Physiology
Lec: 7+8 د. زيـد الاطرقجيCardiovascular system
The baroreceptor reflex mechanisms are fast, neurally mediated reflexes that attempt to keep arterial pressure constant via changes in the output of the sympathetic and parasympathetic nervous systems to the heart and blood vessels
Reflex arc
Sensors for blood pressure;
Afferent neurons, (IX, X )
Brain stem centers, which process the information and coordinate an appropriate response (medulla) cardiovascular centers (which are tonically active)
Efferent neurons, (sympathetic and parasympathetic)
The parasympathetic outflow is the effect of the vagus nerve on the SA node to decrease the heart rate.
The sympathetic outflow has four components: effect on the SA node to increase heart rate, an effect on cardiac muscle to increase contractility and stroke volume, an effect on the arterioles to produce vasoconstriction and increase TPR, and an effect on veins to produce venoconstriction and decrease unstressed volume.
Renin-angiotensin -aldosterone system
The renin-angiotensin -aldosterone system regulates mean arterial pressure( Pa) primarily by regulating blood volume.
This system is much slower than the baroreceptor reflex because it is hormonally, rather than neurally, mediated.
This system is activated in response to a decrease in the Pa, which in turn, produces a series of responses that attempt to restore arterial pressure to normal.
Angiotensin II is an octapeptide with biologic actions in the:
1- Adrenal cortex : stimulates synthesis and secretion of aldosterone which acts on the principal cells of the renal distal tubule and collecting duct to increase Na+ reabsorption and, thereby, to increase ECF volume and blood volume.
Actions of aldosterone require gene transcription and new protein synthesis in the kidney. These processes require hours to days to occur and account for the slow response time of the renin-angiotensin II-aldosterone system.
2- Vascular smooth muscle, direct action on the arterioles to cause vasoconstriction which increase TPR
3- Kidneys, direct action, stimulates Na+-H+ exchange in the renal proximal tubule and increases the reabsorption of Na+ and HCO3
4- Brain acts on the hypothalamus to increase thirst and water intake. It also stimulates secretion of ADH, which increases water reabsorption in collecting ducts. By increasing total body water, these effects complement the increases in Na+ reabsorption (caused by aldosterone and Na+-H+ exchange), thereby increasing ECF volume, blood volume, and blood pressure.
Other regulatory mechanisms for blood pressure
1- Peripheral chemoreceptors for O2 are located in the carotid bodies near the bifurcation of the common carotid arteries and in the aortic bodies along the aortic arch.
They respond to decreased arterial Po2 especially when the Pco2 is increased or the pH is decreased.
When stimulated-----------activate sympathetic vasoconstrictor centers
2- Central (cerebral) Chemoreceptors: the brain is intolerant of decreases in blood flow, chemoreceptors are located in the medulla and they are most sensitive to CO2 and pH and less sensitive to O2. Changes in Pco2 or pH stimulate the medullary chemoreceptors, which then direct changes in outflow of the medullary cardiovascular centers.
3- Antidiuretic hormone (ADH
Its secretion from the posterior pituitary is increased by two types of stimuli: by increases in serum osmolarity and by decreases in blood pressure.
There are two types of receptors for ADH:
V1 receptors, which are present in vascular smooth muscle, and
V2 receptors, which are present in principal cells of the renal collecting ducts.
When activated, the V1 receptors cause vasoconstriction of arterioles and increased TPR. The V2 receptors are involved in water reabsorption in the collecting ducts and the maintenance of body fluid osmolarity.
4- Cardiopulmonary Baroreceptors
They are located in the veins, atria, and pulmonary arteries. They sense changes in blood volume, or the "fullness" of the vascular system. They are located on the venous side of the circulation where most of the blood volume is present.
When there is an increase in blood volume, the resulting increase in venous and atrial pressure is detected by the cardiopulmonary baroreceptors.
The function of the cardiopulmonary baroreceptors is then coordinated to return blood volume to normal, primarily by increasing the excretion of Na+ and water.
The responses to an increase in blood volume include the following:
1- Increased secretion of atrial natriuretic peptide(ANP )which is secreted by atrial cells in response to increase atrial pressure.
Results in vasodilation and decreased TPR. In the kidneys, this vasodilation leads to increased Na+ and water excretion
2- Decreased secretion of ADH.
Pressure receptors in the atria also project to the hypothalamus, where the cell bodies of neurons that secrete ADH are located. In response to increased atrial pressure, ADH secretion is inhibited and, as a consequence, there is decreased water reabsorption in collecting ducts, resulting in increased water excretion
3- Renal vasodilation.
There is inhibition of sympathetic vasoconstriction in renal arterioles, leading to renal vasodilation and increased Na+ and water excretion, complementing the action of ANP on the kidneys.
4-Increased heart rate. Information from the low-pressure atrial receptors travels in the vagus nerve to the nucleus tractus solitarius.
