Regulation of blood circulation

Name: Gustavo Duarte VianaGroup: 17

Teacher: Zotova Oksana

Importance of blood flow regulation Local blood flow Acute control Vasodilator theory Oxygen demand theory Special examples of metabolic control of the local blood flow Reactive hyperemia Active hyperemia Metabolic Mechanism Myogenic Mechanism Long term regulation Angiogenesis Collatel circulation

Index

Homoral regulation of circulation Vasoconstrictor agents No epinephrine and epinephrine Vasopressin Angiotensin Endothelin Vasodilator agents Bradykinin Serotonin Porstaglandins Histamin Vascular Control by Ions and Other

Chemical Factors Vasomotor center Vasomotor tone Vasomotor center controled by higher nervous center Cholinergic and adrenergic fibers

Barorecepts Orthostatic test Orthostatic hypotension Clinostatic test Chemoreceptors in the carotid and aortic

bodies Renin angiotensin aldosterone system

To answer on this question is simple: (think about it) if we allow a very large blood flow all the time through

every tissue of the body, always enough to supply the tissue’s

needs whether the activity of the tissue is little or great, it would require many times more blood flow than the heart can pump.

The blood flow to each tissue usually is regulated at the minimal level that will supply the tissue’s requirements no more and no less. For instance, in tissues for which the most important requirement is delivery of oxygen, the blood flow is always controlled at a level only slightly more than required to maintain full tissue oxygenation, but no more than this.

Importance of Blood flow control

The main function of the circulatory system is to give local blood flow to the tissue. There are special need of the tissue which is: 

delivery of oxygen to the tissue delivery of nutrients to the tissue removal of carbon dioxide from tissue maintaining of normal concentration of ions transform of hormones and other substance to tissue

Also some body tissues need special function by using blood flow for instance the skin, detects heat loss from body and it helps to control the body temperature.Delivery of blood plasma to the kidney also gives excretion of waste.

  If an organ has high metabolism it has high blood flow Eg. Thyroid, adrenal gland, liver, kidney.

Low blood flow to the resting muscle , it has muscle activity and it will increase blood flow. The blood flow to the tissue is minimal level that it can gives its functions, not more or not less, each tissue will need a different amount of blood flow due to its metabolic activity.

  Local blood flow is divided into : 1.acute control 2: long term control

Local control of blood flow

If the metabolism of tissues increases the blood flow increases in sec.

Eg, muscles  One of the most important nutrient is oxygen . So whenever

oxygen level decreases in tissue is due to pneumonia, co poisoning, and cynide poisoning the blood flow to tissue increases , the defect in oxygen in tissues will increase the blood flow.

There are 2 theories that regulates blood flow to tissue which is due to metabolism and oxygen changes in the blood flow.

▸vasodilator theory. ▸Oxygen demand theory.

Acute control

If high metabolism of low oxygen to tissues will be high number of vasodilator substance which is carbon dioxide, lactic acid adenosine, histamine and hydrogen. These substance are released to tissue mainly due to the oxygen deficience. The adenosine is an important vasodilator produced by the heart due to the low blood flow.

Vasodilator Theory

The defect of oxygen to tissues and blood will naturally dilate, also using of oxygen for metabolism also because oxygen gives vasodilatation to the tissues

Tissues also vasodilates due to: Vitamin deficiency Glucose Amino acids derivates

Oxygen demand theory

For more than a century, two different challenges have been used to study metabolic auto regulation: reactive hyperemia and active hyperemia. Reactive hyperemia is the blood flow response to blood flow occlusion, whereas active hyperemia is the blood flow response to increased tissue metabolic activity.

Special examples of metabolic control of the local blood flow

A blood pressure cuff around the biceps was inflated to suprasystolic levels for various periods of time. After the release of pressure from the cuff, the brachial artery blood flow response was measured by ultrasound Doppler techniques. the peak increase in blood flow was related to the duration of occlusion. This observation is consistent with the production and accumulation of metabolites by the ischemic tissue, although the identity of the key metabolite remains unknown.

Thus, if the period of occlusion was of some seconds, the high blood flow after occlusion is removed will be near seconds, but if it was per hours the high blood flow after remove the occlusion will be near an hour.

