Control of CV function is needed to:
A. Insure that perfusion-sensitive organs such as the brain and heart always receive the flow they require to maintain their normal function
B. Match the perfusion of every tissue and organ to its respective metabolism
C. Regulate (maintain) blood pressure so that the cardiac output (flow) can be apportioned among the organs by varying their resistance
All of the above require the control of what 3 paramaters?
CO, blood vessel size (TPR), and regulation of blood volume
The pulmonary circulation is in ____ with the right heart and receives the entire cardiac output. The regional circulations are in ____ btwn the left and right heart aned each of the regional circulations receives some fraction of the left ventricular output.
There are 2 types of control of the distribution of blood btwn the regional circulatory beds: local (endogenous) and central (exogenous). What are the local/endogenous factors that control blood flow? What is active and reactive hyperemia?
What are the central/exogenous factors that control blood flow?
What does it mean for a tissue to be overperfused? underperfused?
For instance, you will note that both skin and kidney receive much higher percentages of the cardiac
output than the percentage of the total oxygen they consume; one can conclude that the "excess"
perfusion is related, not to the tissue metabolism of the organ, but to the function of these organs.
These organs are said to be over-perfused. The kidneys filter blood and make urine. They demand
19% of the blood not because the tissue metabolism demands that much but because it needs that
much to perform its function. Similarly, the skin is involved in thermoregulation.
On the other hand, organs such as the heart, which have high metabolic rates relative to their blood
flow are said to be under-perfused. “Under-perfused” is an unfortunate term because it implies that
these tissues don’t get enough oxygen. They most certainly do get enough. Flow to these tissues is
generally well regulated in order to supply their metabolism in times of need. Therefore they
require little extra flow at rest to use as a “reserve”.
Under perfused tissues also are generally very good at extracting O2 and nutrients from the blood.
This can be seen if we examine the last column in the table, the volume % O2 difference. This is
nothing more than the difference in O2 content between the arterial blood going in to the tissue and
the venous blood coming out of the tissue. Under-perfused tissues have a high O2 difference
because they have extracted more O2 from the blood that they were supplied with. On the other
hand, over-perfused tissues are being supplied with more blood. Since they extract only the O2 that
they need, they tend to have a low volume O2 difference.
What portion of the CO does the pulmonary circulation receive? What is the pressure and resistance of the pulmonary circulation relative to the systemic circulation? What does this mean for filtration and fluid accumulation?
The pulmonary circulation perfuses the gas exchange surfaces in the lungs (the nutritive supply to the lungs is provided by the bronchial circulation, Figure 3.4). It is in series with the right heart and thus receives the entire cardiac output; this distinguishes it from the regional circulations, each of which only receives a fraction of the cardiac output. The pulmonary region is a low pressure (13 mm Hg mean pulmonary artery to 5 mm Hg in left atrium), low resistance circulation (Figures 3.5 & 3.6), this certainly makes sense when you think about it. In order for the flow to be the same at a low pressure, the resistance must be low. The tissue hydrostatic pressure is also very low in the lung (it is full of air, after all). The walls of the membranes that separate the alveolus from the capillary are extremely thin (in order for diffusion to be efficient, barrier must be very small and the exchange surface must be as large as possible). So thin that the shapes of the red blood cells in the capillary can be easily discerned (Figure 3.5). If the hydrostatic pressure in the vessels was as high as it is in the systemic circulation, massive amounts of filtration and fluid accumulation would take place. This has pathological implications as well.
Because of the low pressure in the pulmonary blood vessels and their high compliance, gravity effects the distribution of flow to the lungs. Desribe the difference in flow of the pulmonary vessels in zones A, B, and C of the attached figure.
In zone B, the pressures on the arterial and venous sides of the circulatory system are 15 and 5 mmHg, respectively. In zone C, they are both 10 mmHg higher because they are situated below the pulmonary artery and vein with the blood above pushing down on the region. This is the same situation which you would find in the systemic circulation below the heart, say in the legs and feet (Figure S.25). In Zone A, they are both 10 mmHg lower since they are above the pulmonary artery and vein. This is generally the same situation which you would find in the systemic circulation above the heart.
In Zone C, the transmural pressure (the difference in hydrostatic pressure between the lumen of the vessels and the tissue) is increased because the hydrostatic pressure in the vessels is higher. This “stretches” the walls in the highly compliance pulmonary circulation. The diameter of the lumen increases and the resistance falls. Therefore, the flow is higher in the base of the lung. You might also note that the increased hydrostatic pressure in this region makes increased filtration and edema more likely here as well.
