CVS: Capillary Structure and Function, and Solute and Fluid Movement

Question 1

What does metabolism create a need for?

Answer 1

Transport of solutes + fluids

To do this, solutes + fluids must move across cell membranes which often acts as barriers

Question 2

What controls the rate of solute transport?

Answer 2

• Properties of passive and active transport across membranes
• Fick’s law
• Properties of capillaries

Together, these form the concept of permeability - Allowing solutes/fluids to cross capillary membranes

Question 3

Describe passive transport

Answer 3

• Movement molecules down conc/pressure/osmotic gradient
• DOESN’t need energy
• Simple (O2/CO2) or facilitated (ions,glucose)

Question 4

Describe active transport

Answer 4

• Movement molecules against conc gradient
• NEEDS energy (ATP)
• e.g. ATP-dependent pumps, endocytosis, exocytosis

Question 5

Describe the 4 passive transport processes

Answer 5

• Diffusion
  
  • Concentration gradient -e.g. O2 uptake from lungs into blood
  • Regulated by distance, time taken ∝ distance squared
  • Fast over micro m and slow >1 mm
• Convection
  
  • Pressure gradient -e.g. Circulation
  • Requires pressure gradient, functioning heart - appropriate CO etc.
• Osmosis
  
  • Osmotic pressure (water) gradient - e.g. water uptake by cells
  • Requires balance of filtration, reabsorption and functioning lymphatics
• Electrochemical flux
  
  • Electrical and concentration gradient - e.g. Ion flow during AP
  • Requires - Active/other transport mechanisms to create electrochemical gradients and ion channels to provide ion movement across membranes

Question 6

What does Fick’s law describe?

Answer 6

Properties of solutes and membranes affecting transport

Solute movement - Mass per unit time, m/t (Js)

Determined by 4 factors:

Js = - D A (deltaC/x)

D = Diffusion coefficient of solute – how easy it moves through solvent

A = Area

**DeltaC / x = Concentration gradient (C1-C2) across distance

x, negative value : flowing ‘down’ a concentration gradient**

Question 7

What controls diffusion rate?

Answer 7

Linked to Fick’s law:

• Increased blood flow
  
  • Increases concentration solutes transported to capillaries
• Fall in intracellular concentration (more solute used, metabolism)
  
  • Increase concentration difference (greater concentration gradient)
• Recruitment of capillaries
  
  • Dilation of arterioles - ⬆️number capillaries perfused
  • Increases total SA for diffusion (Fick’s law)
  • Shortens diffusion distance (faster diffusion)

Question 8

At what vessel does most solute and fluid movement occur? Describe it

Answer 8

Capilaries:

• Smallest diameter BV
• Extension of inner lining of arterioles
• Endothelium only 1 cell thick
• Semi-permeable
• Vessels that connect arterioles to venules
• Found near every cell in body but higher density in highly active tissue
• Solute movement (due to passive/active transport and filtration), e.g. O2, glucose, amino acids, hormones, drugs
• Fluid movement (due to pressure gradients, osmotic pressure), e.g. regulation of plasma, interstitial, intracellular fluid

Question 9

Describe the properties and function of continuous capillaries

Answer 9

• Moderate permeability
• Tight gaps b/w neighbouring cells
• Constant basement membrane e.g. blood-brain barrier

Question 10

Describe the properties and function of fenestrated capillaries

Answer 10

• High water permeability
• Fenestration structures
• Modest disruption of basement membrane
• E.g. ‘high water turnover’ tissues such as salivary glands, kidney, synovial joints, choroid plexus (cerebrospinal fluid)

Question 11

Describe the properties and function of discontinuous capillaries

Answer 11

• Very large fenestration structures
• Disrupted basement membrane
• E.g. when movement of cells is requires such as RBCs in liver, spleen, bone marrow

Question 12

How does permeability change as you go from continuous → fenestrated → discontinuous capillaries?

Answer 12

Increasing permeability to solutes + fluids

Question 13

What are the general properties of all capillaries that can influence solute transfer?

Answer 13

• Intercellular cleft - 10-20nm wide, tiny spaces between the endothelial cells that line blood vessels, allow passage of water and small solutes b/w blood and interstitial fluid
• Glycocalyx - Covers endothelium, charged material, acts as sieve for solute permeation. The glycocalyx acts as a barrier, preventing the passage of larger molecules like albumin while allowing smaller molecules like water and small solutes to pass throug
• Caveolae + vesicles - Movement of large molecules, e.g. plasma proteins, lipoproteins. Caveolae play a role in vesicle trafficking, and will allow the migration of vesicles. Vesicles transport larger molecules via transcytosis

Question 14

What are the different routes of solute transport?

Answer 14

• Big gaps in inflammation
• Trans-cellular channels
• Vesicles
• Trans-cellular
• Inter-cellular
• Fenestral route
• Water channels

Question 15

What is the dominant route of solute transport?

Answer 15

• Diffusion, for example, filtration only accounts for 2% glucose transport

Question 16

How does fluid move at the capillary wall?

