Capillaries I

Question 1

what does the H2O solution that leaves capillaries contain?

Answer 1

metabolic end-products

e.g. CO2, urea

Question 2

what does the H2O solution that enters capillaries contain?

Answer 2

O2, glucose, amino acids,
hormones, immune response etc.
– energy, growth & repair

Question 3

what does metabolism create?

Answer 3

a need to transport solutes and fluids

Question 4

if you are a complex animal, what do you need in order to support metabolism?

Answer 4

a transport mechanism which can supply the body with oxygen and nutrients to maintain electrolyte balance

Question 5

what fluid are the metabolites in?

Answer 5

mostly in intracellular fluid

Question 6

how is extracellular fluid split

Answer 6

Extracellular fluid consists of 2 compartments
1. fluid that is bathing the tissues - interstitial fluid

2. fluid that is in the circulatory system - plasma

Question 7

do plasma and interstitial fluid have a similar composition?

Answer 7

yes

Question 8

what is cell metabolism continually generating?

Answer 8

concentration gradients that facilitate the movement of nutrients in and waste products out of cells

The problem is that we need to get across membranes….membranes are a barrier to movement.

Question 9

what are cell membranes a barrier to?

Answer 9

solute transport

-movement of any solute that isn’t lipid soluble (glucose, aa, ions etc.), meaning it acts as a selective barrier

Question 10

cell membrane structure

Answer 10

• Lipid bilayer consists of two layers of amphipathic phospholipids
• Phosphate head is polar (hydrophilic) so it can interact with water
• Fatty acid tails are non-polar (hydrophobic)
• Form bilayers in solution

Question 11

what do polar substances not mix with?

Answer 11

non-polar substances

Question 12

role of the cell membrane

Answer 12

• Provide support and protection
• Cell-to-cell recognition – (recognising different kinds of cells) e.g. immune system, allowing hormones and neurotransmitters to work
• Controls what enters or leaves the cell – e.g. ion movement in nerves
• Regulates cell function – e.g. insulin-mediated glucose uptake

Question 13

phospholipids have what?

Answer 13

both charged and non charged groups – hydrophilic and hydrophobic regions - that creates the bi-lipid membrane

Question 14

its difficult to get solutes across which part of the membrane?

Answer 14

the hydrophobic centre of the membrane

Question 15

other structures in the cell membrane and their role

Answer 15

• transmembrane proteins that span across the membrane and facilitate transport and signalling
• carbohydrates anchoring the proteins and orientating them
• these complicated structures are a barrier and also help things move across the membrane.

Question 16

what are the diff types of transport and when are they used?

Answer 16

passive or active

• use passive transport = move molecules down a gradient
• active transport = against a gradient

Question 17

define passive transport:

Answer 17

• Movement of molecules DOWN a gradient
• gradient can be concentration / pressure / osmotic / electrical
• Does not require energy
• Simple (O2/CO2) or facilitated (ions, glucose)

Question 18

explain the differences between simple and facilitated diffusion:

Answer 18

Simple
-simple diffusion for oxygen and carbon dioxide

Facilitated

• for ions and glucose where specific channels or transmembrane molecules help with the transport
• no external energy needed because the movement is still due to a gradient
• GLUT transporters

Question 19

define active transport:

Answer 19

• Movement of molecules AGAINST a gradient
• Therefore requires energy (uses ATP)
• e.g. ATP-dependent pumps, endocytosis, exocytosis

Question 20

give an example of active transport

Answer 20

sodium potassium ATPase

• taking potassium into the cell and sodium out
• moving potassium into the cell against its concentration gradient

Question 21

Name 4 passive transport processes:

Answer 21

Diffusion
• Concentration gradient
• e.g. O2 uptake from lungs into blood

Convection
• Pressure gradient
• e.g. blood flow from heart to blood vessels

Osmosis
• Osmotic pressure gradient
• e.g. water uptake by cells

Electrochemical flux
• Electrical and concentration gradient
• e.g. ion flow during an action potential in a nerve

Question 22

what occurs at capillaries?

Answer 22

solute and fluid exchange

Question 23

what are capillaries?

Answer 23

• Connect terminal arterioles to venules - extension of inner lining of arterioles.
• Smallest diameter blood vessels
• Endothelium is virtually 1 cell thick, semi-permeable
• Found near every cell in the body but higher density in highly active tissue (muscles, liver, heart, kidney, brain etc.)

Question 24

what kind of exchange can occur in capillaries?

