Forces Acting Across Membranes Flashcards
Difference of chemical composition in ICF and ECF is maintained by
presence of cell membrane (aka plasma membrane; aka plasmalemma)
The ECF consists of
the plasma and interstitial fluid.
Material moving between cells and ECF must cross the cell membrane.
Cell membrane is between the interstitial fluid and intracellular fluid.
Capillary wall separates
plasma from ISF.
Gases pass
freely across both the capillary wall and cell membrane.
Nutrients and waste pass
easily but sometimes need help crossing the cell membrane.
There is no barrier to
H2O movement
Ions pass
freely across the capillary wall so exchange readily between plasma and ISF. They do not penetrate the cell membrane.
[K+] is
high in ICF, low in ECF
[Na+] is
low in ICF, high in ECF.
Plasma is high in
[Na+] and plasma protein.
It’s low in [K+].
Interstitial fluid (ISF) is high in
[Na+].
It’s low in protein and [K+].
Intercellular fluid (ICF) is high in
[K+] and protein.
It’s low in [Na+].
Plasma and ISF are identical in everything except
(plasma) protein concentration
Cell membrane is
a selective barrier.
It is freely permeable to some substances.
e.g. O2 and CO2, but the difference in composition between ECF and ICF shows that permeability is selective and not universal.
Permeability can vary,
may increase or decrease at different times, fundamentally important for various cell functions eg transmission of the nervous impulse.
Structure of membrane:
Very thin bi-layer of lipids.
Major membrane lipids are phospholipids which have a hydrophilic (water loving) phosphate head and a hydrophobic (water repellent) fatty acid tail
Hydrophilic =
lipophobic (lipid repellent);
Hydrophobic =
lipophilic (lipid loving)
Membranes are embedded with
proteins (and associated with carbohydrates).
Membrane carbohydrates:
small amounts linked to proteins and lipids as glycoproteins and glycolipids.
ALL extracellular.
Important roles in cell to cell communication including self vs non-self recognition by the immune system.
Main Functions of Membrane Proteins
- Receptors
- Transporters (Carrier and channel proteins)
- Enzymes
- Maintenance of cell structure
Receptors
Integral to the membrane structure. Penetrate the membrane from ECF to ICF. Allow communication of an extracellular signal e.g. neurotransmitter or hormone, to the intracellular space to create a cellular response.
ligand-receptor complex
triggers intracellular response
Transporters
are proteins which allow movement of ions or molecules across the membrane.
Come in two forms:
- Channels
- Carrier Proteins.
Channel proteins:
create a pore through the membrane through which molecules, usually water and ions, flow.
Can be open (water) or gated (ions).
Carrier Proteins
do not create a continuous pore from ECF to ICF.
Open to ECF, then ICF, but never at the same time. Typically move larger molecules than channels e.g. glucose.
Membrane enzymes
catalyse chemical reactions on the cell membrane. Can be external
e.g. those found in small intestine which break down nutrients into smaller units, or internal such as those associated with converting signals carried from receptors into an intracellular response.
Structural proteins
are peripheral proteins, which are associated with the cell membrane but not incorporated into it. They can anchor the cell membrane both to the intracellular skeleton and to the extracellular matrix (collagen). Dysfunction or loss can cause serious debility (weakness) e.g. lack of dystrophin protein in Duchenne’s Muscular Dystrophy.
Membranes differ in their protein content.
- Myelin: a membrane that serves as an insulator around myelinated nerve fibres has a low content of protein (18%), major component is lipid, very good insulator so ideal for function.
- Plasma membranes of most other cells have much greater activity and protein content is typically 50%.
- Membranes involved in energy transduction such as the inner membranes of mitochondria, have highest protein content, roughly 75%.
Major barrier is the
cell membrane, (and to lesser extent, capillary wall).
Forces which produce movement of H2O and other molecules across these barriers are driven by concentration gradients.
Because the ions creating the concentration gradients are charged particles there is also a difference in charge across the membrane. This creates
an electrical gradient.
The net effect of these two forces create an electrochemical gradient which ultimately drives the direction of passive movement.
Any movement against this gradient requires energy (active transport).
Endocytosis and exocytosis are mechanisms for
moving macromolecules across membranes without disrupting them.
In endocytosis,
there is invagination of the membrane to form a vesicle which eventually disintegrates on the cytoplasmic (inside) surface of the membrane, releasing contents which then migrate within the cell to their destination.
Exocytosis involves the reverse process and so contents leave intracellular fluid.
In the body, diffusion occurs from
one compartment to another, provided the barrier between the 2 compartments is permeable to the diffusing substance.
There is considerable variability in membrane permeability for different substances.
Cell membranes are effectively impermeable
to intracellular proteins and organic anions. These items cannot diffuse in any capacity so they stay inside the cell.
For smaller molecules, it is important to distinguish between diffusion through
the lipid bilayer or via transport proteins embedded in it.
Diffusion through the Lipid bilayer:
- Small
- lipophilic (hydrophobic)
- UNCHARGED
Small, uncharged, lipophilic molecules such as O2 and N2 pass
rapidly through the lipid bilayer.
