The Cardiovascular System: Blood Vessels and Hemodynamics. E. Göran Salerud

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1 The Cardiovascular System: Blood Vessels and Hemodynamics E. Göran Salerud

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3 The main vessels branch into smaller vessels that collectively always have a greater cross sectional area than the parent vessels.

4 Hemodynamics: Factors affecting blood flow Blood flow volume of blood that flows through any tissue in a given period of time (in ml/min) Total blood flow is cardiac output (CO) Volume of blood that circulates through systemic (or pulmonary) blood vessels each minute CO = heart rate (HR) x stroke volume (SV) Distribution of CO depends on Pressure differences that drive blood through tissue Flows from higher to lower pressure Resistance to blood flow in specific blood vessels Higher resistance means smaller blood flow Copyright 2009, John Wiley & Sons, Inc.

5 Physical Laws Describing Blood Flow Blood flows through vascular system when there is pressure difference (ΔP) at its two ends Flow rate is directly proportional to difference (ΔP = P 1 - P 2 )

6 Physical Laws Describing Blood Flow Flow rate is inversely proportional to resistance Flow = ΔP/R Resistance is directly proportional to length of vessel (L) & viscosity of blood (η) Inversely proportional to 4 th power of radius Therefore diameter of vessel is very important for resistance Poiseuille's Law describes factors affecting blood flow Blood flow = Δ Pr 4 π 8ηL

7 Regulation of Circulation Control arterial blood pressure deliver blood to brain* and heart* supply blood to other organs of the body control capillary pressure and interstitial fluid composition Central Cardiovascular Circulation Microcirculation

8 Role of cardiovascular center (CV) In medulla oblongata Helps regulate heart rate and stroke volume Also controls neural, hormonal, and local negative feedback systems that regulate blood pressure and blood flow to specific tissues Groups of neurons regulate heart rate, contractility of ventricles, and blood vessel diameter Cardiostimulatory and cardioinhibitory centers Vasomotor center control blood vessel diameter Receives input from both higher brain regions and sensory receptors Copyright 2009, John Wiley & Sons, Inc.

9 CV Center Copyright 2009, John Wiley & Sons, Inc.

10 Central Cardiovascular System Medullary Cardiovascular Center integrate messages from receptors in the body chemoreceptors - CO 2, O 2 and ph. mechanoreceptors - lung inflation, somatic. thermoreceptors - temperature receptors baroreceptors - blood pressure brain

11 Autonomic Nervous Control Sympathetic fight or flight system increase in arterial blood pressure & cardiac output Parasympathetic vegetative functions drop in arterial blood pressure & cardiac output

12 Arterial Baroreceptors Sites Carotid sinus* Aortic arch Subclavian Common carotid * Pulmonary arteries

13 Carotid Sinus Baroreceptors Response to decrease blood pressure (sympathetic disinhibition) vasoconstriction increases heart rate stronger contractions Cardiac Output Arterial Pressure

14 Arterial Baroreceptors Response to increased blood pressure (sympathetic inhibition vasodilation decreases heart rate Cardiac Output weaker contractions Arterial Pressure

15 Arterial Chemoreceptors Located in the carotid and aortic bodies regulate ventilation regulate cardiovascular system BLOOD CO 2 O 2, ph * If the animal is not breathing CHEMORECEPTOR Increase discharge frequency* P. Vasoconstriction Heart Rate

16 Cardiac Receptors Mechanoreceptors & Chemoreceptors heart spinal cord medullary cardiovascular center other parts of the brain stimulation may modify hormone release reflex responses heart rate cardiac contractility pain

17 Atrial Receptors: Mechanoreceptors Myelinated afferent fibers A-type: respond to heart rate changes B-type: respond to increases in rate filling and volume Unmyelinated afferent fibers C-type: affects both heart rate and heart volume located at the junction between veins and atria

18 Ventricular Receptors Myelinated sensory afferent fibers Chemoreceptors Bradykinin (peptide vessel dilate) stimulation ~ sympathetic output ~ contractility and blood pressure stimulation ~ perception of pain in the heart

19 Neural regulation of blood pressure Negative feedback loops from 2 types of reflexes Baroreceptor reflexes Pressure-sensitive receptors in internal carotid arteries and other large arteries in neck and chest Carotid sinus reflex helps regulate blood pressure in brain Aortic reflex regulates systemic blood pressure When blood pressure falls, baroreceptors stretched less, slower rate of impulses to CV CV decreases parasympathetic stimulation and increases sympathetic stimulation Copyright 2009, John Wiley & Sons, Inc.

