Exchange in and control of the peripheral circulation Flashcards
What are capillaries and what makes them good at their role?
Specialised exchange vessels
- Thin walled = small diffusion barrier
- Lots of them = gases don’t have far to diffuse
- Small diameter = big surface area to volume ratio
What is a capillary made up of?
A single layer of endothelial cells
What’s a junction between endothelial cells called?
Where one endothelial cell meets another
Very tight junctions which stops anything moving across
What is a cleft in capillaries?
The gap between cells
Where are clefts found and what are their role?
Continuous capillaries
Allow water and some dissolved solutes across
What are pores and what do they transport?
Holes across endothelial cells
Macromolecules including proteins
What forms pores?
Vesicles fusing together
What are the 3 classes of capillaries?
Continuous
Fenestrated
Discontinuous
What are the features of continuous capillaries for which locations?
No clefts or pores = brain
Or
Clefts only = muscles and most other capillaries
Why are the capillaries in the brain continuous?
Make up the blood brain barrier
Won’t allow drug molecules and potassium ions through.
Protects brain from changes in extracellular potassium concentrations that would alter resting mem potential and thus alter their function.
What are fenestrated capillaries?
Have both clefts and pores
Where are fenestrated capillaries located and what do they allow?
Specialised for fluid exchange
e.g. intestine and kidney
What are discontinuous capillaries?
Have clefts and massive pores
What do discontinuous capillaries allow for and where are they located?
Allows large proteins to move across
e.g. liver
How does the structure of capillaries relate to their function?
Most exchange is via diffusion
Carrier-mediated transport
How does O2 diffuse out of capillaries?
Higher conc. of O2 in capillaries so moves down conc. gradient into extracellular fluid and into cells.
How are capillaries self-regulating?
PO2 in cell will decrease as O2 is used up, increasing concentration gradient , so more O2 will diffuse from capillaries into ECF and into the cell.
What makes capillaries non-saturable?
No transport proteins involved so won’t be saturated
Where do polar and non-polar substances move out the capillary from?
Polar = clefts and pores
Non-polar = phospholipid membrane
What is an example of carrier-mediated transport?
Glucose transported through the blood brain barrier
What determines bulk flow?
Starlings forces
What are starlings forces?
Capillary hydrostatic pressure vs ISF hydrostatic pressure
Plasma osmotic pressure vs ISF osmotic pressure
How is fluid lost out of the capillaries into the ISF?
- Hydrostatic pressure pushes water through the clefts and pores in the endothelial cells (large molecules such as proteins don’t fit through these and will remain in the blood)
- As you move along, more and more water is going to be pushed out therefore concentration in the capillary is going to increase
What is the net filtration pressure?
§ Difference in hydrostatic pressure in capillary and interstitial fluid:
(Hc - HIF) - (pi c - pi IF)
How much fluid is lost and retained each day?
20L lost and 17L retained
How is some fluid retained?
Build up of osmotic/oncotic pressure which pulls water back into capillary
17L pulled back in by oncotic/osmotic pressure
What happens to the remaining 3L of fluid expelled from capillaries?
Drains into the lymphatic system
Where would the fluid drain to in the lymphatic system (from ISF to back into CVS)?
ISF
Lymphatic capillaries
Lymph nodes
Larger lymphatic vessels
Drains into the vena cava
Lymph is returned to th3 CVS
How does lymph move through lymphatic vessels?
Smooth muscle wall in larger lymphatic vessels that push it back
External compression from skeletal muscle like in veins and venules
What happens to fluid if lymphatic system not functioning properly?
Fluid will accumulate leading to oedema
What can cause fluid accumulation (oedema)?
Raised central venous pressure
Lymphatic obstruction
Hypoproteinaemia
Increased capillary permeability
Why does raised central venous pressure lead to oedema?
Left V failure - left side heart isn’t pumping effectively but right side is, blood accumulates in lungs
Increase in hydrostatic pressure in capillaries leading to pulmonary oedema
What can cause lymphatic obstruction?
