Chapter 6 - Cardiovascular Physiology Flashcards
Separates the right and left parts of the heart
Septum a
Systemic circulation
Portion of cardiovascular system that starts at left ventricle and ends in the right atrium a
Pulmonary circulation
Section of cardiovascular system starting in right ventricle and ending in left atrium (pulmonary and systemic circulations are connected in series) a
Blood volume distribution
Blood volume is distributed between the systemic and pulmonary circulations, so left cardiac output to systemic is the same as the right cardiac output to the pulmonary in order to maintain steady-state blood volumes
a
Right cardiac output = left cardiac output
Frank Starling Mechanism
adjusts cardiac output of each ventricle in proportion to venous return in each ventricle (equalizing right and left cardiac output)
a
Law - Length-force relations of cardiac muscle, an increase in preload leads to an increase in stroke volume, greater filling of ventricle leads to greater volume of blood that is ejected to the circulation, extent of ventricular filling is important determinant of stroke volume and therefore cardiac output
Blood Pressure (arterial vs. venous) and Drivers of Blood Flow (equation)
Arterial blood pressure is much greater than venous because the ventricle pumps blood directly into the arterial system and blood pressure is dissipated during blood flow because of resistance of organs before venous system
a
Blood flow is driven by the difference between arterial and venous pressure
Systemic arterial pressure is greater than pulmonary arterial pressure because systemic vascular resistance is higher (high-pressure high-resistance) vs. pulmonary (low-pressure low-resistance), means that left ventricular wall is much thicker than right ventricular wall
Blood Flow = Change in Pressure / Resistance
Mechanism and Names of Cardiac Valves
Ensure unidirectional blood flow and prevent regurgitation (for example, the aortic valve opens only when the left ventricular pressure is higher than aortic pressure and it closes with the left ventricular pressure is lower than aortic pressure)
a
Right atrioventricular valve - tricuspid valve
Pulmonary Valve
Left atrioventricular valve - mitral valve
Aortic valve
Control of Heartbeat
Heart has an intrinsic pacemaker, can continue to beat in complete separation from the ANS, the ANS can modulate heart rate by altering pacemaker activity
a
Heartbeat generation
Sinoatrial (SA) Node (right atrium) - pacemaker, spontaneously generates action potentials at regular time intervals, conducted directly to atrial cardiac muscles but cannot be conducted directly from atria to ventricles because the fibrous cardiac skeleton physically separates the two atria from the ventricles - but cells in the conductive system can also generate APs, safeguard if SA node fails to generate APs or act as filter if SA is generating APs at exceedingly high frequency
a
–> Atrioventricular (AV) Node - conduction through here is slow, time delay between atrial and ventricular depolarization (to allow active filling of ventricles by atrial contraction before ventricular ejection of blood), downstream parts are very fast to allow simultaneous contraction of both ventricles
–>Bundle of His - rapid conduction of APs to all ventricular cardiac muscle cells
–> right and left bundle branches
–>Purkinje fibers
a
Ionic Basis of sinoatrial AP
Depolarization at SA (Phase 4) is mostly through Na+ influx through “funny” channels (because they increase their open probability in response to hyperpolarization instead of depolarization), also known as hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) because they are activated by cAMP
a
Ca2+ influx also contributes to spontaneous depolarization phase 0 and the repolarization phase 3 is caused by K+ efflux
(No phases 1 and 2 unlike cardiac AP)
Timing of Contraction
SA APs are conducted rapidly through gap junctions at intercalated discs (contain desmosomes and tight junctions) to cardiac muscle cells so the atria can contract as a unit (to fill ventricles) and APs are conducted slower through the AV node to the ventricles which then contract together
Cardiac Arrhythmia, Aneurysm and QT syndrome
Cardiac arrhythmia - loss of electrical synchronization of cells which can lead to decreased cardiac output, BP and death
Aneurysm - protrusion of wall of blood vessel, reduces efficiency and output
QT Syndrome - genetic mutation of potassium channel leading to delayed opening of K+ channels for repolarization, abnormal lengthening of the AP, increased risk of cardiac arrhythmia
Cardiac AP Phases
There are 4 phases:
Phase 4 - resting membrane potential, dominated by K+ efflux through inward rectifying K+ channels
Phase 0 - activation of fast Na+ channels
Phase 1 - following brief depolarization caused by K+ efflux through transient outward K+ channels
Phase 2 - long duration of plateau depolarization (unique to cardiac APs), activation of slow Ca2+ channels and inactivation of K+ channels (Ca2+ entry triggers release of Ca2+ from SR), both Ca2+’s are important for cardiac muscle contraction
Phase 3 - repolarization, opening of voltage sensitive K+ channels
ECG/EKG Explanation
The atria and ventricles undergo depolarization together (like two giant cells) and generate electric currents that can be recorded as changes in voltage on the body surface, ECG measures the potential difference between two points on the body surface (attachment sites of positive and negative terminals)
ECG should look like - what causes each part
