Chapter 14 - Blood Vessels, Blood Flow, and Blood Pressure

Physical Laws Governing Blood Flow and Blood Pressure
     The flow of blood within vessels is directly proportional to the pressure gradient and is inversely proportional to the resistance within the vessel:
Flow =  DP/R
     The pressure gradient is the force that pushes the liquid through the vessel.
Pressure Gradients in the Cardiovascular System
     Whenever there is a difference in pressure between two locations fluid flows from the region of high pressure to that of low by bulk flow. The heart causes blood to flow by creating a mean arterial pressure that is greater than the pressure in the veins. Hence, a pressure gradient drives the blood from the arteries to the veins. 
     As blood flows from the arteries to the veins the pressure decreases. This decrease in pressure is called  a pressure drop. The pressure drop is greatest in the arterioles and greater in the systemic compared to the pulmonary circuit. 
Pressure Gradient Across Systemic and Pulmonary Circuits
     In the systemic circuit the pressure gradient is virtually identical to the mean arterial pressure (the average pressure in the aorta throughout the cardiac cycle) of 85 mm Hg. This is because the pressure at the other end is the central venous pressure which is approximately 2-8 mm Hg and very close to 0 mm Hg. In a similar way the pressure gradient in the pulmonary circuit is about 15 mm Hg which is about equal to the mean pulmonary arterial pressure
     Blood flow through the pulmonary circuit is identical to that through the systemic circuit (5 liters/minute). However, the pressure gradient in the pulmonary circuit is considerably less than that through the systemic circuit. The equality of blood flow through the circuits is due to the lesser resistance offered by the pulmonary circuit. 
     In individual vessels at a given pressure gradient, the higher the resistance the lower the flow. 
   Resistance depends on the following factors:
1. Vessel Radius
   Changes in the resistance in the cardiovascular system is almost always due to this factor. Vascular resistance can be controlled in small arteries and arterioles by contraction (vasoconstriction) or relaxation (vasodilation) of the smooth muscle in the vessel wall. Vasoconstriction increases resistance and vasodilation decreases resistance.
2. Vessel Length
   The longer the vessel the greater the resistance but this is not an important factor for control.
3. Blood Viscosity
   Vascular resistance increases as viscosity increases. But this is not usually an important factor. The major determinant of blood viscosity is the concentration of cells and protein in the blood with viscosity increasing with each. 
Total Peripheral Resistance
     For any blood vessel network the total flow increases in proportion to D P and decreases with R just as with individual vessels. The resistance of a network depends upon the individual resistances within the network.
     Total peripheral resistance is the combined resistances of all the blood vessels within the systemic circuit. The greatest amount of resistance comes from arterioles and small arteries and these are called resistance vessels. Total peripheral resistance is almost entirely due to changes in the diameter of resistance vessels. 
Relating Pressure Gradients and Resistance in the Systemic Circulation
     Cardiac output (flow) is equal to the mean arterial pressure (pressure gradients) over total peripheral resistance (resistance). Hence, CO = MAP/TPR.
Overview of the Vasculature
      Review the anatomy shown in figures 14.5 and 14.6.
     Arteries conduct blood away from the heart and toward the body tissues. The larger arteries have more fibrous tissue in their walls that resist pressure and provide elasticity. The smaller arteries have more smooth muscle in their walls and regulate flow by vasoconstriction and vasodilation. 
Arteries Serve as a Pressure Reservoir
     During systole blood is pumped into the arteries under pressure. Because of the low compliance of arteries, the pressure within the arteries rises rapidly. During diastole the pressure within arteries (held in reserve) is released and contributes to continued flow of blood during diastole. 
Arterial Blood Pressure
     The pressure of blood in the aorta is the arterial blood pressure. Arterial blood pressure varies during the cardiac cycle with maximum pressure called systolic pressure because it occurs during systole and minimum pressure called diastolic pressure because it occurs during diastole. The average arterial pressure during the cardiac cycle is the mean arterial pressure (MAP). 
     The arterioles provide the greatest resistance to blood flow. This is illustrated in the figure below by the large pressure drop that occurs while blood flows through the arterioles. 
     The walls of the arterioles contain smooth muscle that can control the diameter, and hence the resistance, by contracting or relaxing. For this reason, the resistance to flow offered by the arterioles can be regulated. This enables the arterioles to:
1. Control blood flow to individual capillaries.
2. Regulate mean arterial pressure.
     The smooth muscle of arterioles consists of single-unit smooth muscle that have pacemaker cells that spontaneously depolarize. Because of this the smooth muscle spontaneously contract and give the arterioles tone, arterial tone. 