20 Hormonal regulation of blood pressure Renin-angiotensin-aldosterone (RAA) system Epinephrine and norepinephrine Antidiuretic hormone (ADH) or vasopressin Copyright 2009, John Wiley & Sons, Inc.

21 Structure and function of blood vessels 5 main types Arteries carry blood AWAY from the heart Arterioles (muscular + regular) Capillaries site of exchange Venules (muscular + regular) Veins carry blood TO the heart Copyright 2009, John Wiley & Sons, Inc.

22 Basic structure 3 layers or tunics 1. Tunica interna (intima) 2. Tunica media 3. Tunica externa Modifications account for 5 types of blood vessels and their structural/ functional differences Copyright 2009, John Wiley & Sons, Inc.

23 Copyright 2009, John Wiley & Sons, Inc.

24 Structure Tunica interna (intima) Inner lining in direct contact with blood Endothelium continuous with endocardial lining of heart It consists of an inner endothelium (simple squamous epithelium) and a basement membrane. Active role in vessel-related activities Tunica media Muscular and elastic connective tissue layer Greatest variation among vessel types Smooth muscle regulates diameter of lumen Tunica externa Elastic and collagen fibers Vasa vasorum Helps anchor vessel to surrounding tissue forms a protective layer Copyright 2009, John Wiley & Sons, Inc.

25 Arteries 3 layers of typical blood vessel Thick muscular-to-elastic tunica media High compliance walls stretch and expand in response to pressure without tearing The functional properties of arteries are elasticity and contractility 1. Elasticity, due to the elastic tissue in the tunica internal and media, allows arteries to accept blood under great pressure from the contraction of the ventricles and to send it on through the system. 2. Contractility, due to the smooth muscle in the tunica media, allows arteries to increase or decrease lumen Vasoconstriction decrease in lumen diameter Vasodilation increase in lumen diameter Copyright 2009, John Wiley & Sons, Inc.

26 21_01d

27 Elastic Arteries Largest arteries Largest diameter but walls relatively thin Function as pressure reservoir Help propel blood forward while ventricles relaxing Also known as conducting arteries conduct blood to medium-sized arteries Copyright 2009, John Wiley & Sons, Inc.

28 Arteries Muscular arteries Tunica media contains more smooth muscle and fewer elastic fibers than elastic arteries Walls relatively thick Capable of great vasoconstriction/ vasodilatation to adjust rate of blood flow Also called distributing arteries Anastomoses Union of the branches of 2 or more arteries supplying the same body region Provide alternate routes collateral circulation Copyright 2009, John Wiley & Sons, Inc.

29 Arterioles Abundant microscopic vessels Metarteriole has precapillary sphincter which monitors blood flow into capillary Sympathetic innervation and local chemical mediators can alter diameter and thus blood flow and resistance Resistance vessels resistance is opposition to blood flow Vasoconstriction can raise blood pressure Copyright 2009, John Wiley & Sons, Inc.

30 Arterioles Mechanisms involved in adjus1ng arteriolar resistance Vasoconstric.on Refers to narrowing of a vessel Vasodila.on Refers to enlargement in circumference and radius of vessel Results from relaxa1on of smooth muscle layer Leads to decreased resistance and increased flow through that vessel

31 Arteriolar Vasoconstric.on and Vasodila.on

32 Mechanisms for control of arteriolar radius /blood flow to the various organs Blood flow to organ depends on the demands of each organ. a) Local(intrinsic) control of blood flow is the primary mechanism that matches the blood flow to the metabolic needs of the organ (imp in determining distribu1on of cardiac out put). b) Neural or Hormonal(extrinsic) control is important in blood pressure regula1on.

33 Local(intrinsic) control of Arteriolar radius Only blood supply to brain remains constant Changes within other organs alter radius of vessels and adjust blood flow to organ Local chemical influences on arteriolar radius Local metabolic changes Histamine release Local physical influences on arteriolar radius Local application of heat or cold Chemical response to shear stress Myogenic response to stretch

34 Local chemical influences on arteriolar radius Following specific local metabolic factors are produce in the tissue as results of metabolic activity,produces relaxation of arteriolar smooth muscle Decreased O 2 Increased CO 2 Increased acid Increased K + Increased osmolarity These Adenosine factors release produces relaxation od arteriolar smooth muscles Prostaglandin by acting release on vascular endothelium

