What are the normal values for the variables listed?
What is heart failure? What kinds of diseases may cause heart failure and what effects do they have on CO (which part of CO specifically)? Why is heart failure often called congestive heart failure?
Heart failure is a reduced capacity of the heart to pump blood. It may a manifestation of may different cardiac diseases including MI, coronary atherosclerosis, cardiomyopathies, valvular heart disease, HTN, and congenital heart diseases. These conditions can affect the determinant of stroke volume e.g. heart failure can result from decreased contractility and/or increased afterload. A common result is fluid retention which leads to an increased cenral venous pressure. This helps to compensate for the impared function of the heart by increasing ventricular filling (which increases stroke volume). However, high venous pressure leads to edema formation and congestion, hence the common term congestive heart failure.
What are the 2 types of cardiomyopathy?
dilated cardiomyopathy (what case study pt has)
How is hypertrophic cardiomyopathy characterized? What are some of its symptoms/associated diseases? What mutations lead to this disease (when it is inherited) and what do the mutations result in at the cellular level?
Hypertrophic cardiomyopathy causes cardiac muscle cells to grow larger and results in thickening of the walls of the heart. The affected heart does not relax well during the filling phase of the cardiac cycle. It can either be inherited or acquired. Macroscopically, HCM is characterized by increased left ventricular mass (particularly interventricular septum) and is histologically characterized by myofibrillar and myocyte disarray. The myocytes often have bizarre shapes and are arranged in chaotic patterns. These disorganized cells in the ventricle may impair transmission of the AP and predisopose the heart to arrythmias. Additionally, pts may have dyspnea, palpitations, chest pain, syncope, heart failure, or sudden deat, although pts are frequently asymptomatic. Hereditary hypertrophic cardiomyopathies arise from genetic mutations of the sarcomeric contractile proteins, including myosin, tropomyosin, and troponin. These mutations cause muscles to shorten much more slowly than usual with greatly reduced power output so muscle cells enlarge to compensate.
How is dilated cardiomyopathy characterized? What mutations lead to this disease (when it is inherited) and what do the mutations result in? What is the most common inheritance pattern?
Dilated cardiomyopathy (DCM) is characterized by ventricular dilation, increased ventricular volume, and systolic dysfunction. About 30% of all DCM cases are inherited with autsomal dominant inheritance being most common. Hereditary DCM is apparently most commonly caused by a weakening of the myocyte cytoskeleton. Mutations of the genes encoding dystrophin and dystrophin glycoprotein complex have been shown to produce DCMs. Dystrophin and the DGC are thought to play a vital role in muscle by forming connections between the internal cytoskeleton and/or sarcomeric structure and the extracellular matrix surrounding the muscle cells; mutations can
cause problems with force transmission and general muscle cell and membrane integrity.
What are the general fxns of the cardiovascular system?
Transport system that supplies every cell in teh body with required nutrients and removes cells' waste products. Also participates in mechanisms such as temp regulation, humoral communication, and adjustment of O2 and nutrient supply in diff physiological states.
True or false: The cardiovascular system normally provides each tissue and organ with the blood flow that it
requires to sustain its metabolism and to carry out its particular special function(s). It must respond:
1) to the fact that the activity of each tissue and organ varies both acutely (short-term) and chronically (i.e. long-term)
2) to pathology that can give rise to changes in tissue or organ function.
True. For example, the cardiovascular system (CVS) needs to be able to respond to both the short-term,
immediate stress of exercise along with the long-term, gradually developing stress of chronic heart failure. It does this in a variety of different ways.
The CV system is made up of a positive pressure pump, the ____, and a set of blood vessels, the ____, that carry blood to every cell, tissue, and organ.
The heart is a muscular pump which is actually two pumps in ___. The contraction of the left and right heart produces ____ ___ in the blood vessels.
2. elevated pressure
True or false: The blood vessels into which the heart pumps are elastic and thus maintain a non-zeoro pressure in the circulation at all times.
