Capillaries I & II Flashcards
How does metabolism affect solute exchange?
Metabolism creates concentration gradients to transport solutes and fluids for gaseous and nutrient exchange
What is the fate of O₂ , glucose, urea and CO₂ in the body?
O₂ and glucose are transported around the body
CO₂ and urea are removed
Describe the structure of cell membranes?
- consist of 2 layers of ampiphatic phospholipids
- polar phosphate heads (hydrophilic)
- non polar fatty acid tails (hydrophobic)
- form bilayers in solution
Outline the functions of cell membranes
- providing support and function
- cell to cell recognition (immune system)
- controls what enters / leaves cells
- regulates cell function (e.g. insulin mediated glucose
uptake)
How does the membrane allow us to differentiate between cells?
The various membrane functions allow us to differentiate between cells
How do membranes act as barriers to transport?
it’s difficult to get solutes across the hydrophobic centres of the membrane
How does the structure of membranes aid transporting functions?
- contains transmembrane proteins that span across the
membrane and facilitate transport and signalling - carbohydrates anchor proteins and orient them
These complicated structures are a barrier and aid
movement across the membrane
What are the different types of transport?
- passive
- active
What is passive transport?
Random movement of molecules down a gradient of:
- concentration
- pressure
- osmotic
- electrical
Passive - doesn’t require ATP
Works effectively over short distances - t is proportional to distance^2
Describe the features of passive diffusion?
Doesn’t require energy
Simple diffusion O₂ /CO₂
facilitated diffusion is via specific channels or transmembrane molecules (ions/glucose via GLUT)
What is active transport?
The movement of molecules against a gradient requiring energy (ATP)
- ATP dependent pumps, endocytosis + exocytosis
What are the different passive transport processes?
Diffusion
- conc. gradients
e. g. uptake of O₂ from lungs -> blood
Convection
- pressure gradient
e. g. blood flow from heart -> vessels
Osmosis
- osmotic pressure graident
e. g. H₂O uptake in cells
Electrochemical flux
- electrical + concentration gradient
e. g. ion flow during action potentials
Describe the structure of capillaries
Capillaries are made of endothelial cells - 1 cell thick
semi-permeable and amenable to certain types of diffusion over short distances
Where in the body are capillaries found?
Found near every cell in the body, but higher density in highly active tissues (muscle, liver, heart, kidney, brain etc.)
What is solute exchange?
Passive diffusion of O₂ , glucose, amino acids, hormones, drugs etc. between substances
What is the role of fluid exchange?
occurs along pressure gradients and regulates plasma and interstitial fluid volumes
Where does most exchange of solutes occur in the body?
Most exchange occurs at capillaries
Outline the vessel network solutes pass through
arteries branch into arterioles -> capillaries -> venules -> veins towards the heart
What is the role of capillaries in the network of vessels?
capillaries connect terminal arterioles to venules
- extension of inner lining of arterioles
What is the rate of solute transport dependent on?
Depends on properties of:
- passive diffusion (conc. , rate & diffusion)
- solutes + membranes (Fick’s Law)
- Capillaries
combining all of these provides concept of permeability
What is permeability?
How easy it is for the solute to cross the membrane
Describe the movement of molecules during passive diffusion?
Molecules move at random (due to random thermal motion) from an area of high to low concentration, eventually reaching equilibrium
When is diffusion most effective?
Great for lipid-soluble solutes over short distances e.g. O₂ / CO₂
What is the relationship between time and diffusion rate?
t ∝d² time taken (t) for one randomly moving molecule to move a net distance (x) in one specific direction increases with distance squared (d²)
Whys is simple diffusion not applicable for whole body movement?
Movement across a capillary membrane will happen in fractions of a second, but around the body may take years
What are the solute properties that affect transport?
- membrane thickness / composition
- aqueous pores in the membrane
- carrier mediated transport
- active transport mechanisms
How does solute concentration affect diffusion?
[high solute] = faster diffusion
How does solute size affect diffusion rate?
The bigger the solute, the slower the transport across the membrane
How does charge / hydrophobicity affect diffusion?
Lipophilic solutes get across very easily but glucose would struggle as it’s large and charged.
What is the role of membrane aqueous pores?
Membrane aqueous pores act as carriers or active transport mechanisms
What is Fick’s Law?
Js = -DA ΔC / x
D - Diffusion coefficient for solute in solvent
A - area available for diffusion
ΔC - concentration difference
X - distance
(always a negative value)
What are the different types of capillaries?
Continuous capillaries
Fenestrated capillaries
Discontinuous capillaries
Describe the properties of continuous capillaries?
- Tight junctions between the endothelial cells
- very poor permeability as no space to move out from
lumen into interstitial tissue. - Constant basement membrane, which all the cells
adhere to has- no breaks in it. - Useful in blood brain barrier, doesn’t non-selectively
allow things into the brain, but all entry is regulated.
