BRS for physiology Flashcards

Terms Definitions
Describe the relationship between the CO of the left heart and the CO of the right heart.
-CO from the left side of the heart is the systemic blood flow
-CO from the right side of the heart is the pulmonary blood flow
Describe the direction of blood flow.
1. from the lungs to the left atrium via the pulmonary vein
2. from the left atrium to the left ventricle through the mitral valve
3. from the left ventricle to the aorta through the aortic valve
4. from the aorta to the systemic arteries and the systemic tissues (i.e. cerebral, coronary, renal, splanchnic, skeletal muscle and skin)
5. from the tissues to the systemic veins and vena cava
6. from the vena cava (mixed venous blood) to the right atrium
7. from the right atrium to the right ventricle through the tricuspid valve
8. from the right ventricle to the pulmonary artery
9. from the pulmonary artery to the lungs for oxygenation
Describe arteries.
1. deliver oxygenated blood to the tissues
2. are thick-walled with extensive elastic tissue and smooth muscle
3. are under high pressure
4. the blood volume contained in the arteries is called stressed volume
Describe arterioles.
1. are the smallest branches of the arteries
2. are the site of highest resistance in the CV system
3. have a smooth muscle wall that is extensively innervated by the autonomic nerve fibers
4. arteriolar resistance is regulated by the ANS
5. alpha-1 adrenergic receptors are found on the arterioles of the skin, splanchnic, and renal circulation
6. beta-2 adrenergic receptors are found on arterioles on skeletal muscle
Describe capillaries.
1. have the largest total cross-sectional and surface area
2. consists of a single layer of endothelial cells surrounded by basal lamina
3. are thin-walled
4. are the site of exchange of nutrients, water and gases
Describe venules.
1. are formed from merged capillaries
Describe veins.
1. progressively merge to form larger veins, the largest vein (vena cava) returns blood to the heart
2. are thin-walled
3. are under low pressure
4. contain the highest proportion of the blood in the CV system
5. the blood volume contained in the veins is called the unstressed volume
6. have alpha-1 adrenergic receptors
How is the velocity of blood flow calculated?
v = Q/A, where Q = blood flow and A = cross-sectional area
What is the relationship between velocity and area?
blood velocity is higher in the aorta (small cross-sectional area) than in the sum of all of the capillaries (large cross-sectional area), the lower velocity of blood in the capillaries optimizes conditions for exchange of substances across the capillary wall
How is blood flow calculated?
q = changeP / R, where change P = pressure gradient and R = resistance or total peripheral resistance, also CO = (mean arterial pressure – right atrial pressure) / total peripheral resistance
Describe blood flow.
-the equation for blood flow (CO) is analogous to Ohm’s law for electrical circuits (I = V/R), where flow is analogous to current and pressure is analogous to voltage
-the pressure gradient drives blood flow
-thus blood flows from high pressure to low pressure
-blood flow is inversely proportional to the resistance of the blood vessels
How is resistance calculated?
R = (8*viscosity*length) / (pi*r^4)
Describe resistance.
1. resistance is directly proportional to the viscosity of the blood, INCing viscosity by INCing hematocrit will INC resistance and DEC blood flow
2. resistance is directly proportional to the length of the vessel
3. resistance is inversely proportional to radius, very powerful
Give an example in the body for parallel resistance.
is illustrated by systemic circulation, each organ is supplied by an artery that branches off the aorta
How is parallel resistance calculated?
1/Rtotal = 1/Ra + 1/Rb + … + 1/Rn, where Rn are the resistances of the renal, hepatic, and other arteries, the total resistance is less than the resistance of any of the individual arteries
Describe blood flow in parallel resistance.
1. each artery in parallel receives a fraction of the total blood flow
2. when an artery is added in parallel, the total resistance DEC
3. in each parallel artery, the pressure is the same
Give an example in the body for series resistance.
illustrated by the arrangement of blood vessels within a given organ, each organ is supplied by a large artery, smaller arteries, arterioles, capillaries, and veins arranged in series, the total resistance is the sum of the individual resistances
How is series resistance calculated?
Rtotal = Rartery + Rarterioles + Rcapillaries
Describe blood flow in series resistance.
1. the largest proportion of resistance in this series is contributed by the arterioles
2. each blood vessel (e.g. the largest artery) or set of blood vessels (e.g. all of the capillaries) in series receives the same total blood flow, thus blood flow through the largest artery is the same as the total blood flow through all of the capillaries
3. as blood flow through the series of blood vessels, the pressure DEC
Compare laminar flow and turbulent flow.
1. laminar flow is streamlined (in a straight line), turbulent flow is not
2. Reynold’s number predicts whether blood flow will be laminar or turbulent
3. when Reynold’s number is INC, there is a greater tendency for turbulence, which causes audible vibrations called bruits
What causes an INC in Reynolds number?
1. DEC blood viscosity (e.g. DEC hematocrit, anemia)
2. INC blood velocity (e.g. narrowing of a vessel)
Describe capacitance (compliance)
1. describe the distensibility of blood vessels
2. is inversely related to elastance, or stiffness, the greater the amount of elastic tissue there is in a blood vessel, the higher the elastance is and the lower the compliance is
3. describe how volume changes in response to a change in pressure
4. is much greater for veins than for arteries, as a result, more blood volume is contained in the veins (unstressed volume) than in arteries (stressed volume)
How is capacitance calculated?
C = V/P, V = volume and P = pressure
Describe capacitance in veins.
changes in the capacitance of the veins produce changes in unstressed volume, for example, a DEC in venous capacitance DEC unstressed volume and INC stressed volume by shifting from the veins to the arteries
Describe capacitance in arteries.
capacitance of the arteries DEC with age, as a person ages, the arteries become stiffer and less distensible
Describe pressure profile in blood vessels.
1. as blood flow through the systemic circulation, pressure DEC progressively because of the resistance to blood flow
2. thus, pressure is highest in the aorta and large arteries and lowest in the venae cavae
3. the largest DEC in pressure occurs across the arterioles because they are the site of highest resistance
What are the different mean pressures in the systemic circulation?
1. aorta-100 mm Hg
2. arterioles-50 mm Hg
3. capillaries-20 mm Hg
4. vena cava-4 mm Hg
Describe systolic pressure.
1. is the highest arterial pressure during a cardiac cycle
2. is measured after the heart contracts (systole) and blood is ejected into the arterial system
Describe diastolic pressure.
1. is the lowest arterial pressure during a cardiac cycle
2. is measured when the heart is relaxed (diastole) and blood is returning to the heart via the veins
Describe pulse pressure.
1. is the difference between the systolic and diastolic pressures
2. the most important determinant of pulse pressure is stroke volume, as blood is ejected from the left ventricle into the arterial system, arterial pressure INC because of the relatively low capacitance of the arteries, because distaolic pressure remains unchanged during ventricular systole, the pulse pressure INC to the same extend as the systolic pressure
3. DEC in capacitance such as those that occur with the again process cause INC in pulse pressure
Describe mean arterial pressure.
1. is the average arterial pressure with respect to time
2. can be calculated approximately as diastolic pressure plus one-third of pulse pressure
Describe venous pressure.
1. is very low
2. the veins have a high capacitance and therefore can hold large volumes of blood at low pressure
Describe atrial pressure.
1. is slightly lower than venous pressure
2. left atrial pressure is estimated by the pulmonary wedge pressure, a catheter inserted into the smallest branches of the pulmonary artery, makes almost direct contact with the pulmonary capillaries, the measured pulmonary capillary pressure is approx. equal to the left atrial pressure
What is the P wave of the EKG?
1. represents atrial depolarization
2. does not include atrial repolarization which is buried in the QRS complex
What is the PR interval of the EKG?
1. is the interval from the beginning of the P wave to the beginning of the Q wave (initial depolarization of the ventricle)
2. varies with conduction velocity through the AV node (for example, if AV nodal conduction DEC (as in heart block) the PR interval INC)
3. is DEC (INC conduction velocity through AV node) by stimulation of the SNS
4. is INC by stimulation by the PNS
What is the QRS complex of the EKG?
1. represents depolarization of the ventricles
What is the QT interval of the EKG?
1. is the interval from the beginning of the Q wave to the end of the T wave
2. represents the entire period of depolarization and repolarization of the ventricles
What is the ST segment of the EKG?
1. is the segment from the end of the S wave to the beginning of the T wave
2. is isoelectric
3. represents the period when the ventricles are depolarized
What is the T wave of the EKG?
represents ventricular repolarization
Describe the resting membrane potential of the heart.
1. determined by the conductance to K+ and approaches the K+ equilibrium potential
2. inward current brings positive charge into the cell and depolarizes the membrane potential
3. outward current takes positive charge out of the cell and hyperpolarizes the membrane potential
4. the role of Na+-K+ ATPase is to maintain ionic gradient across cell membranes
Describe AP of the ventricles, atria and Purkinje system.
1. have stable resting membrane potentials of about -90 mV, this value approaches K+ equilibrium potential
2. APs are of long duration, especially in Purkinje fibers, where they last 300 msecs
Describe phase 0 of ventricular AP.
1. is the upstroke of the AP
2. is caused by a transient INC in Na+ conductance, this INC results in an inward Na+ current that depolarizes the membrane
3. at the peak of the AP, the membrane potential approaches the Na+ equilibrium potential
describe phase 1 of the ventricular AP.
1. is a brief period of initial repolarization
2. initial repolarization is caused by an outward current, in part because of the movement of K+ ions (favored by both chemical and electrical gradients) out of the cell and in part because of a DEC in Na+ conductance
describe phase 2 of the ventricular AP.
1. is the plateau of the Ap
2. is caused by a transient INC in Ca2+ conductance, which results in an inward Ca2+ current, and by an INC in K+ conductance
3. during phase 2, outward and inward currents are approx. equal, so the membrane potential is stable at the plateau level
Describe phase 3 of the ventricular AP.
1. is repolarization
2. during phase 3, Ca2+ conductance DEC and K+ conductace INC and therefore predominates
3. the high K+ conductance results in a large outward K+ current (Ik) which hyperpolarizes the membrane back toward the K+ equilibrium potential
Describe phase 4 of the ventricular AP.
1. is the resting membrane potential
2. is a period during which inward and outward currents (IK1) are equal and the membrane potential approaches the K+ equilibrium potential
Describe the SA node.
1. is normally the pacemaker of the heart
2. has an unstable resting potential
3. exhibits phase 4 depolarization, or automaticity
4. the AV node and the His-Purkinje systems are latent pacemakers that may exhibit automaticity and override the SA node if it is suppressed
5. the intrinsic rate of phase 4 depolarization (and heart rate) is fastest in the SA node and slowest in the His-Purkinje system (SA node > AV node > his-Purkinje)
Describe phase 0 of the sinoatrial AP.
1. is the upstroke of the AP
2. is caused by an INC in Ca2+ conductance, this INC causes an inward Ca2+ current that drives the membrane potential toward the Ca2+ equilibrium potential
3. the ionic basis for phase 0 in the SA node is different from that in the ventricles, atria and Purkinje fibers (where it is the result of an inward Na+ current)
Describe phase 3 of the sinoatrial AP.
1. is repolarization
2. is caused by an INC in K+ conductance, this INC results in an outward K+ current that causes repolarization of the membrane potential
Describe phase 4 of the sinoatrial AP.
1. is slow depolarization
2. accounts for the pacemaker activity of the SA node (automaticity)
3. is caused by an INC in Na+ conductance, which results in an inward Na+ current called If
4. If is turned on by repolarization of the membrane potential during the preceding AP
Describe phase 1 and 2 of the sinoatrial AP.
are not present in the SA node AP
Describe the upstroke of the AP in the AV node.
upstroke of the AP in the AV node is the result of an inward Ca2+ current (as in the SA node)
Describe conduction velocity of excitation throughout the cardiac tissue.
1. depends on the size of the inward current during the upstroke of the AP, the larger the inward current, the higher the conduction velocity
2. is fastest in the pukinje system
3. is slowest in the AV node (seen as the PR interval on the EKG), allowing time for ventricular filling before ventricular contraction, if conduction velocity through the AV node is INC, ventricular filling may be compromised
Describe excitability of cardiac cells.
1. is the ability of cardiac cells to initiate AP in response to inward, depolarizing current
2. reflects the recovery of channels that carry the inward currents for the upstroke of the AP
3. changes over the course of the AP, these changes in excitability are described by refractory periods
What is the absolute refractory period?
1. begins with the upstroke of the AP and ends after the plateau
2. reflects the time during which no AP can be initiated, regardless of how much inward current is supplied
What is the effective refractory period?
1. is slightly longer than the ARP
2. is the period during which a conducted AP cannot be elicited
What is the relative refractory period?
1. is the period immediately after the ARP when repolarization is almost complete
2. is the period during which an AP can be elicited, but more than the usual inward current is required
What effects do the sympathetic and parasympathetic systems have on heart rate?
1. sympathetic-INC heart rate via beta-1 receptor
2. parasympathetic-DEC heart rate via muscarinic receptors
What effects do the sympathetic and parasympathetic systems have on conduction velocity (AV node)?
1. sympathetic-INC velocity via beta-1 receptor
2. parasympathetic-DEC via muscarinic receptor
What effects do sympathetic and parasympathetic systems have on contractility?
1. SNS-INC via beta-1
2. PNS-DEC (atria only) via muscarinic receptor
What effects does SNS have on skin vascular smooth muscle?
constriction via alpha-1 receptors
What effects does SNS have on skeletal muscle?
constriction via alpha-1 receptors, relaxation via beta-2 receptors
What are chronotropic effects?
1. produce changes in heart rate
2. a negative chronotropic effect DEC heart rate by DECing the firing rate of the SA node
3. a positive chronotropic effect INC heart rate by INCing the firing rate of the SA node
What are dromotropic effects?
