Presentation on theme: "Prof.Dr. Ümmühan İşoğlu-Alkaç İ.Ü. İstanbul Tıp Fakültesi Fizyoloji Anabilim Dalı YU Medical Faculty, 04.10.2013 Regulation of Blood."— Presentation transcript:
Prof.Dr. Ümmühan İşoğlu-Alkaç İ.Ü. İstanbul Tıp Fakültesi Fizyoloji Anabilim Dalı YU Medical Faculty, Regulation of Blood Pressure
Nervous Regulation of the Circulation Adjustment of blood flow tissue by tissue is mainly the function of local tissue blood flow control mechanisms. The nervous control of the circulation has more global functions, such as redistributing blood flow to different areas of the body, increasing or decreasing pumping activity by the heart, and, especially, providing very rapid control of systemic arterial pressure. The nervous system controls the circulation almost entirely through the autonomic nervous system.
Autonomic Nervous System By far the most important part of the autonomic nervous system for regulating the circulation is the sympathetic nervous system. The parasympathetic nervous system also contributes specifically to regulation of heart function.
Autonomic Nervous System
Sympathetic Nervous System Sympathetic vasomotor nerve fibers leave the spinal cord through all the thoracic spinal nerves and through the first one or two lumbar spinal nerves. They then pass immediately into a sympathetic chain, one of which lies on each side of the vertebral column. Next, they pass by two routes to the circulation: (1)through specific sympathetic nerves that innervate mainly the vasculature of the internal viscera and the heart, (2)almost immediately into peripheral portions of the spinal nerves distributed to the vasculature of the peripheral areas.
Anatomy of sympathetic nervous control of the circulation. Also shown by the red dashed line is a vagus nerve that carries Parasympathetic signals to the heart.
Sympathetic Nervous Activation
Sympathetic Innervation of the Blood Vessels In most tissues all the vessels except the precapillary sphincters, metarterioles and capillaries, are innervated. The innervation of the small arteries and arterioles allows sympathetic stimulation to increase resistance to blood flow and thereby to decrease rate of blood flow through the tissues. The innervation of the large vessels, particularly of the veins, makes it possible for sympathetic stimulation to decrease the volume of these vessels.This can push blood into the heart and thereby play a major role in regulation of heart pumping.
Sympathetic Nerve Fibers to the Heart. In addition to sympathetic nerve fibers supplying the blood vessels, sympathetic fibers also go directly to the heart. It should be recalled that sympathetic stimulation markedly increases the activity of the heart, both increasing the heart rate and enhancing its strength and volume of pumping.
Parasympathetic Control of the Heart Function Parasympathetic plays a minor role in regulating of the circulation Its most important circulatory effect is to control heart rate by way of parasymphatetic nerve fibers to the heart (N. Vagus)
Parasympathetic Nervous Stimulation
Sympathetic Vasoconstrictor System and Its Control by the CNS The sympathetic nerves carry tremendous numbers of vasoconstrictor nerve fibers and only a few vasodilatatory fibers This sympathetic vasoconstrictor effect is especially powerful in the kidneys, intestines, spleen and skin but much less potent in skeletal muscle and the brain
Vasomotor Center in the Brain Located in the reticular substance of the medulla and lower pons Important areas in this center: –A vasoconstrictor area –A vasodilatator area –A sensory area, located in the nucleus tractus solitarius Output signals from the sensory area provides a reflex control of many circulatory functions (e.g. baroreceptor reflex)
Vasomotor Center in the Brain
Control of the vasomotor center by higher nervous centers Large numbers of small neurons located throughout the reticular substance of the pons, mesencephalon and diencephalon can excite or inhibit the vasomotor center Role of hypothalamus – Limbic system Many parts of the cerebral cortex can also excite or inhibit the vasomotor center –vasovagal syncope (emotional fainting)
Sympathetic Vasoconstrictor Transmitter Substance Noradrenalin Alpha adrenergic receptors of the vascular smooth muscle (Na + ve Ca 2+ ) Adrenal medullae and their relation to the sympathetic vasoconstrictor system (α receptor, adrenalin and noradrenalin) Sympathetic vasodilator system (β1; HR & kontraction, β 2 ; vasodil.) and its control by the central nervous system –Skeletal muscles and vasodilator fibers…
Role of the nervous system in rapid control of arterial pressure Rapid control of arterial pressure within 5-10 seconds Stimulation of entire vasoconstrictor and cardioaccelerator functions by the sympathetic system –Almost all arterioles of the systemic circulation are constricted –The veins are strongly constricted –The heart itself is directly stimulated by the ANS, further enhancing cardiac pumping
Increase in AP During Muscle Exercise and Other Types of Stress During heavy exercise, skeletal muscle require increased blood flow – role of local vasodilation Increase of AP (30-40%) in heavy exercise increases blood flow Activation of vasomotor center Other types of stress and increased AP –Alarm reaction –Fight or flight
Maintaining Blood Pressure: Short Term Mechanisms - CNS Baroreceptor initiated reflex –located at carotid sinuses and aortic arch –monitors blood pressure –regulates the activity of the sympathetic nervous system (vascular tone)
a.Anatomy: Baroreceptors are clusters of bare sensory nerve endings buried within the elastic layers of the aorta and the carotid sinus. Information from the former is relayed to the brain via sensory afferents traveling in the aortic nerve and the vagus nerve (cranial nerve [CN] X). Afferents from the carotid sinus travel in the sinus nerve, which joins with the glossopharyngeal nerve (CN IX) route to the brainstem.
