Organ Systems Exam 4 Flashcards
- What characteristics change as the vascular system divides into smaller branches down to capillaries. What characterizes medium & large veins compared to the medium & large arteries?
- What characteristics change as the vascular system divides into smaller branches down to capillaries. What characterizes medium & large veins compared to the medium & large arteries?
As the vascular system divides into smaller branches down to the capillaries, the total cross sectional area increases! This means that the velocity (which is highest in the aorta) decreases to its slowest velocity in the capillaries.
Also, Velocity = Q/A (Blood flow / cross sectional area)
Large arteries differ in the amount of elastin & smooth muscle. The large (elastic) arteries (such as the aorta, subclavian, common carotid, etc.) have the following:
>Tunica intima
>Internal elastic membrane
>Tunica media
>Tunica adventitia
Medium (muscular) arteries (brachial, ulnar, radial, coronary):
>TUnica intima
>internal elastic membrane
>Tunica media - MORE Smooth muscle, less elastic
> Tunica adventitia - thick layer of collagen, with less elastin
Medium veins - up to 10mm diameter
>Tunica media: smooth muscle
>Tunica adventitia (externa): thick CT (collagen and elastin)
Large veins (such as inferior vena cava, superior vena cava, etc.) - over 10 mm in diameter
>T. media: few smooth muscle layers
>Tunica adventitia: CT (collagen & elastin), longitudinal smooth muscle
as You can see in the graph below, veins are more compliant than arteries since they have less elastic and fibrous CT
- Describe the main features of the three layers of the vascular wall.
- Describe the main features of the three layers of the vascular wall.
>Tunica Intima (internal layer): Endothelium, subendothelial layer of loose CT, Internal elastic membrane
>Tunica media (middle layer): Smooth muscle (plus elastic & reticular fibers, proteoglycans between SM cells), external elastic lamina
>Tunica externa (adventitia) (outer layer): Loos CT w/ collagen and elastin. Containes vasa vasorum and nervi vascularis (autonomics in larger arteries & veins.
- What is so important about arterioles? What are their characteristic features?
- What is so important about arterioles? What are their characteristic features?
As small arteries divide into arterioles, they simplify their structure.
>Maintain smooth muscle, endothelium and basement membrane
>Lose internal and external elastic membranes
>Arterioles are PRIMARY REGULATORS! of blood pressure and flow
The arterioles have smooth muscle rings over elastic tissues.
Most blood pressure is created by back pressure of arterioles! Constriction of the smooth muscle is the primary determinant of what goes beyond that and to the capillaries.
- What proportion of the blood is in the arterial (not heart, lungs) and venous systems?
- What proportion of the blood is in the arterial (not heart, lungs) and venous systems?
Blood is distributed unevenly in the circulatory system
- Veins 64%
- Arterial side 20%
- Arteries 13%
- Arterioles and capillaries 7%
- Heart/pulmonary 16%
- 2/3 of blood is in the venous system
- Where the blood is depends on
- Blood Flow
- Vascular Resistance
- What is the impact of increases in flow and resistance on blood pressure? Can you predict what happens to the blood pressure if you increase the flow and also reduce the resistance?
- What is the impact of increases in flow and resistance on blood pressure? Can you predict what happens to the blood pressure if you increase the flow and also reduce the resistance?
Blood Flow (which is the rate of fluid movement & is also the Cardiac Output) = Change in pressure / resistance
Q = P1-P2/R
Likewise:
P1-P2 (Change in Pressure) = Q x R
So… Increased flow and resistance will INCREASE the blood pressure.
If you increase the flow and reduce the resistance (since smaller arteries have higher resistance), this could either increase or decrease flow based on their relative differences since Change in Pressure = Q x R
- What does Poiseuille have to say about the impact of changing the radius of a blood vessel on resistance and blood flow?
- What does Poiseuille have to say about the impact of changing the radius of a blood vessel on resistance and blood flow?
Poiseuille’s equation show that R ~ 1/r^4 (1/radius^4), which means that a super small decrease in arteriolar radius (vasoconstriction) causes significant increases in resistance, which reduces the flow or increases pressure difference.
EX: A tube with twice the radius yields 16 times the flow!
- What impact would changing the number of dilated arterioles opening into capillary beds such as the GI system have on the velocity of blood flow in the capillaries? If you exercise right after you eat, what will happen to the blood velocity in the GI tract?
- What impact would changing the number of dilated arterioles opening into capillary beds such as the GI system have on the velocity of blood flow in the capillaries? If you exercise right after you eat, what will happen to the blood velocity in the GI tract?
Velocity is similar to blood flow, but very different.
Flow: Amt. of blood passing in a period of time (volume/sec)
Velocity is a function of flow and cross sectional area.
V = Q/A (flow/cross sectional area)
Sooo….Vasodilation of the arterioles opening into capillary beds such as the GI system will DECREASE velocity (and vice versa)
Sympathetic activity (such as exercise) directs blood to skeletal muscle and heart (B2 vasodilation) and away from internal organs (a1 vasoconstriction)
- What contributes to the viscosity of blood? How would viscosity increase or decrease? How would a greater blood viscosity affect the velocity gradient in an artery? Why?
