REGULATION OF BLOOD FLOW
ANATOMY OF THE SYMPATHETIC NERVOUS CONTROL OF THE CIRCULATION
• Sympathetic Nerves leave the spinal cord through thoracic and lumbar spinal nerves
• Synapse in the sympathetic chain para vertebral ganglia
• Post ganglionic fibers goes to the circulatory system through
– Specific sympathetic nerves innervate the vasculature of the internal viscera and the heart
– the spinal nerves that innervate mainly all the vasculature of the peripheral area except for pre capillary sphincters,capillaries and the metarterioles
• Sympathetics carry mostly vasoconstrictor fibers and a lot are present in the kidney, gut, spleen, skin and less are in the skeletal muscle and brain.
SYMPATHETIC NERVOUS SYSTEM
● Cause vasoconstriction by activation of a-adrenergic receptors on vascular smooth muscle by norepinephrine.
● Vasoconstriction of arterioles àincreased vascular resistance and redistribution of blood flow
● Vasoconstriction of veins à increased circulating blood volume, increased venous returnàleads to increased ventricular filling and stroke volume.
● Increase in the activity of the heart (heart rate and contractility)
● There are also sympathetic vasodilator fibers which release epinephrine acting on β-adrenergic receptors.
PARASYMPATHETIC SYSTEM
• 75% of all parasympathetic nerve fibers are in the vagus nerves (cranial nerve X)
• Pass to the entire thoracic and abdominal regions of the body,including the heart.
• Preganglionic nerves pass all the way to the organ.
• Postganglionic nerves are very short and located entirely in the wall of the organ.
• Play minor role in the regulation of circulation.
– Mainly control heart rate
– Stimulation of vagus nerves results in a decrease in heart rate and contractility
VASOMOTOR CENTRE
• Located in the reticular substance of the medulla and lower pons
• Neuron from this area transmit parasympathetic impulse through vagus nerve to heart
• Transmit sympathetic nerves through the spinal cord and hence sympathetic vasoconstrictor fibers to almost all blood vessels of the body
• Hypothalamus can exert powerful excitatory or inhibitory effects of vasomotor center.
• Motor cortex, anterior temporal lobe, etc can excite vasomotor center.
• Hypothalamus is the principal area of control
AREAS OF THE VASOMOTOR CENTER
Vasoconstrictor Area
• Located bilaterally in antero medial position in medulla
• Neurons secrete norepinephrine which stimulates the vasoconstrictor neurons of the sympathetic nervous system
Vasodilator Area
• Located bilaterally in antero lateral position in lower medulla
• Fibers from neurons in this area project upward to the vasoconstrictor area and inhibit vasoconstrictor activity
Sensory area
• Located bilaterally in tractus solitarus of pons and upper medulla
• Receives sensory nerve signals from the vagus and glossopharyngeal nerves
• Output signals control the activities of both the vasoconstrictor and vasodilator areas
• Providing “reflex” control of many circulatory functions (e.G. Baroreceptor reflex for blood pressure control)
VASOMOTOR TONE
• Under normal condition vasomotor area transmit continuous signals to sympathetic vasoconstrictor fibers
• Sympathetic vasoconstrictor tone
– Continuous firing of sympathetic nerves at the rate of one half -2 impulses per second
• Vasomotor tone
– Partial state of constriction in blood vessels due to sympathetic tone
CONTROL OF HEART BY VASOMOTOR CENTER
• Vasomotor center can either increase and decrease heart activity
• Lateral portion of vasomotor centerà sympathetic nerves to heart à increases heart rate, contractility and AV node conduction
• Medial portion of vasomotor center à vagus nerve to heart à decrease heart rate and contractility
ADRENAL MEDULLA AND VASODILATOR SYSTEM
• Sympathetic nerves transmit impulses to adrenal medulla
• Adrenal medullae secrete both epinephrine and norepinephrine into the circulating blood.,
• Act directly on all blood vessels
• Usually cause vasoconstriction
• in some tissues beta adrenergic receptor stimulation by
epinephrine causes vasodilation
VASO VAGAL SYNCOPE
• Emotional disturbances àdisturbing thoughts to cortexà vasodilatory center in anterior hypothalamusà vagal center of medullaà vagus nerve that transmit cardio inhibitory signals to the heart
• Impulses also travel through spinal cord to symphatetic vasodilator nerves of muscle
• Arterial pressure falls rapidly
• Blood flow to the brain is reduced, result in loss of consequence
• This is called vasovagal syncope.