b. Function: In the absence of stretch, the baroreceptors are inactive. When MAP increases, the walls of the aorta and carotid sinus expand, and the embedded nerve endings are stretched. The nerves respond with graded receptor potentials. If the degree of deformation is sufficiently high, the receptor potentials trigger spikes in the sensory nerve.
Baroreceptors are especially sensitive to changes in pressure, responding to the sharp rise in pressure that occurs during rapid ejection with strong depolarization and a train of high frequency spikes. During reduced ejection and diastole, the depolarization abates and spike frequency drops to a new steady-state level that reflects diastolic pressure.
Baroreceptor Reflexes This reflex is initiated by stretch receptors (baroreceptors or pressoreceptors) located at specific points in the walls of large systemic arteries Carotic and Aortic baroreceptors Signals from carotid baroreceptors – small Herings nerves – N. Glossopharyngeus – NTS in the medulla Aortic baroreceptors – N. Vagus – NTS in the medulla
Sensitivity of Baroreceptors: Stretch-sensitivity varies from one nerve ending to the next, thereby allowing for responsiveness over a wide pressure range. The carotid baroreceptors have a response threshold of around 50 mm Hg and saturate at 180 mm Hg. The aortic baroreceptors operate over a range of 110–200 mm Hg.
Circulatory Reflex Initiated by the Baroreceptors After the signals from baroreceptors enter the NTS, secondary signals inhibit the vasoconstrictor center and excite vagal parasympathetic center The net effects are: –Vasodilation of the veins and arterioles in the peripheral circulatory system –Decreased heart rate and strength of the heart contraction Increased TPR (total peripheral resistance) and decreased cardiac output
Baroreceptors and Changes in Body Posture AP in the head and upper parts of the body tends to fall immediately on standing This may cause loss of consciousness Falling pressure at the baroreceptors elicits an immediate reflex resulting in strong sympathetic discharge Pressure Buffer Function of the Baroreceptor control system Reduction of minute by minute variations in arterial BP Long term regulation of arterial BP
On standing up venous return falls Cardiac output diminishes Arterial blood pressure is reduced Baroreceptor afferent firing reduced Medullary centres inhibition reduced THE BARORECEPTOR REFLEX - AN EXAMPLE CORRECTION OF POSTURAL HYPOTENSION Effect of gravity on venous return Preload diminished - Starlings Law Subject possibly feels faint as cerebral flow is reduced Due to reduced arterial B.P. Vasoconstriction Tachycardia Raised stroke work Tend to restore arterial blood pressure Increased sympathetic tone to arterioles Reduced vagal tone to s.a. node Increased myocardial sympathetic tone
Maintaining Blood Pressure: Short Term Mechanisms - CNS Chemoreceptor initiated reflexes –Carotid bodies, aortic bodies –Monitor changes in indicator chemicals (O 2, CO 2, H +, HCO 3 - ) – CO 2, H +, O 2 (stresses) result in sympathetic activity and BP
Control of the Arterial Pressure by the Carotid and Aortic Chemoreceptors Abundant blood flow and contact with the chemoreceptors Signals from the chemoreceptors excite the vasomotor center and this elevates the AP back to normal Chemoreceptor reflex is not a powerful AP controller until the AP falls below 80 mmHg In low pressures this reflex becomes important
Chemoreceptors Chemoreceptors monitor local metabolite levels, which reflect adequacy of perfusion pressure and flow. Anatomy: There are two groups of chemoreceptors, one located in the brainstem medulla, the other peripheral. Peripheral chemoreceptors are discrete, highly vascularized glomus cell clusters lying close to the aortic arch and carotid sinus (the aortic and carotid bodies, respectively). Sensory fibers from the aortic bodies travel in the vagus nerve, whereas nerves from the carotid bodies travel with the sinus nerve and join the glossopharyngeal trunk en route to the medulla.
