1. REGULATION OF BLOOD PRESSURE DR. MAGDI AWAD SASI MAGDI AWAD SASI 2018 LIMU

2. Objectives MAGDI AWAD SASI 2018 LIMU

3. Blood Pressure Contraction of ventricles generates blood pressure Systolic BP – highest pressure attained in arteries during systole Diastolic BP – lowest arterial pressure during diastole Pressure falls progressively with distance from left ventricle Blood pressure also depends on total volume of blood MAGDI AWAD SASI 2018 LIMU

4. Arterial blood pressure It is the lateral pressure of the blood exerted on the arterial wall. The systolic blood pressure is the maximum pressure reached during ventricular systole ranges from 90 - 140 mmHg with average 120 mmHg. the diastolic blood pressure is the minimal pressure reaches in the arteries during the cardiac diastole, ranges from 60 - 90 mmHg with an average value of 80 mmHg. MAGDI AWAD SASI 2018 LIMU

5. Arterial Blood Pressure (continued) ■ Diastolic pressure is more important, because diastolic period is longer than the systolic period in the cardiac cycle. ■ Pulse pressure = Systolic BP – Diastolic BP. ■ Mean arterial pressure = Diastolic BP + 1/3 Pulse press. In normal adult  120/80 mmHg. MAGDI AWAD SASI 2018 LIMU

6. If the blood pressure drops suddenly, 2 problems confronts the pressure control system : 1-The first if Survival : To return the arterial pressure immediately to near a normal level that the person can live trough the acute episode. 2-The second is to return the blood volume eventually to its normal level : So that the circulatory system can re-establish full normality Including return of the arterial pressure back to its normal value. MAGDI AWAD SASI 2018 LIMU

7. Control of blood pressure BP = CO x TPR (compare Ohm’s law) Cardiac output is controlled by sympathetic and para sympathetic nerves which effect: heart rate force of contraction TPR controlled by nervous and chemical means to effect constriction/dilatation of arterioles and venules MAGDI AWAD SASI 2018 LIMU

8. DETERMINANTS OF ARTERIAL BLOOD PRESSURE MAGDI AWAD SASI 2018 LIMU

9. Q) What are the factors that maintain the ABP? ABP = COP x TPR = SV x HR x TPR 1. Stroke volume: 2. Heart rate 3. TPR MAGDI AWAD SASI 2018 LIMU which depend on : a-Arteriolar diameter. b-The blood viscosity. c-The blood volume. d-Elasticity of aorta and big arteries which prevent excessive elevation of the systolic pressure maintain the diastolic BP by its elastic recoil.

10. FACTORS CONTRIBUTING TO BLOOD PRESSURE 1 Cardiac output-VR,HR,FOC—S.P 2. PERIPHERAL RESISTANCE Elasticity Viscosity Velocity Length of BV Extra vascular compression Radius of BV DP MAGDI AWAD SASI 2018 LIMU

12. REGULATION OF ARTERIAL BLOOD PRESSURE Immediate mechanism Short term mechanism Long term mechanism

13. Immediate Immediate Regulatory Mechanisms: Neural mechanisms 1.Baro-receptor reflexes 2. Chemo receptor reflexes 3. Cerebral ischemic response MAGDI AWAD SASI 2018 LIMU

14. VCC (in M.O) LHC VMC VDC --- +++ Cardiac centres CAC CIC Heart and blood vessels

15. MAGDI AWAD SASI 2018 LIMU VCC (in M.O) LHC VMC VDC --- +++ Cardiac centres CAC CIC Heart and blood vessels sympathetic Vagal stimulation Pressor area Depressor area

16. Brain stem cardiovascular centers Localized in reticular formation of medulla and lower 1/3 of the Pons. Information from IX and X nerves is integrated in nucleus tractus solitaries and redirected to: A. Cardiac accelerator center – SNS – SA node (increase heart rate, conduction velocity through the AV node, contractility) B. Cardiac decelerator center – PNS – n. vagus – SA node – decrease heart rate C. Vasoconstrictor center – SNS – vasoconstriction of arterioles and venules MAGDI AWAD SASI 2018 LIMU