1. produce changes in conduction velocity, primarily by the AV node
2. a negative dromotropic effect DEC conduction velocity through the AV node, slowing the conduction of AP from the atria to the ventricles and INCing the PR interval
3. a positive dromotropic effect INC conduction velocity through the AV node, speeding the conduction of AP from the atria to the ventricles and DECing the PR interval
What are the parasympathetic effects on the heart rate and conduction velocity?
1. the SA node, atria and AV node have parasympathetic vagal innervation, but the ventricles do not, the neurotransmitter is ACh which acts at muscarinic receptors
2. has negative chromotropic and dromotropic effects
Describe the mechanism of negative chronotropic effect.
1. DEC heart rate by DECing the rate of phase 4 depolarization
2. fewer AP occur per unit time because the threshold potential is reached more slowly and therefore less frequently
3. the mechanism of the negative chronotropic effect is DEC If, the inward Na+ current that is responsible for phase 4 depolarization in the SA node
Describe the mechanism of negative dromotropic effect.
1. DEC conduction velocity through the AV node
2. APs are conducted more slowly from the atria to the ventricles
3. INC the PR interval
4. the mechanism of the negative dromotropic effect is DEC inward Ca2+ current and INC outward K+ current
Describe the neurotransmitter and receptor for sympathetic effects on heart.
NE is the neurotransmitter and beta-1 receptors, includes positive chronotropic and dromotropic effects
Describe the mechanism of positive chronotropic effect.
1. INC heart rate by INCing the rate of phase 4 depolarization
2. more AP occur per unit time because the threshold potential is reached more quickly and therefore more frequently
3. the mechanism of the positive chronotropic effects is INC If, the inward Na+ current that is responsible for phase 4 depolarization in the SA node
Describe the mechanism of positive dromotropic effect.
1. INC conduction velocity through the AV node
2. AP are conducted more rapidly from the atria to the ventricles, and ventricular filling may be compromised
3. DEC the PR interval
4. the mechanism of the positive dromotropic effect is INC inward Ca2+ current
what is the sarcomere?
1. is the contractile unit of the myocardial cell
2. is similar to the contractile unit in skeletal muscle
3. runs from Z line to Z line
4. contains thick filaments (myosin) and thin filaments (actin, troponin, tropomyosin)
5. as in skeletal muscle, shortening occurs according to a sliding filament model, which states that thin filaments slide along adjacent thick filaments by forming and breaking cross-bridges between actin and myosin
What are intercalated disks?
1. occur at the ends of the cells
2. maintain cell-to-cell cohesion
What are gap junctions?
1. are present at the intercalated disks
2. are low-resistance paths between cells that allow for rapid electrical spread of APs
3. account for the observation that the heart behaves as an electrical syncytium
What is the role of mito in the heart?
are more numerous in cardiac muscle than in skeletal muscle
What is the role of T tubules in the heart?
1. are continuous with the cell membrane
2. invaginate the cells at the Z lines and carry AP into the cell interior
3. are well developed in the ventricles, but poorly developed in the atria
4. form dyads with the SR
What is the role of the SR in the heart?
1. are small-diameter tubules in close proximity to the contractile elements
2. are the site of storage and release of Ca2+ for excitation-contraction coupling
What are the steps in excitation-contraction coupling?
1. the AP spreads from the cell membrane into the T tubules
2. during the plateau of the AP, Ca2+ conductance is INC and Ca2+ enters the cell from the ECF (inward Ca2+ current)
3. this Ca2+ entry triggers the release of even more Ca2+ from the SR (Ca2+ induced Ca2+ release)
a. the amount of Ca2+ released from the SR depends on the amount of Ca2+ previously stored and on the size of the inward Ca2+ current during the plateau of the AP
4. as a result of this Ca2+ release, intracellular [Ca2+] INC
5. Ca2+ binds to troponin C and tropomyosin is moved out of the way, removing the inhibition of actin and myosin binding
6. actin and myosin bind, the thick and thin filaments slide past each other and the myocardial cell contracts, the magnitidue of the tension that develops is proportional to the intracellular [Ca2+]
7. relaxation occurs when Ca2+ is reaccumulated by the SR by an active Ca2+-ATPase pump
Describe the contractility of the heart.
1. is the intrinsic ability of cardiac muscle to develop force at a given muscle length
2. is also called inotropism
3. is related to the intracellular Ca2+ concentration
4. can be estimated by the ejection fraction (stroke volume/end-diastolic volume) which is normally 0.55 (55%)
5. positive inotropic agents produce an INC in contractility
6. negative inotropic agents produce a DEC in contractility
How does INC hear rate INC contractility?
1. when more APs occur per unit time, more Ca2+ enters the myocardial cells during the AP plateaus, more Ca2+ is released from the SR and greater tension is produced during contraction
2. examples of the effect of INC heart rate are:
a. positive staircase-INC heart rate INC the force of contraction in a stepwise fashion as the intracellular [Ca2+] Inc cumulatively over several beats
b. postextrasystolic potentiation-the beat that occurs after an extrasystolic beat has INC force of contraction because extra Ca2+ entered the cells during the extrasystole
How does sympathetic stimulation via beta-1 receptors INC contractility?
1. it INC the inward Ca2+ current during the plateau of each cardiac AP
2. it INC the activity of the Ca2+ pump of the SR (by phosphorylation of phospholamban) as a result, more Ca2+ is accumulated by the SR and thus more Ca2+ is available for release in subsequent beats
How does cardiac glycosides (digitalis) INC contractility?
1. INC the force of contraction by inhibiting Na/K+ ATpae in the myocardial cell membrane
2. as a result of this inhibition the intracellular [Na] INC, diminishing the Na+ gradient across the cell membrane
3. Na/Ca exchange depends on the size of the Na+ gradient and thus is dimished, producing an INC in intracellular [Ca2+]
How does parasympathetic stimulation via muscarinic receptors DEC contractility?
DEC the force of contraction in the atria by DECing the inward Ca2+ current during the plateau of the cardiac AP
Describe the length-tension relationship in the ventricles.
1. describe the effect of ventricular muscle cell length on the force of contraction
2. is similar to the relationship in skeletal muscle
What is preload?
1. is end-diastolic volume which is related to right atrial pressure
2. when venous return INC, end-diastolic volume INC and stretches or lengthens the ventricular muscle fibers
What is afterload?
1. for the left ventricle is aortic pressure, INC in aortic pressure cause an INC in afterload on the left ventricle
2. for the right ventricle is pulmonary artery pressure, INC in pulmonary artery pressure cause an INC in afterload on the right ventricle
What is the importance of sarcomere length?
1. determines the max number of cross-brdiges that can form between actin and myosin
2. determines the max tension, or force of contraction
Describe the velocity of contraction at a fixed muscle length.
1. is maximal when the afterload is zero
2. is DEC by INC in afterload
Describe the Frank-Starling relationship.
1. describes the INC in stroke volume and CO that occur in response to an INC in venous return or end-diastolic volume
2. is based ont eh length-tension relationship in the ventricle, INC in end-diastolic volume cause an INC in ventricular fiber length, which produces an INC in developed tension
3. is the mechanism that matches CO to venous return, the greater the venous return, the greater the CO
4. changes in contractility shift the Frank-Starling curve upward (INC contractility) or downward (DEC contractility)
What happens with INC or DEC in contractility?
1. INC in contractility cause an INC in Co for any level of right atrial pressure or end-diastolic volume
2. DEC in contractility cause a DEC in CO for any level of right atrial pressure or end-diastolic volume
What is a ventricular pressure-volume loop?
1. are constructed by combining systolic and diastolic pressure curves
2. the diastolic pressure curve is the relationship between diastolic pressure and diastolic volume in the ventricle
3. the systolic pressure curve is the corresponding relationship between systolic pressure and systolic volume in the ventricle
4. a single left ventricular cycle of contraction, ejection, relaxation, and refilling can be visualized by combining the two curves into a pressure-volume loop
Describe the isovolumetric contraction phase on the pressure-volume loop.
the cycle begins during diastole at point 1, the left ventricle is filled with blood from the left atrium and its volume is about 140 mL (end-diastolic volume), ventricular pressure is low because the ventricular muscle is relaxed, on excitation, the ventricle contracts and ventricular pressure INC, the mitral valve closes when left ventricular pressure is greater than left atrial pressure, because all valves are closed no blood can be ejected from the ventricle (isovolumetric)
Describe the ventricular ejection phase on the P-V loop.
the aortic valve at point 2 when pressure in the left ventricle exceeds pressure in the aorta, blood is ejected into the aorta, and ventricular volume DEC, the volume that is ejected in this phase is the stroke volume, thus stroke volume can be measured graphically by the width of the P-V loop, the volume remaining in the left ventricle at point 3 is end-systolic volume
Describe isovolumetric relaxation phase on the P-V loop.
at point 3, the ventricle relaxes, when ventricular pressure DEC to less than aortic pressure, the aortic valve closes, because all of the valves are closed again, ventricular volume is constant (isovolumetric) during this phase
Describe ventricular filling phase on the P-V loop.
once the left ventricular pressure DEC to less than left atrial pressure, the mitral (AV) valve opens and filling of the ventricle begins, during this phase, ventricular volume INC to about 140 mL (end-diastolic volume)
How does INC preload cause a change in ventricular P-V loop?
1. refers to an INC in end-diastolic volume and is the result of INC venous return
2. causes an INC in stroke volume based on the Frank-Starling relationship
3. the INC in stroke volume is reflected in INC width of the P-V loop
How does INC afterload cause a change in the ventricular P-V loop?
1. refers to an INC in aortic pressure
2. the ventricle must eject blood against a higher pressure, resulting in a DEC in stroke volume
3. the DEC in stroke volume is reflected in DEC width of the P-V loop
4. the DEC in stroke volume results in an INC in end-systolic volume
How does INC contractility cause a change in the ventricular P-V loop?
1. the ventricle develops greater tension than usual during systole, causing an INC in stroke volume
2. the INC in stroke volume results in a DEC in end-systolic volume
What is a cardiac and vascular function curve?
are simultaneous plots of CO and venous return as a function of right atrial pressure or end-diastolic volume
Describe the cardiac function (CO) curve.
1. depicts the Frank-Starling relationship for the ventricle
2. shows that CO is a function of end-diastolic volume
Describe the vascular function (venous return) curve.
depicts the relationship between blood flow through the vascular system (or venous return) and right atrial pressure
Describe mean systemic pressure.
1. is the point at which the vascular function curve intersects the x-axis
2. equals right atrial pressure when there is no flow in the CV system
3. is measured when the heart is stopped experimentally, under these conditions, CO and venous return are 0 and pressure is = throughout the CV system
How is mean systemic pressure INC?
by an INC in blood volume or by a DEC in venous compliance (where blood is shifted from the veins to the arteries), an INC in mean systemic pressure is reflected in a shift of the vascular function curve to the right
How is mean systemic pressure DEC?
by a DEC in blood volume or by an INC in venous compliance (where blood is shifted from the arteries to the veins), a DEC in mean systemic pressure is reflected in a shift of the vascular function curve to the left
What determines the slope of the venous return curve?
determined by the resistance of the arterioles
What does a clockwise rotation of the venous return curve indicate?
indicates a DEC in total peripheral resistance (TPR), when TPR is DEC for a given right atrial pressure, there is an INC in venous return (i.e. vasodilation of the arterioles allows more blood to flow from the arteries to the veins and back to the heart)
What does a counterclockwise rotation of the venous return curve indicate?
indicates an INC in TRP, when TPR is INC for a given right atrial pressure, there is a DEC in venous return to the heart (i.e. vasoconstriction of the arterioles DEC blood flow from the arteries to the veins and back to the heart)
What is the significance of combining CO and venous return curves?
1. the point at which the two curves intersect is the equilibrium, or steady-state, point, equilibrium occurs when CO equals venous return
2. CO can be changed by altering the CO curve, the venous return curve or both curves simultaneously, the superimposed curves can be used to predict the direction and magnitude of changes in CO
What effect does positive inotropic agents (digitalis) have on CO curve?
1. produce INC contractility and INC CO
2. the equilibrium or intersection point shifts to a higher CO and a correspondingly lower right atrial pressure
3. right atrial pressure DEC because more blood is ejected from the heart on each beat (INC stroke volume)
What effect does negative inotorpic agents have on CO curve?
produce DEC contractility and DEC CO
what effect does INCing blood volume or DECing venous compliance have on venous return curve?
INC mean systemic pressure, shifting the venous return curve to the right in a parallel fashion, a new equilibrium or intersection point is established at which both CO and right atrial pressure are INC
What effect does DECing blood volume (hemorrhage) or INC in venous compliance have on venous return curve?
DEC mean systemic pressure and a shift of the venous return curve to the left in a parallel fashion, a new equilibrium point is established at which both CO and right atrial pressure are DEC
What do changes in TPR do to the CO and venous return curves?
changes in TPR alter both curves simultaneously
What happens with INCing TPR?
1. causes a DEC in both CO and venous return
2. counterclockwise rotation of the venous return curve, INC TPR results in DEC venous return as blood is retained on the arterial side
3. downward shift of the CO curve is caused by the INC aortic pressure (INC afterload) as the heart pumps against a higher pressure
4. as a result of these simultaneous changes, a new equilibrium point is established at which both CO and venous return are DEC, but right atrial pressure is unchanged
What happens to the CO and venous return cruves with DECing TPR?
1. cause3s an INC in both Co and venous return curves
2. a clockwise rotation of the venous return curve occurs, DEC TPR results in INC venous return as more blood is allowed to flow back to the heart from the arterial side
3. an upward shift of the Co curve is caused by the DEC aortic pressure (DEC afterload) as the heart pumps against a lower pressure
4. as a result of these simultaneous changes, a new equilibrium point is established at which both Co and venous return are INC, but right atrial pressure is unchanged
What is stroke volume and how is it calculated?
