This document discusses various factors that regulate blood flow locally and systemically. It covers topics such as local blood flow regulation including reactive and active hyperemia. It also discusses humoral regulation by various vasoconstrictors like epinephrine, vasopressin, angiotensin, and endothelin as well as vasodilators like bradykinin, serotonin, prostaglandins, and histamine. Finally, it mentions regulation by ions and chemicals in the blood as well as long-term regulation through angiogenesis and collateral circulation development.

1. Name: Gustavo Duarte Viana
Group: 17
Teacher: Zotova Oksana

2.  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

3.  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

4.  Barorecepts
 Orthostatic test
 Orthostatic hypotension
 Clinostatic test
 Chemoreceptors in the carotid and aortic
bodies
 Renin angiotensin aldosterone system

5. 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.

6. 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

7.  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.

8.  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.

9.  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

10.  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.

11.  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.

12. 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.

13. 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.

14. 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.

15. 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.

16.  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.

17.  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.

18.  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.

20.  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.

22. 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 agents
B) Vasodilator agents

23. A)No epinephrine and epinephrine
B) Vasopressin
C)Angiotensin II
D)Endothelin

24. 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.

25. 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.

26. 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.

27. 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.

28. A) Bradykinin
B) Serotonin
C) Porstaglandins
D) Histamin

29. 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.

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

31.  All the body tissues contains this vasodilator
substance.

32.  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

33.  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.

34.  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:

35.  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.

36. 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.

37. 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

38.  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.

39.  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.

40. 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.

41. 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.

43.  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.

44.  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.

45.  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.

46.  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.

47. . 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

48. 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.

49. 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.

51.  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

52. Thank you for your attention