35 Role of endothelial cells Release chemical mediators(vasoac1ve substances) that play key role in locally regula1ng arteriolar caliber Endothelial cells Release locally ac1ng chemical messengers in response to chemical changes as a result of metabolic ac1vity in their environment. Among best studied local vasoac1ve mediators is nitric oxide (NO), a potent vasodialotor

36 Capillaries Capillaries Smallest blood vessels connect arterial outflow and venous return Microcirculation flow from metarteriole through capillaries and into postcapillary venule Exchange vessels primary function is exchange between blood and interstitial fluid Lack tunica media and tunica externa Substances pass through just one layer of endothelial cells and basement membrane Capillary beds arise from single metarteriole Vasomotion intermittent contraction and relaxation Thoroughfare channel bypasses capillary bed Copyright 2009, John Wiley & Sons, Inc.

37 Types of Capillaries Capillaries are grouped according to their leakiness nm holes nm holes nm holes Most common Found in intestine, kidney, glands, choroid plexus. Liver sinusoids

38 Arterioles Capillaries Venule Pre capillary sphincter is present at the junction where the capillary arises from the Meta arteriole. This opens and closes the entrance of capillary and hence regulates the blood flow through the capillary. The capillary wall is thin & consists of a single layer of endothelial cells on basement membrane. Pores are present between the endothelial cells that allow transport of substances including water.

39 Arterioles Capillaries Venule Copyright 2009, John Wiley & Sons, Inc.

40 Venules Thinner walls than arterial counterparts Postcapillary venule smallest venule Form part of microcirculatory exchange unit with capillaries Muscular venules have thicker walls with 1 or 2 layers of smooth muscle Copyright 2009, John Wiley & Sons, Inc.

41 Veins Structural changes not as distinct as in arteries In general, very thin walls in relation to total diameter Same 3 layers Tunica interna thinner than arteries Tunica interna thinner with little smooth muscle Tunica externa thickest layer Not designed to withstand high pressure Valves folds on tunica interna forming cusps Aid in venous return by preventing backflow Copyright 2009, John Wiley & Sons, Inc.

42 Venous Valves Copyright 2009, John Wiley & Sons, Inc.

43 Relative proportions of elastic fibers, smooth muscle, collagen, and endothelial cells. 13-fold 5-fold

44 Blood Distribution Largest portion of blood at rest is in systemic veins and venules Blood reservoir Venoconstriction reduces volume of blood in reservoirs and allows greater blood volume to flow where needed Copyright 2009, John Wiley & Sons, Inc.

45 Control of Microcirculation Meet the demands of tissues Would variations in capillary blood flow be greater in skeletal muscle or brain tissue?

46 What it looks like

47 The Microcirculation and Its Control Arterioles µm diameter, muscular walls innervated by the sympathetic nervous system. The terminal arterioles give rise to a cluster of capillaries. They have few vasomotor nerves and muscle tone is controlled by local metabolites. In a few tissues (mesentery) there is a ring of Smooth muscle at the capillary entrance pre-capillary sphincter.

48 The Microcirculation and Its Control Arteriovenous anastomoses bypass the capillary network in the extremities and are involved in temperature regulation. The capillaries 5-8µm diameter vary in length 500 to 1000µm and unite to form post-capillary venules. Smooth muscle reappears in the walls of venules of about µm diameter. Because of the large cross-sectional area of capillary bed, 800x aorta, flow velocity is very low, allowing for exchange. Only a small fraction of the capillaries is open.

49 Control of Microcirculation Nervous Control sympathetic parasympathetic Local Control endothelium-produced compounds inflammatory and other mediators metabolic conditions

50 Nervous Control Adjust resistance to blood flow in the peripheral circulation to regulate arterial pressure priority system -- brain and heart are top priority What would happen to arterial pressure if all the capillaries had low resistance?

51 Nervous Control Sympathetic stimulation norepinephrine (directly from nerve endings) act via smooth muscle α-adrenoreceptors of arterioles peripheral vasoconstriction & rise in arterial blood pressure Decrease Capillary Blood Flow

52 Nervous Control Sympathetic stimulation [ ] Epinephrine (circulating catecholamines) act via smooth muscle β-adrenoreceptors of arterioles peripheral vasodilation and a rise in arterial blood pressure [ ] Epinephrine (circulating catecholamines) act via smooth muscle a-adrenoreceptors of arterioles peripheral vasoconstriction & increase in arterial blood pressure

53 Nervous Control Parasympathetic stimulation Innervate arterioles in brain and lungs Acetylcholine (ACh) vasodilation in arterioles

