Cardiovascular Pressure Gradients

• Minimum aortic pressure during the cardiac cycle occurs immediately after the closure of the aortic semilunar valve.

Physical Laws Governing Blood Flow and Blood Pressure

• The flow rate of a liquid through a pipe is directly proportional to the pressure difference between the two ends and inversely proportional to the resistance of the pipe.

Pressure Gradients in the Cardiovascular System

• A pressure gradient is the driving force for bulk flow, moving fluids from areas of high pressure to low pressure.
• The heart generates pressure to drive blood flow, creating a pressure difference between arteries and veins

Pressure Gradients Across the Systemic and Pulmonary Circuits

• Systemic circuit blood flow is driven by the pressure gradient between the mean arterial pressure (MAP) and the central venous pressure (CVP).
• The pressure gradient for blood flow in the systemic circuit is approximately equal to the mean arterial pressure (MAP).
• Blood flow through the pulmonary circuit is driven by the pressure gradient between the pulmonary arteries and veins.
• Pulmonary arterial pressure averages approximately 15 mm Hg during the cardiac cycle.
• The pulmonary circuit has a lower resistance compared to the systemic circuit.

Resistance in the Cardiovascular System

• Given the same blood flow in both circuits, the pulmonary circuit offers less resistance due to its physical characteristics, necessitating a smaller pressure gradient.

Resistance of Individual Blood Vessels

• Resistance is a measure of how much a tube hinders the flow of liquid through it.
• Higher resistance yields lower flow for a given pressure gradient.
• Blood flow is greater when resistance is lower with a given pressure gradient.
• Resistance depends on the vessel's radius and length, and on the fluid’s viscosity.
• Decreased radius causes increased resistance, vasoconstriction.
• Increased radius results in decreased resistance, vasodilation.
• Longer vessels have greater resistance, but changes in vascular resistance are rarely attributable to changes in vessel length.
• Vascular resistance increases as blood viscosity increases, but viscosity does not change much under normal conditions.
• The major determinant of blood viscosity is the concentration of cells and proteins in the blood.

Resistance of Blood Vessel Networks: Total Peripheral Resistance

• The resistance of a vascular network depends on the resistances of all the individual blood vessels it contains.
• Vasoconstriction increases the resistance of the network.
• Vasodilation decreases the resistance of the network.
• Total peripheral resistance (TPR) is the combined resistances of all blood vessels within the systemic circuit.

Relating Pressure Gradients and Resistance in the Systemic Circulation

• Cardiac output (CO) is the volume of blood flowing through the systemic circuit each minute.
• The flow is driven by the pressure gradient between the mean arterial pressure (MAP) and central venous pressure (CVP).
• The resistance in the systemic circuit is the total peripheral resistance (TPR).

Overview of the Vasculature

• Arteries and arterioles carry blood away from the heart to capillaries while Venules and veins return blood to the heart.
• Arterioles, capillaries, and venules are called the microcirculation.
• All blood vessels have a hollow interior called the lumen, lined by endothelium.
• The walls of all blood vessels contain various amounts of smooth muscle and fibrous and/or elastic connective tissue.
• Collagen in fibrous connective tissue provides tensile strength.
• Elastin in elastic connective tissue enables blood vessels to expand or contract with pressure changes.

Arteries

• Arteries carry blood away from the heart towards the body’s tissues.
• The aorta, the largest artery, has an internal diameter of about 12.5 mm and a wall that is 2 mm thick.
• Larger arteries have elastic and fibrous tissue to withstand high blood pressures.
• Smaller arteries have less elastic tissue and more smooth muscle.
• Arteries less than 0.1 mm in diameter lose most of their elastic properties, called muscular arteries.
• Smooth muscle enables radius regulation in small arteries.

Arteries: A Pressure Reservoir

• Arteries act as pressure reservoirs, which ensure a continuous blood flow during diastole.
• Elastin fibers store elastic force as arterial walls expand during systole and recoil during diastole.
• The pulse you feel is a pressure wave as a result of blood being pushed into the arteries during systole, this expands arterial walls.
• Arteries must have low compliance, a measure of the relationship between pressure and volume changes to serve as a pressure reservoir.
• Low compliance means small volume increase causes large blood pressure increase.

Arterial Blood Pressure

• Arterial blood pressure is the pressure in the aorta, which varies with the cardiac cycle.
• Systolic pressure is the maximum pressure during systole.
• Diastolic pressure is the minimum pressure during diastole.
• Mean arterial pressure (MAP) is the average arterial pressure during the cardiac cycle.

