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CVS Physiology

CVS PHYSIOLOGY LECTURE # 20 STUDY NOTES: VENTRICULAR ACTION POTENTIAL

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TYPES OF CHANNELS AND CONCENTRATIONS OF VARIOUS IONS

  1. Sodium Channels: The concentration of sodium ions outside the cell membrane is greater than that inside the cell. Therefore, there is a passive movement of sodium ions into the cell as the channels open. The sodium channels are voltage gated as they undergo conformational change in response to differences in potential across the membrane. The sodium channels have two types of gates that control the passage of sodium ions; the ‘H’ gate and the ‘M’ gate. At resting stage, the M gate is closed and the H gate is open. Upon stimulation by an action potential, the M gate opens and the channels become active, allowing sodium ions to travel into the cell. This opening of the channels is limited by time. After a fraction of a second, the H gates close spontaneously rendering the channels inactive. The sodium channels enter a refractory period during which they cannot be activated no matter how strong is the stimulus. At the same time, the M gate closes as well. As soon as the refractory period ends, the H channels open and the sodium channels are restored to their initial inactive state. The M gates remain closed till the arrival of the next action potential and the cycle is repeated.

     

Click Here To Watch Video Lecture For This Topic

 

Different states of the fast sodium channels and relative conformational states of the H and M gates are summarized in the table below:

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SODIUM CHANNEL STATE

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M-GATE (ACTIVATION GATE)

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H-GATE (INACTIVATION GATE)

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Closed (Resting state)

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Closed

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Open

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Open (Active state)

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Open

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Open

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Inactivated

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Open

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Closed

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2. Potassium Channels: Physiologically, the cells are loaded with potassium ions. The concentration of potassium ions is relatively greater inside the cell. As a result, they tend to move out of the cell from a region of higher concentration to a region of lower concentration until -94 mV is the potential difference across the membrane.

There are four types of potassium channels:

  • Potassium Leaky Channels: these are independent of any external factors and allow a constant leakage of potassium ions out of the cell.
  • Inward Rectifying Potassium Channels (IK1): These channels are voltage gated and they open or close in response to changes in membrane potential.
  • Inward Delayed Rectifying Potassium Channels: Also voltage gated.
  • Inward Rectifying Transient Potassium Channels: Open transiently for a very small amount of time.

3. Calcium Channels: The calcium ions tend to move inside the cell as they are present in greater amounts outside the cell. They are classified as fast and slow calcium channels.

4. Na/K ATPase: These are ATP dependent transmembrane proteins that actively pump sodium and potassium ions against their concentration gradient. 3 sodium ions are pumped out of the cell in exchange for 2 potassium ions into the cell. This creates a negative balance across the cell membrane which also corresponds to the negative RMP inside most cells.

ROLE OF IONIC CHANNELS DURING AN ACTION POTENTIAL

  1. Rest State/Phase 4 of Action Potential: The Na/K ATPase works at the expense of energy to keep the resting membrane potential -90mV. Potassium leaky channels allow passive movement of potassium ions out of the cell in order to prevent excess negativity inside the cell and maintain the RMP.

     

  2. Rapid Depolarization/Phase 0 of Action Potential: Upon stimulation, the voltage dependent M gates of sodium channels open and rapidly allow sodium entry into the cells. An immediate spike in the positive direction is observed. The membrane potential rises from -90mV to +20mV. At this point, the H gates close and the sodium channels become refractory. The leaky potassium channels remain open.

     

  3. Transient Repolarization/Phase 1 of Action Potential: The inward rectifying transient potassium channels open. This happens for a very brief period of time during which potassium ions move out of the cell. A consequent drop in membrane potential is observed.

     

  4. Plateau/Phase 2 of Action Potential: The membrane potential remains constant during this part of the cycle as the resultant movement of ions in opposite directions balances the charge across the membrane. The calcium channels were triggered to open along with sodium ions at the start of the action potential. Due to their slow nature, the calcium channels take time to open. Opening of these channels and the movement of calcium ions inside the cell will oppose the negative charge produced by movement of potassium ions out of the cell. The movement of potassium ions is conducted by delayed rectifying potassium channels. Hence, the membrane potential is maintained at a constant value the entire time the calcium channels remain open.

     

  5. Repolarization/Phase 3 of Action Potential: At the end of Phase 2, the calcium channels start to close. The inward rectifying potassium channels open and along with the already open delayed rectifying potassium channels, they conduct potassium outflow. This would create a burst of positive charge leaving the cell. The membrane potential falls back to the RMP. The Na/K ATPase are reactivated to maintain RMP.

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Categories
CVS Physiology

CVS PHYSIOLOGY LECTURE # 19 STUDY NOTES: AUTONOMIC CONTROL OF NODAL ACTION POTENTIAL

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INNERVATION OF THE HEART

 

  • PARASYMPATHETIC NERVOUS SYSTEM (PANS)

The right and left Vagus nerve (CN10) supply the SA node and the AV node respectively. Apart from the two nodes, the Vagus nerve also innervates the atrial muscles and the AV bundle. Parasympathetic supply to the ventricular muscles is very sparse as only a few vagal branches innervate the ventricles. Therefore, it is safe to say that the Vagus supply is limited to the two nodes and the atrial muscles only. PANS causes a marked decrease in heart rate (negative chronotropic effect) and a slight decrease in heart muscle contractility (negative inotropic effect).

Click Here To Watch Video Lecture For This Topic

 

  • SYMPATHETIC NERVOUS SYSTEM (SANS)

On the other hand, the sympathetic supply to the heart is global as it supplies the two nodes as well as the atrial and ventricular muscles. SANS increases the heart rate and the contractility of the myocardium i.e. positive chronotropic and inotropic effect.

 

RATE OF DISCHARGE OF NODAL TISSUE

There is a gradual increase in the RMP of nodal tissues from -55mV to -40mV and this is referred to as the slope of depolarization. Phase 4 is followed by the Phase 0 of action potential. At -55mV, the fast sodium channels (also known as ‘funny’ channels) are in a semi-open state which allows leakage of positive ions into the nodal cells. Leakage of sodium ions causes an increase in the membrane potential in the positive direction (towards 0). The membrane potential gradually increases to          -40mV. Upon reaching this threshold potential, the sodium channels close and remain closed for the rest of the action potential as they enter a state of refractoriness.

An increase in the slope of depolarization will cause the SA node to generate action potentials at a higher rate. Flattening of the slope will result in decreased number of action potentials in a given time which greatly reduces the rate at which the heart beats.

The action of the ANS on the Phase 0 of the action potential brings about changes in heart rate. SANS acts to increase the slope of depolarization so that the threshold potential (-40mV) is reached earlier than normal. This results in an increase in the heart rate. The PANS, via the vagal stimulation, causes a decrease in the slope of depolarization which causes a delay in reaching the threshold potential for spontaneous depolarization. This subsequently results in an increase in the duration of action potential, thereby decreasing the heart rate (negative chronotropic effect).

Additionally, changes in ionic conduction across the cell membrane also cause changes in the heart rate. However, the part of action potential that undergoes changes relies on the type of ions involved:

  • Changes in sodium ion conduction cause a change in the slope of depolarization. This is similar to the effects of the autonomic nervous system.
  • Calcium channel conduction affects the rapid upstroke or Phase 0 of depolarization.  
  • The repolarization phase is dependent upon the conductance of potassium ions. Hence, any changes in potassium ion conductance will affect the time taken for the nodal tissue to repolarize.

Faster the conduction of the above mentioned ions across the cell membrane, higher would be the frequency of depolarizations and vice versa. Dromotropy is a property of the cardiac conducting system which determines the conduction velocity of impulses across the cardiac conduction system. Impulse velocity is determined by the conductance of above mentioned ions. SANS causes positive dromotropic effect, thereby increasing the conduction velocity across the conduction system of the heart. On the other hand, PANS results in a negative dromotropic effect. Negative dromotropic effect will result in decreased conduction velocity across the cardiac conduction system.

Rate changes in the SA node occur mainly via the action of autonomic nervous system. Whereas, the AV node and rest of the conduction system exhibit changes in their rate of depolarizations secondary to the movement of ions across their cell membranes.

 

TERMS USED TO DESCRIBE HEART RATE & CONTRACTILITY

  1. Chronotropy: It refers to the rate of cardiac activity. For example, the parasympathetic nervous system causes negative chronotropy and the sympathetic nervous system causes positive chronotropy.
  2. Dromotropy: This term is used to describe the velocity of conduction within the conducting fibers. Negative dromotropic agents decrease the velocity of conduction. Positive dromotropy occurs when there is an increase in the velocity of conduction.
  3. Inotropy: This is a term used to describe the contractility of the cardiac musculature (ventricular muscle mainly). SANS has a positive inotropic effect whereas PANS stimulation has a mildly negative chronotropic effect which isn’t that pronounced.

 

MECHANISM OF ACTION OF AUTONOMIC NERVOUS SYSTEM AT MOLECULAR LEVEL

Primary neurotransmitters (Acetylcholine in PANS stimulation and adrenaline or noradrenalin in SANS stimulation) activate the G-coupled proteins present on the cell membrane of the conducting tissues. This results in the detachment of intracellularly bonded alpha subunit of the G proteins which acts on the sodium and calcium channels. The channels get activated or deactivated depending on the type of stimulation that occurs initially.

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Categories
CVS Physiology

CVS PHYSIOLOGY LECTURE # 18 STUDY NOTES: NODAL ACTION POTENTIAL

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NODAL ACTION POTENTIAL VS. VENTRICULAR ACTION POTENTIAL

The nodal tissues and the Purkinje fibers exhibit automaticity in their properties as they are able to undergo spontaneous depolarizations. In other words, these tissues do not require the need of an external stimulus or a trigger to undergo depolarization. This is in contrast to ventricular fibers that do not show automaticity. The reason behind this phenomenon can be explained as follow:

Click Here To Watch Video Lecture For This Topic

  • The resting membrane potential (RMP) of nodal tissues is less negative than the RMP of ventricular fibers. This allows the nodal tissue channels to operate in a semi-activated state even during the resting phase of the action potential. The comparatively more negative ventricular fibers do not show this property and hence, are not easily activated by low voltage impulses.

  • Secondly, the presence of fast sodium channels and slow calcium channels, in ventricular fibers and nodal tissue respectively, play an important role in the automaticity of a cell. The slow calcium channels in the nodal tissues are responsible for the peak voltage occurring during a nodal action potential. Whereas, in the ventricular muscle fibers, the fast sodium channels are responsible for the same voltage spike and the calcium channels are involved only during the plateau phase.

PHASES DURING AN ACTION POTENTIAL

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PHASE OF ACTION POTENTIAL

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VENTRICULAR MUSCLE FIBER

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NODAL TISSUES

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Phase 0

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Opening of Sodium channels (Depolarization)

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Opening of Calcium channels (Depolarization)

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Phase 1

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Opening of transient Potassium & Chloride channels

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Does not occur

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Phase 2

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Plateau phase: Opening of slow Calcium channels

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Does not occur

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Phase 3

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Repolarization: Opening of Potassium channels

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Repolarization: Opening of Potassium channels

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Phase 4

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Resting Membrane Potential

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Resting Membrane Potential

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PHASES DURING AN ACTION POTENTIAL

There is a gradual increase in the RMP of nodal tissues from -55mV to -40mV. This is known as the slope of depolarization, after which occurs the Phase 0 of action potential. This slope is important as multiple factors, such as the ANS and certain drugs, act to alter this phase and bring about changes in the rate and rhythm of cardiac activity. An increase in the slope of depolarization will cause the SAN to generate action potentials at a higher rate. Flattening of the slope will result in fewer numbers of action potentials in a given time which greatly decreases the rate at which the heart beats.

CONTROL OF HEART RATE & CONDUCTION VELOCITY

 

An isolated SA node has the highest intrinsic rhythm of impulse generation, i.e. 100 beats/min. This intrinsic rhythm of SAN is regulated down to 72 beats/min under the influence of the autonomic nervous system. Similarly, the AV node has the ability to depolarize at a rate of 60 beats/min. SAN, having a considerably higher frequency of depolarization, overrides the pace maker activity of the AVN. This causes the AV node to generate action potentials at a rate similar to SA node. Upon cessation of high frequency impulses from SA node, as happens during bundle blocks, the AV node is shown to beat at its own inherent frequency. There is a respective decrease in the frequency of depolarization as we move along the bundle of His and the Purkinje fibers. This relative difference in the intrinsic rhythm of different parts of the cardiac conduction system allows a uni-directional flow of impulses across the entire conducting system.

As described above, the SA node has the highest rate of depolarization and therefore, it dictates the rate of cardiac activity. Altering with the mechanics of SA node will cause alterations in the rate of heart beat as a whole. Similarly, the velocity of conduction is controlled by the AV node and AV bundles as the speed of impulse travelling through them is the slowest. Dromotropes act on these areas of the conducting system and cause changes in the velocity of impulse conduction.