Because blood flows from high to low pressure and the rate of flow is proportional to the pressure difference, what is the consequence of the heart pumping with more force?
A greater pressure difference resutls within arteries, and therefore, more flow results. Ohm's Law
Flow is inversely proportional to _____.
resistance. Ohm's law
True or false: Flow is distributed to the various organs to meet physiological needs by maintaining a more of less constant pressure gradient across the circulation
and varying the resistance to flow of each tissue or organ.
In order to maintain appropriate flow to all parts of the body in the face of changing needs and physiological disturbances, what 2 parameters does the CV system regulate? How does the CV system regulate these parameters? What is the difference btwn a regulated and controlled parameter? Give an example in the body.
The CV system regulates (holds more or less constant) mean arterial pressure (MAP) and blood volume (BV). It does this through sensory receptors that measure MAP and BV. All other CV parameters are controlled in a manner that contributes to regulating MAP and BV. For example, baroreceptors in the carotid sinuses in the aortic arch sense changes in blood pressure and reflexively elicit inverse changes in heart rate. MAP is regulated (i.e. the body tries to keep it constant), HR is controlled by the body to maintain the regulated parameter.
Describe the anatomy of the aorta, arteries, arterioles, capillaries, venules, and veins as it relates to diameter, thickness, and contents (endothelium, elastic tissue, smooth muscle, fibrous tissue).
• The aorta has a large diameter, thick walls, has a high
percentage of elastic tissue.
• The arteries are of intermediate diameter, thick walled, and have a high percentage of smooth muscle.
• The arterioles are of small diameter, relatively thick
walled, and have a high percentage of smooth muscle. They are the stopcocks of the body: control flow to tissues by adjusting degree of contraction (decreases radius, increases resistance).
• Capillaries are small in diameter, have walls one cell
thick and are the level on which nutrient exchange takes place.
• Venules are small in diameter, have thicker walls and are mostly fibrous tissue.
• Veins are large in diameter, have thick walls and are
largely smooth muscle.
Blood entering the right ventricle through the right atrium is pumped through the pulmpnary arterial system at a mean pressure of about ______ of the systemic arteries.
Pulmonary artery pressure (s/d/m) 25/7/13 mmHg
Aortic pressure (s/d) 120/70 mmHg
Pressures in the body are expressed relative to _____ pressure. Negative pressures (which exist in the thorax) merely represent pressures that are less than ____ (same as previous blank) pressure.
atmospheric. 100 mg of Hg is 100 mmHg greater than atmospheric pressure.
How does flow change as you go from the aorta, to arteries, to arterioles, etc.?
It doesn't! The flow, which is the sum of the movement of blood in all of the vessels in a particular section of the circulation, is the same in all parts of the system. The flow of blood in the aorta is equal to the flow of blood in all of the little capillaries (when added all together).
Remember that the flow in any system is directly proportional to the pressure gradient and is inversely proportional to the resistance. If there is a large pressure difference form one end of a particular class of vessels to another, what does this mean for resistance?
If there is a large pressure gradient from one end of a class of vessels to another, there is large resistance to flow.
So, if flow is constant when the resistance goes up, the pressure difference rises as well.
What is the pressure in the aorta as compared to arteries and what does this mean for resistance? Where in the vascular system is there a pressure difference? How is this pressure difference obtained and why? How does this effect pressure in vasculature that come after it?
Pressure is generally maintained from the aorta to the larger arteries which means that resistance is relativley small. The arterioles are the principal points of resistance to blood flow in the circulatory system. These vessels are primarily responsible for regulating flow into organs and tissues and they increase resistance through vasoconstriction (decreasing radius). Because the resistance in this section is relatively high, there is a large pressure drop across this class of vessels. That is, it takes a large pressure gradient to drive the flow through the high resistance arterioles. On the other hand, it takes a small pressure difference to drive the same flow through the low resistance arteries and veins. Since the pressure drops so much across arterioles, the hydrostatic pressure is low in capillaries and is even slightly lower in venules and veins.