Reactive hyperemia

When any tissue becomes highly active, such as an exercising muscle, a gastrointestinal gland during a hypersecretory period, or even the brain during rapid mental activity, the rate of blood flow through the tissue increases. Here again, by simply applying the basic principles of local blood flow control, one can easily understand this active hyperemia.

The increase in local metabolism causes the cells to devour tissue fluid nutrients extremely rapidly and also to release large quantities of vasodilator substances. The result is to dilate the local blood vessels and, therefore, to increase local blood flow. In this way, the active tissue receives the additional nutrients required to sustain its new level of function. As pointed out earlier, active hyperemia in skeletal muscle can increase local muscle blood flow as much as 20-fold during intense exercise.

Active hyperemia

The metabolic theory can be understood easily by applying the basic principles of local blood flow regulation discussed in previous sections. Thus, when the arterial pressure becomes too great, the excess flow provides too much oxygen and too many other nutrients to the tissues.These nutrients (especially oxygen), then cause the blood vessels to constrict and the flow to return nearly to normal despite the increased pressure.

Metabolic Mechanism

when high arterial pressure stretches the vessel, this in turn causes reactive vascular constriction that reduces blood flow nearly back to normal. Conversely, at low pressures, the degree of stretch of the vessel is less, so that the smooth muscle relaxes and allows increased flow.

Myogenic mechanism

During period of hours, days and weeks a long term type of local blood flow will develop. This regulation is much more complete than the acute regulation.

  Eg. If b.p 150mmg after a week of a time again the b.p comes to

normal.  So when the metabolism changes in tissue also long term regulation

occurs. If the met becomes overachieve and need high level of nutrients it also needs increase blood flow for sometimes weeks.

  Changes due to tissue vascularity, if the metabolism increases, This

occurs rapidly. This will occur quickly in new tissues and it can et more time in blood tissues, also for long term regulation. It will need oxygen. If low oxygen tissues increase the blood flow it is due to supporting its needs.

Long term

Almost all tissues develop a vascular network that provides cells with nutrients and oxygen and enables them to eliminate metabolic wastes. Once formed, the vascular network is a stable system that regenerates slowly.

In physiological conditions, angiogenesis occurs primarily in embryo development, during wound healing and in response to ovulation.

However, pathological angiogenesis, or the abnormal rapid proliferation of blood vessels, is implicated in over 20 diseases, including cancer, psoriasis and age-related macular degeneration.

Angiogenesis

The angiogenic process, as currently understood, can be summarized as follows:

a) A cell activated by a lack of oxygen releases angiogenic molecules that attract inflammatory and endothelial cells and promote their proliferation.

b) During their migration, inflammatory cells also secrete molecules that intensify the angiogenic stimuli.

c) The endothelial cells that form the blood vessels respond to the angiogenic call by differentiating and by secreting matrix metalloproteases (MMP), which digest the blood-vessel walls to enable them to escape and migrate toward the site of the angiogenic stimuli.

d) Several protein fragments produced by the digestion of the blood-vessel walls intensify the proliferative and migratory activity of endothelial cells, which then form a capillary tube by altering the arrangement of their adherence-membrane proteins.

e) Finally, through the process of anastomosis, the capillaries emanating from the arterioles and the venules will join, thus resulting in a continuous blood flow.

Steps of Angiogenesis

The normal regulation of angiogenesis is governed by a fine balance between factors that induce the formation of blood vessels and those that halt or inhibit the process. When this balance is destroyed, it usually results in pathological angiogenesis which causes increased blood-vessel formation in diseases that depend on angiogenesis. 

More than 20 endogenous positive regulators of angiogenesis have been described, including growth factors, matrix metalloproteinases, cytokines, and integrins. Growth factors, such as vascular endothelial growth factor (VEGF), transforming growth factors (TGF-beta), fibroblast growth factors (FGF), epidermal growth factor (EGF), angiogenin, can induce the division of cultured endothelial cells thus indicating a direct action on these cells.