DIFFERENT ION CHANNELS AND THEIR AFFECT ON THE ACTION POTENTIAL

VENTRICULAR ACTION POTENTIAL

  • The Phase 0 of ventricular action potential is brought about by fast voltage gated sodium channels. This phase is referred to as the upstroke of action potential and corresponds to the QRS complex of the ECG.

  • At the end of depolarization, there is a brief fall in the voltage of action potential as a result of opening of transient chloride and potassium channels. This is Phase 1 of the depolarization. Fast sodium channels transition to their inactivated state.

  • L-type Calcium channels open in the Phase 2 of action potential. The inward calcium current balances the outward potassium current and there’s little change in membrane potential, which explains the plateau. During this plateau phase no change in the voltage is registered. Phase 2 or the plateau phase of the ventricular action potential corresponds to ST segment of the ECG.

  • Phase 3 corresponds to repolarization during which Potassium channels open in response to voltage and ion concentration difference. By this time L-type Calcium channels, which were open during the plateau phase, have also closed. Repolarization corresponds to the T-wave on the ECG. Inward Potassium current enters via the:
  • IK1 channels: Inward rectifying K current
  • IK channels: Slow and rapid rectifying K current
  • The action potential is brought back to the resting membrane potential or Phase 4. The sodium-potassium ATP-ase is responsible for the maintenance of RMP until the arrival of the next action potential. Fast Na+, L-type Ca2+, and rectifying K+ channels (IKR) close, but IKchannels remain open.

NODAL ACTION POTENTIAL

It’s important to understand that the nodal tissue (SA and AV) lacks fast Na+ channels. Thus, the upstroke of the action potential is mediated by inward calcium current rather than the sodium current. In addition, note that phases 1 and 2 are absent in the nodal tissue.

  • The RMP (Phase 4) in nodal tissue is kept at -55mV by the Na-K ATPase pump. The less negative RMP of nodal tissue, compared to -70mV of ventricular tissues, allows it to exhibit automaticity. At -55mV, the fast sodium channels (also known as ‘funny’ channels) are in a semi-open state which causes leakage of positive ions into the nodal cells. Leakage of ions causes an increase in the membrane potential in a positive direction. The membrane potential gradually increases to -40mV. Upon reaching this threshold potential, the sodium channels close and remain closed for the rest of the action potential as they enter a state of refractoriness.
  • At this point the slow-gated T-type calcium channels open which creates the spike of depolarization (Phase 0). These differ from the L-type calcium channels (in the ventricular tissue) in that they open at a more negative membrane potential (-70 mV). The calcium ions that enter the cells during this phase are also involved in excitation-contraction coupling of the myosin light chains with actin filaments.
  • Repolarization (Phase 3) in nodal tissue is similar to that of ventricular muscle fibers. Inward Potassium current enters via the IK& IK(rectifying K currents) channels. The fall in membrane potential will result in activation of the sodium-potassium ATPase and the cycle is repeated.

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Categories
CVS Physiology

CVS PHYSIOLOGY LECTURE # 16 STUDY NOTES: BLOOD PRESSURE CONTROL BY BARORECEPTORS

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The MAP, also considered as the perfusion pressure, is taken as the pressure difference between the arteries and the veins. The regulation of blood pressure is done in order to maintain the MAP. The MAP hence dictates the amount of oxygen and nutrients that is supplied by the blood vessels and the waste that is carried away from the tissues.

 

Click Here To Watch Video Lecture For This Topic

 

The body has the ability to counteract long term as well as short term changes in blood pressure. The long term pressure changes cause the body to respond through the activation of renin-angiotensin system.Rapid/short term changes in blood pressure compel the body to activate the following receptors:

  • Baroreceptor present on the arch of aorta
  • Chemoreceptors present in the carotid sinuses
  • Atrial receptors present on the wall of right atrium

These receptors are modified nerve endings that are sensitive to rapid offsets in blood pressure. Rapid offsets in pressure can occur, for example, in a previously standing person who suddenly sits down. During the process, a large volume of blood is shifted from the peripheral to the central regions of the body. Consequently, a large volume of blood enters the heart and this volume overload (increased preload) causes the heart to increase its cardiac output. A simultaneous increase in blood pressure will also be observed with increase in cardiac output. The increase in blood pressure is registered by the baroreceptors which are densely situated on the walls of the arch of aorta and the carotid arteries.

Similarly, a drop in blood pressure is registered by the baroreceptors when the person stands up suddenly from a sitting position. These pressure sensing bodies are modified nerves with stretch receptors on their ends. These stretch receptors are attached to the cytoskeleton present within the nerve endings. High blood pressure in the blood vessels causes stretch of these receptors which results in movement of sodium ions into the nerve endings, thereby, initiating an action potential.

These baroreceptors have a baseline firing pattern. That means they have an intrinsic potential to generate action potentials at a particular frequency at all times. This frequency is increased when the baroreceptors receive a stretch stimulus secondary to increase in blood pressure. The carotid sinuses increase their rate of impulse generation when the pressure in them builds up to values greater than 50 mm Hg. Below this threshold pressure, the carotid baroreceptors fail to initiate an action potential. On the other hand, the arch of aorta can record drops in blood pressure up to 30 mm Hg. The upper limit for blood pressure, after which the frequency of action potential stops increasing, is 175 mm Hg. The normal MAP is calculated to be 93 mm Hg. At this pressure, the baroreceptors are believed to be the most sensitive and even slight changes in pressure will result in rapid firing of action potentials. At blood pressures lower than 30 mm Hg, the chemoreceptors come into play. The chemoreceptors function by sensing the arterial concentration of carbon dioxide, oxygen and other metabolites rather than detecting changes in blood pressure.

STRUCTURE OF THE CAROTID SINUS

 The carotid sinus is present on the base of internal carotid artery at the level of bifurcation of the common carotid artery. The sinus area is slightly dilated as the tunica media which is normally comprised of muscles, is relatively thin. The tunica adventitia, on the other hand, is thicker than usual. This is the layer of the blood vessels where the nerve receptors are situated. Same is true for the location of baroreceptors on the arch of aorta.

THE BARORECEPTOR REFLEX

The baroreceptor reflex, like other reflex arcs, is comprised of three units:

  1. Afferent nerve carrying impulses from the receptors,
  2. Central processing unit
  3. An efferent nerve that innervates the effector

Afferent impulses from the carotid sinus are carried by the Herring nerve, a branch of Glossopharyngeal nerve (CN-9). In the case of baroreceptors present on the arch of aorta, the Vagus nerve (CN-10) is the afferent nerve that carries impulses to the spinal cord. Both, the Vagus nerve and the Glossopharyngeal nerve, feed impulses from the baroreceptors into the nucleus of tractus solitarius. These nuclei are situated in the medulla of the spinal cord and their job is to process the incoming afferent impulses. Also within the Medulla and lower 1/3rd of the Pons, there are vasoconstricting center, the vasodilatory center and the cardio-inhibitory center. These centers receive processed impulses from the nucleus of tractus solitarius and from here efferent impulses in the form of sympathetic and parasympathetic nerves arise. Impulses are carried to the heart via the parasympathetic Vagus nerve. Sympathetic impulses travel down the intermedio-lateral segment of the spinal cord and give rise to efferent motor spinal nerves which enter the sympathetic ganglion running parallel to the spinal cord. Postganglionic sympathetic nerves ultimately supply the heart and the peripheral vasculature. Another preganglionic sympathetic nerve also supplies the adrenal medulla which results in the release of epinephrine and norepinephrine, which further contribute in enhancing the sympathetic activity. The end result is either an increase or decrease in the blood pressure, thereby correcting the disturbance in hemodynamics of the body. This phenomenon is also referred to as the buffering effect, since the change in pressure is buffered back to normal. The Vagus and Glossopharyngeal nerves, because of the same reason, are therefore known as the buffering nerves.

The factors responsible for change in mean arterial pressure are formulated as follows:

  • MAP = Heart Rate x Cardiac Output

Whereas, CO = SV x TPR

Therefore, MAP = HR x SV x TPR

The stroke volume is altered by altering the force of contractility of the heart muscles. The sympathetic nerves supplying the heart muscles affect the stroke volume. The parasympathetic nerves supplying the SA and AV node are responsible for producing changes in heart rate. The TPR can be increased or decreased by changing the diameter of peripheral vasculature which is under the control of the sympathetic nervous system.

EFFECTS OF BARORECEPTORS DURING VARIOUS CONDITIONS

 

  • DUE TO CHANGES IN BLOOD PRESSURE
  1. Reduced Blood Pressure: Reduction in blood pressure will result in a decrease in the number of afferent impulses from the baroreceptors. The sympathetic activity will increase and as a result, the TPR, HR and the stroke volume will all increase. At the same time, the parasympathetic input will taper down. All these changes will result in increasing the blood pressure back to normal.

     

  2. Increased Blood Pressure: This happens in situations like exercise or stress. Increased blood pressure will result in stretching of the stretch receptors. This increases the frequency of afferent impulses. Sympathetic supply will decrease and the parasympathetic system will take over. Finally, the blood pressure is decreased back to normal.

 

  • DUE TO CHANGES IN CARDIAC OUTPUT
  1. Decreased Cardiac Output: Occurs in situations of vomiting, diarrhea, hemorrhage etc. As a result of these, both the volume, and therefore pressure of the blood decreases. Afferent impulse firing of the baroreceptors decreases. As a consequence, there’s a sympathetic overflow which causes an increase in HR, TPR and SV. Due to an increase in these parameters, the blood pressure is raised back to normal.
  2. Increased Cardiac Output: There’s an increased impulse generation from the baroreceptors due stretch caused by increased volume of blood. This increased afferent input from the baroreceptors results in activation of the PANS. Once activated, the parasympathetic nervous system decreases the blood pressure back to normal.

  • MASSAGING THE CAROTID SINUS

Massaging the carotid sinuses physically increases the pressure on the baroreceptors present there. The carotid baroreceptors respond by increasing the rate of afferent impulse firing. The sympathetic system will be shut down and the parasympathetic system is activated. This results in events leading to decrease in blood pressure of the body.

 

  • STENOSIS OF CAROTIDS

Stenosis of carotids proximal to the sinus or obstruction of the carotids due to atherosclerosis will cause the baroreceptors to register a decrease in pressure. Therefore, sympathetic system activation follows. Increased sympathetic activity causes a resultant increase in blood pressure. This increase in blood pressure may cause hypertension in an otherwise normal person.

The above factors and their affect on the baroreceptor response are summarized in the table below:

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Factor

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Afferent

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Sans Activity

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Pans Activity

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Blood Pressure

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Heart Rate

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↓BP

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↑ towards normal

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↑BP

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↓ towards normal

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↓CO

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↑ towards normal

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↑CO

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↓ towards normal

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Carotid Massage

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↓ towards normal

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Carotid Stenosis

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↑ towards normal

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It’s important to understand that baroreceptor control of BP is a short term regulation of blood pressure. Any short term derangements are dealt via the baroreceptor response, whereas long term control of the BP is controlled via the RAAS (Renin Angiotensin Aldosterone System). The baroreceptors also have the ability to adapt to chronic changes in blood pressure. If the mean pressure is changed over time to a new value, the baroreceptors will start using that MAP as the baseline. Any subsequent blood pressure changes will then be rectified keeping in view the new baseline value of MAP.

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CVS Physiology

CVS PHYSIOLOGY LECTURE # 15 STUDY NOTES: AUTOREGULATION – CORONARY BLOOD FLOW

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ORGANIZATION OF THE CVS

The coronary vasculature supplies blood to the muscles of the heart (myocardium). These coronary arteries are the first branches (right & left coronary arteries) that arise from the aorta, and they run on the surface of the heart’s muscle. Branches from the arteries penetrate the muscle in order to supply blood to deeper myocardial tissues. When the heart contracts during systole, the small arteries that are embedded deeply within the heart musculature are also squeezed along with the heart. This mechanical compression of coronary arteries causes a brief period of occlusion of coronary blood flow during systole. Therefore, it should be established that the whole body receives oxygenated blood during systole except for the heart itself. The heart will be supplied with the oxygenated blood when the atria and ventricles are in a relaxed state which happens during diastole. At that time, the coronary vasculature is not compressed and the perfusion is at a maximum. The right heart muscles contract with lesser force compared to the left heart. Hence, a relatively small amount of perfusion is maintained in the right heart even during systole.

Click Here To Watch Video Lecture For This Topic

Even under normal resting conditions, the heart tissue extracts 80% of the total oxygen content from the blood that is supplied to it. This high extraction of oxygen is necessary to meet the demands of highly active muscles of the heart. The demand for oxygen is increased substantially when there is an increase in the heart rate, as happens during exercise. Compared to the cardiac muscle, the skeletal muscle extracts only 20% of oxygen from the blood at normal resting conditions. In other tissues, when oxygen demand increases, vasodilatory metabolites such as H+ ions and carbon dioxide cause a rightward shift of the oxygen dissociation curve. This allows greater dissociation of oxygen from the hemoglobin. However, this rightward shift of the hemoglobin oxygen dissociation curve is not valid for the blood in the coronary circulation. This is because the extraction of oxygen by heart tissue is already at maximum level even under normal resting conditions. Therefore, the increased demand for oxygen during exercise can only be compensated by increasing the blood flow rate of the coronary circulation.