1. is the volume ejected form the ventricle on each beat
2. stroke volume = end-diastolic volume – end-systolic volume
How is CO calculated?
CO = stroke volume * heart rate
What is ejection fraction and how is it calculated?
1. is the fraction of the end-diastolic volume ejected in each stroke volume
2. is related to contractility
3. is normally 0.55 or 55%
4. ejection fraction = stroke volume / end-diastolic volume
What is stroke work and how is it calculated?
1. is the work the heart performs on each beat
2. is equal to pressure * volume, for the left ventricle, pressure is aortic pressure and volume is stroke volume
3. stroke work = aortic pressure * stroke volume
What is O2 consumption of the heart?
1. is directly related to the amount of tension developed by the ventricles
2. INC by:
a. INC afterload (INC aortic pressure)
b. INC size of the heart (Laplace’s law states that tension is proportional to the radius of a sphere)
c. INC contractility
d. INC heart rate
What is the Fick principle?
used for measuring CO
CO = O2 consumption / (O2pulmonary vein – O2pulmonaryartery)
How are the values for the Fick principle obtained?
1. O2 consumption is for the whole body
2. pulmonary vein O2 is measure in a peripheral artery
3. pulmonary artery O2 is measured in systemic mixed venous blood
What is atrial systole during the cardiac cycle?
1. is preceded by the P wave, which represents electrical activation of the atria
2. contributes to, but is not essential for, ventricular filling
3. the INC in atrial pressure (venous pressure) caused by atrial systole is the a wave on the venous pulse curve
4. filling of the ventricle by atrial systole causes the fourth heart sound, which is not audible in normal adults
What is isovolumetric ventricular contraction during the cardiac cycle?
1. begins after the onset of the QRS wave which represents electrical activation of the ventricles
2. when ventricular pressure beomces greater than atrial pressure, the AV valves close, their closure corresponds to the first heart sound, because the mitral valve closes before the tricuspid valve, the first heart sound may be split
3. ventricular pressure INC isovolumetrically as a result of ventricular contraction, however no blood leaves the ventricle during this phase because the aortic valve is closed
What is rapid ventricular ejection during the cardiac cycle?
1. ventricular pressure reaches its maximum value during this phase
2. when ventricular pressure becomes greater than aortic pressure, the aortic valve opens
3. rapid ejection of blood into the aorta occurs because of the pressure gradient between the ventricle and the aorta
4. ventricular volume DEC dramatically because most of the stroke volume is ejected during this phase
5. atrial filling begins
6. the onset of the T wave, which represents repolarization of the ventricles marks the end of both ventricular contraction and rapid ventricular ejection
Describe reduced ventricular ejection during the cardiac cycle.
1. ejection of blood from the ventricle continues, but is slower
2. ventricular pressure begins to DEC
3. aortic pressure also DEC because of the runoff of blood form large arteries into smaller arteries
4. atrial filling continues
Describe isovolumetric ventricular relaxation during the cardiac cycle.
1. repolarization of the ventriles is now complete (end of the T wave)
2. the aortic valve closes, followed by closure of the pulmonic valve, closure of the semilunar valves corresponds to the second heart sound, inspiration causes splitting of the second heart sound
3. the AV valves remain closed during most of this phase
4. ventricular pressure DEC rapidly because the ventricle is now relaxed
5. ventricular volume is constant (isovolumetric) because all of the valves are closed
6. the blip in the aortic pressure tracing occurs after closure of the aortic valve and is called the dicrotic notch or incisura
7. when ventricular pressure becomes less than atrial pressure, the mitral valve opens
Describe the rapid ventricular filling phase during the cardiac cycle.
1. the mitral valve is open and ventricular filling from the atrium begins
2. aortic pressure continues to DEC because blood continues to run off into the smaller arteries
3. rapid flow of blood from the atria into the ventricles causes the third heart sound, which is normal in children but in adults is associated with disease
Describe the reduced ventricular filling (diastasis) phase during the cardiac cycle.
1. is the longest phase of the cardiac cycle
2. ventricular filling continues, but at a slower rate
3. the time required for diastasis and ventricular filling depends on heart rate, INC in heart rate DEC the time available for ventricular filling
what is the most important mechanism for regulating arterial pressure?
is a fast, neurally mediated baroreceptor mechanism and a slower, hormonally regulated renin-angiotensin-aldosterone mechanism
What is the baroreceptor reflex?
1. includes fast, neural mechanisms
2. is a negative feedback system that is responsible for the minute-to-mintue regulation of arterial blood pressure
3. barorceptors are stretch receptors located within the walls of the carotid sinus near the bifurcation of the common carotid arteries
What is the first step in the baroreceptor reflex?
a DEC inarterial pressure DEC stretch on the walls of the carotid sinus
1. because the baroreceptors are most sensitive to changes in arterial pressure, rapidly DECing arterial pressure produces the greatest response
2. additional baroreceptors in the aortic arch respond to INC but not to DEC in arterial pressure
What is the second step in the baroreceptor reflex?
DEC stretch DEC the firing rate of the carotid sinus nerve [Hering’s nerve, CN IX], which carries information to the vasomotor center in the brainstem
What is the third step in the baroreceptor reflex?
the set point for mean arterial pressure in the vasomotor center is about 100 mm Hg, therefore if mean arterial pressure is less than 100 mm Hg, a series of autonomic responses is coordinated by the vasomotor center, these changes will attempt to INC blood pressure toward normal
What is the fourth step in the baroreceptor reflex?
the responses of the vasomotor center to a DEC in mean arterial blood pressure are coordinated to INC the arterial pressure to 100 mm Hg, the responses are DEC parasympathetic (vagal) outflow to the heart and INC sympathetic outflow to the heart and blood vessels
What four effects attempt to INC the arterial pressure to normal?
1. INC heart rate, resulting from DEC parasympathetic tone and INC sympathetic tone to the SA node of the heart
2. INC contractility and stroke volume, resulting from INC sympathetic tone to the heart, together the INC in heart rate, the INC in contractility and stroke volume produce an INC in CO that INC arterial pressure
3. INC vasoconstriction of arterioles, resulting from the INC sympathetic outflow, as a result, TPR and arterial pressure will INC
4. INC vasoconstriction of veins (venoconstriction), resulting from the INC sympathetic outflow, constriction of the veins causes a DEC in unstressed volume and an INC in venous return to the heart, the INC in venous return causes an INC in CO by the Frank-Starling mechanism
Describe the Valsalva maneuver.
1. the integrity of the baroreceptor mechanism can be tested with the valsalva maneuver (expiring against a closed glottis)
2. expiring against a closed glottis causes an INC in intrathoracic pressure which DEC venous return
3. the DEC in venous return causes a DEC in CO and arterial pressure (Pa)
4. if the barorceptor reflex is intact, the DEC in Pa is sensed by the baroreceptors, leading to an INC in sympathetic outflow to the heart and blood vessels, in the test an INC in heart rate would be noted
5. when the person stops the maneuver, there is a rebound INC in venous return, CO and Pa, the INC in Pa is ensed by the baroreceptors, which direct a DEC in heart rate
Describe the renin-angiotensin-aldosterone system in regulating blood pressure.
1. is a slow, hormonal mechanism
2. is used in long-term BP regulation by adjustment of blood volume
3. renin is an enzyme
4. angiotensin I is inactive
5. angiotensin II is physiologically active
6. angiotensin II is degraded by angiotensinase, one of the peptide fragments, angiotensin III, has some of the biologic activity of angiotensin II
What are the steps involved in the renin-angiotensin-aldosterone system?
1. a DEC in renal perfusion pressure causes the juxtaglomerular cells of the afferent arteriole to secrete renin
2. renin is an enzyme that catalyzes the conversion of angiotensinogen to angiotensin I in plasma
3. angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II, primarily by the lungs
What enzymes block conversion of angiotensin I to angiotensin II?
1. ACE inhibitors (e.g. captopril) block the conversion of angiotensin I to angiotensin II and therefore DEC BP
2. angiotensin receptor (AT1) antagonists (e.g. loartan) block the action of angiotensin II at its receptor and DEC blood pressure
What are the effects of angiotensin II?
1. stimulates the synthesis and secretion of aldosterone by the adrenal cortex
a. aldosterone INC Na+ reabsorption by the renal distal tubule, thereby INCing ECF volume, blood volume, and arterial pressure
b. this action of aldosterone is slow because it requires new protein synthesis
2. it INC Na+-H+ exchange in the proximal convoluted tubule
a. this action of antiotensin II directly INC Na+ reabsorption, complementing the indirect stimulation of Na+ reabsorption via aldosterone
b. this action of angiotensin II leads to contraction alkalosis
3. it INC thirst
4. it causes vasoconstriction of the arterioles thereby INCing TPR and arterial pressure
What happens to regulating arterial blood pressure with cerebral ischemia?
1. when the brain is ischemic, the partial pressure of CO2 in brain tissue INC
2. chemoreceptors in the vasomotor center respond by INCing sympathetic outflow to the heart and blood vessels
a. constriction of arterioles causes intense peripheral vasoconstriction and INC TPR, blood flow to other organs is significantly reduced in an attempt to preserve blood flow to the brain
b. MAP can INC to life-threatening levels
3. the Cushing reaction is an example of the response to cerebral ischemia
Describe Cushing reaction.
INCs in intracranial pressure cause compression of the cerebral blood vessels, leading to cerebral ischemia and INC cerebral PCO2, the vasomotor center directs an INC in sympathetic outflow to the heart and blood vessels, which causes a profound INC in arterial pressure
Describe chemoreceptors in the carotid and aortic bodies.
1. are located near the bifurcation of the common carotid arteries and along the aortic arch
2. have very high rates of O2 consumption and are very sensitive to DEC in the partial pressure of O2
3. DEC in PO2 activate vasomotor centers that produce vasoconstriction an INC in TPR and an INC in arterial pressure
Describe vasopressing (ADH).
1. is involved in the regulation of BP in response to hemorrhage, but not in minute-to-minute regulation of normal BP
2. atrial receptors respond to a DEC in blood volume and cause the relase of vasopressin from the posterior pituitary
3. vasopressin has two effects that tend to INC BP toward normal
What are the effects of vasopressin on BP regulation?
1. it is a potent vasoconstrictor that INC TPR by activating V1 receptors on the arterioles
2. it INC water reabsorption by the renal distal tubule and collecting ducts by activating V2 receptors
Describe atrial natriuretic peptide (ANP).
1. is released from the atria in response to an INC in blood volume and atrial pressure
2. causes relaxation of vascular smooth muscle, dilation of the arterioles and DEC TPR
3. causes INC excretion of Na+ and water by the kidney which reduces blood volume and attempts to bring arterial pressured down to normal
4. inhibits renin secretion
Describe the structure of the capillary beds.
1. metarterioles branch into the capillary beds, at the junction of the arterioles and capillaries is a smooth muscle band called the precapillary sphincter
2. true capillaries do not have smooth muscle, they consist of a single layer of endothelial cells surrounded by a basement membrane
3. clefts (pores) between the endothelial cells allow passage of water-soluble substances, the clefts represent a very small fraction of the SA (< 0.1%)
4. blood flow through the capillaries is regulated by contraction and relaxation of the arterioles and the precapillary sphincters
Describe the passage of lipid-soluble substances through the capillary wall.
1. corss the membranes of the capillary endothelial cells by simple diffusion
2. include O2 and CO2
Describe the passage of small water-soluble substances through the capillary wall.
1. corss via the water-filled clefts between the endothelialc cells
2. include water, glucose and amino acids
3. generally, protein molecules are too large to pass freely through the clefts
4. in the brain, the clefts between endothelial cells are exceptionally tight (blood-brain barrier)
5. in the liver and intestine the clefts are exceptionally wide and allow passage of protein, these capillaries are called sinusoids
Describe the passage of large water-soluble substances throught the capillary wall.
can cross by pinocytosis
What is the starling equation?
Jv = Kf * [(Pc – Pi) – (pi c – pi i)]
where Jv = fluid movement, Kf = hydraulic conductance, Pc = capillary hydrostatic pressure, Pi = interstitial hydrostatic pressure, pi c = capillary oncotic pressure, pi i = interstitial oncotic pressure
Describe the values of Jv in the starling equation?
1. when Jv is positive, there is net fluid movement out of the capillary (filtration)
2. when Jv is negative, there is net fluid movement into the capillary (absorption)
Describe the values of Kf.
it is the hydraulic conductance (water permeability) of the capillary wall
Decribe the values of Pc.
1. an INC in Pc favors filtration out of the capillary
2. Pc is determined by arterial and venous pressures and resistances
3. an INC in either arterial or venous pressure produces an INC in Pc, INC in venous pressure have a greater effect on Pc
4. Pc is higher at the arteriolar end of the capillary than at the venous end (except in glomerular capillaries, where it is nearly constant)
Describe the values of Pi.
1. an INC in Pi opposes filtration out of the capillary
2. it is normally close to 0 mm Hg (or it is slightly negative)
Describe the values of pi c.
1. an INC in pi c opposes filtration out of the capillary
2. pi c is INC by INC in the protein concentration in the blood (dehydration)
3. pi c is DEC by DEC in the protein concentration in the blood (e.g. nephritic syndrome, protein malturation, liver failure)
4. small solutes do not contribute to pi c
Describe the values of pi i.
1. an INC in pi i favors filtration out of the capillary
2. pi i is dependent on the protein concentration of the interstitial fluid, which is normally quite low because very little protein is filtered
What factors INC filtration?
