Circulation 4: Microcirculation and Lymphatics

Question 1

What are precapillary resistance vessels?

Post capillary resistance vessels?

Describe their qualities and basic function/purpose. Which is more prominent: pre or post capillaries?

Answer 1

Precapillary resistance vessels:
arterioles
metarterioles (shunts, do not exchange gas)
precapillary sphincter

Post capillary resistance vessels:
venules

(post capillary resistance, venules have v little vascular smooth muscle so they don’t really control resistance v much. most of resistance is on pre-capillary side. ratio between pre capillary and post is about 4:1. 4x as much pre capillary resistance than post capillary resistance- imp. to understanding pathology of heart failure.)

sphincters and meta arterioles that have vascular smooth muscle on them. shunts between arterial and venous system and they do not exchange O and CO2 like capillaries, have vascular smooth muscle, not exchange vessels. but can contribute to pre-capillary resistance-resistance of blood flow from arterial to venous side.

Question 2

What are exchange vessels

Answer 2

capillaries (no VSM- 5 metameter diameter)

one cell layer thick of endothelial cells. no vascular smooth must. cells. v small in diameter. lot of them… total cross sectional area of all capillaries is enormous.

Question 3

Describe the characteristics of capillary blood flow.

Answer 3

low velocity, intermittent (vasomotion)
direction (pressure gradients)
not uniform
Rouleaux formation ( can form at high protein plasma conditions like myeloma, cancer, inflammation)

normal blood flow is v low velocity through capillaries bc total cross sectional area is huge.

intermittent, vaso-motion. blood flow not continuous through all capillaries bed. some open some closed. looks chaotic. dep. on pre-capillary sphincters, pressure gradients, can flow backwards sometimes, dep. on sphincters and pressure gradients. not uniform.

Question 4

Describe how RBC create Rouleaux formation.

Why does this become a problem in sickle cell anemia?

Answer 4

Rouleaux can form at high protein plasma
conditions: myeloma, cancer, inflammation

RBC create Reuleaux formation…. RBC about 8microns in diameters and capillaries are about 5microns in diameters. so RBC squeeze through capillaries. line up next to each other on angle- considered Reuleaux formation. happens bc membrane of capillaries touching membrane of RBC- allow for good gas exchange… between O and CO2. that formation is normal

normal RBC very flexible (shaped like dumbell) can bend when go through capillary and can squeeze themselves … sickle-cell don’t have normal gas exchange… bc abnormal shaped RBC has difficult time going through capillaries. so shape and char. of membrane are v imp. in normal O and CO2 exchange.

Question 5

Describe the factors that govern transcapillary fluid exchange. What causes it?

plasma oncotic pressure
capillary hydrostatic pressure
tissue oncotic pressure
interstitial hydrostatic pressure

Answer 5

Movement of fluid and exchange of nutrients out of and into the capillary. Starling law of the heart. four forces that det. movement of fluid from inside capillary to interstitum of interstiium back to capillary

a. Plasma oncotic pressure: an osmotic pressure exerted by substances found in the plasma, primarily plasma proteins. (proteins are solutes and exert osmotic pressure. make fluid hyper or hypo-osmotic)
b. Capillary hydrostatic pressure: mean capillary blood pressure.
c. Tissue oncotic pressure: an osmotic pressure exerted by substances dissolved in the interstitium, such as proteins. Counterpart to plasma oncotic pressure.
d. Interstitial hydrostatic pressure: hydrostatic pressure caused by the volume of fluid within the interstitium.

hydrostatic here not related to gravity. in capillaries its synonymous w bp and in interstitum, its really water pressure. in capillary hydrostatic pressure-mean capillary bp.

then also tissue oncotic pressure (interstitum) v little protein in interstitum.

in interstitial hydrostatic pressure- not bp, water pressure caused by volume of fluid in interstitum. really 2 forces, oncontic pressure in plasma and in interstitum. hydrostatic pressure in capillary and in interstitum. 2 forces either inside or outside of capillary.

Question 6

Describe fluid exchange between capillaries and interstitum - What kind of things leak out of capillaries?

Answer 6

fluid exchange. between vascular system (inside of capillary and interstitium) fluid usually always leaking out of capillaries- carries O , nutrients, glucose, cells, can get through fenestrated capillaries (holes in them) and even continuous capillaries, fluid in and out, carries nutrients, washes interstitial space of waste produces, equilibrates ions between intercellular space and interstitium, movement of fluid critical to maintaining healthy tissue

Question 7

Describe the Starling hypothesis of transcapillary fluid exchange.
Describe the overall difference in pressure from arterial to venous side and pressure differences in the interstitum vs plasma. What does this indicate about oncotic pressure inside/outside the capillary?