- What contributes to the viscosity of blood? How would viscosity increase or decrease? How would a greater blood viscosity affect the velocity gradient in an artery? Why?
Viscocity is the internal friction generated by the interaction between molecules and particles, and an increase in viscosity reduces flow → Q ~ 1/n (1/viscosity)
Velocity gradient is created by blood viscosity and friction from walls.
> A higher viscosity increases the velocity gradient (since along the central axis, velocity is maximal)
>A greater velocity gradient increases shear stress which alter vascular properties
>Excess rbc synthesis in response to hypxia (polycythemia) increase viscosity, impairing blood flow.
Viscous:
—–>
———->
—–>
- What are the conditions that could increase blood turbulence? Where are some sites that turbulence is more likely to occur?
- What are the conditions that could increase blood turbulence? Where are some sites that turbulence is more likely to occur?
Blood turbulence would be INCREASED with: high velocity, large vessel diameter, high fluid density, and low viscosity. Turbulence typically occurs in narrow, atherosclerotic vessels (high velocity), aortic arch (large diameter), bifucations (eg aorta).
Blood turbulence: cross currents flow in all directions, incresing resistance, dissipating energy, and reducing streamline flow. Excess transmural (lateral) pressure increases risk of rupture.
- What is shear stress? How is it affected by changes in vessel radius and blood flow? How can it affect phenotypic expression of endothelial cells?
- What is shear stress? How is it affected by changes in vessel radius and blood flow? How can it affect phenotypic expression of endothelial cells?
Shear stress: Excess velocity of laminar flow produces shear stress (viscous drag) on endothelial cells
>Temporary shear stress can be compensated by vasodilation (autoregulation).
Shear stress: INCREASES with viscosity, flow and velocity
DECREASES with radius increase
Prolonged shear stress can damage blood vessels, and excess shear stress due to occlusion alters gene expression via cycoskeletal signaling.
- How do the individual resistances of the organ systems add up to the total peripheral resistance?
- How do the individual resistances of the organ systems add up to the total peripheral resistance?
TPR = ChangeinP/Q = P aorta/CO
P(aorta) is esstimated by the MAP, which is defined below:
TPR = MAP/CO = MAP / CO
++Note: Flow is the cardiac output. The pressure gradient is:
ChangeinPressure = (Paorta - Pvena cava) >>>Pvena cava is small and thus eliminated!
- If you change the resistance of an organ system vasculature, how does it impact: Local blood pressure? Total systemic blood pressure? Local blood flow? Blood flow in other organ systems?
- If you change the resistance of an organ system vasculature, how does it impact: Local blood pressure? Total systemic blood pressure? Local blood flow? Blood flow in other organ systems?
Changes in resistance impact local and global aspects of circulation differently!
>>>In a single organ, if the resistance increases, the local blood flow decreases, and the local pressure drop increases. INcrease in local pressure diverts blood to other organs. As blood flow increases in other organs, total flow still equals cardiac output. Enhanced pressure spreads out to the rest of the circulation, increasing the MAP.
Thus, an increase in one organ will: 1. Produce and increased in overal ChaingeinPressure, (MAP)
Decrease flow in the organ, but increase it in all other organs without changing the overall blood flow
- How does the sympathetic nervous system regulate vascular resistance? What is the difference between stimulating α1 and β2 receptors on blood flow and resistance? How do these receptors affect shunting of blood between organ systems?
- How does the sympathetic nervous system regulate vascular resistance? What is the difference between stimulating α1 and β2 receptors on blood flow and resistance? How do these receptors affect shunting of blood between organ systems?
The sympathetic nervous system regulates vascular resistance through using NE and EPI, which cause constriction. Parasympathetic vasodilation is localized to a few structures, such as the cerebral and genital vessels.
>>Alpha and beta receptors both bind NE and EPI, but produce opposite responses.
A1 receptors - sympathetic stimulation with NE (neural) or EPI (hormonal) triggers vasoconstriction via IP3
B2 receptors - Epinephrine (hormonal) triggers vasodilation via cAMP.
Shunting of blood: Sympathetic activity (during exersie) directs blood to skeletal muscle and heart (B2 vasodilation) and away from the internal organs (a1 vasoconstriction).
>>However, most vasodilation in continuing muscle activity is due to build up of metabolites.
- What are the major differences between regulation of local versus systemic circulation?
- What are the major differences between regulation of local versus systemic circulation?
Local regulation ensures adequate blood supply to individual organs, while central mechanisms maintain adequate MAP (blood pressure) for sufficient perfusion pressure to all organs). Blood flow through individual organs depends on resistance of organ’s vessels, while blood flow through the entire system depends on the TPR.
Also, local control (autoregulation) 1. maintains constant blood flow to an organ in response to changes in blood pressure, and 2. readjusts blood flow to an organ according to local changes in its metabolic activity. Local control also optimizes blood flow and O2 delivery in specific organs or muscles by using metabolites, myogenic and endothelial mechanisms.