RAPID CONTROL OF ARTERIAL PRESSURE BY NERVOUS SYSTEM
Arterial blood pressure is regulated by several interrelated systems with specific functions
Rapid Contro
Baroreceptor
CNS ischemic mechanism
Chemoreceptors
Combine to cause venoconstriction, increasing venous return, increase heart rate and contractility, arteriolar constriction
Intermediate Control (during this time nervous mechanisms usually fatigue
and become less important) Long-Term Control (Renal-body fluid pressure control mechanism -hours to days)
Aldosterone
Renin Angiotensin System interaction with aldosterone
RAPID NERVOUS CONTROL OF ARTERIAL BLOOD PRESSURE
• Most important control is to increase blood pressure rapidly (e.g.In hemorrhage, shock)
• Entire vasoconstrictor and cardio accelerator functions of the SNS are stimulated as a unit
• Reciprocal inhibition of the normal parasympathetic vagal inhibitory signals.
• Results in following changes to increase BP
– Arteriolar constrictionà increase TPRà increase BP
– Large vessel constriction (especially veins)à increases circulating blood volume and venous return à increased cardiac contractility and stroke volume àincrease in arterial pressure
– Direct stimulation of the heart (HR increases up to 3 fold and contractility is increased)
• These effects can double arterial pressure within 10-15 sec
• Sudden inhibition can decrease pressure by half within 10-40 sec.
RAPID NERVOUS CONTROL OF ARTERIAL BLOOD PRESSURE
IN EXERCISE AND STRESS
•During exercise active muscles require greatly increased blood flow achieved by:
– Local vasodilatory mechanisms
Elevation of arterial blood pressure (increase of 30-40% can increase blood flow by 2 fold
•Increase in arterial pressure during exercise results mainly from the following effect:
– The motor areas of the brain become activated to cause exercise
– Most of the reticular activating system of the brain stem is also activated
– Greatly increased stimulation of the vasoconstrictor and cardio acceleratory areas of the vasomotor center
– Increase the arterial pressure instantaneously to keep pace with the increase in muscle activity
•May occur in other type of stress
•Alarm reaction–during extreme fright, the arterial pressure sometimes rises to as high as double normal within a few seconds
• provides an excess of arterial pressure that can immediately supply blood to any or all muscles of the body that might need to respond instantly to cause flight from danger.
BARORECEPTOR REFLEX
Receptor: spray-type nerve endings
baroreceptor, pressoreceptors)
Location: in the wall of large arterial vessels
• internal carotid artery above bifurcation in CAROTID SINUS
• In the wall of aortic arch;
Stimulus: Stretch
Pathway:
•carotid sinus transmits impulses through Herring’s nerve to the
glossopharyngeal nerve à tractus solitarius in the medulla
•Signals from the aortic arch transmitted through the vagus nerves into medulla
MECHANISM
•Rise in arterial pressureà stretches the baroreceptors à transmit signals into the central nervous systemàfeed back signals
•“Feedback” signals are then sent back through the autonomic nervous system to the circulation to reduce arterial pressure downward toward the normal level.
•System optimal at normal range of arterial pressure
FUNCTION OF BARORECEPTOR REFLEXDURING CAHNGE IN POSTURE
• Person stands from sitting
• Blood pools up in lower extremity due to gravity
• Blood pressure in head and upper limbs suddenly decreases
• Baroreceptor senses this change in pressure and respond rapidly to return it to normal
• Failure of this function of baroreceptor reflexes in some diseased people result in dizziness and ocassional fainting due to transient low BP in brain —-orthostatic hypotension
RESETTING OF BARORECEPTORS
• Rate of firing of baroreceptors adjust to normal value over a period
• Of 1-2 days during prolonged exposure to abnormally high or low Arterial pressure.
• Can effectively control arterial pressure only during relatively short periods of time (~minutes to hours).
• Unimportant for long-term regulation of the mean arterial pressure.
• Long-term regulation is achieved primarily by renal-body fluid-pressure control system and associated hormonal mechanisms
CAROTID AND AORTIC CHEMORECEPTORS
Closely associated with the baroreceptors
Stimulus: lack of O2, excess of CO2, or excess of H+
Receptor:
Located in several small organs (1-
Each body has close contact with the arterial blood.
