W7 - Microcirculation, lymph (2.10)

Question 1

Describe the general structure of a capillary bed.

How is the blood flow in such a capillary bed regulated?

Answer 1

arterioles → capillaries → venules

smooth m. precapillary sphincter (btw arteriole + capillary) + arteriole regulate blood flow by contraction and relaxation

Question 2

What are the 2 roles of microcirculation?

Answer 2

• nutritive: metarterioles
• non-nutritive: shunt (e.g. in glomeruli of kidney, blood flow through skin for T regulation, etc.)

Question 3

What is a thoroughfare channel?

Answer 3

channel btw arteriole and venule, shortcut through capillary network (e.g. metarteriole)

Question 4

Differentiate btw the 3 types of capillaries.

Give one example for each type.

Answer 4

• continuous capillaries: most common type, interendothelial junctions 10 - 15nm, e.g. in skeletal m.
• fenestrated capillaries: perforated endothelium (50 - 80nm holes), e.g. in small intestine
• discontinuous capillaries (= sinusoids): fenestrations + large gaps (100 - 1000nm) in btw cells, e.g. liver sinusoids

Question 5

Which structures form tight junctions btw endothelial cells?

Where can they characteristically be found?

Answer 5

claudins 1, 3, 5 + occludin

e. g. in CNS → blood-brain barrier
* (esp. CLDN 5 + occludin)*

Question 6

What are the 4 routes of transport across a capillary?

Answer 6

• transcellular route
• small-pore paracellular route
• large-pore paracellular route
• transcytosis

Question 7

What is the mechanism of transcellular transport?

Which molecules undergo this kind of transport?

Answer 7

by simple diffusion

• gases
• lipid soluble molecules (anesthetics)
• water (via aquaporin-1)

Question 8

Describe the model of August Krogh’s tissue cylinder.

Answer 8

single capillary supplies cylinder-shaped volume of a tissue, many cylinders adjacent to each other resemble capillary bed in tissue

⇒ predicts how [O₂] within capillary lumen falls along the length as O₂ exits
→ highest at arterial end, lowest at venous end

_{describes transcellular transport of gases in capillaries}

Question 9

Which factors determine the [O₂] along the length of a capillary?

Answer 9

1. concentration of free O₂ in the arteriolar blood + O₂ content of the blood (usually 20%)
2. radial diffusion coefficient (how fast O₂ diffuses out of capillary lumen)
3. dimension of capillary (r, l) and tissue cylinder (r)
4. capillary blood flow
5. O₂ consumption

​BUT: capillary flow + metabolic demand are the most important ones

Question 10

Describe how [O₂] changes in response to metabolic demand and capillary flow.

Answer 10

• ↑ flow → more O₂ → smaller fraction of [O2] needed to satisfy tissue’s needs
• ↑ metabolic demand → tissue extracts more O₂

​

Question 11

What does the radius of Krogh’s tissue cylinder determine?

Physiological consequence?

Answer 11

capillary density
the larger the cylinder, the more distant the next capillary

⇒ during increased O₂ consumption (e.g. exercise) arterioles + precapillary sphincters dilate to open all capillaries → reduce radius of Krogh cylinder

_{NOTE: in resting state only 20% of all capillaries open}

Question 12

What is the mechanism of small-pore paracellular transport?

Which molecules undergo this kind of transport?

Answer 12

by diffusion through intercellular clefts, gaps, fenestrae

• water soluble molecules
• small polar molecules (less than albumin size)

Question 13

Which law describes the flux of paracellular transport?

Formula.

Answer 13

Fick’s law of diffusion
solute flux that crosses a distinct capillary surface is proportional to the conc. difference across the wall + the permeability for this solute

J = -PS (C_outside - C_inside)

• J = solute flux
• P = capillary permeability
• S = capillary surface
• C_outside - C_inside = concentration difference

Question 14

What is the difference btw flow- and diffusion limited transport?