- What is autoregulation? What types are there in the vascular system? How does active hyperemia work? What are some metabolic vasodilators? Which organ systems are more dependent on metabolic vasodilators?
- What is autoregulation? What types are there in the vascular system? How does active hyperemia work? What are some metabolic vasodilators? Which organ systems are more dependent on metabolic vasodilators?
Local control, known as “autoregulation,” maintains the specific basal blood nutrient requirement that must be maintained homeostatically regardless of changes in the boy’s blood pressure (MAP) or the organ’s level of metabolic activity.
>>With autoregulation, flow is kept at a constant level by balance of dilation and constriction of vessels.
>>If pressure drops, blood vessels dilate to maintain flow
>>If pressure increases, blood vessels constrict to reduce blood flow
The mechanisms for autoregulation include the following:
Metabolic hyperemia
Myogenic
Endothelial
- Active hyperemia - increase in organ blood flow with increased physical or metabolic activity - increases vasodilation of arteries. Metabolic vasodilators are specific to organs and include:
Adenosine (Ado) - inhibits contraction via cAMP in coronary and possibly skeletal muscle arterioles
K+ and PO4 - dilate skeletal muscle vasculature
CO2, H+ dilate cerebral vasculature
- Myogenic autoregulation - vascular smooth muscle contracts in response to increased transmural pressure, and relaxes upon decreased pressure. Pressure activates cell pathways that increase both Ca ++ influx and Ca++ binding to myosin light chains. Myogenic responses minimize arterial pressure build up in legs and feet during standing.
Endothelial autoregulation - positive feedback of myogenic vasoconstriction balanced by local vasodilators: NO, prostacyclin, endothelin
- What is myogenic autoregulation? Why can’t it provide homeostatic control of blood flow by itself?
- What is myogenic autoregulation? Why can’t it provide homeostatic control of blood flow by itself?
Myogenic autoregulation - vascular smooth muscle contracts in response to increased transmural pressure, and relaxes upon decreased pressure. Pressure activates cell pathways that increase both Ca ++ influx and Ca++ binding to myosin light chains. Myogenic responses minimize arterial pressure build up in legs and feet during standing.
>>Myogenic autoregulation can’t provide homeostatic control of blood flow by itself since metabolic autoregulation & endothelial autoregulation are needed to control blood flow in other regions.
- What is NO and how is it generated? How does it regulate blood flow through a region? Describe two other vasodilators and how they work.
- What is NO and how is it generated? How does it regulate blood flow through a region? Describe two other vasodilators and how they work.
NO - nitric oxide, and it is synthesized from arginine via nitric oxide synthase, NOS. NO is generated in response to shear stress, and the following chemicals: Ach, ATP, hypoxia, histamine, bradykinin. NO diffuses from endothelial to smooth muscle cells to generate cGMP. cGMP inhibits Ca ++ actions on myosin light chain kinase, leading to its relaxation. Also, NO regulates proliferation of SM cells.
2 other vasodilators: 1. Prostaglandins (prostacyclin), PG
Similar stimuli generate PG, which uses cAMP to inhibit Ca ++ mediated smooth muscle contraction.
Adenosine (Ado) - A metabolic vasodilator that inhibits contraction via cAMP in coronary and possibly skeletal muscle arterioles
- Describe endothelin in terms its stimulation and action. How do endothelin and NO change in hypertension?
- Describe endothelin in terms its stimulation and action. How do endothelin and NO change in hypertension?
Endothelin ET-1
>Vasoconstricts (IP3 & Ca++) and induces proliferation of smooth muscle cells
>Induced by vasoconstrictive and inflammatory substances
>Normal counterbalance to NO, but excess levels in disease
In hypertension, ET-1 is up regulated, while NO is down regulated. Endothelial cells hypertrophy and smooth muscles proliferate.
- Why is the preferred location to measure blood pressure on the brachial artery?
- Why is the preferred location to measure blood pressure on the brachial artery?
The brachial artery is around the same height as the heart/aorta, making it the preferred location to measure BP when standing, sitting, or lying down. Since the body is a column of fluid and pressure within the fluid varies by height, we want to be consistent when measuring BP. If you measure BP on the leg while the patient is standing, the measurement will be higher than that of the aorta because a greater volume of fluid is pressing down on the lower extremities. However, if you measure on the leg while the patient is lying down flat it should match aortic pressure.
- What is the difference among perfusion, transmural and gravity blood pressures?
- What is the difference among perfusion, transmural and gravity blood pressures?
Perfusion: pressure along vessel length
Transmural: pressure across vessel wall (what you measure)
ΔP across vessel wall
generates stress (σ) within wall (based on LaPlace’s equations T=PR and σ=T/h) σ= PR / h
Tension (T) = Pressure (P) * Lumen Radius (R)
Stress (σ) = Tension (T) / Wall Thickness (h)
Vessels that produce little stress can tolerate high pressures
small diameter vessels (capillaries)
thick walled vessels (aorta)
aneurism? (can be caused by high BP)
Gravity: the body is a column of fluid, with higher pressures at the feet and lower pressures at the head.
