Why is it important to regulate MAP?
To ensure that all organs receive the same driving force of blood flow. To ensure that alteration in flow to a given tissue does not significantly impact other tissue vascular beds
Explain the measurment of arterial BP
Inflate the cuff so that there is no blood flow through the artery. Release the pressure just enough so that flow is turbulent and produces Korotkoff sounds. When the vessel is open enough to allow for laminar flow, no sound will be heard
What is stage 2 hypertension?
Systolic = greater than or = to 160
Diastolic greater than or = to 100
How is BP regulated short term (secs to mins)
By neural control acting on the heart, vasculature, adrenal medulla
How is the BP regulated long term (hours-days)?
endocrine/paracrine control acting on the vasculature and kidneys (maintenance of ECF)
What are the two types of receptors involved in the neural reflexes involved in BP regulation?
What are baroreceptors and what are two types?
Mechanoreceptors that detect stretch/distention
1. High pressure receptors
2. Low pressure receptors
Where are the primary CNS integration centers for the regulation of BP?
Medulla, cerebral cortex, hypothalamus
What are the effectors in the neural reflexes involved in BP regulation?
1. Cardiac myocytes (pacemaker and contractile)
2. Arterial and Venous vascular SM cells (VSMCs)
3. Adrenal medulla
How do the high pressure baroreceptors respond to increased stretch (pressure)?
With receptor potentials. Depolarizing inward current. This is a graded response - the amplitude is proportional to the amount of stretch
Why are high-pressure barorecpetors considered a bi-phasic response?
Large initial depolarization (dynamic), steady depolarization (static)
What do the high-pressure barorecptors detect and what is their response?
Detect waveform and amplitude of pressure fluctuations. Increase both firing rate and number of receptors to communicate increases in pressure up to about 200 mm Hg
What is the baroreceptor reflex?
Stretch detected by carotid and aortic baroreceptors = vasodilation and bradycardia
Explain (step by step) the baroreceptor reflex.
1. baroreceptors detect a rise in pressure
2. relay this message to the medulla vai afferent pathways.
3. Medulla is the coordinating center that then sends out signals via efferent pathways to the heart and blood vessels
4. Heart and blood vessels respond with bradycardia and vasodialtion to counteract the increased MAP
What does the medullary cardiovascular center receive input from?
1. Baroreceptors (high and low pressure receptors)
2. Chemoreceptors (centeral and peripheral)
3. Higher brain centers (hypothalamus and cerebral cortex)
4. Respiratory center in the medulla
What does increased baroreceptor firing produce in the ANS?
Inhibition of sympathetic output and excitation of parasympathetic output
What results from normal tonic output of the baroreceptors (in terms of TPR)
Promotes vasoconstriction. Excitation of neurons in the vasomotor area leads to vasoconstriction
What effect does the increased pressure have on baroreceptors in terms of TPR?
Increases baroreceptor firing -> inhibition of vasomotor area inhibits vasoconstriction. Results in vasodilation
What effects does increased pressure have on the baroreceptors in terms of HR?
Increased pressure increases baroreceptor firing -> excitation of neurons in the cardioinhibitory area -> promotes parasympathetic response -> decreased heart rate
How does a decreased CO (and likely decrease in MAP effect arterial PO2, PCO2 and H+?
Decreased CO likely decreases MAP which can lead to a decreased arterial PO2, increased PCO2 and H+
How do the peripheral chemoreceptors respond to a decrease in arterial PO2, increased PCO2 and H+ in terms of TPR?
Peripherial chemoreceptors excite the vasomotor center causing vasoconstriction (this is the opposite of the baroreceptor response)
How do peripheral chemoreceptors respond to a decrease in arterial PO2, increase in PCO2 and H+ in terms of HR?
Peripheral chemoreceptors excite the cardioinhibitory center leading to a decreased HR (similar to baroreceptor response)
What is the isolated chemoreceptor response (independent of respirtation?)
1. decrease in PO2 and increased PCO2 and H+ is detected by the peripheral chemorecptors
2. Afferent paths send the signal to the medulla
3. Medulla sends message down efferent path to the effectors (heart and blood vessels) resulting in bradycardia and vasoconstriction
What is the difference in HR produced by the chemoreceptor when breathing is prevented and when it is not?
Bradycardia occurs only when ventilation is fixed or prevented (ie breath holding). The effects of breathing overcome the intrinsic cardiovascular response producing tachycardia
What is the intrinsic effect of chemorecptor response to hypoxia?
Vasoconstriction and bradycardia (oberved during forced apnea - isolated from respiratiory response)
What is the integrated response to hypoxia? Why?
Tachycardia. In the medulla, respiratory center response to chemoreceptor input impacts the cardiovascular center response
What is responsible for the overall increase in HR as a response to hypoxia?