Function: Peripheral chemoreceptors activate when arterial O 2 levels fall (60 mm Hg) or when PCO 2 or H levels rise (PCO 2 40 mm Hg or pH 7.4). Medullary chemoreceptors are sensitive to the pH of brain interstitial fluid, which is dependent on arterial PCO 2. The chemoreceptors seem designed to monitor lung function and are principally involved in respiratory control, but hypercapnia and acidosis can also reflect low perfusion pressures.
Other Reflexes Regulating Blood Pressure Atrial and pulmonary artery reflexes that help regulate AP and other circulatory factors: –Both atria and pulmonary arteries have in their walls stretch receptors called low-pressure receptors Atrial reflexes that activate the kidneys ( volume reflex ) –Stretch of the atria also causes reflex dilation of afferent arterioles in the kidney
Cardiopulmonary receptors (Atrial and pulmonary artery reflexes) : A second set of baroreceptors is found in low-pressure regions of the cardiovascular system. They provide the CNS with information about the fullness of the vascular system, and their principal role is in modulating renal function. However, because fullness correlates with ventricular preload, they also have a role in maintaining MAP.
Anatomy: The receptors are similar to those found in the arterial system: bare sensory nerve endings embedded in walls of the vena cavae, the pulmonary artery and vein, and the atria. They relay information back to the CNS via the vagal nerve trunk.
Function: Atria contain two functionally distinct populations of baroreceptors. A receptors respond to tension that develops in the atrial wall during contraction. B receptors are sensitive to atrial wall stretching during filling. B receptors are also involved in raising HR when central venous pressure (CVP) is high, a response known as the Bainbridge reflex.
Other Reflexes Regulating Blood Pressure Atrial reflex control of the heart rate (Bainbridge reflex) –Increased atrial pressure also increases heart rate –Direct effect of increased atrial volume to stretch the sinus node –Additional 40-60% increase in rate is caused by a nervous reflex (Bainbridge reflex) that transmits afferent signals to the medulla of the brain
Central Nervous System Ischemic Response Most nervous control of BP is achieved by baroreceptors, chemoreceptors and low-pressure receptors: These are all located in the peripheral circulation However, cerebral ischemia causes strong excitation of the vasomotor center Accumulation of carbon dioxide Other factors (build up of lactic acid) CNS ischemic response is one of the most powerful of all the activators of the sympathetic vasoconstrictor system Importance of the CNS ischemic response Activated only at 60 mmHg or below Emergency pressure control system
Special Features of Nervous Control of Arterial Pressure Abdominal compression reflex –Compression of large abdominal veins and other vessels by skeletal muscles of the body, especially abdominal muscles Increased cardiac output and arterial pressure caused by skeletal muscle contraction during exercise –Compression of blood vessels by skeletal muscles
Respiratory Waves in the Arterial Pressure 4 to 6 mmHg fall in AP during respiratory cycle 1)Breathing signals arise in the respiratory center of the medulla spill over into the vasomotor center with each respiratory cycle 2)With inspiration, pressure in thoracic cavity becomes negative allowing blood vessels in the chest to expand * This reduces the venous return and decreases the cardiac output 3)Pressure changes in the thoracic vessels by respiration can excite vascular and atrial stretch receptors
Long Term Regulation of Arterial Blood Pressure and Hypertension Balance Between Fluid Intake and Output
LONG-TERM CONTROL PATHWAYS A drop in arterial pressure activates the baroreceptor reflex, but it also initiates pathways that require 24– 48 hr to become fully effective. These pathways converge on the kidney, which is responsible for long-term control of blood pressure through regulation of vascular fullness (circulating blood volume).
LONG-TERM CONTROL PATHWAYS Because blood is principally water, this necessarily involves regulation of water output and water intake, but it also requires regulation of Na levels because this is the ion that governs how water partitions between the intracellular and extracellular compartments.
Water output Water output is controlled by ADH, a peptide that is synthesized by the hypothalamus and then transported to the posterior pituitary for release. It stimulates water reabsorption by the renal collecting tubule and collecting ducts. At high concentrations, ADH also increases SVR by constricting resistance vessels.
Water output Several sensors and pathways regulate ADH release including osmoreceptors, baroreceptors, and Ang-II.
1. Osmoreceptors: The brain contains a number of regions that have the potential to monitor plasma osmolality, including areas surrounding the third ventricle in close proximity to the hypothalamus Tissue osmolarity is a reflection of total body water and salt concentration. When osmolarity exceeds 280 mOsm/kg, the receptors cause ADH to be released into the circulation.