What controls solute diffusion rates?
Permeability is the rate of solute transfer by diffusion across unit are of membrane per unit concentration difference - it’s a measure of how freely a solute crosses a membrane
Js = -PAm ΔC
Or
Js / Am = - PΔC
What is Starling’s Principle of solute exchange?
Fluid movement across the capillary wall is proportional to pressure difference across the capillary wall
Balance between pressures that favour filtration (hydrostatic - increased arterial BP) and reabsorption (osmotic pressure due to plasma proteins, as long as they can’t pass through)
What are fenestrated capillaries?
Fenestrated structures are protein structures that act as a sieve for small molecules to pass through.
Describe the features of fenestrated capillaries
- More permeable due to fenestrated structures (holes in
the endothelial cells) - Permeable to water & small solutes (not bigger)
- Good where a lot of water is required e.g. salivary
glands - lots of water leaves the capillaries into the
interstitial space to make saliva. - Present in all areas where fluid moves out of plasma.
What are the features of Discontinuous capillaries?
- Allow everything through
- Have very large fenestrations and disrupted basement
membrane - Incredibly leaky so large molecules & some cells
(rbc & immune cells) move out
Where are the different capillaries distributed in the body?
The 3 distinct types of capillaries, found in different parts of the body, depending on the specific functions of cells and tissues.
Describe the anatomy of capillaries
The capillary anatomy is a single layer of endothelial cells forming the endothelium.
What other capillary wall structural features influence solute transfer?
- Intercellular cleft - 10-20 nm wide
- Caveolae & vesicles - large pore system
- Glycocalyx - covers endothelium, negatively charged
material, blocks solute permeation and access to
transport mechanisms, highly regulated
Describe the role of intercellular clefts in capillaries
Intercellular clefts are in between adjacent cells, not linked by tight junctions. This allows solutes and fluids to move between the cells,aiding permeability.
What is the role of Caveolae & vesicles?
Caveolae and vesicles is where substances are taken up on one side of the membrane, and moved to the other side => endocytosis & exocytosis
Explain the role of endocytosis & exocytosis in solute exchange at the capillaries
Endocytosis followed by exocytosis which will move the solute from the lumen across into the interstitial space…also related to selective large pores
What is the glycocalyx?
A negatively charged carbohydrate mesh that sits on the top of the endothelial cells next to the lumen
What is the function of the glycocalyx?
Acts as an extra barrier - it is very dynamic can be broken down and remade as required. Cells can regulate this
What is permeability?
The rate of solute transfer by diffusion across unit area of membrane per unit concentration difference
How does a porous membrane affect diffusion?
A porous membrane interferes with the diffusion of lipid insoluble solutes in multiple ways
Reduction in area for diffusion (A)
Increased path length through membrane (x)
Restricted diffusion in pore produces hydrostatic issues (D)
What factors determine permeability (Fick’s Law)?
passive diffusion
solute properties
membrane properties
capillary types
How does inflammation affect solute exchange?
During inflammation big gaps can form between cells causing large lipophobic proteins (plasma protein) to move out.
What type of movement occurs for lipophilic molecules?
Transcellular diffusion (O₂ / CO₂)
How do small lipohilic molecules move?
via intercellular channels or fenestrations
How does water move around cells?
Water can move by a variety of means including specific water channels.
Compare and contrast Diffusion and filtration
Diffusion is passive down a concentration gradient
Filtration is through pores, gaps and fenestrations etc.
so when fluid moves glucose moves with it
How Describe the movement of fluid in our body
We have a constant cycling of fluid being filtered from our capillaries and joining the interstitial fluid, through the lymphatic system and eventually recycling it into the plasma.
How much glucose is in our blood plasma?
Glucose concentration in plasma is 1 g / litre
How much plasma filtrate flows into tissues every day?
Total volume of plasma filtrate flowing into tissues per day = 8 litres
What is the maximum filtration of glucose a day?
Maximum filtration of glucose = 8 g / day
Approximately how much glucose is consumed a day?
400 g/day
How much of glucose transport does filtration account for?
Therefore filtration transport only accounts for 2% glucose transport
98% of glucose transport into interstitial space via passive diffusion – via GLUT transporter system
What 3 factors control the rate of diffusion around the body?
Blood flow
Fall in [Interstitial]
Capillary recruitment
Explain how Blood flow alters diffusion rate
- more blood flow = more solutes in capillaries
- more blood volume = less time for equilibrium to occur
across capillaries
v. slow blood flow causes O₂ and CO₂ to exchange over a short space allowing them to reach equilibrium
=> less diffusion
How does a fall in [interstitial] change diffusion rates?