Small, uncharged, lipophobic molecules such as CO2 and urea
diffuse relatively easily across lipid bilayers.
Large, uncharged lipophobic molecules such as glucose
diffuse much more slowly through bilayer.
Small, charged particles such as ions
diffuse extremely slowly
Diffusion of ions (charged particles) through the lipid bilayer
bilayer is extremely slow.
Ions such as Na+ K+, and Cl-, do cross membranes at a much faster rate than predicted by their lipid permeability because
ions use Transport Proteins. These can either be
- channels
- mediated transport proteins.
Diffusion through channels
transmembrane proteins provide an aqueous route through the membrane for the diffusion of water and ions. Only allow the passage of mineral ions such as Na+ and K+, Cl-, Ca2+, H+ and H2O. Too small to allow molecules such as glucose to go through.
H2O passes freely through
aquaporins, specific family of water channels, ubiquitously distributed. There is NO barrier to water
Ions can cross the membrane using
channels. These are typically gated. They remain closed until a stimulus (chemical or change in electrical charge across the membrane) causes them to open.
Voltage gated channels =
open/close in response to alterations in the membrane electrical potential (charge difference either side of the membrane). Found extensively in muscle and nerve cells.
Ligand gated channels =
open/close when they bind a chemical such as neurotransmitter or hormone to a receptor binding site on the channel protein.
Multitasking membrane proteins
act as both receptor & transporter
Electrical or chemical stimulus
causes a conformational change in the configuration of the channel proteins causing them to open or close their channel as appropriate.
For diffusion across membranes, need to consider
the electrical gradient AND the concentration gradient.
inside of the cell carries a
______ charge with respect to the outside.
negative
The electrochemical gradient is a
combined gradient (chemical and electrical) down which ions will flow.
Electrochemical equilibrium is reached when
the chemical and electrical gradients are in balance.
Carrier-mediated transport systems
Carrier-mediated transport proteins have binding sites for solutes such as glucose. When they bind the solute, the carrier undergoes a change in shape which exposes the binding site on the other side of the membrane. The solute moves away and the carrier returns to its original configuration.
Mechanism of movement between compartments:
- Endocytosis and Exocytosis
- Diffusion
- directly through the lipid
bilayer - protein channels
- directly through the lipid
- Mediated Transport – facilitated diffusion vs active transport
- Osmosis
- Filtration (across capillary walls)
Movement of molecules through transport proteins down their electrochemical gradients
is facilitated diffusion
Movement of molecules through transport proteins against their electrochemical gradients requires energy (ATP) and is known as
active transport.
If the electrochemical gradient opposes movement then
energy in the form of ATP is required to move the molecule against this gradient. In these cases the carrier protein also functions an enzyme (ATPase) as it hydrolyses ATP to release energy.
Sometimes active transporters are called
“pumps”, eg. Na+/K+ ATPase or Na+/K+ pump.
Na+/K+ ATPase occurs in
ALL cells and helps maintain this difference by continually pumping out 3 Na+ ions and pumping in 2 K+ ions (both against concentration gradients) for each molecule of ATP hydrolysed.
In doing so it produces net movement of positive charge out of the cell = electrogenic pump (creates an charge difference across the membrane)
40% of resting energy of the body is used
by Na+/K+ ATPase
Osmosis is the
Net movement of H2O from regions of high H2O concentration to regions of low H2O concentration
Diffusion is the
Net movement of solute from regions of high solute concentration to regions of low solute concentration
water movement vs solute movement between cells and in ECF
Water can move freely between cells and the ECF so that the body is in osmotic equilibrium. Not all solutes move freely.
H2O concentration is inversely related to the
concentration of solute, ie the more solute particles there are in solution, the more they will displace H2O molecules lowering the concentration of H2O.
If a solution of different concentration is separated by a membrane permeable to H2O only, then
after a time it will end up with equal concentration on either sides of membrane but different volumes.
Assuming the compartments are expandable
osmotic pressure
the pressure required to prevent water movement If we try to oppose this increase in volume.
Where we have diffusion we also have
osmosis (water and solute move, in opposite directions).
Where we have osmosis, we may or may not have diffusion – if the membrane is only permeable to water, then water moves but the solute does not (so no diffusion).
This can cause a change in cell volume.
Cell membranes act as
semipermeable membranes. They are permeable to H2O and gases but some molecules in the ECF and ICF are unable to cross the membrane.
Ions pass
freely across the capillary wall so exchange readily between plasma and ISF but they do not penetrate the cell membrane hence differential distribution between ECF and ICF
osmolarity is the
number of solute particles, NOT molecules, which determine the osmotic effect on [H2O].
This can be misleading because some molecules dissociate in solution. eg- NaCl
1 mole of glucose added to 1L H2O decreases [H2O] by 1 mole/L
1 mole of NaCl added to 1L H2O decreases [H2O] by 2 moles/L because it generates 1 mole of Na+ and 1 mole of Cl-
“Osmolarity” measures the
concentration of biological solutions in units of “OSMOLES” and describes the number of particles/L of solution.