Transmural pressure - literally trans mural or “across the wall”; the pressure difference between the inside and outside of a hollow structure in the body
Perfusion pressure - pressure force driving blood through the circulation of an organ; usually synonymous with the blood pressure in the artery supplying an organ or tissue
Transmural pressure varies according to velocity of flow; perfusion pressure does not
Velocity related to radius
Bernoulli’s principle
increased velocity decreases transmural pressure in constricted vessels
decreased velocity increases transmural pressure in expanded vessels such as aneurisms
- In a typical manometer reading of blood pressure, what vascular events signal the level of systolic and diastolic pressures? What are Korotkow sounds and what causes them?
- In a typical manometer reading of blood pressure, what vascular events signal the level of systolic and diastolic pressures? What are Korotkow sounds and what causes them?
Korotkoff sounds - sounds made by the first spurts of blood escaping from a compressed artery (i.e. brachial artery) as the compression is slowly released; they are detected by stethoscope in the measurement of arterial pressure by sphygmomanometer and used as the indicator of peak systolic pressure.
Above systolic pressure, applied pressure occludes the brachial artery during both systole and diastole.
At systolic pressure, blood pressure just exceeds applied pressure and artery opens briefly (Korotkoff sounds are audible).
At diastolic pressure, the blood pressure exceeds applied pressure and artery remains open (sounds cease).
Blood pressure is the force that blood exerts against the vessel wall. During a normal cardiac cycle, blood pressure reaches a high point and a low point. The high point is referred to as systole and occurs when the ventricles of the heart contract, forcing blood into the aorta. The low point is referred to as diastole and occurs when the ventricles relax and minimal pressure is exerted against the vessel wall.
A normal blood pressure for a healthy adult ranges from 90 to 120 mm Hg systolic and from 60 to 80 mm Hg diastolic.
- What is the difference between perfusion and transmural pressures? In a typical blood vessel, are they the same? Why?
- What is the difference between perfusion and transmural pressures? In a typical blood vessel, are they the same? Why?
(See #1)
Transmural pressure is the pressure difference between the inside and the outside of a structure. For example, the pressure difference between the inside and the outside of the left ventricle, or the pressure difference between the inside and outside of a blood vessel.
Perfusion pressure on the other hand is the difference in pressure between two different sites in a system of tubes where fluid is flowing or has the potential to flow from one point to another. Perfusion pressure is also called the pressure head or the driving pressure. Perfusion pressure is equal to one transmural pressure minus a second transmural pressure; for example, one located at one point in a hydraulic system minus the transmural pressure at another point in a hydraulic system. Mean arterial (aortic) pressure minus mean venous pressure yields the perfusion pressure. It is largely responsible for the blood flowing through the systemic circulation from the aorta to the vena cavae.
Transmural Pressure
PT.M. = Pi - Po
where Po = pressure outside, Pi = pressure inside
Perfusion Pressure (pressure head, driving pressure)
Pp = PT.M.1 - PT.M.2 (The difference between two transmural pressures)
or E = IR (Ohm’s Law)
e.g. Pp = Pa - Pv
Where: Pa = mean arterial pressure, Pv = mean venous pressure
Perfusion pressure = Flow x Resistance (like, voltage (E) = current (I) x resistance (R))
(A) If any given flow of blood is forced through progressively smaller cross-sectional areas, the velocity of blood flow must increase. The Bernoulli principle states that increased flow of velocity reduces the lateral pressure of the flow stream exerted against the wall of the vessel.
The total energy of blood flow in a blood vessel is the sum of its potential energy (represented as pressure against the vascular wall) and its kinetic energy resulting from its velocity (KE = 1/2 mv^2). The total of potential and kinetic energy at any point in a system is constant. Consequently, any increase in one form of energy has to come at the expense of the other. In the figure above for example, as flow velocity increases lateral pressure must decrease to keep the total energy of the system constant.
Transmural pressure varies according to velocity of flow; perfusion pressure does not
Velocity related to radius
Bernoulli’s principle
increased velocity decreases transmural pressure in constricted vessels
decreased velocity increases transmural pressure in expanded vessels such as aneurisms
- Why do arterioles have the biggest ΔP in the vascular system? What is its significance in regulation of blood flow in individual organ systems?
- Why do arterioles have the biggest ΔP in the vascular system? What is its significance in regulation of blood flow in individual organ systems?
Arterioles have the largest pressure gradient due to their high resistance. Pressure is high at arterial end of arterioles, and lower at capillary end. BP (& pulsation) diminishes with distance from the heart. Pressure in venules and veins is low with increased compliance.
In individual organ systems, oxygenated blood in the arteries goes down the pressure gradient to the capillaries where the organs are located.
Differences in resistances affect blood flow in the vascular system.
Blood flow through individual organs depends on the resistance of the organ’s vessels.