The flow of coronary vasculature is under the influence of both intrinsic and extrinsic mechanisms. The extrinsic mechanisms include the sympathetic and parasympathetic nervous systems.

  • The PANS input is relayed by the right and left vagus nerves. Right vagus nerve innervates the SAN, while the left vagus nerve innervates the AVN. The PANS regulates the blood flow indirectly by controlling the heart rate (chronotropy) and the force of contraction (inotropy).
  • The SANS innervates the SAN &AVN, the myocardium and also the vascular smooth muscle of coronary vessels.  Hence, SANS regulates the heart rate, force of contraction of ventricular myocardium and the flow into the coronary vasculature. However, the extrinsic mechanisms involved in vascular diameter changes are ineffective during physiological conditions. Although there is sympathetic stimulation on the vascular smooth muscles, the effects are negated by the constant release of nitric oxide from the endothelium. If this nitric oxide release is blocked by an atherosclerotic plaque, the unchecked sympathetic stimulation causes vasoconstriction leading to the pain of angina. Atherosclerosis decreases coronary perfusion by reducing the coronary artery lumen and also by blocking the release of NO from the coronary artery endothelium.  

Under physiological conditions, the metabolism induced changes in vascular caliber are more prominent. The metabolites produced by the heart tissue responsible for vasodilation are:

  • H+ ions
  • K+ ions
  • Adenosine
  • Bradykinin and Prostaglandins

Volume – Work Relationship

There is a direct relationship between the volume of blood entering the heart (preload) and the work done by the heart to pump it out. The pressure remains the same as there is no change in myocardial contractility or afterload. This can be observed when a person is exercising during which the volume of blood returning to the heart increases.

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Pressure – Work Relationship

There is a direct relationship between the pressure developed in the peripheral vasculature and the work done by the heart against it. The demand for oxygen in pressure overload situations is higher than in volume overload. Patients with atherosclerosis show this kind of pressure – work relationship in their cardiovascular system.

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    CVS Physiology

    CVS PHYSIOLOGY LECTURE # 14 STUDY NOTES: AUTOREGULATION – CEREBRAL BLOOD FLOW

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    The vessels supplying the brain tissue are separated from the CSF by a blood-brain barrier. Blood flow in these vessels is autoregulated through intrinsic mechanisms (autoregulation). The brain does have sympathetic nerves innervating its blood vessels but these nerves do not play any role in regulating the blood flow. Intrinsic mechanisms that are involved in autoregulation of cerebral blood flow are theorized as follows:

    Click Here To Watch Video Lecture For This Topic

    1. Myogenic theory: This theory states that increase in blood flow in cerebral vasculature is counteracted by contraction of smooth muscles surrounding the blood vessels. This action helps to nullify the increase in blood flow and pressure.

       

    2. Metabolic theory: According to the metabolic theory, the brain has the ability to autoregulate blood flow in response to changes in pH of the blood. The pH of blood circulating in the cerebral vasculature is different from that in the CSF. In other words, it is not necessary that the CSF will undergo changes in its pH if the blood being delivered to the brain has a different pH. This is explained by the fact that H+ ions, being positively charged, cannot travel across the blood-brain barrier. The pH of blood changes regularly with changes in the body. Hypoventilation causes respiratory acidosis which causes the pH to decrease. Similarly, ingesting drugs like aspirin, sulfonamides etc also cause marked changes in pH of blood. Therefore, if the H+ ions were allowed to pass uninterruptedly across the blood-brain barrier, the consequent changes in pH would have caused devastating effects on the brain tissue. On the other hand, gases such as carbon dioxide and oxygen can cross the blood-brain barrier as they don’t carry a charge. The relation of blood flow with carbon dioxide is linear, i.e. increase in carbon dioxide concentration will directly cause increase in blood flow. The effects of oxygen on the cerebral blood flow are negligible; however, pathologically increasing oxygen concentration will show a prominent decrease in blood flow.

    Hypoventilation

    It causes carbon dioxide levels to increase in the blood. After crossing the blood brain barrier, carbon dioxide enters the CSF where it reacts with water and forms hydrogen carbonate. The hydrogen carbonate formed disassociates into hydrogen ion and hydrogen bicarbonate. The H+ ions act on the ventrolateral part of medulla which is the central chemoreceptor of the body. The chemoreceptor zone detects changes in the chemical content of the body. The role of central chemoreceptors is different from that of the peripheral chemoreceptors in maintaining the homeostasis in the body. When triggered, it sends impulses to the nuclei present on the lower 1/3rd of Pons and upper parts of Medulla. These areas of brain are involved in cardiovascular and respiratory changes that are carried out through sympathetic and parasympathetic nerves. As a result, the vessels in the body as well as in the brain vasodilate and the blood flow increases. Moreover, intrinsic metabolites which are released by the cerebral tissues cross the blood-brain barrier and act on the vascular smooth muscles. This causes further vasodilation of the cerebral vessels. These vasodilator metabolites include the following:

    • K+ ions
    • H+ ions
    • Bradykinin
    • Nitric Oxide

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    The Monroe Kelly Doctrine:

    The principle says that the combined volume of blood and CSF in the cranial vault is maintained at a constant value in all circumstances. If a change in volume occurs in either of the constituents, the volume of the other fluid is shifted out or into the cranium in order to compensate for the change.

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      Categories
      CVS Physiology

      CVS PHYSIOLOGY LECTURE # 13 STUDY NOTES: AUTOREGULATION – CUTANEOUS BLOOD FLOW

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      The cutaneous blood flow is primarily regulated by extrinsic factors, i.e. the sympathetic and parasympathetic nervous system. Another extrinsic factor, exclusive to cutaneous blood flow, is the regulation of blood flow due to thermal changes. Therefore, skin is the only organ whose blood supply is regulated with alterations in temperature.

      Click Here To Watch Video Lecture For This Topic

      REGULATION OF BLOOD FLOOD FLOW VIA THE AUTONOMIC NERVOUS SYSTEM (ANS)

      The blood vessels of skin are innervated by both PANS and SANS. The receptors present are predominantly α-1 adrenergic receptors which are G-q coupled. α-1 adrenergic receptors, when stimulated, cause vasoconstriction of the blood vessels perfusing the skin. This results in reduced blood flow and hence, reduced blood volume supplied to the cutaneous regions. This vasoconstriction is also accompanied with pressure changes within the cutaneous blood flow. Vasoconstriction in arterioles causes a decrease in downstream pressure and an increase in the upstream pressure with respect to the area of constriction. The significance of these changes lies in the fact that lesser amount of blood is now exposed to a large surface area through which heat exchange is carried out.

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      REGULATION OF BLOOD FLOW DUE TO CHANGES IN TEMPERATURE

      The anterior neurons of hypothalamus are modified to detect changes in temperature. This enables the hypothalamus to work as a thermostat of the body. If the temperature of the body undergoes changes, as happens during fever, the hypothalamus makes some adjustments in the body in order to bring the temperature back to normal (homeostasis). During a fever, the default thermostat of the hypothalamus which is normally set at 37’C, is disturbed and is raised to a higher value. Inflammatory mediators, such as Interleukin-1 and PGE2, play a major role in disturbing this set temperature point. The temperature of the body is raised in order to equalize the newly set temperature by the hypothalamus. The following events occur in the body in order to raise the body’s temperature:

      • Shivering: This is caused by rapid contraction and relaxation of the muscles. A large amount of heat is generated during the process. This heat is utilized to raise the temperature of the body.

      • Cutaneous Vasoconstriction: The arterioles and the venules supplying the superficial parts of the body begin to constrict. This is mediated by increase in SANS outflow to the superficial vessels. As a result, the fractional volume of blood exposed for heat conduction reduces and minimal amount of heat is dissipated via the superficial vessels. This cutaneous vasoconstriction causes a decrease in cutaneous blood pressure, blood flow and blood volume; however, the velocity of the blood in these cutaneous vessels increases. All these changes ensure that less heat is dissipated to allow for conservation of heat within the core of the body.

      • Decreased Sweating: Decreased cholinergic sympathetic activity causes the sweat glands to suppress sweat production. Heat is, therefore, prevented from losing through evaporation of sweat.

      • Hair Erection: The contraction of pilorector muscle causes the hair on skin to stand on their ends. These hair trap air which acts as an insulator (air is a poor conductor of heat). Hence, heat loss is minimized.

      The opposite of the aforementioned sequence happens when fever is broken and the pyretic (fever causing) agents are neutralized. The hypothalamic set point is normalized and the body’s temperature is brought back to 37’C through the reversal of events described earlier:

      • Cutaneous Vasodilation: SANS outflow to cutaneous vessels is reduced. This increases the cutaneous blood flow allowing for more heat dissipation from the superficial vessels. . This cutaneous vasodilation causes an increase in cutaneous blood pressure, blood flow and blood volume; however, the velocity of the blood in these cutaneous vessels decreases. All these changes ensure that more heat is dissipated to allow for less conservation of heat within the core of the body.

      • Increased Sweating:  Increased cholinergic sympathetic outflow to sweat glands increases perspiration. This sweat, upon evaporation, has a cooling effect on the body.

      • Hair erection: The pilorector muscles relax and the cutaneous hair are relaxed. The insulating effect of trapped air is reduced. More heat is lost from the body.

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        Categories
        CVS Physiology

        CVS PHYSIOLOGY LECTURE # 12 STUDY NOTES: AUTOREGULATION – MUSCLE BLOOD FLOW

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        The metabolic requirements of a muscle change during exercise compared to when it is at rest.  The blood flow also changes accordingly with the metabolic demands of the muscle. Therefore, the purpose of this lecture is to establish a better understanding of the regulation of blood flow to a muscle, both during rest and exercise. Both of these regulations will be discussed separately:

        Click Here To Watch Video Lecture For This Topic

        BLOOD FLOW TO A RESTING MUSCLE

        The blood flow to a muscle at rest is controlled globally along with the rest of the body through extrinsic regulation. Blood flow is extrinsically regulated through the following auto-regulatory mechanisms:

        • Sympathetic Nervous System [SANS]
        • Para sympathetic Nervous System [PANS]
        • Hormonal Control

        The vascular smooth muscles possess both, alpha-1 (α-1) and beta-2 (β-2)receptors on their surface membrane that are innervated by the SANS. It is worth noting that during sympathetic outflow, the β-2 response is dominant over the α-1 response. This explains why sympathetic stimulation, which occurs in situations of flight and fight, causes the vessels supplying the skeletal muscles to dilate while causing the vessels supplying the visceras to constrict. This allows shunting of maximum amounts of blood towards the skeletal muscles.

        The α-1 receptors are G-q coupled receptors that cause contraction of the vascular smooth muscle upon stimulation. The β-2 receptors are innervated by sympathetic supply as well, but their effect is inhibitory. This is because the β-2 receptors are G-i coupled transmembrane proteins that decrease the intracellular levels of cAMP, thereby causing relaxation of the vascular smooth muscle and vasodilation follows. As mentioned above, the β-2 response is predominant over the α-1 response. However, the response can be shifted towards α-1 if sympathetic overflow occurs. With SANS response, there’s an overflow of epinephrine. At low concentration, epinephrine occupies β-2 receptors and encourages vasodilation of vessels perfusing the skeletal muscle. However, at high concentration, epinephrine occupies α-1 receptors and encourages vasoconstriction of vessels perfusing the skeletal muscle.

        So, at rest the blood flow to skeletal muscles is predominantly regulated by SANS.  This SANS control is predominantly mediated via the β-2 receptors. Since these receptors are G-i coupled, the response generated encourages vasodilation.

        [Note: In the lecture it’s mentioned that β-2 receptor is G-s coupled. However this is not the case. In fact, β-2 receptors are G-i coupled, and there response is inhibitory. Please correct this.]

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        BLOOD FLOW TO AN EXERCISING MUSCLE (ACTIVE STATE)

        During exercise, the control of vascular smooth muscles becomes totally dependent on intrinsic regulatory factors. The extrinsic control becomes unresponsive and is overwhelmed by the intrinsic control. This is justified by the fact that during exercise, the demand for oxygen and the need to remove metabolic waste increases multiple folds. Therefore, the vascular caliber increases in order to increase blood flow and provide for the increase demand. The factors responsible for intrinsic control are actually waste metabolites that also have vasodilatory properties.

        These vasodilator metabolites include the following:

        • H+ ions
        • Lactic acid
        • Carbon dioxide
        • Adenosine
        • Potassium ions.

        These above mentioned metabolites also diminish norepinephrine’s ability to vasoconstrict the arterioles. Moreover, the increased endothelial shear-stress of increased blood flow liberates nitric oxide from the endothelium itself. This NO diffuses into the vascular smooth muscle and activates the cGMP pathway discussed previously (CVS Physiology Lecture#11: Nitric Oxide). This eventually causes vasodilation.

