Control & Regulation of ABP 2024-2025 PDF

CONTROL & REGULATION OF ABP MEDICAL PHYSIOLOGY DEPARTMENT 1  ILOs: Identify the different types of blood pressure. Differentiate between myogenic and metabolic autoregulation. Discuss the role of different vasoactive substances in the control of ABP eit...

CONTROL & REGULATION OF ABP MEDICAL PHYSIOLOGY DEPARTMENT 1  ILOs: Identify the different types of blood pressure. Differentiate between myogenic and metabolic autoregulation. Discuss the role of different vasoactive substances in the control of ABP either locally or systematically. List the different mechanisms regulating the ABP. Recognize the short, intermediate, and long-term mechanisms regulating ABP. Discuss the role of baroreceptors in preventing significant changes in ABP. Understand the importance of chemoreceptors in the control of ABP. Explain the role of the kidney in the long-term regulation of ABP. 2  ARTERIAL BLOOD PRESSURE (ABP) Systolic BP: Highest pressure in the aorta and other large arteries during systole. Normal range: 90 - 140 mmHg (about: 120 mmHg). Diastolic BP: Lowest pressure in the aorta and other large arteries during diastole. Normal range: 60 - 90 mmHg (about: 80 mmHg). Pulse pressure (P.P): The difference between systolic and diastolic pressures (average 30 - 50 mmHg). Mean arterial pressure (MAP) = SBP+DBP+DBP/3=120+80+80/3= 93 mmHg (average 90 - 100 mmHg); nearer to diastole {because diastole duration (0.5 sec) is nearly twice systole duration (0.3 sec)}. 3  REGULATION OF THE DIAMETER OF ARTERIOLES  The diameter of arterioles is adjusted by: Vascular autoregulation. Regulation of blood flow locally in Substances secreted by the endothelium {autocoids (i.e., local hormones). particular tissues. Circulating vasoactive substances. Systemic regulation of ABP & redistribution of blood all over the body e.g.: in muscular exercise or Nerves that innervate arterioles. hemorrhage. 4  AUTOREGULATION  Definition: Intrinsic capacity of the vascular beds to compensate for moderate changes in perfusion pressure by changing vascular resistance so, that blood flow remains constant.  It is well-developed in the kidneys, brain, and heart.  Aim: To maintain constant blood flow to an organ despite fluctuation in its perfusion pressure. Types of autoregulation Myogenic Metabolic 5  MYOGENIC AUTOREGULATION  Definition: It is an intrinsic contractile response of the vascular smooth muscle cells (VSMCs) to stretch. Mechanism: ↑↑↑Blood flow →↑↑↑Blood pressure in the blood vessels → Stretch of VSMCs → Ca ++ entry (stretch sensitive Ca++ channels) → Contraction of VSMCs→ Vasoconstriction (VC) → ↑↑↑ Resistance → flow nearly returns to its initial value. Flow = Pressure / Resistance "Ohm's Law" 6  MYOGENIC AUTOREGULATION 7 Flow = Pressure / Resistance “Ohm's Law “  METABOLIC AUTOREGULATION  Aim: to maintain a constant blood flow to an organ despite the decrease in its perfusion pressure.  Mechanism: - ↓ Perfusion pressure → ↓ blood flow → hypoxia and accumulation of vasodilator metabolites e.g.; K+, adenosine, lactic acid & CO2→ relaxation of the arterioles and precapillary sphincters → ↓↓ Vascular resistance → ↑↑ Blood flow. - In addition, the local rise of temperature e.g.; in contracting muscles → Vasodilation (Active hyperemia). 8 METABOLIC AUTOREGULATION ↓Perfusion pressure ↓ Blood flow 9  SUBSTANCES SECRETED BY THE ENDOTHELIUM 1. Nitric oxide (NO): Stimuli Acetylcholine Bradykinin Endothelial NO synthase (e-NOS) Shear stress L-arginine (endothelial cells) NO  Stimuli (activate e-NOS): - Acetylcholine. - Bradykinin.