Blood flow through the entire system depends on total peripheral resistance
- What is the mean arterial pressure, MAP? How does it differ from pulse pressure, PP?
- What is the mean arterial pressure, MAP? How does it differ from pulse pressure, PP?
PRESSURE WAVE
pressure force during systole & diastole; provides three measures of BP:
Mean arterial pressure (MAP)
Pulse Pressue (PP) & compliance
Pulse waves
MAP - average pressure in cardiac cycle
MAP = Pd + (Ps - Pd)/3
Pulse Pressure and compliance
C = ChangeinV/ChangeinP = amt. filled/applied pressure
Stretchability
PP = difference between systolic and diastolic pressures = Ps - Pd
PP = SV/C = stroke volume/compliance
- How does increasing the stroke volume affect the MAP and the PP?
- How does increasing the stroke volume affect the MAP and the PP?
MAP = Pd + (Ps - Pd)/3 = Pd + PP/3
PP = Ps - Pd = SV/C
Slope of volume-pressure curve changes with varying compliance (steeper slope = more elastic). Increasing SV in a tissue with a given compliance would cause a corresponding increase in systolic pressure, thus raising the pulse pressure.
Also note:
Decreased SV decreases PP amplitude
Aortic stenosis: low SV
Hypothyroidism: decreased heart contractility
P = Q x R
MAP = CO x TPR
- What is meant by vascular compliance and elasticity? How do these variables affect pulse pressure? How would atherosclerosis impact the pulse pressure?
- What is meant by vascular compliance and elasticity? How do these variables affect pulse pressure? How would atherosclerosis impact the pulse pressure?
compliance - (1) change in volume in a segment of blood vessel or vessels per unit of change in transmural pressure, or V/P; (2) capability of a region of the gut to adapt to an increased intraluminal volume.
elasticity - ability of a material when stretched to return to its unstretched position (e.g. a balloon). This property differs from plasticity (the capability of being stretched, but not returning to its unstretched position, e.g., putty).
Decreased compliance of arteries also increases PP
Increases arterial systolic pressure: elasticity normally absorbs and diminishes some of the pressure. Low compliance results in higher
==
Arterial rigidity/stiffening associated with atherosclerosis reduces compliance.
progresses with age and extrinsic influences
Several causes, but note
loss of elastin
increase cross-linking of collagen
In younger people, diastolic pressure is a better index of vascular resistance. In people over 60, PP is a better index of vascular compliance (level of atherosclerosis).
- What are the wave components of the pulse wave and how do they reflect the compliance of blood vessels? How would decreased vascular compliance affect the perfusion of coronary arteries?
- What are the wave components of the pulse wave and how do they reflect the compliance of blood vessels? How would decreased vascular compliance affect the perfusion of coronary arteries?
Waveform of pulse pressure is also an index of vascular compliance (sum of the forward wave and reflected wave, separated by dicrotic notch).
Forward (incident) traveling wave generated by left ventricular contraction.
Reflected (rebound) wave returning from high resistance points , e.g. aortic and other vascular bifurcations (why pulse amplitudes increase in peripheral arteries)
Decreased compliance → less coronary artery perfusion in diastole (reflected wave is added to forward wave in systole)
- How do pulse waves change with distance from the aorta? How do they change with age?
- How do pulse waves change with distance from the aorta? How do they change with age?
(See #10 - “Age and PP amplification”)
Decreased compliance with age changes the pulse waveform.
Decreased arterial compliance (increasing stiffness) increases velocity (see below) of both forward (incident) and reflected pulse waves
Reflected wave is added to the forward wave into systole
Increase systolic pressure amplitude (increase risk of stroke)
Less coronary artery perfusion in diastole.
>Also, a wave of distention travels to peripheral vessels, accelerating as it goes!
- How do changes in levels of sympathetic activity and NO affect the pulse waveform?
- How do changes in levels of sympathetic activity and NO affect the pulse waveform?
Reduced compliance is due to:
>Vascoconstriction/atherosclerosis
>Reduction in dilatory response
Reduced sympathetic activity & nitric oxid cause vasodilation, which reduces amplitude and velocity of the reflected wave.
Increased sympathetic activity, decreased NO responsiveness to pulse pressure, and atherosclerosis cause vasoconstriction: Increase in amplitude and increase in velocity of the reflected wave
- What are the ways that venous blood is returned to the heart particularly with regard to the effects of gravity?
- What are the ways that venous blood is returned to the heart particularly with regard to the effects of gravity?
Venous blood is propelled to the heart
Venoconstriction increases venous return to the heart for enhanced SV and CO
Contracting skeletal muscles (walking, running, etc.) overcome the effects of gravity by pushing blood up a staircase of valves increasing venous return and minimizing venous pressure in the lower extremity
Respiratory inhalation reduces intrathoracic pressure thus drawing blood up from the abdomen.
- What do the cardiac function and the vascular function curves tell you? What is the significance of their intersection point?
- What do the cardiac function and the vascular function curves tell you? What is the significance of their intersection point?
