Capillaries Flashcards
What does H2O solution contain in + out cells?
IN: O2, glucose, AA, hormones, immune response etc.
OUT: metabolic end products CO2, urea
Role of cell membranes + eg?
Support and protection
Cell-to-cell recognition eg immune system
Controls what enters or leaves the cell eg ion movement in nerves
Regulates cell function eg Insulin-mediated glucose uptake
What are the two layers of amphipathic phospholipids?
polar phosphate head (hydrophilic)
non-polar FA tails (hydrophobic)
eg of passive transport processes?
Diffusion: conc gradient, O2 uptake from lungs into blood
Convection: pressure gradient, circulation
Osmosis: osmotic pressure gradient, water uptake by cells
Electrochemical flux: electrical + conc gradient, ion flow during an AP in a nerve
Describe capillaries
Small diameter
Extension of inner lining of arterioles
Endothelium only – 1 cell thick
Semi-permeable
Role of capillaries?
Connect terminal arterioles to venules
Higher density in active tissue (muscles, liver, heart, kidneys, brain)
Solute exchange (passive diffusion, filtration): O2, glucose, AA, hormones, 💊
Fluid exchange (flow down pressure gradients): regulation of plasma + interstitial fluid volumes
What controls rate of solute transport?
Properties of passive diffusion
Properties of solutes + membranes (Fick’s law)
Properties of capillaries
Permeability
Properties of passive transport?
No ATP
Molecules move randomly
Move from high -> low conc
Transport of lipid-soluble solutes over short distances
Why does passive transport only work over short distances?
Time taken (t) for a randomly moving molecule to move net distance (x) in 1 specific direction increases when distance squared
t = x² / 2D
D : diffusion coefficient for molecule within medium
eg D for O2 in water vs air are diff
Properties of the solute?
Conc gradient
Size
Lipid solubility
Properties of the membrane?
Thickness/composition
Aq pores
Carrier-mediated transport
AT mechanisms
What’s Fick’s law?
Jₛ = - DA (ΔC/x)
D : Diffusion coefficient of solute-ease via solvent
A : Area
ΔC/x : Conc gradient (C1-C2) across distance x
Jₛ : Solute movement, mass per unit time m/t
Why’s Fick’s law negative?
flowing ‘down’ a conc gradient
3 types of capillaries?
Continuous capillaries (least permeable) Fenestrated capillaries Discontinuous capillaries (most permeable)
Describe continuous capillaries
Moderate permeability
Tight gaps between neighbouring cells
Constant basement membrane
eg of continuous capillaries?
BBB
Describe fenestrated capillaries
High water permeability
Fenestration structures
Disrupts basement membrane
eg of fenestrated capillaries?
‘high water turnover’ tissues:
salivary glands, kidney, synovial joints, choroid plexus (CSF)
Describe discontinuous capillaries
Large fenestration structures
V disrupted basement membrane
eg of discontinuous capillaries?
When movement of cells is required:
🔴 in liver, spleen, bone marrow
What’s an intercellular cleft?
10-20 nm wide
What’s a glycocalyx?
covers endothelium -ve charged blocks solute permeation+access to transport mechanisms regulated controls movement of molecules
What are caveolae + vesicles?
large pores system
Define permeability
rate of solute transfer by diffusion across unit area of membrane per unit conc diff
’how freely a solute crosses a membrane’
How does a porous membrane interfere with diffusion of lipid insoluble solute?
reduction in area for diffusion (A), increased path length through membrane (x), restricted diffusion in pore produces hydraulic issues (D)
ALL FACTORS = permeability (P)
What’s the modified Fick’s law for a porous membrane?
Jₛ = -PAₘΔC Jₛ : Rate of solute transport P : Permeability [pore size, length (x), diffusion coefficient (D)] Aₘ = SA of capillary ∆C = Conc gradient
How do large lipophobic proteins get transported?
big gaps in inflammation, trans-cellular channels, vesicles (endocytosis + exocytosis)
How do lipophilic O2, CO2 diffuse?
trans-cellular
How do small lipophobic glucose get transported?
filtration via inter-cellular, fenestral route
How does water get transported?
filtration via inter-cellular, fenestral route, water channels
How much of glucose is transported by diffusion?