        The skeletal muscles are also responsive to Angiotensin II. Angiotensin II predominantly causes vasoconstriction but it can also cause vasodilation to some extent. The vasodilating effect is carried out to balance out the more potent vasoconstricting effect of Angiotensin II. The vasodilating effect of Angiotensin II involves its binding to the ATII receptors on the endothelium which subsequently releases NO.  This NO then diffuses into the vascular smooth muscle and causes vasodilation to occur.

        Also, during exercise the muscle activity increases. This enables the muscles to act as muscular pumps that increase the blood flow and allows for rapid removal of metabolic waste.

        SUMMARY

        At rest, the blood flow is controlled mainly by increasing or decreasing SANS mediated alpha-1 (α-1) and beta-2 (β-2) adrenergic activity.

        During exercise, the blood flow is taken in control by intrinsic factors that are metabolites with vasodilating properties. The rapidly contracting and relaxing muscles during exercise act as pumps that help increase blood flow.

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        Categories
        CVS Physiology

        CVS PHYSIOLOGY LECTURE # 11 STUDY NOTES: AUTOREGULATION – NITRIC OXIDE

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        Nitric Oxide is called an endothelium derived relaxing factor (EDRF) as it is released by the endothelium of the blood vessel. EDRF cause relaxation of the vascular smooth muscle, and as a result cause vasodilation of the blood vessel. The following factors contribute to the release of nitric oxide from the endothelium:

         

        Click Here To Watch Video Lecture For This Topic

         

        1. Blood travelling at high velocity causes a shearing effect on the wall of the blood vessels. As the endothelial cells endure a drag force produced due to friction. This results in a mechanical trigger which stimulates release of nitric oxide.

        2. Vasoactive Amines are chemical mediators that mediate the release of nitric oxide.

           

        3. The endothelium possesses Histamine H1 receptors that also take part in nitric oxide release.

           

        4. Prostacyclins are also said to be responsible for the release of nitric oxide.

        Mechanism of Action of Nitric Oxide

        Nitric oxide, when released, triggers the soluble guanylate cyclase to convert cGTP to cGMP. The increased levels of cGMP cause activation of cGMP dependent kinases which activate the enzyme Myosin Light Chain Phosphatase (MLCP). The activated MLCP enzyme in turn dephosphorylates myosin light chains which results in relaxation of the contractile apparatus. As a result, the vessels become dilated.

        Atherosclerosis is the formation of fibromuscular plaques on the endothelium lining of the blood vessel. These atherosclerotic plaques render the endothelium non functional. The endothelium is therefore unable to produce sufficient amounts of nitric oxide. Consequently, the levels of cGMP reduce as less cGTP is converted to cGMP. This reduction in cGMP levels in turn leads to increased levels of Myosin Light Chain Kinases (MLCK) which are enzymes with activity opposite to that of MLCP. The contractile apparatus is activated as MLCK causes cross bridging of actins and myosin heads. The tension produced within the vascular smooth muscle as a result of the vascular smooth muscle contraction in turn causes vasoconstriction of the blood vessel.

        Angiotensin II receptors are present on both the vessel endothelium and also the smooth muscle surrounding the blood vessel. Depending on the receptor activated, Angiotensin II can have vasodilating or vasoconstricting effects. At times these opposing effects are balanced out and one effect compensates for the other.   

        • The vasoconstricting activity of Angiotensin II is mediated via two pathways. If Angiotensin II binds to the Gq-coupled receptors on the vascular smooth muscle, it will cause direct deactivation of MLCP enzyme. It also causes the production of IP3 which enables the release of calcium ions from the sarcoplasmic reticulum. The calcium ions activate MLCK. The activation of MLCK and inactivation of MLCP results in contraction of the smooth muscles surrounding the blood vessel. This is the vasoconstricting effect.

        • The vasodilating effect of Angiotensin II occurs simultaneously to mitigate the vasoconstricting effects to some extent. This effect is mediated by binding of the Angiotensin II to its receptor on the vascular endothelium. This activation of endothelial Angiotensin II receptor cause active release of nitric oxide from the endothelium. This NO diffuses into the vascular smooth muscle and stimulates the activity of guanylate cyclase enzyme which converts cGTP to cGMP. The increases cGMP levels cause activation of the MLCP enzyme. The activated MLCP enzyme in turn dephosphorylates myosin light chains, which results in relaxation of the contractile apparatus of the blood vessel. As a result, the vessels become dilated.

        Sildenafil (Viagra) is a drug that is used to treat erectile dysfunction. It is a Phosphodiesterase-5 (PDE-5) inhibitor. PDE-5 is an enzyme that binds to and cleaves cGMP. As a result, the half life of cGMP is reduced as its levels fall. Sildenafil acts by binding to PDE-5 and antagonizes its function. As a result, the cGMP levels remain high for a longer period of time. Therefore, the penile vasculature remains dilated and engorged with blood and, hence, erection is maintained.

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        Categories
        CVS Physiology

        CVS PHYSIOLOGY LECTURE # 10 STUDY NOTES: AUTOREGULATION OF BLOOD FLOW

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        When we talk about autoregulation, it’s not the blood pressure we are talking about but it’s rather the blood flow over a changing pressure which is being regulated. In terms of hemodynamics, the flow across a blood vessel is determined by the pressure gradient across its two ends, assuming that the vessel diameter (resistance) remains unchanged.

         

        Click Here To Watch Video Lecture For This Topic

         

        1. The equation for blood flow across a vessel is as following:

          • Flow = ΔP/ R

          Flow = [P1 – P2]/ R

          Where,

          ΔP = Pressure gradient

          R       = Resistance to blood flow across the vessel

          Blood flow change can occur if any of the following factors change:

          • Blood volume
          • Vessel diameter i.e., the resistance to blood flow changes

          It’s important to understand that any pressure changes of the blood result in flow changes across capillaries supplying blood to the tissues. If the flow changes, there can be derangements in the perfusion of the tissues. One of the major functions of cardiovascular system is to provide optimal perfusion to the tissues. Perfusion ensures optimal delivery of nutrients and oxygen and removal of metabolic waste products from the tissues. So for this reason, if there are any pressure changes then the body will try to regulate the blood flow accordingly in order to maintain optimal perfusion of the systemic tissues. So it’s safe to assume that it is the blood flow which is regulated as part of hemodynamics, not the vascular resistance (arteriolar diameter). In fact, vascular resistance is altered in order to regulate blood flow.

          Autoregulating tissues are those which exhibit local blood flow regulation, thereby maintaining a constant blood flow even if the perfusion pressure changes (MAP). The blood pressure range over which an autoregulating tissue can maintain a constant blood flow is called the autoregulatory range. The autoregulatory range in our body is from a MAP of 70 mm of Hg to 175 mm of Hg. Outside the autoregulatory range (MAP < 70 and MAP > 175), the flow doesn’t remain constant. There is a proportional decrease or increase in flow if the MAP falls below 70 mm Hg or increases above 175 mm Hg, respectively.

          Following is a brief summary of what’s happening to the flow at points A, B & C on the autoregulation graph in drawn in the lecture:

          • Point A: This point falls outside the lower limit of autoregulatory range (MAP < 70). Up till point A, as the MAP increases from 0 to 70 mm Hg, the blood vessel is maximally dilated. The blood vessel is as relaxed as possible and as the blood flow through it increases, there’s a proportional increase in the blood pressure of the vessel.

          • Point B: This point falls within the autoregulatory range. The increased blood pressure resulting from an increased flow results in smooth muscle contraction of the vessel. This reduces the diameter of the blood vessel and the flow is kept constant. The blood vessel continues to constrict until the upper limit of the autoregulatory range is reached

          (MAP = 175).

          • Point C: This point falls outside the upper limit of autoregulatory range (MAP > 175). Outside this range, the vasculature can’t constrict any further so the blood flow can’t be kept constant anymore. Hence, any further increase in the blood pressure will always be accompanied by an increase in blood flow.

          NOTE: THE BLOOD FLOW IS PRIMARILY GOVERNED BY DILATING OR CONSTRICTING THE SMOOTH MUSCLE WITHIN THE WALLS OF THE ARTERIOLES, PROVIDED THAT OTHER FACTORS SUCH AS VISCOSITY OF BLOOD, BLOOD VOLUME AND OTHER PHYSIOLOGICAL FACTORS ARE KEPT CONSTANT.

          There are several types of blood flow regulations:

          1. Long term regulation: This is done by achieved by increasing the size and diameter plus increasing the number of blood vessels. It can take from months to years to achieve such kind of a change. This long term blood flow regulation will later be discussed in a separate lecture.
          2. Acute regulation: This responds to the local needs of a metabolically active tissue. Only those tissues which require greater blood flow owing to their metabolic activity receive a greater blood flow. This ensures that the blood flow to whole of the body is not increased if a particular tissue needs more perfusion. Overall, this makes sure that the workload on the heart doesn’t increase too much. Acute regulation of blood flow is further divided into the following types:
          • Extrinsic regulation involves SANS and PANS input to regulate vascular diameter. Extrinsic regulation will be discussed later in a separate lecture.
          • Intrinsic regulation involves mediators released from the tissue itself which ensure that adequate perfusion to the tissue is maintained. Autoregulating tissues fall under this category of tissues which have their perfusion regulated by the tissue itself, and examples of these are as following:
          • Cerebral circulation
          • Coronary circulation
          • Skeletal muscle vasculature (during exercise)
          • Renal Circulation

          There are two major mechanisms which are used to explain intrinsic regulation (autoregulation). These include the metabolic and myogenic mechanisms. Both these mechanisms cause vasodilation of the blood vessel which leads to an increase in the perfusion of the tissues supplied. Metabolic mechanism is the primary theory which regulates the local vascular diameter of the vessel. The myogenic theory is the subordinate theory to the metabolic theory.

          3.  Vascular system control on the blood flow: It is also involved in the regulation of blood flow to tissues. It falls both under both the intrinsic and the extrinsic categories, so it’s                           discussed separately here. Certain substances such as EDRF (endothelium derived relaxing factor) and Endothelin are released which act on the endothelium itself and subsequently                         regulate  the blood flow to the tissues. EDRF acts to cause vasodilation whereas Endothelin causes vasoconstriction.

        VASCULAR SMOOTH MUSCLE CONTRACTION OR RELAXATION AND THE RESULTANT CHANGE IN BLOOD FLOW

        The blood supply to a tissue brings oxygen and nutrients and removes the carbon dioxide and other waste products away as part of the perfusion. The blood vessel is surrounded by smooth muscle within its wall. Relaxation of vascular smooth muscle causes vasodilation, allowing more blood flow through the blood vessel. On the other hand, the contraction of vascular smooth muscle results in vasoconstriction of the blood vessel which decreases the diameter of the vessel and reduces forward flow. The cascade of events which occur during the vascular smooth muscle contraction are explained below:

        1. On the smooth muscle surface membrane there are T-tubules along which the action potential travels.

        2. Sarcoplasmic reticulum is the site for intracellular calcium, which is released when depolarization of the smooth muscle cell occurs.

        3. Calcium is released from the sarcoplasmic reticulum. This increases the intracellular Calcium levels. In a smooth muscle the interaction of actin and myosin is controlled by a protein called calmodulin (Tropnin-C molecule is not present is smooth muscle). Calcium-calmodulin complex forms when a single molecule of calmodulin binds to 4 calcium ions.

        4. Myosin molecule has a myosin head and a myosin light chain. Myosin light chain has an enzyme called myosin light chain kinase (MLCK). The calcium-calmodulin complex activates the enzyme myosin light chain kinase (MLCK). Calcium-Calmodulin complex is responsible for regulating the cross-bridge cycling in a smooth muscle.

        5. MLCK is activated by increased intracellular calcium levels. Upon activation MLCK phosphorylates the myosin light chain utilizing an ATP molecule. When a phosphate binds to myosin light chain, it activates the myosin head which brings about a conformational change of the myosin head. The myosin head now binds to the exposed myosin binding site on the actin molecule.
        6. After binding to its binding site on actin, the myosin head initiates a power stroke which results in movement of the actin filament. In a smooth muscle this cross-bridging of actin and myosin plus subsequent power stroke together result in an increased tension in the smooth muscle. Increased tension of the vascular smooth muscle results in vasoconstriction of the blood vessel.
        7. There’s another enzyme called myosin light chain phosphatase (MLCP), which has function opposite to that of MLCK. Post the power stroke, MLCP functions to remove the ADP from the myosin molecule. Once the ADP molecule is detached from the myosin head, the myosin head returns to its normal relaxed state. This decreases the tension inside the vascular smooth muscle and there’s vasodilation of the blood vessel.

        NOTE: Activation of MLCK results in the contraction of vascular smooth muscle, and the resultant diameter of the vessel is reduced. In contrast, MLCP activation results in relaxation of the vascular smooth muscle and this subsequently results in vasodilation of the blood vessel.