54 Control of Microcirculation Local Control endothelium-produced compounds inflammatory and other mediators metabolic conditions

55 Control of Microcirculation Endothelium-produced compounds nitric oxide relaxation of vascular smooth muscle stimulated by Ca 2+, ACh, ATP, hypoxia. endothelins vasoconstrictive proteins Prostacyclin vasodilation and anticoagulant

56 Control of Microcirculation Inflammation and other mediators histamine - tissue edema causes localized vasodilation following injury increase in capillary permeability vasodilators active at sites of injury histamine - promote filtration plasma kinins vasoconstrictors angiotensin II - promote absorption of fluid into the blood

57 Control of Microcirculation Inflammation and other mediators vasodilators active at sites of injury histamine - promote filtration plasma kinins vasoconstrictors angiotensin II - promote absorption of fluid into the blood

58 The function of the circulatory system is to maintain an optimal environment for cellular viability. This is achieved by control of nutritive, waste, and hormonal concentrations, gas tension, and temperature. As the demands of the body are both continuous and variable it needs: Continuous flow Variable amount Variable distribution What we are describing is TRANSPORT which is achieved via: Circulation of blood in a closed system of vessels and Exchange of materials between blood and extravascular tissue 10/10/14

59 Capillary exchange Movement of substances between blood and interstitial fluid 3 basic methods 1. Diffusion 2. Transcytosis 3. Bulk flow Copyright 2009, John Wiley & Sons, Inc.

60 Diffusion Most important method Substances move down their concentration gradient O 2 and nutrients from blood to interstitial fluid to body cells CO 2 and wastes move from body cells to interstitial fluid to blood Can cross capillary wall through intracellular clefts, fenestrations or through endothelial cells Most plasma proteins cannot cross Except in sinusoids proteins and even blood cells leave Blood-brain barrier tight junctions limit diffusion Copyright 2009, John Wiley & Sons, Inc.

61 Oxygen, CO 2, small solutes, nutrients move across capillaries primarily through diffusion. Concentration gradient Electrochemical Fluid or water moves across capillary membranes through convection. Hydrostatic and Osmotic pressure

62 Transcytosis Small quantity of material Substances in blood plasma become enclosed within pinocytotic vesicles that enter endothelial cells by endocytosis and leave by exocytosis Important mainly for large, lipid-insoluble molecules that cannot cross capillary walls any other way Copyright 2009, John Wiley & Sons, Inc.

63 Bulk Flow Passive process in which large numbers of ions, molecules, or particles in a fluid move together in the same direction Based on pressure gradient Diffusion is more important for solute exchange Bulk flow more important for regulation of relative volumes of blood and interstitial fluid Filtration from capillaries into interstitial fluid Reabsorption from interstitial fluid into capillaries Copyright 2009, John Wiley & Sons, Inc.

64 NFP = (BHP + IFOP) (BCOP + IFHP) Net filtration pressure (NFP) balance of 2 pressures promote filtration Blood hydrostatic pressure (BHP) generated by pumping action of heart Falls over capillary bed from 35 to 16 mmhg Interstitial fluid osmotic pressure (IFOP) 1 mmhg Copyright 2009, John Wiley & Sons, Inc.

65 NFP = (BHP + IFOP) (BCOP + IFHP) Net filtration pressure (NFP) balance of 2 pressures promote reabsorption Blood colloid osmotic pressure (BCOP) promotes reabsorption Due to presence of blood plasma proteins to large to cross walls Averages 36 mmhg Interstitial fluid hydrostatic pressure (IFHP) Close to zero mmhg Copyright 2009, John Wiley & Sons, Inc.

66 Starling s Law Nearly as much reabsorbed as filtered At the arterial end, net outward pressure of 10 mmhg and fluid leaves capillary (filtration) At the venous end, fluid moves in (reabsorption) due to -9 mmhg On average, about 85% of fluid filtered in reabsorpbed Excess enters lymphatic capillaries (about 3L/ day) to be eventually returned to blood Copyright 2009, John Wiley & Sons, Inc.