     The contractile state of the arterioles can be increased or decreased by external factors. Contraction of smooth muscles causes vasoconstriction or decrease in diameter and increase in resistance. Relaxation of smooth muscle causes vasodilation or increase in diameter and decrease in resistance. 
Intrinsic Control of Blood Flow (Distribution to Organs)
     Changes in the percentage of the total blood flow to individual organs are due to changes in the vascular resistance of each individual organ. In other words, intrinsic mechanisms regulate the distribution of blood flow among organs. In addition, intrinsic mechanisms also control the distribution of blood flow to capillary beds within the organ. 
     Intrinsic control mechanisms are particularly important in the heart, brain and skeletal muscle for two reasons: 
1. constant blood flow to the brain and heart is essential;
2. blood flow in skeletal muscle and cardiac muscle needs to adjust to varying metabolic demand. This is also true to a lesser extent in the brain where blood flow needs to increase in regions that are more active. 
Smooth Muscle Effects Intrinsic Control
     Smooth muscle itself changes vascular resistance by contracting or relaxing in response to the following factors:
1. Metabolic Activity
   Changes in metabolic activity change the concentration of a number of substances including oxygen and carbon dioxide. Concentration of these substances effect whether smooth muscle contracts or relaxes. Except for the pulmonary circulation, increased metabolic activity causes vasodilation and decreased metabolic activity causes vasoconstriction. 
   For example, when metabolic activity rises, oxygen decreases and carbon dioxide increases and blood flow becomes insufficient to meet demand. This condition is called ischemia. However, smooth muscles responds by relaxing which increases blood flow. The increased blood flow supplies more oxygen and removes more carbon dioxide. The increased blood flow associated with increased metabolic activity is called active hyperemia. 
2. Blood Flow
   If blood flow either increases or decreases above or below metabolic needs this causes change in oxygen and carbon dioxide concentration which leads to the changes described above. The increase in blood flow that follows a reduction in blood flow is called reactive hyperemia. A rise in blood flow also elicits an intrinsic control mechanism that causes vasoconstriction so this mechanism also works in reverse.
   The mechanism for the changes that occur in response to changes in blood flow is the same as that that occurs with changes in metabolic activity. In both cases there is a change in the concentration of key molecules. The only difference is in the cause of the change. 
3. Stretch of Arterial Smooth Muscle
   Some arterial smooth muscle fibers are stretch-sensitive fibers. When blood flow increases these fibers are stretched and they respond by contracting. On the other hand, when blood flow decreases the tension on these fibers decreases and the muscles relax. This response of the muscle themselves to physical blood flow is called the myogenic response.
   The key variable that is regulated by this mechanism is blood flow. 
4. Locally Secreted Chemical Messengers
    A variety of chemicals affect vascular smooth muscle. Most of these cause vasodilation. These include chemicals secreted by endothelial cells such as nitric oxide which is secreted on a continual basis. Bradykinin and histamine are released by cells in response to tissue injury and stimulate nitric oxide synthesis and vasodilation that is associated with the inflammatory response. Prostacyclin is a potent vasodilator that helps prevent blood clots. Adenosine is an important vasodilator in coronary arteries. 
    A chemical that is secreted by endothelial cells that promotes vasoconstriction is endothelin-1.
    See Table 14.1 for a list of these chemicals. 
Extrinsic Control of Arteriole Radius and Mean Arterial Pressure
     Mean arterial pressure is related to arteriole radius by the equation:


     Since arteriole radius is the most important factor influencing TPR, understanding the extrinsic control of arteriole radius is important for understanding the regulation of mean arterial pressure. 
  Sympathetic Control of Arteriole Radius
     Sympathetic neurons innervate the smooth muscle of most arterioles. The norepinephrine that is released as the neurotransmitter binds to a adrenergic receptors and causes vasoconstriction. This increases MAP by increasing TPR.
     Epinephrine released by the adrenal medulla bind to both a and 2 adrenergic receptors. Activation of  2 receptors causes vasodilation. Because a1 receptors outnumber 2 receptors in most locations, epinephrine at high concentration causes vasoconstriction and increases MAP. 2 receptors predominate in the vessels of the heart and skeletal muscle and promote blood flow into these organs during stress by causing vasodilation. Hence, blood flow needed by the heart and skeletal muscle during vigorous activities is maintained. 
  Hormonal Control of Arteriolar Resistance
     In addition to epinephrine two other hormones cause vasoconstriction and increase MAP:
  Vasopressin (ADH)
    Vasopressin increases mean arterial pressure by promoting vasoconstriction. It also promotes an increase in MAP by limiting urine output and raising blood volume. This is why it is also called antidiuretic hormone. 