        [The steps involved in the vascular smooth muscle contraction aren’t correctly explained in the lecture.  The steps explained in the lecture are the ones involved in the skeletal muscle contraction. However, a blood vessel has a smooth muscle component so the steps involved should be those of a smooth muscle excitation-contraction coupling.

        In the lecture it’s mentioned that Tropnin-C is and tropomyosin molecules are covering the binding site of the myosin heads on the actin molecule. However, Troponin C is absent in smooth muscle. Instead, calmodulin molecule is present in the vascular smooth muscle. With smooth muscle depolarization there’s an influx of calcium ions. The calmodulin molecule (like Troponin molecule in skeletal muscle) binds to four calcium ions. This calcium-calmodulin complex is what’s responsible for activating the MLCK enzyme. The subsequent cross-bridging sequence is similar in both smooth and skeletal muscle.

        Also the enzymes MLCK & MLCP are only present in the smooth muscle and not in the skeletal muscle.]

        METABOLIC THEORY OF AUTOREGULATION

        The metabolic theory proposes that the oxygen delivery to a metabolically active tissue is determined by two factors:

        • Presence or absence of oxygen in the tissue.
        • Presence or absence of metabolites in the tissue.

        Oxygen & Metabolic theory: Putting oxygen into the metabolic theory equation suggests that oxygen delivery can be matched to the oxygen consumption of that tissue by varying the diameter of the arterioles, which in turn alters the blood flow. As a tissue performs active metabolism, it utilizes the oxygen delivered to it via the arterioles. As a result the oxygen levels of the local arteriolar blood tend to drop. This means that less oxygen is available for the arteriolar endothelium and smooth muscle. Within the arteriolar smooth muscle, less oxygen is available for the phosphorylating activity of the MLCK. As a result the actin-myosin cross bridging is disrupted and the arteriolar smooth muscle tends to relax. End result of this cascade is that the arterioles undergo vasodilation and there is a relatively reduced resistance to the flow. Consequently tissue perfusion increases secondary to arteriolar vasodilation and increased flow.

        Metabolic Vasodilators & Metabolic theory: Actively metabolizing tissues produce certain vasodilatory metabolites which can regulate the blood flow to the tissue itself. The concentration of these metabolites is directly proportional to the level of metabolic activity performed by that particular tissue. Increased concentration of metabolites results in vasodilatation of the arterioles, which results in decreased resistance to the blood flow. This increased blood flow is in coherence with the increased oxygen demands of the tissue. In contrast, the arterioles constrict if the concentration of these metabolites decrease. Several key vasodilator metabolites are mentioned below:

        • Adenosine: ↑Adenosine → + G-stimulatory protein → + cAMP (cyclic AMP) → – MLCK.

        As the kinase function of the MLCK is inhibited, the vascular smooth muscle relaxes and vasodilation follows.

        • Carbon Dioxide
        • H+ ions
        • K+ ions
        • Lactate
        • Prostaglandins: Also use the G-stimulatory coupled cAMP pathway.
        • Prostacyclins

        These vasodilator metabolites can be produced both due to oxygen demand or oxygen supply mismatch situations.

        • Oxygen demand mismatch: Active metabolism by the tissue cells utilizes the oxygen available to them. There’s a resultant increase in oxygen demand by the tissues, while the supply remains unchanged. This is what happens in a rapidly exercising muscle cell. In order to match the oxygen demand, the flow to the muscle needs to be increased.
        • Oxygen supply mismatch: Alternatively there can be an oxygen supply mismatch. In this case the tissue need remains unchanged but the perfusion to the tissue decreases due to some reason. Following are the situations which can lead to a supply mismatch situation:
        • High Altitude (decreased atmospheric pressure)
        • Carbon Monoxide poisoning (CO has greater affinity for Hemoglobin than Oxygen)
        • Cyanide poisoning (Cyanide inhibits cytochrome c oxidase and renders the electron transport chain non-functional)
        • Mechanical block to blood vessels perfusing the tissue
        • Pneumonia (can cause ventilation perfusion mismatch in the lungs, which decreases the flow available to tissues)

        In another scenario let’s assume that there is a spontaneous increase the perfusion to a tissue. This increase in perfusion can be secondary to an increase in blood volume (transfusion) or stroke volume (inotropic drugs). In the beginning, there will be an increase in blood flow that will deliver more oxygen for metabolic activity and simultaneously “wash out” the vasodilator metabolites. Consequently, there will be a local dilution of vasodilator metabolites around the tissue. Decreased vasodilator metabolites result in arteriolar vasoconstriction and a compensatory decrease in blood flow back to the normal level.

        Metabolic theory also explains the phenomena of active hyperaemia and reactive hyperaemia:

        • Active Hyperaemia explains that blood flow to a metabolically active tissue is directly proportional to its metabolic needs. For example, as a result of strenuous exercise the metabolic demands of the skeletal muscle are greatly increased. As compensation, the blood flow (perfusion) to the skeletal muscles is readily increased in order to meet the metabolic demands of the tissue.  Active hyperaemia can be explained by both the metabolic and the myogenic theories of autoregulation.
        • Reactive Hyperaemia refers to an increase in blood flow to a tissue which received a decreased perfusion due to some reason. The reason for decreased perfusion can be arteriolar occlusion of the arterioles supplying the tissue. Over time, due to decreased blood flow the tissue switches to anaerobic means of respiration which creates an oxygen debt situation within the tissue.  Also due to occluded blood supply, there’s a build up vasodilator metabolites within the tissue which aren’t washed up due to decreased perfusion.  These vasodilator metabolites with time increase in concentration and result in vasodilatation of the arterioles which perfuse the tissue. As the blood supply resolves, the tissue receives a greater than normal perfusion until the oxygen debt situation is resolved.  Reactive hyperaemia is governed by the law of compensation of blood flow.  Reactive hyperaemia can only be explained by the metabolic theory of autoregulation; the myogenic theory cannot be used to explain it.

        MYOGENIC THEORY OF AUTOREGULATION

        Myogenic theory of autoregulation suggests that the vascular smooth muscle itself is also responsible for its own control of contraction and relaxation. An inherent property of the smooth muscle is that that it contracts in response to stretch. Thus, if arterial pressure is suddenly increased, the arterioles are stretched and the vascular smooth muscle in their walls contracts in response to this stretch. The decreased arteriolar resistance ensures that the flow doesn’t increases significantly. 
        If there’s a sudden drop in flow, there’s a reduced stress placed on the arterial walls and therefore the vascular smooth muscle relaxes. The compensatory vasodilation ensures that blood flow to the tissue doesn’t drop significantly.

        There are sodium channels within the vascular smooth muscle cells. These sodium channels are normally closed and are connected to the cytoskeleton of the smooth muscle cell. As the blood flow within the vessel increases, it stretches the blood vessel plus the smooth muscle surrounding the blood vessel. This stretch will also cause the microtubules within the cytoskeleton to stretch. The stretch on microtubules will create a mechanical pull upon the closed sodium channels and cause them to open. Sodium channels will cause an influx of sodium ions into the smooth muscle cells and bring about depolarization. Result of this cascade is that the vascular smooth muscle contracts and decreases the lumen of the vessel. Decreased lumen will decrease the flow back to the normal.

        The concept of reactive hyperaemia is explained above. It’s important to remember that reactive hyperaemia cannot be explained in terms of myogenic theory.

        THE ROLE OF EDRF, NITRIC OXIDE & ENDOTHELIN IN REGULATING LOCAL BLOOD FLOW

        EDRF and Endothelin are chemical substances released by the endothelium which act on the vascular smooth muscle to alter the diameter of vessel. Nitric oxide is one of the most important very important EDRF. Blood travelling at high velocity causes a shearing effect on the wall of the blood vessels as the endothelial cells endure a drag force produced due to friction. This results in a mechanical trigger which stimulates release of nitric oxide.

        Nitric oxide, after its release from the endothelium, diffuses into the vascular smooth muscle. Inside the vascular smooth muscle, the NO triggers the guanylate cyclase to convert cGTP to cGMP. The increased levels of cGMP cause activation of the enzyme Myosin Light Chain Phosphatase (MLCP). The activated MLCP enzyme in turn dephosphorylates myosin light chains, which results in relaxation of the contractile apparatus of the blood vessel. As a result, the vessels become dilated.

        Angiotensin II receptors are present on both the vessel endothelium and also the smooth muscle surrounding the blood vessel. When Angiotensin II acts directly on the its endothelial receptor, it results in release of NO. This NO causes vasodilation by the mechanism explained above. If the Angiotensin II acts directly on its receptor on the vascular smooth muscle, then it’ll cause vasoconstriction of the blood vessel. Angiotensin II receptor on the vascular smooth muscle is Gq coupled, and when bound to this receptor, Angiotensin II can act as a powerful vasoconstrictor.

        Sidenafil is a drug that is used to treat erectile dysfunction. It is a Phosphodiesterase (PDE-5) inhibitor.  Normally, PDE-5 is an enzyme that binds to and cleaves cGMP. As a result, the half life of cGMP is reduced as its levels fall. Sidenafil acts by binding to PDE-5 and antagonises its function (decreasing cGMP levels). With PDE-5 inhibited, the cGMP levels remain high for a longer period of time. The effect of parasympathetic NS and acetylcholine results in release of NO. This Nitric Oxide diffuses inside the vascualr smooth muscle of the arteries which are responsible for penile erectile tissue perfusion. Within the vascular smooth muscle, the NO results in formation of large quantities of cGMP. Inhibited PDE-5 can no longer cleave the cGMP which stays for a longer time. cGMP activates enzyme MLCP which promotes relaxation of the vascular smooth muscle. Therefore, the penile vasculature remains dilated and engorged with blood and the erection is maintained for a longer period.

        Endothelin is released from damaged endothelium. After its release, Endothelin binds to its receptor on the vascular smooth muscle. Endothelin receptor is a Gq coupled receptor, which upon activation inhibits the MLCP enzyme. The inhibition of MLCP enzyme promotes contraction of the vascular smooth muscle and the vessel undergoes vasoconstriction. Hence the vascular diameter is decrease to reduce the blood flow through the damaged vessel. This is important in order to prevent blood loss at the site of damaged endothelium.

        Another important function of EDRF is that these not only increase the local blood flow. EDRF also causes vasodilation of upstream blood vessels for the tissues that need greater perfusion. This makes sure that overall blood flow is directed to those tissues which are in need of greater perfusion due to their metabolic demands.

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        Categories
        CVS Physiology

        CVS PHYSIOLOGY LECTURE # 9 STUDY NOTES: BLOOD PRESSURES

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        This lecture is about various pressures relating to the cardiovascular system and the different factors which affect them.

        STROKE VOLUME (SV):

        Stroke volume is the amount of blood ejected through the left ventricle during one systole. Therefore stroke volume is the difference between the amount of blood in the ventricles prior to ejection (end-diastolic volume) and the amount of blood that remains in the ventricles after the ventricular contraction or systole (end-systolic volume). Normally the stroke volume in a healthy adult is roughly 70mL.

        • Stroke volume (SV) = EDV – ESV

        TOTAL PERIPHERAL RESISTANCE (TPR):

        Total resistance offered by systemic arteries to the blood flow across them is referred to as TPR. TPR is responsible for maintaining the diastolic blood pressure. The major contribution to the TPR is provided by the systemic arterioles.

        By the time the blood reaches the systemic arterioles, its pressure has dropped to 50 mm of Hg in overcoming the vascular resistance encountered up till now. By the time blood flows across the arterioles, the blood pressure further drops to 20 mm of Hg. This means that a 30 mm of Hg of blood pressure is required to overcome the resistance of the systemic arteries in order for the blood to flow across them. The sympathetic and parasympathetic stimulation can decrease or increase the diameter of systemic arterioles and that will affect the resistance offered by these systemic arterioles.

        Hence, it is safe to assume that systemic arterioles are the functional sphincters of the cardiovascular system and the primary contributor to the TPR.

         

        COMPLIANCE

        It refers to the distensibility of the blood vessels when it’s accommodating a blood volume. Elasticity of a blood vessel refers to the recoil of its wall which allows the forward flow of the blood. Both compliance and elasticity come as a result of the elastic fibers within the walls blood vessels (especially arteries). Compliance of a blood vessel reduces with age and some pathological conditions such as atherosclerosis.

        Compliance of a blood vessel is defined as the blood volume which it can hold at a given pressure. Compliance can be calculated by the following equation:

        • Compliance, C = V/P

        V = Volume (mL)

        P = Pressure (mm of Hg)

         

        SYSTOLIC BLOOD PRESSURE (SBP):

        It’s defined as the peak pressure measured in a systemic artery during the cardiac cycle. This peak pressure coincides with ventricular systole phase of the cardiac cycle. In a normal healthy individual the SBP is measured to be 120 mm of Hg.

        Stroke volume is directly proportional to the SBP and it’s also the biggest determinant of the SBP. An increase in the stroke volume causes greater distensibility of systemic arteries and hence greater recoil, thereby resulting in a greater pressure exerted on the walls of systemic arteries.

