Medical Physiology Block 3 Week 2

Question 1

Describe the branching anatomy of the vascular system (connectivity, size, numbers of vessels).

Answer 1

Normally a first order arteriole is connected to a second order arteriole (and even a third and fourth order arteriole), which are connected to higher order venules through a system of capillaries; the radius (and cross-sectional area) of an individual vessel decreases from the aorta to the capillaries; a fundamental law of vessel branching is that at each branch point, the combined cross-sectional area of daughter vessels exceeds the cross-sectional area of the parent vessel; the number of vessels increases enormously from a single aorta to 10 million arterioles and 40 billion capillaries

Question 2

Are all capillary beds open at rest?

Answer 2

No

Question 3

Examine the differences in cross-sectional area, blood velocity, blood volume, and blood pressure between the different compartments of the vascular tree.

Answer 3

Aggregate cross-sectional area is high in the systemic capillaries beds and highest in pulmonary capillaries (velocity is minimal in capillaries beds; flow = area x velocity; the different branches of the circulation receive the same amount of aggregate flow); high pressure vasculature describes the ventricles, arteries, and arterioles (the rest of the system experiences low pressure, particularly pulmonary circulation); most of the blood volume is in the systemic veins (very low blood volume in the pulmonary circulation and heart chambers)

Question 4

T/F: Blood pressure oscillates in the capillaries and venous system

Answer 4

False

Question 5

What determines the longitudinal (axial) pressure drops in the circulation?

Answer 5

The pressure drop between any two point along the circuit depends critically on the diameter (radius) of the vessels between these two points (aggregate resistance); The pressure fall (deltaP) between an upstream checkpoint and a downstream checkpoint increases as the resistance between these 2 points increases (Rpost/Rpre); Under normal physiological conditions, arteriole resistance is greater than venular resistance and the capillary pressure tends to be closer to venular pressure than arteriolar pressure

Question 6

Describe the hemodynamic properties conferred by the arteriolar bed: dynamic changes in vascular resistance (establish the factors affecting the local intravascular pressure at a site in the circulation).

Answer 6

venular dilation (or arteriolar constriction) decreases capillary pressure; total arteriolar resistance normally exceeds total capillary resistance; Increasing arteriolar and venular resistance by the same factor does not change capillary pressure (assumption: driving pressure does not change; normal Rpost/Rpre = 0.3); vascular resistance varies in time and depends critically on the action of vascular smooth muscle cells (major site of control is the feed arteries or arterioles); finally, the resistance profile at a particular site (based on Rpost/Rpre) effects upstream and downstream vessels; think of a circuit connected in series)

Question 7

Describe the cellular and tissue architecture of arteries and veins.

Answer 7

the wall of blood vessels consists of three layers (artery): the tunica intima (endothelium), elastic fibers, the tunica media (smooth muscle), elastic fibers and tunica aventitia (connective tissue: collagen fibers); the highest abundance of elastic fibers is in the aorta (smallest in the precapillary sphincter); the highest abundance of smooth muscle is in the precapillary sphincter (lowest in the aorta; most of the systemic circulation has plenty of smooth muscles); collagen abundance is highest in the aorta (decreases with branching); endothelial cells have low abundance throughout circulation; venules have similar profile to capillaries (only endothelium) and veins have similar profile to arteries

Question 8

Describe how the components of vessels contribute to their function as conductance, resistance, or capacitance vessels.

Answer 8

Resistance vessels- muscular arteries have a rather stable resistance (low compliance); capacitance vessels- veins can accept large volume of blood with little buildup of pressure (volume reservoirs; high compliance)

Question 9

What is vessel compliance and how does it differ in arteries and veins?

Answer 9

Compliance (change in volume/change in pressure) is the slope of a pressure-volume diagram (steeper slope equates to more compliance, or distension); arteries have relatively low compliance; at low transmural pressure (equal to driving pressure), veins are highly compliant (at unphysiologically high transmural pressure, compliance of veins is very low because perimeter of the vessel increases; perimeter does not change at lower transmural pressures because the vein’s ellipsoidal geometry becomes circular with an increase in pressure)

Question 10

Compare/contrast: wall tension, transmural pressure, stress, and strain.