2. Baroreceptors: A decrease in circulating blood volume causes CVP to fall, which is sensed by the cardiopulmonary receptors. Loss of preload also causes arterial pressure to fall and triggers a baroreceptor reflex. The CNS cardiovascular control centers respond by increasing sympathetic activity and promoting ADH release.
3. Angiotensin II: Activating the renin-angiotensin-aldosterone system (RAAS) causes circulating Ang-II levels to rise. The list of target organs for Ang-II includes the hypothalamus, where it stimulates ADH release.
B. Water intake Water enters the body along with food, but the bulk of liquid intake occurs through drinking, driven by thirst. The sensation is triggered by decreasing blood volume and arterial pressure, suggesting a prominent role for the cardiovascular control center. C. Sodium output Osmoreceptors control water retention and excretion, but they sense the saltiness of body fluids rather than water per se. Thus, if tissue osmolality remains high, they will urge retention of water regardless of total accumulated volume. The primary determinant of circulating blood volume is Na concentration, which is regulated through RAAS
1. Renin-Angiotensin-Aldosterone system: Renin is a proteolytic enzyme synthesized by granular cells in the wall of glomerular afferent arterioles. The cells form a part of the juxtaglomerular apparatus (JGA), which senses and regulates Na recovery by the renal tubule. When the JGA is stimulated appropriately, it releases renin into the bloodstream. Here, renin breaks down angiotensinogen (a circulating plasma protein formed in the liver), to release angiotensin I.
1. Renin-Angiotensin-Aldosterone system: The latter serves as a substrate for angiotensin- converting enzyme (ACE). ACE is expressed by many tissues, including the kidney, but conversion largely occurs during transit through the lungs. The product is Ang-II, which constricts resistance vessels, stimulates ADH release from the posterior pituitary, stimulates thirst, and promotes aldosterone release from the adrenal cortex.
2. Aldosterone: Aldosterone targets principal cells in the renal collecting tubule epithelium. It has multiple actions, all of which promote recovery of Na and osmotically obligated water from the tubule. Aldosterone acts by modifying expression of genes that encode Na channels and pumps, which is why it takes up to 48 hours for this pressure control pathway to become maximally effective.
3. Renin: The afferent arteriole of the renal glomerulus is a baroreceptor that triggers renin release from the granular cells when arteriolar pressure falls. Release is potentiated by the SNS, which activates following a drop in MAP.
4. Atrial natriuretic peptide: Atrial myocytes synthesize and store atrial natriuretic peptide (ANP), releasing it when stretched by high filling volumes. ANP has multiple sites of action along the length of the kidney tubule, all of which are geared toward excretion of Na and water. The ventricles release a related compound, brain natriuretic peptide, which has similar release characteristics and actions as ANP.
D. Sodium intake Just as thirst stimulates water intake, salt craving triggers a need to ingest NaCl. Salt appetite is controlled through the nucleus accumbens in the forebrain and is stimulated by aldosterone and Ang-II.
Pressure Natriuresis. Arterial pressure is a signal for regulation of NaCl excretion. arterial pressure NaCl reabsorbed in the proximal tubule more NaCl to the macula densa TGF autoregulation RBF, GFR. Pressure Natriuresis. Arterial pressure is a signal for regulation of NaCl excretion. arterial pressure NaCl reabsorbed in the proximal tubule more NaCl to the macula densa TGF autoregulation RBF, GFR. Pressure natriuresis can normalize BP by decreasing the effective circulating volume – this response connects BP and ECFV.