Measuring Arterial Blood Pressure

• Arterial pressure is estimated by measuring pressure in the brachial artery in the upper arm.

• A sphygmomanometer measures blood pressure, with an inflatable cuff and a pressure-measuring device.

• A stethoscope is used to listen for Korotkoff sounds, produced by turbulent blood flow.

• Systolic arterial pressure is the cuff pressure when Korotkoff sounds first appear.

• Diastolic arterial pressure is the cuff pressure when Korotkoff sounds disappear.

• Blood pressure is recorded as systolic pressure (SP) over diastolic pressure (DP), SP/DP.

• Average normal blood pressure is 110/70 mm Hg.

• Pulse pressure (PP) is the difference between systolic and diastolic pressure: PP = SP - DP.

• Using normal numbers, the pulse pressure is 110 mm Hg - 70 mm Hg = 40 mm Hg.

• High pulse pressure in older people may indicate hardening of the arteries.

• Mean arterial pressure (MAP) is the average pressure in the arteries during one cardiac cycle.

Arterioles

• Arterioles are small vessels that lead into capillaries.
• The walls of arterioles contain circular smooth muscle enabling regulation of the radius.
• Arterioles regulate resistance to blood flow.

Arterioles and Resistance to Blood Flow

• Blood flow depends on the pressure gradient and resistance to blood flow
• Arterioles provide the greatest resistance to blood flow; more than 60% of TPR.
• Blood pressure decreases gradually from arteries to veins, the largest pressure drop occurring along the arterioles.
• The major function of arterioles is to regulate resistance to blood flow and control blood flow to individual capillary beds and regulate MAP.
• Arteriolar smooth muscle is partially contracted in the absence of external factors, a state called arteriolar tone.
• Increased smooth muscle contraction causes decreased radius (vasoconstriction) and increased resistance.
• Smooth muscle relaxation causes increased radius (vasodilation) and decreased resistance.

Intrinsic Control of Blood Flow Distribution to Organs

• Blood flow gets distributed among organs based on need.

• Extrinsic control provides adequate arterial pressure, while individual organs regulate their own blood flow through local control.

• Intrinsic control is especially important in the heart, brain, and skeletal muscles.

• Distribution of blood flow to organs changes due to changes in vascular resistance of individual organs.

• Vascular resistance of an organ is altered by contraction or relaxation of smooth muscle in arterioles.

• Intrinsic control mechanisms regulate the distribution of blood flow not only among the organs, but also within organs.

Regulation in Response to Changes in Metabolic Activity: Active Hyperemia

• Arteriolar smooth muscle responds to chemical substances, including oxygen, carbon dioxide, potassium, and hydrogen ions.
• Changes from metabolic activity cause vasodilation: decreased oxygen, increased carbon dioxide, and other metabolic factors.
• Changes decreasing metabolic activity leads to vasoconstriction.
• Active hyperemia is an increase in blood flow following an increase in metabolic activity.

Regulation in Response to Changes in Blood Flow: Reactive Hyperemia

• Blocked or reduced blood flow causes decreased oxygen and increased carbon dioxide levels, inducing vasodilation.
• An increase in blood flow in response to a previous reduction in blood flow is reactive hyperemia.
• Basic mechanism: Decreases in tissue oxygen and increases in metabolite concentrations induce vasodilation and an increase in blood flow.
• If blood flow exceeds metabolic needs, intrinsic control mechanisms induce vasoconstriction.

Regulation in Response to Stretch of Arteriolar Smooth Muscle: Myogenic Response

• Stretch-sensitive fibers in arteriolar smooth muscle respond to stretch by contracting.
• A change in vascular resistance in response to stretch of blood vessels is a myogenic response; does not require nerves, hormones, or other chemical agents.
• Perfusion pressure is the pressure gradient driving blood flow through an organ or tissue.
• If perfusion pressure increases, blood flow increases and arteriolar pressure rises thus stretching arteriolar walls, in response, smooth muscle contracts, increasing resistance and decreasing blood flow.
• Local regulation maintaining constant blood flow is called flow autoregulation.

Regulation by Locally Secreted Chemical Messengers

• Contractile activity of vascular smooth muscle is affected by chemical substances.
• Nitric oxide is released by endothelial cells, promoting vasodilation.
• Bradykinin and histamine stimulate nitric oxide synthesis.
• Prostacyclin is an eicosanoid that prevents blood clots while adenosine is a vasodilator in the coronary arteries.
• Endothelin-1 promotes vasoconstriction.