Answer 7

its really either filtration or absorption

arterial side on L, venous side bc pressure 32 mmHg and 15 mmHg …pressure going down from arterial to venous side (thats what the solid line indicates…has nothing to do w arrows) decline in bp from arterial to venous side. hydrostatic pressure inside. normally in interstitum hydrostatic pressure is 0. all fluid pressure inside capillary. oncotic pressure related to proteins floating around and you have much more proteins in plasma than interstitum so you have significant osmotic pressure inside the vessel and v little outside under normal conditions. oncotic pressure outside is negligible …

Question 8

What is oncotic pressure doing if pressure inside the vessel is around 25 and 0 outside, what will happen?

Answer 8

force pushing fluid out down pressure gradient) oncotic pressure significant inside and v little protein outside.

Question 9

What happens if there is more solutes in a solution?

Answer 9

if more solutes in solution then pulls fluid from hypo. osmotic fluid to hyper osmotic fluid. so oncotic pressure holding fluid inside vascular space.

Question 10

Which way are oncotic and hydrostatic pressures directed?

If you have 25mm Hg of oncotic pressure on the venous side and 32 mmHg on the arterial side, how will hydrostatic and oncotic pressure be affected?

Answer 10

2 forces going opposite directions. you have hydrostatic forcing fluid out and oncotic. pressure pulling fluid in. oncotic-absoprtion, hydrostatic- filtration

question of balance, which is greater. in diagram normally oncotic pressure around 25mmHg. so if your hydrostatic pressure on arterial side is 32, the diff of force pushing out and force in is 7mmHg OUT. on arterial side, net force is greater than oncotic. force so you have a net force of fluid out.

as hydrostatic pressure drops to venous side, situation reversed bc now oncotic pressure greater than venous pressure so you will have fluid being pulled into the vessel. so absorption.

Question 11

Filtration occurs in some vascular beds and absorption in some because of balance of hydrostatic/oncotic pressure.

What vascular bed is always filtering fluid?

Answer 11

glomerulus… special capillary bed, hydrostatic pressure of about 80 mmHg… rest is around 32 to 15. glomerulus high hydrostatic pressure is there to filter fluid all time bc always higher than oncotic/pressure

Question 12

Where do you want to avoid having fluid? What does this imply about hydrostatic/oncotic pressure in this area?

Answer 12

alveoli in lungs. alveoli in interstitum and if had fluid there sinking into alveoli you’d have pulmonary edema.

capillary system has lower pressure. R ventricle only generates 25mmHg. arterial pressures in pulmonary circuit low pressures -hydrostatic always lower than oncotic- keep lung dry. always absorption.

Question 13

In skeletal muscles do you mostly filter or absorb fluid? Why?

Answer 13

most skel. muscle you’re filtering fluid all time, washing cells around to equilibrate with fluid, waste taken away.

Question 14

Where does extra fluid go?

Answer 14

where does extra fluid go? fluid washed out goes into interstitum… lymphatic system pick up. has valves and shunts blood back to R side of heart. lymphatics move fluid- has to do w muscle contracting, squeezing the lymphatics- they’re v thin walled structures, v easily compressed and your movements - push fluid back to CV system on R side of heart. this is normal system.

Question 15

What is the key factor that holds fluid within capillaries?

Answer 15

osmotic pressure of plasma proteins (oncotic pressure)

Question 16

What is the most clinically relevant protein in determining plasma oncotic (osmotic) pressure? Why?

Answer 16

The most clinically relevant protein is albumin. Albumin exerts a greater osmotic force than can be accounted for solely on the basis of the number of molecules dissolved in a unit volume of plasma. In other words, based on its concentration in the plasma, albumin contributes a disproportionately large percentage of the plasma oncotic pressure. This is due to the electrostatic interaction of albumin with negatively charged ions (chloride) resulting in the retention of more sodium within the vascular space.

albumin 51% (65% of plasma oncotic pressure)
globulin 17%
fibrinogen 4%
others 28%

-its a positively charged protein, attracts Cl- which is neg charged ion. negativity brings Na onto albumin. bc of charge it attracts NaCl… increases osmotic force of albumin and holds more fluid than you’d expect.
v important protein - most imp. protein in blood bc of these charged. albumin is most important protein in blood in terms of oncotic force.