98% of glucose transport into interstitial space
via passive diffusion – via GLUT transporter system
How much of glucose is transported by filtration?
2% glucose transport via fenestrations/intercellular gaps
Why’s filtration of glucose much less than diffusion?
[glucose] in plasma is 1 g / L
Daily volume of plasma filtrate flowing into tissues = 8 L
Max filtration of glucose = 8 g / day
but glucose consumption of adult is 400 g / day
What controls diffusion rate?
Increased blood flow
Fall in interstitial conc (more solute used, metabolism)
Recruitment of capillaries
How increased blood flow controls diffusion rate?
- increased conc of solutes in capillaries
- more exchange along capillaries in lungs
- less time for eq of O2/CO2 to occur between interstitial spaces + capillaries - reduces exchange
How a fall in interstitial conc controls diffusion rate?
- use more O2
- increases conc diff for O2 to move in
- metabolism increases blood flow - metabolic hyperaemia
- more O2 delivery
How a recruitment of capillaries controls diffusion rate?
- dilation of arterioles
- more capillaries perfused
- increases SA for diffusion
- shortens diffusion distance
- faster diffusion
Why does O2 transport from blood to muscle
increases over 40 times during exercise?
- increase CO (blood flow)
- use more O2 (fall in tissue concentration)
- open up more capillaries (recruitment)
Importance of fluid exchange?
Normal physiological function
H2O for chemical reactions
Abnormalities –> oedema/tissue swelling
Controlling blood, interstitial, cell volumes after drop in BP/poor end organ perfusion eg haemorrhage, sepsis, during surgery, dehydration
What’s hydraulic pressure?
Pressure exerted when fluid moves across membrane into interstitial space due to blood flow
OUUUUUTTTTTTTT
What’s oncotic pressure?
pressure exerted by plasma proteins that cannot pass through membrane, which creates suction force to move fluid from interstitial space into capillary
INNNNN
What’s Starling’s principle of fluid exchange?
Fluid movement depends on balance between hydraulic + oncotic pressures across the capillary wall
What are the Directions of Fluid Movements dominated by?
P꜀ and πₚ
P꜀: capillary BP
πₚ: plasma proteins
Why does the hydraulic pressure mean easy movement across the membrane?
P꜀ > Pᵢ
P꜀: capillary BP
Pᵢ: interstitial fluid pressure
Why does the osmotic pressure mean movement via intercellular gaps?
πₚ > πᵢ
πₚ: plasma proteins
πᵢ: interstitial proteins
Equation of Starling’s principle of fluid exchange?
Jᵥ = Lₚ A [ (P꜀ - Pᵢ) - σ(πₚ - πᵢ) ] Jᵥ ∝ (P꜀ - Pᵢ) - (πₚ - πᵢ) Jᵥ: net filtration Lₚ: Hydraulic conductance of endothelium, how Leaky endothelium is to fluid A: wall area σ: Reflection coefficient for intercellular gaps (P꜀ - Pᵢ): hydraulic pressure diff (πₚ - πᵢ): osmotic pressure diff
What does it mean if σ for a plasma protein is 0.9?
10% plasma proteins are conducted across capillary wall into interstitial space
What happens to σ if small gaps?
plasma proteins stay in lumen exerting osmotic pressure = 1
Equation of effective osmotic pressure?
effective osmotic pressure = σ x potential osmotic pressure
What does Starling’s principle tells us
- constant osmotic p πₚ=25
- first part of capillary P꜀=35mmHg so filtration
- lose pressure down capillary
- P꜀=πₚ both 25mmHg
- more drop so P꜀=10mmHg so reabsorption
Problems with Starling’s principle?
- Fluid filtration throughout length of capillaries
- No reabsorption - vital for fluid replacement
- πᵢ not small, πₚ = πᵢ
- Glycocalyx central to fluid exchange
- Starling’s principle states that increasing πₚ + reabsorption with colloid fluids should increase blood volume but they don’t expand plasma volume
What’s the revised equation of Starling’s principle of fluid exchange?