1. INC Pc-caused by INC arterial or venous pressure
2. DEC Pi
3. DEC pi c-caused by DEC protein concentration in the blood
4. INC pi i-caused by inadequate lymphatic function
What is the function of lymph?
1. normally, filtration of fluid out of the capillaries is slightly greater than absorption of fluid into the capillaries, the excess filtered fluid is returned to the circulation via the lymph
2. lymph also returns any filtered protein to the circulation
Describe the unidirectional flow of lymph.
1. one-way flap valves permit interstitial fluid to enter, but not leave, the lymph vessels
2. flow through larger lymphatic vessels is also unidirectional and is aided by one-way valves and skeletal muscle contraction
Describe edema.
1. occurs when the volume of interstitial fluid exceeds the capacity of the lymphatics to return it to the circulation
2. can be caused by excess filtration or blocked lymphatics
Describe endothelium-derived relaxing factor (EDRF).
1. is produced in the endothelial cells
2. causes local relaxation of vascular smooth muscle
3. mechanism of action involves the activation of guanylate cyclase and production of cGMP
4. one form of EDRF is NO
5. circulating ACh causes vasodilation by stimulating the production of NO in vascular smooth muscle
Describe the autoregulation method of local intrinsic control of blood flow.
1. blood flow to an organ remains constant over a wide range of perfusion pressures
2. organs that exhibit autoregulation are the heart, brain and kidney
3. for example-if perfusion pressure to the heart is suddenly DEC, compensatory vasodilation of the arterioles will occur to maintain a constant flow
Describe the active hyperemia method of local intrinsic control of blood flow.
1. blood flow to an organ is proportional to its metabolic activity
2. for example-if metabolic activity in skeletal muscle INC as a result of strenuous exercise, blood flow to the muscle will INC proportionately to meet metabolic demands
Describe the reactive hyperemia method of local intrinsic control of blood flow.
1. is an INC in blood flow to an organ that occurs after a period of occlusion of flow
2. the longer the period of occlusion is, the greater the INC in blood flow is above preocclusion levels
What is the myogenic hypothesis that explains local control of blood flow?
1. explains autoregulation, but not active or reactive hyperemia
2. is based on the observation that vascular smooth muscle contracts when it is stretched
3. for example-if perfusion pressure to an organ suddenly INC, the arteriolar smooth muscle will be stretched and will contract, the resulting vasoconstriction will maintain a constant flow (without vasoconstriction, blood flow would INC as a result of the INC pressure)
what is the metabolic hypothesis that explains local control of blood flow?
1. is based on the observation that the tissue supply of O2 is matched to the tissue demand for O2
2. vasodilator metabolites are produced as a result of metabolic activity in tissue, these vasodilators are CO2, H+, K+, lactate and adenosine
What are some examples of active hyperemia?
1. if the metabolic activity of a tissue INC both the demand for O2 and the production of vasodilator metabolites INC, these metabolites cause arteriolar vasodilation, INC blood flow and INC O2 delivery to the tissue to meet demand
2. if blood flow to an organ suddenly INC as a result of a spontaneous INC in arterial pressure then more O2 is provided for metabolic activity, at the same time, the INC flow “washes out” vasodilator metabolites, as a result of this washout arteriolar vasoconstriction occurs, resistance INC, and blood flow is DEC to normal
Describe sympathetic innervation of vascular smooth muscle.
1. INC in sympathetic tone cause vasoconstriction
2. DEC in sympathetic tone cause vasodilation
3. the density of sympathetic innervation varies widely among tissues, skin has the greatest innervation, whereas coronary, pulmonary and cerebral vessels have little innervation
Describe histamine.
1. causes arteriolar dilation and venous constriction, the combined effects of arteriolar dilation and venous constriction cause INC Pc and INC filtration out of the capillaries resulting in local edema
2. is release in response to tissue trauma
Describe bradykinin.
1. causes arteriolar dilation and venous constriction
2. produces INC filtration out of the capillaries (similar to histamine) and causes local edema
Describe serotonin (5-hydroxytryptamine).
1. causes arteriolar constriction and is released in response to blood vessel damage to help prevent blood loss
2. has been implicated in the vascular spasms of migraine headaches
Describe prostaglandins.
1. prostacyclin is a vasodilator in several vascular beds
2. E-series prostaglandins are vasodilators
3. F-series prostaglandins are vasoconstrictors
4. thromboxane A2 is a vasoconstrictor
Describe coronary circulation.
1. is controlled almost entirely by local metabolic factors
2. exhibits autoregulation
3. exhibits active and reactive hyperemia
4. the most important local metabolic factors are hypoxia and adenosine
5. for example-INC in myocardial contractility are accompanied by an INC demand for O2, to meet this demand, compensatory vasodilation of coronary vessels occurs and both blood flow and O2 delivery to the contracting heart muscle INC (active hyperemia)
6. durings systole, mechanical compression of the coronary vessels reduces blood flow, after the period of occlusion, blood flow INC to repay the O2 debt
7. sympathetic nerves play a minor role
Describe cerebral circulation.
1. is controlled almost entirely by local metabolic factors
2. exhibits autoregulation
3. exhibits active and reactive hyperemia
4. the most important local vasodilator for the cerebral circulation is CO2, INC in PCO2 cause vasodilation of the cerebral arterioles and INC blood flow to the brain
5. sympathetic nerves play a minor role
6. vasoactive substances in the systemic circulation have little or no effect on cerebral circulation because such substances are excluded by the BBB
Describe the sympathetic innervation of skeletal muscle.
1. is the primary regulator of blood flow to the skeletal muscle at rest
2. the arterioles of skeletal muscle are densely innervated by sympathetic fibers, the veins also are innervated but less densely
3. there are both alpha1 and beta2 receptors on the blood vessels of skeletal muscle
4. stimulation of alpha1 receptors causes vasoconstriction
5. stimulation of beta2 receptors causes vasodilation
6. the state of constriction of skeletal muscle arterioles is a major contributor to the TPR (because of the large mass of skeletal muscle)
Describe the local metabolic control of skeletal muscle.
1. blood flow in skeletal muscle exhibits autoregulation and active and reactive hyperemia
2. demand for O2 in skeletal muscle varies with metabolic activity level and blood flow is regulated to meed demand
3. during exercise when demand is high, these local metabolic mechanisms are dominant
4. the local vasodilator substances are lactate, adenosine and K+
5. mechanical effects during exercise temporarily compress the arteries and DEC blood flow, during the postocclusion period, reactive hyperemia INC blood flow to repay the O2 debt
Describe the innervation to the skin.
1. has extensive sympathetic innervation, cutaneous blood flow is under extrinsic control
2. temperature regulation is the principal function of the cutaneous sympathetic nerves, INC ambient temperature leads to cutaneous vasodilation, allowing dissipation of excess body heat
3. trauma produces the triple response in skin, a red line, a red flare and a wheal, a wheal is local edema that results from the local release of histamine, which INC capillary filtration
What are the following changes that occur when an individual moves from a supine position to a standing position?
1. when a person stands, a significant volume of blood pools in the lower extremities because to the high compliance of the veins (muscular activity would prevent this pooling
2. as a result of venous pooling and INC local venous pressure Pc in the legs INC and fluid is filtered into the interstitium, if net filtration of fluid exceeds the ability of the lymphatics to return it to the circuklation, edema will occur
3. as a result of the DEC in venous return both stroke volume and CO DEC
4. arterial pressure DEC because of the reduction in CO, if cerebral blood pressure becomes low enough, fainting may occur
5. compensatory mechanisms will attempt to INC BP to normal, the carotid sinus baroreceptors respond to the DEC in arterial pressure by DECing the firing rate of the carotid sinus nerves, a coordinated response from the vasomotor center that INC sympathetic outflow to the heart and blood vessels and DEC parasympathetic outflow tot eh heart, as a restul, heart rate, contractility, TPR and venous return INC and BP INC toward normal
What is orthostatic hypotension?
fainting or lightheadedness on standing, may occur in individuals whose baroreceptor reflex mechanism is impaired
What effect does the central command (anticipation of exercise) have on the body during exercise?
1. originate in the motor cortex or from reflexes initiated in muscle proprioceptors when exercise is anticipated
2. sympathetic outflow to the heart and blood vessels is INC, at the same time, parasympathetic outflow to the heart is DEC, as a result, heart rate and contractility (stroke volume) are INC and unstressed volume is DEC
3. CO is INC, primarily as a result of the INC heart rate and to a lesser extent the INC stroke volume
4. venous return is INC as a result of muscular activity and venoconstriction, INC venous return provides more blood for each stroke volume
5. arteriolar resistance in the skin, splanchnic regions, kidneys and inactive muscles is INC, accordingly blood flow to these organs is DEC
What effect does INC metabolic activity of skeletal muscle have on the body during exercise?
1. vasodilator metabolites (lactate, K+ and adenosine) accumulate because of INC metabolism of the exercising muscle
2. thee metabolistes cause arteriolar dilation in the active skeletal muscle, thus INCing skeletal muscles blood flow (active hyperemia)
3. as a result of the INC blood flow, O2 delivery to the muscle is INC, the number of perfused capillaries is INC so that the diffusion distance for O2 is DEC
4. this vasodilation accolunts for the overall DEC in TPR that occurs with exercise, note that activation of the SNS alone (by the central command) would cause an INC in TPR
What are the compensatory responses to acute blood loss?
1. a DEC in blood volume produces a DEC in mean systemic pressure, as a result there is a DEC in both CO and arterial pressure
2. the carotid sinus baroreceptors detect the DEC in arterial pressure, as a result of the baroreceptor reflex, there is INC sympathetic outflow to the heart and blood vessels and DEC parasympathetic outflow to the heart and blood vessels and DEC parasympathetic outflow to the heart producting INC heart rate, INC contractility, INC TPR (due to arteriolar constriction), venoconstriction, which INC venous return, constriction of arterioles in skeletal, splanchnic and cutaneous vascular beds, however it does not occur in coronary or cerebral vascular beds, ensuring that adequate blood flow will be maintained to the heart and brain, these responses attempt to restore normal arterial BP
3. chemoreceptors in the carotid and aortic bodies are very sensitivei to hypoxia, they supplement the baroreceptor mechanism by INCing sympathetic outflow to the heart and blood vessels
4. cerebral ischemia causes an INC PCO2 which activates chemoreceptors in the vasomotor center to INC sympathetic outflow
5. arteriolar vasoconstriction causes a DEC in Pc, as a result capillary absorption is favored which helps to restore circulating blood volume
6. the adrenal medulla releases epinephrine and NE, which supplement the actions of the SNS on the heart and blood vessels
7. the renin-angiotensin-aldosterone system is activated by the DEC in renal prefusion pressure, because angiotensin II is a potent vasoconstrictor, it reinforces the stimulatory effect of the SNS on TPR, aldosterone INC NaCl reabsorption in the kidney, INCing the circulating blood volume
8. ADH is released when atrial receptors detect the DEC in blood volume, ADH causes both vasoconstriction and INC water reabsorption, both of which tend to INC BP
What is tidal volume?
is the volume inspired or expired with each normal breath
What is inspriatory reserve volume?
is the volume that can be inspired over and above the tidal volume, is used during exercise
What is the expiratory reserve volume?
is the volume that can be expired after the expiration of a tidal volume
What is residual volume?
is the volume that remains in the lungs after a maximal expiration, cannot be measured by spirometry
What is anatomic dead space?
is the volume of the conducting airways, is normally approx. 150 mL
What is physiologic dead space?
1. is a functional measurement
2. is defined as the volume of the lungs that dos not participate in gas exchange
3. is approx. equal to the anatomic daead space in normal lungs
4. may be greater than the anatomic dead space in lung diseases in which there are ventilation/perfusion defects
How is physiologic dead space calculated?
Vd = Vt * ((PACO2 – PECO2) / PACO2), where Vd = physiologic dead space, Vt = tidal volume, PACO2 = PCO2 of alveolar gas = PCO2 of arterial blood, PECO2 = PCO2 of expired air
How is minute ventilation calculated?
minute ventilation = tidal volume X breaths/min
How is alveolar ventilation calculated?
alveolar ventilation = (tidal volume – dead space) * breaths/min
What is inspiratory capacity?
is the sum of tidal volume and IRV
What is functional residual capacity?
1. is the sum of ERV and residual volume
2. is the volume remaining in the lungs after a tidal volume is expired
3. includes the residual volume so it cannot be measured by spirometry
What is vital capacity, or forced vital capacity (FVC)?
1. is the sum of tidal volume, IRV and ERV
2. is the volume of air that can be forcibly expired after a maximal inspiration
What is total lung capacity?
1. is the sum of all four lung volumes
2. is the volume in the lungs after a maximal inspiration
3. includes residual volume, so it cannot be measured by spirometry
What is forced expiratory volume?
1. FEV is the volume of air that can be expired in the first second of a forced maximal expiration
2. FEV is normally 80% of the forced vital capacity which is expressed as FEV/FVC = 0.8
3. in obstructive lung disease, such as asthma, FEV is reduced more than FVC so that FEV/FVC is DEC
4. in restrictive lung disease, such as fibrosis, both FEV and FVC are reduced and FEV/FVC is either normal or is INC
What are the muscles of inspiration?
1. diaphragm-is the most important muscle for inspiration, when the diaphragm contracts, the abdominal contents are pushed downward and the ribs are lifted upward and outward INCing the volume of the thoracic cavity
2. external intercostal and accessory muscles-are not used for inspiration during normal quiet breathing, are used during exercise and in respiratory distress
What are the muscles of expiration?
1. expiration is normally passive, because the lung-chest wall system is elastic, it returns to its resting position after inspiration
2. expiratory muscles are used during exercise or when airway resistances is INC because of disease (e.g. asthma)
3. abdmonal muscles-compress the abdominal cavity, push the diaphragm up and push air out of the lungs
4. internal intercostal muscles-pull the ribs downward and inward
What is the compliance of the respiratory system?