Answer 10

Wall tension = change in pressure(transmural pressure) x radius; stress is the force per unit cross-sectional area; strain = the change in length divided by original length; Stress = elastic modulus x strain OR the transmural pressure is the distending stress (F/A) that tends to increase the strain (change in circumference) of the vessel (this force is opposed by wall tension)

Question 11

T/F Elastin fibers have a lower elastic modulus than collagen fibers?

Answer 11

True; Elastin fibers are capable of more stretch than collagen fibers

Question 12

What changes as a blood vessel becomes distended?

Answer 12

Compliance

Question 13

Identify how the elasticity of the vessels contributes to the relationship between blood volume and blood pressure (understand the physical equilibrium between transmural pressure and vessel wall tension in normal physiology and pathophysiology)

Answer 13

Laplace’s law tells us that a high wall tension is required to withstand a high pressure; the amount of elastic tissue correlates extremely well with wall tension (very poorly with transmural pressure); the higher the tension (takes radius into account) the vessel must bear, the greater its complement of elastic tissue; Elastin fibers are compliant and once they cannot change volume for a certain increase in pressure, they recruit collagen fibers; wall tension also has a component that is analogous to compliance (stretching of the aorta greatly increases wall tension while stretching of vena cava does not up at physiological transmural pressure; reflective of the components of the vessel, particularly elastin and collagen fiber density)

Question 14

What is the effect of aging on the elastic behavior of vessels?

Answer 14

As an individual ages, the ratio of elastin : collagen fibers decreases (which increases the relative wall tension to a maintain a certain radius); pulse pressure increases with aging

Question 15

Understand the complementary role of active smooth muscle and passive elastic tension in vessels.

Answer 15

With active tension (VSMC shortening), there is a decrease in the wall tension that muscle must exert to maintain the smaller radius; elasticity allows for stable inflation or deflation of a vessel; in a system with only VSMCs (no elastic fibers), an increase in pressure would rupture the vessel and a decrease in pressure with the same sympathetic output would cause the vessel to collapse

Question 16

How does the elastic property of blood vessels diverge from flow in a rigid tube?

Answer 16

With an increase in pressure, radius in blood vessels increases, effectively decreasing the resistance (non-linear pressure-flow relationship) (in a rigid tube, resistance is constant); a low driving pressures, resistance increases to infinity (flow ceases at the critical closing pressure, which is greater than zero; active tension of VSMCs increase resistance and reduces flow while increasing the pressure at which a vessel reaches its critical closing pressure)

Question 17

Describe the components and anatomical characteristics of the microcirculation.

Answer 17

components: a single arteriole and venule, between which extends a network of capillaries (metarterioles- short arterioles and fenestrated; precapillary sphincter)

Question 18

Describe a capillary (describe the three types)

Answer 18

True capillaries consist of a single layer of endothelial cell surrounded by a basement membrane (collagen fibers and some pericytes); tight junctions formed by claudins or occludins; continuous = endothelial cells are connected to each other by claudins; fenestrated = holes in the plasma membrene; sinusoidal (discontinuous) = fenestrated and have large gaps between neighboring endothelial cells; glycocalyx; caveolae

Question 19

Use the Krogh cylinder model to analyze the factors that influence gas exchange between blood and tissues.

Answer 19

The oxygen extraction ratio decreases with increased flow but increases with increased oxygen consumption (Poxygen in the artery - Poxygen in the vein) = oxygen consumption/flow)

Question 20

Use Fick’s Law and an understanding of the capillary anatomy to evaluate the factors that influence diffusion of small solutes between the blood and tissues.

Answer 20

according to Fick’s law, the diffusion of small, water-soluble solutes across a capillary wall depends on both the permeability (diffusion coefficient, thickness of capillary wall, and surface area of capillary wall) and the concentration gradient

Question 21

what is the extraction ratio for oxygen?