P = initial first depolarization
PR Interval = first depolarization and flat until the QRS complex
PR Segment = flat part at resting membrane potential
QRS Complex = Slight dip, then AP then another larger dip
Q = slight hyperpolarization
R = peak of depolarization
S = slightly larger hyperpolarization then Q
ST segment = flat part at resting membrane potential after S
T = 3rd depolarization (similar size to P)
QT Interval = from flat part of PR interval to end of T
P wave - atrial depolarization of the atrial cardiac AP (repolarization isn’t visible)
QRS Complex - ventricular depolarization (Phase 0) of ventricular cardiac AP
T wave - ventricular repolarization (Phase 3) of ventricular cardiac AP
ECG Problems - atrioventricular block, atrial fibrillation, complete heart block, S-T elevation, V fib
Atrioventricular block - multiple atrial depolarizations (P waves) are generated before each ventricular depolarization (QRS complex), can have 2:1 block (2 P-waves, etc.), HR decreases
Atrial Fibrillation - abnormal electrical patterns prior to QRS sequence, frequency of QRS (HR) increases
Complete heart block (third-degree block) - occurrence of P waves and QRS complexes become independent of one another, some impulses generated by SA node do not reach AV node and others do, P waves are not followed by QRS complex
ST elevation - voltage in the ST segment (which should be 0 because all cardiac muscle cells should be in depolarization state) is an indicator of nonuniform depolarization of the ventricle, associated with hypoxia of the heart, Vtach
V fib - total lack of normal electrical activity
Time Intervals
PR Interval - time between atrial depolarization and ventricular depolarization (atrioventricular conduction time)
QT interval - time between ventricular depolarization and repolarization is duration of ventricular AP and an estimate of ventricular contraction time
R-R Interval - duration of one cardiac cycle
Electrical Axis and ECG lead placement (general)
During ventricular depolarization and repolarization - the base of the ventricle is negative (top) and the tip (apex, bottom) is positive, because base of the ventricle is near the atria so this part depolarizes first and spreads downward (repolarization starts at the apex)
Electrical axis - base, upper right is negative, apex, lower left in positive
When an ECG lead is positioned in the same direction of the electrical axis of the heart, the QRS and T complexes are recorded as positive voltages, when an ECG lead is positioned opposite the direction of the electrical axis, the QRS and T wave are recorded as negative voltages
Place the positive terminal near the ventricular apex (lower left part of body) and the negative terminal near the ventricular base (upper right part of body), the beginning of the process will show a positive reading because the base will be positive relative to the apex and at the end because the base will still be positive as the apex begins to depolarize
Standard Leads
Positive and negative terminals are attached to different limbs
Lead I - positive terminal on Left Arm (LA) and negative terminal on right arm (RA)
Lead II - positive terminal on left leg (LL) and the negative terminal on the right arm (RA), generally highest voltage because right along axis
Lead III - positive terminal on left leg (LL) and negative terminal on left arm (LA)
Augmented Leads
Positive terminal is attached to one limb, negative terminal is attached to two other limbs, they are oriented down the middle between two standard leads
aVr - positive terminal is on right arm (RA), negative terminal is on left arm and left leg (LA, LL), this is inverted because the positive terminal is placed near the negative end of the electrical axis
aVl - positive terminal is on LA, negative terminal is on RA and LL
aVf - positive terminal is on LL, negative terminal is on RA and LA
Precordial Leads
6 leads - the positive terminal is attached to one point on the chest wall (along rib) and the negative terminal is attached to the right arm, left arm, and left leg together (oriented from center of heart outward)
Regulation of Cardiac Muscle Contraction and how AP ends
Striated muscle cell, it is regulated by Ca2+-troponin-tropomyosin system (like skeletal) except the increase in Ca2+ in response to an AP is mediated by 2 mechanisms: Ca2+ influx across cell membrane and intracellular Ca2+ release from SR
Membrane depolarization during the plateau depol. of a cardiac AP stimulates Ca2+ influx into cardiac muscle cells through VG L-type Ca2+ channels on the cell membrane, this initial increase is Ca2+ then triggers Ca2+ release from intracellular SR via ryanodine channels (Ca2+ induced Ca2+ release)
At termination of AP, cardiac muscle relaxation is induced when intracellular Ca2+ is pumped back into SR by Ca2+-ATPase (SERCA) on the SR membrane, then intracellular Ca2+ is removed by the Na+/Ca2+ exchanger (NCX) and Ca2+-ATPase (CaP) on cell membrane - intracellular Na+ is then pumped out by Na+/K+ ATP-ase
Binding of Ca2+ to troponin causes conformational change in the troponin-tropomyosin complex and removes inhibitory effect so cyclic interactions between actin and myosin cross bridges for muscle contraction
Cardiac Output (ventricular vs. atrial)
left ventricle does most of the work in pumping cardiac output against the high resistance (atrial contractions only contribute 10-20% of the filling of ventricles)
Systole and Diastole (and the phases of the cardiac cycle)