17. Role of cardiovascular center (CV) Site ---In medulla oblongata Action ---Helps regulate heart rate and stroke volume Divisions----- a. Cardio-stimulatory and cardio-inhibitory centers b. Vasomotor center control blood vessel diameter Contents---Groups of neurons regulate heart rate, contractility of ventricles, and blood vessel diameter Also controls neural, hormonal, and local negative feedback systems that regulate blood pressure and blood flow to specific tissues Receives input from both higher brain regions and sensory receptors MAGDI AWAD SASI 2018 LIMU

18. Brain stem regions of CV control Area postrema Nucleus tractus solitarius Nucleus ambiguous Cardiac decelerator center Caudal ventrolateral Medulla Fibers from this neurons project to the vasoconstrictor area and inhibit it MAGDI AWAD SASI 2018 LIMU

19. CV Center MAGDI AWAD SASI 2018 LIMU

20. Control of blood pressure Outline Short term control (baroreceptors) Location Types of baroreceptor Baroreceptor reflex Other stretch receptors Long-term control Renin/ angiotensin/ aldosterone system Vasopressin Atrial natiuretic peptide MAGDI AWAD SASI 2018 LIMU

21. Baroreceptors Baroreceptors are mechanoreceptors – sensitive to changes in pressure or stretch located within the walls of the carotid sinus and the aortic arch Located in highly distensible regions of the circulation to maximise sensitivity – Carotid sinus - afferent IX. C.N. – Aorctic arch – (increase in arterial pressure) X. C.N. – cardiovascular vasomotor centers in the brain stem Baroreflex - fast regulation – via changes in the output of sympathetic and parasympathetic NS MAGDI AWAD SASI 2018 LIMU

22. Baroreceptors reflex: MAGDI AWAD SASI 2018 LIMU  BP + Baroreceptors = V.M.C++ C.I.C = Sympathetic Vasodilatation &  TPR + Parasympathetic Slowing of SA node (  HR) &  CO

23. Increase in ABP decreased sympathetic outflow Decrease of heart rate Increased parasymp. outflow Stimulation of NTS Activation of baroreceptors Increase firing rate in IX., X. vasodilatation decrease of heart rate contractility Increased activity of NA Decreased activity CAC Decreased activity VC CAC - cardiac accelerator center, VC – vasoconstrictor center cardiac decelerator center MAGDI AWAD SASI 2018 LIMU

24. BARO RECEPTOR REFLEXES (MAREY’S REFLEXES) BP  Stimulation of baroreceptors (carotid sinus and aortic arch)  Tractus solitarius stimulation Inhibition of VMC Stimulation of CIC (nucleus ambiguous) SNS Vagus  Symp tone Vagal tone  Blood Vessels Heart Rate Decreased - Vasodilatation - Venodilatation Bradycardia BP MAGDI AWAD SASI 2018 LIMU

25. Net effect  Peripheral resistance  Myocardial contractility  Heart rate (Bradycardia)  Fall in BP BARORECEPTOR REFLEX MAGDI AWAD SASI 2018 LIMU

26. Baroreceptor output (from single fibres) MAGDI AWAD SASI 2018 LIMU Rapid decrease in mean pressure Rapid increase in mean pressure Response to pulse pressure

27. Two types of baroreceptor Type A High sensitivity High firing rate Type C Lower sensitivity Lower firing rate Higher threshold (before firing starts) Therefore can deal with higher pressures than type A which become “saturated” MAGDI AWAD SASI 2018 LIMU From “An Introduction to Cardiovascular Physiology” J.R. Levick

28. Baroreceptor reflex MAGDI AWAD SASI 2018 LIMU Blood pressure falls Aortic arch Carotid sinus Constriction of veins & arterioles Increased stroke volume Increased heart rate Increased heart rate Vasoconstriction Cardiac stimulation Cardiac inhibition Nucleus tractus solitarius Increased peripheral resistance Increased cardiac output Increased blood pressure Neural integration Sensors Effectors

29. Rapidly Acting Control Mechanisms: Acts within. seconds / minutes. [ Fast Response ( S h o r t - T e r m ) ] Concerned by regulating Cardiac output & Peripheral resistance. Reflex mechanisms that act through autonomic nervous system: Centers in medulla oblongata: Vasomotor Center (VMC) … Sympathetic nervous system. Cardiac Inhibitory Center (CIC).. Parasympathetic nervous system MAGDI AWAD SASI 2018 LIMU