Extrinsic Control of Arteriole Radius and Mean Arterial Pressure

• Intrinsic controls redistribute blood flow while extrinsic controls regulate MAP.
• Cardiac output (CO) is stroke volume (SV) multiplied by heart rate (HR): CO = SV × HR.

Sympathetic Control of Arteriolar Radius

• Sympathetic nervous system innervates smooth muscle of most arterioles.
• Norepinephrine binds to α adrenergic receptors causing vasoconstriction, increasing TPR and MAP.
• Epinephrine secreted from the adrenal medulla can bind to both α and β2 receptors.
• Binding to α receptors causes vasoconstriction.
• Binding of epinephrine to β2 receptors causes vasodilation, reducing resistance to blood flow.
• Epinephrine binds to β2 receptors, promoting vasodilation as it has the greater affinity.
• High concentrations of epinephrine usually promote vasoconstriction as only α receptors are present on most arteriole smooth muscle.
• β2 receptors predominate in cardiac and skeletal muscle resulting in vasodilation in these tissues.
• Vasoconstriction decreases blood flow to nonessential tissues, increases TPR and MAP.
• Parasympathetic nervous system causes vasodilation through arteriole smooth muscle of the external genitalia.

Hormonal Control of Arteriolar Resistance

• Vasopressin (ADH) promotes vasoconstriction.
• Angiotensin II is a protein derived from angiotensinogen.
• Angiotensinogen is converted to angiotensin I by renin and then to angiotensin II by angiotensin converting enzyme.
• Angiotensin II promotes vasoconstriction, increasing TPR and MAP.

Capillaries and Venules

• Capillaries are where exchange of nutrients and waste products between blood and tissue occurs.

Capillary Anatomy

• Capillaries: Smallest blood vessels are 1 mm long and 5–10 μm in diameter.
• Capillary walls: Thin, consisting of a single layer of endothelial cells with a basement membrane.
• Extensive branching results in 10–40 billion capillaries and a large surface area for exchange between blood and tissue of approximately 600 square meters.
• almost all body cells are within 1 mm of a capillary.
• Capillaries exist in networks called capillary beds.
• Total cross-sectional area of capillaries is greater than that of other blood vessels.
• Velocity of blood flow decreases as blood enters capillary beds which allows for exchange.
• Velocity of blood flow through the capillaries is about 0.1 mm/sec.
• Exchange is enhanced by the leakiness of the capillary wall, which varies in different tissues.
• Tight junctions between endothelial cells within the central nervous system produce produce blood-brain barrier.

Continuous Capillaries

• Most common type, endothelial cells joined by tight junctions with narrow intercellular clefts to limit passage.
• Permeable to small water-soluble substances and lipid-soluble substances permeable to membranes of the endothelial cells.
• Water-soluble molecules have difficulty passing, and proteins and other macromolecules have very low permeability.

Fenestrated Capillaries

• Possess large pores (fenestrations) approximately 60–80 nm in diameter that allow diffusion of small water-soluble substances.
• Found in organs whose functions depend on movement across capillary walls, including the kidneys, intestines, and endocrine glands.

Discontinuous Capillaries and Sinusoids

• Discontinuous capillaries serve as a transition from fenestrated capillaries to sinusoids.
• Found in the spleen, liver, and bone marrow and form sinusoids where proteins and cells must cross the endothelium
• Sinusoids: Function in the exchange of substances between blood and tissue.
• Sinusoids are lined by highly fenestrated endothelium but no basement membrane.
• In the liver, sinusoidal exchange allows newly synthesized proteins such as albumin or clotting factors to enter the plasma.
• They enable blood cells to move to the spleen for filtering or exit the bone marrow after they have been synthesized.

Local Control of Blood Flow Through Capillary Beds

• Local control of smooth muscle regulates blood flow through microcirculation.
• Metarterioles: Structures intermediate between arterioles and capillaries.
• Metarterioles possess isolated rings of smooth muscle acting as gatekeepers.
• Metarterioles act as bypass channels, directly connecting arterioles to venules.
• Metarteriole smooth muscle contracts or relaxes to regulate blood flow.
• When resistance to blood flow is high, blood flow through the capillary beds increases, and vice versa.
• Regulation of metarteriole smooth muscle is local control by metabolites.
• Smooth muscle surrounds capillaries on the arteriole end, called precapillary sphincters; contracts or relaxes.
• Contraction of precapillary sphincters constricts the capillaries, increasing their resistance to blood flow.
• Precapillary sphincters are only affected by local controls: metabolites.
• Increased metabolites cause relaxation and increased blood flow, vice versa.
• Relaxation/contraction of precapillary sphincters is vasomotion.