- more solute used in tissues = increased [ ] difference
- metabolism increases blood flow + increased O₂
delivery controlled by arterioles
What pathological reason can cause decreased diffusion due to decreased blood flow?
Sepsis
- low blood flow & pressure
- tissue can become ischaemic
=> flow limited diffusion
Explain how capillary recruitment alters diffusion rate?
Increase blood flow opens up more capillaries
- Not all the capillaries are full all of the time,
=> as blood flow increases more open up
Dilation of arterioles -> more perfused capillaries increasing, the total SA for diffusion
How does exercise affect the rate of diffusion?
In exercise you go from 5 L/min to 20 L/min, reducing the distance between capillary and cell so diffusion occurs quicker.
How does strenuous exercise affect O₂ transport?
O₂ transport from blood to muscle increases over 40x during strenuous exercise. We increase cardiac output (blood flow), using more O₂ (fall in tissue [interstitial]) opening up more capillaries (recruitment)
What controls solute diffusion rates?
Permeability is the rate of solute transfer by diffusion across unit are of membrane per unit concentration difference - it’s a measure of how freely a solute crosses a membrane
Js = -PAm ΔC
Or Js / Am = - PΔC
Fluid exchange
What are the different hydrostatic and oncotic pressures in a normal capillary bed ?
Four pressures determine filtration (or reabsorption) rate Pᵢ - interstitial fluid pressure Pᶜ - capillary BP Πᵢ - interstitial proteins Πp - plasma carotid osmotic pressure
Jv = LpA {(Pᶜ - Pᵢ) - (Πp - Πᵢ)}
Jv is proportional to hydraulic pressure difference - osmotic pressure difference
How does hypovolemia affect the pressures in a capillary bed?
Hypovolemia is caused by severe blood loss via haemorrhages (water, solutes, cells)
- Osmotic pressure exerted by plasma proteins remains
the same
Hydrostatic pressure decreases causing:
- less water/volume,
- less venous return
- preload decreases therefore by Starling’s law;
=> decreased SV reduces CO leading to decreased
arterial BP
Arterioles will constrict - capillaries closed off reducing BP
Constriction occurs to increase TPR, increasing BP via sympathetic output via baroreceptor reflex BP = CO x TPR and CO = BP x SV
Do capillaries normally reabsorb or filter, and why?
Most capillaries filter > reabsorption
They hydrostatic pressure > osmotic pressure favouring filtration
Excess fluid returned via lymphatics system
What are the lymphatics, and what is their role?
Accumulation of excess of fluid within the interstitial space - imbalance between filtration, reabsorption and lymph function
What is oedema?
a condition characterised by an excess of watery fluid collecting in the cavities or tissues of the body.
How do changes in Pc , πP, and inflammation cause oedema?
Anything increasing hydrostatic pressure or decreasing reabsorption, favouring filtration can lead to oedema and inflammation
Pᶜ Increasing capillary hydrostatic pressure favours filtration
Πp Decrease in plasma osmotic pressure favours filtration
Inflammation : increased blood flow, increased permeability, leakage
Venous return impairment causes build up of blood at venous end - decreases CO
Low plasma protein - liver failure causes low osmotic pressure
What is the significance of fluid exchange?
Fluid exchange is important for normal physiological function
-> water is required for chemical reactions
Describe the benefits of fluid reabsorption
fluid reabsorption from tissues to blood can maintain circulation during haemorrhage
What are the consequences of fluid exchange abnormalities?
Abnormalities in fluid exchange can caus eoedema and tissue swelling
Describe the structure of capillaries
Endothelial cells on the outside
followed by a basement membrane containing fibroblasts
epithelium lines the capillary
connective tissue with interstitial matrix
Why is fluid movement able to occur at the capillary wall?
the capillary wall is a semi permeable membrane
How is hydraulic pressure created
Fluid moves across the membrane into interstitial space due to blood flow which exerts hydraulic pressure
How is oncotic pressure generated?
Large molecules (e.g. plasma proteins) aren’t able to pass through the membrane so exert an osmotic pressure which creates a suction force to move fluid into the capillary
Describe the effects of increasing pressures and fluid movement
Increased hydraulic pressure
=> fluid moves into intertstitial fluid
Increased oncotic pressure
=> fluid moves into capillary
What controls fluid movement across capillaries?
Fluid movement across capillaries depends on the balance between hydraulic and oncotic pressures
What determines the filtration rate?
4 pressures determine the rate of filtration:
Oncotic pressures:
πp - plasma proteins; high osmotic pull against filtration
πᵢ - interstitial proteins; moderate osmotic pull out of
vessels
Hydraulic pressures:
Pc - capillary BP
Pi - Interstitial fluid pressure
What is starling’s principle of fluid exchange?