  Angiotensin II
    Angiotensin II is derived from angiotensinogen which is present in the plasma. Angiotensinogen is converted to angiotensin I by renin which is secreted by the kidney. Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE) which is present on the inner surface of the blood vessels particularly in the lungs.
    Capillaries are the smallest and most numerous of blood vessels. The thin wall of capillaries consist of only an endothelial cell and the supporting basement membrane. The thinness of the capillary wall promotes the rapid and efficient exchange of material between the blood and the tissue. 
 Movement of Materials Across Capillary Walls
    The permeability of capillary walls to water and small solutes allows bulk flow of fluid across the wall. Movement of fluid from the plasma to interstitial fluid is called filtration and movement of fluid from interstitial fluid to plasma is called absorption. A net shift of fluid from plasma to interstitial fluid causes tissue swelling called edema. 
    The forces that drive movement of fluid into and out of capillaries are called Starling forces and includes:
  1. Capillary hydrostatic pressure (Pcap) or the hydrostatic pressure of fluid in the capillaries.
  2. Interstitial hydrostatic pressure (Pif) or the hydrostatic pressure of fluid outside the capillary.
  3. Capillary osmotic pressure (Πcap) due to the presence of non-permeating solutes inside the capillaries.
  4. Interstitial fluid osmotic pressure (Πif) due to the presence of non-permeating solutes outside the capillaries.
Hydrostatic Pressure Gradient
     The hydrostatic pressure gradient is equal to the difference of the hydrostatic pressure within the capillary and the hydrostatic pressure in the interstitial fluid. The pressure inside the capillary is about 38 mm Hg at the arteriolar end and 16 mm Hg at the venous end. The interstitial hydrostatic pressure is about 1 mm Hg. Hence, there is a net hydrostatic pressure pushing fluid out of the capillaries of 37 mm Hg at the arteriolar end and 15 mm Hg at the venous end. 
Osmotic Pressure Gradient
     Water flows from a region where the osmotic pressure is lower to a place where it is higher when separated by a semipermeable membrane. Osmotic pressure differences between capillaries and the interstitial fluid is due to a  difference in the protein concentration. The osmotic pressure exerted by the proteins is called colloid osmotic pressure or oncotic pressure. Because there is a higher concentration of proteins in the capillaries compared to the interstitial  fluid the oncotic pressure gradient is directed inward. That is, it drives water into the capillaries. The oncotic pressure gradient across the capillary wall is about 25 mm Hg
Net Filtration Pressure
     The direction of water movement is determined by net filtration pressure. Net filtration pressure is determined by the difference between the hydrostatic pressure gradient and the oncotic pressure gradient. Filtration is associated with a positive net filtration pressure while absorption is associated with a negative net filtration pressure (see Table 14.3). 
     Under normal conditions both filtration and absorption are occurring in the capillaries. At the arteriolar end of the capillary where the hydrostatic pressure exceeds oncotic pressure there is filtration, at the venous end where hydrostatic pressure is less than oncotic pressure there is absorption.
     Under normal conditions 20 liters of fluid is filtered every day and about 17 liters are absorbed for a net filtration of about 3 liters of fluid. The 3 liters of fluid that is filtered is returned by the lymphatic system.
   Factors Affecting Filtration and Absorption Across Capillaries
     A nonpathological factor that alters net filtration in the lower extremities occurs as the result of standing. Prolonged standing increases capillary hydrostatic pressure and increases net filtration.
     Pathological factors that increase net filtration include:
    Tissue injury that results in loss of fluid and plasma proteins associated with capillary damage and the inflammatory response.
    Liver disease that results in decrease of plasma protein and a consequent decline in capillary oncotic pressure.
    Kidney disease that results in retention of fluid and/or loss of plasma protein.
    Heart disease that increases hydrostatic pressure in the pulmonary capillaries and causes pulmonary edema.
     Veins have roughly the same diameter as arteries but have walls about one-half as thick. The thinness of the wall reflects the fact that blood pressure is much lower in the veins.
  Veins Serve as a Volume Reservoir
     Veins can accommodate a large increase in blood volume because of their high compliance (expansion due to pressure). This enables the veins to hold a large volume of blood at a given pressure. Veins also contain a larger proportion of blood volume than any other part of the circulation.
    The existence of this volume reserve is important because it enables the circulation to sustain a loss of total blood volume without a loss of central venous pressure and as a means by which central venous pressure can be increased during exercise.