Answer 16

• Capillary wall semi-permeable - allows H2O pass through
• Fluid moves across membrane into interstitial space due to capillary BP
• Large molecules (e.g. plasma proteins) can’t pass, instead they exert osmotic pressure termed oncotic pressure
• Oncotic pressure creates suction force to move fluid from interstitial space into capillary
• Fluid movement depends on balance b/w capillary BP and oncotic pressure across capillary wall - revised Starling’s principle of fluid exchange

Question 17

Describe the revised Starling’s principle of fluid exchange

Answer 17

The Starling Principle states that fluid movements between blood and tissues are determined by differences in hydrostatic and colloid osmotic (oncotic) pressures between plasma inside microvessels and fluid outside them

Hydrostatic pressure = The pressure exerted by plasma on the capillaries

Oncotic pressure = The pressure exerted by plasma proteins, such as albumin on the capillaries. They’re too large to pass through and create an osmotic gradient, driving the movement of fluid into the capillaries

Jv = Lp A { ( Pc - Pi ) - sigma (pp - pg) }

Jv (net filtration) µ Blood/fluid pressures difference (Pc - Pi )

- Osmotic pressure difference (pp - pg)

LP - Conductance of endothelium

A - Endothelium plasma membrane area

Sigma - Reflection coefficient - related to intracellular gaps

Fraction (sigma) of osmotic pressure is exerted by gaps

Effective osmotic pressure = Sigma x potential osmotic pressure

Sigma for plasma protein = 1 so no conduction across

Sigma for plasma protein = 0 so free conduction across

Plasma proteins move from lumen into interstitial space via vesicle system, NOT via intercellular spaces as glycocalyx acts as barrier
Stream of fluid filtration into interstitial space carries plasma proteins away from endothelium into pii, creating low pg (subglycocalyx region)
Pp = Pi
Hence, osmotic gradient is Pp - Pg

Question 18

What does Revised Starling’s principle mean? How does this differ to the previous Starling’s principle?

Answer 18

Revised Starling principle - Balance of pressures cannot halt fluid exchange because microvessels are permeable to macromolecules

• Less Pc than at arterial end
• Means plasma proteins diffuse into subglycocalyx region
• Pii - PiG which are also same as PiP
• Filtration continues at venous end as even though Pc is low it is still greater than osmotic gradient to absorb
• Filtration occurs across length of capillaries

Starling’s principle initially said that filtration occurs at the arterial end, and reabsorption occurs at the venous end. In reality, filtration still occurs, though much lower due to lower BP, at the venous end due to the movement of proteins into the sub-glycocalyx gradient maintaining an oncotic pressure gradient. This will help drive fluid into the subglycocalyx region, where it’s drawn through intercellular clefts into the interstitial fluid, hence filtering

Question 19

Describe the role of lymphatic circulation in constant filtration

Answer 19

• Lymphatic circulation returns excess tissue fluid/solutes back to cardio-vascular system
• Lymph vessels have valves and smooth muscle
• Spontaneous contractions of smooth muscle contributes to lymph flow
• Surrounding skeletal muscle contractions/relaxation also contributes to lymph flow

Question 20

What happens if Pc becomes very low?

Answer 20

Hypovolemia:

• Drop in blood volume leads to drop in CO and BP, therefore Pc is reduces
• Pip becomes dominant

Question 21

What does ECF balance depend on?

Answer 21

• Capillary filtration - Fluid moves out of the capillaries into the interstitial fluid
• Capillary reabsorption - Fluid from the interstitial fluid moves back into the capillaries
• Lymphatic system

Question 22

What occurs when the balance between filtration, reabsorption and lymphatic function is not maintained?

Answer 22

Oedema - Excessive fluid in interstitial space

Question 23

Why does increased capillary pressure lead to oedema?

Answer 23

Increased Pc across capillaries (gravitational from standing too long, cardiac failure, DVT) causes increased flitration

Question 24

Why does decrease osmotic pressure lead to oedema?

Answer 24

Decreased osmotic pressure can be caused by low protein oedema or malnutrition/malabsorption, hepatic failure, nephrotic syndrome (this is protein loss in urine that is much greater than the amount of protein being produced by the liver)

Liver disease - not enough albumin being made

• Reduced plasma protein concn
• Reduce plasma oncotic pressure, greater influence of Pc
• Excessive fluid filtration from capillaries into interstitial fluid
• Oedema

Question 25

Describe inflammatory-mediated oedema

Answer 25

- Swelling triggered by local chemical mediators of inflammation - Increase capillary permeability - become ‘leaky’

Question 26

What are problems caused by lymphatic dysfunction?

Answer 26

Lymphatic obstruction: - Filariasis/elephantitis - nematode infestation, larvae migrate to lymphatic system, grow/mate/form nests - block lymphatic drainage Lymphatic removal: - Lymphoedema - caused by surgery, removal of lymphatics Continued filtration leads to build up of fluid in interstitial space