEecting Cardiac Output If EDV = end diastolic volume ESV = end systolic volume Factors aEecting Stroke Volume Preload = amount of stretch during diastole I when the ventricles Wll with blood AGerload = the pressure against which the heart must work to eject blood during systole Factors A6ec7ng Contrac7lity Starling’s Law of the Heart (The Frank-Starling Mechanism) E hYps://image3.slideserve.com/6609117/starling-s-law-of-the-heart-the-frank-starling-mechanism-l.jpg Pressure Flow and Resistance Flow is from High to Low Pressure Pressure, Flow & Resistance MAP = CO (Cardiac Output) x PVR (Peripheral Vascular Resistance) E6ect of Blood Volume on Blood Pressure Blood volume ~ 5 Litres Arteries = low volume ~ 11% total blood volume Veins = high volume ~ 70% circula>ng blood volume CO HR Sun Increased blood volume (Hypervolaemia) = Increased BP blood fillmove Increased preload strategist f = increased stroke volume= increased cardiac output = increased blood pressure Decreased blood volume (Hypovolaemia) = decreased blood pressure Compensatory mechanisms BP Hypovolaemic shock Factors a6ec7ng blood volume 0 = accumula>on duid Oedema 0 in inters>>al space Disrup>on in duid exchange between blood and >ssues Factors disrup>ng balance a – eg heart failure – back pressure 1. Increased hydrosta>c pressure 8 2. Decreased plasma protein concentra>on – osmo>c balance disrupted 3. Increase in inters>>al proteins Ques7ons 1. If the lef ventricle fails to pump normally where would you expect oedema to occur? 2. Malnourished children can suher from a condi>on called ascites (swollen bellies due to oedema of the abdomen). Why does malnutri>on cause ascites? decrease in PlasmaProtien concentration Vascular Tone Vascular Tone: Refers to the degree of constric>on experienced by a blood vessel rela>ve to its maximally dilated state (max lumen= max capacity). All arterial and venous vessels under basal condi>ons exhibit some degree of smooth muscle contrac>on that determines the diameter, and hence tone, of the vessel. o Vascular Tone: balance between contrac>on and dilata>on in a vessel Contrac>on and dilata>on depends on: 1) Composi>on of the vessels 2) Control by Intrinsic and extrinsic factors Smooth Muscle Contraction The mechanisms by which Extrinsic and Intrinsic mechanism induences either constrict or relax blood vessels involve a variety of signal transduc>on mechanisms that ul>mately induence the interac>on between ac>n and 00myosin in the smooth muscle promo>ng contrac>on/relaxa>on. Calcium changes inside the muscle cells are coupled to 60 contrac>on/relaxa>on of the cell. Smooth Muscle Contrac>on T.uaaivated Cardiovascular Physiology Control mechanisms Nervous/cytokine/autoregulatory ANS/RAAS NO, PGs etc.. Baroreceptors Stretch-sensi>ve mechanoreceptors Found in Aor>c arch and caro>d sinus Increased/Decreased Blood Pressure BP Increases/Decreases Stretch on Vessel Wall Increased/Decreased Wring rate from Baroreceptor Medullary Cardiovascular Control Centre Altered Sympathe>c / Parasympathe>c Ac>vity hYps://th.bing.com/th/id/OIP.gSmmo75s81ZjDNef3qW_rgAAAA?rs=1&pid=ImgDetMain Baroreceptor ReTex and Autonomic Nervous System Autonomic Nervous System Sympathe>c – Fear Wght dight Parasympathe>c – Rest and digest Sympathe7c Noradrenaline – adrenoreceptors Alpha and Beta Parasympathe7c Acetylcholine - muscarinic receptors Ganglia (both) Acetylcholine – Nico>nic receptors so What ehect will the sympathe>c nervous system have on Tightorflight Heart rate increase Force of Contrac>on