  Factors That Influence Venous Pressure and Venous Return
     Venous pressure has an important affect on mean arterial pressure because it affects venous return to the heart and influences end-diastolic volume. This in turn increases stroke volume and cardiac output according to Starling's law of the heart. Venous pressure is due to the pressure difference between the peripheral veins and the right atrium. It is about 15 mm Hg
     Factors that affects venous pressure include:
  Skeletal Muscle Pump
   Muscle contraction forces blood toward the heart because of the one-way valves within the veins. By alternately contracting and relaxing, the skeletal muscles drive blood toward central veins and increases venous pressure.
  Respiratory Pump
   During inhalation the pressure in the thoracic cavity falls and abdominal pressure rises. This creates a pressure gradient that moves blood from the abdominal veins to the thoracic ones. During exhalation flow back into the abdominal veins is prevented by one-way valves and an increase in thoracic pressure drives the blood toward the heart.  
  Blood Volume
   An increase in blood volume produces an increase in venous pressure and a decrease has the opposite effect. Blood volume may decrease due to dehydration or blood loss. Blood volume may increase due to kidney failure
   The high compliance of the veins may result in venous pooling or accumulation of blood in the veins. This lowers mean arterial pressure by lowering venous pressure. 
  Venomotor Tone
   Neurons of the sympathetic nervous system increase the contractile activity in the venous smooth muscle and increase venomotor tone. An increase in venomotor tone:
1. Increases venous pressure in peripheral veins and increases blood flow to the central veins;
2. Reduces the venous compliance and thereby increases venous pressure. Venous return increases which increases stroke volume and mean arterial pressure rises.  
  Lymphatic System
     The 3 liters of fluid filtered out of the capillaries returns to the cardiovascular system by the lymphatic system. Fluid enters the lymphatic system by way of blind-ended ducts called lymphatic capillaries. The capillaries carry the fluid by a system of ducts to two large ducts that finally drain into the blood stream. Lymph flows through these ducts by means of skeletal muscle contraction and one-way valves. Larger ducts also have smooth muscles in their walls.
     Lymph nodes are located along the lymph vessels. Foreign organisms (bacteria) and particles are filtered in these lymph nodes where they can be phagocytized by macrophages and where lymphocytes can react with the foreign substances to stimulate an immune response.
Mean Arterial Pressure
     Mean arterial pressure is determined by :
1. Heart rate Both determine CO
2. Stroke volume
3. Total peripheral resistance
     When mean arterial pressure is steady, flow into and out of the aorta remains steady. When cardiac output suddenly increases and total peripheral resistance remains the same, the mean arterial pressure increases. If there is a sudden increase in total peripheral resistance and cardiac output remains the same there is also an increase in mean arterial pressure.
Regulation of Mean Arterial Pressure
     Mean arterial pressure needs to be maintained at a proper level for the organs to function properly. Control of mean arterial pressure is accomplished by the central nervous system and circulating hormones. There is both short term and long term control of MAP. Short term operates from seconds to minutes and is our major concern. 
Neural Control of MAP
     MAP is regulated by negative feedback control. MAP is the regulated variable that is monitored by arterial baroreceptors sensors.
  Arterial Baroreceptors
     Arterial receptors are found in
1. Aortic arch
2. Carotid sinuses of the carotid arteries. 
     Baroreceptors respond to changes in pressure within the CV system. When the walls of arteries stretch in response to an increase in pressure the sensory endings of baroreceptors neurons are stretched and this induces depolarization. The depolarization triggers action potentials that then travel to the central nervous system.
     When MAP changes these neurons make the appropriate changes in the heart and blood vessels.
  Cardiovascular Control Center of Medulla Oblongata 
     The neural control of mean arterial pressure resides primarily in the medulla oblongata. Sensory input to the medulla include:
1. Arterial baroreceptors
2. Baroreceptors in the heart and large systemic veins that sense venous pressure (volume receptors). 
3. Chemoreceptors that sense oxygen, carbon dioxide and hydrogen ion concentration
4. Proprioceptors in skeletal muscle and joints
5. Receptors in internal organs
Input from higher brain centers to the medulla include:
1. Hypothalamus
   Controls flight-or-fight responses 
   Regulates resistance of blood vessels in skin for temperature control
2. Cerebral Cortex
   Controls response to pain and emotion and to exercise
   Modulates medulla's response to sensory inputs
  Autonomic Inputs to Cardiovascular Effectors
     The cardiovascular centers of the medulla exerts control over the sympathetic and parasympathetic neurons that innervate the heart and blood vessels. Sympathetic input travels via preganglionic fibers that emerge from the spinal cord and synapse with postganglionic fibers in the sympathetic trunk ganglia and collateral ganglia. Parasympathetic input travels to the heart via preganglionic fibers in the vagus nerve (X) that synapse with postganglionic neurons in the heart itself. 