Answer 21

(Poxygen in the artery - Poxygen in the vein)/ Poxygen in the artery (relevant for any solute)

Question 22

How are macromolecules exchanged in the microcirculation?

Answer 22

small polar molecules (favor positively charged ions) and proteins can diffuse through interendothelial clefts (more common at the venular end; permeability increases along the capillary); can be carried by water during convection (solvent drag); caveolae and transcytosis are responsible for exchange of large molecules

Question 23

Use the Starling equation to describe the transfer of water between the blood and tissues (understand what determines the parameters of the Starling equation and how these parameters may change in space and time).

Answer 23

flux = hydraulic conductivity [hydrostatic pressure difference - (reflection coefficient x colloid osmotic pressure difference)]; reflection coefficient refers to the osmotic effect of proteins (plasma proteins have an reflection coefficient of 1; molecules with a reflection coefficient of 0 passively move with water); positive flux = filtration; hydrostatic pressure falls along the capillary (hydrostatic pressure of interstitial fluid and osmotic pressure of the capillary do not change along the capillary; interstitial colloid osmotic pressure slightly increases along the capillary); generally filtration occurs at arteriolar and absorption occurs at venular end

Question 24

What are critiques of the Starling equation?

Answer 24

changes in extravascular (if) protein have less effect on fluid exchange than changes in intravascular protein (c) indicating an apparent asymmetry; The effective oncotic barrier that acts across capillary endothelium is not homogeneous. Instead, the endothelial surface glycocalyx covering the entire capillary endothelium, serves as the primary molecular filter for plasma proteins; P and π in an intra-endothelial compartment, the subglycocalyx, vary with the direction of fluid movement

Question 25

Why do vessels have hydrostatic pressure? what is the hydrostatic pressure of interstitial fluid and cells? why is the colloid osmotic pressure of a capillary so high?

Answer 25

The reason for the hydrostatic pressure in the capillary is the heart (a pump); negative pressure; abundance of albumin with a reflection coefficient of roughly 1

Question 26

What are improvements to the Starling equation?

Answer 26

Positive flux (by Starling model) induces increase in subglycocalyx fluid hydrostatic pressure and decrease colloid osmotic pressure of subglycocalyx fluid opposing further filtration; Negative flux (by Starling model) induces decrease in subglycocalyx fluid hydrostatic pressure and significantly increases colloid osmotic pressure of subglycocalyx fluid strongly opposing absorption

Question 27

Understand the control of interstitial volume/composition and interstitial fluid pressure (identify the unique characteristics of the lymphatic system)

Answer 27

Transient increases in interstitial fluid hydrostatic pressure temporarily raise Pif above Plymph (normally the hydrostatic pressure in lymph is greater than in the interstitium) and cause opening of microvalves in initial lymphatics; During the compression phase, hydrostatic pressure inside the initial lymphatic rises closing the microvalves and opening the secondary lymph valves causing fluid to flow downstream in collecting lymphatics (compression phase caused by external pressure (intermittent compression and relaxation of lymphatics occur during respiration, walking, and intestinal peristalsis); absent from the brain; Large lymphatics ultimately drain into the left and right subclavian veins

Question 28

How is the overall fluid balance maintained in the circulation?

Answer 28

the excess fluid filtered by the surrounding tissues are drained back into the circulation through lymphatics; all protein filtered out of capillaries is returned to the circulation (primarily by lymph; glucose does not return back into the circulation)

Question 29

Describe smooth muscle contraction. What causes relaxation?

Answer 29

calcium binds to calmodulin; complex binds to myosin light chain complex and leads to phosphorylation of the myosin light chain, allowing myosin to interact with actin (dephosphorylation of myosin light chain causes relaxation)

Question 30

Distinguish nervous, paracrine, endocrine, and metabolic regulation of vascular tone

Answer 30

neural vasoconstriction: epinephrine, ATP, and Neuropeptide Y; neural vasodilation: acetycholine, VIP, and epinephrine (beta 2 receptor); endocrine/paracrine vasoconstriction: angiotensin, vasopressin, serotonin, and neuropeptide Y; endocrine/paracrine vasodilation: histamine, VIP, and atrial natriuretic protein; increase in metabolism (sensed by chemoreceptors) causes vasoconstriction

Question 31

What are mechanisms for activating VSMC contraction? relaxation?