67 Starling s Law of the Capillary P c = hydrostatic pressure of capillary π c = protein (oncotic) pressure of capillary P i = hydrostatic pressure of interstitial fluid π i = protein osmotic (oncotic) pressure of the interstitial fluid K f = filtration coefficient Net movement out of capillary into interstitium (ml/min) FLOW net = K f (P c P i ) (π c π i ) Basically, movement is governed by (hydrostatic pressure protein (oncotic) pressure) P c π c = 35 mmhg = 28 mmhg A P c π c V P c π c = 15 mmhg = 28 mmhg P i = -2 mmhg P i = -2 mmhg π i = 3 mmhg π i = 3 mmhg Net = +12 mmhg Filtration P i π i Absorption Net = -8 mmhg

68 Vascular resistance Opposition to blood flow due to friction between blood and walls of blood vessels Depends on 1. Size of lumen vasoconstriction males lumen smaller meaning greater resistance 2. Blood viscosity ratio of RBCs to plasma and protein concentration, higher viscosity means higher resistance 3. Total blood vessel length resistance directly proportional to length of vessel 400 miles of additional blood vessels for each 2.2lb. of fat Copyright 2009, John Wiley & Sons, Inc.

69 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 Copyright 2009, John Wiley & Sons, Inc.

70 Coordinated Control of blood and tissue transport! Recruitment Varying the number of open capillaries! regulate the delivery of solute and the removal of waste! vary the total area available for exchange! recruitment is achieved by dilation of the terminal arterioles Local Blood Flow Control Blood flow distribution can be controlled centrally (neural mechanisms) and at the local level. In organs that maintain a constant flow in the face changing vascular pressure are said to "autoregulate"! alter vascular resistance (remember, to keep flow constant if pressure changes, resistance has to change in the opposite direction = Q = *P/R)! two hypotheses: the Metabolic Hypothesis and the Myogenic Hypothesis 10/10/14

71 The steepest pressure drop in the systemic circulation occurs in the arterioles. The drop in pressure depends on aggregate resistance. The more vessels in parallel, the smaller the aggregate resistance. Resistance is partially determined by radius of vessel.

72 Smooth muscle cells also determine vascular resistance (mostly by vasoconstriction/dilation changing radius) ( resistance) As if R post /R pre <<1 ( resistance) See Table 19-7 Chemical agents R post /R pre >1 Note ΔP is same Site of control of vascular resistance. (and again, largest pressure drop)

73 Relationship between Velocity of Blood Flow and Total Cross-sectioned area in Different Types of Blood Vessels Copyright 2009, John Wiley & Sons, Inc.

74 Two basic mechanisms that explain local control of blood flow (auto regulation) When MAP falls as in hemorrhage, blood flow to organs reduces 1. Myogenic mechanism decrease in blood flow Decrease Stretches on the vessel Relaxa1on of vascular smooth muscle Increase blood flow back to normal

75 Local physical response to stretch Myogenic response to stretch Increase in blood flow Stretches the vessel Contrac1on of vascular smooth muscle Decrease blood flow back to normal

76 Fick s lag

77 Fick s lag

78 Autoregulation: Local Regulation of Blood Flow Autoregulation automatic adjustment of blood flow to each tissue in proportion to its requirements at any given point in time Blood flow through an individual organ is intrinsically controlled by modifying the diameter of local arterioles feeding its capillaries MAP remains constant, while local demands regulate the amount of blood delivered to various areas according to need

79 Metabolic Controls Declining tissue nutrient and oxygen levels are stimuli for autoregulation Hemoglobin delivers nitric oxide (NO) as well as oxygen to tissues Nitric oxide induces vasodilation at the capillaries to help get oxygen to tissue cells Other autoregulatory substances include: potassium and hydrogen ions, adenosine, lactic acid, histamines, kinins, and prostaglandins

80 Myogenic Controls Inadequate blood perfusion or excessively high arterial pressure: Are autoregulatory Provoke myogenic responses stimulation of vascular smooth muscle Vascular muscle responds directly to: Increased vascular pressure with increased tone, which causes vasoconstriction Reduced stretch with vasodilation, which promotes increased blood flow to the tissue

81 Arterioles Capillaries Venule Active Hyperemia - When any tissue becomes highly active [eg. Skeletal muscle during exercise]. the rate of blood flow through the tissue increases.(as a results of vasoactive metabolites) When cells are metabolically more active they need more blood to bring in O 2 and nutrients and remove metabolic waste. Increase blood flow meets these increase local needs

82 LOCAL CONTROL OF BLOOD FLOW Reactive hyperemia When blood flow to a tissue is blocked for few seconds and then is unblocked, the flow through tissue increases almost 4-7 times normal. When blood flow to any region is blocked the arteriole in the region dilate due to Myogenic relaxation in response to decrease stretch Changes in local chemical composition ( similar to metabolically induced hyperemia) After the occlusion is removed, blood flow to previously deprived tissue is transiently higher than normal due to widely dilated arterioles

83 End

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