Factor of activation and inhibition of angiogenesis

When an artery or a vein is blocked in virtually any tissue of the body, a new vascular channel usually develops around the blockage and allows at least partial resupply of blood to the affected tissue. The first stage in this process is dilation of small vascular loops that already connect the vessel above the blockage to the vessel below. This dilation occurs within the first minute or two, indicating that the dilation is simply a neurogenic or metabolic relaxation of the muscle fibers of the small vessels involved. After this initial opening of collateral vessels, the blood flow often is still less than one quarter that needed to supply all the tissue needs. However, further opening occurs within the ensuing hours, so that within 1 day as much as half the tissue needs may be met, and within a few days often all the tissue needs. The collateral vessels continue to grow for many months thereafter, almost always forming multiple small collateral channels rather than one single large vessel. Under resting conditions, the blood flow usually returns very near to normal, but the new channels seldom become large enough to supply the blood flow needed during strenuous tissue activity.

Collateral circulation

Humoral control of the circulation means control by substances secreted or absorbed into the body fluids—such as hormones and ions. Some of these substances are formed by special glands and transported in the blood throughout the entire body. Others are formed in local tissue areas and cause only local circulatory effects. Among the most important of the humoral factors that affect circulatory function are the following.

A) Vasoconstrictor agentsB) Vasodilator agents

Humoral regulation of the circulation

A)No epinephrine and epinephrine B) VasopressinC)Angiotensin IID)Endothelin

Vasoconstrictor agents

Are prolonged vasoconstrictions (hormones), also some times they act as vasodilator to dilate coronary arteries in high heart activities. When SNS is stimulated in body these endings will synthesize noepinephrine to the heart , vein and arteriols. The SNS will stimulate to the adrenal medulla and also give noepinephrine and epinephrine synthesis to blood. Then these circulates all over the body and gives excitatory effects.

No epinephrine and epinephrine

Angiotensin II is another powerful vasoconstrictor substance. As little as one millionth of a gram can increase the arterial pressure of a human being 50 mm Hg or more.

The effect of angiotensin II is to constrict powerfully the small arterioles. If this occurs in an isolated tissue area, the blood flow to that area can beseverely depressed.

Angiotensin II

It is even more powerful than angiotensin II as a vasocons- trictor, thus making it one of the body’s most potent vascular constrictor substances. It is formed in nerve cells in the hypothalamus of the brain, but is then transported downward by nerve axons to the posterior pituitary gland, where it is finally secreted into the blood.

It is clear that vasopressin could have enormous effects on circulatory function. Yet, normally, only minute amounts of vasopressin are secreted,so it plays a little role.

Vasopressin has a major function to increase greatly water reabsorption from the renal tubules back into the blood, and therefore to help control body fluid

volume. That is why it is also called Antidiuretic hormone.

Vasopressin (also called Antidiuretic

hormone)

Still another vasoconstrictor substance requires only nanogram quantities to cause powerful vasoconstriction.

This substance is present in the endothelial cells of all or most blood vessels. The usual stimulus for release is damage to the endothelium, such as that caused by crushing the tissues or injecting a traumatizing chemical into the blood vessel. After severe blood vessel damage, release of local endothelin and subsequent vasoconstriction helps to prevent extensive bleeding from arteries as large as 5 millimeters in diameter that might have been torn open by crushing injury.

Endothelin

A) BradykininB) SerotoninC) PorstaglandinsD) Histamin

Vasodilator agents

Bradykinin causes both powerful arteriolar dilation and increased capillary permeability. For instance, injection of 1 microgram of bradykinin into the brachial artery of a person increases blood flow through the arm as much as sixfold, and even smaller amounts injected locally into tissues can cause marked

local edema resulting from increase in capillary pore size thus increasing the permeability.

Bradykinin

Is present in intestestinal tissues, also contains platletes. It has vasoconstrictor or vasolidator effects. It depends on thye condition.

Serotonin

All the body tissues contains this vasodilator substance.

Porstaglandis

Histamine is released in essentially every tissue of the body if the tissue becomes damaged or inflamed or is the subject of an allergic reaction. Most of the histamine is derived from mast cells in the damaged tissues and from basophils in the blood.