1. C = V/P, C is compliance, V is volume, P is pressure
2. describes the distensiblity of the lungs and chest wall
3. is inversely related to elastance, which depends on the amount of elastic tissue
4. is inversely related to stiffness
5. is the slope of the pressure-volume curve
6. is the change in volume for a given change in pressure, pressure refers to transmural, or transpulmonary, pressure
Describe compliance of the lungs.
1. transmural pressure is alveolar pressure minus intrapleural pressure
2. when the pressure outside of the lungs is negative the lungs expand and lung volume INC
3. when the pressure outside of the lungs is +, the lungs collapse and lung V DEC
4. inflation of the lungs (inspiration) follows a different curve that deflation of the lung (expiration), this difference is called hysteresis
5. in the middle range of pressures, compliance is greatest and the lungs are most distensible
6. at high expanding pressures, compliance is lowest, the lungs are least distensible and the curve flattens
Describe compliance of the combined lung-chest wall system.
1. compliance of the lung-chest wall system is less than that of the lungs alone or the chest wall alone (the slope is flatter)
2. at rest, lung volume is at FRC and the pressure in the airways and lungs is equal to atmospheric pressure (i.e. zero), under these equilibrium conditions, there is a collapsing force on the lungs and an expanding force on the chest wall, at FRC, these two forces are equal and opposite and therefore the combined lung-chest wall system neither wants to collapse nor expand (i.e. equilibrium)
3. as a result of these two opposing forces, intrapleural pressure is negative
What happens when intrapleural pressure is negative?
if air is introduced into the intrapleural space (pneumothorax) the intrapleural pressure becomes equal to atmospheric pressure, the lungs will collapse (their natural tendency) and the chest wall will spring outward (its natural tendency)
What happens with changes in lung compliance in a patient with emphysema?
lung compliance is INC and the tendency of the lungs to collapse is DEC, therefore, at the original FRC, the tendency of the lungs to collapse is less than the tendency of the chest wall to expand, the lung-chest wall system will seek a next, higher FRC so that the two opposing forces can be balanced, the patient’s chest becomes barrel-shaped, reflecting this higher volume
What happens with changes in lung compliance in a patient with fibrosis?
lung compliance is DEC and the tendency of the lungs to collapse is INC, therefore at the original FRC, the tendency of the lungs to collapse is greater than the tendency of the chest wall to expand, the lung-chest wall system will seek a new, lower FRC so that the two opposing forces can be balanced
Describe surface tension of the alveoli.
1. results from the attractive forces between liquid molecules lining the alveoli
2. creates a collapsing pressurue that is directly proportional to surface tension and inversely proportional to alveolar radius (Laplace’s law), as shown in the following equation: P = 2T / r, where P = collapsing pressure on alveolus (or pressure required to keep alveolus open), T = surface tension and r = radius of alveolus
Describe surface tension in large alveoli.
have low collapsing pressures and are easy to keep open
Describe surface tension of small alveoli.
have high collapsing pressures and are more difficult to keep open, in the absence of surfactant, the small alveoli have a tendency to collapse (atelectasis)
Describe surfactant.
1. lines the alveoli
2. reduces surface tension by disrupting the intermolecular forces between liquid molecules, this reduction in surface tension prevents small alveoli from collapsing and INC compliance
3. is synthestized by type II alveolar cells and consists primarily of the phospholipid dipalmitoyl phsphatidylcholine (DPPC)
4. in the fetus, surfactant synthesis is variable, surfactant may be present as early as gestational week 24 and is almost always present by gestational week 35
5. generally a lecithin:sphingomyelin ratio greater than 2:1 in amniotic fluid reflects mature levels of surfactant
Describe neonatal respiratory distress syndrome.
can occur in premature infants because of the lack of surfactant, the infant exhibits atelectasis (lungs collapse), difficulty reinflating the lungs (as a result of DEC compliance) and hypoxemia (as a result of DEC V/Q)
Describe airflow.
1. is driven by and is directly proportional to the pressure difference between the mouth (or nose) and the alveoli
2. is inversely proportional to airway resistance, thus the higher the airway resistance, the lower the airflow, this inverse relationship is shown in the following equation: Q = changeP / R, where Q = airflow, changeP = pressure gradient, and R = airway resistance
How is resistance of the airways calculated?
R = (8*viscosity*l) / (pi*r^4), where l = length and r = radius
Where is airway resistance resistance?
1. the major site of airway reistance is the medium-sized bronchi
2. the smallest airways would seem to offer the highest resistance, but they do not because of their parallel arrangement
Describe contraction or relaxation of bronchial smooth muscle.
1. changes airway resistance by altering the radius of the airways
2. parasympathetic stimulation, irritants, and the slow-reacting substance of anaphylaxis (asthma) constrict the airways, DEC the radius and INC the resistance to airflow
3. sympathetic stimulation and sympathetic agonists (isoproterenol) dilate the airways via beta2 receptors, INC the radius and DEC resistance to airflow
How does lung volume affect airway resistance?
1. alters airway resistance because of the radial traction exerted on the airways by surrounding lung tissue
2. high lung volumes are associated with greater traction and DEC airway resistance, patients with INC airway resistance (e.g. asthma) learn to breathe at higher lung volumes to offset the high airway resistance associated with their disease
3. low long volumes are associated with less traction and INC airway resistance, even to the point of airway collapse
How does viscosity or density of inspired gas affect airway resistance?
1. changes the resistance to airflow
2. during a deep-sea dive, both air density and resistance to airflow are INC
3. breathing a low-density gas, such as helium, reduces the resistance to airflow
Describe pressures and airflow at rest (before inspiration begins).
1. alveolar pressure = atmospheric pressure, because lung pressures are expressed relative to atmospheric pressure, alveolar pressure is said to be 0
2. intrapleural pressure is negative-the opposing forces of the lungs tyring to collapse and the chest wall trying to expand create a negative pressure in the intrapleural space between them, intrapleural pressure can be measured by a balloon catheter in the esophagus
3. lung volume is the FRC
Describe pressures and airflow during inspiration.
1. the inspiratory muscles contract and cause the volume of the thorax to INC
a. as lung volume INC, alveolar pressure DEC to less than atmospheric pressure (i.e. becomes negative)
b. the pressure gradient between the atmosphere and the alveoli now causes air to flow into the lungs, airflow will continue until the pressure gradient dissipates
2. intraplueral pressure becomes more negative
a. because lung volume INC during inspiration, the elastic recoil strencth of the lungs also INC, as a result, intrapleural pressure becomes even more negative than it was at rest
b. changes in intrapleural pressure during inspiration are used to measure the dynamic compliance of the lungs
3. lung volume INC by one TV
a. at the peak of inspiration, lung volume is the FRC plus one TV
Describe pressure and airflow during expiration.
1. alveolar pressure becomes greater than atmospheric pressure
a. the alveolar pressure becomes greater (i.e. becomes positive) because alveolar gas is compressed by the elastic forces of the lung
b. thus alveolar pressure is now higher than atmospheric pressure
2. intrapleural pressure returns to its resting value during a normal (passive) expiration
a. however during a forced expiration, intraplueral pressure actually becomes positive, this + intrapleural pressure compresses the airways and makes expiration more difficult
b. in chronic obstructive pulmonary disease (COPD) in which airway resistance is INC, patients learn to expire slowly with pursed lips to prevent the airway collapse that may occur with a forced expiration
3. lung volume returns to FRC
Describe asthma.
1. is an obstructive disease in which expiration is impaired
2. is characterized by DEC FVC, DEC FEV and DEC FEV/FVC
3. air that should have been expired is not, leading to air trapping and INC FRC
Describe COPD.
1. is a combination of chronic bronchitis and emphysema
2. is an obstructive disease with INC lung compliance in which expiration is impaired
3. is characterized by DEC FVC, DEC FEV, and DEC FEV/FVC
4. air that should have been expired is not, leading to air trapping, INC FRC, and a barrel shaped chest
What are pink puffers?
primarily emphysema, have mild hypoxemia and because they maintain alveolar ventilation, normocapnia (normal PCO2)
What are blue bloaters?
primarily bronchitis, have severe hypoxemia with cyanosis and because they do not maintain alveolar ventilation, hypercapnia (INC PCO2), they have right ventricular failure and systemic edema
Describe fibrosis.
1. is a restrictive disease with DEC lung compliance in which inspiration is impaired
2. is characterized by a DEC in all lung volumes, because FEV is DEC less than FVC, FEV/FVC is INC (or may be normal)
What is Dalton’s law of partial pressures?
partial pressure = total pressure * fractional gas concentration
What is the partial pressure of H2O in the trachea?
47 mmHg, used when calculating total pressure in humidified tracheal air
Describe partial pressures of O2 and CO2 in inspired air, alveolar air and blood.
approx. 2% of systemic CO hypasses the pulmonary circulation (physiologic shunt), the resulting admixture of venous blood with oxygenated arterial blood makes the PO2 of arterial blood slightly lower than that of alveolar air
How is concentration of dissolved gases calculated?
dissolved [gas] = Pgas X solubility of gas in blood, the amount of gas dissolved in a solution (such as blood) is proportional to its partial pressure
Describe the diffusion of gases such as O2 and CO2.
the diffusion rates of O2 and CO2 depend on the partial pressure differences across the membrane and the area available for diffusion, for example the diffusion of O2 from alveolar air into the pulmonary capillary depends on the partial pressure difference for O2 between alveolar air and pulmonary capillary blood, normally capillary blood equilibrates with alveolar gas, when the partial pressures of O2 become equal, then there is no more net diffusion of O2
Describe perfusion-limited exchange.
1. is illustrated by N2O and by O2 under normal conditions
2. in perfusion-limited exchange, the gas equilibrates early along the length of the pulmonary capillary, the partial pressure of the gas in arterial blood becomes equal to the partial pressure in alveolar air
3. thus, for a perfusion-limited process, diffusion of the gas can be INC only if blood flow INC
Describe diffusion-limited exchange.
1. is illustrated by CO and by O2 during strenuous exercise
2. is also illustrated in disease states, in fibrosis, the diffusion of O2 is restricted because thickening of the alveolar membrane INC diffusion distance, in emphysema, the diffusion of O2 is DEC because the SA for diffusion of gases is DEC
Describe equilibration in diffusion-limited exchange.
in diffusion-limited exchange, the gas does not equilibrate by the time blood reaches the end of the pulmonary capillary, the partial pressure difference of the gas between alveolar air and pulmonary capillary blood is maintained, diffusion continues as long as the partial pressure gradient is maintained
What are the forms that O2 is transported in?
1. O2 is carried in blood in two forms: dissolved or bound to hemoglobin (most important)
2. hemoglobin, at its normal concentration, INC the O2 carrying capacity of blood seventyfold
What are the characteristics of hemoglobin?
1. globular protein of four subunits
2. each subunit contains a heme moiety which is iron-containing porphyrin
3. the iron is in the ferrous state (Fe2+) which binds O2 (if iron is in the ferric state (Fe3+), it is methemoglobin, which does not bind O2)
4. each subunit has a polypeptide chain, two of the subunits have alpha chains and two of the subunits have beta chains, thus normal adult hemoglobin is called alpha2beta2
Describe fetal hemoglobin.
1. in fetal hemoglobin, the beta chains are replaced by gamma chains, thus fetal hemoglobin is called alpha2gamma2
2. the O2 affinity of fetal hemoglobin is higher than the O2 affinity of adult hemoglobin (left-shift) because 2,3 diphosphoglycerate (DPG) binds less avidly
3. because the O2 affinity of fetal hemoglobin is higher than the O2 affinity of adult hemoglobin, O2 movement from mother to fetus is facilitated
Describe O2-binding capacity of blood.
1. is the maximum amount of O2 that can be bound to Hb in blood
2. is dependent on the Hb concentration in blood
3. limits the amount of O2 that can be carried in blood
4. is measured at 100% saturation
Describe the O2 content of blood
1. is the total amount of O2 carried in blood, including bound and dissolved O2
2. depends on the hemoglobin concentration, the PO2, and the P50 hemoglobin
3. is given by the equation- O2 content = (O2 binding capacity * %saturation) + dissolved O2
What is the hemoglobin-O2 dissociation curve?
1. hemoglobin combines rapidly and reversible with O2 to form oxyhemoglobin
2. the hemoglobin-O2 dissociation curve is a plot of percent saturation of hemoglobin as a function of PO2
According to the hemoglobin-O2 dissociation curve, what is % saturation at PO2 of 100 mm Hg?
Hb is 100% saturated, O2 is bound to all four heme groups on all Hb molecules
According to the hemoglobin-O2 dissociation curve, what is % saturation at PO2 of 40 mm Hg?
Hb is 75% saturated, which means that on average, three of the four heme groups on each Hb molecule have O2 bound
According to the hemoglobin-O2 dissociation curve, what is % saturation at PO2 of 25 mm Hg?
Hb is 50% saturated, the PO2 saturation is the P50, fifty percent saturation means that on average two of the four heme groups of each Hb molecule have O2 bound
Describe the shape of the Hb-O2 dissociation curve.
the sigmoid shape of the curve is the result of a change in the affinity of Hb as each successive O2 molecule binds to a heme site (called positive cooperativity)
Describe positive cooperativity in Hb-O2 dissociation curve.
1. binding of the first O2 moleucle INC the affinity for the second O2 molecule and so forth
2. the affinity for the fourth O2 molecule is the highest
3. this change in affinity facilitates the loading of O2 in the lungs (flat portion of the curve) and the unloading of O2 at the tissues (steep portion of the curve)
Describe the Hb-O2 dissociation curve in the lungs.