Parasite - filarial worm that lives in lymphatic nodes blocks drainage, fluid accumulates in legs
Surgery - damage to lymph nodes, may be unilateral oedema
What brings about hypoproteinaemia?
Nephrotic syndrome
Liver failure
Malnutrition
What is hypoproteinaemia and how does it cause oedema?
Not enough protein in diet
Protein in capillaries builds up osmotic pressure which pulls fluid back in
What brings about increased capillary permeability?
Inflammation
- Rheumatism
What is rheumatism and how does it lead to oedema?
Autoimmune disease where body attacks the joints (particularly those in hands/feet)
- Massive increase in capillary permeability leading to loss of fluid and protein
- Don’t have enough protein to pull fluid back in leading to oedema
What is Darcey’s law?
Flow = change in pressure/resistance
What is Poiseuille’s law?
Resistance = nL8/r^4pi
What happens to resistance if you half radius of a tube?
Resistance increases by 16 fold
What effect does changing radius of a vessel have of flow?
By changing the radius of resistance vessels (arterioles) you can control blood flow and redirect blood
Useful for regional redirection of blood
What does MAP equal?
MAP = CO x TPR
What happens if MAP is too low?
You get decreased perfusion through vascular beds
- Causes light headedness and fainting
What happens if MAP is too high?
No immediate effects seen
- Hypertension and high BP increases risk of coronary artery disease and stroke
How can MAP be regulated?
Changing cardiac output or TPR
- Varying radius of resistance vessels not only controls region redirection of blood flow but also controls TPR and therefore regulates MAP
What happens to MAP when you decrease TPR but CO stays the same?
MAP decreases
How can MAP decrease with decreased TPR?
Controlling radius controls resistance of arterioles, it affects flow through individual vascular beds.
Affecting MAP
How is TPR controlled?
Via smooth muscle surrounding arterioles
- Local (intrinsic) mechanism
- Central (extrinsic) mechanism
What do intrinsic mechanism control with TPR?
Concerned with meeting selfish needs of each individual tissue/region
Who do extrinsic mechanism control with TPR?
Concerned with ensuring that the TPR and therefore MAP of the whole body stays in the right ballpark
What are some intrinsic mechanism controlling MAP?
Active (metabolic) hyperaemia
Pressure (flow) autoregulation
Reactive hyperaemia
What is the mechanism of active (metabolic) hyperaemia?
Increasing blood flow via metabolic activity
- Increased metabolic activity in skeletal muscle leads to increased concentration of metabolites in capillaries
- This inc in conc is sensed by endothelium lining capillary wall and trigger it to release a paracrine signal
- Causes arteriole to dilate and resistance will decrease increasing blood flow
What is the relationship between blood flow and metabolite production at rest?
Matched so they are washed away as they are produced
What signal is released by endothelial cells when metabolite concentration increases?
Paracrine signal (or local chemical signal)
- May be endothelial driving relaxing factor - EDRF
What is the effect of releasing paracrine signal?
Diffuses into skeletal muscle surrounding the arteriole causing it to dilate
- radius increases, resistance goes down and blood flow is increased
What effect does increased blood flow have on metabilites?
Decreases concentration of metabolites as they are washed away more quickly
What is the trigger for active (metabolic) hyperaemia?
Increase in local metabolism
What is the trigger of pressure (flow) autoregulation?
Decrease in perfusion pressure
What is the effect of a decrease in perfusion pressure?
Increased MAP and decreased flow
Leads to metabolite accumulation
What signal is released in pressure (flow) autoregulation?
Paracrine signal
- EDRF or NO
What effect does the release of a paracrine signal have? (perfusion autoregulation)
Arterioles dilate and flow is restored to normal
Metabolites are washed away more quickly so conc goes down and steady state is reached.
What is the trigger for reactive hyperaemia?
Occlusion of blood supply
What are some examples of occlusion of blood supply?
Inflation of a BP cuff
What happens to metabolites when blood supply is cut off?