Cardiac function curve = Frank-Starling:
CO is function of venous pressure (preload)
Vascular function curve = venous pressure is a function of CO.
Venous pressure drops with increasing CO; heart draws on incoming venous blood
CO is independent variable; axes reversed to compare with cardiac function.
Equilibrium point:
There can be only one value of CO and venous pressure.
System centers onto a single equilibrium point where the opposing actions of CO and venous pressure are equal and opposite, i.e. at their intersection point.
Homeostasis - cardiac and vascular mechanisms regulate venous pressure and CO to maintain homeostasis of CO and venous pressure, within normal oscillations of activity.
- How does increased cardiac contractility or venoconstriction affect the relationship of venous pressure to cardiac output?
I
- How does increased cardiac contractility or venoconstriction affect the relationship of venous pressure to cardiac output?
Contractility and vascular function:
Equilibrium points can move with changes in heart or vascular activity
Changing the curves resets the equilibrium point to a new level
Increasing heart contractility moves the cardiac curve upward.
Cardiac contractility alone would be expected to increase CO from point A to C.
But, venous pressure drops with increase in CO.
Vascular response to increase in CO will change equilibrium point to B.
At point B, CO is enhanced and venous pressure is reduced.
CO is balanced between the effects of cardiac and vascular changes.
Changes in vascular function reset equilibrium point for CO
Altering venous input into heart shifts equilibrium point for CO & PRA.
Venoconstriction or a drop in systemic vascular resistance increases venous flow (preload) into heart.
At the new intersection points (V1 & V2), CO & PRA are both set higher.
Venous pressure is higher for a given level of CO
Venoconstriction maintains CO when standing
Decreased vascular resistance permits more venous blood to enter heart.
- How does increased cardiac contractility or venoconstriction affect the relationship of venous pressure to cardiac output?
- How does increased cardiac contractility or venoconstriction affect the relationship of venous pressure to cardiac output?
Contractility and vascular function:
Equilibrium points can move with changes in heart or vascular activity
Changing the curves resets the equilibrium point to a new level
Increasing heart contractility moves the cardiac curve upward.
Cardiac contractility alone would be expected to increase CO from point A to C.
But, venous pressure drops with increase in CO.
Vascular response to increase in CO will change equilibrium point to B.
At point B, CO is enhanced and venous pressure is reduced.
CO is balanced between the effects of cardiac and vascular changes.
Changes in vascular function reset equilibrium point for CO
Altering venous input into heart shifts equilibrium point for CO & PRA.
Venoconstriction or a drop in systemic vascular resistance increases venous flow (preload) into heart.
At the new intersection points (V1 & V2), CO & PRA are both set higher.
Venous pressure is higher for a given level of CO
Venoconstriction maintains CO when standing
Decreased vascular resistance permits more venous blood to enter heart.
- How do changes in both contractility and venoconstriction affect the relationship of venous pressure to cardiac output?
- How do changes in both contractility and venoconstriction affect the relationship of venous pressure to cardiac output?
Combined effects of cardiac contractility and vascular changes during exercise:
Cardiac stimulation and increased venous input together produce significant increases of CO for relatively less preload.
At points B,C & D, note how CO is higher than normal, but at a relatively lower venous pressure.
Combining lower arterial blood pressure (or venoconstriction) with greater cardiac contractility, the heart becomes more efficient, i.e. it pumps more blood per amount of preload.
- What role does the RVLM have in regulating sympathetic activity and baseline blood pressure? How do changes in sympathetic activity generate vasoconstriction and vasodilation?
- What role does the RVLM have in regulating sympathetic activity and baseline blood pressure? How do changes in sympathetic activity generate vasoconstriction and vasodilation?
BARORECEPTION PATHWAYS
BRAIN STEM 1.Solitary Nucleus (NTS)
- Receives baroreceptor afferents • Projects excitatory activity to:
- Caudal ventrolateral medulla (CVLM) • Nucleus ambiguus (nAmb)
- Caudal ventrolateral medulla (CVLM) • Projects to RVLM
- Rostral Ventrolateral Medulla (RVLM) • Pacemaker for basal sympathetic activity • Projects to sympathetic preganglionic neurons in spinal cord.
ANS 4. Nucleus Ambiguus
• Parasympathetic preganglionic neurons that project to heart via vagus nerve (CN X)
- Sympathetic pathway • Preganglionic and postganglionic neurons to heart and blood vessels
===
How does the CNS reset the baroreflex to maintain different levels of blood pressure?
- PVN of hypothalamus temporarily enhances sympathetic vasoconstriction or causes baroreceptors to become less sensitive to changes in blood pressure; chronic hypertension will do the same
- Changing the sensitivity of baroreceptors to higher levels of blood pressure causes a rightward shift in the equilibrium point for baroreception , i.e. blood pressure is maintained homeostatically at a new higher level. (Very typical mechanism in systems regulation)
- Resetting set point in chronic hypertension only aggravates an already inappropriate high blood pressure
- Compare smooth muscle cells to skeletal muscle fibers in terms of: cell size, number of nuclei, caveolae vs T-tubules, cytoskeleton (esp dense bodies)
- Compare smooth muscle cells to skeletal muscle fibers in terms of: cell size, number of nuclei, caveolae vs T-tubules, cytoskeleton (esp dense bodies)
Skeletal muscle fibers
multi-nucleated
tructure of muscle fibers[edit]
3D rendering of a skeletal muscle fiber.