In Zone A, the transmural pressure is reduced because the hydrostatic pressure in the vessels is reduced. Because of this, the pressure is below the alveolar tissue pressure surrounding the capillaries. The capillaries are therefore collapsed. Note that in the normal individual with low tissue hydostatic pressure, the vessels don’t collapse. Nevertheless, the diameter of the vessels is decreased because the hydrostatic pressure in the very compliant vessels is decreased. Therefore the resistance is still increased and the flow is less at the apex of the lungs.
In Zone B, the venous end is below the alveolar tissue pressure and the arterial end is above this pressure. The capillaries therefore "flutter" open and closed as the capillaries collapse, the pressure behind them builds and they reopen. In the normal (i.e. no positive pressure ventilation) erect individual, the intravascular pressures still increase from apex to base and the transmural pressures increase accordingly. Because of this, the diameter of the vessels increases from apex to base and the vascular resistance decreases. Flow is therefore higher in the erect individual in Zone C.
True or false: The pulmonary circulation is highly sensitive to neural control and plays a part in the baroreceptor reflex.
False. The pulmonary circulation is relatively insensitive to neural control and plays no role in the baroreceptor reflex.
Why does the pulmonary circulation exhibit hypoxic vasoconstriction? What is the systemic circulation's response to hypoxia?
Note that the pulmonary circulation exhibits hypoxic vasoconstriction (when outside of pulmonary arterioles become hypoxic they vasoconstrict unlike arterioles in the rest of the body which vasodilate). This is, of course, the exact opposite of the response of the systemic circulation to hypoxia where flow is increased. It does make sense if you think about it. If you have a region of the lung which is hypoxic, it means that there is no oxygen available for the blood to pick up. Therefore vasoconstriction takes place to reduce flow to this area and shunt it to other areas which do have oxygen. So the response matches ventilation and perfusion and the less oxygen available, the less blood the body sends to the area. Like the systemic response, the response in the lung is local (and it is not a reflex).
Summary of pulmonary circulation.
Explain why our case pt is having a difficult time breathing while lying down (has to sleep sitting up), is coughing, has JVD (jugular venous distension), and has crackles heard in the bases.
The pts heart is in a negative intropic state. To increase CO, the kidneys retain more fluid to increase CVP and therefore increase CO (see attached figure). This why the pts jugular vein is distended.
Because her CVP is increased, this means that the mid-capillary pressure in the pulmonary circulation is increased which increases filtration and causes fluid accumulation (pulm vasculature is very compliant and is particularly vulnerable to resultant tendency to increase filtration and fluid accumulation results) . This can be heard as crackles upon ausculation. Just as in the systemic circulation with fluid accumulation in the lower extremities, gravity causes fluid accumulation in the base of the lungs due to increased hydrostatic pressure. At night, when the pt lies down, the fluid distributes more evenly throughout the lungs and the pt has a hard time breathing.
The heart has a high metabolic rate relative to its flow. 89% of the O2 consumption is due to the pumping activity of the heart-consumption is proportional to cardiac demand and that demand is very high under conditions when cardiac output is high. We know that that coronary system is underperfused and this is noted in its large (a-v) O2 difference. What does this value mean for the hearts ability to extract oxygen during times of increased demand and/or when the heart is diseased?
First, you will note that there is a large (a-v) O2 difference in this circulation (see Figure 3.3). This is because the heart does a very good job of extracting oxygen and other nutrients from the blood that it gets. Unfortunately, this means that the heart has a limited ability to extract more oxygen from the flow perfusing it. So this is an option that it won’t have to compensate for low flow in times of increased demand and/or disease.
The heart has a limited anaerobic capacity. What does this mean for the regulation of coronary flow?
The heart has limited anaerobic capability. That means it can’t function well if its oxygen supply is cut down or insufficient in times of high demand. And the demand does increase substantially with increased cardiac work. What this means is that the coronary flow has to be very well regulated so that when the heart needs more blood it will get it. This is, in fact, the case.
What is the principal determinant of coronary resistance? What does this mean for coronary flow when demand for O2 is increased?
How may the heart receive blood supply if the lumen of a coronary artery is narrowed?
How much of a role in blood supply to the heart does neural control play?
Metabolic control of the coronary circulation is very strong and it is the principal determinant of coronary resistance (although these vessels do receive an autonomic input). This means that the heart is very good at increasing flow with increased demand. You will also note that the heart has a large capillary reserve (i.e. collateral vessel development). When the lumen of a coronary artery is narrowed, these collaterals will develop and transport blood around the obstruction. These collateral vessels are believed to originate from pre-existing arterioles that undergo proliferative changes of the endothelium and smooth muscle.
