KIN 292 1nd Edition Lecture 25 Outline of Last Lecture I. 13.6 Cardiac Output and Its ControlOutline of Current Lecture I. 14.1 Physical Laws Governing Blood Flow and Blood PressureII. 14.2 Overview of the VasculatureIII. 14.3 ArteriesIV. 14.4 Arterioles – part 1V. 12.6 Smooth MuscleCurrent Lecture14.1 Universal Flow Rule- Flow rate of a liquid through a pipe is directly proportional to the difference between thepressures at the two ends of the pipe (pressure gradient) and inversely proportional to the resistance of the pipe.- Pressure gradient (∆P) = magnitude of force pushing the blood exerted by blood- Resistance (R) = the various factors resisting the flow of liquid in a pipe. What are they?Flow = P/R. We’ll consider ∆P 1st and then R. You will see the impact of both in your labexercises for this week- the pressure gradient is what matters, not the absolute amount of pressure- A gradient must exist throughout the circulatory system to maintain blood flow- Heart - creates a pressure gradient for bulk flow – how much is flowing, not how it is distributed- Note: Pressure in vena cava actually slightly above 0, but is so small that author choosesto ignore it for “simplicity”. So MAP approximately = to ∆P- Figure 14.3 Mean (average) Pressures and pressure drops in the pulmonary and systemic circuits at rest.These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.o Note: ∆P higher in systemic. What about flow and resistance comparison in two circuits?o CVP, central venous pressure in large veins in thoracic cavity; RA, right atriumResistance in the Cardiovascular System- Factors affecting resistance to flowo Radius of vessel Arterioles (and small arteries)— only vessels that can regulate radiuso Length of vessel – essentially constant in blood vesselso Viscosity of fluid =  Blood viscosity depends on amount of RBCs and proteins—usually constant- R = 8  L / r4; this is Poiseuille's Lawo recall that Flow = P/Ro Putting these together Flow = P r4 / 8  L o Since denominator is constant, Flow = P r4 - Rules governing flow, resistance and pressure are the same for individual vessels and for a network of vessels, which are the total blood vessels in the entire systemic or pulmonary circuits or an individual organ. - Regulation of radius of arterioles (and small arteries) is biggest factor in blood flowo Vasoconstriction  Decreased radius  increased resistance  decreased flow through vessel or networko Vasodilation  Increased radius  decreased resistance  increased flow through vessel of networkRelating Pressure Gradients and Resistance in the whole Systemic Circulation (Flow = ∆P/R).- For systemic circulation:- Flow = cardiac output (CO)- ∆P = mean arterial pressure (MAP)- R = total peripheral resistance (TPR), where TPR = combined resistance of all blood vessels within the entire systemic circuit, which is a vast network of blood vessels.- Flow = ∆P/R becomes CO = MAP / TPR14.2 Overview of Vasculature- Arteries: rapidly carry blood away from heart- Microcirculationo Arterioleso Capillaries: site of exchangeo Venules- Veins: return blood to heartArteries - Pressure reservoir – keeps blood flowing after LV ejects it- Aorta and large arterieso Thick, elastic arterial walls with Low compliance - Small increase in blood volume causes a large increase in pressureo Expand as blood enters arteries during systole and Recoil during diastole (dicroticnotch in chapter 13)- Muscular arterieso Less than 0.1 mm in diametero Little elastino Smooth muscle regulates radius – helps regulate flow distribution similar to arterioles- Arterial Blood Pressure Determination; Measurement principles and calculations you willdo in labo Estimates aortic pressure usually measured in brachial arteryo The measured BP is shown as systolic pressure/diastolic pressure (SP/DP). Example: 110 / 70 o Pulse pressure = SP – DP. Example: 110 – 70 = 40 mm Hgo MAP = SP + (2 x DP) / 3 Example: (110 + 140) / 3 = 83.3 mm Hg- Arterioles: resistant vessels (main control of resistance to flow). Contain rings of smooth muscle to regulate radius and, therefore, resistance12.6 Smooth Muscle- Found in internal organs and blood vessels- Lacks striations – that’s how it gets its name- Contains actin and myosin, but no sarcomeres- Myosin ATPase contraction is 10–100 times slower in smooth muscle than in skeletal muscle- Dense bodies – where thick/thin filaments attach to connective tissue inside cell to transmit contractile force- Under involuntary control by the autonomic nervous system and certain metabolites- Spindle-shaped- Small—approximately 1/10 the size of skeletal muscle- Single and multi-unit smooth muscleo Single-unit smooth muscle. Most common. Includes arterioles, respiratory tract,intestinal tracto Electrical signals transmitted to all cells via gap junctions. All cells contract as a single unit – like cardiac- Steps of excitation-contraction coupling1. Most Ca2+ comes from outside the cell2. Through Voltage-gated Ca2+ channels in plasma membrane3. Ca2+ triggers release of Ca2+ from sarcoplasmic reticulum4. Ca2+ binds to calmodulin5. Ca2+-calmodulin activates myosin light-chain kinase (MLCK)6. MLCK phosphorylates myosin7. Crossbridge cycling- Relaxationo Ca2+ removed from cytoplasm as in hearto Phosphatase removes phosphate from myosinSmooth Muscle in Arterioles- Tone = basal level of contraction. Has pacemaker cells that result in low level of contraction, which can be modified by various factors - regulation of arteriole smooth muscle – increases/decreases tension compared to toneo Intrinsic control – local metabolites that increase blood flow (vasodilate) to match metabolic needs of cells in the region. Most common mechanism is opening K+ channels causing hyperpolarization, thus decreasing chance of reaching threshold potentialo Extrinsic control - autonomic nervous system and hormones leads to either constriction or dilation depending on what receptor and what organ. Most common mechanism is altering MLCK and MLCPCa++ sensitivity of contraction determined by MLCP- Myosin light chain phosphatase (MLCP) removes phosphate from myosin- Inhibiting MLCP activity results in prolonged phosphorylation of MLC, thus increasing contraction at any given Ca++ concentration. This increases Ca++ sensitivity of