Note that flow cannot take place without some kind of pressure gradient. Although it appears presure is the same in the aorta and arteries, it must (and does) drop.
Veins are more compliant than arteries. What is compliance? What anatomical differences lead veins to be more compliant?
Compliance: meausre of stretchiness. Measured by determining Δvolume/Δpressure (that is, the
change in volume that is observed for each unit change in observed pressure). If I blow up a balloon,
the pressure inside goes up. As this happens, there is a measurable increase in the balloon volume.
Its walls have a relatively high compliance. If I blow into a container made of steel, the pressure
will go up but the volume will not increase very much. The walls of the steel container have a relatively low compliance.
Arteries and arterioles have relatively thick, muscular walls and veins and venules have relatively
thin walls. It therefore makes sense that it would take less pressure to increase the volume of a vein
and, indeed, it does. You may also think of it the other way, it takes more volume to increase the
pressure in a vein. Veins are therefore considered to be more compliant than arteries.
In what vessels is most of the blood volume contained? What property of these vessels allows them to store so much blood?
Most (2/3) of the blood volume is to be found in the venous compartment. This is by far the vascular compartment with the most blood. Indeed, whereas the arteries are often referred to as “resistance vessels” because of their regulatory role, the veins are often referred to as “capacitance vessels” because of their role in storage of blood as a reserve. The high compliance of the veins makes this storage function possible as the veins can keep large volumes of blood at relatively low pressure.
Note that very little blood is contained within arterioles. Blood volume within the arteriolar compartment therefore does not change a great deal when they contract.
What are the differences btwn velocity of blood flow and rate of blood flow in a vessel? How is velocity of blood flow calculated?
The velocity of blood flow is NOT the same as the rate of flow in a blood vessel. The velocity of blood flow is perhaps better designated as the "linear velocity" which refers to the rate of displacement with respect to time (cm/s). The flow or "volume flow" has the dimensions of volume per time (ml/s). The linear velocity is related to the flow and cross sectional area (cm2):
Q=v x A
As cross-sectional area decreases, velocity increases.
How does velocity change as blood travels through the aorta and to increasingly smaller vasculature?
As shown in Figure S.8, the velocity decreases progressively as the blood travels through the aorta,
progressively through the smaller and smaller branches to the arterioles. Note that the total flow is constant (top panel) through out the system. A minimal value is reached at the level of the capillaries. As the blood traverses the venules to the veins and the vena cavae, the velocity gradually increases again. The relative velocities in each of these components are related to their total cross-sectional areas. Note that though the cross-sectional area in each individual capillary is
small, there are so many that the sum total cross-sectioanl area of the compartment (i.e. all of the
capillaries added together) is relatively large. The larger the total area, the smaller the velocity!
True or false: Compliance is more or less constant over the range of physiological pressures.
Fill in this table.
What are the 3 functions of the arterial compartment of the cardivascular system?
1. Creation of the elevated pressure head that brings about continuous perfusion of tissue. This elevated pressure is actually generated by the heart, which forces a large volume of blood into the aorta and its branches. The pressures within the aorta and the arterial branches from it are very large and it’s this pressure which drives the flow of blood.
2. Containment and transport of blood ("conduit" function). The arteries carry the blood from the heart to the general vicinity of the organs which need it.
3. Control of the resistance to flow (in individual pathways and in the CV system as a whole). The
arterial system distributes blood to the capillary beds throughout the body through the action of the
arterioles which constrict to raise resistance and restrict flow to the bed and dilate to decrease resistance and increase that flow
What is hydraulic filtering? What effect does this have on capillaries?
Hydraulic filtering is the process by which the distensibility of the aorta and the arteries converts
the intermittent output of the heart into continuous (but pulsatile) tissue perfusion (Figure S.9).
Thus, the rapid ejection of blood from the heart is converted to a continuous flow. Here’s how it works. The entire stroke volume of the heart is ejected into the arterial system in about 300 ms or approximately the first 1/3 of the cardiac cycle. Most of this is ejected in the first 150 ms or so. While the flow to the capillaries increases some during this phase, it doesn’t increase
enough to compensate for the increased flow into the arteries as the heart contracts - nor would we
want it to. A slower, steadier flow will be more efficient for nutrient exchange.