Pathway: same as baroreceptor
Reflex: mainly imp in detecting low bp
Low pressureàdecreased blood flowà reduces oxygen, build up of carbon dioxideà stimulates the chemo receptorsàvasomotor centeràexcitement àincrease arterial BP
Not strongly stimulated until pressure falls below 80 mmhg.
ATRIAL AND PULMONARY ARTERY LOW PRESSURE RECEPTORS
Stimulus: Stretch
Receptor: spray-type nerve endings
Function: minimize arterial pressure changes in response to changes in blood volume
Pathway: similar to the baroreceptors
Reflex: elicit reflexes parallel to the baroreceptor reflexes to make the total reflex system more potent
OTHER REFLEXES THAT CAN CONTROL BP
VOLUME REFLEX
• Increase in BP à Stretch of atria à reflex dilatation of the afferent arterioles in the kidneysàincrease in filtration of fluid into the kidney tubules.
• aAdecrease in secretion of antidiuretic hormone by the hypothalamus, which diminished the re absorption of water from then tubules.
• Both effects lead to reduction of blood volume and ultimately BP.
BAIN BRIDGE REFLEX
• Increase in arterial BP causes an increased heart rate
– Direct stretch of SA-nodal area causes an increase in the heart rate
– In addition, atrial stretch receptors transmit signals to the medulla of the brain and stimulates sympathetic system
– prevent damming of blood in the veins, atria, and pulmonary circulation.
CNS ISCHEMIC RESPONSE
• Reduction in blood flow to brain results in ischemia
• Carbondioxide and acidic substance accumulate
• Cause profound excitation of medullary vasoconstricor area and sympathetic nervous system
• most powerful response of all the activators of the sympathetic vasoconstrictor system
Last ditch stand”
• CNS ischemic response does not play any role until arterial pressure drops below
• Maximum of the response is reached at 15-20 mmHg, which is dangerously close to lethal state
CUSHING”s REACTION
• Incresed CSF pressure compresses the arteries in brain
• Reduction in blood flow excites CNS ischemic responseResult in increase in BP
• When BP becomes more than CSF pressure flow is restored
ADDITIONAL MECHANISMS
ABDOMINAL COMPRESSION REFLEX
• Stimulation of sympathetic vasoconstriction system is usually accompanied by skeletal nerves and skeletal muscles stimulation
• Abdominal muscles are stimulated, translocating blood from abdominal vascular reservoirs toward the heart
• results in an increase of cardiac output
Skeletal Muscles
• Skeletal muscle contraction during exercise cause translocation of significant amounts ofblood from peripheral vessels into the heart and lungs.
• increases cardiac output up to 7 fold during severe exercise
• Arterial pressure rises by 20-60%.
RESPIRATORY WAVES
• Each cycle of respiration causes synchronous oscillations in arterial
• pressure 4-
• pressure rises during an early phase of expiration and falls during the rest of respiratory cycle due to
– (1) “Spill over” of nerve impulses from respiratory center of the medulla into vasomotor center
– (2) inspiration and expiration causes changes in the intrathoracic pressure directly pushing the heart and vessels changing amount of blood in the heart and therefore cardiac output
– (3) pressure changes in the thoracic vessels can excite vascular and atrial stretch receptors
ARTERIAL PRESSURE VASOMOTOR WAVES
• Much larger waves as great as 10 to
• These waves are called vasomotor waves or “Mayer waves.”
• The cause of vasomotor waves is “reflex oscillation” of one or more nervous pressure control mechanisms
– Baroreceptor reflex
– CNS ischemic response
– Chemoreceptor Reflex
Role of Kidneys in blood pressure control
Ø Kidneys are the main controllers of long term blood pressure maintenance
Ø They do so by increasing or decreasing the excretion of water and salt from the body
Ø As the arterial blood pressure increases , the urinary output increases
Ø This phenomenon is called as Pressure diuresis and the curve is called as renal function curve
Thus, it is impossible to change the long-term mean arterial pressure level to a new value without changing one or both of the two basic determinants of long-term arterial pressure
(1) the level of salt and water intake or
(2) the degree of shift of the renal function curve along the pressure axis.