Main article: Myocyte
Individual muscle fibers are formed during development from the fusion of several undifferentiated immature cells known as myoblasts into long, cylindrical, multi-nucleated cells. Differentiation into this state is primarily completed before birth with the cells continuing to grow in size there after. Skeletal muscle exhibits a distinctive banding pattern when viewed under the microscope due to the arrangement of cytoskeletal elements in the cytoplasm of the muscle fibers. The principal cytoplasmic proteins are myosin and actin (also known as “thick” and “thin” filaments, respectively) which are arranged in a repeating unit called a sarcomere. The interaction of myosin and actin is responsible for muscle contraction.
T tubules are the pathways for action potentials to signal the sarcoplasmic reticulum to release calcium, causing a muscle contraction. Together, two terminal cisternae and a transverse tubule form a triad.[1]
Smooth muscle (SM) structure
• Bundled fusiform cells, 40-600 μm long, each with one nucleus
• Embryonic smooth cells do not fuse unlike skeletal muscle
• Capable of dividing (mitosis) to replace damaged or aging cells
• Synthesize basilar layer and extracellular matrix, including collagen
and elastin (endomysium)
• Caveolae: cell indentations similar to T-tubules
Cytoskeleton
• •
Non-striated: Z-lines not aligned Dense bodies, equivalent to Z- lines, anchor actin and intermediate fibers to sarcolemma.
• Intermediate filaments link the dense bodies into a cytoskeletal network.
Thin filaments attach to dense bodies • Consist of actin and tropomyosin,
but no troponin (see below)
Thick filaments: myosin II, isomer for slower contraction
- Describe the extracellular matrix-basement membrane complex and their function in adhering smooth muscle tissue.
- Describe the extracellular matrix-basement membrane complex and their function in adhering smooth muscle tissue.
Intercellular SMC connections are made using dense bodies and reticular CT:
Intercellular dense bodies (attachment plaques) act as cell adhesion molecules, providing continuity of force transmission between cells, and linking actin cytoskeleton to membrane adhesion sites.
Reticular CT stroma/matrix permeates SM; collagen, elastic fibers and endomysium (produced by SMCs) bind to dense bodies, providing structural integrity to tissue
Thus, SM has properties of muscle, CT & epithelium.
- Describe how Ca stimulates muscle contraction and how it differs from skeletal muscle. Describe the role of phosphate on the myosin light chain and its role in the latch phenomenon.
- Describe how Ca stimulates muscle contraction and how it differs from skeletal muscle. Describe the role of phosphate on the myosin light chain and its role in the latch phenomenon.
SMC sliding filament contraction:
***SM contraction does NOT use troponin!
***Light chain phosphate gives permission, ATP is motivation to contract.
In relaxed state (top picture), light chain is NOT phosphorylated and myosin head is NOT bound to actin chain (myosin head is bound to ADP and phosphate group).
Regulation by Ca++: MLCK (myosin light chain kinase) is responsible for phosphorylation of the myosin light chain. MLCK is activated when complexed with Ca++ and calmodulin. Thus, increasing Ca++ concentration activates MLCK, and decreasing Ca++ turns MLCK off.
Cross-bridge cycling:
***Myosin light chain must be phosphorylated for this to occur! Do not confuse w/ the other phosphate group!
Latch state: With MLCK activated, the light chain phosphate is bound to the myosin head, giving the Myosin-ADP-P head permission to bind to the actin filament.
Power stroke: As binding occurs, ADP & P are released and the cross-bridges bend.
Detachment: ATP comes in and binds the myosin head, hydrolyzing the cross-bridge; myosin head detaches from actin filament, resetting head.
As ATP is hydrolyzed by ATP-ase, it is converted back to ADP + P. If light chain phosphate is still attached, another cycle of contraction may proceed.
Deactivation: Myosin phosphatase removes light chain phosphates (reverse reaction of MLCK).
Latch state (similar to rigor) permits continuous contraction w/ minimal ATP use (goes around the circle very slowly). After continuous contraction actin-myosin cycling slows down as more light chain phosphates are removed by myosin phosphatase.
5.What are the two sources of Ca++ for contraction and how does this differe fom skeletal muscle?
- What are the two sources of Ca++ for contraction and how does this differe fom skeletal muscle?
- What are the two sources of Ca++ for contraction and how does this differ from skeletal muscle?
Smooth muscle can be activated in 2 ways:
SR release of Ca++
Entry of extracellular Ca++ (through L-type Ca channels)
In contrast, skeletal and cardiac muscle contraction relies solely on Ca++ release from the SR activated by an AP; L-type Ca channels that permit entry of extracellular Ca++ are used only to trigger further release from the SR (trigger calcium is for skeletal/cardiac only).