The primary effect of arterial chemoreceptor stimulation on HR is to excite the cardiac vagal center in the medulla and thus decrease HR. Chemoreceptor stimulation also excites the respiratory center in the medulla. The consequent hypocapnia and increases in lung inflation tend to inhibit the medullary vagal center. Thus, the overall increase in HR response is the result of these opposing influences.
What is the effect of chemoreceptors on ventilation in response to a drop in PO2/increase in PCO2/H+? Where are these changes detected?
Decreased PO2 detected by peripheral chemoreceptors. Increased PCO2 and H+ is detected by central chemoreceptors. Both variables stimulate increased ventilation
How does an increase in ventilation lead to an increase in HR, TPR and MAP?
1. Afferents from the pulmonary stretch receptors inhibit the cardioinhibitory center resulting in an increased HR
2. Increased ventilation lowers PCO2 (decreased H+) in the brain, inhibiting the cardioinhibitory center -> increased HR
3. Ultimately results in increased sympathetic output (increasing HR, TPR, MAP)
How does the central chemoreceptor influence the vasomotor center and what is the response.
A high arterial PCO2 (ie low brain pH) stimulates the central chemoreceptors, disinhibits the vasomotor center. This results in an increasein sympathetic output and vasoconstriction
summarize the response of chemoreceptors to changes in PO2 and PCO2
A low PO2 acting on the periopheral chemorecptor and a high PCO2 acting on the central chemoreceptor act in concert to enhance vasoconstriction.
How do low pressure baroreceptors respond to increased VR and atrial filling?
Response to increased low pressure baroreceptor activity due to increased VR and atrial filling is to try to eliminate fluid by increasing HR and by decreased vasoconstriction to the kidneys (increased renal blood flow - increased urine output)
Where are low pressure baroreceptors found?
A type receptors are mainly in the body of the right atrium B type receptors are mainly in the superior and inferior vena cava
What do the B fibers monitor?
Atrial volume (fire during ventricular systole, increase rate with atrial filling)
What impacts atrial filling and volume?
Central venous pressure (CVP) which is indicative of effective circulating volume and VR
What provides the counterbalance to the baroreceptor reflex for regulation of HR?
Increased stretch of high pressure receptors -> decreases HR
Increased stretch of low pressure receptors -> increases HR
How does increased right atrial pressure influence the HR via the baroreceptor reflex?
Increases right atrial pressure -> increased CO ->increased arterial pressure -> baroceptor reflex -> decreased HR
How does increased right atrial pressure influence HR via the Bainbridge reflex?
Increased Right atrial pressure leads to stimulated atrial receptors which stimulates the Bainbridge reflex which results in increased HR
What would determine the change in HR induced by an IV infusion?
HR results from the opposing reflex actions of the Bainbridge reflex increasing HR and the baroreceptor reflex decreasing it
What are the sympathetic effects on MAP?
Increases TPR by vasoconstriction. Increases CO by increasing HR (CO = HRxSV)
What is the sympathetic influence on the adrenal medulla and therefore on MAP
Sympathetic influence promotes the release of Epi and some NE into the blood. Epi acts on the heart and vasculature (contributing to the hormonal regulation of BP)
What sympathetic receptors produce vasoconstriction of arteriolar SM and what do they like to bind?
alpha 1 and preferentially NE
What sympathetic receptors produce vasodialation of arteriolar SM and what do they like to bind? Where do you find these receptors?
Beta-2 preferentially bind Epi (skeletal muscle, cardiac muscle, liver, adrenal medulla)
What is the parasympathetic influence on arterioles and TPR?
Does not have general widespread impact on arterioles, minimal influence on TPR
What are 4 extrinsic controls of arteriolar radius?
1. sympathetic activity (vasoconstricion)
2. Epi and NE
3. Angiotensin II
4. Vasopressin (ADH)
What are 4 intrinsic (local) controls of arteriolar radius?
1. Local metabolic changes in O2 CO2 and other metabolites
2. Histamine (involved in injury and allergic response)
3. Heat, cold application (therapeutic use)
4. Myogenic response to stretch
What are two major contributors to blood viscosity?
1. Number of RBCs
2. Concentration of plasma proteins
What sympathetic fibers innervate muscular arteries and arterioles and veins?
Postganglionic sympathetic fibers
Where are vasoconstrictor fibers found? (places with most and least)
Widely dispersed but most concentrated in kidneys and skin least concentrated in heart and brain
How dor sympathetic fibers produce vasoconstriction? What is the exception the general rule?
NE binds adrenoceptors on VSMC resulting in generalized vasoconstriction. Exception is skeletal muscle where sympathetic response can promote vasodilation
How does vasodilation occur in muscular arteries, arterioles and veins?