However, if either of these is changed, one finds the arterial pressure thereafter to be regulated at a new pressure level, at the pressure level at which the two new curves intersect
TOTAL PERIPHERAL RESISTANCE AND LONG TERM BLOOD PRESSURE CONTROL
When the total peripheral resistance of the body increases acutely , the blood pressure also increases acutely , but is brought back to its original normal value in a day or so if the kidneys are working normally
SALT INTAKE AND CONTROL OF BLOOD PRESSURE
Ø Increase in salt intake is more important in increasing the blood pressure as compared to increases in water intake
Ø Two primary reasons for this:
1. Increased salt concentration increases the osmolarity of ECF , which stimulates the thirst center in hypothalamus , making the person to drink more water , thus increasing the ECF volume
2. Increases in osmolarity also causes the secretion of Anti diuretic hormone form the posterior pituitary , which cause reabsorption of water from kidneys , thus increasing the ECF volume
VOLUME OVERLOAD HYPERTENSION
Ø Means hypertension caused by excess of extra-cellular fluid
Ø Happens because the kidneys are not removing the excess salt and water from the body
Ø It can happen in two ways
· Removal of kidneys
· Disease process going in kidneys
If the kidneys mass is reduced to 30% and if 6 times more water and salt is given , then there will be an acute increases in :
1.Blood volume 2. ECF volume and
3. Cardiac output
The blood pressure will also rise , but not so acutely as the other three variables
The reason is initially the total peripheral resistance decreases because the baroreceptors were stimulated by increase blood volume , which tried to prevent an increases in arterial pressure
· But after 2-3 days , the baroreceptors adapted to this increase , thus the blood pressure rises to maximum value despite TPR is still normal
· After few days , the blood volume , the ECF volume and cardiac output returns to normal
· This is because the remaining kidney has now adapted to this increase volume overload condition and started excretion of increased fluid and salt
· The increased cardiac output which occurred initially , caused increase in flow of blood to different organs , which reacted to this situation by causing vasoconstriction in their arterioles
· This contributed to increase in TPR which increased progressively as the days passed
· Thus increase in blood pressure contributed to the increase in total peripheral resistance in the long term
RENIN – ANGIOTENSIN SYSTEM
Components of this system are:
1. Renin:
a. Form in JG cells of kidneys as proenzyme activated by low arterial
blood pressure
b. Cause activation of another substance called ANGIOTENSINOGEN
present in blood
2. Angiotensinogen:
Is present in blood , activated by renin to form ANGIOTENSIN I
3. Angiotensin I:
This is converted to ANGIOTENSIN II in lungs by an enzyme called
Angiotensin converting enzyme (ACE)
4. Angiotensin II:
Is a powerful vasoconstrictor , but remains for 1-2 minutes in blood
as it is rapidly degraded by angiotensinases
Angiotensin II
Ø Elevate the blood pressure by two means:
1. Direct vasoconstrictive effects on the arterioles all over the body , thus increasing the total peripheral resistance , thus causing an increases in blood pressure
2. Decreases the excretion of both salt and water by the kidneys (more powerful effect as compared to vasoconstrictive effect)
Actions of angiotensin II
Ø Angiotensin decreases the excretion of salt and water by the kidneys by two processes:
1. Direct effect on kidneys
2. Stimulating aldosterone secretion so as to reabsorb more sodium and water from the renal tubules
Direct effect of angiotensin on kidneys
It does this by three means:
1. Vasoconstricting renal arterioles → less plasma will filter out
2. Slow flow of blood causes the peri-tubular capillaries to reabsorb more and more fluid
3. Directly stimulated the tubular cells of kidney to reabsorb sodium and water
Angiotensin II stimulates aldosterone
Ø Angiotensin directly stimulates the aldosterone ( a steroid hormone released from the adrenal gland)
Ø Aldosterone causes increases absorption of sodium , which inturn , draw the water along with it , thus increasing the salt and fluid volume of the ECF
Renin angiotensin system and control of Blood pressure
RENIN ANGIOTENSIN SYSTEM AND CONTROL OF BLOOD PRESSURE
• The renin angiotensin system , also called as Renin – Angiotensin – Aldosterone System (RAAS) , can effectively maintain the blood pressure whatever the amount of salt is ingested
