Microvasculature

Question 1

Calculating mean arterial pressure (MAP)

Answer 1

• MAP = CO x TPR
• Therefore MAP will increase if CO increases and TPR is constant, or if TPR increases and CO is constant
• MAP will not increase if one increases and the other decreases as long as the product is the same

Question 2

Differences btwn arterial and venous systems

Answer 2

• Arterial: low resistance, high BP, low volume (10%), low compliance
• Venous: low resistance, low BP, high volume (70%), high compliance

Question 3

Factors affecting venous return

Answer 3

• Residual BP after capillaries (Pv)
• Venoconstriction via sympathetic output on veins
• Skeletal muscle pumps
• Respiratory pump (negative pressure from expanding thorax during inspiration drives blood back to heart)
• Cardiac suction: movement of heart during early systole sucks blood into atria

Question 4

Functions of microcirculation

Answer 4

• Regulates TPR
• Regulates distribution of blood flow
• Site of exchange of solutes btwn blood and tissue (regulated by permeability of vessels)
• Movement of fluid btwn vascular and interstitial space

Question 5

Architecture of microvasculature 1

Answer 5

• There are arterial-venous shunts (anastomoses) btwn some arterioles and venues
• There are pre-capillary sphincters (vascular smooth muscle cuffs) at the entrance of capillaries (arteriole side), largely determine Pa

Question 6

Architecture of microvasculature 2

Answer 6

• There are post-capillary resistance vessels that determine Pv
• Metarteriole connects arterioles to venules, but also sends out capillary branches to the capillary bed
• Arterioles, metarterioles and large venules/veins are innervated by sympathetics and have smooth muscles (less so in veins/venules)

Question 7

Pre-capillary resistance vessels

Answer 7

• Small arteries and arterioles have high degree of tone at rest, but this tone is the major site of TPR regulation
• Arterioles change diameter in response to more or less sympathetic stimulation, and its the diameter change in arterioles that regulates TPR
• The resistance in these vessels is also controlled by local factors
• The vessels determine the number of capillaries open and perfused at any moment, and thus control the capillary surface area exposed for solute exchange

Question 8

Physics of capillaries

Answer 8

• Due to the extremely large overall cross-sectional area, there is very slow flow thru capillaries to facilitate transport
• The blood has a greatly increased area of contact w/ surrounding tissue when it is in a small diameter vessel
• The ratio of pre-capillary resistance (resistance in arterioles, Ra) to post-capillary resistance (resistance in venules, Rv) determines the pressure in the capillary themselves (Pc)

Question 9

Vascular tone

Answer 9

• The tone in pre-capillary beds is due to physical factors (BP in vessels), chemical factors (local metabolites), and neural input
• Some pre-capillary beds have high resting tone (SKM), some have low (renal)

Question 10

Vascular smooth muscle categories

Answer 10

• Multi-unit: minimal electrical communication btwn muscle cells, depends on nerve impulses to initiate contraction
• Single-unit: capable of cell-cell propagation of APs and contains pacemaker cells (can be innervated)
• The pacemaker cells respond to stretch by increasing frequency of firing, which yields contraction of the vessel
• Single-unit vessels are very responsive to local environmental changes, while multi-unit muscles can respond to environmental changes but are mostly driven by innervation

Question 11

Distribution of different SM unit types

Answer 11

• Large arteries have mostly multi-unit, with medium sized arteries having both and arterioles having mostly single-unit
• Capillaries do not have SM
• Small venues have mostly single unit, medium veins have both, and large veins have mostly multi-unit
• Key note: The blood vessels in the brain are all exclusively single units that are not innervated, therefore blood flow to regions of the brain depend solely on local changes

Question 12

Neural control of blood flow

Answer 12

• Single units can be innervated by sympathetics, but the pre-capillary sphincters are not (local only)
• NE induces contraction of SM (alpha-adrenergic vasoconstriction)
• Inhibition of NE release leads to muscle relaxation and vasodilation

Question 13

Hormonal control of blood flow

Answer 13

• Epinephrine at low concentrations combines w/ b2 receptors and dilates blood vessels, lowering TPR
• At higher concentrations the a1 affects outweigh the b2 effects and there is vasoconstriction, increasing TPR

Question 14

Metabolic regulation of blood flow

Answer 14

• Most local metabolites will cause vasodilation, and the importance of each factor varies from bed to bed
• Increase in these factors leads to vasodilation and increase in flow
• The increase in flow decreases the amount of these factors, leading to more vasoconstriction and increased pressure

Question 15

Myogenic regulation of blood flow

Answer 15

• Only in single-unit SM, which have pacemakers that respond to stretch
• The stretch is a function of the pressure across the wall and the compliance of the wall
• Increasing the stretch increases pacemaker firing, and the smooth muscle cells respond by contracting
• Usual reason for increased stretch is increased blood pressure

Question 16

Autoregulation

Answer 16

• Only local factors impart the ability of auto regulation, where as neural and endocrine factors are extrinsic regulation
• The purpose of auto regulation is to maintain a constant blood flow, thus if there is increased pressure -> increased gradient -> increased flow then the body vasoconstricts (due to stretch-> increased pacemaker firing-> vasoconstriction) to increase resistance and restore flow to normal levels

Question 17

Solute exchange

Answer 17

• The most important mechanism for solute exchange is diffusion
• Lipid soluble substance (including CO2, O2 and H2O) can pass through the endothelial cells and thus diffuse thru any type of capillary bed (freely diffusible)
• Small molecules and ions (glc, K, Na) can pass thru pores in fenestrated and discontinuous capillaries (restricted diffusion)
• Large molecules must move through large pores/channels or via pinocytosis
• Overall, small things diffuse thru capillary walls faster than big things (smaller diffusion coefficient)

Question 18

Filtration-absorption 1

Answer 18

• The way in which fluid is moved btwn the circulatory system and interstitial fluid (ISF)
• What moves btwn the two is an ultra-filtrate of plasma not containing large proteins or cells
• This is a balance of essentially 2 factors: pressure in the capillary (Pc; pushing out) and oncotic pressure of plasma (due to plasma proteins/albumin; pulling in)
• Oncotic pressure is 25 mmHg, thus as long as Pc > 25 there is net filtration (fluid moves out of capillaries)
• If the Pc < 25 there is net absorption (fluid moves into capillaries

Question 19

Filtration-absorption 2

Answer 19

• Generally, in the upstream areas of capillaries (near arterioles) the pressure is above 25 and filtration dominates
• As the blood moves further down to the venous side Pc falls below 25 and absorption dominates
• Pc is determined by the ratio of arteriole resistance to venule resistance (Ra/Rv)
• High Ra means less flow thru arterioles and thus lower Pc
• Low Ra means more flow thru arterioles into capillaries and thus higher Pc

Question 20

Filtration-absorption 3

Answer 20

• If Ra/Rv increases (arterioles constrict), Pc decreases and absorption is more favored
• If Ra/Rv decreases (arterioles relax), Pc increases and filtration is more favored
• Since the resistance of arterioles is what most changes, Ra/Rv is largely determined by Ra (Rv is relatively static)
• It is worth noting that since Ra/Rv is generally around 5, a single unit increase in Rv has a 5x greater impact on the ratio as a single unit on Ra

Question 21

Overview of transport

Answer 21

• Bulk flow of fluid btwn ISF and capillaries: filtration-absorption
• Movement of solutes in and out of the capillaries: diffusion
• The lymphatic system picks up and recycles the excess filtrate that is not reabsorbed by the capillaries (about 2-4L/day excess filtrate)