     The primary neural control of cardiovascular function is exerted by the sympathetic neurons to:
1. the sinoatrial node to control heart rate
2. the ventricular myocardium to control ventricular contractility
3. the arterioles to control vascular resistance
4. the veins to control venomotor tone
     The parasympathetic only exerts control over the heart rate at the sinoatrial node.
Baroreceptor Reflex
     A drop in MAP is detected by arterial baroreceptors and this results in a decrease in frequency of action potentials. This results in decreased parasympathetic activity and increased sympathetic activity. The increased sympathetic activity results in increased heart rate, stroke volume and total peripheral resistance all which increase MAP. 
     Figure above illustrates the baroreceptor reflex during blood loss. The stroke volume and cardiac output drops and brings down the mean arterial pressure. The baroreceptor reflex then causes the heart rate and total peripheral resistance to increase which raises the mean arterial pressure. The baroreceptor reflex triggers an increase in total peripheral resistance by sympathetic stimulation of vasoconstriction. Certain organs are spared because of their need for a continual blood flow. These vital organs include the heart and the brain.  
     The baroreceptor reflex produces only a quick temporary fix. Long term fixes require an adjustment in blood volume that can be achieved by regulation of fluid intake and excretion. 
Hormonal Control of MAP
    Epinephrine affects both cardiac output and total peripheral resistance. 
    At the heart, epinephrine binds to receptors at the SA node and increases heart rate by increasing the frequency of action potentials. Epinephrine also binds to receptors on the ventricular myocardium which increases cardiac contractility.
    At the vasculature, epinephrine causes vasoconstriction in most vascular beds but can cause vasodilation in skeletal and cardiac muscle. Most often the effect of epinephrine is to increase total peripheral resistance.
    Hence, epinephrine increases mean arterial pressure by increasing heart rate, stroke volume and total peripheral resistance. 
   Vasopressin (ADH)
   Acts by promoting vasoconstriction in most tissue and thereby increasing total peripheral resistance (TPR) and mean arterial pressure. Also known as antidiuretic hormone because it also acts upon the kidneys to decrease urine production (diuresis). This helps to maintain blood pressure by conserving blood volume.
   Angiotensin II
   Angiotensin II is derived from angiotensinogen which is present in the plasma. Angiotensinogen is converted to angiotensin I by renin which is secreted by the kidney. Angiotensin I is converted to angiotensin II by angiotensin converting enzyme which is present on the inner surface of the blood vessels particularly in the lungs.
   Angiotensin II increases mean arterial pressure by promoting vasoconstriction, reducing urine output by the kidneys, and stimulating thirst. 
Other Cardiovascular Regulatory Processes
   Respiratory Sinus Arrhythmia
     This is a rhythmic variation in heart rate in which inspiration is accompanied by an increase in sympathetic activity and heart rate whereas expiration is accompanied by an increase in parasympathetic activity and a decrease in heart rate.
   Chemoreceptor Reflexes
     When arterial carbon dioxide levels rise, chemoreceptors in the carotid sinus and brain trigger a decrease in heart rate and in increase in peripheral resistance. This helps to conserve oxygen and to insure that the brain continues to receive an adequate supply of oxygen. This reflex also prevents a widespread drop in mean arterial pressure due to local reflexes causing vasodilation in response to decreased oxygen and increased carbon dioxide levels.
   Thermoregulatory Responses
     Thermoreceptors in various locations around the body provide input to the hypothalamus where the thermoregulatory center is located. When the body's temperature rises the decrease in sympathetic activity in the nerves supplying the skin causes vasodilation and heat loss through the skin. A decrease in body temperature increases the sympathetic activity in the nerves supplying the skin and causes vasoconstriction and conservation of heat by shunting blood away from the skin.
   Response to Exercise  
     During exercise cardiac output increases blood flow. Flow to skeletal muscles, cardiac muscle and skin increase while flow to the liver and gastrointestinal tract decrease. There is a total overall drop in total peripheral resistance but this does not cause a drop in MAP because of the increase in cardiac output.
     These responses to exercise is triggered by cortical and limbic regions of the brain that influence the output of sympathetic and parasympathetic neurons. As a result:
There is an increase in sympathetic and a decrease in parasympathetic activity to the heart that increases heart rate and ventricular contractility.
There is an increase in sympathetic activity to digestive organs and other organs that causes vasoconstriction.
There is a decrease in sympathetic activity to the skin that causes vasodilation.
     Other mechanisms that promote an increase in the venous return and thereby increase cardiac output are
The skeletal muscle pump,
The respiratory pump,
An increase in venomotor tone.