        Heart rate has an inversely proportional relationship with the SBP. Reduced heart rate results in an increased filling time and hence a greater preload in the left ventricle. Increased preload places an increased stretch on the left ventricular myocardium. This increased myocardial stretch develops a greater force of left ventricular contraction and consequently the stroke volume is increased. Increased stroke volume as explained earlier, causes an increase in SBP.

        Compliance refers to how easily a vessel tends to distend. If the vessel has a low distensibility, then more pressure is required for the blood to enter it and hence the SBP is measured to be high. On the other hand, reduced compliance results in a decreased recoil ability of the vessel. As a result, the vessel wall is unable to squeeze hard on the blood. This reduces the diastolic blood pressure. So a decrease in compliance (as in arteriosclerosis) results in an increased SBP and a decreased DBP.

        DIASTOLIC BLOOD PRESSURE (DBP):

        It’s defined as the lowest pressure measured in a systemic artery during the cardiac cycle. This lowest pressure coincides with ventricular diastole phase of the cardiac cycle. In a normal healthy individual the DBP is measured to be 80 mm of Hg.

        The most important factor which determines the DBP is the total peripheral resistance (TPR). DBP is increased if a greater volume of blood remains in the systemic arteries at the end of diastole. However, it is the TPR which resists flow of blood through a vessel; longer the blood stays within a vessel the more pressure it exerts on the vessel wall. So a decrease in the TPR allows more blood to flow across the vessel and the DBP is low. Since TPR is majorly contributed by the arterioles, it’s better to understand this concept at the arteriolar level. Dilation of the arterioles decreases TPR and DBP also decreases. Constriction of the arterioles increase TPR and as a result the DBP also increases.

        PULSE PRESSURE (PP):

        It’s the difference between the SBP and the DBP. Various conditions may result in widening or narrowing of the PP:

        A decrease in vessel compliance requires a greater SBP to allow for blood flow across the vessel. Decreased compliance also results in reduced recoil of the vessel which reduces the DBP. Overall decreased vessel compliance results in an increased gap between SBP and the DBP, so the PP widens. Such a situation can arise during arteriosclerosis which decreases the overall compliance of systemic arteries.

        A reduced stroke volume causes a decrease in the SBP, however the DBP remains unchanged. This causes narrowing of the gap in between the SBP and DBP, effectively reducing the PP.

        MEAN ARTERIAL PRESSURE (MAP):

        MAP is the average pressure within a blood vessel during one cardiac cycle. It’s not the arithmetic mean because the time spent in diastole and systole isn’t equal, so MAP averaged out over the time spent during each phase. One third of the time of a single cardiac cycle is spent in systole, while two thirds of the cardiac cycle is spent in diastole. MAP is used instead of SBP to determine whether there’s enough nourishing pressure to allow perfusion across the tissues. Normally if the MAP is less than 60% of the SBP, then the nourishment of the systemic tissues is compromised. MAP can be determined by the following equation:

        • MAP = (CO x TPR) + CVP {CVP=0, so it can be ignored}

        So, MAP = (CO x TPR)

        In physiological conditions, the MAP needs to be maintained. Therefore, if there’s an increase in the cardiac output, then the TPR needs to be reduced to ensure the MAP doesn’t change. In contrast if the TPR increases the cardiac output needs to be reduced to maintain the MAP.

        If the SBP and the DBP are known then the MAP can be determined by the following formulae:

        • MAP = DBP + 1/3 (SBP – DBP) {For a normal healthy adult, DBP = 120 & SBP = 80}

        So, MAP = 80 + 1/3 (120 – 80)

        MAP = 80 + 1/3 (40)

        MAP = 80 + 13.33

        MAP = 93 mm of Hg (After rounding off)

        Alternatively MAP can also be calculated by the following formula:

        • MAP= 2/3 DBP + 1/3 SBP

        MAP= (2/3 x 80) + (1/3 x 120)

        MAP= 53.33 + 40 = 93 mm of Hg

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        CVS Physiology

        CVS PHYSIOLGY LECTURE # 8 STUDY NOTES: HEMODYNAMICS – REYNOLDS NUMBER

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        Definition

        Reynolds Number is used to predict the type of blood flow in a blood vessel. There are two types of blood flow:

        Click Here To Watch Video Lecture For This Topic

         

        • Laminar Flow: The laminar flow is described as the flow of fluid which is travelling in a calm, layered fashion. The layer of fluid flowing in the center most region of the blood vessel is said to have the highest velocity. Moving peripherally, the velocity of the layers decrease and the outer most layer, which is running along the vessel wall, is said to be travelling with the lowest velocity. This is due to friction which results in a backward drag produced by the wall on the layer adjacent to it. It is important for a blood vessel to exhibit laminar flow in order to maintain its physical integrity and carry out various cardiovascular functions. Laminar flow allows margination to occur efficiently among other functions. Margination is the process of adherence of blood cells to the vessel wall and their subsequent exit through the wall of the blood vessel to areas of need. This process gets largely disrupted if blood flow is not laminar.

        • Turbulent Flow:Blood flowing viciously and in a haphazard fashion produces turbulence within a blood vessel. The aorta normally contains blood with turbulent flow. This type of blood flow results in the production of Eddy currents within a blood vessel. These currents cause the blood to hit against the vessel wall with considerable amount of force. Repeated impaction of high pressure, turbulent blood on the vessel wall damages the elastic fibers within the tunica media. As a consequence, the elastic fibers break into smaller fragments, rendering the fibers non functional.

        A small Reynolds number signifies that the blood is flowing in a smooth and laminar fashion. If the Reynolds number is high, the blood flowing through the blood vessel would be turbulent.

        Murmurs and bruits point to the presence of turbulence in blood flow. These can be appreciated upon auscultation at the relevant areas. Murmurs are sounds of blood splattering on the rest of the blood due to turbulence. These disturbances result in vibrations that resonate through the walls of blood vessels or the heart itself. These are picked up as distinct sounds upon auscultation.

         

        • Reynolds Number=density x velocity x diameterviscosity

        The formula says that the value of Reynolds number is directly proportional to density of the blood, the blood’s velocity and the diameter of the blood vessel. Increasing the magnitude of any of these parameters will result in an increase in Reynolds number, and add turbulence to the blood flow. Therefore, the aorta having the largest diameter compared to the rest of blood vessels, and the highest rate of blood flow, will give a large Reynolds number. Hence, the flow is turbulent.

        The viscosity of blood has an inverse relationship with the Reynolds number. Increased viscosity of a fluid results in its flow becoming more laminar. Increased viscosity will also decrease the velocity of the blood flow. Similarly, decreasing the viscosity of the fluid will result in more viscous and turbulent flow. In terms of hemodynamics of the blood flow, changing the heamtaocrit value results in a change in the viscosity of blood. Anemia causes a decrease in the viscosity of blood and hence is attributable to generation of Eddy currents due to high turbulent blood flow.

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        CVS Physiology

        PHYSIOLGY LECTURE # 7 STUDY NOTES: HEMODYNAMICS – VASCULAR RESISTANCE

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        Resistance can be integrated into two types of circuits; parallel and serial circuit.

        Series Circuit 

        The heart is placed in series with the pulmonary vasculature and as well as the rest of the body. It pumps blood to the lungs, from where the blood travels back to the left side of the heart. The left heart pumps blood to the rest of the body after which the blood is returned back to the right heart. Therefore, the pulmonary and systemic circuits are connected in series via two pumps, which are the right heart and left heart respectively.

        Click Here To Watch Video Lecture For This Topic

         

        Calculating Resistance in Series

        The total resistance in series is calculated by taking the sum of all the resistances present in the circuit.

        Total Resistance = R1 + R2 +R3 … Rn

        It should be noted that if resistance is added in a series circuit, the pressure of blood proximal to the new resistance will increase and the pressure downstream will decrease. The flow remains the same.

        Parallel Circuit

        Various arteries branch off from the aorta in order to deliver blood to various organ systems of the body. These arterial branches are an example of parallel circuitry. The different organ systems and their visceras (CNS, GIT, Skeletal, and Renal etc.) are connected in a parallel fashion with respect to each other. Therefore, when blood is transported to these organ systems via the aorta, the total resistance offered will be the same as that offered by a parallel circuit.

        Calculating Resistance in Parallel

        The total resistance in a parallel circuit is calculated by adding the reciprocals of each resistor.

        (1/TR) = (1/R1) + (1/R2) + (1/R3) … (1/Rn)

        As blood flows past a resistor in parallel circuit, a fraction of the blood enters the branch of blood vessel delivering blood to the resistor. Increasing the number of branches will allow blood to get distributed even more among the branches. The volume, and hence the pressure, decreases as a result. Therefore, the total resistance decreases as we add more branches to a circuit. It can be further deduced that the total resistance in a parallel circuit is always less than the value of the smallest resistor in that circuit.

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        CVS Physiology

        PHYSIOLGY LECTURE # 6 STUDY NOTES: HEMODYNAMICS – VASCULAR COMPLIANCE

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        Capacitance is defined as the distensibilty of a blood vessel. In other words, capacitance is the ability of an object to get stretched. In contrast, elasticity is defined as the object’s ability to recoil or return to its previous shape after being stretched. Elastance is produced by elastin fibers present in the vascular wall. Take for example the aorta; it has the most layers (around 50 layers) of elastin fibers in its tunica media which makes it the most elastic blood vessel in the body. If the aorta is compressed or stretched, it will recoil back to its normal shape.

         

        Click Here To Watch Video Lecture For This Topic

         

        Compliance of a vessel is the opposite of its elastance. The veins are said to be compliant because if you keep increasing the volume of blood in the veins, their walls will distend allowing for more blood to be accommodated.

        Arteries and veins possess relative percentage of both, elasticity and compliance. However, arteries are said to be relatively more elastic and less compliant owing to the fact that they have more elastic fibers. This explains why the aorta resists distension when blood at high pressure is pumped into it by the heart. The increase in pressure causes a small stretch in the wall (due to compliance) of aorta which is immediately diffused as the aorta recoils back (due to elasticity) to its original shape. Greater the amount of elastic tissue in a vessel wall, the higher is the elastance, and the lower is the compliance of the blood vessel. As the person’s age increases, the arteries become stiffer and further lose their compliance. Pathological conditions such as atherosclerosis also further decreases the arterial compliance.

        The opposite is true for the veins. The walls of the veins, being very compliant, will keep on stretching as more blood is added to the veins. There will be a small degree of recoil as well but the resultant force is not as strong as that in the arteries.
        Formulae:

        • Compliance = Volume (ml)/ Pressure (mm Hg)

        As seen in the formula, compliance can be written as a ratio of volume and pressure. This shows that more compliant vessels will allow more volume of blood to be added without causing any changes in pressure. On the other hand, the arteries try to resist changes in volume by generating more pressure as they are less compliant. This is the reason why the volume of blood in arteries is called stressed volume whereas the volume in veins is called unstressed volume. . Systemic veins are 20 times more compliant relative to systemic arteries. Due to this, the veins easily distend in response to high volumes of blood. Because of their ability to capacitate, the veins accommodate roughly 70% of the systemic blood volume. For this reason the systemic veins are a major blood reservoir of the body.

        The table below contrasts the different properties of arteries and veins and the effect they have on hemodynamics. The result are further explained below:

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        Arteries

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        Veins

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        Compliance (Distensibility)

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        +

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        Elastance (Recoil ability)

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        Stress

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        Volume

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        +++++

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        Pressure

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        • Compliance: Arteries are less compliant and veins are more compliant.
        • Elastance: The arteries are more elastic. This property makes up the basis for “windcastle effect” in the aorta. The aorta distends in response to the high pressure blood pumped by the heart and recoils back thereby maintaining the pressure between 120/80 mm Hg. The elastance of veins is low.
        • Stress: The arteries face stress as the blood running in them is at high pressure. The stress on the walls of the veins is negligible.
        • Volume: The arteries are not capable of housing large volumes of blood. The veins have more capacity as they are more distensible and compliant in the face of volume changes.
        • Pressure: The pressure in the arteries is greater than that in the veins. Arterial wall recoils due to presence of elastic fibers, and this recoil is responsible for the arterial pressure. Veins on the other hand don’t have that much of an elastic component and therefore lack recoil ability and consequently the blood pressure is relatively low in the veins.
        • Flow: The flow is equal in both, the arteries and the veins, as the blood is flowing in a closed circuit. As the blood moves in a closed circuit, the flow is equal at all points.

        COMPLIANCE GRAPHS FOR VOLUME VS PRESSURE

        X-axis = Volume (mL)

        Y-axis = Pressure (mm Hg)

        The graphs in the lecture compare the compliance of aorta with that of systemic veins. For understanding purpose, compliance can be referred to as the pressure change in the blood vessel when unit volume of blood is added to the vessel (aorta or the veins). The compliance of each vessel can be calculated as the gradient of the graph at any point.