Question 17

Describe the effect of the following determinants of capillary hydrostatic pressure:

arterial pressure
venous pressure

Answer 17

arterial pressure- exerts a relatively small effect on capillary hydrostatic pressure because of significant pre-capillary resistnace (prevents P from being transferred into capillary)

venous pressure- exerts a larger effect on capillary hydrostatic pressure bc of little post-capillary resistance

Question 18

If you decrease the pre/post capillary ratio how will this affect capillary hydrostatic pressure?

Answer 18

increase in capillary hydrostatic pressure

In other words, an increase in venous pressure will exert a greater increase in capillary hydrostatic pressure than an increase in arterial pressure.

Question 19

If you increase the pre/post capillary ratio how will this affect capillary hydrostatic pressure?

Answer 19

decrease capillary hydrostatic pressure

In other words, an increase in venous pressure will exert a greater increase in capillary hydrostatic pressure than an increase in arterial pressure.

Question 20

Will arterial pressure or venous pressure have a larger effect on capillary hydrostatic pressure.

Answer 20

capillary hydrostatic pressure is primarily determined by the pre/post capillary resistance ratio.

arterial side has significant pre-capillary resistance which prevents pressure from being transmitted from arterial side to capillary. venous side has v little post-cap resistance so any little increase in pressure can be transmitted backward into capillary.

for ratio- of pre capillary to post cap. is 4 to 1

Question 21

If you get a spike in arterial pressure how will this affect pre-capillary sphincters?

Answer 21

if get spike in arterial pressure its not transmitted bc of way vascular smooth muscle responds but that increase in pressure stretches the vascular smooth muscle of pre-capillary resistors. smooth muscle- increasing diameter of vessel, response of smooth muscle is to contract and increase resistance to prevent downstream increases in pressure. arterial pressure doesn’t cause much increase in capillary hydrostatic pressure

Question 22

How will capillary hydrostatic pressure be effected in a patient with hypertension?

Answer 22

pt w hypertension- don’t have higher capillary hydrostatic pressure than us. if get spike in arterial pressure its not transmitted bc of way vascular smooth muscle responds but that increase in pressure stretches the vascular smooth muscle of pre-capillary resistors. smooth muscle- increasing diameter of vessel, response of smooth muscle is to contract and increase resistance to prevent downstream increases in pressure. arterial pressure doesn’t cause much increase in capillary hydrostatic pressure

Question 23

What will happen if venous pressure goes up? (L ventricle not contracting normally … what will result?)

Answer 23

increase in venous pressure has large effect on capillary hydrostatic pressure. if L ventricle not contracting normally that pressure backs up, leave more ESV behind makes more difficult to fill, pressure backs to L atrium, then pulmonary veins… this is saying if venous pressure goes up that backs up fluid in capillaries and causes high capillary hydrostatic pressure and if you’re at high capillary hydrostatic pressure and exceeds 25 mmHg (which is oncotic pressure in blood) then you get filtration… fluid into interstitum surrounding alveoli and ultimately it sinks into alveoli and have pulmonary edema.

Question 24

Why don’t you have pulmonary edema if you have pulmonary hypertension?

Answer 24

don’t have pulmonary edema if you have pulmonary hypertension bc pulmonary hypertension is on arterial side (not affecting capillary hydrostatic pressure)

Question 25

What will happen if a patient has pulmonary hypertension. (Which side of heart is failing?)

Answer 25

on R side - pulmonary hypertension for ex. (R heart failure).. don’t have pulmonary edema if you have pulmonary hypertension bc pulmonary hypertension is on arterial side (not affecting capillary hydrostatic pressure)

if you have pulmonary hypertension is a higher afterload on R ventricle, R ventricle fails, backs up to R atrium and now fluid goes to venous system on R side, IVC backs up into liver, can get portal hypertension, cirrhosis of liver. get increase in venous pressure in viscera, all parallel w e/o .. stomach, intestines, fluid seeps out and patients get accumulation of fluid in abdomen- bc venous pressure backing up from heart goes to organ systems. also have swelling in ankles bc when stand up higher pressure on lower body. art. pressure not significant in raising capillary pressure but venous pressure is and venous can become abnormally elevated

Question 26

When you lift weights and muscles expand for 2-3 hours then go back down, what is happening?

Answer 26

muscles expand then 2-3 hours go down again.. muscles not getting bigger in hour or 2 but by increasing isometric tension in muscles squeezes venous side of system, squeezes vessels and closes them down, increase venous resistance and therefore blood comes in normally into cap. and pressure in cap goes up and causes more filtration and interstitial fluid goes up and you feel tighter. when you stop, fluid recedes and goes back to CV system. during exercise get tremendous increases in pressure in capillary system. get lots of filtration of fluid and lymphatics circulate fluid back and forth throughout system.