Jv = LpA {(Pᶜ - Pᵢ) - 𝛔(Πp - Πᵢ)}
Pᵢ - interstitial fluid pressure Pᶜ - capillary BP Πᵢ - interstitial proteins Πₚ - plasma carotid osmotic pressure 𝛔 - reflection coefficient (fraction of osmotic pressure exerted) for plasma proteins = 0.9
Where does filtration occur in capillaries?
In well perfused capillaries filtration occurs across the entire length
How does filtration differ at the arteriole and venous end?
The pressure drops as you move down the capillary so filtration decreases by the time you reach the venous end
Pᶜ and Πp alters along capillary length
How is lymph related to fluid exchange?
Lymph becomes part of the interstitial fluid and later returned to the blood plasma
What is the role of lymphatic circulation?
Returns excess tissue fluid / solutes back to the cardiovascular system (approx. 8 litres a day)
How does lymph flow occur?
lymph vessels have valves and smooth muscle
Spontaneous smooth muscle and surrounding skeletal muscle contraction & relaxation contributes to lymph flow
What does the overall control of extracellular fluid balance depend on?
- capillary filtration
- capillary reabsorption
- lymphatic system uptake
How does Starling’s Law affect fluid balance?
Starling’s Factor determine changes in fluid balance within:
- circulation
- interstitial fluid
- lymphatic system
What is the effect of hypovolemia on fluid exchange?
Low capillary pressure Pc
Decreased blood volume -> drop in preload
Decreased Contraction force
Decreased diastolic pressure
Starling’s Law doesn’t help - CO decreases
Haemorrhage leads to drop in BP affecting capillaries
What is the benefit of interstitial fluid moving into the blood after a haemorrhage?
life preserving
- supports CVP
- increases CO
- Raises BP
- Greater Blood flow
What causes the interstitial fluid to move into blood after haemorrhage?
Caused by sympathetic nerve induced vasoconstriction of pre-capillary arterioles leading to a drop in downstream capillary pressure
Explain in terms of pressure how interstitial fluid is able to move into blood following a haemorrhage?
Filtration occurs to begin with, followed by reabsorption as:
Osmotic pressure > hydraulic pressure
- useful self correcting mechanism during low BP allowing more fluid to be absorbed back into circulation => increasing Blood volume
How does the movement of interstitial fluid into blood relieve haemorrhage?
Leads to greater preload -> greater CO -> returns BP to normal maintaining blood flow to the heart and brain
How does a drop in cardiac output affect capillary pressure?
Drop in Co leads to a drop in BP causing a reduction in Pc (capillary pressure)
What is oedema?
Excess fluid within the interstitial space due to the imbalance between filtration, reabsorption and lymph function
What are the causes of oedema?
Increased capillary Pc
Decreased πₚ
Inflammatory Response
Lymphatic Problems
What may be the causes of Increased Capillary pressure?
- dependent gravitational oedema - prolonged orthostasis
- DVT - deep vein thrombosis
- Cardiac Failure
What is DVT?
Deep vein thrombosis is the prevention of venous return, increasing venous pressure causing ‘back up’ of pressure leading to increased Pc across capillaries and increased filtration
How can [plasma protein] affect venous return?
reduced [plasma protein] -> reduced plasma oncotic pressure => greater Pc and πi influence -> fluid efflux from capillaries into interstitial fluid => causes oedema
What pathological causes may result in low protein oedema?
Malnutrition / malabsorption
- not enough protein intake to make plasma proteins
Nephrotic Syndrome
- urinary protein loss, replaced by liver production
Liver Disease
- not enough endogenous albumin produced
What is Kwashiorkor?
a malnutrition disease linked to decreased osmotic pressure
How does low [plasma protein] increase filtration?
Less plasma proteins in plasma = less osmotic force to absorb fluid from interstitial fluid
Balance is shifted towards hydraulic pressure, increasing filtration
What is the cause of inflammatory mediated oedema?
Swelling triggered by local chemical mediators of inflammation causing a large increase in capillary permeability -> increased Lp (hydraulic conductance of endothelium)
What is increased protein permeability during inflammatory mediated oedema caused by?
chemicals insect bites infection physical trauma autoimmune diseases nettle stings
What is lymphatic obstruction caused by?
filariasis / elephantiasis - nematode infestation larvae migrate to lymphatic system to grow, mate and form nests blocking lymph drainage
What is the cause of lymphatic removal?
Lymphodema caused by surgery to treat testicular cancer
What are the 2 main capillary functions?
Solute exchange
- nutrition of tissue, hormone & drug delivery
- individual molecules move down diffusion gradient
- obey Fick’s Law
Fluid exchange - regulation of plasma & IF volumes - bulk flow of all molecules together down pressure gradients - obey Starling's Law