30. Effects of Rapidly Acting Pressure Control Mechanisms : 1.To cause constriction of the veins and provide transfer of blood into the heart. 2. To cause increased heart rate and contractility of the heart and provide greater pumping capacity by the heart. 3. To cause constriction of the peripheral arterioles to impede the flow of the blood out of the arteries. All these effects occur almost instantly to raise the arterial pressure back into a survival range MAGDI AWAD SASI 2018 LIMU

31. Other stretch receptors Coronary artery baroreceptors Respond to arterial pressure but more sensitive than carotid and aortic ones Veno-atrial mechanoreceptors Respond to changes in central blood volume Lie down, lift your legs and cause peripheral vasodilatation Unmyelinated mechanoreceptors Respond to distension of heart Ventricular ones during systole; atrial ones during inspiration MAGDI AWAD SASI 2018 LIMU

32. Location of receptors in and near the heart MAGDI AWAD SASI 2018 LIMU From “An Introduction to Cardiovascular Physiology” J.R. Levick Spinal cord Baroreceptors in coronary arteries and aortic arch Sympathetic afferents & unmyelinated nociceptors Cardiac pain Nucleus tractus solitarius Cardiac vagal afferents unmyelinatedmyelinated

33. Overview of short-term control mechanisms MAGDI AWAD SASI 2018 LIMU From: Introduction to Cardiovascular physiology. J.R. Levick. Arnold 4th edition

34. MAGDI AWAD SASI 2018 LIMU

35. Importance of the baroreceptor reflex : To keep the arterial pressure relatively constant in the rang of (70 mmHg -150 mmHg ), maintain the mean blood pressure at about 100 mmHg Pressure buffer system – reduce the blood fluctuation during the daily events, such as changing of the posture Baroreceptor Resetting : Baroreceptor will adapt to the long term change of blood pressure. If the blood pressure is elevated for a long period of time, several days or years, the set point will transfer to the elevated mean blood pressure. That makes the baroreceptor system unimportant for long-term regulation of arterial pressure. MAGDI AWAD SASI 2018 LIMU

36. Baroreceptor Reflex Mechanism During Changes in Body Posture Immediately on standing, Arterial pressure in the head & upper part of the body tends to fall,cause loss of consciousness. Falling pressure at the baroreceptors elicits an immediate reflex,resulting in strong sympathetic discharge throughout the body. This minimizes the decrease in pressure in the head & upper body Denervation of the baroreceptors can lead to paroxysmal hypertension. “ MAGDI AWAD SASI 2018 LIMU

37. CHEMORECEPTORS Chemoreceptors reflex > work with baroreceptors only in the situation of low blood pressure “it doesn’t work if the blood pressure is high” “in case of emergency, such as hemorrhage, ischemia” MAGDI AWAD SASI 2018 LIMU

38.  BP <60 mm Hg Hypoxia Chemoreceptors NTS Respiratory centre CIC VMC stimulation N ambiguus Vagus SNS action  Vagaltone Net effect  Pulmonary ventilation,  BP,  Heart rate Chemo receptor reflexes MAGDI AWAD SASI 2018 LIMU

40. Stimulation of chemoreceptors leads to a reflex increase in vasomotor tone which causes generalized vasoconstriction and hence a rise in blood pressure. Chemoreceptor mechanism is important in regulation of blood pressure when it fall below the range in which baroreceptors act (70 mmHg). Chemoreceptor reflex is useful in regulation of blood pressure when it falls to a level between (40 and 70 mmHg). But if the blood pressure below 40 mmHg, the last ray of hope for survival is the central nervous system (CNS) ischemia response. So it sometimes called the “last ditch stand” pressure control mechanism. MAGDI AWAD SASI 2018 LIMU

41. CNS Ischemic Response “Last ditch stand” pressure control mechanism It is not one of the normal mechanisms for regulating ABP. It acts rapidly & very powerfully whenever blood flow to the brain ↓ dangerously close to the lethal level. It operates principally as an emergency pressure control system to prevent further decrease in arterial pressure. Local concentration of CO2 ↑ greatly. This has an extremely potent effect in stimulating the sympathetic vasomotor nervous control areas in the brain’s medulla. MAGDI AWAD SASI 2018 LIMU