Answer 14

• flow-limited transport: only blood flow restricts rate of diffusion due to rapid equilibration of small molecules across the capillary
• diffusion-limited transport: diffusion is restricted if no equilibrium across the capillary (?)

Question 15

What is the mechanism of large-pore paracellular transport?

Which molecules undergo this kind of transport?

Answer 15

very slow diffusion through large pores

• protein-sized molecules

Question 16

What is the mechanism of transcytosis?

Which molecules undergo this kind of transport?

Answer 16

vesicular transport

• translocation of macromolecules

Question 17

What is convection?

Another name.

Answer 17

also: solvent drag

water can cause diffusion of dissolved solute together with own bulk movement through aquaporin 1

Question 18

What are the 2 driving forces of convection?

Answer 18

• hydrostatic pressure difference (ΔP_c-if):
  difference btw intra- and extravascular pressure
• oncotic pressure difference (Δπ_c-if):
  difference btw intra- and extravascular osmotic pressure caused by plasma proteins

Question 19

Which formula is used to determine whether there is a net fluid movement into or out of the capillary?

What does the plus or minus sign indicate?

Answer 19

Starling equation
if J_v > 0 → filtration (out of cap.)
if J_v < 0 → absorption (into cap.)

J_v = K_f [(P_c - P_i) - σ(π_c - π_i)]

• J_v = fluid flow
• K_f = filtration coefficient
• P_c = capillary hydrostatic pressure
• P_i = interstitial hydrostatic pressure
• σ = reflection coefficient
• π_c = capillary oncotic pressure
• π_i = interstitial oncotic pressure

Question 20

What is the unit of the filtration coefficient?

What does it describe?

Another name.

Answer 20

also: hydraulic conductance

describes water permeability of capillary wall by ensemble of AQP1 channels and paracellular pathway

in [ml/min * mmHg]

Question 21

What does the reflection coefficient describe?

Answer 21

how a semipermeable barrier reflects solute X as water moves across the barrier, btw 0 and 1

• 0 = solute does not cause osmotic pressure, moving perfectly with water across the membrane
• 1 = solute cannot cross the membrane, causes osmotic pressure

Question 22

What does P_c describe?

Value.

What is its effect?

Answer 22

capillary hydrostatic pressure
35 mmHg arteriolar end → 15 mmHg venous end

Question 23

How can it P_c changed?

What is its effect?

Answer 23

↑P_art, ↑P_ven, arteriolar dilation, venous constriction
→ ↑ P_c

⇒ the greater P_c, the greater filtration
(bc fluid is forced into interstitium)

_{<u>NOTE:</u> ↑ Pven increases Pc more than ↑ Part does}

Question 24

What does P_i describe?

Value.

Answer 24

interstitial hydrostatic pressure
∽ 0 mmHg

• usually slightly negative bc of fluid removal by lymph
• in encapsulated organs slightly positive due to expansion of high-P vessels pushing interstitial fluid agains capsule

Question 25

How does P_i have to be changed in order to increase filtration?

Answer 25

⇒ the smaller P_i, the greater filtration

(bc effect of fluid forced into interstitium is increased)

Question 26

What does π_c describe?

Value.

Answer 26

capillary oncotic pressure
∽ 25 mmHg in normal plasma with standard mixed protein concentration of 7 g/dl

Question 27

How can π_c be changed?

What is its effect?

Answer 27

↓ [protein] → ↓ π_c

⇒ the smaller π_c, the greater filtration
(bc less water is retained by proteins in capillary)

_{<u>NOTE:</u> small solutes do not contribute to πc}

Question 28

What would be causes for an increase or decrease in π_c?

Answer 28

• increase: dehydration (rel. [protein] in blood is incr., due to decr. volume)
• decrease: nephrotic syndrome, protein malnutrition, liver failure (rel. [protein] in blood is decr.)

Question 29

What does π_i describe?

Value.

