Week 1: Properties of the microcirculation

Question 1

Define vascular tone. List 3 principal categories of stimuli that modify the tone of the pre-capillary resistance vessels.

Answer 1

-the state of partial contraction of vascular smooth muscle at rest
Categories of stimuli
1. physical factors (bp/stretch)
2. chemical factors (local metabolites)
2. neural input (sympathetic nerves)

Question 2

Describe the response of vascular smooth muscle when plasma levels of norepinephrine are altered. Indicate the receptor that is activated

Answer 2

• norepi interacts with alpha-receptors
• response is called alpha-adrenergic vasoconstriction, causes contraction of smooth muscle (remember that a1 activation causes vasoconstriction)
• the sympathetic nerves are tonically active, inhibition of these nerves leads to relaxation and vasodilation
• few vessels have neurally mediated vasodilation.

Question 3

Define the term “auto regulation” in terms of blood flow in response to changes of perfusion pressure. Indicate the two likely mechanisms involved in this local response.

Answer 3

• Autoregulation=the ability of a vascular bed or organ to maintain blood flow constant when perfusion pressure (i.e. input arterial bp) is altered over a certain range
• local control mechanisms all probably involved
• Two likely mechanisms
  1. myogenic regulation: increase pressure dilates and stretches SM->pacemaker fires leading to contraction and decreased diameter-> increased resistance leads to decreased flow
  2. Metabolic regulation: (vasodilators present in blood), increased pressure-> increased flow -> wash out vasodilators and returns to normal blood flow if local increase of vasodilators is terminated

Question 4

Describe the influence of the ratio of pre-capillary to post-capillary resistance on mean capillary blood pressure.

Answer 4

Pc=[Pv(Ra/Rv)+Pa]/[1+(Ra/Rv)]
-Ra/Rv is the ratio of arterial resistance to venous resistance. Pc is mean capillary bp
-for many vascular beds, ratio is 5:1
meaning:
1. an increase in venous pressure by a given amount has 5x the effect of Pc as does the same increase in arterial pressure
2. If arterial inflow obstructed (Ra=infinity), Pc approaches Pv
3. If venous outflow is totally obstructed (Rv=infinity), Pc approaches Pa

Question 5

define diffusion and filtration. Indicate the site in the capillary wall for exchange of lipid soluble molecules, for water soluble molecules and for large macromolecules.

Answer 5

-Diffusion is most important for exchange of solutes, gases, nutrients and waste products between capillaries and cells (due to concentration gradients)
-Filtration-absorption (starling landis forces) is important for movement of fluid between blood and tissue due to pressure forces
Sites of exchange
1. lipid soluble: entire endothelial surface
2. water soluble: water filled channels of limited dimensions-pores
3. Macromolecules: large slits, or vesicles

Question 6

Describe the forces responsible for filtration-absorption along a capillary. Indicate how the summation of these forces determines filtration-absorption and which of the forces is normally changing during our daily activities. Which factors involved in these forces are most important?

Answer 6

-pressure favoring movement of fluid out of vessel (filtration): bp and oncotic pressure of interstitial fluid
-pressure favoring movement of fluid into vessel (absorption): plasma oncotic pressure and fluid pressure in interstitial space
-Starling Landis Equation
F=Qf=k[(Pc+OPif)-(Pi+OPpl)]
OPif=interstitial fluid oncotic pressure
Pi=pressure in interstitial space
OPpl=plasma oncotic pressure
-Remember that Q=deltaP/R
-Pc is most important factor in equation, affected by resistance to blood flow prior to and after capillaries and arterial and central venous bp
-Ra is more important than Rv

Question 7

Compare, in very general terms, the approximate magnitude of daily cardiac output, lymph flow, diffusion exchange and filtration-absorption exchange. Describe function of lymphatic system.

Answer 7

Values per 24hrs
Daily CO: 7200L
Lymph flow: 2-4L
protein in lymph: 75-195g
diffusion exchange: 80,000L
glucose exchanged: 20,000g
filtration absorption: 
protein filtered: 80-200g
protein absorbed: 5g
volume filtered: 20L
volume absorbed: 16-18L
Lymphatic system: lymph volume contains much of plasma protein lost through filtration and diffusion. Helps maintain circulating blood volume via its ability to return plasma protein to blood. otherwise lower plasma oncotic pressure would lead to decreased blood volume.

Question 8

What is the primary factor responsible for adjustment of blood flow in the microcirculation?

Answer 8

-ability of smooth muscle in vessel walls to response to various stimuli by contraction or relaxation. Basically, change in vessel diameter.

Question 9

Describe the arrangement of vascular smooth muscle.

Answer 9

Two types

1. Multi-unit: tends to be larger vessels Minimal electrical connection between muscle cells. Depends on nerve imposes to initiate contraction
2. Single-Unit: small arteries and arterioles
   - have pacemaker cells, capable of cell cell propagation of electrical stimuli. Respond to stretch by increasing frequency of firing, which causes contraction of vessel.

Question 10

What are the local vs. remote/central control of vascular tone?

Answer 10

REMOTE/CENTRAL
1. Vasoconstrictor nerve fibers
2. blood-born excitatory or inhibitory agents
3. vasodilator nerve fibers
LOCAL
1. metabolic agents
2. muscle cell stretch (myogenic regulation)
3. Nitric Oxide (NO)

Question 11

What physical law governs the process of diffusion?

Answer 11

Fick’s Equation
J=-DA dc/dx
Meaning: ability of solutes to traverse pore depends on size of molecule relative to size of pore, cross sectional area for diffusion (A), concentration gradient