Systole - ventricular depolarization and ventricular contraction (Isovolumic contraction + Ejection)
Diastole - ventricular repolarization and ventricular relaxation (Isovolumic Relaxation + Filling)
Left Ventricular Volume
4 phases of cardiac cycle are clearly defined by time course of left ventricular volume
Immediately before QRS complex, the left ventricular volume is at its highest (end-diastolic volume), it is at the end of ventricular filling after left atrial contraction (mitral valve remains open at the end of filling because pressure is equalized but aortic valve remains closed because ventricular pressure is lower than aortic pressure), ventricular pressure is about to increase which will close the mitral valve and then open the aortic valve for ejection of blood
Isovolumic Contraction Phase
Brief period between the closing of the mitral valve and the opening of the aortic valve when ventricular volume remains constant but left ventricular pressure is rising, mitral and aortic valves are both closed because left ventricular pressure is higher than left atrial pressure but lower than aortic pressure
Ejection Phase (contraction)
After isovolumic contraction - left ventricular pressure exceeds the aortic pressure and causes opening of the aortic valve and ejection of blood (stroke volume) into circulation, left ventricular volume reaches its lowest level (end-systolic volume) during ejection phase, takes up 40% of the cardiac cycle time
Only time in cardiac cycle that the aortic valve is open
Stroke Volume
Blood volume ejected into circulation during one cardiac cycle (difference between end-diastolic volume and end-systolic volume, which is typically non-zero because heart doesn’t completely empty its contents during ejection)
Stroke Volume = End-Diastolic Volume - End-Systolic Volume
Ejection Fraction
The fraction of end-diastolic volume that is ejected as stroke volume into circulation during one cardiac cycle, this is a measure of cardiac contractility (contractile strength of heart, in a healthy heart it should be relatively high, above 50%, in a failing heart it is relatively low, less than 30%)
Ejection Fraction = Stroke Volume/End-Diastolic Volume
Onset of T wave
End of the ejection phase and the beginning of ventricular repolarization, ventricular diastole (relaxation) and closing of the aortic valve
Isovolumic Relaxation
Brief period between closing of aortic valve and opening of mitral valve when ventricular volume stays the same but left ventricular pressure is decreasing, both aortic and mitral valves are closed because left ventricular pressure is lower than aortic pressure but higher than left atrial pressure
Passive Filling (Part of Filling Phase)
Passive filling phase begins shortly after isovolumic contraction when left ventricular pressure falls below left atrial pressure so the mitral valve opens and blood from left atrium flows into the left ventricle, ventricular relaxation drives blood flow from the atrium to the ventricle, this passive filling contributes to 80-90% of total ventricular filling
Onset of P wave
Beginning of atrial depolarization, atrial contraction, and active filling phase
Active Filling phase
Atrial contraction drives blood flow from the atrium to the ventricle, at the end of this phase, left ventricular volume reaches its highest level (end-diastolic volume)
Four Phases of Cardiac Cycle
Electrical events precede mechanical event, atrial and ventricular contraction and relaxation lead to changes in pressure and volume in cardiac chambers and circulation
Isovolumic Contraction –> Ejection –> Isovolumic Relaxation –> Filling –> Isovolumic Contraction
Filling Phase - T-Q, left ventricular pressure is lower than left atrial pressure and lower than aortic pressure so the mitral valve is open and the aortic valve is closed, blood begins to fill the ventricle
Isovolumic Contraction (IVC) - left ventricular pressure is higher than left atrial pressure but lower than aortic pressure, mitral and aortic valves are closed, pressure increases but (high) volume stays the same
Ejection - (Q-T), left ventricular pressure is higher than aortic pressure and atrial pressure, aortic valve is open and mitral is close, blood is ejected into aorta
Isovolumic Relaxation (IVR) - left ventricular pressure is higher than atrial but lower than aortic, both valves close and (low) volume stays the same but pressure decreases
Left Ventricular Pressure throughout the cardiac cycle
Major driver of ventricular ejection and ventricular filling, fluctuates over large range (diastolic ventricular pressure is near zero, ventricular systolic pressure is high, around 120mmHg)
The low ventricular pressure is necessary for ventricular filling and the high ventricular systolic pressure is necessary for overcoming aortic pressure during ejection
During isovolumic contraction phase, left ventricular pressure is rising (volume stays constant), then during ejection it continues to rise until it is above aortic pressure and continues to rise during ejection phase and peaks in the middle of the phase before falling in the second half of the ejection phase due to the decrease in ventricular volume
At onset of T wave when ventricular depol/relaxation begins there is a quick fall in left ventricular pressure (when below aortic but above atrial is the isovolumic relaxation phase), then it falls below left atrial pressure and mitral valve opens and we enter the passive filling phase, once the active filling phase begins there is a slight increase in left ventricular pressure, then after the filling phase the pressure decreases to lowest (diastolic) level, near 0