Metabolites are sill being produced but not washed away as quickly so they build up
What does a build up in metabolites produce? (Reactive hyperaemia)
Sensed by endothelium
Release a paracrine signal (NO)
Arterioles dilate
What happens when blood supply is returned? (Reactive hyperaemia)
Blood will rush back through very dilated arterioles causing redness
What fibres are activated when you injure yourself?
C fibres are activated
What do C fibres do?
Fire action potentials along the spinal cord via the dorsal root ganglion
- Signals sent to brain tell you pain!
What is sent along collateral branches of C-fibres?
AP sent back along them
What is the basic mechanism of injury response?
C fibres activated
Substance P released
Acts of mast cells
Histamine released
Arteriolar dilation
How does histamine act on arterioles in the skin?
Relaxes smooth muscles
Arteriole dilate
Increases blood flow
Acts on capillaries
What effect does histamine have on capillaries?
Opens up junctions and increases permeability
What effect does increased blood flow have during injury response?
Injury site becomes red
Increased blood flow and permeability helps leukocytes (WBCs) to injury site so they can attack invading pathogens
What are the neural controls of arteriolar tone?
Sympathetic nerves
Parasympathetic nerves
How does sympathetic fibres have an effect on arterioles?
Releases noradrenaline which binds to A1 receptors on smooth muscle surrounding arterioles.
Causes arteriolar constriction
What is the overall effect of sympathetic fibres?
Decreases blood flow through that tissue and tends to increase TPR and MAP
What is the effect of parasympathetic fibres on arteriolar tone?
Usually have little effect as parasympathetic nerves don’t usually innervate blood vessels
What are the exceptions to parasympathetic nerves acting on arteriolar tone and what is the effect?
Genitalia
Salivary glands
Increased blood flow
What hormone is released in hormonal control of arteriolar tone and where from?
Adrenaline from the adrenal medulla
What does adrenaline act on?
Binds to A1 receptors on smooth muscle of arterioles
What effect does adrenaline have on arteriolar tone?
Arteriolar constriction
Decreases blood flow through that tissue and tends to increase TPR and MAP
What are the exceptions to adrenaline action?
Arterioles suppling skeletal and cardiac muscle express more B2 receptors
What effect does adrenaline have on skeletal and cardiac muscles have?
Smooth muscle relaxation
Causes arteriolar dilation
Blood flow increases through that tissue and TPR decreases
When is smooth muscle relaxation helpful?
During exercise
- Need more blood to skeletal and cardiac muscle
What interrupts blood supply to the coronary circulation?
During systole (when heart is contracting)
What happens when the heart contracts and how does this effect coronary arteries?
Builds up really big pressure in ventricles that you need to push blood into pulmonary/systemic circulation.
Also increases pressure in heart walls = intramural pressure.
- Squishes the coronary blood vessels
What is the demand on coronary circulation during exercise?
Increased
How does the coronary circulation adapt to increased demand during exercise?
Excellent active hyperaemia:
- Endothelium is very sensitive to even small changes in concentration of metabolites.
- Will cause local paracrine single to be released and leading to arteriole dilation.
Express many B2 receptors:
- Adrenaline will bind to these and lead to smooth muscle relaxation and arteriolar dilation.
How is cerebral circulation kept stable?
Excellent pressure autoregulation
- If MAP was to fall from 95 mmHg to 40/50 mmHg arterioles in cerebral circulation would dilate and dilate to maintain perfusion
Why does cerebral circulation have to kept stable?
If brain isn’t getting enough oxygen it lead to light headedness and fainting.
How can pulmonary circulation effect arterioles?
Decrease in PO2 will cause arteriolar constriction
Why does low PO2 cause arteriolar constriction in pulmonary circulation?
Constricts arterioles so blood can be redirected to regions of the lung that have better ventilation and can increase how much O2 in the blood is taken up.
What is the main job of renal circulation?
Filtration
- Dependent on pressure
Why must filtration rate be kept relatively constant?
Filtration rate kept relatively constant during normal fluctuations in MAP
- Protects the glomeruli from high BP which would cause damage.
- Due to excellent pressure autoregulation