42.  BP < 40 mm Hg (or)  Intracranial pressure Cerebra ischaemia Cerebral hypoxia Direct effect on VMC SNS action  Vasoconstriction Cerebral Ischaemic Response  BP with reflex bradycardia Cushing’s Reflex MAGDI AWAD SASI 2018 LIMU

43. Delayed or Intermediate Mechanism Renin –Angiotensin System Whenever there is a fall in B.P, there is a decrease in the blood flow to the kidney. This results is ischaemic kidney. Renin is released from J.G. cells Renin Angiotensin Angiotensin I ACE Angiotensin I Angiotensin II ACE - Angiotensin Converting Enzyme ( Present in the lungs) MAGDI AWAD SASI 2018 LIMU

44. Stress Relaxation Phenomenon:  BP Blood vessels are stretched Stress relaxation Increased capacity Decreased effective blood volume BP decreased relaxation  BP MAGDI AWAD SASI 2018 LIMU

45. Long term Regulatory Mechanisms: All the mechanisms that tend to alter the blood volume participate in Long term regulatory mechanisms MAGDI AWAD SASI 2018 LIMU

46. Atrial natriuretic peptide (ANP) Released by cells of atria Released in response to stimulation of atrial receptors Increases salt excretion via kidneys By reducing water reabsorption in the collecting ducts relaxes renal arterioles inhibits sodium reabsorption in the distal tubule Lowers blood pressure by causing vasodilation and promoting loss of salt and water in urine Reduces blood volume MAGDI AWAD SASI 2018 LIMU

47. Renal –body fluid system:  ECF or Blood volume -  BP B.P is brought back to the normal level  ECF or Blood volume -  BP B.P is slowly raised to the normal level.  GFR  urine output  GFR BP  urine output MAGDI AWAD SASI 2018 LIMU

48. HORMONAL REGULATIONS 1 ) Catecholamines 2) Mineralocorticocoid 3) Glucocorticoid 4) Thyroxine 5) ADH 6) Atrial Natriuretic Factor 7) Nitric Oxide 8) Histamine 9) Angiotensin 10) Serotonin

49. Autoregulation of blood pressure Ability of tissue to automatically adjust its blood flow to match metabolic demands Demand of O 2 and nutrients can rise tenfold during exercise in heart and skeletal muscles Also controls regional blood flow in the brain during different mental and physical activities 2 general types of stimuli 1. Physical – temperature changes, myogenic response 2. Vasodilating and vasoconstricting chemicals alter blood vessel diameter MAGDI AWAD SASI 2018 LIMU

50. Relationship between Pressure, Flow, and Resistance F=ΔP/R Flow (F) through a blood vessel is determined by: 1) The pressure difference (Δ P) between the two ends of the vessel 2) Resistance (R) of the vessel MAGDI AWAD SASI 2018 LIMU

51. Laplace’s Law: Myogenic mechanism MAGDI AWAD SASI 2018 LIMU TENSION = PRESSURE X RADIUS (dynes/cm) (dynes/cm 2 ) (cm) PRESSURE TENSION RADIUS (to maintain tension constant)

52. Vasodilator Theory for Blood Flow Control Local Vasodilators: Adenosine, CO2, Lactic acid, ADP compounds, Histamine, K + ions, H + ions, Prostacyclin, Bradykinin, and Nitrous oxid (NO) MAGDI AWAD SASI 2018 LIMU TISSUE METABOLISM BLOOD FLOW ARTERIOLE RESISTANCE RELEASE OF VASODILATORS

53. Arteriole Resistance: Control of Local Blood Flow MAGDI AWAD SASI 2018 LIMU

54. Humoral Regulation of Blood Flow Vasoconstrictors Norepinephrine and epinephrine Angiotensin Vasopressin Endothelin Vasodilator agents Bradykinin Serotonin Histamine Prostaglandins Nitric oxide MAGDI AWAD SASI 2018 LIMU

55. Blood Flow: Brain Blood flow to the brain is constant, as neurons are intolerant of ischemia Metabolic controls – brain tissue is extremely sensitive to declines in pH, and increased carbon dioxide causes marked vasodilation Myogenic controls protect the brain from damaging changes in blood pressure Decreases in MAP cause cerebral vessels to dilate to insure adequate perfusion Increases in MAP cause cerebral vessels to constrict MAGDI AWAD SASI 2018 LIMU