Histamine has a powerful vasodilator effect on the arterioles and, like bradykinin, has the ability to increase greatly capillary porosity, allowing leakage of both fluid and plasma protein into the tissues. In many pathological conditions, the intense arteriolar dilation and increased capillary porosity produced by histamine cause tremendous quantities of fluid to leak out of the circulation into the tissues, inducing edema. The local vasodilatory and edema-producing effects of histamine are especially prominent during allergic reactions

Histamin

1. An increase in calcium ion concentration causes Vasoconstriction. Effect of calcium to stimulate smooth contraction.

2. An increase in potassium ion concentration causes vasodilation. the ability of potassium ions to inhibit smooth muscle contraction.

3. An increase in magnesium ion concentration causes powerful vasodilatation because magnesium ions inhibit smooth muscle contraction.

4. An increase in hydrogen ion concentration (decrease in pH) causes dilation of the arterioles.

5. Anions that have significant effects on blood vessels are acetate and citrate, both of which cause mild degrees of vasodilatation.

6. An increase in carbon dioxide concentration causes moderate vasodilatation in most tissues, but marked vasodilatation in the brain. Also, carbon dioxide in the blood, acting on the brain vasomotor center, has an extremely powerful indirect effect, transmitted through the sympathetic nervous vasoconstrictor system, to cause widespread vasoconstriction throughout the body.

Vascular Control by Ions and OtherChemical Factors

Located bilaterally mainly in the reticular substance of the medulla and of the lower third of the pons, is an area called the vasomotor center. This center transmits parasympathetic impulses through the vagus nerves to the heart and transmits sympathetic impulses through the spinal cord and peripheral sympathetic nerves to virtually all arteries, arterioles, and veins of the body.

Although the total organization of the vasomotor center is still unclear, experiments have made it possible to identify certain important areas in this center, as follows:

Vasomotor center

1. A vasoconstrictor area located bilaterally in the anterolateral portions of the upper medulla. The neurons originating in this area distribute their fibers to all levels of the spinal cord, where they excite preganglionic vasoconstrictor neurons of the SNS.

2. A vasodilator area located bilaterally in the anterolateral portions of the lower half of the medulla. The fibers from these neurons project upward to the vasoconstrictor area, they inhibit the vasoconstrictor activity of this area, thus causing vasodilation.

3. A sensory area located bilaterally in the tractus solitarius in the posterolateral portions of the medulla and lower pons. The neurons of this area receive sensory nerve signals from the circulatory system mainly through the vagus and glossopharyngeal nerves, and output signals from this sensory area then help to control activities of

both the vasoconstrictor and vasodilator areas of the vasomotor center, thus providing “reflex” control of many circulatory functions. An example is the baroreceptor reflex for controlling arterial pressure.

Under normal conditions, the vasoconstrictor area of the vasomotor center transmits signals continuously to the sympathetic vasoconstrictor nerve fibers over the entire body, causing continuous slow firing of these fibers at a rate of about one half to two impulses per second. This continual firing is called sympathetic vasoconstrictor tone. These impulses normally maintain a partial state of contraction in the blood vessels, called vasomotor tone.

Vasomotor tone

stimulation of the anterior temporal lobe,the orbital areas of the frontal cortex, the anterior part of the cingulate gyrus, the amygdala, the septum, and the Hippocampus, cerebral cortex and hypotalamus can all either excite or inhibit the vasomotor center, depending on the precise portions of these areas that are stimulated and on the intensity of stimulus.Thus, widespread basal areas of the brain can have profound effects on cardiovascular function.

Those areas of the cerebral cortex has a strong network connection with the vasomotor center

Control of the vasomotor center by the higher nervous center

Most arteries and veins in the body are innervated by sympathetic adrenergic nerves, which release norepinephrine (NE) as a neurotransmitter. Some blood vessels are innervated by parasympathetic cholinergic or sympathetic cholinergic nerves, both of which release acetylcholine (ACh) as their primary neurotransmitter. Neurotransmitter binding to the adrenergic and cholinergic receptors activates signal transduction pathways that cause the observed changes in vascular function.

Cholinergic and adrenergic fibers

includes the fast, neural mechanisms. is responsible for the minute-to-minute

regulation of arterial blood pressure produces vasoconstrictor activity tonically,

which accounts for vasomotor tone.Baroreceptors are stretch receptors located

within the walls of the carotid sinus near the bifurcation of the common carotid arteries.