Answer 29

interstitial oncotic pressure
same as lymph, varies from tissue to tissue, 0 - 10mmHg

BUT: increases along axis of capillary, lowest near arteriolar end (bc only protein-free filtration)

Question 30

How can π_i be changed?

How does π_i have to be changed in order to increase filtration?

Answer 30

inadequate lymphatic function → ↑ π_i

⇒ the larger π_i , the greater filtration
(bc more fluid attracted by accumulating proteins into interstitium)

Question 31

Illustrate how the individual and net pressures change along a capillary.

Answer 31

• P_c ↓
• P_i = constant
• π_c = constant
• π_i ↑

​⇒ filtration at arteriolar end, absorption at venous end

Question 32

Describe the features of the revised model for fluid exchange across continuous endothelia w/ interendothelial junctions.

Answer 32

• primary barrier for oncotic pressure is not capillary, but only glycocalyx overlying paracellular clefts
• glycocalyx not in direct contact w/ interstitium, but subglycocalyx fluid (2^nd compartment)
• intercellular cleft (3^rd compartment), interstitium (4^th compartment)

BUT: similar to Starling model when 0 net fluid movement

Question 33

Describe ultrafiltration w/r/t the revised model of fluid exchange.

Answer 33

P_subglyco > P_cleft and P_i

→ J = positive = ultrafiltration at arteriolar end of capillary into interstitium

Question 34

Describe absorption w/r/t the revised model of fluid exchange.

How do you call the observable mechanism?

Answer 34

J = negative = absorption
H₂0 + small solutes from subglycocalyx space to cap. lumen

→ concentrating protein in subglycocalyx space
→ incr. π_sg opposes further absorption + quickly brings it to a halt

⇒ osmotic assymetry/rectification

Question 35

What is the function of lymph?

Answer 35

normally filtration > absorption

→ excess filtered fluid + leaked proteins returned to circulation via the lymph

Question 36

At which rate is lymph produced?

How much of the total filtrate becomes lymph?

Answer 36

120 ml/h → 2-4 l/d

1/10 of filtration → lymph

Question 37

Describe the structure of the interstitium.

Answer 37

2 phases:

• proteoglycan mesh traps H₂0 molecules → tissue gel / gel phase
• small free fluid vesicles (< 1%) = sol phase

Question 38

Explain the general structure of lymphatics.

Answer 38

thin-walled endothelial channels similar to capillaries, endothelial cells overlap to form primary lymph valves

anchoring filaments tether lymphatics to interstitium

Question 39

How does the interstitium respond to an increased filtration load?

Answer 39

↑ filtration → ↑ P_i

• part of fluid taken up by gel → expansion - atmospheric P level (then primary lymph valves open + fluid leaves into lymphatics)
• larger part accumulates as free fluid vesicles → rapid V incr. > atmospheric P level

_{NOTE: if too accumulation > lymph flow → edema}

Question 40

Describe the lymph flow through the body, listing the different types of lymph vessels.

Answer 40

1. interstitium → initial lymphatics w/ primary lymph valves
2. fuse to collecting lymphatics w/ secondary lymph valves
3. eventually drain into v. subclava dex./sin.

Question 41

How does the pressure in initial lymphatics differ from that in collecting lymphatics?

Answer 41

• initial lymphatics: -1 - 1mmHg
• collecting lymphatics: 1 - 10 mmHg

Question 42

Lymph flow is unidirectional.

Why?

Answer 42

primary lymph valves permit interstitial fluid to enter, secondary lymph valves prevent retrograde lymph flow, then pushed forward by sk. muscle contraction

Question 43

Lymph flow depends on… ?

Answer 43

depends on P_i
↑P_i → ↑lymph flow

Question 44

What is an edema?

Causes?

Answer 44

occurs when volume of interstitial fluid exceeds capacity of lymphatics to return it to the circulation

due to excess filtration/blocked lymphatics (e.g. by tumors, parasites)

Question 45

What are the effects of histamine?

Answer 45

• arteriolar dilation
• venous constriction

⇒ large ↑ P_c + local edema