of the heart increase Blood Pressure increase  Systems work to oppose each other SNS increases (+) heart’s ac>ons leading to:  rate/chronotropy (tachycardia)  force of contrac>on/inotropy  relaxa>on during diastole (lusitropy) Slight  impulse conduc>on (dromotropy) Excitability is also increased PNS decreases (-) heart’s ac>ons leading to: II  rate/chronotropy (bradycardia), dromotropy Slight  inotropy, lusitropy  Innervation of the Heart RIGHT LEFT Sympathe>c Postganglionic Wbres from ganglion chain Innervate atria, esp SA node, ventricles, including conduc>on system Parasympathe>c Vagus nerves (Xth) Right to SA, Lef to AV, but lef/right innerva>on some>mes overlaps Some atrial muscle, less so ventricles (hence why less control of inotropy/lusitropy) 26  Adrenergic receptors - Sympathetic Fight or Flight Heart Vessels Receptor Func>on Receptor Func>on Inotropy Chronotropy Dromotropy Vasoconstric>on Vasodila>on Entranton Rate imputinitation Norepinephrine α1... α1 Y. (noradrenaline) β1 ++ ++ ++ β1 indirect. β2 + + + β2. Y Acetylcholine M2 -- -- -- M2 Y. Adapted from World J Cardiol. 2015 Apr 26; 7(4): 204–214. 27  Muscarinic receptors - Parasympathetic Heart Vessels Receptor Func>on Receptor Func>on Inotropy Chronotropy Dromotropy Vasoconstric>on Vasodila>on Norepinephrine α1... α1 Y. (noradrenaline) β1 ++ ++ ++ β1 indirect. β2 + + + β2. Y Acetylcholine M2 -- -- -- M2 Y. Adapted from World J Cardiol. 2015 Apr 26; 7(4): 204–214. 28 Blood Vessels Sympathe>c System Main Beta 2 receptors -vasodila>on I Alpha 1 receptors - vasoconstric>on Heart Vessels Receptor Func>on Receptor Func>on Inotropy Chronotropy Dromotropy Vasoconstric>on Vasodila>on Norepinephrine α1... α1 Y. (noradrenaline) β1 ++ ++ ++ β1 indirect. β2 + + + β2. Y Acetylcholine M2 -- -- -- M2 Y. Won’t Alpha 1 (vasoconstric>on)and Beta 2 (vasodila>on) ehects just counteract each other?  Adrenaline – neurohormone Preganglionic Wbres pass through the sympathe>c ganglia and extend to adrenal medulla These Wbres terminate on special hormone secre>ng cells Chromaun cells. They release: Noradrenaline (20%) Adrenaline (80%) Adrenaline s>mulates all major adrenergic receptors, including α1, α2, β1, and β2 receptors s 31  Adrenaline α1 s>mulated by noradrenaline – vasoconstric>on NeurotransmiYer ehect lonelow I I Low [adren]: β2-selec>ve -> mostly vasodilata>on High [adren]: also s>mulates α1, and Q Q vasoconstric>on (mediated by β1 receptors, producing α1 receptors) increased heart rate & contrac>lity (β1 receptor as we saw earlier) Renin- Angiotensin Aldosterone System (RAAS) Angiotensin I 2 Angiotensin CO HRXSV Renin F Stored in juxtaglomerular (JG) cells e S>mulus for release 1 Decrease in sodium chloride concentra>on Nacl 2 Decreased rate of blood dow through the macula densa of kidneys 3 Baroreceptor detected decrease in blood pressure Mode of ac>on Converts angiotensinogen (synthesised in liver) into angiotensin I (ATI) Renin- Angiotensin Aldosterone System (RAAS) Angiotensin Conver7ng Enzyme Forms ACE and ACE2 (COVID virus binding) Fron>ers | Angiotensin-Conver>ng Enzyme 2 (ACE2) in the Pathoge nesis of ARDS in COVID-19 (fron>ersin.org) Expressed predominantly in lung on Converts ATI into Angiotensin II (ATII) Inhibited by ACE inhibitors (ACEI) e.g. captopril Tramiprit Renin- Angiotensin Aldosterone System (RAAS) Angiotensin II Octapep>de 0 0 and AT2 Acts via angiotensin receptors AT1 Ac7ons of ATII 1. Vasoconstrictor 2. ADH (vasopressin) release 3. Increased Sympathe>c nervous system ac>vity 