Jᵥ = Lₚ A [ (P꜀ - Pᵢ) - σ(πₚ - πg) ]
Jᵥ: net filtration
Lₚ: Hydraulic conductance of endothelium, how Leaky endothelium is to fluid
A: wall area
σ: Reflection coefficient for intercellular gaps
(P꜀ - Pᵢ): hydraulic pressure diff
(πₚ - πg): osmotic gradient
Role of glycocalyx?
Glycocalyx acts as a barrier so plasma proteins move from lumen into interstitial space via vesicle system not via intercellular spaces as
Why’s πₚ = πᵢ ?
Stream of fluid filtration from endothelium carries plasma proteins into interstitial space creating low πg (subglycocalyx region) - πₚ = πᵢ
Why’s there filtration at venous end despite low P꜀?
Filtration occurs across length of capillaries
Less P꜀ at venous end means πᵢ moves into πg – less (πₚ - πg) osmotic gradient
Why colloid fluid doesn’t expand blood volume in sick patient?
shedding of glycocalyx
Why’s there brief reabsorption during haemorrhage?
- less CO, less BP
- sympathetic so vasoconstriction
- low P꜀ (hypovolemia)
- less blood volume
- increased osmotic pressure>25mmHg
- so fluid reabsorption to lower osmotic pressure
- reabsorb 500ml over 0.5hr
- stops when osmotic p normal
Purpose of brief reabsorption during haemorrhage?
Life-preserving Supports CVP Increases CO Rises BP Greater end organ perfusion
Role of lymphatic circulation?
returns excess tissue fluid/solutes back to the cardio-vascular system
Features of lymph vessels?
valves + smooth muscle
What contributes to lymph flow?
Spontaneous contractions of smooth muscle
Surrounding skeletal muscle contractions / relaxation
Organization of lymphatic thoracic duct system?
- initial lymphatic plexus
- collecting lymphatic
- afferent lymphatic
- high endothelial venule
- lymphocyte
- lymph node
- efferent lymphatic
- cysterna chyli
- lacteal
- thoracic duct
What does overall control of ECF balance depend on?
Capillary filtration
Capillary reabsorption
Lymphatic system
What changes happen if imbalance of ECF?
Starling’s factors
Efficiency of lymphatic system
Influence fluid balance between intravascular + interstitial spaces
What causes oedema?
Excess interstitial fluid by imbalance between
filtration, reabsorption, lymphatic function, glycocalyx function
Factors that promote filtration?
increased P꜀
increased πg
increased Lₚ
decreased πₚ
Factors that promote reabsorption?
decreased P꜀
increased πₚ
Eg of clinical scenarios where there’s increased P꜀?
Dependent (gravitational) oedema – ‘standing up for long periods’
Deep venous thrombosis
Cardiac failure
Describe DVT
- prevention of venous return
- increases venous pressure –> ‘back-up’ of pressure
- increased P꜀ across capillaries
- increased filtration
What causes decreased πₚ?
Malnutrition/malabsorption, hepatic failure, nephrotic syndrome
What’s Nephrotic syndrome?
protein lost in urine that isn’t replaced by liver production
How does liver disease decrease πₚ
insufficient endogenous albumin produced
Describe how kwashiorkor happens
- reduced plasma protein conc
- reduced oncotic pressure πₚ
- greater P꜀
- fluid from capillaries -> interstitial fluid
- oedema
eg of how inflammatory-mediated oedema occurs?
Insect bites/stings, infection, trauma, autoimmune disease
Describe how inflammation causes oedema?
- local chemical mediators of inflammation cause swelling
- increase capillary permeabilty Lₚ
- decreased σ
- increased protein permeability
- so πₚ = πg = πᵢ
- increased P꜀
- more filtration
What’s filariasis/elephantitis?
nematode infestation, larvae migrate to lymphatic system grow/mate/form nests – block lympathetic drainage
What’s lymphoedema?
from surgery to treat testicular cancer – removal of lymphatics
eg of what causes dysfunctional glycocalyx
inflammation, sepsis, during surgery
What happens if there’s dysfunctional glycocalyx?
- giving fluids (crystalloids or colloids) causes movement of plasma proteins via intercellular gaps
- so πₚ = πg = πᵢ
- increased P꜀
- more filtration
- oedema