Renal-Body Fluid System for Arterial Pressure Control When the body contains too much extracellular fluid, the blood volume and arterial pressure rise Pressure Diuresis and Pressure Natriuresis At high pressure, the kidneys excretes the excess volume into urine and relieves the pressure At low pressure, the kidney excretes far less fluid than is ingested
Pressure Control by Renal-Body Fluid Mechanism Over the long period, water and salt output must equal intake Equlibrium point Return of the arterial pressure always exactly back to the equlibrium point in the infinite feedback gain principle
Failure of increased TPR to elevate the long-term level of AP if fluid intake and renal function do not change AP = Cardiac output x Total Peripheral Resistance So, increase in TPR should elevate AP But this acute rise in AP is not maintained if the kidneys function properly Why? Pressure diuresis and pressure natriuresis
Failure of increased TPR to elevate the long-term level of AP if fluid intake and renal function do not change
Increased Fluid Volume Can Elevate AP by Increasing Cardiac Output or Total Peripheral Resistance
Importance of salt (NaCl) in the renal-body fluid diagram for arterial pressure regulation An increase in salt is far more likely to elevate AP than is an increase in water intake Water can be eliminated easily, but salt not Accummulation of salt in the body –Stimulation of thirst center in the brain –Increased osmotic pressure stimulates release of vasopressin (ADH)
Hypertension Hypertension is defined as sustained abnormal elevation of the arterial blood pressure
Hypertension Leads to wear and tear is a major risk factor for cardiovascular diseases such as: STROKESTROKE HEART FAILUREHEART FAILURE ATHEROSCLEROSISATHEROSCLEROSIS 30% of worlds deaths
Complications Complications as a result of hypertension include: Stroke Dementia Myocardial Infarction Congestive Heart Failure Retinal Vasculopathy Renal Disease or Failure
Chronic Hypertension is Caused by Impaired Renal Function Mean Arterial Pressure > 110 mmHg (normal is about 90 mmHg) Systolic >140, diastolic >90 mmHg Hypertension can be lethal –Heart failure –Damage of a large vessel in the brain (cerebral infarct or stroke) –Kidney failure Volume-loading hypertension means hypertension caused by excess accumulation of extracellular fluid in the body
Volume-loading hypertension: Two separate sequential stages The first stage: increased fluid volume causing increased cardiac output hypertension The second stage: High blood pressure, high TPR but return of the cardiac output near the normal 1)Hypertension 2)Marked increase in TPR 3)Almost complete return of the extracellular fluid volume blood volume and cardiac output back to normal Volume-loading hypertension in patients who have no kidneys and need for dialysis
Hypertension caused by primary Aldosteronism Another type of volume-loading hypertension is caused by excess aldosterone in the body – (other steroids) A small tumor of adrenal glands and primary aldosteronism Aldesteron increases reabsorbtion of salt and water increased blood volume and reduced urine output Consequently, hypertension develops
The Renin-Angiotensin System Pressure control and Hypertension Renin is an enzyme released by the kidneys when the arterial pressure falls too low It is synthesized and stored in inactive form called prorenin in juxtaglomerular cells JG cells are modified smooth muscle cells in the walls of afferent arterioles Renin acts on angiotensinogen (a plasma globulin) Half life of renin is about 30 mins Angiotensin I, converting enzyme and Angiotensin II
The Renin-Angiotensin System Pressure control and Hypertension
Rapidity and Intensity of Vasoconstrictor Pressure Response to the Renin-Angiotensin System Renin-angiotensin vasoconstrictor system requires about 20 mins to become fully active
Effect of Angiotensin in the Kidneys to Cause Renal Retention of Salt and Water 1)Angiotensin acts directly on the kidneys to cause salt and water retention -Makes the kidneys retain salt and water -Causes vasoconstriction in renal arteries 2)Angiotensin causes the adrenal gland to secrete aldosterone - Aldosterone increases salt and water retention by the kidneys
Role of Renin-Angiotensin System in Maintaining a Normal Arterial Pressure Despite Wide Variations in Salt Intake When the renin- angiotensin system functions normally, pressure rises no more than 4 to 6 mmHg in response to as much as a 50- fold increase in salt intake
Primary (Essential) Hypertension 90 to 95% of hypertension cases are of primary It is of unknown origin –Genetics: there is a strong hereditary tendency –Environment: Excess weight and sedentary life style –Neurohormonal mediators
Some Characteristics of Primary Hypertension 1)Cardiac output is increased due to additional blood flow required for the extra adipose tissue and increased metabolism 2)Sympathetic nerve activity (especially in kidneys) is increased in OW patients (leptin – vasomotor center ?) 3)Angiotensin II and aldosterone are increased (sympathetic stimulation-renin-aldosterone …) 4)Renal-pressure natriuresis mechanism is impaired If hypertension is not treated, there may also be vascular damage in the kidney that can reduce glomerular filtration rate
Summary for Arterial Pressure Regulation AP is regulated not by a single pressure controlling system (several inter-related systems) To achieve –Survival –Returning the blood volume and pressure back to normal Mechanisms 1)Rapidly acting pressure control mechanisms 2)Intermediate mechanisms that act after several minutes – hours 3)Long-term arterial pressure regulation
Intermediate mechanisms that act after several minutes – hours Renin-Angiotensin vasoconstrictor mechanism Stress-relaxation of the vasculature Shift of fluid through capillary walls in and out of circulation * These mechanisms become mostly activated within 30 mins to several hours
Role of the kidneys Many factors can affect pressure-regulating level of the renal-body fluid mechanism –Aldosterone –Renin-Angiotensin system –Nervous system (increased sympathetic activity) Long term mechanisms for AP regulation