Answer 31

increase calcium, decrease cAMP, decrease cGMP (relaxation is the opposite)

Question 32

What are the principal regulators of angiogenesis?

Answer 32

promote angiogenesis: VEGF, FGF, angiogenin, and angiopoetin-1; inhibit: angiostatin and angiopoetin-2

Question 33

What is autoregulation and where is it present?

Answer 33

vascular capillary beds where changes in perfusion pressure have little effect on flow (increases in pressure lead to increases in resistance to regulate flow and maintain flow when perfusion pressure is decreased); brain, heart, & kidneys

Question 34

How is vascular tone controlled through myogenic mechanisms, tissue metabolites and endothelium-derived vasoactive substances?

Answer 34

Myogenic response: stretch of VSMC membrane activates stretch receptors resulting in depolarization, opening of Cav channels in the plasma membrane, and contraction; high CO2, low pH, low O2 around the capillary (metabolism) cause vasodilation; Endothelin released by endothelial cells causes vasoconstriction through Gαq; nitric oxide acts through cGMP and may act on either MLCK or SERCA pump

Question 35

Identify the molecular regulators of contraction (relaxation) of vascular smooth muscle and their cellular targets.

Answer 35

norepinephrine (a1 Galpha q; a2 Galpha i); epinephrine (dilation: beta 2 Galpha s); acetylcholine (on a neighboring cell; M2: G alpha I (blocks adrenergic repsonse); M3: Galpha q (stimulates nitric oxide synthase); M3 gland: Galpha q (stimulates kallikreins and bradykinin); angiotensin (AT1: Galpha q); vasopressin (G alpha q); serotonin (Galpha q); neuropeptide Y (Galpha i); histamine (Galpha s); ANP (same as NO); VIP (Galpha s)

Question 36

What is the source of phasic changes (describe these changes) in peripheral blood flow and pressure

Answer 36

because of the resistive, compliant, and inertial properties of vessels and blood, the farther the vessels are from the aorta, the more different the pressure and flow waves become; peak systolic flow becomes smaller as one moves from the aorta toward the periphery (there is also a diastolic blood flow component that is a result of arterial vessel compliance); the peak pressure gradually increases in height and becomes narrower (pulse pressure) with increasing distance from the heart (a secondary pressure oscillation also appears in the periphery suggestion distortion of pressure waves)

Question 37

What event closes the aortic valve? why is this different from the closing of other valves?

Answer 37

A reflux (negative flow) of blood through the valve (known as the dicrotic notch); inertial component of blood flow across the valve (considerable kinetic energy)

Question 38

Where does damping of the pressure wave occur in the circulation?

Answer 38

pulse pressure waves dampen in terminal arteries and arterioles and capillaries (where damping is so strong that oscillations of pressure waves disappear; with increased pulse pressure (pathophysiology), pulsations occur in the capillaries

Question 39

How does the role of the elastic aorta maintain end-systolic pressure?

Answer 39

During the interval of the cycle when the driving pressure falls to zero, the expanded rubber vessel delivers its stored volume downstream; resulting in some forward flow despite the absence of any pressure head

Question 40

Explain the phenomena of pressure wave propagation and its effects on pressure and flow waveforms

Answer 40

blood vessels conduct the palpable pulse as a pressure wave; velocity of pressure waves increases in stiffer vessels (high frequency and low frequency waves are dampened; also with aging); higher frequency waves undergo more damping in general

Question 41

T/F Pressure pulsations are absent from the pulmonary and systemic circulation

Answer 41

False (they are present in pulmonary circulation)

Question 42

Define damping

Answer 42

a decrease in the amplitude of an oscillation as a result of energy being drained from the system to overcome frictional or other resistive forces.