Movement of Material Across Capillary Walls

• Movement of material across capillary walls exchanges material and distributes extracellular fluid.

Exchange Across Capillary Walls

• Material exchanges across capillary walls through simple diffusion, transcytosis, and mediated transport.
• Small solutes move across capillary walls by simple diffusion.
• Small lipid-soluble solutes diffuse across plasma membranes, while small water-soluble solutes diffuse through water-filled pores.
• Small lipid-soluble solutes diffuse across plasma membranes, while small water-soluble solutes diffuse through water-filled pores.
• Direction of diffusion depends on the electrochemical gradient for a specific substance.
• Nutrients and oxygen diffuse from blood to tissue, while waste products and carbon dioxide diffuse from tissue to blood.
• Large water-soluble solutes (proteins) transported across endothelial cells through transcytosis; endothelial cells selectively transport proteins across.
• In transcytosis, plasma proteins are engulfed by endocytosis and then ferried across the cells by vesicular transport, and subsequently released in to the interstitial fluid on the other side.
• Brain capillary endothelial cells block the movement of small water-soluble solutes between cells; solutes are transported across endothelial cells by mediated transport.

Bulk Flow Across Capillary Walls

• Water and small solutes move from blood to interstitial fluid (filtration) or from interstitial fluid to blood (absorption) based on pressure gradients.
• Maintains balance between extracellular compartments.
• Shifts in fluid from plasma to interstitial fluid causes edema.
• Starling forces drive the movement of fluid into and out of capillaries include: capillary hydrostatic pressure (PCAP), interstitial fluid hydrostatic pressure (PIF), capillary osmotic pressure (πCAP), and interstitial fluid osmotic pressure (πIF.
• The net filtration pressure is the difference in the filtration pressures and the absorption pressures
• Capillary hydrostatic pressure (PCAP) favors filtration along the capillary
• Interstitial fluid hydrostatic pressure (PIF) favors absorption.
• Capillary osmotic pressure (πCAP ) favors absorption due to nonpermeating solutes drawing water into the capillary.
• Interstitial fluid osmotic pressure (πIF) favors filtration; proteins in the interstitial fluid draw fluid out of the capillary.

Net Filtration Pressure

• Equation is: NFP = (PCAP + πIF ) - (PIF + πCAP).
• Positive is filtration across the capillary
• A negative is absorption across the capillary
• In the capillary there is higher NFP at the arteriole end, lower at the venule end.
• Fluid leaves a capillary closer to the arteriole end but near the venule end, returns to the blood.

Factors Affecting Filtration and Absorption Across Capillaries

• The rate at which fluid is filtered or absorbed across capillary walls is influenced by any factor that alters the relative sizes of the Starling forces.
• Increase in capillary hydrostatic pressure or interstitial fluid osmotic pressure favors increased filtration, or a decrease in interstitial fluid hydrostatic pressure or capillary osmotic pressure.
• The volume of fluid that moves by bulk flow across capillary walls is considerably higher than total blood volume.
• The lymphatic system picks up/returns filtered fluid to the cardiovascular system.
• Increased capillary filtration occurs standing due to increased capillary hydrostatic pressure in the lower parts of the body.
• Increased capillary filtration and tissue swelling result from high protein fluid escaping from damaged capillaries to the interstitium: histamine released and damaged capillaries.
• Reduced osmotic pressure and reduced protein quantities or protein filtration triggers increased capillary filtration and cause swelling.
• Damage to the heart can result in pulmonary edema, where heart is unable to maintain cardiac output, causing increased venous pressure translating to upstream vessels like pulmonary capillaries.

Venules

• Venules are formed when capillaries come together.
• Venulues average about 20 μm in diameter.
• Venules consist of a single layer of endothelium that allows exchange of materials between blood and interstitium
• Exchange between blood and interstitium occurs in both capillaries and small venules.

Veins

• Veins are formed as venules come together.
• On average, veins have slightly larger diameters than arteries, but have walls about half as thick.
• Veins walls contain smooth muscle and elastic and fibrous connective tissue
• Under same pressure, veins hold more volume than arteries, veins are more compliant as relatively small increase in pressure within creates relatively larger increase in volume.
• equipped with valves that permit unidirectional blood flow toward the heart.
• Valves present in peripheral veins.