Therefore, in order to compensate for this rapid ejection of blood, the arterial walls stretch and the volume increases. During diastole, the elastic recoil of the arterial walls continues to maintain a pressure head which results in sustained capillary flow. As the volume drops, the pressure gradually declines but slowly. The resultant pressure wave in the arterial compartment is illustrated in Figure S.10.
What determines pressure within arteries? State the equation. What determines the volume of blood in the arteries?
Recall that compliance of a vessel is the rship btwn volume and pressure (∆V/∆P). The pressure in the
arteries is determined by the volume of the fluid contained within the arteries and by their compliance
In turn, the volume within the system is determined simply by the amount of fluid entering and the amount of fluid leaving the system. The amount of fluid entering is the cardiac output. The amount leaving the system is determined by the flow of blood through the resistance vessels (the terminal
arterioles). If the inflow exceeds the outflow, the arterial volume increases and the arterial walls are
stretched more and pressure rises. When the outflow exceeds the inflow, pressure declines. This is
effectively what is happening during the pressure wave in Figure S.10, which shows the features of
the aortic (arterial) pressure pulse wave. Note: Although the pressure in the left ventricle fluctuates
between essentially 0 and 120 mm Hg, the pressure in the aorta fluctuates between 80 and 120 mm Hg
What is mean arterial pressure (MAP)? What two ways may it be calculated? Why is MAP important?
MAP is the average, over the time of one cycle, of arterial pressure. The approximate value of MAP can be calcuated from the systolic (Ps) and diastolic (Pd) blood pressure values:
MAP=PD + (PS-PD)/3
MAP is important bc it describes, in one term, the average pressure on the arterial side of the circulation.
Refer to attached diagram. Blood flows from right to left as you look at the diagram. The high, arterial pressure drives that flow in the direction of the low venous pressure. In between we have sources of resistance which control the flow to the individual tissues and organ systems (Circled with heavy, black lines). If we consider the total effect of all of the individual resistances upon the systemic circulation as a whole from right to left, arterial to venous, we can lump them together as one number, the total peripheral resistance or TPR. Therefore, over the entire circulatory system:
1) is the pressure in the arterial system or the MAP
2) is the pressure in the venous system (PV)
3) is the cardiac output (CO)
4) is the total peripheral resistance (TPR)
But, Pv is normally very smal and more or less constant and hence it can usually be ignored. Therefore , we can write:
NOTE ITS SIMILARITY TO OHM'S LAW!!!
What are the main determinants of MAP? How is MAP regulated? How is CO controlled? How are the parameters of CO related to MAP?
MAP=CO(TPR) is a statement of causality, i.e. MAP is determined by the CO and TPR. This equation can be rearranged to calculate the other values but only this equation is a statement of causality. CO and TPR are controlled to regulate MAP.
In the same way, the body does not change CO by changin MAP. Instead, the following holds for CO as a statement of causality:
CO=HR x SV
CO (and therefore MAP) goes up with SV and HR. Teh body changes HR and SV to determine CO.
Note in the attached figure that the decrease mean pressure along the length of the large arterial arteries is very small. What property of the vessels allows for the pressure differences to be so small?
The pressure along the arterial tree really only declines slightly from the heart to the periphery bc the resistance posed by the arteries is low. That’s not to say that pressure doesn’t decline at all. It does. Indeed it must in order for blood to flow. But the pressure decline along the course of the vessels in the system doesn’t become dramatic until the level of the arterioles is reached.
Because the arterioles offer the greatest level of resistance to flow of blood, what role do they have in maintenance of arterial blood pressure? What about their anatomy allows them to play this role? What is Poiseuille's Law?