- Shear stress (tangential force of the flowing blood on the endothelial surface of the blood vessel).  Mechanism of action: NO acts on VSMCs (paracrine action) →++ guanylate cyclase enzyme (GC) → ↑ intracellular cyclic guanosine monophosphate (cGMP) → ++ Protein kinase G (PKG) → Vasorelaxation. N.B:  Continuous release of NO is necessary for the maintenance of normal ABP.  ↓↓NO → hypertension.  NO → VD of penile arterioles → erection of the penis. 10  MECHANISM OF ACTION OF NO Stimuli Acetylcholine e-NOS Bradykinin L-arginine (endothelial cells) Shear stress Phosphodiesterase-5 5 GMP Erection Vasodilator-Stimulated Phosphoprotein VD 11 2. ENDOTHELINS (ET):  Types: ET-1: the most potent vasoconstrictor agent yet known. ETA ETB ET-2 is found in the kidneys and intestines. ET-3 is mainly found in the brain.  Receptors: 1. ETA: specific for endothelin-1. 2. ETB: can bind all endothelins.  Stimuli of ET-1 secretion: - Angiotensin II. - Catecholamines. - Vasopressin. -Thrombin. – ROS (Reactive oxygen species).  Inhibitors of ET-1 secretion: - NO. - Prostacyclin (PGI2). - Atrial natriuretic peptide (ANP). 12  ACTIONS OF ENDOTHELIN  Actions: 1. Vasoconstriction of most blood vessels including renal and coronary vessels. ET-1 & ETA receptors (on VSMCs) → + Phospholipase C (PLC)→ ↑ inositol triphosphate (IP3) → Ca2+ influx → VSMCs contraction → VC. 2. Positive inotropic and chronotropic effects. 3. Bronchoconstriction. 4. Increase secretion of renin, aldosterone, and catecholamines. 5. Increase secretion of atrial natriuretic peptides (ANP) and NO (The VD effect of both 13 substances modulates the VC effect of endothelin) via (ETB).  ENDOTHELIN (ET) VD NO Prostacyclin (PGI2) Angiotensin II ANP ANP Catecholamines + - - Vasopressin + Thrombin + ROS (Endothelin converting enzyme) + Catecholamines + RAAS PLC VC +ve Inotropic 14 +ve Chronotropic Bronchoconstriction  SYSTEMIC REGULATION BY HORMONES  Vasoconstrictor hormones:  Vasopressin.  Epinephrine & Norepinephrine.  Angiotensin II.  Vasodilator hormones:  Natriuretic peptides. 15  1. VASOPRESSIN; ANTI DIURETIC HORMONE (ADH)  Secreted from the Supraoptic nucleus (mainly) & Paraventricular nucleus of the hypothalamus where it is released from the posterior pituitary.  Receptors and mechanisms of action: V1 (V1A): acts through G coupled protein → + IP3 → Ca2+ influx. V2: acts through G coupled protein → + AC → + cAMP. V3: (V1B): acts through G coupled protein → + phospholipase to produce prostaglandins from the membrane phospholipids.  Stimuli: Increased plasma osmolarity (1%). Hypovolemia (a decrease of about 10%). 16  FUNCTIONS OF ADH On V 1 receptors in the vascular system→↑↑ intracellular Ca 2 + → vasoconstriction →↑ ABP e.g.: in case of hemorrhage. On V 2 receptors of the late distal tubule (principal cells), cortical collecting tubule & medullary duct via c-AMP → ++ exposure of water channels (aquaporin 2) → ↑↑Water reabsorption & ↓↓urine volume (antidiuresis). On V 3 receptors in the renal vascular system → local production of (prostaglandin E2; vasodilator) to maintain renal perfusion. 17 SECRETION, RECEPTORS AND MECHANISMS OF ACTION OF ADH  ↑↑ Osmolarity (1%) “ Most potent stimulus”  ↓↓ Blood volume (≥10%) V2→ “Mainly” (V1) V3 (V1B) Phospholipase Prostaglandin E2 VD VC 18  2. EPINEPHRINE & NOREPINEPHRINE  Secretion: From adrenal medulla. Postganglionic sympathetic nerves.  