Increase in pressure at the venous low-pressure receptors produces an increase in heart rate. The low-pressure atrial receptors, sensing that blood volume is too high, direct an increase in heart rate and, thus, an increase in cardiac output; the increase in cardiac output leads to increased renal perfusion and increased Na+ and water excretion.
Capillaries:
Are the sites for exchange of materials between blood and tissue cells, branch extensively to bring blood within the reach of every cell. Materials are exchanged across capillary walls mainly by diffusion.
Diffused molecules have only a short distance to travel between blood and surrounding cells because of the thin capillary wall and small capillary diameter coupled with the close proximity of every cell to a capillary. This short distance is important because the rate of diffusion slows down as the diffusion distance increases.
Capillary walls are very thin 1 micron in thickness in contrast; the diameter of human hair is 100 micron.
Each capillary is so narrowed 7 micron average diameter that red blood cells 8 micron diameter have to squeeze through. Consequently plasma contents are either in direct contact with inside of the capillary wall or are only a short diffusing distance from it.
Because of extensive capillary branching no cell is farther than 0.01 cm from a capillary.
Total number of capillaries 10-40 billion capillaries. Capillaries contain 5% of cardiac output. Blood flows more slowly in the capillaries than elsewhere in the circulatory system. The extensive capillary branching is responsible for this slow velocity of blood flow through capillaries.
Because the circulatory system is a closed system the volume of blood flowing through any level of the system must equal the cardiac output.
For example if the heart pumps out 5 liters of blood per minute and 5 liters per minute of blood return to the heart then 5 liters per minute must flow through the arteries, arterioles, capillaries and veins. Therefore the flow rate is the same at all levels of the circulatory system.
However the velocity with which blood flows through the different segments of the vascular tree varies because velocity of flow is inversely proportional to the total cross sectional area of all the vessels at any given level of the circulatory system. The cross sectional area of all the capillaries added together is about 1300 times greater than the cross sectional area of the aorta because there are so many capillaries accordingly blood slows considerably as it passes through the capillaries.
This slow velocity allows adequate time for exchange of nutrients and adequate time for exchange of metabolic end products between blood and tissue cells which are the sole purpose of the entire circulatory systems. As the capillaries rejoin to form veins the total cross- sectional area is once again reduced and the velocity of blood flow increases as blood returns to the heart.
Also because of the capillaries tremendous total cross- sectional area the resistance offered by all the capillaries is much lower than that offered by all the arterioles even though each capillary has a smaller radius than each arteriole. Furthermore arteriolar caliber and accordingly resistance is subjected to control whereas capillary caliber cannot be adjusted.
Water fills capillary pores which permit passage of small water soluble substances. In most capillaries water fill gaps or pores lie at the junctions between the cells these pores permit passage of water soluble substances. Lipid soluble substances such as 02 and CO2 can readily pass through the endothelial cells themselves by dissolving in the lipid bilayer barrier.
The size of the capillary pores varies from organ to organ. At one extreme the endothelial cells in brain capillaries are joined by tight junctions so that pores are nonexistent, these junctions prevent trans-capillary passage of materials between the cells. Thus constitute part of the protective blood brain barrier.
In most tissues small water soluble substances such as ions, Glucose and amino acids can readily pass through the water filled pores but large non lipid soluble material that cannot fit through the pores such as plasma proteins are kept from passing. Liver capillaries have such large pores that even proteins pass through readily.
The leakiness of various capillary beds is therefore a function of how tightly the endothelial cells are joined, which varies according to the different organ cells.
Recent studies however suggest that endothelial cells can actively change to regulate capillary permeability that is in response to appropriate signals. Thus the degree of leakiness does not necessarily remain constant for given capillary bed. For example histamine increases capillary permeability by triggering contractile responses in endothelial to widen the intercellular gaps. (This is not a muscular contraction because no smooth muscle cells are present in capillaries).
Because of these enlarged pores the affected capillary wall is leakier as a result normally retained plasma proteins escape into the surrounding tissue where they exert an osmotic effect. A long with histamine induced vasodilatation the resulting additional local fluid retention contribute to inflammatory swelling
Vesicular transport also plays a limited role in the passage of materials across the capillary wall .large non-lipid soluble molecule such as protein hormones that must be exchanged between blood and surrounding tissues are transported from one side of the capillary wall to the other in endocytotic exocytotic vesicle.
Pre-capillary sphincters are not innervated but have a high degree of myogenic tone and sensitive to local metabolic changes .they control blood flow through the particular capillary that each one guards.
Capillaries themselves have no smooth muscle so they can not actively participate in regulating their own blood flow.
Generally tissues that are more metabolically active have a greater density of capillaries. Muscles for example have relatively more capillaries than their tendinous attachments.
Only about 10% of the pre-capillary sphincters in a resting muscle are open at any moment so blood is flowing through only about 10% of the muscles capillaries.