Because they offer the greatest resistance to flow of blood pumped to the tissues by the heart, they are important in maintenance of arterial blood pressure. The main component of the walls of these vessels is smooth muscle which can vary the size of the vessel lumen from complete obliteration to maximal dilation. At any given time at least some arterioles must be at least partially closed. If all of them dilated at once, blood pressure would drop to dangerous levels.
R =η x l x 8/(π x r4)
η =viscosity, l=length, r=radius
Note well the r (radius) to the fourth power in the denominator of this equation. This means that as radius goes down and up in relatively small amounts, the resistance increases and decreases dramatically. It is, therefore, important that you remember that, although the other parameters do have their effects and you should be aware of them, resistance, R, is most powerfully determined by the radius (r) of the blood vessel (R ∝ 1/r4).
The radius of arterioles is a function of the state of contraction of smooth muscle in the walls of the arterioles. What 2 classes of factors determine the state of contraction of the smooth muscle in arterioles?
What is autoregulation?
There are several basic mechanisms by which the flow of blood is adjusted locally. The first basic mechanism which we will address is the maintenance of constant flow through a vessel locally in response to a change in pressure with no change in metabolic activity. This mechanism is commonly referred to as autoregulation and the concept is demonstrated in Figure S.16. This data is from a renal preparation where these autoregulatory effects tend to be exaggerated. The pressure within the vascular bed was increased with no changes is any other factor (with no endothelium
present). Initially, the flow increases or decreases with the pressure as you would expect based
upon Ohm’s law. But note what happens at the middle pressures. The flow stays at nearly the same level. This is because the blood vessels dilate or constrict to decrease or increase resistance in response to the pressure to increase or decrease the flow, respectively.
The reason behind this constancy of blood flow in the presence of altered pressure is unknown but it appears to be best explained by the myogenic mechanism. According to this explanation, the vascular smooth muscle contracts and relaxes in response to a change in transmural pressure (i.e. pressure across the vascular wall). Since this response is seen in isolation, it seems to be a property of the smooth muscle itself.
What role may the endothelium play in local regulation of blood flow? Under what circumstances do they regulate local blood flow?
It can be shown that if you increase flow without increasing the transmural pressure across the vessel wall, you can cause vasodilation. This mechanism is dependent upon the presence of the endothelium and is presumably caused by nitric oxide, which is released from the endothelial cells in response to sheer stress.
What is the main factor in the local regulation of blood flow? How/by what mechanisms is this regulation achieved? (hint: there are 6 of them)
Tissue metabolic activity is the main factor in regulation of local blood flow. Anything that results in an inadequate O2 supply to tissues results in the release of metabolites and vasodilation. These metabolites act locally upon the smooth muscle to cause dilation.
Though increased and decreased PO2 definitely does lead to contraction and relaxation vascular smooth muscle through this general mechanism, the exact mechanism is unknown. There are several potential candidates though none is completely satisfactory and though many or all may play a role, their relative contributions are still being determined (Figure S.17):
a) Lactic acid: released due to anaerobic metabolism.
b) CO2: released with increased mitochondrial activity in active tissue
c) H+ ions: decreased pH is caused by CO2 and lactic acid
d) K+ ions: increased in response to increased membrane depolarization in some active tissues
(particularly striated muscle).
e) Phosphate and adenosine: increased due to increased breakdown of ATP (into ADP, AMP, and adenosine + phosphate) in active tissue.
f) Osmolaity: increases in active skeletal muscle
What is basal tone? What factors are responsible for basal tone in arterioles?
Control of blood flow by vasodilator mechanisms is predicated on the existence of a certain tonic, basal level of contraction. In contrast to the situation with skeletal muscle, the tone in smooth muscle is independent of the nervous system. The factor(s) which is responsible for basal tone is unknown but the possibilities include:
a) Myogenic activity in response to the normal blood pressure.
b) The high O2 tension in arterial blood.
c) The presence of calcium ions in the plasma.
d) Some other unknown factor in the plasma.
Local mechanims of vascular control always predominate extrinsic control. However, there are central mechanisms which the body uses to control tone and regulate flow to different regions. Of these mechanims, which is the most important?