Normal human plasma has an osmolarity of 285 mOsmol/l which is the same as within cells, (often taken as 300 for ease of remembering).
Osmolarity says nothing about
the NATURE of the particles, critically it does not tell us if the particles can cross cell membranes.
the volume of a cell at any time is dependent on
the concentration of non-penetrating solutes on the either side of the membrane.
Non-Penetrating solutes in ICF vs ECF
In ECF, Na+ and Cl- act as non-penetrating solutes.
In ICF, K+ (and organic anions) act as non-penetrating solutes.
Osmolarity vs Tonicity
Osmolarity describes the number of penetrating (urea) and non-penetrating (ions) particles in solution
Tonicity describes the number of non-penetrating particles in solution. eg-ions
tonicity determines
cell volume.
Osmolarity:
isosmotic
Solutions that have the same total number of solute particles as normal ECF (plasma).
Osmolarity:
hypo-osmotic
Solutions with fewer total solute particles
Osmolarity:
hyper-osmotic
Solutions with greater number of total solute particles
Tonicity:
isotonic
Solutions that have the same number of non-penetrating solute particles as normal ECF (plasma).
Tonicity:
hypotonic
Solutions with fewer non-penetrating solute particles
Tonicity:
hypertonic.
Solutions with greater number of non-penetrating solute particles.
Cells in hypotonic solutions
swell – because water enters down a chemical gradient
Cells in hypertonic solutions
shrink – because water leaves down a chemical gradient
Intravascular haemolysis
(cells bursting) can kill.
Lysed (burst) cells introduce protein to ISF, increasing tonicity of ECF in an uncontrolled manner, making management very complicated.
NEVER transfuse a patient with pure water!
RBC placed in hyperosmotic urea will
swell and burst.
This is because urea is a penetrating particle and because the urea is in an aqueous hypotonic solution, it enters the cell until equilibrium is reached (equal numbers of urea particles inside and out).
However, there are lots of other things inside cells in addition to urea, so the water concentration remains greater outside than inside. This causes water to enter by osmosis leading to the bursting of the cell.
What will happen to the volume of red blood cells in patients with ureamia (excess urea in their plasma)?
Very little!
Although the cells burst in the presence of hyperosmotic urea, they did so because they were in a hypotonic solution to start with (pure water).
The urea makes NO DIFFERENCE to the osmotic movement of water in a living person.
Difference is in vivo there is lots of NaCl in the ECF and this is isotonic, so when you add urea to an iso-tonic solution, and it equilibrates across the membrane, the
resulting ECF
remains iso-tonic, so no net movement of particles occurs.
The ICF and ECF osmolarity has changed by the same amount of penetrating particle, but the non-penetrating particles remain unchanged so the ECF remains isotonic (despite now being hyper-osmotic).
Brain is most sensitive organ to
changes in tonicity.
A solution containing 100mM urea, 200mM NaCl is
Hypertonic
200mM NaCl splits to give 200mM Na+ ions and 200mM Cl- ions. Both ions are non-penetrating thus contribute to tonicity. 200 + 200 = 400 mosmol/L. Normal ECF is ~300mosmol/L so solution is hypertonic.
While given 100 + 200 = 300 the solution is not iso-osmotic because we have 400 mosmol/l ions so the osmolarity of the solution is actually 500 mosmol/L (hyperosmotic)
Cells placed in the solution containing 100mM urea, 200mM NaCl will
Shrink
Because the solution is hypertonic (400mosmol/L) the cells will lose water to the ECF and therefore shrink.
What about cells placed in a solution containing 100mM urea and 150mM NaCl will
Not change volume
This solution is isotonic (2 x 150 = 300mosmol/L) so there will be no change in cell volume. While the solution is hyperosmotic (150+150+100 = 400mosmol/L) the urea is a penetrating particle so equilibrates across the membrane and has no osmotic pull.
Why can there NOT be a difference between ICF and ECF osmolarity?
Because water will always move down any osmotic gradient.
Ions are non-penetrating particles and cannot cross membranes without some form of help – channel proteins, mediated carriers etc and only then move under specific conditions e.g. action potential of nerves.
If you drink 1litre of water, where will the water go?
33% in the ECF, 67% in the ICF
Water moves freely between ECF and ICF.
We have 2x as much ICF as ECF so the distribution is 33% ECF: 67% ICF
If you were to transfuse 1litre of isotonic saline, where would it go?
All in the ECF
The saline solution will remain in the ECF as the ions cannot cross the cell membrane and therefore effectively “hold” the water in the ECF due to their osmotic effect. The Na+ and Cl- ions prevent the water moving into the cell. Most effective way to increase plasma volume quickly.
What would happen to human red blood cells placed in a hyperosmotic and isotonic solution
nothing - tonicity determines cell size an tonicity is normal as it’s isotonic
What would happen to human red blood cells placed in a hyperosmotic and hypotonic solution
swell - water enters down a chemical gradient
What would happen to human red blood cells placed in a hyperosmotic and hypertonic solution
shrink - water leaves down a chemical gradient
What would happen to human red blood cells placed in a isosmotic and hypotonic solution
swell - water enters down a chemical gradient