Answer 24

Solute exchange (passive diffusion): O2, glucose, amino acids, hormones, drugs

Fluid exchange along pressure gradients. Regulation of plasma and interstitial fluid volumes - need to maintain BV in order to maintain BP and adequate perfusion of tissues. Bulk movement needs to be balanced.

Question 25

what factors affect the rate of solute transport?

Answer 25

permeability, how easy it is to cross the membrane: * Properties of passive diffusion e.g. concentration, rate, distance * Properties of solutes and membranes e.g. Fick’s law * Properties of capillaries: affect movement (affect solute exchange and bulk movement of fluid between plasma and interstitial fluid)

Question 26

give some properties of passive diffusion:

Answer 26

Does not require energy (no ATP) Molecules move randomly Move from area of high to low concentration Great for transport of lipid-soluble solutes over very short distances, eg. O2, CO2.

Question 27

why is passive diffusion good for only short distances?

Answer 27

because the time taken (t) for one randomly moving molecule to move a net distance (x) in one specific direction increases with the distance squared t = x^2/2D D = diffusion coefficient for molecule within the medium e.g. D for O2 in water and O2 in air are different

Question 28

Properties of solutes that affect transport

Answer 28

* Concentration gradient * Size of the solute * Lipid solubility of solute (lipophilic/lipophobic nature)

Question 29

Properties of membrane that affect transport

Answer 29

* Membrane thickness/composition * Aqueous pores in the membrane (made of proteins, the more channels means the more diffusion that can take place) * Carrier-mediated transport * Active transport mechanisms

Question 30

what is Fick's Law and what is it used for? | look at notes for the equation

Answer 30

Used to investigate how much of a substance is transported per time Solute movement (it’s a flow) - mass per unit time m/t (Js) determined by 4 factors: • D = Diffusion coefficient of solute, means the physical property of a solvent that determines the ease of movement through solvent. • A = Area (the greater the A the greater the solute movement) Decrease the area available to diffuse through membrane, we decrease amount of material transferred • ΔC = concentration gradient (C1-C2) Increase the concentration gradient – more movement as Js goes up • x = distance (between C1 and C2) Increase the distance, less movement per time

Question 31

why is Fick's Law negative?

Answer 31

negative value as the movement is downhill from a high to low concentration

Question 32

name the different types of capillaries in order of increasing permeability:

Answer 32

Continuous Capillaries Fenestrated capillaries Discontinuous capillaries

Question 33

what are continuous capillaries?

Answer 33

Moderate permeability: * Tight gaps between neighbour cells, making them relatively impermeable * Constant basement membrane * Single layer of endothelial cells (produce NO), * Pericytes on outside of basement membrane * Few intercellular clefts – where things get through * Mainly channels and transported to open and close selectively * Blood-brain barrier - Muscle, skin, fat, and connective tissues

Question 34

explain the relevance of continuous capillaries having tight junctions

Answer 34

• Means no space for fluid to move out from lumen into interstitial tissue

Question 35

give an example of why having a constant basement membrane in continuous capillaries is useful?

Answer 35

• useful in certain situations such as the blood brain barrier, as this is not going to non-selectively allow things into the brain, but it will make sure all entry is regulated

Question 36

what are fenestrated capillaries?

Answer 36

* Permeable to water and small solutes but not larger things * High water permeability * Present in areas where there is a “high water turnover”, areas where we need fluid out of the plasma (salivary glands, kidney, synovial joints, anterior eye, choroid plexus, gut mucosa) * Same structure, but have pores called fenestrations and more intercellular clefts * Some pinocytotic vesicles for more active transport going on

Question 37

what are fenestrations?

Answer 37

not just holes but are protein structures that allow small molecules to pass through

Question 38

explain the importance of fenestrated capillaries having a high water permeability:

Answer 38

means they are good where a lot of water is required e.g. in salivary glands a lot of water can leave the capillaries go into the interstitial space and be used to make saliva

Question 39

what are discontinuous capillaries?

Answer 39

* Incredibly leaky * Very large fenestration (hole) structures which are relatively specialised * Disrupted membrane * Large intercellular cleft * Incomplete basement membrane so even cells can move through * Spleen, bone marrow, liver, where blood cells need to go in and out

Question 40

what are the 3 structural features of the capillary walls which can influence solute transfer?