1. alveolar gas has a PO2 of 100 mmHg
2. pulmonarycapillary blood is arterialized by the diffusion of O2 from alveolar gas into blood, sot that the PO2 of pulmonary capillary blood also becomes 100 mmHg
3. the very high affinity of Hb for O2 at a PO2 of 100 mmHg facilitates the diffusion process, by tightly binding O2, the free O2 concentration and O2 partial pressure are kept low, thus maintaining the partial pressure gradient (that drives the diffusion of O2)
4. the curve is almost flat when the PO2 is between 60 mm Hg and 100 mmHg, thus humans can tolerate changes in atmospheric pressure (and PO2) without compromising the O2-carrying capacity of Hb
Describe the Hb-O2 dissociation curve in the peripheral tissues.
1. O2 diffuses from arterial blood to the cells
2. the gradient for O2 diffusion is maintained because the cells consume O2 for aerobic metabolism, keeping the tissue PO2 low
3. the lower affinity of Hb for O2 in this steep portion of the curve facilitates the unloading of O2 to the tissues
Describe right ward shifts of the Hb-O2 dissociation curve.
1. occur when the affinity of Hb for O2 is DEC
2. the P50 is INC and unloading of O2 from arterial blood to the tissues is facilitated
3. for any level of PO2, the percent saturation of Hb is DEC
What can cause a rightward shift in Hb-O2 dissociation curve?
1. INC in PCO2 or DEC in pH
2. INC in temperature (e.g. during exercise)
3. INC in 2,3-DPG concentration
Describe INC in PCO2 or DEC in pH in Hb-O2 dissociation curve.
1. shift the curve to the right, DECing the affinity of Hb for O2 and facilitating the unloading of O2 in the tissues (Bohr effect)
2. for example, during exercise, the tissues produce more CO2 which DEC tissue pH and through the Bohr effect, stimulates O2 delivery to the exercising muscle
Describe INC in temperature in Hb-O2 dissociaotn curve.
1. shift the curve to the right
2. the shift to the right DEC the affinity of Hb for O2 and facilitates the delivery of O2 to the tissues during this period of high demand
Describe INC in 2,3 DPG in Hb-O2 dissociation curve.
1. shift the curve to the right by binding to the beta chains of dexoyhemoglobin and DECing the affinity of Hb of O2
2. the adaptation to chronic hypoxemia (e.g. living at high altitude) includes INC synthesis of 2,3 DPG which binds to Hb and facilitates unloading of O2 in the tissues
Describe leftward shifts of the Hb-O2 dissociation curve.
1. occur when the affinity of Hb for O2 is INC
2. the P50 is DEC, and unloading of O2 from arterial blood into the tissues is more difficult
3. for any level of PO2, the percent saturation of Hb is INC
What can cause a leftward shift to the Hb-O2 dissociation curve?
1. are the mirror image of those that cause a shift to the right
2. include DEC PCO2, INC pH, DEC temperature and DEC 2,3 DPG
Describe HbF in Hb-O2 dissociation curve.
does not bind 2,3 DPG as strongly as does adult Hb, DEC binding of 2,3 DPG results in INC affinity of HbF for O2, DEC P50 and a shift of the curve to the left
Describe CO poisoning.
1. CO competes for O2-binding sites on Hb, the affinity of Hb for CO is 200 times its affinity for O2
2. CO occupies O2-binding sites on Hb, thus DECing the O2 content of blood
3. in addition, binding of CO to Hb INC the affinity of remaining sites for O2, causing a shift of the curve to the left
What is hypoxemia?
1. is a DEC in arterial PO2
2. A-a gradient can be used to compare causes of hypoxemia and is described by the following equations: A-a gradient = PAO2 – PaO2
How is alveolar PO2 calculated?
from the alveolar gas equation, PAO2 = PIO2 – (PACO2 / R), where PIO2 = inspired PO2, and R = respiratory exchange ratio or respiratory quotient (CO2 production/O2 consumption)
What are the normal A-a gradient values?
1. is < 10 mmHg, since O2 normally equilibrates between alveolar gas and arterial blood, PAO2 is approx. equal to PaO2
2. the A-a gradient is INC (> 10 mmHg) if O2 does not equilibrate between alveolar gas and arterial blood (e.g. diffusion defect, V/Q defect, right-to-left shunt)
What is hypoxia?
1. is DEC O2 delivary to the tissues
2. O2 delivery is described by the following equation (O2 delivery = CO * O2 content of blood)
3. O2 content of blood depends on Hb concentration, O2-binding capacity of Hb, and % saturation of Hb by O2 (which depends on PO2)
4. thus hypoxia can be caused by DEC CO, DEC O2-binding capacity of Hb or DEC arterial PO2
What are the different forms of CO2 in the blood?
CO2 is produced in the tissues and carried to the lungs in the venous blood in three forms
1. dissolved CO2 (small amount), which is free in solution
2. carbaminohemoglobin (small amount) which is CO2 bound to Hb
3. HCO3- (from hydration of CO2 in the RBC) which is the major form (90%)
Describe the transport of CO2 as HCO3-.
1. CO2 is generated in the tissues and diffuses freely into the venous plasma and then into the RBCs
2. in the RBCs, CO2 combines with H2O to form H2CO3, a reaction that is catalyzed by carbonic anhydrase, H2CO3 dissociates into H+ and HCO3-
3. HCO3- leaves the RBCs in exchange for Cl- (chloride shift) and is transported to the lungs in the plasma, HCO3- is the major form in which CO2 is transported to the lungs
4. H+ is buffered inside the RBCs by deoxyhemoglobin, because deoxyhemoglobin is a better buffer for H+ than is oxyhemoglobin, it is advantageous that Hb has been deoxygenated by the time blood reaches the venous end of the capillaries (i.e. the site where CO2 is being added)
5. in the lungs, all of the above reactions occur in revers, HCO3- enters the RBCs in exchange for Cl-, HCO3- recombines with H+ to form H2CO3 which decomposes into CO2 and H2O, thus CO2 originally generated in the tissues is expired
Describe pressure in pulmonary circulation.
1. are much lower in the pulmonary circulation than in the systemic circulation
2. for example, pulmonary arterial pressure is 15 mmHg (compared with aortic pressure of 100 mmHg)
Describe resistance in pulmonary circulation.
is also much lower in the pulmonary circulation than in the systemic circulation
Describe CO of the right ventricle and pulmonary circulation.
1. is pulmonary blood flow
2. is equal to CO of the left ventricle
3. although pressures in the pulmonary circulation are low, they are sufficient to pump the CO because reistance of the pulmonary circulation is proportionately low
Describe the distribution of pulmonary blood flow in the supine and standing position.
1. when a person is supine, blood flow is nearly uniform throughout the lung
2. when a person is standing, blood flow is unevenly distributed because of the effect of gravity, blood flow is lowest at the apex of the lung (zone 1) and highest at the base of the lung (zone 3)
Describe zone 1 of the lung.
1. blood flow is lowest
2. alveolar pressure > arterial pressure > venous pressure
3. the high alveolar pressure may compress the capillaries and reduce blood flow in zone 1, this situation can occur if arterial BP is DEC as a result of hemorrhage or if alveolar pressure is INC because of + pressure ventilation
Describe zone 2 of the lung.
1. blood flow is medium
2. arterial pressure > alveolar pressure > venous pressure
3. moving down the lung, arterial pressure progressively INC because of gravitational effects on hydrostatic pressure
4. arterial pressure is greater than alveolar pressure in zone 2 and blood flow is drivein by the difference between arterial pressure and alveolar pressure
Describe zone 3 of the lung.
1. blood flow is highest
2. arterial pressure > venous pressure > alveolar pressure
3. moveing down toward the base of the lung, arterial pressure is highest because of gravitational effects and venous pressure finally INC to the point where it exceeds alveolar pressure
4. in zone 3, blood flow is driven by the difference between arterial and venous pressures as in most vascular beds
Describe the regulation of pulmonary blood flow via hypoxic vasoconstriction.
1. in the lungs, hypoxia causes vasoconstriction
2. this response is the opposite of that in other organs, where hypoxia causes vasodilation
3. physiologically, this effect is important because local vasoconstriction redirects blood away from poorly ventilated, hypoxic regions of the lung and toward well-ventilated regions
Describe fetal pulmonary vascular resistance
fetal pulmonary vascular resistance is very high because of generalized hypoxic vasoconstriction, as a result, blood flow through the fetal lungs is low, with the first breath, the alveoli of the neonate are oxygenated, pulmonary vascular resistance DEC and pulmonary blood flow INC and becomes equal to CO (as occurs in the adult)
Describe right-to-left shunts.
1. normally occur to a small extent because 2% of the CO bypasses the lungs
2. may be as great as 50% of CO in certain congenital abnormalities
3. are seen in teratology of Fallot
4. always result in a DEC in arterial PO2 because of the admixture of venous blood with arterial blood
5. the magnitude of a right-to-left shunt can be estimated by having the patient breathe 100% O2 and measuring the degree of dilution of oxygenated arterial blood by nonoxygenated shunted (venous) blood
Describe left-to-right shunts.
1. are more common than right-to-left shunts because pressures are higher on the left side of the heart
2. are usually caused by congenital abnormalities (e.g. patent ductus arteriosus) or traumatic injury
3. do not result in a DEC in arterial PO2, instead PO2 will be elevated on the right side of the heart because there has been admixture of arterial blood with venous blood
What is V/Q ratio?
1. is the ratio of alveolar ventilation (V) to pulmonary blood flow (Q), ventilation and perfusion matching is important to achieve the ideal exchange of O2 and CO2
2. if the freq., tidal volume and CO are normal, the V/Q ratio is approx. 0.8, this V/Q ratio results in an arterial PO2 of 100 mmHg and an arterial PCO2 of 40 mmHg
Describe blood flow in the different parts of the lung.
is lowest at the apex and highest at the base because of gravitational effects
Describe ventilation in the different parts of the lung.
is lowest at the apex and higher at the base, but the regional differences for ventilation are not as great as for perfusion
Describe V/Q ratio in the different parts of the lung.
is higher at the apex of the lung and lower at the base of the lung
What is the result of the regional differences in V/Q ratio?
there are corresponding differences in the efficiency of gas exchange and in the resulting pulmonary capillary PO2 and PCO2, regional differences for PO2 are greater than those for PCO2
1. at the apex (higher V/Q), PO2 is highest and PCO2 is lower because there is more gas exchange
2. at the base (lower V/Q), PO2 is lowest and PCO2 is higher because there is less gas exchange
What is the V/Q ratio in airway obstruction?
1. if the airways are completely blocked (e.g. by a piece of steak caught in the trachea), then veintlation is zero, if blood flow is normal, then V/Q is zero which is called a shunt
2. there is no gas exchange in a lung that is perfused but not ventilated, the PO2 and PCO2 of pulmonary capillary blood (and therefore of systemic arterial blood) will approach their values in mixed venous blood
3. there is an INC A-a gradient
What is the V/Q ratio in pulmonary embolism?
1. if blood flow to a lung is completely blocked (e.g. by an embolism occluding a pulmonary artery) then blood flow to that lungs is zero, if ventilation is normal, then V/Q is infinite, which is called dead space
2. there is no gas exchange in a lung that is ventilated but not perfused, the PO2 and PCO2 of alveolar gas will approach their values in inspired air
Describe the control of breathing.
1. sensory information (PCO2, lung stretch, irritants, muscle spindles, tendons and joints) is coordinated in the brain stem
2. the output of the brain stem controls the respiratory muscles and the breathing cycle
Where is the medullary respiratory center located and what groups make it up?
is located in the reticular formation, consists of dorsal and ventral respiratory group
Describe the dorsal respiratory group.
1. is primarily responsible for inspiration and generates the basic rhythm for breathing
2. input to the dorsal respiratory group comes from the vagus and glossopharyngeal nerves, the vagus nerve relays information from peripheral chemoreceptors and mechanoreceptors in the lung, the glossopharyngeal nerve relays information from peripheral chemoreceptors
3. output from the dorsal respiratory group travels, via the phrenic nerve, to the diaphragm
Describe the ventral respiratory group.
1. is primarily responsible for expiration
2. is not active during normal, quiet breathing, when expiration is passive
3. is activated, for example, during exercise, when expiration becomes an active process
Describe the apneustic center.
1. is located in the lower pons
2. stimulates inspiration, producing a deep and prolonged inspiratory gasp (apneusis)
Describe the pneumotaxic center.
1. is located in the upper pons
2. inhibits inspiration and therefore regulates inspiratory volume and respiratory rate
Describe the cerebral cortex.
1. breathing can be under voluntary control; therefore a person can voluntarily hyperventilate or hypoventilate
2. hypoventilation (breath-holding) is limited by the resulting INC in PCO2 and DEC in PO2, a previous period of hyperventilation extends the period of breath-holding
Describe the central chemoreceptors in the medulla.
1. are sensitive to the pH of the CSF, DEC in the pH of the CSF produce INC in breathing rate (hyperventilation)
2. H+ does not cross the BBB as well as CO2 does
Describe the role of CO2 in activating central chemoreceptors.
1. CO2 diffuses from arterial blood into the CSF because CO2 is lipid-soluble and readily crosses the BBB
2. in the CSF, CO2 combines with H2O to produce H+ and HCO3-, the resulting H+ acts directly on the central chemoreceptors
3. thus, INC in PCO2 and [H+] stimulate breathing, and DEC in PCO2 and [H+] inhibit breathing
4. the resulting hyperventilation or hypoventilation then returns the arterial PCO2 toward normal
Describe peripheral chemoreceptors in the carotid and aortic bodies.
1. the carotid bodies are located at the bifurcation of the common carotid arteries
2. the aortic bodies are located above and below the aortic arch
What happens with DEC in arterial PO2 in peripheral chemoreceptors in the carotid and aortic bodies?