Question 27

What are endothelium vasodilators?

Answer 27

prostacyclins, EDRF, NO, and metabolites

metabolites (adenosine, H+, CO2, K+) - cause relaxation; vasodilation.

Nitric Oxide (NO) - acts via cGMP/PKG to phosphorylate myosin light chain kinase (MLKC) which inhibits MLCK, decreases MLC phosphorylation and decreases actin-myosin interaction, resulting in relaxation, i.e. vasodilation.

prostacyclins – increases cAMP to phosphorylate myosin light chain kinase (MLKC) which inhibits MLCK, decreases phosphorylation of MLC, decreases actin-myosin interaction resulting in relaxation, i.e. vasodilation.

Question 28

What is a endothelium vasoconstrictor?

Answer 28

endothelin (ET) - ET receptors on vascular smooth muscle cells (VSMC) activate phospholipase C (PLC) to release IP3 which in turn releases intracellular Ca2+, causing vasoconstriction.

Question 29

Describe adenosine. How is it produced, what does it release/what is its function?

Answer 29

adenosine- ATP broken down to adenosine-powerful vasodilator. production of NO through vagal stimulation in this case

Question 30

What does endothelial cell do?

Answer 30

release vasoconstrictors/vasodilators and regulate to some extent pre/post capillary resistance

Question 31

What is the function of lymphatics?

Answer 31

Collects and returns interstitial fluid to the circulatory system.

structures that take fluid back to heart…

Question 32

Describe the structure/characteristics of lymphatics.

Answer 32

unidirectional tissue fluid flow (water) bc of valves. thin wall structures, large collecting vessels return lymphatic fluid to subclavian veins which bring back to R side of heart.

a. unidirectional flow of tissue fluid (plasma) and protein back to the heart.
b. valves (like veins) but thinner wall structure.
c. non-fenestrated endothelium, little to no basal lamina; no smooth muscle.
d. large collecting vessels return lymphatic fluid to subclavian veins.

Question 33

What are factors governing lymph flow?

Answer 33

a) amount of capillary filtration
b) skeletal muscular activity
c) lymphatic unidirectional valves

more fluid in interstitum then more lymph flow, skel. muscle squeezes them just like veins.

Question 34

Why do you get swelling after surgery?

Answer 34

if you operate you destroy lympathic system of tissue- thats why get tremendous swelling after surgery- have damaged capillaries, fluid leaking out.. and no lymphatic system to pull that fluid away… so put drainage tubes in to drain fluid out to compensate for loss of lymphatics. they do grow back hopefully. sometimes they don’t and people have problems w fluid accumulation in bodies …lymphatics important

Question 35

What is edema? What are clinical manifestations?

Answer 35

An accumulation of excess fluid within the interstitial space.
(under normal condition trans-capillary fluid movement normal to bathing cells to bring nourishment and bring away waste. abnormal conditions edema is the result- reduction of plasma protein- lose albumin then lose oncotic pressure and that oncotic pressure holding fluid in so get more filtration of fluid)

Clinical manifestations: swelling of the ankles, ascites, pulmonary edema.

Question 36

What are precipitating factors of peripheral edema in regards to plasma protein concentration, capillary hydrostatic pressure, permeability of capillary membrane and lymphatics?

Answer 36

a) reduction in plasma protein concentration (serum albumin

Question 37

What are some possible causes of edema? (heart, venous return, renal, liver, injury…)

Answer 37

a) congestive heart failure
b) mechanical obstruction of venous return
c) renal disease - loss of protein
d) liver disease - lack of protein (albumin) synthesis
e) burn – increases capillary permeability.

lose albumin (prod. in liver) so if you have liver disease, lack of albumin synthesis.. cirrhosis of liver causes acites (accumulation of fluid) increase in cap.

increase in permeability of capillaries- burns… increases cap. permeability and fluid leaks out of capillaries and can’t maintain vascular volume, fluid leaks out, bp drops. infection too. local burn to finger, swells. damaged capillaries and fluid leaking out locally and causing increase in tissue pressure. over whole body.. or large percentage..

these are mechanisms that affect/precipitate this- anything that obstructs flow back to heart (venous return) will increase pressure distally and that will increase edema formation. (could be tumor etc)

Question 38

Describe how congestive heart failure on L side and R side can lead to edema.

Answer 38

congestive heart failure L and R ventricle depressed w contractility .. on L side fluid backs up into lungs and on R side it backs up into systemic venous system -can ascites, pulmonary edema, swelling of ankles, can get whole thing from congestive heart failure.