Before and Onset of QRS Complex on Left Ventricular Pressure
Immediately before QRS complex, ventricular pressure is at its lowest (diastolic) level because the left ventricle is in its relaxed state
Beginning of QRS complex is beginning of ventricular depolarization, contraction and rise in ventricular pressure
Aortic Pressure
During 3 phases of cardiac cycle when aortic valve is closed (no ventricular output), blood flow does not fall to zero because the artery-venous pressure continues to drive blood flow through systemic circulation
Aortic pressure fluctuates between a lowest (diastolic) and a highest (systolic) value, typical is 120/80 mmHg
After the onset of the QRS wave (ventricular depot/contraction) there is a time delay between rise in ventricular pressure and rise in aortic pressure (this is the isovolumic contraction phase), once the valve opens, it causes aortic pressure to rise to its systolic during the middle of the ejection phase (aortic pressure is almost identical to left ventricular pressure at this point)
T wave is beginning of ventricular repolarization/relaxation, fall in left ventricular pressure AND aortic pressure, aortic falls gradually toward its diastolic value due to outflow of blood from the aorta to the venous system via the organ systems
Left Atrial Pressure
Atrial pressures are relatively low (less than 5mmHg) during a cardiac cycle, the left atrium receives blood from pulmonary veins and small fluctuations in pressure are due to venous return to atrium, contraction of atrium and contraction of ventricle
QRS wave is beginning of ventricular depol/contraction and there is a short increase in left atrial pressure (c wave) caused by the vibration of mitral valve during ventricular contraction, the left atrial pressure also increases during ventricular ejection due to the accumulation of pulmonary venous return in the left atrium
the T wave is beginning of ventricular repol/relaxation, when left ventricular pressure falls below atrial the mitral valve will open and passive filling will begin, causing decrease in left atrial pressure (v wave is transition from blood returning from pulmonary veins to the outflow of blood from left atrium to left ventricle)
Sometime after opening of mitral valve, P wave marks atrial depolarization/contraction, causing short increase in left atrial pressure (a wave)
v wave = venous return
a wave = atrial contraction
c wave = ventricular contraction
Phonocardiogram
Heart sound: Lub-dub, lub-dub
First heart sound - Lub (S1), comes from the synchronized closing of the tricuspid and mitral valves at the beginning of ventricular contraction (systole), beginning of QRS wave
Second Heart sound - Dub (S2) is from the synchronized closing of the aortic and pulmonary valves at the beginning of ventricular relaxation (diastole), T wave in ECG
Time interval between first and second sound (lub-dub interval) is the systolic time, time interval between a pair of consecutive heart sounds (dub-lub interval) is the diastolic time, systolic time is shorter than diastolic time
The Third Heart sound (S3), occurs in early diastole and is an indicator of cardiac failure
Determinants of Cardiac Output (and definition/equation)
Cardiac Output - volume of blood pumped into circulation per minute, generally approximately 5000mL/min at rest and can increase so 12,500 mL/min during exercise
Cardiac Output = Heart Rate x Stroke Volume
Heart Rate - Regulated by sinoatrial node which is modulated by the ANS, the parasympathetic (vagal) stimulation decreases HR and sympathetic stimulation of SA node increases HR (athletes have low HR and high SV)
Preload - Extent of ventricular filling (measured by end-diastolic volume) prior to ventricular contraction, increase in preload leads to increase in stroke volume (this is the Frank-Starling curve for the heart), this is determined mostly by blood volume and venous compliance - severe hemorrhage and dehydration can lead to decrease in blood volume and decrease in preload, causing decrease in stroke volume and cardiac output, dependent on venous return from the heart from the vascular system
Afterload - The load against which the heart ejects its stroke volume, ex. mean arterial pressure, which left ventricular pressure must exceed to open the aortic valve for ejection, moderate increase in after load (mean arterial pressure) doesn’t change stroke volume significantly because of compensatory mechanisms but in a failing heart, an increase in after load (mean arterial pressure) can decrease stroke volume due to exhaustion of compensatory mechanisms, an increase in after load means higher workload and oxygen consumption by the heart which can result in cardiac failure, after load is dependent on total vascular resistance of the circulation, a normal heart is relatively insensitive to after load up to 140mmHg arterial pressure, for a failing heart cardiac output is decreased significantly by an increase in after load
Cardiac Contractility - Contractile strength of heart, can be measured in terms of Frank-Starling curve, increase in cardiac contractility shifts the curve left and upward (and vice versa for lower cardiac contractility), another measure of cardiac contractility is ejection fraction, at a given end-diastolic volume, a heart with higher cardiac contractility ejects a larger stroke volume (and vice versa), sympathetic stimulation of heart increases cardiac contractility by activating B-adrenergic receptors on cardiac muscle cells with sympathetic NT (NE) or sympathetic stimulation of adrenal medulla increases epinephrine, activating B-adrenergic receptors on cardiac muscle cells - parasympathetic stimulation of heart can decrease heart rate but doesn’t directly change contractility of cardiac muscle cells BUT parasympathetic decrease of HR decreases the intracellular Ca2+ levels (because of decrease in frequency of stimulation) so this indirectly affects cardiac contractility