Baroreceptors

a. An increase in arterial pressure stretches the walls of the carotid sinus.‑Because the baroreceptors are most sensitive to changes in arterial pressure.- Additional baroreceptors in the aortic arch respond to increases, but not to decreases, in arterial pressure.b. Stretch increases the firing rate of the carotid sinus nerve (Hering's nerve, cranial nerve IX), which carries information to the vasomotor center in the brainstem.

1. Steps in the baroreceptor reflex

c. The set point for mean arterial blood pressure in the vasomotor center is about 100 mm Hg. Therefore, if mean arterial pressure is greater than 100 mm Hg, a series of autonomic responses are coordinated by the vasomotor center to reduce it.

d. The responses of the vasomotor center to an increase in mean arterial pressure are coordinated to decrease the arterial pressure back to 100 mm Hg. The responses are increased parasympathetic (Vagal) outflow to the heart and decreased sympathetic outflow to the heart and blood vessels.

The examined is laying for 10-15 minutes, in this position, we measure blood pressure and pulse rate until the measurement is constant. After that, examined must stand for 10 minutes, we measure blood pressure and pulse rate again till constant.

Orthostatic test

Orthostatic hypotension (fainting or lightheadedness upon standing) can occur in individuals whose baroreceptor reflex mechanism is impaired (e.g.,

individuals treated with sympatholytic agents). This may occur after a very severe diarrhea, the

quantity of blood in this person decrease drastically, and the amount of blood pumped by the heart is not enough to come against the gravity force that is bring the blood to the lower part of the body, thus the brain is affected by the low supply of O2 and nutrients to supply all its requirements, that is why when such patient stand up, they feel nausea and dizziness.

Orthostatic Hypotension

In the standing position, as the result of gravity the mean arterial blood pressure is in lower limb is 180-100 mmHg, venous pressure = 85-90 mmHg, the arterial pressure at the head level = 60-75 mmHg.

If the individual doesn’t move 300-500 mm of blood collect in the venous vessels of the legs.

Fluid also accumulates in the interstitial spaces and increases hydrostatic pressure in the capillaries. Cardiac output in decreased to 40%, in not present compensatory cardiovascular changes, the reduction in of cerebral flow and consciousness will lost.

The major compensation in upright position begin from low pressure and high pressure baroreceptors.

Result: heart rate increase and this maintain cardiac output, arise vasoconstriction in the periphery and arterioles.

Clinostatic test

are located near the bifurcation of the common carotid arteries and along the aortic arch.

have very high rates of 02 consumption and therefore are very sensitive to hypoxia. A decrease in mean arterial pressure causes a reduction in O2 delivery to the chemoreceptors. In turn, information is sent to the vasomotor center to activate mechanisms to restore blood pressure.

Chemoreceptors in the carotid and aortic bodies

. Renin-angiotensin-aldosterone system is a slow, hormonal mechanism. is used in long‑term blood pressure regulation by

adjustment of blood volume. Renin is an enzyme that catalyzes the conversion

of angiotensinogen to angiotensin I in the plasma. Angiotensin I is inactive. Angiotensin II is physiologically active. Angiotensin II is degraded by angiotensinases.

One of the peptide fragments, angiotensin III, has some of the biologic activity of angiotensin II

Renin angiotensin aldosterone system

Steps in the renin-angiotensin-aldosterone system

a. A decrease in renal perfusion pressure causes release of renin from the juxtaglomerular cells of the afferent arteriole.

b. Angiotensinogen is converted to angiotensin I in plasma, catalyzed by renin.

c. Angiotensin I is converted to angiotensin II, catalyzed by angiotensin‑converting enzyme (ACE). The primary site of this reaction is the lung. Inhibitors of ACE can lower the blood pressure by blocking the production of angiotensin II.

d. Angiotensin II has two effects: It stimulates release of aldosterone from the adrenal cortex in the gromerular layer, and it causes vasoconstriction of arterioles (increased TPR).

e. Aldosterone increases reabsorption of salt by the distal tubule of the kidney.

This action is slow because it requires the synthesis of new protein by the kidney.

Increased salt and water reabsorption increases blood volume and mean arterial pressure.

Lecture of physiology of KSMU by Professor Dr. Avdeeva Elena

Guyton and Hall. Textbook of medical physiology. The eleventh edition. 2006. Unit IV. Ch 17-18

References

Thank you for your attention