There is also some neural control though it is weaker than the local control. Flow increases with sympathetic stimulation and both alpha (constrictor) and beta (dilator) receptors are present in the smooth muscle. Since the increase in flow is accompanied by stronger contraction and tachycardia, the effect is limited because the vessels are compressed.
How does coronary blood flow change during the cardiac cycle? What does this mean for coronary blood flow in an ischemic heart and/or heart failure?
The coronary flow does vary with the stage of the cardiac cycle. In other tissues, where the flow peaks during ejection (i.e. during systole). The coronary flow during the cardiac cycle is shown in Figure 3.9 (attached). Note that flow in the left coronary artery is maximum during diastole (unlike the situation in the right coronary artery or other tissue beds). This occurs because during systole the contraction of the left ventricular myocardium compresses the left coronary vessels increasing their resistance and thus decreasing their flow. During systole, contraction of the myocardium applies a high pressure to the blood vessels in the walls of the heart. This high transmural pressure makes the vessels smaller (they are "squeezed") and their resistance increases.
Think carefully about the effect of increasing HR upon the perfusion of the left ventricle. Figure 3.9 represents a cardiac cycle of 1 second and a heart rate of 60 bpm. But what if we increase the rate to 120 bpm? Recall from Membrane Workshop 2 that most of the increase comes from decreasing the period of diastole, cutting it more than in half. This means less time to perfuse the cardiac tissue at a time when demand is greatly increasing. This does not mean that the heart doesn't get enough O2 when you exercise. It does. But if you add the effects of ischemia and heart failure to this system (increasing muscle mass and compression), it may become a significant factor.
Think about our CHF patient. The pulse rate is diminished. This means that her stroke volume is down. Also recall that her MAP is down. We also previously determined that the wall tension is increased because the diameter of the cardiac chambers is increased (Law of LaPlace). What does increased wall tension mean for coronary flow?
The increased wall tension means that the coronary arteries are even more compressed. All of this adds up to a picture where coronary flow is or may become limiting. Note that increased wall thickness in hypertrophic cardiomyopathy also compresses coronary blood vessels and decreases flow.
Summary of coronary circulation physio.
What is the major specialized function of the skin? How is resistance in the cutaneous bed primarily determined?
The major specialized function of the skin is participation in temperature regulation. Resistance in the cutaneous bed is determined primarily by ANS signals that ultimately originate in the hypothalamus (thermoregulatory centers).
The anatomical arrangement of the cutaneous circulation makes it particularly well suited for a thermoregulatory fxn. As compared to skeletal muscle, there are fewer capillaries. Also, arterioles and venules are quite close. Why is this significant for fxn in thermoregulation?
You will note that the skin has fewer capillaries (it really doesn’t need that many to meet the metabolic demands of the tissue). You will also note that the arterioles and the venules are quite close. The end result is one of counter-current flow in the limbs. This arrangement limits heat loss through the skin in a cold environment and maximizes it when the body gets hot.
When the external environment is cold, vasoconstriction occurs, reducing flow to the skin and reducing the exposure to the blood to the outside environment. In addition, heat is transferred from the arterial blood to the venous blood. Thus warmer blood is returned and heat loss is minimized. When the external environment is warm, heat is transferred from the venous blood to the arterial blood, thus cooler blood is returned. Generalized cutaneous vasodilation takes place when the body overheats, decreasing resistance and increasing flow and allowing for maximal heat loss to the environment through the skin.
What are the 2 types of resistance vessels in skin? (just list)
arterioles and AV shunts (arteriovenous anastamoses)
What is the fxn of AV shunts? How are they controlled?
AV anastomoses are specialized to assist the cutaneous circulation in its function. These AV anastomoses shunt blood from arterioles to venules and bypass the capillary bed. The AV anastomoses are almost exclusively sympathetic (which constricts them).
As stated, the arterial and venous vessels are anatomically very close allowing optimal exchange of heat. When the external environment is cold, vasoconstriction occurs, reducing flow to the skin and reducing the exposure to the blood to the outside environment. In addition, heat is transferred from the arterial blood to the venous blood. Thus warmer blood is returned and heat loss is minimized. When the external environment is warm, heat is transferred from the venous blood to the arterial blood, thus cooler blood is returned. Generalized cutaneous vasodilation takes place when the body overheats, decreasing resistance and increasing flow and allowing for maximal heat loss to the environment through the skin. AV anastomoses allow capillary beds to be bypassed making this decreased resistance more dramatic. AV shunts have a larger diameter than capillaries and therefore play a larger role in regulating TPR.