The most important aspect of extrinsic vascular control are associated with autonomic innervation.
We know there are sympathetic and parasympathetic branches of the autonomic nervous system and that innervation of arterioles by the ANS is the most important extrinsic mechanism of vascular control. What types of receptors do the sympathetic and parasympathetic branches of the ANS stimulate? What is the dominant effect of sympathetic stimulation to arterioles in skeletal muscle?
The sympathetic system can activate α and β receptors and in some cases cholinergic receptors while the parasympathetic system activates cholinergic receptors.
The dominant effect of sympathetic stimulation to arterioles in skeletal muscle is activation of α-receptors and vasoconstriction. Also keep in mind that local metabolic controls are likely to dominate the
vascular response in active (exercising) muscle.
see pg 44 of notes for more in depth explanation
True or false: There is no parasympathetic innervation of the vasculature (with a few exceptions like external genitalia).
True or false: The effects of NE and E released from the adrenal medulla are just as important as NE produced by sympathetic nerve activity.
False. Although the adrenal glands do release epinephrine and norepinephrine, the effect of
catecholamine release from the adrenal medulla is of lesser importance than the norepinephrine
produced by sympathetic nerve activity under physiological conditions.
Describe the reason for the differences in distribution of blood to each organ. Hint: involves Ohm's law.
Organs are strung in parallel btwn the aorta and vena cava. At rest, CO is divided btwn the various tissue beds as shown in the figure.
Ohm's Law: Q=(P1-P2)/R
For the entire system show in the attached figure, P1 or Pa is arterial pressure and P2 or Pv is venous pressure. Note that aortic and large artery resistances are small so mean pressure changes very little along the arterial tree and that the venous resistance is small so venous pressure changes very little along the venous tree. So the Pa-Pv (i.e. ΔP) is essentially the same for all organs.
Note the percentage distribution of the blood to each type of circulatory bed on the right hand side
of the figure. Since blood flow through any tissue bed is ΔP/R and since the arterial and venous pressure gradient across each bed is approximately the same, the differences in flow must represent differences in the resistance to flow posed by each of these circulatory beds. The greater the resistance in any particular bed or organ, the less blood flow to that bed and the lower the
percentage of the total cardiac output that bed is supplied with. In its most basic form, this is how
the cardiovascular system operates.
Like arteries, veins serve as conduits for transport of blood (in this case from vascular beds) to the right atrium. Note that the pressure gradient within the system is relatively small within the venous compartment. What is a potential issue that this low gradient poses for the body?
This low pressure gradient causes problems for the body. For instance, consider what happens to the legs when a person stands after lying in a recumbent position. The pressure within the veins increases dramatically because they suddenly have a column of blood pushing down from above. Such a sudden pressure change could potentially cause havoc in terms of blood flow. Because of this, the venous flow is assisted in its function in a variety of ways.
How is venous return assisted? What is the role of venules in venous return? What are the skeletal muscle and respiratory pumps? What important role does the skeletal muscle pump play during exercise? What about the anatomy of veins allows these pumps to function?
When a relaxed individual stands, the volume of the veins in of the legs increases only gradually due to the presence of one-way valves. These valves tend to permit only blood flow toward the heart and prevent a large volume of blood in the veins from falling rapidly toward a person's feet. In the mean time,
while the valves are still closed, the venules continue to supply the larger veins with blood. As they do this, the volume of blood behind the valves increases and the pressure rises. Then the pressure behind the valve exceeds the pressure in front of the valve, it opens and blood flows toward the heart again.
The presence of venous valves allows skeletal muscel pump to assist in the return of blood to the heart. Surrounding skeletal muscle literally squeezes blood out of the veins and one way valves only allow the flow to take place toward the heart. This is referred to as muscle pumping and it plays an important role in enabling the CV system to enormouslyincrease blood flow during exercise. Please see pg 54 of notes for detailed explanation of muscle pumping as illustrated in attached figure.