Skeletal muscle - sympathetic response can produce vasodilation
Most other tissues - vasodilation occurs by decreasing sympathetic vasoconstriction
How does the sympathetic NS increase HR?
Binding of B1 adrenergic receptors in pacemaker cells results in increased HR. B1 agonists stimulate:
1. If (diastolic Na+ current): increases steepness of phase 4 slow depolarization
2. Ica (Ca current): increases steepness of phase 4 slow depolarization.
Results in increased rate of slow depolarization phase 4 (phase 4) and negative shift in the AP -> shorter AP duration which results in an increased HR
How does the sympathetic NS increase contractility?
Receptors in the atrial and ventricular myocardial contractile cells. Catecholamines increase contractility (pos inotrophy) by increasing calcium availability for increased contractile force
How do catecholamines increase Ca++ availability for increased contractile force?
1. Increase Ca++ influx (increased calcium influx and increased calcium dependent calcium release from the SR)
2. Increased sensitivity of the SR calcium release channel to calcium
3. Increased SERCA calcium pump activity increasing Ca++ stores
4. Increased calcium influx increases SR calcium stores over time
What are the parasympathetic effects on MAP?
TPR (primarily indirect promotion of vasodilation)
CO=HRxSV (decreased HR)
But it has less influence on TPR than the sympathetic NS does
Where are parasympathetic vasodilator fibers found?
1. Salivary and GI glands
2. Erectile tissue of the external genitalia
How does the parasympathetic indirectly cause vasodilation?
Postganglionic parasympathetic ACh indirectly causes vasodilation
What is the effect of the parasymp NS on HR and SV
Decreases HR (slows conduction)
Some decreased contractility (decreases SV)
How does the parasympathetic NS slow the HR?
by hyperpolarization of pacemaker cell membrane and decreased slope of slow depolarization phase (phase 4). Increased K current, decreased funny and calcium current
What is the effect of decreased funny current in the SA node?
Decreases slow depolarization rate (steepness of phase 4)
What is the effect if decreased calcium current in the SA node?
Decreases slow depolarizaton rate (steepness of phase 4) Threshold more pos
What is the higher control of the cardiovascular end organs?
Medullary cardiovascular control center -> hypothalamus mesencephalon -> cortex of brain
How does the Para NS effect the SA node?
Decreases rate of depolarization to threshold, decreases HR
How does the Symph NS affect the SA node?
Increases rate of depolarization to threshold; increases HR
How does the parasymp NS affect the ventricullar conduction pathway and the ventricular muscle?
How does the symph NS effect the ventricular conduction pathway?
Increases excitability, hastens conduction through bundle of His and purkinje cells
How does the symp effect the atrial and ventricuar muscle?
increases contractility, strengthens contraction
How does the sympathetic NS effect the adrenal medulla?
Promotes adrenomedullary secretion of Epi, a hormonone augments the sympathetic NS actions on the heart
How does the sympathetic NS effect the veins?
Increases venous return which incresaes strength of cardiac contraction through Frank Starling mechanism
What are the two opposing influences on the SA nodal firing rate?
1. Parasymp Activation: decreases HR decreases contractility (ACh on muscarinic receptors)
2. Sympathetic activation: increases HR and increases contractility (NE on B1 receptors)
What are the four major hormones that regulate BP by controlling the blood vessel radius?
2. Angiotensin II (ANG II)
4. Arginine Vasopression (AVP, Vasopressin)
What are the 4 main hormones that regulate the BP by controlling the blood volume?
2. Arginine Vasopressin (AVP, Vasopressin)
4. Atrial natriurtic peptide (ANP)
What are 5 vasoactive endocrine/paracrine factors that impact vasoconstriction (impact blood flow and MAP?)
1. Epi (through a1 receptors)
3. ANG II
What are 6 vasoactive endocrine/paracrine factors that impact vasodialation (impact blood flow and MAP)? These have an intermediate/long term response.
1. Epi (through beta 2 receptors)
5. PGE2, PGI2
What is more powerful, paracrine or endocrine control of blood vessel contraction/relaxation?
Paracrine - usually
How do vasoactive endocrine/paracrine compounds effect BP?
Released into blood or near vascular SM which influences vasomotor tone impacting TPR and the BP
Where does Epi come from and what does it do?
Vasoconstriction via alpha 1
Vasodilation via Beta 2
Where does ANGII come from and what does it do?
Converted from ANG I by ACE in lungs
Vasoconstricttion (ie: released during blood loss or exercise. Reduction of renal BP -> stimulates renin release)
Where do ADH/AVP come from and what do they do?
From post pit gland, causes vasoconstriction (ie: released during hemorrhagic shock)
Where does histamine come from and what does it do?
Released in response to tissue trauma. arteriolar vasodilation, venoconstriction
How does the endocrine system control BP in long term response time?
