3- Microcirculation and the Lymphatic System: Capillary Fluid Exchange, Interstitial Fluid, and Lymph Flow

Question 1

Capillary permeability

Answer 1

• permeable to water, O2, CO2 and some small molecules (there is constant movement of water all along the capillary even if there is no net movement)
• impermeable to proteins (are transported through vesicles)
• protein is in high concentration in the blood and low concentration in the interstitial space a balance of forces is set up that retains fluid in the circulation

Question 2

Microcirculation conforms to structure of tissue, explain 2 examples

Answer 2

1. skeletal muscle: capillaries run b/w muscle fibers parallel to each other
2. cardiac epithelium: very high metabolic activity, so it has very high density of capillaries for rapid delivery of nutrients and removal of waste products

Question 3

size of arterioles and capillaries and RBCs

Answer 3

arterioles- 20 microns
capillaries- 5-9 microns

RBCs- 7-8 microns (they deform to fit into capillaries)

Question 4

metarterioles vs venules and smooth muscle

How this affects capillary blood flow and what causes it

Answer 4

metarterioles- intermittent smooth muscle cells around vessel

venules- less smooth muscle but can still contract

• capillary blood flow is intermittent
• vasomotion causes intermittency: metarterioles and precapillary sphincters contract/relax

Question 5

edema

Answer 5

movement of water out of the circulation and into the tissues

Question 6

what determines vasomotion

Answer 6

• tissue O2 concentration
• low tissue O2 relaxes
• high tissue O2 contracts sphincters

Question 7

billions of individual capillaries so despite intermittent opening and closing we consider

Answer 7

• average rate of flow
• average capillary pressure
• average rate of transfer of substances

Question 8

Structure of capillary wall

Answer 8

single layer of endothelial cells and thin basement membrane

1. Intercellular cleft (slit pore)
   - 6-7 nm wide
   - <1/1000 total surface area
   - most water-soluble molecules and small solutes easily diffuse
   - slightly narrower than diameter of albumin molecule
2. Plasmalemmal vesicles (aka caveolae)
   - small packets of plasma or ECF that move through the endothelial cell

Question 9

capillary location/area details

Answer 9

• nearly every cell is close to a capillary ~ within 20-30 microns
• 500-700 square meters (10^10 capillaries)

Question 10

capillary exchange has 4 pathways

Answer 10

1. Intercellular clefts (hydrophilic substances)
2. Pinocytotic vesicles (large hydrophilic molecules)
3. Fenestrae and aquaporins (large amounts of fluid)
4. Transcellular (lipophilic substances)

Question 11

Diffusion rate determined by

Answer 11

1. concentration gradient
2. surface area
   - capillaries can dilate and constrict depending on how much O2 is needed in those tissues
   - ex: skeletal muscle and heart capillaries open more during exercise
3. diffusion coefficient (determined by molecule and capillary type)
   - brain: tight junctions, very closed for only small molecules
   - liver: pores very open
   - intestine: intermediate b/w liver and brain
   - kidney glomerulus tufts: penetrate through middle of endothelial cells

Question 12

Net transport in capillaries

Answer 12

higher to lower concentrations – down concentration gradient

1. O2 tends to diffuse into tissues
2. CO2 tends to diffuse into capillaries

high rate of diffusion- only slight gradient is sufficient for adequate transport

Question 13

capillary beds differ dependent on size of pores

Answer 13

generally as size of molecule increases, relative permeability decreases

• liver is highly permeable to proteins
• kidney glomerulus is highly permeable to fluids/electrolytes
• capillary permability can be altered in disease states

Question 14

Starling Forces

Answer 14

Typically flow out of capillary

1. Capillary Pressure
2. Interstitial fluid colloid osmotic pressure

Typically flow into capillary

3. Plasma colloid osmotic pressure
4. Interstitial fluid pressure

Question 15

Interstitial space

Answer 15

• area b/w cells
• composed of collagen (high tensile strength), proteoglycans (tissue gel), and water
• interstitial fluid–> much like composition of plasma but with fewer proteins

“free fluid” is usually less than 1% but in edema 50% can be free

Question 16

interstitial fluid pressure (numerically)

Answer 16

Typically a negative number and depends on how much fluid is in the space and how compliant the space is

ranges from -10 to +10 depending on the tissue (higher during edema)

-subcutaneous tissue: -2 to -6 mmHg

tightly encased tissue: 
-brain- +4 to +6 mmHg 
csf= 10
-kidney- +6 mmHg
capsular pressure = 13

Question 17

Plasma Colloid Osmotic Pressure (aka. oncotic pressure/ COP)

Answer 17

• due to balance of forces that attempts to abolish protein concentration gradient
• More plasma proteins – increased colloid osmotic pressure
• Fewer proteins – lower oncotic pressure

Question 18

effects of different plasma proteins on COP

Answer 18

• osmotic pressure is determined by number of molecules dissolved and not by mass
• SO albumin is the most important contributor to the colloid osmotic pressure due to the number of albumin molecules present in the blood

Question 19

Starling equilibrium for capillary exchange

Answer 19

Outward forces - Inward forces = Net force

(mean capillary pressure + interstitial fluid colloid osmotic pressure) - (plasma colloid osmotic pressure + interstitial free fluid pressure)

Question 20

Filtration coefficient

Answer 20

greater in tissues with large pores, very low in brain and muscle

Question 21

what could alter balance fluid balance?

Answer 21

• Increase capillary pressure could increase flow of fluid into interstitium – edema
• Decreased capillary pressure, fluid moves inward
• Increased capillary permeability, increased plasma proteins in interstitium, increased colloid oncotic pressure
• Dilution of plasma proteins, decreased plasma colloid oncotic pressure, fluid moves outward

Question 22

Lymphatic system

Answer 22

• fluid + proteins + other large molecules carried away from interstitial spaces
• most fluid filtered is reabsorbed into venous ends of capillaries
• about 1/10 of the fluid enters lymphatic capillaries ~ 2-3 liters/day
• fluid pushes through one-way valves formed by endothelial cell flaps
• Lymph flows up thoracic duct from lower body and left side of body and empties into venous system at juncture of subclavian vein and left jugular.
• Right head and neck emptied into right lymph duct and right subclavian.

-Lymph similar in composition to interstitial fluid at first.
Absorption of fats from GI tract.
2/3 of total lymph derived from liver and intestines.

-Collects bacteria that are destroyed by lymph nodes.

Question 23

Factors that influence lymph flow

Answer 23

1. elevated capillary pressure
2. decreased plasma COP
3. increased interstitial fluid COP
4. Increased permeability of the capillaries (to water which causes blood fluid to move out)
5. Lymph pump (note role of valves)
   - collecting lymphatics have myogenic responses
   - contraction of surrounding muscles (lymph flow active during exercise)
   - movement of body parts
   - pulsations of adjacent arteries
   - compression of tissues by external forces

Question 24

main factors that determine lymph flow rate

Answer 24

• interstitial fluid pressure

- lymphatic pump activity

Question 25

safety factors that prevent edema

Answer 25

1. low compliance of tissues in negative pressure range
2. lymphatic capacity for increasing flow
3. dilution of interstitial protein

Question 26

lymphatic capacity for increasing flow

Answer 26

1. return the circulation fluids and proteins filtered from capillaries into the interstitium
2. without with function, decrease plasma volume and edema occurs
3. lymph flow increases 10-50 fold when fluid start to accumulate
4. safety factor = 7 mmHg