A similar assist to venous return as muscle pumping is provided by the pumping action of movement of the thorax (respiratory pump). In this case, the decrease in pressure during inspiration aids in blood flow and the valves prevent backflow during respiration. (remember that a pressure gradient is required for flow and blood flows from low to high pressure. negative intrathoracic pressure during inspiration causes blood to flow into the lungs.)
We know that venous volume is quite large compared with arterial blood volume and the size of the venous compartment is determined in part by the compliance of the venous compartment (large compliance results in relatively high volume at a relatively low pressure). The high volume of the venous compartment allows it to act as a sort of reserve storage compartment for blood within the body. What activity of veins reduces the size (capicty) of the venous compartment? What stimulates this activity?
Venomotor activity (contraction of vascular smooth muscle in the walls of the veins) reduces the size (capacity) of the venous compartment and mobilizes blood volume (i.e. augments venous return of blood to the heart). Contraction of venous smooth muscle also decreases the compliance of the venous compartment (the walls are stiffer) and thus, for the same volume, increases the pressure that is present. This increased pressure also acts to augment venous return. The increase in venomotor activity is usually due to sympathetic stimulation in response to stimuli such as exercise or hemorrhage.
What are the effects of lying down vs standing up on the venous system?
Note that the pressures in a person standning up (part B of figure) are before any CV reflexes kick in. The pressures in the person lying down are practically the same everywhere. All of the vascular beds are more or less at the level of the heart. The BP is determined in th heart. When the persno stands up, pressures at the heart do not initially change bc this is where MAP is regulated (not really true but will learn differently later). The lower vascular bed which can be called the feet is now below th heart. The pressure on either side of the vascular bed is now increased.
The change in arterial and venous pressures is due to vertical columns of blood (fluid) that are present. Gravity pulls down on these columns and increases the pressure. The increased pressure doesn’t change the volume on the arterial side much because the compliance of the arteries is low. However, since venous compliance is high, the increased pressures below the heart cause an increase in volume of blood in the peripheral venous vessels. Thus, there is a redistribution of blood volume between peripheral compartment away from the heart) and the central venous compartment (near the heart - i.e. peripheral venous volume is increased while central venous
volume is decreased with erect posture).
Note that the pressure gradient along any circulatory path below the heart is unchanged (arterial and venous pressures are equally incremented) but that the absolute pressures vary in the erect individual depending on location above or below the heart. Therefore the pressure gradient acrossthe beds which drives blood flow is not immediately changed by standing up.
What is the functional anatomy of arterioles as it pertains to capillary beds? What is the difference in the amount of capillaries present in skeletal muscle vs skin?
The arterioles are the “stop cocks” of the cell. As noted above they have a thick smooth muscle layer which makes them ideal for this function. The arterioles can rise to capillaries directly or they can give rise to metarterioles which can either give rise to capillaries or can serve as bypasses which directly interface with venules.
Note the presence of arteriolar-venular shunts. In both muscle and skin the enterance to the capillary is controlled by a muscular precapillary sphincter which, when contracted, limits blood flow to the bed.
Note that capillaries in an active tissue such as skeletal muscle are more numerous than in the less active tissue.
What constitutes the wall of a capillary? What controls capillary size?
Capillaries consist of basement membrane and a layer of endothelial cells. Since there is no smooth muscle, the changes in capillary diameter are passive and are controlled completely by the pre and post capillary resistance.
What is the primary way in which solutes get from the capillary lumen to cells? What is the equation for calculating the rate of this process? Note which factors of this process are directly and inversely proportional to its rate.
The primary way in which solutes get from the capillary lumen to cells is through diffusion.
Js = Ds (A)([S1] - [S2])/x
Js = rate of transfer of substance S (amt/time)
Ds = diffusion constant for S (inversely related to molecular weight)
([S1] - [S2]) = concentration difference of S across capillary wall
A = surface area available for the diffusion of S
x = diffusion distance across the wall.