Stimuli of secretion: 1. Diffuse sympathetic stimulation (emergency conditions). 2. Stress. 3. Hypoglycemia. 4. Hypovolemia. 5. Exposure to cold.  Vascular effects: - Vasodilation via (β2 receptors) in: Blood vessels in the skeletal muscles and the liver via →↓ Total peripheral resistance (TPR). Coronaries. - Vasoconstriction in almost all organs via α1 receptors. 19  3. RENIN ANGIOTENSIN ALDOSTERONE SYSTEM (RAAS)  It takes 20-30 minutes. + H2O intake ADH Hypovolemia Hypotension Renal ischemia ↓↓ glomerular filtration rate (GFR) PCT Sympathetic stimulation (β1) AT1 AT1 Aminopeptidase A Ang III (100% aldosterone & 40% Ag II) Catecholamines (Medulla) (Cortex) DCT (Principal cells) 20  ACTIONS OF ANGIOTENSIN II  Actions through angiotensin receptor type 1 (AT1):  Peripheral vasoconstriction of arterioles and veins.  Sympathetic stimulation and increased catecholamines secretion from adrenal medulla.  Aldosterone secretion from the adrenal cortex {thus increasing Na+ reabsorption by distal convoluted tubules (DCT) principal cells}.  Stimulates reabsorption of Na+ by direct action on proximal convoluted renal tubules.  Vasopressin secretion to decrease water loss in urine.  Stimulation of thirst center to increase water intake.  Stimulation of cardiac and vascular hypertrophy.  Inhibition of renin secretion (-ve feedback). N.B: - Angiotensin II Aminopeptidase A Angiotensin III (removal of one amino acid). - Angiotensin III has - 100% of the aldosterone stimulating effect. - 40% of the vasoconstrictor effect of angiotensin II. 20  ACTIONS OF ANGIOTENSIN II  Actions through angiotensin receptor type 2 (AT2):  Vasodilation.  Diuresis (increased water excretion by the kidneys).  Natriuresis (increased Na+ excretion by the kidneys).  Apoptosis (programmed cell death).  Two classes of drugs are used to inhibit the RAAS:  Angiotensin-converting enzyme inhibitors (ACEI): (inhibit the conversion of Angiotensin I to Angiotensin II) e.g.: Enalapril, Captopril, Ramipril.  Angiotensin receptor blockers (ARBs) that block the AT1 receptor e.g.: Losartan, Valsartan, Candesartan. 22  NATRIURETIC HORMONES  Types: 1. Atrial natriuretic peptide (ANP) released by atrial myocytes. 2. Brain natriuretic peptide (BNP) released by myocytes of heart ventricles. It is also synthesized in the brain. 3. C-type natriuretic peptide (CNP) present in the vascular endothelial cells of the brain and kidneys (local effect). N.B: The blood level of BNP is a sensitive biomarker of heart failure. 23  NATRIURETIC HORMONES  Stimuli of secretion: - Stretch of atrial muscle fibers: If ↑↑ ECF volume e.g.: ingestion of high-salt diet → ↑ Venous return → ↑ Central venous pressure (CVP). - Raised sodium concentration in extracellular fluid. - Sympathetic stimulation (β2-adrenoceptors). - Angiotensin-II (AT2). - Endothelin (ETB). 24  ACTIONS OF NATRIURETIC HORMONES  Vascular actions: (Vasodilator) 1. Relaxation of the vascular smooth muscles via (↑↑cGMP; same as NO). 2. Inhibition of the vasoconstrictor effects of catecholamines & angiotensin II.  Renal actions: 1. Increase sodium excretion. 2. Inhibition of the conversion of prorenin to renin. 3. Inhibition of the action of aldosterone on the Na+/K+ ATPase.  