As chemical concentrations start to change in a region of the muscle tissue supplied by closed down capillaries, the pre-capillary sphincters and arterioles in the region relax, restoring the chemical concentrations to normal. As a result of increased blood flow to that region removes the impetus for vasodilatation so the pre capillary sphincters close once again and the arterioles return to normal tone.
In this way blood flow through any given capillary is often intermittent as a result of arteriolar and pre-capillary sphincter action working in concert.
When the muscle as a whole becomes more active a greater percentage of the pre-capillary sphincters relax simultaneously opening up more capillary beds while concurrent arteriolar vasodilatation increases total blood flow to the organ. As a result more blood flowing through more open capillaries, the total volume and surface area available for exchange increase and the diffusion distance between the cells and an open capillaries decreases.
Thus local blood flow through a particular tissue [assuming a constant blood pressure] is regulated by:
1. The degree of resistance offered by the arteriole in the organ controlled by sympathetic activity and local factors.
2. The number of open capillaries controlled by the action of the same local metabolic factors on pre-capillary sphincters.
Exchange between blood and tissue cells are not made directly. Interstitial fluid is the true internal environment which is in immediate contacts with cells. Only 20% of the ECF circulate as plasma, the remaining 80% consists of interstitial fluid which baths all the cells in the body.
Movement across the plasma membrane may be either
1. Passive [that is by diffusion down electro-chemical gradient or by facilitated diffusion]
2. Active [that is by active carrier- mediated transport or by vesicular transport].
Exchange across the capillary wall between plasma and interstitial fluid are largely passive. The only transport across this barrier that require energy is the limited vesicular transport.
Because capillary wall are highly permeable, exchange with the interstitial fluid takes on the same components as incoming arterial blood with the exception of the large plasma proteins that usually do not escape from the blood. Therefore when we speak of exchanges between blood and tissue cells we actually include interstitial fluid as a passive intermediary.
The chemical composition of arterial blood is carefully regulated to maintain the concentration in the appropriate direction across the capillary walls.
Bulk-flow:
Is a volume of protein free plasma actually filters out of the capillary, Mixes with surrounding interstitial fluid and the reabsorbed. It called bulk because the various constituents of the fluid are moving together in bulk or as a unit.
The capillary wall acts like a sieve with fluid moving through its water filled pores.
When a pressure inside the capillary exceeds pressure on the outside fluid is pushed out through the pores in a process known as ultra-filtration [filtration]. The fluid which moves out of the capillary is protein free. The filtration process always needs pressure.
Reabsorption: it is a process which moves fluid toward the lumen of capillary. When inward driving pressures exceed outward pressures across the capillary wall net inward movement of fluid from the interstitial fluid into the capillaries takes-place through the pores.
Bulk flow occurs because of differences in the hydrostatic and colloid osmotic pressures between plasma and interstitial fluid.
Capillary-blood pressure: on average the hydrostatic pressure is 37mmHg at the arteriolar end of a tissue capillary [compared to a mean arterial of 93mmHg]. It decline even further to 17mmHg at the capillary venular end.
Therefore the two pressures that tend to force fluid out of the capillaries are capillary blood pressure and interstitial fluid colloid osmotic pressure. The two opposing pressure that tend to force fluid into the capillary are plasma colloid osmotic pressure and interstitial fluid hydrostatic pressure.
A positive net exchange pressure [when the outward pressure exceeds the inward pressure] represents an ultra-filtration pressure.
A negative net exchange pressure [when the inward pressure exceeds the outward pressure] represents a reabsorptive pressure.
Ultra-filtration takes-place at the beginning of the capillary as this outward pressure gradient forces a protein free filtrate through the capillary pores.
Reabsorption of fluid take place as this inward pressure gradient forces fluid back into the capillary at its venular end.
No active forces or local energy expenditure are involved in the bulk exchange of fluid between the plasma and the surrounding interstitial fluid.
Bulk flow is extremely important however in regulating the distribution of ECF between the plasma and interstitial fluid. If the plasma volume is reduced for example by hemorrhage blood pressure falls the resulting is lowering of capillary blood pressure which alters the balance of forces across the capillary walls. Because the net outward pressure is decreased while the net inward pressure remains unchanged the extra fluid is shifted from the interstitial compartment into the plasma as a result of reduced filtration and increased reabsorption.
The extra fluids from the interstitial fluid provide additional fluid for the plasma temporarily compensating for the loss of blood.
Conversely if the plasma volume becomes over expanded as with excessive fluid intake the resulting rise in capillary blood pressure forces extra fluid from the capillaries into the interstitial fluid temporarily relieving the expanded plasma volume until the excess fluid can be eliminated from the body by long term measures such increasing urinary output.
These internal fluid shifts between the two ECF compartments occur automatically and immediately whenever the balance of forces acting across the capillary walls is changed . They provide a temporary mechanism to help keeping plasma volume fairly constant.
Response of baroreceptor reflex to increased arterial pressure
Response of the Baroreceptor Reflex to Hemorrhage