1. stimulate the peripheral chemoreceptors and INC breathing rate
2. PO2 must DEC to low levels (< 60 mmHg) before breathing is stimulated, when PO2 is less than 60 mmHg, breathing rate is exquisitely sensitive to PO2
What happens with INC in arterial PCO2 in perhipheral chemoreceptors in the carotid and aortic bodies?
1. stimulate peripheral chemoreceptors and INC breathing rate
2. potentiate the stimulation of breathing caused by hypoxemia
3. the response of the peripheral chemoreceptors to CO2 is less important than the response of the central chemoreceptors to CO2 (or H+)
What happens with INC in arterial [H+] in peripheral chemoreceptors in the carotid and aortic bodies?
1. stimulate the carotid body peripheral chemoreceptors direcetly, independent of changes in PCO2
2. in metabolic acidosis, breathing rate is INC (hyperventilation) because arterial [H+] is INC and pH is DEC
Describe lung stretch receptors in controlling breathing.
1. are located in the smooth muscles of the airways
2. when these receptors are stimulated by distention of the lungs, they produced a reflex DEC in breathing frequency (Hering-Breuer reflex).
Describe irritant receptors in controlling breathing.
1. are located between the airway epithelial cells
2. are stimulated by noxious substances (e.g. dust, pollen)
Describe J (juxtacapillary) receptors in controlling breathing.
1. are located in the alveolar walls, close to the capillaries
2. engorgement of the pulmonary capillaries, such as many occur with left heart failure, stimulates the J receptors, which then cause rapid, shallow breathing
Describe joint and muscle receptors.
1. are activated during movement of the limbs
2. are involved in the early stimulation of breathing during exercise
What is the response of the respiratory system on exercise?
1. during exercise, there is an INC in ventillatory rate that matches the INC in O2 consumption and CO2 production by the body, the stimulus for the INC ventilation rate is not completely understood, however, joint and muscle receptors are activated during movement and cause an INC in breathing rate at the beginning of exercise
2. the mean values for arterial PO2 and PCO2 do not change during exercise
a. arterial pH does not change during moderate exercise, although it may DEC during strenuous exercise because of lactic acidosis
3. on the other hand, venous PCO2 INC during exercise because the excess CO2 produced by the exercising muscle is carried to the lungs in venous blood
4. pulmonary blood flow INC
Why does pulmonary blood flow INC during exercise
because CO INC during exercise, as a result more pulmonary capillaries are perfused and more gas exchange occurs, the distribution of V/Q ratios throughout the lung is more even during exercise than when at rest and there is a resulting DEC in the physiologic dead space
Describe the response of the respiratory system to high altitude.
1. alveolar PO2 is DEC because the barometric pressure is DEC, as a result, arterial PO2 is also DEC (hypoxemia)
2. hypoxemia stimulates the peripheral chemoreceptors and INC ventilation rate (hyperventilation), this produces respiratory alkalosis, which can be treated by administering acetazolamide
3. hypoxemia also stimulates renal production of erythropoietin, which INC the production of RBCs, there is INC hemoglobin concentration, INC O2-carrying capacity of blood and INC O2 content of blood
4. 2,3 DPG concentration are INC, shifting the Hb-O2 dissociation curve to the right, there is a resulting DEC in affinity of Hb for O2 that facilitates unloading of O2 in the tissues
5. pulmonary vasoconstriction is another result of hypoxemia (hypoxic vasoconstriction), consequently there is an INC in pulmonary arterial pressure, INC work of the right side of the heart against the higher resistance and hypertrophy of the right ventricle
Describe total body water in the human.
1. total body water is approx. 60% of body weight
2. the percentrage of TBW is highest in newborns and adult males and lowest in adult females and in adults with a large amount of adipose tissue
What is intracellular fluid (ICF)?
1. is two-thirds of TBW
2. the major cations of ICF are K+ and Mg2+
3. the major anions of ICF are protein and organic phosphates [ATP, ADP and AMP]
What is extracellular fluid (ECF)?
1. is one-third of TBW
2. is composed of interstitial fluid and plasma
3. the major cation of ECF is Na+
4. the major anions of ECF are Cl- and HCO3-
5. plasma is ¼ of the ECF, thus it is 1/12 of TBW (the major plasma proteins are albumin and globulins
6. interstitial fluid is ¾ of the ECF (thus it is ¼ of TBW) (the composition of interstitial fluid is the same as that of plasma except that it has little protein, thus interstitial fluid is an ultrafiltrate of plasma
Describe the 60-40-20 rule.
1. TBW is 60% of body weight
2. ICF is 40% of body weight
3. ECF is 20% of body weight
Describe the dilution method of measuring the volumes of fluid compartments.
1. a known amount of a substance is give whose volume of distribution is the body fluid compartment of interest
2. the substance is allowed to equilibrate
3. the concentration of the substance is measured in plasma and the volume of distribution is calculated as follows (V = amount/concentration)
Give an example for the use of dilution method in measuring fluid compartment volume.
1. tritiated water is a marker for TBW that distributes wherever water is found
2. mannitol is a marker for ECF because it is a large molecule that cannot cross cell membranes and is therefore excluded from the ICF
3. evans blue is a marker for plasma volume because it is a dye that binds to serum albumin and is therefore confined to the plasma compartment
What substances is used to measure TBW?
tritiated water and D2O
What substances are used to measure ECF?
sulfate, inulin and mannitol
What substances are used to measure plasma?
radioiodinated serum albumin (RISA) and Evans blue
What substances are sued to measure interstitial fluid?
measured indirectly (ECF volume – plasma volume)
What substances are used to measure ICF?
measured indirectly (TBW – ECF volume)
What are the basic principles of the shifts of water between compartments?
1. at steady state, ECF osmolarity and ICF osmolarity are equal
2. to achieve this equality, water shifts between the ECF and ICF compartments
3. it is assumed that solutes such as NaCl and mannitol do not cross cell membranes and are confined to ECF
What shift in water occurs when isotonic NaCl is infused (addition of isotonic fluid)?
1. ECF volume INC, but no change occurs in the osmolarity of ECF or ICF, because osmolarity is unchanged, water does not shift between the ECF and ECF compartments
2. plasma protein concentration and hematocrit DEC because the addition of fluid to the ECF dilutes the protein and RBCs, because ECF osmolarity is unchanged, the RBCs will not shrink or swell
3. arterial BP INC because ECF volume INC
What shift in water occurs during diahhrea (loss of isotonic fluid)?
1. is also called isosmotic volume contraction
2. ECF volume DEC, but no change occurs in the osmolarity of ECF or ICF, because osmolarity is unchanged, water does not shift between the ECF and ICF compartments
3. plasma protein concentration and hematocrit INC because the loss of ECF concentrates the protein and RBCs, because ECF osmolarity is unchanged, the RBCs will not shrink or swell
4. arterial BP DEC because ECF volume DEC
What shift in water occurs during excessive NaCl intake (addition of NaCl)?
1. is also called hyperosmotic volume expansion
2. the osmolarity of ECF INC because osmoles (NaCl) have been added to the ECF
3. water shifts from ICF to ECF, as a result of this shift, ICF osmolarity INC until it equals that of ECF
4. as a result of the shift of water out of the cells, ECF volume INC (volume expansion) and ICF volume DEC
5. plasma protein concentration and hematocrit DEC because of the INC in ECF volume
What shift in water occurs during sweating in a desert-loss of water?
1. is also called hyperosmotic volume contraction
2. the osmolarity of ECF INC because sweat is hyposmotic (relatively more water than salt is lost)
3. ECF volume INC because of the water retention, water shifts into the cells, as a result of this shift, ICF osmolarity DEC until it equals ECF osmolarity and ICF volume INC
4. plasma protein concentration INC because of the DEC in ECF volume, although hematocrit might also be expected to INC, it remains unchanged because water shifts out of the RBCs, DECing their volume and offsetting the concentrating effect of the DEC ECF volume
What shift in water occurs during syndrome of inappropriate antidiuretic hormone (SIADH) (gain of water)?
1. is also called hyposmotic volume expansion
2. the osmolarity of ECF DEC because excess water is retained
3. ECF volume INC because of the water retention, water shifts into the cells, as a result of this shift, ICF osmolarity DEC until it equals ECF osmolarity, and ICF volume INC
4. plasma protein concentration DEC because ot he INC in ECF volume, although hematocrit might also be expected to DEC, it remains unchanged because water shifts into the RBCs, INCing their volume and offsetting the diluting effect of the gain of ECF volume
What shift in water occurs during adrenocortical insufficiency (loss of NaCl)?
1. is also called hyposmotic volume contraction
2. the osmolarity of ECF DEC, as a result of the lack of aldosterone in adrenocrotical insufficiency, the kidneys excrete more NaCl than water
3. ECF volume DEC, water shifts into the cells, as a result of this shift, ICF osmolarity DEC until it equals ECF osmolarity and ICF volume INC
4. plasma protein concentration INC because of the DEC in ECF volume, hematocrit INC because of the DEC ECF volume and because the RBCs swell as a result of water entry
5. arterial blood pressure DEC because of the DEC in ECF volume
What is the clearance equation?
1. indicates the volume of plasma cleared of a substance per unit time
2. the units of clearance are mL/min
3. C = UV/P, where C = clearance, U = urine concentration, V = urine volume, P = plasma concentration
Describe renal blood flow.
1. is 25% of the CO
2. is directly proportional to the pressure difference between the renal artery and the renal vein, and is inversely proportional to the resistance of the renal vasculature
3. vasoconstriction or vasodilation of renal arterioles
Describe what happens during vasoconstriction of renal arterioles.
leads to DEC in RBF, is produced by activation of the sympathetic nervous system and angiotensin II, at low concentrations, angiotensin II preferentially constricts efferent arterioles, thereby protecting the GFR, angiotensin-converting enzyme (ACE) inhibitors, dilate efferent arterioles and produce a DEC in GFR, these drugs reduce hyperfiltration and the occurrence of diabetic neuropathy in diabetes mellitus
Describe wheat happens during vasodilation of renal arterioles.
which leads to an INC in RBF, is produced by prostaglandins E2 and I2, bradykinin, NO and dopamine
Describe autoregulation of RBF.
1. is accomplished by changing renal vascular resistance, if arterial pressure changes, a proportional change occurs in renal vascular resistance to maintain a constant RBF
2. RBF remains constant over the range of arterial pressures from 80 to 200 mmHg (autoregulation)
Describe the myogenic mechanism of autoregulation.
renal afferent arterioles contract in response to stretch, thus, INC renal arterial pressure stretches the arterioles, which contract and INC resistance to maintain constant blood flow
Describe the role of tubuloglomerular feedback in autoregulation.
in which INC renal arterial pressure leads to INC delivery of fluid to the macula densa, the macula densa senses the INC load and causes constriction of the nearby afferent arteriole, INCing resistance to maintain constant blood flow
How is renal plasma flow measured (RPF)?
1. PAH (para-aminohippuriv acid) is filtered and secreted by the renal tubules
2. clearance of PAH is used to measure RPF
3. clearance of PAH measures effective RPF and underestimates true RPF by 10% (clearance of PAH does not measure renal plasma flow to regions of the kidney that do not filter and secrete PAH)
4. RPF = Cpah = ([U]pah*V)/[P]pah
What is the measurement of RBF?
RBF = RPF / (1-hematocrit), not the denominator in this equation, 1- hct, is the fraction of blood volume occupied by plasma
Describe the measurement of the GFR.
clearance of inulin, inulin is filtered but not reabsorbed or secreted by the renal tubules, the clearance of inulin is ued to measure GFR, as shown in the equation: GFR = ([U]inulin*V)/[P]inulin)
How can GFR be estimated using blood urea nitrogen (BUN) and serum [creatinine]?
1. both BUN and serum [creatinine] INC when GFR DEC
2. in prerenal azotemia (hypovolemia), BUN INC more than serum creatinine and there is an INC BUN/creatinine ratio (> 20:1)
3. GFR DEC with age, although serum [creatinine] remains constant because of DEC muscle mass
What is filtration fraction?
1. is the fraction of RPF filtered across the glomerular capillaries, as shown in the following equation: GFR/RPF
2. is normally about 0.20, thus 20% of RPF is filtered, the remaining 80% leaves the glomerular capillaries by the efferent arterioles and becomes the peritubular capillary circulation
3. INC in the filtration fraction produce INC in the protein concentration of peritubular capillary blood which leads to INC reabsorption in the proximal tubule
4. DEC in the filtration fraction produce DEC in the protein concentration of peritubular capillary blood and DEC reabsorptiono in the proximal tubule
How is GFR determined (starling forces)?
1. the driving force for glomerular filtration is the net ultrafiltration pressure across the glomerular capillaries
2. filtration is always favored in glomerular capillaries because the net ultrafiltration pressure always favors the movement of fluid out of the capillary
3. GFR can be expressed by the Starling equation (GFR = Kf [(Pgc – Pbs) – (pi gs – pi bs)]
4. GFR is filtration across the glomerular capillaries
What is Kf in the starling equation?
1. Kf is the filtration coefficient of the glomerular capillaries
2. the glomerular barrier consists of the capillary endothelium, basement membrane, and filtration slits of the podocytes
3. normally, anionic glycoproteins line the filtration barrier and restrict the filtration of plasma proteins, which are also negatively charged
4. in glomerular disease, the anionic charges on the barrier may be removed, resulting in proteinuria
What is Pgc in the starling equation?
1. glomerular capillary hydrostatic pressure, is constant along the length of the capillary
2. it is INC by dilation of the afferent arteriole or constricting of the efferent arteriole, INC in Pgc cause INC in net ultrafiltration pressure and GFR
What is Pbs in the starling equation?