Adrenal action: 1. Inhibition of aldosterone secretion by the adrenal cortex. N.B: ANP is a counter-regulatory system for the RAAS. “Neutral endopeptidase; NEP” inactivates the natriuretic peptides → So, NEP inhibitors (NEPis) are useful in the treatment of heart failure and hypertension in combination with ACEis or ARBs. 25  ACTIONS OF NATRIURETIC HORMONES (NEPis; used in ttt of HF & HTN) (↑ECF volume or Na+) - - (Β2) “Neutral endopeptidase; NEP” (AT2) Endothelin (ETB) - - - - + c-GMP Catecholamines 26 MECHANISM OF REGULATION OF ARTERIAL BLOOD PRESSURE Regulation of ABP Intermediate Long term Rapid (Nervous) (Minutes-hours) (Seconds) (Days) Cardiac Capillary Pressure Vasomotor inhibitory Stress relaxation fluid shift RAS natriuresis ANP ADH RAAS area mechanism area 27  RAPID NERVOUS REGULATION OF ABP Vasomotor area (VMA or VMC) Cardiac inhibitory area (CIA) Present in medulla Contains medullary neurons that mediate Contains medullary neurons the sympathetic discharge to the blood that mediate the vagal vessels & heart. discharge to the heart. Stimulation of this area leads to: Stimulation of this area 1. Elevation of ABP through: leads to: ↑Arteriolar constriction →↑peripheral ↓HR →↓CO →↓ABP. resistance →↑ABP. Venoconstriction:↑VR→↑CO→↑ABP. 2. ↑HR &↑SV→↑CO→↑ABP. 29  NEURONS OF VMA & CIA RECEIVE IMPULSES FROM: Arterial baroreceptors. Chemoreceptors. Cardio-pulmonary stretch receptors. 29 ARTERIAL BARORECEPTORS (HIGH-PRESSURE RECEPTORS) Site: in the aortic arch (afferent: aortic depressor nerve; branch of vagus) and carotid sinus (afferent: carotid sinus nerve; branch of glossopharyngeal).  Response: At normal mean ABP (90 mm Hg): baroreceptors send tonic inhibitory signals to the VMA and excitatory signals to the CIA. When ABP increases, baroreceptors send more inhibitory signals to the VMA leading to (VD, ↓HR &↓SV) and more excitatory signals to the CIA leading to (↓HR), to decrease the ABP. When ABP decreases, baroreceptors decrease their discharge so, they send less inhibitory signals to the VMA →↑sympathetic stimulation (↑VC, ↑HR & ↑SV) and send less excitatory signals to the CIA leading to (↑HR), to increase the ABP. 30 ARTERIAL BARORECEPTORS (PRESSURE BUFFER SYSTEM) “Aortic depressor nerve” 31  FUNCTIONS OF BARORECEPTORS Arterial baroreceptors Normal ↑↑MAP ↓↓MAP MAP ↑inhibition ↑excitation to ↑↑excitation to cardiac ↑↑inhibition ↓↓inhibition ↓↓excitation to to cardiac to vasomotor to vasomotor cardiac inhibitory vasomotor inhibitory area inhibitory area area area area area VD ↑↑VD VC ↓HR&↓SV ↓HR (↓CO) ↓↓HR&↓↓SV ↓↓HR (↓↓CO) ↑HR&↑SV (↑CO) ↑HR (↑CO) (↓CO) (↓↓CO) Main BP at low normal range ↓↓ BP ↑↑ BP N.B: In chronic HTN, the baroreceptor reflex “ resets” to maintain an elevated rather than normal blood pressure (loss of baroreceptors control; neurogenic HTN). 33  PERIPHERAL CHEMORECEPTORS  Site: Carotid bodies (in the bifurcation of common carotid arteries) & aortic bodies (adjacent to the aorta).  The main stimulus is hypoxia (↓PaO2).  Decreased BP to 40 - 60 mmHg →↓Blood flow to carotid & aortic bodies so they will suffer from hypoxia that will stimulate peripheral chemoreceptors.  Response: Activation of sympathetic VMA & inhibition of CIA → V.C, ↑HR &↑SV (↑ CO) → ↑ABP. N.B: Normal PaO2 = 100 mmHg. 33 PERIPHERAL CHEMORECEPTORS (40 - 60 mm Hg) + + - - 34 CARDIO-PULMONARY STRETCH RECEPTORS  Site: Receptors in the atria, pulmonary artery, and pulmonary veins.  Stimulus: Distension of atria or pulmonary circulation by increased venous return or blood volume.  Response: ↑HR (to get rid of this high blood volume). Vasodilation (VD): to decrease the blood pressure (↓BP). Hyperventilation (to oxygenate this extra volume of blood). 