Vascular System
For each organ: arteries –> arterioles –> capillaries –> venules –> veins
All of these have a lumen covered with a single layer of endothelial cells (provides non clotting surface for blood flow and releasing nitric oxide for vasodilation)
Arteries have a thick stiff wall for withstanding high blood pressure and storing mechanical energy during ventricular ejection, arterioles have a lot of vascular smooth muscle for controlling arteriolar diameter in regulation of blood flow, capillaries are made of single layer of endothelial cells to help with rapid diffusion between blood and surrounding cells and venules/veins have relatively thin and compliant walls for holding the majority of the blood volume in circulation
Arteries as Pressure Reservoir
Arteries are pressure reservoir to maintain continuous blood flow to organs, when blood is ejected into arteries the arterial walls expand and this stored mechanical pressure is used to drive the continuous blood flow through circulation
Arterial pressure is highest (systolic) in the middle of ventricular ejection and lowest (diastolic) at the end of isovolumic contraction immediately before ejection
Pulse Pressure
Difference between systolic pressure and diastolic pressure, represents change in arterial pressure in response to ejection of stroke volume into arterial system, major determinants include stroke volume and arterial compliance (decrease in stroke volume due to hemorrhage can lead to decrease in pulse pressure, stiffening of arterial wall in atherosclerosis can lead to increase in pulse pressure)
Pulse Pressure = Systolic Pressure - Diastolic Pressure
Mean Arterial Pressure
Time-Average of arterial pressure is useful for examining blood pressure homeostasis (by averaging values of arterial blood pressure measured at regular time intervals during a cardiac cycle)
Mean Arterial Pressure = Diastolic Pressure + Pulse Pressure/3
It is closer to diastolic than systolic because ventricular diastole is the majority of the cardiac cycle (60%)
Systemic mean generally 93.3, pulmonary mean generally 13.7
Arterioles as Resistance Vessels/Organ Blood Flow
Arterioles are resistance vessels that help regulate blood flow to organs, pressure drop is proportional to vascular resistance in each segment of vascular system and arterioles have the largest pressure drop (so largest resistance)
The total vascular resistance in an organ is the sum of the resistance in the artery, arterioles, capillary, venue, and veins so can control total vascular resistance by controlling resistance of arterioles by vasoconstriction and vasodilation
Organ Blood Flow = (Arterial Pressure - Venous Pressure) / Vascular Resistance
Vascular Resistance/Pressure Drop
Same blood flow through each part of vascular system but pressure drop through each part is different
Vascular Resistance = (Pressure in - Pressure out)/Blood Flow
Capillaries and Resistance/Poiseuille’s Law
Capillaries have less total resistance than arterioles because vascular resistance of single blood vessel is linearly proportional to vessel length and viscosity and inversely proportional to the fourth power of radius (most important variable*), two-fold increase in radius causes 16 fold decrease in resistance
Resistance of a single blood vessel AKA Poiseuille’s Law:
Resistance = (8 * Length * Viscosity) / (pi * r^4),
This explains low vascular resistance in large blood vessels (aorta) and high vascular resistance in small blood vessels (arterioles and capillaries), so each individual arteriole would have a lower resistance than a capillary BUT because capillaries are arranged in parallel and there are many more of them, their total resistance is less than the total resistance of the arterioles (Rtotal = R single/Ncapillaries)
Auto regulation of Organ Blood Flow/Vasodilator Hypothesis/Myogenic Hypothesis
Blood flow to an organ is driven by distance between arterial and venous pressure and is regulated by the organs vascular resistance
Maintenance of relatively constant blood flow by local mechanisms over a range of different arterial pressures, arterioles regulate this by proportionally increasing vascular resistance (constricting) as arterial pressure increases (in the range of 70-175mmHg, the auto regulatory range)
Organ Blood Flow = (Arterial Pressure - Venous Pressure) / Vascular Resistance
Vasodilator Hypothesis - Explains the maintenance of constant blood flow despite increases in arterial pressure within auto regulatory range because decrease in arterial pressure leads to insufficient blood flow and oxygen in tissues causing an increase in release of vasodilator (a product of anaerobic metabolism) by cells leading to arteriolar dilation and increase in blood flow until supply matches oxygen demand and an increase in arterial pressure causes an oversupply of blood flow and oxygen causing a decrease in vasodilator by cells and arteriolar vasoconstriction until oxygen supply matches demand
HOWEVER this vasodilator has not yet been identified