Nonvasoactive factors impact the effective circulating blood volume through regulation of extracellular fluid volume. (impacts MAP and CO)
What is the key effector organ in the long-term regulation of blood volume? (MAP)
The kidney (rate of sodium excretion and water in the urine)
What is the renin angiotensin aldosterone system?
A slow, hormonal mechanism used in the long-term blood pressure regulation by adjustment of blood volume
What are renin, angiotensin I & II?
Renin is an enzyme. Angiotensin I is inactive. Angiotensin II is physiologically active
What degrades angiotensin II?
Angiotensinase. One of the peptide fragments (angiotensin III) has some of the biological activity of angiotensin II
What are the steps in the renin-angiotension-aldosterone system?
1. Decrease in renal perfusion pressure causes the juxtaglomerular cells of the afferetnt arteriole to secrete renin.
2. Renin is an enzyme that catalyzes the conversion of angiotensinogen to angiotensin I in plasma.
3. Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II primarily in the lungs
How do ACE inhibitors work?
Block the conversion of angiotensin I to angiotensin II and therefore decrease BP
How do angiotensin receptor antagonists work?
Block the action of ANG II at its receptor and decrease BP
What are the 4 effects of ANG II?
1. Stimulates the synthesis and secretion of aldosterone by the adrenal cortex
2. Increases sodium and H+ exhange in the proximal convoluted tubule (directly increases Na+ reabdorption, complementing the indirect stimulation of sodium reabsorption via aldosterone
3. Increases thirst
4. Causes vasoconstriction of the arterioles, thereby increasing TPR and arterial pressure
What does aldosterone do?
Increases sodium reabsorption by the renal distal tubule, thereby increasing extracellular fluid vol, blood vol and arterial pressure. The action of aldosterone is slow b/c it requires new protein synthesis.
What is the result of the actions of RAAS?
Increased sodium reabsorption = increased osmolarity, increased ECF vol, increased BP
What does the renal juxtaglomerular apparatus do?
Macula densa cells detect a decrease in osmolarity, decreased ECF volume and decreased BP so they secrete renin
what are the 2 effects of ANGII?
Stimulates production of aldosterone by adrenal gland
What does aldosterone do?
Secretuon by the adrenal cortex triggered by angiotensin II. Promotes sodium reabsorption by the kidneys (sodium moves back into the blood) water follows by osmosis
Where does atrial natiuretic peptide come from and what does it do?
Cardiac atrial cells (low pressure baroreceptors) detect increased wall stretch (indicates inreased blood volume). They secrete ANP (vasodilator and diuretic). This results in decreased sodium reabsorption. Increased excretion leads to natriuresis. Water follows in urine. Results in decreased osmolarity, decreased ECF volume, decreased BP. Opposes RAAS.
How does the hypothalamus regulate water reabsorption?
The hypthalamus detects an increase in osmolarity and decides that fluid needs to be retained. It stimulates the post pit gland to secrete Vasopressin (ADH), increased water permeability of the distal tubule and collecting duct (increased aquaporins) increased water reabsorption
What does ADH/Vasopressin do?
Opens aquaporinins, forms concentrated urine, conserves water through reabsorption, increases BP
Summarize the effetcs of RAAS, ANH/ANP, ADH/AVP on BP
RAAS: increase BP
ANH/ANP: decrease BP
ADH/AVP increases BP
What is responsible for fast acting regulation of BP?
1. CNS ischemic
What is responsible for intermediate acting regulation of BP?
2. Capillary fluid shift
3. Renin angiotension vasoconstriction
What is responsible for long term regulation of BP?
2. renin-blood volume pressure controle
What are the receptors in short term regulation of BP (central and neural)
High and low prssure baroreceptors
What results from high pressure baroreceptor reflex?
Bradycardia and vasodilation (increased parasymp, decreased sympathetic)
What results from intrinsic and intergrated chemoreceptor reflexes?
Intrinsic: Bradycardia and vasoconstriction
Integrated with respiration: tachycardia and vasoconstriction
What resulst from low pressure baroreceptor reflexes?
tachycardia and decrease blood volume (via renal vasodilation, increased urine output)
What are the sympathetic NS effects on MAP?
Increase MAP by:
1. Increased HR (beta-1) increasedd funny and calcium current (inceases steepness of phase 4 slow depolarization)
2. Increase TPR (primarily through alpha 1) widespread vasoconstriction
3. Increase SV (calcium, contractility)
What are the parasympathetic NS effects on MAP?
1. Decrease HR (via muscarinic receptors) - potassium current increased, funny and calcium decreased. (hyperpolarization of pacemaker cell membrane and decreased slope of slow depolarization phase (phase 4)
What is the time frame for hormonal regulation of BP and how does it work?
Intermediate and long term