- Describe the mechanisms that release Ca from the SR including ligands, second messengers, sympathetic nervous system.
- Describe the mechanisms that release Ca from the SR including ligands, second messengers, sympathetic nervous system.
CALCIUM DIRECT ENTRY:
3 types of Ca channels in SMC’s:
Ligand-gated channels - opened by hormones/transmitters
ligands (NE, EPI, ACh, endothelin, etc) activate G-proteins → IP3 formation
Postganglionic autonomic neurons release transmitters as paracrines from varicosities
gap jxn’s help NE get to lower layers of cells
Voltage-gated channels - AP induces opening of channel; AP’s enter via gap jxn’s
Physically gated channels - stretching SM stimulates its own contraction by opening these channels
CALCIUM ENTRY VIA 2ND MESSENGER:
Agonist → receptor → G-protein → Phospholipase C → PIP2 to IP3 + DAG → IP3 releases Ca++ from SR
No AP is needed to release Ca++ from SR, only activation of the receptors.
Some SR release of Ca++ is triggered by entry of extracellular Ca++ as in cardiac muscle.
Note: the amount of Ca++ entry from extracellular space is sufficient to activate MLCK (unlike skeletal or cardiac).
Extracellular Ca++ source is necessary because SR cannot provide enough Ca++ during continuous contraction.
Regulation of SM contraction:
Ligand-gated channels:
IP3 stimulates Ca++ release from SR
Ligands (NE, EPI, ACh, endothelin, etc) activate G proteins → formation of IP3
IP3 releases Ca++ from SR (no AP needed); some SR release of Ca++ is triggered by entry of extracellular Ca++ as in cardiac muscle
NE stimulates
- Describe the role of physically gated channels in the myogenic response of SM.
- Describe the role of physically gated channels in the myogenic response of SM.
Myogenic Response
- Myogenic response of SM is the shortening/contraction of muscle fibers following an abrupt stretch of the arterial wall caused by an increase in blood pressure.
- Physically gated Ca++ channels creates an AP & muscle contraction
- Physically gated Na/Cl channels activate cell signaling that generates IP3 and Ca++ release from the SR
- Note dual sources of Ca++
- How do beta receptors and NO relax smooth muscle? Explain the issue of how NE can both contract and relax smooth muscle.
- How do beta receptors and NO relax smooth muscle? Explain the issue of how NE can both contract and relax smooth muscle.
Smooth muscle relaxation occurs via several mechanisms, some involving second messengers:
- How do smooth muscle velocity-tension and length-tension dynamic differ from skeletal muscle?
- How do smooth muscle velocity-tension and length-tension dynamic differ from skeletal muscle?
Velocity - tension relationship
- Smooth muscle contraction slower than either skeletal or cardiac muscle
- SM myosin isomer has lower ATP-ase activity and hence contracts slower, much like type I, slow skeletal muscle
- Oxidative phosphorylation is more important than anaerobic glycolysis.
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Mechanical plasticity and length-tension relationship
- Smooth muscle maintains tension at a wide range of lengths because of wide length tension curve
- Wide range due transient remodeling of actin filaments.
- Short term stretch induces polymerization of actin fibers and elongation of sarcomeres
- Describe the major issues of SM phenotypic plasticity in normal and abnormal functions.
- Describe the major issues of SM phenotypic plasticity in normal and abnormal functions.
Phenotypic plasticity
- In hypertension, high tension of vascular wall triggers smooth muscle hypertrophy which reduces diameter of blood vessels.
- Vascular injury following hypertrophy represses genes that normally maintain smooth muscle properties. Note the histone methylation and heterochromatin formation in the dedifferentiated state.
- Smooth muscle forms CT matrix and loses contractility. Golgi apparatus and rough ER replace myofilaments, i.e. SM becomes CT
- Describe capillary Starling forces in terms of hydrostatic and oncotic pressures. What is meant by net filtration pressure? Net absorption pressure?
- Describe capillary Starling forces in terms of hydrostatic and oncotic pressures. What is meant by net filtration pressure? Net absorption pressure?
Note:
Osmotic pressure = pressure exerted by ions across cell membranes
Oncotic pressure = osmotic pressure exerted by proteins across epithelium
How capillary fluid leaves the arterial end and returns to the venous ends of capillaries:
Net Filtration Pressure (NFP): capillary hydrostatic pressure exceeds oncotic pressure
Net Absorption Pressure (NAP): capillary oncotic pressure exceeds hydrostatic pressure
Hydrostatic pressure diminishes along the length of the capillary dropping below the level of oncotic pressure.
- Describe the lymph drainage system of the whole body and its asymmetry. Where are the concentrations of lymph nodes?
- Describe the lymph drainage system of the whole body and its asymmetry. Where are the concentrations of lymph nodes?
Lymph flows from the afferent lymphatic vessels to the sinuses of the lymph nodes, which drain into the efferent lymph vessel. While in the gland, the lymph fluid percolates through the parenchyma.
