W7 - Microcirculation, lymph (2.10) Flashcards Preview

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Flashcards in W7 - Microcirculation, lymph (2.10) Deck (45)
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1
Q

Describe the general structure of a capillary bed.

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

A

arterioles → capillaries → venules

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

2
Q

What are the 2 roles of microcirculation?

A
  • nutritive: metarterioles
  • non-nutritive: shunt (e.g. in glomeruli of kidney, blood flow through skin for T regulation, etc.)
3
Q

What is a thoroughfare channel?

A

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

4
Q

Differentiate btw the 3 types of capillaries.

Give one example for each type.

A
  • 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
5
Q

Which structures form tight junctions btw endothelial cells?

Where can they characteristically be found?

A

claudins 1, 3, 5 + occludin

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

6
Q

What are the 4 routes of transport across a capillary?

A
  • transcellular route
  • small-pore paracellular route
  • large-pore paracellular route
  • transcytosis
7
Q

What is the mechanism of transcellular transport?

Which molecules undergo this kind of transport?

A

by simple diffusion

  • gases
  • lipid soluble molecules (anesthetics)
  • water (via aquaporin-1)
8
Q

Describe the model of August Krogh’s tissue cylinder.

A

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

9
Q

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

A
  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

10
Q

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

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

11
Q

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

Physiological consequence?

A

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

12
Q

What is the mechanism of small-pore paracellular transport?

Which molecules undergo this kind of transport?

A

by diffusion through intercellular clefts, gaps, fenestrae

  • water soluble molecules
  • small polar molecules (less than albumin size)
13
Q

Which law describes the flux of paracellular transport?

Formula.

A

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 (Coutside - Cinside)

  • J = solute flux
  • P = capillary permeability
  • S = capillary surface
  • Coutside - Cinside = concentration difference
14
Q

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

A
  • 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 (?)
15
Q

What is the mechanism of large-pore paracellular transport?

Which molecules undergo this kind of transport?

A

very slow diffusion through large pores

  • protein-sized molecules
16
Q

What is the mechanism of transcytosis?

Which molecules undergo this kind of transport?

A

vesicular transport

  • translocation of macromolecules
17
Q

What is convection?

Another name.

A

also: solvent drag

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

18
Q

What are the 2 driving forces of convection?

A
  • hydrostatic pressure difference (ΔPc-if):
    difference btw intra- and extravascular pressure
  • oncotic pressure difference (Δπc-if):
    difference btw intra- and extravascular osmotic pressure caused by plasma proteins
19
Q

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?

A

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

Jv = Kf [(Pc - Pi) - σ(πc - πi)]

  • Jv = fluid flow
  • Kf = filtration coefficient
  • Pc = capillary hydrostatic pressure
  • Pi = interstitial hydrostatic pressure
  • σ = reflection coefficient
  • πc = capillary oncotic pressure
  • πi = interstitial oncotic pressure
20
Q

What is the unit of the filtration coefficient?

What does it describe?

Another name.

A

also: hydraulic conductance

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

in [ml/min * mmHg]

21
Q

What does the reflection coefficient describe?

A

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
22
Q

What does Pc describe?

Value.

What is its effect?

A

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

23
Q

How can it Pc changed?

What is its effect?

A

↑Part, ↑Pven, arteriolar dilation, venous constriction
→ ↑ Pc

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

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

24
Q

What does Pi describe?

Value.

A

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
25
Q

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

A

⇒ the smaller Pi, the greater filtration

(bc effect of fluid forced into interstitium is increased)

26
Q

What does πc describe?

Value.

A

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

27
Q

How can πc be changed?

What is its effect?

A

↓ [protein] → ↓ πc

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

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

28
Q

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

A
  • 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.)
29
Q

What does πi describe?

Value.

A

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)

30
Q

How can πi be changed?

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

A

inadequate lymphatic function → ↑ πi

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

31
Q

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

A
  • Pc
  • Pi = constant
  • πc = constant
  • πi

⇒ filtration at arteriolar end, absorption at venous end

32
Q

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

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

BUT: similar to Starling model when 0 net fluid movement

33
Q

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

A

Psubglyco > Pcleft and Pi

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

34
Q

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

How do you call the observable mechanism?

A

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

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

osmotic assymetry/rectification

35
Q

What is the function of lymph?

A

normally filtration > absorption

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

36
Q

At which rate is lymph produced?

How much of the total filtrate becomes lymph?

A

120 ml/h → 2-4 l/d

1/10 of filtration → lymph

37
Q

Describe the structure of the interstitium.

A

2 phases:

  • proteoglycan mesh traps H20 molecules → tissue gel / gel phase
  • small free fluid vesicles (< 1%) = sol phase
38
Q

Explain the general structure of lymphatics.

A

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

anchoring filaments tether lymphatics to interstitium

39
Q

How does the interstitium respond to an increased filtration load?

A

↑ filtration → ↑ Pi

  • 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

40
Q

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

A
  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.
41
Q

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

A
  • initial lymphatics: -1 - 1mmHg
  • collecting lymphatics: 1 - 10 mmHg
42
Q

Lymph flow is unidirectional.

Why?

A

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

43
Q

Lymph flow depends on… ?

A

depends on Pi
↑Pi → ↑lymph flow

44
Q

What is an edema?

Causes?

A

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)

45
Q

What are the effects of histamine?

A
  • arteriolar dilation
  • venous constriction

⇒ large ↑ Pc + local edema