4. Increased sodium/water reabsorp>on 5. Aldosterone Release 1. Vasoconstric7on AT1 receptors Increases Blood Pressure MAP = CO x PVR Vasoconstric7on hYps://www.researchgate.net/proWle/Gaetano-Santulli/publica>on/341106326/Wgure/Wg4/AS:887924056940552@1588709000659/ Angiotensin-conver>ng-enzyme-inhibitors-ACEi-and-blockers-of-the-angiotensin-receptor.png Ac7ons of ATII 2. S7mulates ADH (Vasopressin) release of S7mulates AT1 receptors in hypothalamus so Release of ADH Increased water reabsorp7on Ac7ons of ATII 3. Increased SNS ac7vity Increased sympathe>c neurotransmission centrally , at the autonomic ganglia, spinal cord, and end-organs (also decreased PNS) contractability or The renin–angiotensin system in cardiovascular autonomic control: recent develo pments and clinical implica>ons | SpringerLink Ac7ons of ATII 4. Increased sodium/water reabsorp7on Increases sodium reabsorp>on in proximal tubule 5. Aldosterone Release Aldosterone Mineralocor>coid F I Steroid hormone released form adrenal gland From adrenal cortex (zona glomerulosa) Hormonal / Paracrine Regula7on Vascular endothelium Release of a number of mediators e.g nitric oxide, endothelin , prostaglandins etc. Nitric Oxide ~1980 FurchgoY showed that vasodila>on induced by acetylcholine (a neurotransmiYer) was dependent on vascular endothelium and a substance they subsequently called EDRF. Also showed that EDRF could s>mulate soluble guanylate cyclase leading to ↑ cyclic GMP levels in VSMC. Realised that EDRF shared many of same proper>es as NO and subsequently shown that they were the same.  Nitric Oxide Ac>ons Vasodila7on controls platelet aggrega>on, immunomodulatory S>mulus for produc>on Acetylcholine IF Histamine, bradykinin, serotonin Shear stress on blood vessels Synthesised from arginine by nitric oxide synthase (NOS) Ach Di6erent forms of NOS 0 00 0 so Endothelin Opposite ehect to NO Vasoconstric>on I Posi>ve inotropic/chronotropic am ehects 000ET-3 Three isoforms - ET-1, ET-2, ET-1 main for cardiovascular ehects (produced by endothelium and also VSMC (vascular smooth muscle cells) in indamma>on) Receptors ETA and ETB Endothelin Synthesis ECE = endothelin conver>ng enzyme Receptors ETA - vasoconstric>on ETB – vasoconstric>on and vasodila>on via NO/PGI2 Prostaglandin I2 (PGI2; prostacyclin) PGI2 = synthesised from arachidonic acid Vasodilator Inhibits platelet aggrega>on An>-indammatory ehects Natriure7c Pep7des ANP – A- Type Natriure7c Pep7de; Atrial Natriure7c Pep7de BNP – B-Type Natriure7c Pep7de; Brain Natriure7c Pep7de Increase sodium excre>on in urine Opposite ehect to Angiotensin II diastole Released from atria (ANP)and ventricles (BNP)in response to stretch a as BNP used as a biomarker for heart failure  Receptors - NPRA, NPRB and NPRC p p hYps://www.researchgate.net/publica>on/285773841/Wgure/Wg2/AS:614007702560768@1523402252173/ Natriure>c-pep>de-binding-receptors-intracellular-signalling-and-degrada>on-processes.png E6ects of Natriure7c Pep7des Brain IF I I Markers of Haemodynamic stress Heartfailure B-type Natriure7c Pep7de BNP BNP- and NT-ProBNP Levels in plasma are used in diagnosis Sacubitril / Valsartan. (Entresto) Valsartan – ARB Sacubitril – Neprilysin Inhibitor  Reduce increase European J of Heart Fail, Volume: 19, Issue: 4, Pages: 469-478, First published: 14 December 2016, DOI: (10.1002/ejhf.705)  I Neprilysin Inhibitors in Heart Failure: The Science, Mechanism of Action, Clinical Studies, and Unanswered Questions J Am Coll Cardiol Basic Trans Science. 2023 Jan, 8 (1) 88–105