True or false: The splanchnic cirulation is composed of gastirc, small intestina, coloinc, pancreatic, hepatic, and splenic circulations. The GI tract must support the various functions such as motility and absoprtion of products of digestion.
What is the capillary hydrostatic pressure of capillaries in the GI tract and why?
GI blood flow is high and increases during absorption of digested food. What is this an example of?
1. Capillary hydrostatic pressure is relatively low-favors absorption of water and nutrients
2. active hyperemia
What role does the splanchnic circulation play in sympathetic stimulation? Is the neural control of this circulation primarily sympathetic or parasympathetic?
Neural controls are predominately sympathetic and play a role in the baroreceptor reflex and in responses to exercise (or fight-or-flight). The vasoconstriction under these conditions shunts the blood to the skeletal and cardiac muscles where it is most needed. Indeed, the splanchnic bed is a major blood "reservoir" and thus participates in reflex control of blood pressure and volume in a major way.
What is the anatomical arrangement of the GI circulation? Why is it this way?
The arrangement of the GI circulation is another classic example of a countercurrent mechanism, this time designed to preserve O2. The villae of the intestines (attached figure) maximize surface area for absorption of food. The problem is that this also maximizes O2 loss. Countercurrent exchange of O2 from the arterial blood to the venous blood minimizes this loss.
What is a portal circulation? Describe the hepatic portal circulation. Be sure to include discussion of pressures and what effect pressure in this circulation has.
The hepatic circulation is a classic example of a portal circulation. A portal circulation connects two capillary beds in series. In this case, the blood drains from the intestines to the liver through the hepatic portal vein.
There is very low hydrostatic pressure in the portal vein (only about 10 mmHg) with a relatively low O2 content. Because of this, the blood from the portal vein is mixed with that of the hepatic artery and it is this vessel which supplies the needed oxygen to the liver. Of course, other nutrients are drained in directly from the intestines.
Not too surprisingly, the hydrostatic pressure in the sinusoids of the liver (basically the hepatic capillaries) is also low. This causes a low difference between the tissue and the capillary lumen which would ordinarily favor reabsorbtion of water. This is not the case, however. The sinusoids are also extremely permeable to protein and water. Protein is produced in the liver and must be able to make its way into the circulation there. Because of this high permeability, the oncotic pressure difference across the wall of the sinusoids is minimal and the situation, in contrast to what might be expected, actually favors conditions which increase filtration. This is important when considering the phenomenal of ascites (i.e. fluid accumulation in the abdomen). In heart failure, the CVP is increased which means the mid-capillary pressure is increased. This favors filtration and there is not much reabsorption to counter it-ascites
Summary of liver.
The renal circulation must meet the metabolic needs of the kidneys, which are relatively high (as indicated by high number of ml O2/100 g/min in table). What additional needs must the renal circulation meet causing the kidneys to be overperfused?
In addition to metabolic needs of the kidney, the renal circulation must also support the primary kidney functions of filtration, reabsorption and secretion. Thus the kidney is said to be over-perfused because the blood supply to supports these functions is in excess of what in needed to provide metabolic support, in spite of the fact that these metabolic needs are relatively high as well.
True or false: Anatomically, there is another portal system in the kidney, this time connecting the glomerulus, which filters the blood, with the vasa recta, which wraps around the renal tubules to allow for reabsorption and furter secretion of susbstances. The two capillary systems are connected by the efferent arteriole.
The vasa recta is another example of a countercurrent exchange system. Describe how this exhcnage system works. What would occur if this exchange system was not present?
The vasa recta dips into the renal medulla as it wraps around the Loops of Henle. As the artery goes deeper and deeper into the medulla, the Na around it becomes more and more concentrated. As you will learn later in the quarter, this high Na is used by the Loop of Henle to help concentrate the urine. For now, just be aware that the Na equilibrates across the capillary wall. The vasa recta therefore picks up Na on the way down.
Figure 3.16, bottom left, (attached) shows what would happen without the countercurrent exchange. NaCl would diffuse freely from the medulla to the circulation resulting in tremendous loss of this substance from the medulla. This does not happen, however. Instead, as the vasa recta rises back out of the medulla in parallel to the circulation going in (Figure 3.16, bottom right), NaCl is allowed to diffuse back out. Thus there is an exchange of NaCl between the 2 sides allowing only minimal loss on NaCl from the medulla.
Summary of renal.