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) _{NOTE: 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