1. is Bowman’s space hydrostatic pressure and is analogous to Pi in systemic capillaries
2. it is INC by constriction of the ureters, INC in Pbs cause DEC in net ultrafiltration pressure and GFR
What is pi gc in the starling equation?
1. is glomerular capillary oncotic pressure, it normally INC along the length of the glomerular capillary because filtration of water INC the protein concentration of glomerular capillary blood
2. it is INC by INC in protein concentration, INC in pi gc cause DEC in net ultrafiltration pressure and GFR
What is pi bs in the starling equation?
1. is Bowman’s space oncotic pressure
2. it is usually zero because only a small amount of protein is normally filtered
How is reabsorption and secretion rates calculated?
1. the reabsorption or secretion rate is the difference between the amount filtered across the glomerular capillaries and the amount excreted in urine
2. if the filtered load is greater than the excretion rate, then net reabsorption of the substance has occurred, if the filtered load is less than the excretion rate, then net secretion of the substance has occurred
How is filtered load calculated?
filtered load = GFR * [plasma]
How is excretion rate calculated?
excretion rate = V * [urine]
How is reabsorption rate calculated?
reabsorption rate = filtered load – excretion rate
How is secretion rate calculated?
seceretion rate = excretion rate – filtered load
Describe the filtered load of glucose.
INC in direct proportion to the plasma glucose concentration (filtered load of glucose = GFR * [P]glucose)
Describe the reabsorption of glucose.
1. Na+-glucose cotransport in the proximal tubule reabsorbs glucose from tubular fluid into the blood, there are a limited number of Na+ glucose carriers
2. at plasma glucose concentrations less than 250 mg/dL, all of the filtered glucose can be reabsorbed because plenty of carriers are available, in this range the line for reabsorption is the same as that for filtration
3. at plasma glucose concentrations greater than 350 mg/dL, the arriers are saturated, therefore, INC in plasma concentration above 350 mg/dL do not result in INC rates of reabsorption, the reabsorptive rate at which the carriers are saturated is the Tm
Describe the excretion of glucose.
1. at plasma concentrations less than 250 mg/dL, all of the filtered glucose is reabsorbed and excretion is zero, threshold (defined as the plasma concentration at which glucose first appears in the urine) is approx. 250 mg/dL
2. at plasma concentrations greater than 350 mg/dL, reabsorption is saturated (Tm), therefore as the plasma concentration INC, the additional filtered glucose cannot be reabsorbed and is excreted in the urine
Describe splay.
1. is the region of the glucose curves between threshold and Tm
2. occurs between plasma glucose concentrations of approx. 250 and 350
3. represents the excretion of glucose in urine before saturation of reabsorption (Tm) is fully achieved
4. is explained by the heterogeneity of nephrons and the relatively low affinity of the Na+-glucose carriers
Describe the filtered load of PAH.
as with glucose, the filtered load of PAH INC in direct proportion to the plasma PAH concentration
Describe secretion of PAH.
1. secretion of PAH occurs from peritubular capillary blood into tubular fluid (urine) via carriers in the proximal tubule
2. at low plasma concentrations of PAH, the secretion rate INC as the plasma concentration INC
3. once the carriers are saturated, further INC in plasma PAH concentration do not cause further INC in the secretion rate (Tm)
Describe the excretion of PAH.
1. excretion of PAH is the sum of filtration across the glomerular capillaries plus secretion from peritubular capillary blood into urine
2. the curve for excretion is steeper at low plasma PAH concentrations (lower than at Tm), once the Tm for secretion is exceeded and all of the carriers for secretion are saturated, the excretion curve flattens and becomes parallel to the curve for filtration
3. RPF is measured by the clearance of PAH at plasma concentrations of PAH that are lower than at Tm
What are the substances with the highest clearances?
are those that are both filtered across the glomerular capillaries and secreted from the peritublar capillaries into urine (e.g. PAH)
What are the substances with the lowest clearances?
are those that either are not filtered (e.g. protein) or are filtered and subsequently reabsorbed into peritubular capillary blood (e.g. Na+, glucose, amino acids, HCO3-, Cl-)
What are the substances with clearances equal to GFR?
1. are glomerular markers
2. are those that are freely filtered, but not reabsorbed or secreted (e.g. inulin)
What are the relative clearances for the different substances?
PAH > K+ (high-K+ diet) > inulin > urea > Na+ > glucose, amino acids, and HCO3-
Describe weak acids.
1. have an HA form and an A- form
2. the HA form, which is uncharged and lipid-soluble, can “back-diffuse” from urine to blood
3. the A- form, which is charged and not lipid-soluble, cannot back-diffuse
4. at acidic urine pH, the HA form predominates, there is more back-diffusion, and there is DEC excretion of the weak acid
5. at alkaline urine pH, the A- form predominates, there is less back-diffusion, and there is INC excretion of the weak acid, for example, the excretion of salicylic acid can be INC by alkanizing the urine
Describe weak bases.
1. have a BH+ from and a B form
2. the B form, which is uncharged and lipid-soluble, can back diffuse from urine to blood
3. the BH+ form, which is charged and not lipid-soluble, cannot back-diffuse from urine
4. at acidic urine pH, the BH+ form predominates, there is less back-diffusion, and there is INC excretion of the weak base
5. at alkaline urine pH, the B form predominates, there is more back-diffusion, and there is DEC excretion of the weak base
What is tubular fluid?
is urine at any point along the nephron
What is plasma?
is systemic plasma, it is considered to be constant
What is TF/Px ratio?
compares the concentration of a substance in tubular fluid at any point along the nephron with the concentration in plasma
What happens if TF/P = 1.0?
then either there has been no reabsorption of the substance or reabsorption of the substance has been exactly proportional to the reabsorption of water
for any freely filtered substance, TF/P = 1.0 in Bowman’s space (before any reabsorption or secretion has taken place to modify the tubular fluid)
What happens if TF/P < 1.0?
then reabsorption of the substance has been greater than the reabsorption of water and the concentration in tubular fluid is less than that in plasma
for example, if TF/Pna = 0.8, then the [Na+] in tubular fluid is 80% of the [Na+] in plasma
What happens if TF/P >1.0?
then either reabsorption of the substance has been less than the reabsorption of water or there has been secretion of the substance
What is TF/Pinulin?
is used as a marker for water reabsorption along the nephron
INC as water is reabsorbed
because inulin is freely filtered, but not reabsorbed or secreted, its concentration in tubular fluid is determined solely by how much water remains in the tubular fluid
the following equation shows how to calculate the fraction of the filtered water that has been reabsorbed (fraction of filtered H2O reabsorbed = 1 – (1 / [TF/P]inulin)
Describe the [TF/P]x/[TF/P]inulin ratio
corrects the TF/Px ratio for water reabsorption, this double ratio gives the fraction of the filtered load remaining at any point along the nephron
Give some general information about Na+ reabsorption.
1. Na+ is freely filtered across the glomerular capillaries, therefore, the [Na+] in the tubular fluid of Bowman’s space equals that in plasma (i.e. TF/Pna = 1.0)
2. Na+ is reabsorbed along the entire nephron and very little is excreted in urine (<1% of the filtered load)
What role do the proximal tubules have on Na+ reabsorption along the nephron?
1. reabsorbs 2/3, or 67% of the filtered Na+ and H2O, more than any other part of the nephron
2. is the site of glomerulotubular balance
3. the process is isosmotic, the reabsorption of Na+ and H2O in the proximal tubule are exactly proportional, therefore, both TF/Pna and TF/Posm = 1.0
What are some special features of the early proximal tubules?
1. reabsorbs Na+ and H2O with HCO3-, glucose, amino acids, phosphate, and lactate
2. Na+ is reabsorbed by cotransport with glucose, amino acid, phosphate, and lactate, these cotransport processes account for the reabsorption of all of the filtered glucose and amino acids
3. Na+ is also reabsorbed by countertransport via Na+-H+ exchange, which is linked directly to the reabsorption of filtered HCO3-
4. carbonic anhydrase inhibitors (e.g. acetazolamide) are diuretics that act in the early proximal tubule by inhibiting the reabsorption of filtered HCO3-
What are some special features of the late proximal tubule?
1. filtered glucose, amino acids, and HCO3- have already been completely removed from the tubular fluid by reabsorption in the early proximal tubule
2. in the lat proximal tubule, Na+ is reabsorbed with Cl-
What is the purpose of glomerulotubular balance in the proximal tubule?
maintains constant fractional reabsorption (2/3 or 67%) of the filtered Na+ and H2O
What is the mechanism of glomerulotubular balance?
1. is based on Starling forces in the peritubular capillaries, which alter the reabsorption of Na+ and H2O in the proximal tubule
2. the route of isomotic fluid reabsorption is from the lumen, to the proximal tubule cell, to the lateral intercellular space, and then to the peritubular capillary blood
3. Starling forces in the peritubular capillary blood govern how much of this isosmotic fluid will be reabsorbed
4. fluid reabsorption is INC by INC in pi c of the peritubular capillary blood and DEC by DEC in pi c
5. INC in GFR and filtration fraction cause the protein concentration and pi c of peritubular capillary blood to INC, this INC in turn produces an INC in fluid reabsorption, thus there is matching of filtration and reabsorption or glomerulotubular balance
What are the effects of ECF volume on proximal tubular reabsorption?
1. ECF volume contraction INC reabsorption, volume contraction INC peritubular capillary protein concentration and pi c, and DEC peritubular capillary Pc, together, these changes in Starling forces in peritubular capillary blood cause an INC in proximal tubular reabsorption
2. ECF volume expansion DEC reabsorption, volume expansion DEC peritubular capillary protein concentration and pi c and INC Pc, together these changes in Starling forces in peritubular capillary blood cause a DEC in proximal tubular reabsorption
Describe the thick ascending limb of the loop of Henle.
1. reabsorbs 25% of filtered Na+
2. contains a Na+-K+-2Cl- cotransporter in the luminal membrane
3. is the site of action of the loop diuretics (furosemide, ethacrynic acid, bumetandie) which inhibit the Na+-K+-2Cl- cotransporter
4. is impermeable to water, thus NaCl is reabsorbed without water, as a result, tubular fluid [Na+] and tubular fluid osmolarity DEC to less than their concentrations in plasma (i.e. TF/Pna+ and TF/Posm < 1.0), this segment therefore is called the diluting segment
5. has a lumen-+ potential difference, although the Na+-K+-2Cl- cotransporter appears to be electroneutral, some K+ diffuses back into the lumen, marking the lumen electrically positive
Describe the early distal tubule.
1. reabsorbs NaCl by a Na+-Cl- cotransporter
2. is the site of action of thiazide diuretics
3. is impermeable to water as is the thick ascending limb, thus reabsorption of NaCl occurs without water, which further dilutes the tubular fluid
4. is called the cortical diluting segment
Describe the principal cells of the late distal tubule.
1. reabsorb Na+ and H2O
2. secrete K+
3. aldosterone INC Na+ reabsorption and INC K+ secretion, like other steroid hormones, the action of aldosterone takes several hours to develop because new protein synthesis is required, about 2% of overall Na+ reabsorption is affected by aldosterone
4. ADH INC H2O permeability by directing the insertion of H2O channels in the luminal membrane, in the absence of ADH, the principal cells are virtually impermeable to water
5. K+ sparing diuretics (spironolactone, triamteren, amiloride) DEC K+ secretion
Describe the alpha-intercalated cells of the late distal tubule.
1. secrete H+ by a H+-adenosine triphosphatase (ATPase) which is stimulated by aldosterone
2. reabsorbs K+ by a H+, K+-ATPase
Describe the shifts of K+ between the ICF and ECF.
1. most of the body’s K+ is located in the ICF
2. a shift of K+ out of cells causes hyperkalemia
3. a shift of K+ into cells causes hypokalemia
Describe renal regulation of K+ balance.
1. K+ is filtered, reabsorbed and secreted by the nephron
2. K+ balance is achieved when urinary excretion of K+ exactly equals intake of K+ in the diet
3. K+ excretion can vary widely from 1% to 110% of the filtered load, depending on dietary K+ intake, aldosterone levels and acid-base status
Describe the glomerular capillaries.
filtration occurs freely across the glomerular capillaries, therefore, TF/Pk in Bowman’s space is 1.0
Describe the role of the proximal tubule in K+ regulation.
reabsorbs 67% of the filtered K+ along with Na+ and H2O
Describe the role of thick ascending limb of the loop of Henle in K+ regulation
1. reabsorbs 20% of the filtered K+
2. reabsorption involves the Na+-K+-2Cl- cotransporter in the luminal membrane of cells in the thick ascending limb
Describe the reabsorption of K+ in the distal tubule and collecting duct.
involves a H+, K+ ATPase in the luminal membrane of the alpha-intercalated cells
occurs only on a low-K+ diet, under these conditions, K+ excretion can be as low as 1% of the filtered load because the kidney conserves as much K+ as possible
Describe the secretion of K+ in the distal tubule and collecting duct.
1. occurs in the principal cells
2. is variable and accounts for the wide range of urinary K+ excretion
3. depends on factors such as dietary K+, aldosterone levels, acid-base status and urine flow rate
Describe the mechanism of distal K+ secretion.
at the basolateral membrane, K+ is actively transported into the cell by Na+-K+ pump, as in all cells, this mechanism maintains a high intracellular K+ concentration
at the luminal membrane, K+ is passively secreted into the lumen through K+ channels, the magnitude of this passive secretion is determined by the chemical and electrical driving forces on K+ across the luminal membrane
maneuvers that INC the intracellular K+ concentration or DEC the luminal K+ concentration will INC K+ secretion by INCing the driving force
4. maneuvers that DEC the intracellular K+ concentration will DEC K+ secretion by DECing the driving force
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