The process of diffusion is driven by the concentration gradient for the solute (i.e. the difference in
the solute concentration divided by the distance). So the rate of diffusion is inversely proportional to distance, and to the size of the molecule and directly proportional to the concentration gradient and the surface area
How do lipid soluble solutes travel across the capillary wall? O2 and CO2? Electrolytes and biological molecules?
Lipid soluble solutes can diffuse across the entire wall of the capillary since they are lipid soluble (e.g. the respiratory gases oxygen and carbon dioxide). But electrolytes and all small biological molecules diffuse through the fluid filled pores. This process is the predominant mode of solute transfer. Electrolytes and small molecules are also carried by the bulk flow of fluid through the pores.
Note that while gasses, substrates, and waste products are transported primarily by diffusion, bulk fluid transfer is mainly attributable to what 2 processes?
filtration and reabsorption
What is filtration? What is the force behind filtration?
What is reabsorption? What is the force behind reabsorption?
How is the net force determined? What does calculation of the net force tell you?
filtration: transfer from capillary (vascular component) to the interstitial compartment
The force behind filtration is primarily the difference in hydrostatic pressure between the capillary lumen and the interstitial fluid
Pc - Pi
Pc = capillary blood pressure
Pi = interstitial fluid pressure
The capillary pressure is usually higher than the interstitial fluid under normal physiological circumstances.
reabsorption: transfer of solutes from the interstitial compartment into the capillary
The main resorptive force is the difference in oncotic pressure:
σ(πc - πi)
where πc and πi are the oncotic pressures (σ is the reflection coefficient, a measure of the permeability of the capillary wall for a substance, in this case, the plasma proteins; its value is 0 for a substance that freely crosses the wall and 1 for a substance that cannot pass across the wall). Reabsorptive force results from the impermeability of the capillary wall to proteins. Since the larger proteins such as albumin can’t cross the capillary wall, water flows back into the lumen in an
effort to equalize the concentration gradients.
The net force is determined by the balance of these 2 factors at any point along the capillary as filtration pushes fluid out and reabsorption pulls it back in:
net force = net filtration force - net reabsorption force
(Pc - Pi) -σ(πc - πi)
This balance determines the direction of fluid movement at that point, i.e. filtration or reabsorption.
READ PG 65 OF NOTES FOR EXPLANATION OF PIC
The average daily imbalance btwn filtration and reabsorption is small and equals the daily ____ _____. How large is this value?
lymph production, 1-3 L/day
How is the rate of fluid transfer along a capillary determined?
The rate of fluid transfer at each point along capillary =
P x S x net force
(where P = hydraulic permeability, S = surface area) P depends upon capillary wall structure. S depends upon surface area of individual capillaries and number of capillaries open. Molecular sieving limits the filtration transport of large molecular weight solutes.
What is the function of the lymphatic system? Where does lymph collect and how is it returned to the circulation? Why is it crucial that lymph be returned to the circulation? What occurs when interstitial fluid formation exceeds ability of lymphatics to drain interstitial fluid?
The ultrafiltrate that leaves the vascular compartment across the walls of the capillaries is returned to the vascular compartment in the lymph nodes and via drainage from the lymph system into the vena cava. The lymphatic system functions to drain interstitial fluid (ISF) and return contents to blood circulation and effectively remove foreign substances from body. The lymphatic system starts with “sacs” within the tissues of the body (lymphatic bulbs). In all organ systems, more fluid is filtered than reabsorbed by the capillaries and plasma proteins escape into the interstitial spaces. The terminal sacs and the vessels at this point are permeant to proteins and therefore collect proteins which escape over time from the capillaries. These proteins need to be removed or they will accumulate and eventually prevent reabsorption of fluid at the capillary level due to increased tissue oncotic pressure.The lymph vessels coalesce and become larger, eventually forming the thoracic duct where the lymph is returned to the blood stream. The lymph is transported mechanically through contraction of smooth muscle via a form of the myogenic mechanism and through a form of muscle pumping similar to that found in veins.Note that edema occurs when interstitial fluid formation exceeds ability of lymphatics to drain ISF.