Myogenic Hypothesis - Proposes that the increase in vascular resistance in response to increased arterial pressure is caused by mechanical stretch-induced activation of vascular smooth muscle cells
Exercise Hyperemia
Blood flow increases spontaneously to skeletal muscle during exercise to level necessary to provide enough oxygen (independent of ANS), vasodilator hypothesis explains that an increase in muscle metabolism during exercise leads to higher oxygen demand and release of more vasodilators for more supply
Hypoxic Vasodilation
Physiologic response of all organs in response to hypoxia (not enough oxygen) where blood flow spontaneously increases to these organs independently of ANS, explained by vasodilator hypothesis by proposing that hypoxic cells release more vasodilator
Vascular Dilation by Endothelial Cells (NO)
Endothelial cells can release factors for relaxation and contraction of vascular smooth muscle cells in wall of blood vessels and can also release factors for contraction of vascular smooth muscle (endothelin)
Nitric Oxide (NO) is an endothelium-derived relaxing factor, shear stress (mechanical rubbing) and receptor activation of endothelial cells induce NO release by increasing intracellular Ca2+ which activates Ca2+-dependent endothelial nitric oxide synthase for synthesis of NO from L-arginine (there are 3 forms of this enzyme that produce NO in different cell types)
NO can cause vasodilation, vasoprotection, inflammation, synaptic plasticity and immune defense - it is also responsible for penile erection, can inhibit phosphodiesterase to treat erectile dysfunction
NO diffuses across cell membranes of smooth muscle cells into cytoplasm where it activates guanylyl cyclase, that catalyzes synthesis of cGMP from GTP, cGMP then induces smooth muscle relaxation by activating cGMP-dependent kinase and other effector proteins (this is terminated by degradation of cGMP to GMP by phosphodiesterase)
NO –> activates guanylyl cyclase –> turns GTP into cGMP
–> activates cGMP dependent kinases and other effector proteins –> smooth muscle relaxation
(to terminate): phosphodiesterase –> degrades cGMP into GMP
Renin-Angiotensin-Aldosterone System
This system consists of an enzyme (renin), a peptide (angiotensin) and a steroid hormone, and is an important regulator of arterial blood pressure by controlling blood pressure through regulating vascular resistance and blood volume in circulation
Decrease in BP and renal blood flow ==> release of renin into circulation by juxtaglomerular cells in the kidney ==> renin catalyzes breakdown of angiotensinogen in plasma into angiotensin I (relatively inactive) ==> transported to pulmonary circulation where angiotensin converting enzyme on surface of endothelial cells cause breakdown of angiotensin I into angiotensin II (active) ==> activates angiotensin II receptors on vascular smooth muscle ==> causes vasoconstriction and increases vascular resistance, also stimulates release of aldosterone (steroid hormone) by adrenocortical cells in adrenal gland ==> renal reabsorption of Na+ ==> increase blood volume ========> higher BP
Inhibitors of this system can be used to treat hypertension (angiotensin II is potent cause of hypertension)
Baroreceptor Reflex for Buffering Arterial Pressure
Negative feedback mechanism used for short term stabilization of BP in response to external perturbations (ex. change in posture from standing to squatting which compresses peripheral veins and raises BP and decreases HR due to this reflex)
Arterial blood pressure is sensed by baroreceptors (present in carotid sinus and aortic sinus) which transmit signals to the cardiovascular center of the brain stem, an increase in BP above a set point causes the center to activate the parasympathetic nervous system and inhibit the sympathetic nervous system to the heart, causing a decrease in heart rate, cardiac contractility and total peripheral resistance, causing BP to decrease
Going from squatting to standing causes BP to decrease by decreased blood volume from gravity-induced expansion of veins in the lower extremities, the baroreceptor reflex will cause an increase in HR to combat this and BP will gradually increase
If this reflex is removed there are wide fluctuations in arterial pressure in a 24-hour period, can test in patients using a tilt-table test where patients are secured to a table that can be changed rapidly between laying down and standing up, patient without the reflex may faint
The reflex reacts to long-term changes in arterial pressure by adjusting its set point with mean arterial pressure (so it is active even in hypertensive or hypotensive individuals) and is generally not a cause of arterial hypertension
Capillaries as diffusional transport center
Capillaries consist of a single layer of endothelial cells, provide large surface area and short distance for diffusional exchange between blood and cells, diameter of capillaries is similar to the diameter of RBCs which reduce the distance of diffusion btw RBCs and the surrounding cells
Capillary wall is very permeable to lipid-soluble molecules like CO2 and O2, and gaps between endothelial cells (in all areas except the CNS) allow for the diffusion of larger and charged molecules like ions (Na+, K+, Cl-) and glucose between capillary plasma and interstitial fluid, in CNS these gaps don’t exist (blood-brain barrier) and things have to be moved across by transporters