35 INTERMEDIATE TERM REGULATION OF ABP 1. Stress relaxation. 2. Capillary fluid shift mechanism. 3. Activation of the renin-angiotensin system (RAS); discussed before. 36 INTERMEDIATE TERM REGULATION OF ABP 1- Stress relaxation: 2- Capillary fluid shift mechanism: A sudden increase in blood volume (i.v fluids)→ ↑Blood volume→↑BP will ↑ capillary hydrostatic initial increase in BP will cause relaxation of the pressure which favors more filtration, so, it will ↓ blood vessels (VD), which will decrease the BP venous return→↓CO→↓BP, and vice versa. again to normal. 37  LONG TERM REGULATION OF ABP 1. Renal pressure natriuresis. 2. Atrial natriuretic peptide secretion (discussed before). 3. ADH secretion (discussed before). 4. Activation of RAAS (discussed before). 38  LONG TERM REGULATION OF ABP 1. Renal pressure natriuresis: is the basic, very powerful & most important mechanism. a. ↑ABP→↓renin secretion from the juxtaglomerular apparatus (JGA) →↓angiotensin II→↑renal excretion of Na + & H 2 O→↓ECF→↓VR → ↓CO→↓ABP. b. Downregulation of Na + -H + ATPase and Na + - K + ATPase in proximal convoluted tubules →↓reabsorption of Na+. It continues until ABP returns to normal. 39 RENAL PRESSURE NATRIURESIS ↓Renin ↓Ang II & ↓aldosterone 40 Urine  CONCLUSIONS: Most tissues can control their local blood flow in proportion to their specific metabolic needs. The sympathetic nervous system plays a major role in the short-term regulation of ABP. RAAS upregulation is highly essential in controlling hypotension. The kidneys play a major role in the long-term regulation of ABP. Renal pressure natriuresis is the most important mechanism controlling ABP in the case of HTN. Uncontrolled HTN may lead to renal failure. 42  REFERENCES: G U Y T O N A N D H A L L T E X T B O O K O F M E D I C A L PHYSIOLOGY, 13 th edition Unit IV: Chapter 17-19 pages 195- 243. ISBN: 978-1-4557-7005-2. Ganong’s Review of Medical Physiology. A LANGE medical book. 26th edition, section V: Chapter 32, pages 1333- 1362. ISBN: 978-0-07-184897-8. 42  BCS-MCQ: A group of investigators is studying hemodynamic regulatory mechanisms in a human volunteer subject. The volunteer is administered a stimulant drug and a sudden increase in blood pressure is observed. It is hypothesized that the increase in blood pressure causes stretching of the atria. Increased atrial stretch would most likely lead to which of the following changes? A. Increased excretion of potassium and hydrogen ions B. Vasodilation and decreased platelet aggregation C. Decreased reabsorption of sodium D. Increased reabsorption of solute-free water E. Vasoconstriction and stimulation of thirst 43  BCS-MCQ: A 55-year-old man comes to the physician for the evaluation of recurrent headaches over the past 6 months. The patient states that his headaches are worse in the mornings. He also reports several episodes of dizziness and blurry vision. He has a history of type 2 diabetes mellitus. He has smoked one pack of cigarettes daily for the past 30 years. His only medication is metformin. His blood pressure is 160/90 mm Hg. Physical examination shows no abnormalities. Laboratory studies are within normal limits. Two weeks later, the patient's blood pressure is 155/90 mm Hg in both arms. Treatment with losartan has begun. Which of the following is the most likely effect of his new medication? A. A B. B C. C D. D E. E F. F https://next.amboss.com/us/questions/yBA6dWmnc/1 44 Thank You 45