1) Microvascular Fluid Dynamics

How do solutes and gases cross capillary walls?

Simple diffusion

What are the 2 main routes across capillary endothelium?

1. Through endothelial cells (transcellular)

2. Between cells (paracellular)

What determines whether a substance uses transcellular vs paracellular route?

Lipid solubility

How do O₂ and CO₂ cross capillary walls? What mainly determines the transport of O₂ and CO₂ across capillaries?

Method: lipid-soluble diffusion

• determined by Pressure gradient & SA

How do water, ions, glucose, and amino acids cross capillaries?

paracellular pathways (b/c they’re not lipid-soluble)

Can proteins cross continuous (non-fenestrated) capillaries?

No b/c they’re too large, they can only cross via fenestrated & discontinuous (sinusoidal) capillaries

What are the major determinants of fluid movement across capillaries?

1. Osmotic pressure

2. Hydrostatic pressure

When is osmotic pressure greatest?

when solute can’t cross the semi-permeable membrane

What does osmotic pressure depend on?

# of molecules on each side of the membrane (not size)

How does membrane permeability affect osmotic pressure?

↑ permeability → ↓ osmotic pressure

Why do proteins create high osmotic pressure in capillaries?

too large to cross continuous capillaries (tight junctions)

What is colloid (oncotic) osmotic pressure?

pressure created from proteins or sugars

What’s the difference between filtration vs absorption?

Filtration = pressure-driven fluid movement OUT of capillaries

Absorption = pressure-driven fluid movement INTO capillaries

What determines how much fluid moves for a given pressure difference?

Hydraulic conductance- water permeability of the capillary wall

What is Starling Equation?

FLOW_net(Jv) = K_f [(P_c– P_i) – (π_c– π_i)]

• K_f = Hydraulic conductance (mL/min/mmHg) → permeability of the wall b/w inside and outside

• Pc = capillary hydrostatic pressure (mmHg)

• Pi = interstitial* hydrostatic pressure (mmHg)

• πc = capillary oncotic pressure (mmHg)

• πi = interstitial* oncotic pressure (mm Hg)

Units of J_v = mL/min

At the arterial end, what forces are at play? What is the dominant driver?

→ filtration

1. Capillary hydrostatic pressure (P_c) (dominant)

2. Capillary oncotic pressure (π_c) (small %)

   • plasma proteins and ions that couldn’t diffuse out get concentrated in the vessel lumen

At the venous end, what forces are at play? What is the dominant driver?

→ Absorption

1. Capillary oncotic pressure (π_c) (dominant)

2. Capillary hydrostatic pressure (P_c) (small %)

   • due to fluid loss from the capillary and lower venous vascular tone

What happens at the midpoint of a capillary?

Hydrostatic force = oncotic force

What drives O₂, CO₂, and nutrient exchange at the midpoint?

Diffusion down concentration gradients

What are the oncotic pressures (π_c) & hydrostatic pressures (P_c) in the arterial, middle and venous end?

True or False: The amount of fluid leaving and the amount returning are equal, resulting in 0 net forces.

False - 4L/day of excess fluid left in all of your interstitial tissues combined (more is filtered than absorbed)

What happens to this remaining interstitiual fluid (4L/day)?

enters lymphatic system to be returned back to circulation

Is the excess fluid (4L/day) left per day detrimental? What occurs once this fluid has left the bloodstream?

→ No, it’s the normal amount that’s left behind to keep tissues hydrated

• risk of exposure to contaminating microbes/antigens once it leaves the bloodstream

• this is why the excess fluid is taken up by lymphatics first to be cleaned, before entering blood stream

What does interstitial volume depend on?

1. Filtration rate

2. Reabsorption

3. Lymphatic flow

What maintains transcapillary fluid equilibrium?

Filtration = Reabsorption + Lymphatic flow

• remember this is what interstitial volume depends on

What factors ↑ P_c (capillary hydrostatic pressure)?

• Arteriolar dilation

• ↑ Arterial pressure

• Venous constriction/obstruction

• ↑ Venous pressure

• Right HF

• ECF volume expansion

What factors ↓π_c (capillary oncotic pressure)?

• ↓ [plasma protein]

• Severe liver failure (can’t make proteins)

• Protein malnutrition

• Nephrotic syndrome (protein loss in urine)

What factors ↑ K_f (hydraulic conductance)?

• Burn

• Trauma

• Inflammation (histamine/bradykinin/cytokine release)

What factors caused impaired lymphatic drainage?

• Standing (no SM compressing on the lymphatics)

• Removing/irradicating lymph nodes (e.g., due to breast cancer)

• Parasitic infection of lymph nodes (e.g., filariasis)

List the factors that cause Edema.

1. ↑ P_c

2. ↓ π_c

3. ↑ K_f (Capillary permeability)

4. Lymphatic obstruction

What is the normal lymphatic flow in the body?

Thoracic duct: ~100 mL/hr (~2.4 L/day)

Other lymphatic vessels: ~25 mL/hr (~0.6 L/day)

Total: ~4–5 L/day → closely matches the ~4 L/day of excess fluid left in tissues after capillary filtration and reabsorption, preventing edema