Vascular Function 2 PDF

Vascular Function 2 Hemodynamics: The relationship between blood flow, pressure and resistance. A variation of Ohm’s law Where: ∆P BF =...

Vascular Function 2 Hemodynamics: The relationship between blood flow, pressure and resistance. A variation of Ohm’s law Where: ∆P BF = BF = blood flow R R = resistance to blood flow There must be a pressure difference (ΔP, pressure gradient, pressure ‘head’, driving pressure) to drive blood flow—flow will be directly proportional to the pressure difference With a relatively even pressure head, flow will tend to distribute the most blood to areas (vascular networks) where the resistance is the least → flow will be inversely proportional to resistance The vascular system (primarily arterioles) provides the resistance to blood flow Resistance to blood flow can be created by extravascular factors – cardiac or skeletal muscle COMPRESSING (squeezing) arterioles and capillaries (microvasculature) Hemodynamics We assume that compared to MAP, venous pressure is negligible. Thus, regulation of blood flow (BF) to any individual organ/tissue: MAP MAP MAP BFTissue X = BFMuscle = BFKidney = RTissue X RMuscle RKidney The individual tissue’s R represents the resistance to flow provided by the blood vessels in that tissue Resistance η∙L R∝ 4 r Where: η = blood viscosity. Blood viscosity is determined by hematocrit (Hct), which is the volume % of RBCs in a certain volume of blood. L = length of the blood vessel of interest. r = radius. Radius can change acutely based on VSM tone. Vasoconstriction (↑tone) = ↓r. Vasodilation (↓ tone) = ↑ r ↑ r = ↓↓R = ↑ ↑BF  Extremely important equation Describes the basic fluid mechanics -blood, air…. ΔP= change pressure R= radius N= viscosity L= length With laminar flow, flow increases Laminar flow looks like a cone. linearly with driving pressure. Why? Not so with turbulent The vessels wall slows down molecules in contact. Drag Blood is thicker than water…. The viscosity of blood is greater than water (and plasma) because of cell (mostly RBC). The higher the hematocrit (RBC) the higher the viscosity. Non-linear relationship. As viscosity get very higher, blood becomes very viscous. This can prevent the proper flow of blood. What else would happen…..  Polycythemia (poly= lots, emia=blood) When does this occur Dehydration- Loss of plasma results in the relative ratio of RBC to increase in blood. i.e. The number of RBC is the same, but there is less plasma. This occurs to a relatively mild degree at the onset of exercise. But in this case, fluid moved into interstitial space High altitude- Low inspired oxygen pressure results in less oxygen in the blood. The lower oxygen being delivered is sensed as an error and requires correction. The correction is the release of erythropoietin (EPO) which stimulates RBC production Hypoxic diseases- Same as above, but the disease causes low blood oxygen. Blood doping  Why is polycythemia a bad thing? The heart has to work very hard to move the viscous blood. This is especially hard on the Right ventricle as pulmonary pressure get very high with a high hematocrit. As such, they both hypertrophy. Penaloza et al. Circulation. 2007 Local control of vascular tone Factors regulating Vascular Tone: Extrinsic factors Local factors In general, when SNS activity (eg SNS) increases, there is an increase (paracrine factors) in VSM tone (i.e. (mechanical i.e. autoregulation) vasoconstriction). However, Nitric oxide metabolites released by the tissues surrounding arterioles can interact with VSM on the arterioles and cause vasodilation. NOTE: This couples tissue metabolism to blood flow!! Since, the concentration of metabolites in the interstitial fluid is directly proportional to tissue metabolic rate (i.e. MVO2). And, the vasodilatory effect of the metabolites is directly proportional to their concentration in the interstitial fluid In general, SNS outflow is global (maybe not….but beyond this course). That means all vessels regardless of location get this impulse. As such, all blood vessels will vasoconstrict. But, those that are more metabolically active will dilate instead due to local factors (more later). Flow is proportional to driving pressure, but modulated by SNA. The higher the tone, the lower the flow for a given driving pressure. Likewise, the specific