        Compliance = ΔV/ΔP

        For Aorta, when unit volume of blood is added to it, there’s a significant rise in its pressure.  The gradient of the volume vs. pressure curve is relatively less steep. This suggests that the aorta has a low compliance. Increase in pressure can also be explained by the greater recoil (elastance) of the aorta.

        For veins, when blood is added to them, there’s no significant change in pressure. The gradient of the volume vs. pressure is very steep, which suggests that their compliance is very high.  The veins can hold greater volume of blood without any increase in their pressure because they are very distensible. However, as we continue to add blood, there comes a point when the curve starts to flatten out and the vein cannot accommodate any more blood. The compliance at this point is zero.

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        CVS Physiology

        PHYSIOLGY LECTURE # 5 STUDY NOTES: HEMODYNAMICS – POISUILLES EQUATION

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        The Poisuilles Equation takes into account factors such as blood viscosity, length and cross sectional area of a blood vessel and uses it to determine the resistance to the flow of blood.

        R=8 n Lπr^4  (Assuming that the flow is laminar and the volume is constant)

        • Where: n: Viscosity of the blood

                      L: Length of the blood vessel

                      r: Radius of the blood vessel

        Click Here To Watch Video Lecture For This Topic

         

        FACTORS CONTRIBUTING TO THE POISUILLES EQUATION

        Blood viscosity

        has a direct relation with resistance, according to the Poisuilles equation. This means that increasing the viscosity of blood will result in an increase in resistance. Blood viscosity undergoes changes with alterations in the hematocrit. Hematocrit is the percentage of total number of particulate matter (RBCs, WBCs, proteins etc) in a given volume of blood. Under normal conditions, the value of hematocrit is 45%. Changes in the hematocrit can occur with both, physiological and pathological conditions. Dehydration causes decrease in the volume of blood which results in a relative physiological increase in hematocrit. Similarly, secondary polycythemia also causes physiological increase in the value of hematocrit as a result of increased production of red blood cells by the bone marrow. Pathological increase in the hematocrit is primarily seen in malignancy of the bone marrow in which large numbers of undifferentiated cells are produced leading to an increase in the cell number. Multiple Myeloma is the neoplastic proliferation of plasma cells which produce excess immunoglobulins. This results in an increased protein content of the blood and a resultant increase in hematocrit.

        On the other hand, anemia will cause a decrease in hematocrit and hence, a decrease in viscosity of blood. As mentioned earlier, a decrease in blood viscosity will result in a decrease in resistance to the flow of blood. Flow rate increases when there’s a decrease in resistance offered to blood flow. Increase in the flow rate can be problematic because it generates Eddy currents within the blood vessels. These Eddy currents cause pressure damage to the blood vessel and cause the blood flow to become turbulent. Turbulent blood flow within the heart results in murmurs. Turbulent blood flow within the blood vessels results in bruit. Most common sites of bruit are carotid artery and the aorta. Both murmur and bruit can be appreciated upon auscultation at the relevant sites.

        The resistance to blood flow within the blood vessel is inversely proportional to the radius of the blood vessel raised to the fourth power. If the cross sectional area of the cylindrical blood vessel is decreased, there’s a resultant increase in resistance to blood flow in that vessel. So that basically means, if we take the radius and simply divide it by two (decreasing the radius of the vessel to half), the resistance would increase by a factor of 16. This would result in a considerable decrease in the flow rate of the blood. Application of this concept is seen in pathological cases, such as the narrowing of blood vessels in atherosclerosis and arteriosclerosis, resulting in increased resistance and reduced blood flow. The diameter of blood vessels in our body is physiologically controlled by our body’s autonomic nervous system (ANS). Arterioles are the vessels in which the autonomic effects are seen most prominently. For this reason they are also known as the resistance vessels or the functional sphincters of the cardiovascular system. The smooth muscles surrounding the arterioles contract or relax under the effect of the autonomic nervous system. When stimulated by the sympathetic nervous system (SANS), the alpha 1 receptors on the arteriolar smooth muscle get activated. These receptors are coupled intracellularly with Gq proteins which get activated and increase intracellular levels of second messengers, namely IP3 and DAG. The second messengers cause movement of calcium ions into the sarcoplasmic reticulum resulting in contraction of the smooth muscles. The same sympathetic innervation when stimulates the Beta 2 adrenergic receptors on the arteriolar smooth muscle of arterioles perfusing skeletal muscles, a Gi coupled response is initiated. This will cause a decrease in cAMP levels in smooth muscle cells of the arterioles. As a consequence, the smooth muscle will relax and the arteriole will dilate allowing more blood to perfuse the skeletal muscles. The distribution of extracellular receptors (beta 2, alpha 1, etc) on vascular smooth muscles depends on the demand for blood by different organs according to the situation. For example, during a fight and flight response, the blood vessels of the skeletal smooth muscles (innervated by beta 2 receptors) will dilate to provide more blood to the muscles. At the same time, the vascular smooth muscles of arterioles perfusing the visceras (GIT, Kidneys, etc) will contract, and the lumen will constrict in order for the blood to redirect to parts where it is needed more.

        USE OF POISUILLES EQUATION IN THE FLOW EQUATION

        The value of the resistance, calculated using the POISUILLES EQUATION, can be plugged into the flow equation (given below) to determine the flow rate:

        • Flow = ΔP/R,

        ΔP = MAP – Right Atrial Pressure

        Therefore,

        Flow = (MAP – RAP) /Resistance

        ΔP: change in Pressure

        R: Resistance

        MAP: Mean Arterial Pressure

        So, according to the equation, increase in resistance will cause a decrease in the flow of blood through a vessel. The resistance of a blood vessel is increased in conditions such as atherosclerosis and vasospasm due to increased sympathetic activity. Similarly, if the resistance is decreased, the flow of blood through a vessel will increase.

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        CVS Physiology

        PHYSIOLGY LECTURE # 4 STUDY NOTES: HEMODYNAMICS – BLOOD FLOW

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        Basic Metric system:

        1m = 39.37 inches

        1ml = 1 cubic centimetre (cm^3)

        A cubic centimetre is diagrammed as a small cube which has all its lengths equal to 1 centimetre.

         

        Click Here To Watch Video Lecture For This Topic

         

        Cross-Sectional Area

        The cardiovascular system is seen as a network of cylindrical tubes. If a cylinder is cut at normal (right angle) and the cross section viewed, it will appear as a circle. The area of a circle is calculated by the formula, (A=πr2). The radius of the circle is determined by measuring the length from the centre of circle to any point along its circumference. The unit for the cross sectional area is cm^2.

        Velocity vs. Flow

        Velocity is defined as the distance covered in unit time (cm/s). For simplicity, velocity is defined as the speed of movement of a particle. Velocity of a particle in a fluid is independent of the total volume of the fluid itself. The velocity of the blood is equal to the distance it covers in unit time, irrespective of the volume moved.

        Flow however is dependant of the fluid volume. Flow refers to the volume of fluid that passes through a cross sectional area in unit time. With respect to hemodynamics, flow is measured as the volume of blood that passes through a particular area in unit time (ml/min).

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        Formulae:

        • Velocity (cm/s) = Flow/Cross Sectional Area

                     = Q/A (Unit: [ml/m]/cm^2)

        Assumptions: For the purpose of this lecture, the flow of blood in an average, healthy adult is assumed as 5L/min, which is also the cardiac output.

        After being pumped from the heart, the blood first flows into the aorta and then into the major arteries. From there, the blood enters arterioles of the respective functional organ systems. The arterioles divide into small capillaries which anastomose with capillaries of the venules within the organ system. The venules empty into veins and the veins after collecting blood from all parts of the body, empty into the Superior and Inferior Vena Cava which deliver the blood back to the heart, completing the circuit. Together these components of the systemic vasculature form a closed circuit.

        Therefore, the cross sectional area of the vessels changes as the blood flows through the body with subsequent changes in the velocity as well. According to the formula devised earlier, the velocity of blood is inversely proportional to the diameter of the blood vessel, given that the flow rate remains constant. For example, the aorta has the smallest diameter and a cross sectional area of 2.5cm^2. In a healthy individual, the velocity of blood in the aorta can be calculated by dividing the flow rate (approximated earlier as 5000ml) by the cross sectional area (2.5cm^2) of the vessel. This would give a value for the velocity of blood flowing through the aorta as 20 meters/min. The calculation for the velocity of blood flowing through the aorta is summarized below:

        • Cross-sectional area of Aorta = 2.5cm^2

                             A=πr2= 2.5cm^2

                          Diameter of Aorta = 1.78cm

        • Velocity of the blood flow through Aorta:

        V (cm/s) =Q (ml/min)A (cm^2)

        5000(ml/min)]2.5(cm^2)  {ml and cm^3 can be substituted interchangeably}

        5000 (cm^3/min)2.5 (cm^2)

        = 2000 cm/min

        = 20 m/min

        = 33 cm/s

        Before moving on, it should be noted that the diameter, and hence the cross sectional area, of the branching arteries is taken as the sum of all the arteries at that level and not of a single artery individually.  The capillaries, as a result, have a collective cross sectional area of 3000cm^2, a value which is 1000 folds greater than the cross sectional area of the aorta. Hence, the velocity of the blood drops considerably (1.6cm/min) as it reaches the capillaries. The calculation for the velocity of blood flowing through the capillaries is summarized below:

        • Total Cross-sectional area of Capillaries = 3000cm^2
        • Velocity of the blood flow through the Capillaries:

        V (cm/s) =Q (ml/min)A (cm^2)

        5000(ml/min)]3000(cm^2)  {ml and cm^3 can be substituted interchangeably}

        5000 (cm^3/min)3000 (cm^2)

        = 1.6 cm/min

        = 0.016 m/min

        = 0.027 cm/s

        The significance of these large differences in velocities is immense. The aorta is functionally a conducting vessel; therefore it contains blood travelling at a relatively high velocity so that the blood can reach the desired target organs efficiently. In contrast, the velocity of the blood drops significantly (1.6cm/min) as it reaches the capillaries. Therefore, the capillaries contain the blood with minimal velocity which allows for efficient exchange of gases and transport of nutrients and waste products across them.

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        Categories
        CVS Physiology

        PHYSIOLGY LECTURE # 3 STUDY NOTES: HEMODYNAMICS – BLOOD FLOW VELOCITY

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        The assumptions made in this lecture to understand the velocity of blood flow are as follows:

         

        Click Here To Watch Video Lecture For This Topic

         

        • 1 meter = 39.37 inches
        • 1 millilitre = 1 cubic centimetre
        • A cubic centimetre is diagrammed as a small cube which has all its lengths equal to 1 centimetre. Cardiac Output at rest: 5000mL

        Let’s assume that the blood vessels are like cylinders and their cross section appear to be circular. Hence, the cross sectional area of a blood vessel is equal to the area of the circle. This can be calculated by the formula A=πr^2.

        Velocity vs. Flow

        Velocity is defined as the speed of blood in unit time.

        Flow is the amount of blood moving per unit time.

        Velocity and Flow can be integrated in the same equation as per the following formula:

        V (cm/s) =Q (ml/m)]A (cm^2)

        Where:  V = velocity

                      Q = Flow

                      A = Cross sectional area of the vessel.

        This shows that the velocity is inversely proportional to the cross sectional area and directly proportional to the flow of blood in the vessel. This principle is analogous to water pouring out of a water hose. Squeezing the outlet of the hose and making it narrower (decreasing the cross-sectional area) will cause the water to eject with higher than normal speed.

        The cross sectional area, of any part of the vasculature is taken as the sum of all the vessels at that level and not of a single vessel individually. Hence, the aorta which is a single vessel, has the smallest cross sectional area of 2.5cm^2. On the other hand, the sum of cross-sectional areas of all the capillaries is calculated to be 3000cm^2.

        The calibre of the blood vessels changes as the aorta divides into arteries, arterioles and capillaries during the process of transporting blood to the tissues. The change in vessel calibre is met with a subsequent change in the blood velocity. The aorta, with a cross sectional area of 2.5cm^2 , has blood travelling at a velocity of 20m/min. By the time the blood reaches the capillaries, the velocity of blood drops to 1.6cm/min. This is because the cross sectional area of all the capillaries when summated becomes equal to 3000cm^2, a value which is 1000 folds greater than the cross sectional area of aorta. Following calculations can be used to calculate velocity of blood flowing through the aorta and the capillaries respectively:

        Velocity of the blood flow through Aorta:

        • V (cm/s) =Q (ml/min)A (cm^2)

        5000(ml/min)]2.5(cm^2)  {ml and cm^3 can be substituted interchangeably}

        5000 (cm^3/min)2.5 (cm^2)

        = 2000 cm/min

        = 20 m/min

        = 33 cm/s

        Velocity of the blood flow through the Capillaries:

        • V (cm/s) =Q (ml/min)A (cm^2)

        5000(ml/min)]3000(cm^2)  {ml and cm^3 can be substituted interchangeably}

        5000 (cm^3/min)3000 (cm^2)

        = 1.6 cm/min

        = 0.016 m/min

        = 0.027 cm/s

        To summarize, the aorta acts as a conducting vessel as it conducts blood at high velocity to the rest of the body. The capillaries on the other hand, need to contain the blood with minimal velocity which allows for efficient exchange of gases and transport of nutrients and waste products.