Distance between neighboring capillaries is the intercapillary distance which is important determinant of diffusional transport between capillary and surrounding cells (half of this distance is the max diffusion distance between a capillary and the cells surrounding a capillary), this distance is regulated by precapillary sphincters that control the number of capillaries that are open for perfusion (process called capillary recruitment), pre capillary sphincters are terminal arterioles containing a single layer of vascular smooth muscle cells, relaxation of these leads to opening of sphincter for capillary perfusion and contraction of these cells leads to the closing of capillaries for perfusion - reducing diffusion distance via capillary recruitment is important mechanism for enhancing diffusional transport (more relaxation = shorter distance = better diffusion)
Protein Retention in Plasma and Osmotic/Hydrostatic Pressure
Gaps between endothelial cells are too small for proteins so there is protein retention in plasma and this raises the osmotic pressure in the plasma compared to the interstitial fluid which generates a pressure gradient across the capillary wall which is counteracted by the hydrostatic pressure gradient that is generated by the relatively high BP in the capillary compared to the interstitial fluid
Colloid Osmotic Pressure Gradient = pi(c) - pi(if)
Hydrostatic Pressure Gradient = Pressure(c) - Pressure(if)
Hydrostatic pressure gradient factors diffusion of water from capillary to interstitial whereas the osmotic pressure gradient favors diffusion of water in the opposite direction, net fluid movement is determined by the difference between the two pressure gradients (as well as capillary permeability, K)
Fluid Movement Across Capillary Wall = (P(c) - P(if) - pi(c) + pi(if) ) * K
Events as Blood Moves Across Capillary
As blood moves across the capillary the net hydrostatic pressure decreases because of the decrease in capillary blood pressure due to the capillary resistance
As blood moves through capillary, osmotic pressure stays about the same because there is a pretty low change in capillary volume in organs with low capillary permeability (like skeletal muscle and cardiac muscle)
Therefore fluid filtration (fluid moving into interstitial) happens at the beginning of a capillary and fluid absorption (fluid moving into blood) happens at the end of a capillary (although net fluid movement tends to be small because of low permeability), goes from 30mmHg to 10 mmHg (and osmotic stays around 20 mmHg)
Purposes of circulation
Carry oxygen and CO2 molecules, carry hormones for regulation, nutrients for consumption, and other waste products out of the blood
Veins as Volume Reserve
Venous system is volume reserve for the cardiovascular system because the high compliance of veins allows a lot of the blood volume to accumulate in the venous system without causing a large increase in venous BP, 70% of blood volume is stored in the venous system but the pressure remains low (central systemic venous pressure is near 0 and central pulmonary venous pressure is 2-3mmHg)
Unstressed venous volume is the volume necessary to be in the venous system before there can be any increase in venous pressure, the stressed venous volume is above the unstressed venous volume (imagine tank with wide diameter), takes a lot of increase in the stressed volume to increase venous pressure, central venous pressure (CVP) drives venous return to the heart and is determined by stressed venous volume and venous compliance
During exercise, venous system is volume reserve for increasing circulating blood volume, sympathetic stimulation causes venous constriction, this decreases unstressed volume and venous compliance and shifts blood from venous system into circulation for increasing venous return, ventricular filling, and cardiac output
In severe hemorrhage, venous constriction helps restore cardiac output by putting more blood into circulation
Orthostatic (postural) Hypotension
Drop in BP that occurs in the standing posture, venous system acts as volume sink for decreasing circulation blood volume (gravity causes shift in blood from circulation to veins in lower extremities and decreases the circulating volume, cardiac output and blood pressure), this can result in fainting because it will cause a person to lie down and facilitate the return of venous pressure from the lower extremities to circulation for the restoration of cardiac output and blood pressure
Cardiovascular Response to Hemorrhage
Loss of blood volume leads to decrease in ventricular end-diastolic volume, stroke volume, and cardiac output, cardiovascular system tries to maintain arterial BP for perfusion to critical organs (heart and brain) by increasing HR, cardiac contractility, total peripheral resistance and venous return (increase in HR is mediated by sympathetic nervous system stimulating the SA node and conductive system, it increases contractility by stimulating cardiac muscle cells), increase in total peripheral resistance is mediated by preferential vasoconstriction of arterioles in organs that are most sensitive to sympathetic stimulation (kidneys, GI tract, and skin, less important organs), venous return is increased by sympathetic stimulation of venous system to increase circulation by shifting blood volume and enhancing ventricular filling, additionally, the decrease in capillary BP (as result of decrease in arterial BP) leads to increase in fluid absorption from interstitial fluid to the capillary and moderately increases the blood volume (if transfusion isn’t available, can give IV fluid to increase blood volume)
Cardiovascular Response to Exercise