resistance changes for a given driving pressure. More tone, more resistance. Changes in hematocrit in vascular system In large vessels, there is an axial accumulation of blood cells, such that the relative amount of plasma is greater on the periphery. At a branch, this ‘skims’ off some of the plasma. As results, the daughter vessels has relative more plasma than RBC (lower hematocrit). This continues until the capillaries where the hematocrit is quite low Adrenergic control of blood flow from sympathetic nerves Sympathetic nerves release norepinephrine. Three types (that we are discussing) of adrenergic receptors Alpha 1- binds with norepinephrine (and slightly less so to epinephrine). Causes vasoconstriction Alpha 2- Bind similarly and cause vasoconstriction. But also bind on presynaptic receptors. This helps form a negative feedback look to prevent runaway constriction Beta 2- Binds with norepinephrine and epinephrine (greater affinity) and cause vasodilation Adrenergic control of blood flow from sympathetic nerves The net result of the sympathetic stimulation is in part due to the relative number of alpha vs. beta receptors. E.g. More beta receptors will result in less vasoconstriction for a given amount of sympathetic nerve activity (or catecholamine concentration). What does this look like in practice? How age and sex interact for cardiovascular control Prevalence of hypertension What do you notice? When is it more prevalent in men vs. women? What happens around age 45-55? Sympathetic activity and blood pressure. Not related? Young healthy individuals. No relationship between MSNA and MAP. How can this be given MSNA causes vasoconstriction Important Caveat This is cross- sectional across individuals. Showing the variability. Within a person, increasing MSNA will generally increase MAP  How are MSNA and Blood pressure not related? 18 healthy male subjects 10 BP = 95 +/-2 r2= 0.50 9 r = 0.71 MSNA, ECG, Arterial catheter 8 7 CO When MSNA goes up, (L/min) 6 cardiac output goes down 5 4 3 10 20 30 40 50 60 70 80 MSNA (bursts/100 hb) Total peripheral resistance and cardiac output vs. MSNA Men: Women: Positive No relationship relationship between with either. MSNA and Changing TPR. More MSNA has no MSNA = impact on Greater TPR or Q resistance. Negative relationship between Q and MSNA. As MSNA goes up, Q down. What is causing the difference in women? Most likely candidate is estrogen. Which is sympatho-inhibitory and may increase Beta 2 adrenergic population. With supplemented estrogen, MSNA will decrease in 8 weeks.  FVC= Forearm vascular conductance. Experimental testing Conductance is the inverse of resistance. More conductance, more blood flow. MEN A relative (sex differences) decrease in FVC suggests a decrease in blood flow to the area (vasoconstriction) NA= Noradrenaline =norepinephrine. Infused into brachial artery. Open circles are during Beta blockade Experimental testing Increasing NA has little impact on FVC. (in men it causes vasoconstriction or a decrease in FVC) Little to no vasoconstriction happening. But with Beta blockade, an increasing dose of NA causes and progressive decrease in FVC. Now we are getting vasoconstriction. Looking at them together Women MEN Remember before MSNA and MAP & TPR A way to test Estrogen. Menopause Post menopausal women. Without blockade, they have more of a decrease in FVC with increasing NA. No effect of the beta blockade for post menopausal women They have a response that is similar to men. Aging Unlike young subjects, older individuals do have a significant relationship between MSNA and blood pressure. Summary -For a given level of SNA, men get more vasoconstriction due to greater alpha receptors -Women are ‘protected’ due to estrogens upregulation of Beta receptors. Thus, the vasoconstriction is opposed by vasodilation. As such, increased SNA does not increase resistance. -This relationship does not exist in older women and older men. -One of the reasons why hypertension is quite uncommon in young women and become a large issue in post-menopausal women Key Concepts Blood flow resistance is principally related to blood viscosity, vessel length and mostly diameter The autonomic nervous system can alter blood vessel diameter acutely Male and females regulate blood pressure differently and is likely due to the impact of estrogen