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        Categories
        CVS Physiology

        PHYSIOLOGY LECTURE # 2 STUDY NOTES: PROPERTIES OF PULMONARY VASCULATURE

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        The heart pumps a volume of blood into the lungs which after getting oxygenated is transported back to heart. This oxygenated blood is then pumped out of the heart and into the aorta and subsequently into the systemic circulation. As a consequence, at any given time the lungs (pulmonary vasculature) contain around 500ml of blood, thereby allowing them to function as a reservoir of the blood. This reservoir volume is increased by 500 ml when the person is in the supine or lying down position. This is because in supine position there’s an increased venous return (due to the effect of gravity) to the right heart from the peripheries and therefore more blood accumulates in the central parts of body. Upon standing up, this extra 500ml of blood gets redistributed under the effect of gravity, to the now more dependent parts of the body which includes the peripheral tissues and the lower extremities.

         

        Click Here To Watch Video Lecture For This Topic

         

        The division of vasculature in the pulmonary circuit is somewhat different from that in the systemic circulation. The arteries in the pulmonary circuit divide in a binary fashion, thereby following the pattern of division of the airways. The veins too exhibit a pattern similar to the arterioles and the bronchioles, thereby finally converging into forming one large pulmonary vein. These pulmonary veins transport the oxygenated blood back to the heart.

        Apart from the primary function of lungs to deliver oxygenated blood to the heart, it has several secondary functions as well:

         

        Filtration: Pulmonary vascular bed acts as a filter for the blood received by the right side of the heart and before this blood leaves the left side of the heart to enter the systemic circulation. Blood arriving from the right side of the heart to the lungs may contain an embolus or a thrombus or any foreign particle that may result in obstruction of the vessels. The pulmonary artery divides into numerous small capillaries with diameters too small to allow passage of any dislodged particles into the pulmonary artery and subsequently in to the left side of the heart. Therefore, the pulmonary vascular bed acts as a filtration barrier that prevents introduction of any particles into the systemic circulation.

         

        Metabolic Functions: The pulmonary vasculature also has some metabolic functions:

        1. The endothelium of the pulmonary vessels is lined by fibrinolytic enzymes that cause lysis of the fibrin clots which get stuck in the pulmonary vasculature.

           

        2. The pulmonary capillary endothelium is lined by another enzyme as well. This enzyme is called the Angiotensin Converting Enzyme (ACE). ACE functions to covert Angiotensin Ito Angiotensin II. ACE is also present in the endothelium of other vascular beds and the plasma, however, the amount present in the pulmonary vascular bed is the highest.  ACE within the pulmonary vascular bed is responsible for more than 70% of the total conversion of Angiotensin I to Angiotensin II in the body.

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        Categories
        CVS Physiology

        PHYSIOLOGY LECTURE # 1 STUDY NOTES: GENERAL PRINCIPLES OF CARDIOVASCULAR PHYSIOLOGY

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        ORGANIZATION OF THE CVS

         

        HEART AS 2 PUMPS: The human heart has 4 chambers which are the two atria and the two ventricles. These 4 chambers are divided into 2 functional units referred to as the left heart and the right heart. These atria and ventricle in a single functional unit are separated by the atrioventricular valves. These AV valves are one way valves and allow blood flow in the forward direction only.

        Click Here To Watch Video Lecture For This Topic

        Right heart is formed by the right atrium and the right ventricle, and it forms one functional unit. The right atrium receives the venous deoxygenated blood from three sources, namely:

        1. Superior vena cava: brings deoxygenated blood from the head, neck and upper limb region
        2. Inferior vena cava: brings deoxygenated blood from the lower extremities, the abdominal region and the rest of the body except the heart itself.
        3. Coronary sinus: brings deoxygenated blood from the veins of the heart itself.

        During diastole when the atria contract, this deoxygenated blood is pumped into the right ventricle. During systole, the right ventricle pumps this deoxygenated blood out of the heart and into the pulmonary circuit via the pulmonary artery*. The right heart plus the pulmonary arteries, capillaries and veins together form the pulmonary circulation. The right side of the heart deals with deoxygenated blood only and it functions to send this deoxygenated blood to the pulmonary circulation to get oxygenated.

        Left heart forms another functional unit and consists of the left atrium and left ventricle. The left atrium receives oxygenated blood from the pulmonary circuit via the 4 pulmonary veins*(two from each lung). When the atria contract, the left atrium pumps this oxygenated blood into the left ventricle. During systole, this oxygenated blood is pumped out of the heart via aorta, when the left ventricle contracts. The aorta then carries this oxygenated blood into the systemic circulation. The left heart plus the systemic arteries (starting at the aorta), capillaries and veins together form the systemic circulation. For simplicity, it can be assumed that the left heart deals with the oxygenated blood and sends it to the systemic circulation via the aorta.

        NOTE: Arteries conduct blood away from the heart towards the tissues. Arteries normally carry oxygenated blood away from the heart, but an exception to this rule are the pulmonary arteries and the umbilical arteries(during fetal life only) which carry deoxygenated blood away from the heart and toward the lungs & placenta respectively. Veins normally carry deoxygenated blood, except the pulmonary veins in adults and the umbilical vein (during fetal life only) which bring back oxygenated blood to the heart from the lungs and the placenta respectively.

        SYSTEMIC TISSUES:

        As part of the systemic perfusion, the oxygenated blood in the aorta is eventually transported to the following 6 major systemic tissues. These systemic tissues receive blood via a parallel system of arteries which originate at various levels from the aorta itself.

        1. Cerebral: The CNS plus the head & neck region. 15% of the cardiac output enters the cerebral arteries.
        2. Coronary: The myocardium itself which receives oxygenated blood during diastole in contrast to the rest of the body which receives oxygenated blood as part of systole. 5% of the total cardiac output is designated for the myocardial perfusion via the kidneys.
        3. Splanchnic: The gastrointestinal system and its accessory organs such as the liver, spleen, pancreas and the biliary system. 25% of the total cardiac output reaches the GIT system via the splanchnic arteries.
        4. Renal: The kidneys and the genitourinary system. Kidneys, as part of the renal system, receive 25% of the total cardiac output.
        5. Skeletal: Roughly 25% of the total cardiac output is reaches the skeletal system. Exercise increases the percentage of cardiac output which is made available for the skeletal system. Bones and the musculature of the body form part of this system.
        6. Cutaneous: The skin and its associated structures (sebaceous glands, hair follicles). Around 5% of the total cardiac output reaches the cutaneous circulation.

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        BLOOD FLOW DIRECTION & THE CHEMICAL COMPOSITION OF THE VENOUS & ARTERIAL BLOOD:

        There are 4 pulmonary veins which bring back oxygenated blood from the lungs to left atrium. This blood is rich in oxygen (PaO2=100 mm Hg) and low in carbon dioxide (PaCO2=40 mm Hg). The mitral valve which forms the left atrioventricular valve, allows passage of blood from the left atrium into the left ventricle during the diastole phase. When the left ventricle begins to contract and its pressure rises more than the left atrial pressure, the mitral valve closes to prevent backflow of the blood. This ensures anterograde flow of blood in to the aorta i.e., the forward direction of blood flow. Backflow from the aorta back into the left atrium is prevented by the semilunar aortic valve. It’s important to remember that all the valves of the heart are tricuspid i.e., having three cusps, except the mitral valve which is bicuspid i.e., having two cusps. However, only the right atrioventricular valve is referred to as the tricuspid valve.

        From the aorta, the blood is transported to the systemic tissues which are mentioned above. The aorta divides into large and medium sized arteries, which eventually give arise the arterioles. The arterioles continue to form capillaries, and these capillaries merge together to form venules at their venous ends. The venules eventually end up forming the veins. The veins are low pressure vessels which return the deoxygenated blood back to the right heart via the three above mentioned sources of venous return to the heart. This deoxygenated blood is low in oxygen (40 mm Hg) and rich in carbon dioxide (47 mm Hg). The right atrioventricular valve, which is also referred to as the tricuspid valve, allows this deoxygenated blood to flow from the right atrium into the right ventricle. During ventricular systole when the left ventricle contracts, this deoxygenated blood is pumped out of the right side of the heart via the pulmonary artery. The backflow of this deoxygenated blood into the right side of the heart during ventricular diastole is prevented by the semilunar pulmonary valve. This deoxygenated blood reaches the lungs and enters the pulmonary circuit to get deoxygenated. At this point the blood completes its route both around the pulmonary and systemic circuits.  

        SERIES & PARALLEL CIRCUITS

        The right and left sides of the heart are connected in a series circuit to both the pulmonary and systemic tissues respectively. By series circuit, what’s meant here is that quantitatively, the blood flow through the lungs is equal to the blood flow through the rest of the body. For simplicity in understanding, it should be considered that the lungs are connected to the rest of the body in a series circuit. During a single cardiac cycle, the right and left ventricular outputs are the same.

        However, the blood supply of the systemic tissues is connected in a parallel circuit. This means that each organ system is supplied by an artery which originates as a branch of the aorta. This ensures that the blood which reaches a particular organ system is perfused at the same partial pressure of oxygen, as that of the site at which the branch originated from the aorta. If the organ systems were connected and perfused via a series circuit, by the time the blood reached the last organ system, it would have been completely depleted of oxygen and nutrients. The sum of blood flow to these individual systems adds up to the total left ventricular output (the cardiac output).

        VARIOUS PRESSURES IN THE CVS

        • SYSTOLIC BLOOD PRESSURE (SBP): Systole is time interval when the ventricles are contracting. Systolic BP therefore is the pressure in the systemic arteries when the left ventricle is contracting. Therefore, SBP is the highest blood pressure in the systemic arteries during a cardiac cycle.

        Average SBP in healthy adults is 120 mm of Hg.

        • DIASTOLIC BLOOD PRESSURE (DBP): Diastole is the time interval when the ventricles are relaxing and therefore receiving blood from the atria. Diastolic BP is the pressure in the systemic arteries when the left ventricle is relaxing.  DBP therefore is the lowest pressure in systemic arteries during a cardiac cycle. Average DBP in healthy adults is 80 mm of Hg.

        • PULSE PRESSURE (PP): This is the difference between the systolic blood pressure and the diastolic blood pressure in the systemic arteries at any given time. Pulse pressure can therefore be calculated as following:

           

        • Pulse pressure, PP = Difference between the systolic & diastolic blood pressures.

                      PP= SBP- DBP

                      PP = 120-80= 40 mm of Hg

        • MEAN ARTERIAL PRESSURE: MAP is the average arterial pressure of the systemic arteries. However, quantitatively it’s not an arithmetic mean of the SBP & DBP. Since the ventricular muscle spends 2/3 of the time of a cardiac cycle in diastole, the MAP is closer to the DBP, than it’s to the SBP.

        MAP signifies the perfusion pressure of the tissues. If the MAP of the patient decreases below 60 mm of Hg, then it should be a cause of concern for the doctor. What this signifies is that a perfusion pressure below 60 mm of Hg would not be able to meet the nutritional needs of the systemic tissues. So, the MAP, which is easier to calculate quantitatively, can be used in lieu of systemic perfusion pressure.

        • MAP = (CO x SVR) + CVP {CVP=0, so it can be ignored}

        So, MAP = (CO x SVR)

        SVR is the sum of resistance of all the vessels in the systemic circuit. However, the major component of systemic vascular resistance is the arteriolar resistance.

        Also, MAP can be calculated by using the following formula if the SBP and DBP are known:

        • MAP = DBP + 1/3 (SBP – DBP)

        {For a normal healthy adult, DBP = 120 & SBP = 80}

        So, MAP = 80 + 1/3 (120 – 80)

              MAP = 80 + 1/3 (40)

              MAP = 80 + 13.33

              MAP = 93 mm of Hg (After rounding off)

        Alternatively MAP can also be calculated by the following formula:

        • MAP= 2/3 DBP + 1/3 SBP

        MAP= (2/3 x 80) + (1/3 x 120)

        MAP= 53.33 + 40 = 93 mm of Hg

         

        • PERFUSION PRESSURE: The pressure necessary to bring blood supply to the systemic tissues to ensure their nutritional needs.

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        Categories
        CVS EKG CVS Physiology

        Ventricular Action Potentials

        Channels:

        Na+ fast channels. Active briefly during the phase 0.

        Slow and fast Ca++ channels. Active during the phase 2.

        Leaky K+ channels. Always active.

        Inward rectifying transient K+ channels. Active during the phase 1.

        Inward rectifying delayed K+ channels. Active during the phase 2 early part and phase 3.

        Inward rectifying K+ channels. Active during the phase 3. Primary channels to help restore resting potential.

        Na+/K+ ATPase pump. Restores the ionic imbalance after an action potential has occurred. Moves K+ in and Na+ out of the cells.