Question 43

What are the effects of the respiratory cycle and skeletal muscle contraction on venous return?

Answer 43

during inspiration, the diaphragm descends, causing intrathoracic pressure to decrease and intra-abdominal pressure to increase (the venous return from the head and upper extremities transiently increases and decreases from lower extremities); the pumping action of the leg muscles on leg veins and the action of the venous valves as hydrostatic relays stations (prevent retrograde movement) causes the venous pressure in the foot to decrease (when the exercise ceases, the venous pressure rises again)

Question 44

Describe baroreceptor control of arterial pressure.

Answer 44

increased mean arterial pressure causes stretching of baroreceptors (located in the aortic arch and carotid sinus; TRP channels) and increased firing of the baroreceptor nerve (encode pulse pressure, as well); nerve projects to NTS, which send inhibitory projections to the C1 vasomotor area (sympathetic tone) and cardioacceleratory area, in addition to excitatory projections to the cardioinhibitory area; the result of the reflex is bradycardia and vasodilation (with decreased MAP, baroreceptor firing decreases resulting in disinhibition of the CA vasomotor area (vasoconstriction) and tachycardia

Question 45

How are high pressure baroreceptors in the aortic arch and carotid sinus different?

Answer 45

An increase in carotid sinus pressure has a greater effect on the systemic arterial pressure than does an increase in the aortic arch pressure (aortic arch receptor has a higher threshold; carotid sinus signal saturates quicker); aortic arch afferent pathway involves the vagus nerve; carotid sinus afferent pathway involves the sinus nerve, which joins to the glossopharyngeal nerve

Question 46

Describe the intrinsic cardiovascular chemoreceptor response.

Answer 46

A fall in arterial partial pressure of oxygen stimulates peripheral chemoreceptors OR decrease in brain pH stimulates central chemoreceptors to increase their firing rate (results in vasoconstriction and bradycardia); sensor are glomus cells found in aortic and carotid bodies (project to NTS)

Question 47

Why does the integrated response induce tachycardia?

Answer 47

high CO2 stimulates central chemoreceptors, which induce hyperventilation (a decrease in CO2 and stretch of receptors in the lungs combined with hypoxia sensed by peripheral receptors inhibit the cardioinhibitory area of the medulla (resulting in tachycardia)

Question 48

What is the effect of acidosis on the myocardium?

Answer 48

decreases contractility and cardiac output

Question 49

Describe the Bainbridge reflex.

Answer 49

Atrial B fibers detect changes in central venous pressure (project to NTS through vagus nerve); Increased stretch of these fibers raises heart rate (and decreases sympathetic vasoconstriction stimulation to the kidney or renal vasodilation and increase in urine output (diuresis))

Question 50

Does decrease in blood volume sensed by low pressure atrial B fibers change heart rate?

Answer 50

No

Question 51

What is the relationship of stroke volume, heart rate, and cardiac output with increases in blood volume? decreases in blood volume?

Answer 51

Increases in blood volume increase cardiac output (stroke volume is unchanged due to baroreceptor reflex and heart rate increases through Bainbridge reflex); decreases in blood volume decrease stroke volume and increase heart rate (baroreceptor reflex; cardiac output is lower than normal)

Question 52

What happens to the right atrial pressure in cardiac arrest?

Answer 52

Increase to 7 mm Hg (mean systemic filling pressure); result of the elasticity or compliance of cardiovascular system

Question 53

What is the effect of arterial dilation on venous return?

Answer 53

raises central venous pressure and thus increases venous return

Question 54

What is the effect of blood transfusion on means systemic filling pressure?

Answer 54

increases the mean systemic filling pressure (also increases venous return)

Question 55

How are increases in right atrial pressure counteracted?

Answer 55

initially, increases in RAP increase stroke volume and cardiac output; venous return would decrease due to the lower driving pressure for venous return (CVP-RAP); elevated cardiac output “sucks the right atrium dry” reducing RAP