Skeletal muscle is dependent on oxygen that comes from cardiac output, this means vasodilation in muscles which causes decrease in total peripheral resistance in the systemic circulation and significant increase in venous return to the heart
To maintain normal arterial BP during exercise, heart increases cardiac output to match increase in venous return by increase HR and stroke volume (HR increase up to 300% by sympathetic stimulation of SA node and conductive system and stroke volume can increase by up to 50% by an increase in cardiac contractility via stimulation of cardiac muscle cells from sympathetic nervous system)
Frank-Starling curve shifts up (BUT not left because end-diastolic volume stays same) during exercise (increase in stroke volume and end-diastolic volume)
Sympathetic system also cause compression of veins, pumps some blood from venous system into circulation to increase ventricular filling and end-diastolic volume
Muscle pumping and contraction causes the valves above muscles to open and facilitates venous return
To direct blood flow more to important skeletal muscles, cardiovascular system decreases blood flow to the kidney and GI tract during intense exercise by sympathetic nervous system causing arteriolar vasoconstriction in these organs
Cardiovascular Response to Congestive Heart Failure
CHF primary cause is significant decrease in cardiac contractility which lowers the ability of the heart to pump stroke volume into the circulation (causes decrease in cardiac output and a resulting increase in systemic venous pressure)
Patients with CHF are lethargic because low cardiac output, compensatory response of body direct limited output to critical organs for immediate survival (heart and brain) and reduced blood flow to other organs (kidneys and GI tract), kidneys respond by increasing reabsorbance of Na+ and water causing expansion of extracellular fluid volume and increase in central venous pressure (this is bad because this results in an enlarged heart with a greater end-diastolic volume which is energetically inefficient, increases cardiac oxygen consumption and results in further deterioration of the heart, additionally, increase in central venous pressure due to more extracellular fluid volume causes increase in capillary hydrostatic pressure which drives fluid from capillaries into interstitial, also causes swelling in abdomen, ankles, left, PE, shortness of breath, coughing, tiredness, excess fluid around lungs and excess fluid in lungs
In Frank Starling - CO vs. right arterial pressure, acute cardiac failure shows decrease in CO and slight increase in EDV, CHF shows decrease is CO and large increase in EDV because of fluid retention
Intercalated Discs
Cardiac muscle is connected by intercalated discs which are junctional structures between neighboring cardiac muscle cells for mechanical connection (via desmosomes) and electrical synchronization (via gap junctions)
Cardiac Muscle Cells
Striated muscle cells that are regulated by the Ca2+ troponin/tropomyosin system
Autonomic Regulation of Cardiovascular system
Sympathetic - raises HR (B1 adrenergic receptor by increasing rate of spontaneous depolarization Phase 4 in SA node by activating funny channels), raises cardiac contractility (B1-adrenergic receptor), vasoconstriction (alpha-adrenergic receptor)
Parasympathetic - just lowers HR (muscarinic ACh receptor), induces hyperpolarization in SA node by activating K+ channels, Phase 3
B-Adrenergic Pathway
NE –> Beta adrenergic receptor –> GPCR –> AC –> ATP into cAMP –> stimulate SA node (increase HR and contractility)
Diastolic and Systolic Heart Failures
Diastolic - major cause is abnormally low ventricular compliance (stiff heart) resulting in abnormally low ventricular filling and low stroke volume, ejection fraction is usually normal
Systolic - Major cause is abnormally low cardiac contractility (weak heart) characterized by abnormally low ejection fraction
Vena Caval Pressure
Generally about 0, flow=cardiac output
Regulation of Capillary Filtration
Regulation of hydrostatic pressure - dependent on blood volume (ex. fluid retention in CHF) and arteriolar tone
Regulation of Osmotic pressure - depends on plasma protein concentration (ex. starvation-induced tissue swelling)
Regulation of Filtration Coefficient - dependent on endothelial barrier function (allergic run induced high permeability contributes to tissue swelling)
The lymphatic network
Normal net capillary filtration for whole body - 2 mL/ min
Lymphatics - carry filtrate back to venous system through right lymphatic duct and thoracic duct
Lymphatic capillaries - system originates in tissue as blind-ended, highly permeably, capillaries
Lymphatic valves - all channels have valves to ensure unidirectional flow
Muscle Pumping - contractions of lymph vessels and muscular compression drive lymph flow into the circulation
Main complications of persistent high BP
Brain - strokes
Blood - elevated sugar levels
Heart - MI or heart failure
Kidneys - renal failure
Cardiac Factors - high HR, high contractility, caused by sympathetic tone
Vascular Factors - high total peripheral resistance, cause by high sympathetic tone and high plasma (angiotensin II)
Coupling factors - high preload caused by high blood volume
Regulation of Mean Arterial Pressure
MAP = Cardiac Output x Total Peripheral Resistance
CO = HR x stroke volume
HR Cardiac Factor (HR)
SV Cardiac Factor (contractility), coupling factor: preload
Total peripheral resistance, vascular factors are sympathetic stimulation, angiotensin II, NO