Answer 40

• Intercellular clefts – 10-20nm wide (no cells through, but water and proteins can). Intercellular clefts are in between adjacent cells that are not linked by tight junctions and this allows solutes and fluids to move through between the cells, this is going to aid permeability • Caveolae and Vesicles – Large pores which allow big substance movement through the membrane. Substances can be taken up on one side of the membrane and moved to the other side - so you have endocytosis followed by exocytosis and that will move the solute from the lumen across into the interstitial space • Glycocalyx – carbohydrate material, highly negatively charged, covers the entire endothelial surface next to the lumen. It acts like an extra barrier, blocking solute permeation and access to transport mechanism, highly regulated. Very dynamic, broken down and remade as required

Question 41

What is permeability?

Answer 41

Permeability is the rate of solute transfer by diffusion across unit area of membrane per unit concentration difference i.e. how freely solute crosses a membrane

Question 42

how does a porous membrane interfere with the diffusion of a lipid insoluble solute?

Answer 42

o Reduction in area for diffusion (A) o Increased path length through membrane (x) o Restricted diffusion in pore produces hydrostatics issues (D)

Question 43

how can the permeability of a membrane vary?

Answer 43

- pore size | - width

Question 44

if more potassium channels are open, which parameter in Fick’s law is increased?

Answer 44

A (surface area of capillary involved in transport) because you have more area available for diffusion because ion channels are needed for diffusion.

Question 45

transport of large lipophobic molecules eg. plasma proteins:

Answer 45

only through big gaps • In inflammatory situations – big gaps are formed so they can go through these • Otherwise, can go through transcellular channels • transport through pinocytosis, phagocytosis, and vesicles • Permeability of membrane – won’t go through lipids and membrane – modifying Fick’s law.

Question 46

transport of small lipophilic molecules:

Answer 46

* O2 and carbohydrates dissolve in most polar and nonpolar solvents, and go straight through * May move via intercellular channels or fenestrations

Question 47

transport of small lipophobic molecules:

Answer 47

* through intercellular channels and big fenestrations * Often, using specialised transporters * Proteins embedded in membrane have conformational changes, when bound to glucose, to allow it to enter * Water only allowed through specific aquaporin channels and big fenestrations (oedema)

Question 48

what is the difference between diffusion or filtration, and which is more dominant?

Answer 48

Diffusion is going to be passive, down its concentration gradient whereas filtration is going to be through pores, gaps and fenestrations 98% of glucose transport into interstitial space via passive diffusion – via GLUT transporter system

Question 49

name the factors that influence the control of diffusion rate:

Answer 49

1. Blood flow 2. Fall in interstitial concentration 3. Recruitment of capillaries

Question 50

how does blood flow affect diffusion rate?

Answer 50

* More blood brings more solutes, by dilating arterioles. Increased BV means less time for equilibration to occur across capillaries * Fast flow of blood = maintenance of the big difference in concentration from blood to tissue * Maximum rate of diffusion as concentration gradient is large all the time * Slow flow = allows time for blood to flow through capillary to equilibrate and concentration gradient lessens, slowing diffusion rate * Say you have a length of capillary, if you have very slow blood flow, then oxygen and carbon dioxide exchange over a short space and then for the rest of the capillary they are at equilibrium and there is less diffusion. * E.g. flow limited diffusion, where there is slow flow in a long capillary. As blood enters, a lot of oxygen and little co2. The beginning has maximum exchange but at the end, the blood flows slowly, the concentration gradient is very small and as a result there is not much diffusion * That’s why capillaries are short – rate of blood flow affects rate of diffusion. * Sometimes occurs in sepsis where blood pressure and flow are low, can lead to ischaemia.

Question 51

how does fall in interstitial concentration affect diffusion rate?

Answer 51

* As more solute is used in the tissues the concentration difference increases * During metabolism more solute is used up, thereby increasing the concentration difference * Also, metabolism increases blood flow – increased O2 delivery, controlled by the arterioles * If more metabolism, use of more nutrients and so have more concentration gradient * Metabolic activity, fast or slow, affects concentration * If tissue is metabolising rapidly, uses more O2 and makes CO2, makes concentration gradient bigger and diffusion faster

Question 52

how does recruitment of capillaries affect diffusion rate?

Answer 52

* Dilation of arterioles leads to increased number of perfused capillaries which increases total surface area (A) for diffusion (Fick’s Law). Also, this shortens diffusion distance between capillary and cell * Increase flow by dilating arterioles * If you need a bigger SA, for increased diffusion, increase perfusion of that tissue with blood and get more transport that way

Question 53

how is diffusion rate affected during exercise?

Answer 53

increased e.g. blood to muscle increases 40x during strenuous exercise. Increase CO (blood flow), use more oxygen in metabolising tissue (fall in tissue concentration), open up capillaries (recruitment)