Physiology 1st yr MBBS presentation based on Guytons Physiology book

1. TRANSPORT ACROSS CELL MEMBRANE
Dr. Murad H Kazi

3. QUESTIONS
What holds all the cells
together and why is it
important??

4. Extracellular Matrix
• The extracellular matrix (ECM) is an intricate meshwork of fibrous
proteins embedded in a watery, gel-like substance composed of
complex CHO. The ECM serves as the biological “glue”. The watery
gel provides a pathway for the diffusion of nutrients, wastes and
other water-soluble traffic between the blood and the tissue cells.
• It is usually called interstitial fluid. Interwoven within the gel are
three major types of protein fibers: collagen, elastin and fibronectin.
• Functions of the ECM:
1. Composition of the ECM varies according to the different tissues.
2. Scaffolding for cellular attachment among cells.
3. Plays a role in growth and differentiation.
4. Cells can only survive in the ECM.

5. •What is cell adhesion and Why
do we need Cell-Cell Adhesions?
Cell adhesion is the binding of a cell to the
surface of another cell using cell-cell
adhesions (as we will study) or to the ECM,
using cell adhesion molecules (CAMs) as
integrins, selectins (CAMs work as
‘Velcro’).

6. Types of Cell Adhesions:
1. Desmosomes
2. Tight
Junctions
3. Gap
Junctions

7. DESMOSOMES
• Definition:
It is a circular, dense body
that forms at the site of
attachment/ adhesion
between 2 adjacent cells,
consisting of a dense plate in
each cell separated by a thin
layer of extracellular
material.
• These are also called
macula adherens.
• Act like ‘spot rivets’.
• Anchor together two
closely adjacent but
nontouching cells.

8. STRUCTURE OF A
DESMOSOME:
A desmosome has 2
components:
1. A pair of dense, button-
like cytoplasmic
thickenings known as
plaque located on the
inner surface of each of
the two adjacent cells.
2. Strong glycoprotein
filaments that extend
across the space between
the two cells and attach
to the plaque on both
sides.

9. FUNCTIONS OF DESMOSOMES
1. Abundant in tissues subjected to considerable
stretching e.g. skin, heart and uterus. In these tissues,
the cells are joined together by desmosomes that extend
from one cell to the next, then to the next and so on.
2. A continuous network of strong fibers extend
throughout the tissue, both through the cells and
between the cells: they are like a continuous line
of people holding hands.
3. Provides tensile strength.
4. Reduces the chances of tissue being torn when
stretched.

10. TIGHT JUNCTIONS:
Definition:
It is an intercellular junction,
where adjacent cells firmly bind
with each other at points of
contact to seal off the
passageway between the two
cells.
• The tight junctions are
impermeable.
• Passage across the epithelial
barrier, must take place
through the cells, not between
the cells: the traffic across the
cell is regulated by means of
the carriers and channels
present.
• Tight junctions thus prevent
undesirable leaks within
epithelial cells.

11. TIGHT JUNCTIONS

12. Definition:
Gap junctions are
communicating junctions. It is
a gap which exists between
adjacent cells, which are linked
by small, connecting tunnels
formed by connexons.
• Abundant in cardiac muscle
and smooth muscle where
they transmit electrical
activity.
• In non-muscle tissues they
permit small nutrient
molecules e.g. glucose, aa,.
• Serve as roads for transfer
of small signaling molecules
from one cell to next.
• GAP JUNCTIONS:

14. GAP JUNCTIONS
It has a small diameter that allows
water and water-soluble particles
to pass between the connected cells
but does not allow large molecules
like intracellular proteins.
These molecules can be exchanged
between cells without ever entering
the ECF.
They do not seal membranes
together, but permit small
molecules to shuttle from one cell
to another and link their interiors.
They allow electrical and metabolic
signals to pass from one cell to
another.

15. Cell-Cell Adhesions

17. Permeability of a membrane
Anything that passes between a cell and the
surrounding ECF must be able to pass through the
plasma membrane.
• If a substance can pass thru the membrane, the
membrane is said to be permeable to that
substance;
• if a substance cannot pass, the membrane is
impermeable to it.
• The plasma membrane is selectively permeable
in that it permits some substances to pass through
while excluding others.

18. Cell
Membrane
Permeable
Selectively
Permeable
1. Relative solubility of
the particle in Lipids
Lipid-
Soluble
Permeate the
Membrane:
Passive
Transport
Diffusio
n
Osmosis
Lipid-
Insoluble
2. Size of the particle
Size: Less than
0.8nm in
diameter
Protein
Channel
(e.g. for
NA+ ,
K+)
Size: more than
0.8 nm
in diameter
Assisted Transport
or Carrier-mediated
Transport
Active
Transport
Facilitated
Diffusion
Impermeable

19. KEY WORDS
• Solvent: (relatively large amount of a substance which
is the dissolving medium; in the body is water).
• Solute: (relatively small amount of a substance which is
the dissolved substance and it dissolves in the solvent).
• Solution: is a homogenous mixture of a solute in a
solvent.
• Concentration: of a solvent is the amount of solute
dissolved in a specific amount of solution.
• Concentration gradient: difference in the
concentration of a solute on two sides of a permeable
membrane.
• Equilibrium: exact balance between 2 opposing forces.
• Dynamic: continuous motion or movement.

21. • What happens when you spray a can of an air
freshener in the front of the classroom…. After
some time can the people at the back or the
other end of the room smell it…?

22. Diffusion of a Liquid Molecule

24. A good example is a drop of blue ink being dropped into a beaker
containing water. The way the blue ink spreads till it evenly spreads out is
called diffusion…..
Another good example is open bottle of cologne in a room… the cologne
spreads out in the room, u can smell it after a while even at the other end of
the room.

25. DIFFUSION
& a semi-permeable membrane:

26. Definition:
Diffusion is the passive movement of molecules from
an area of higher concentration of the molecule to an
area of lower concentration of the molecule.
(diffusere means “to spread out”)
Particles that can permeate the membrane diffuse
passively down their concentration gradient.
e.g. In our body, O2 is transferred across the lung
membrane by diffusion….

27. Diffusion
Diffusion is:
1. Passive.
2. Requires a concentration gradient.
3. Occurs until a dynamic equilibrium is reached.
4. Rapid over short distance, slow over long distance.
5. Increased at increased temperature.
6. Inversely related to molecular size, as molecular size
increases the resistance.
7. Can occur in an open system or across a membrane.

28. Factors affecting rate of Diffusion
1. Concentration Gradient: the rate of diffusion is directly proportional to
the concentration difference across the cell membrane. Thus, when the
gradient is zero, there will be no diffusion. Diffusion will only occur as long as a
concentration gradient exists. (Net diffusion α co-ci)
2. Temperature: Rate of Diffusion is directly proportional to Temperature.
As the temperature increases, so does rate of diffusion.
3. Pressure Difference: increases the rate of diffusion.
4. Molecular Weight: Rate of Diffusion is inversely proportional to the
molecular weight of the substance. (heavier molecules move more slowly than
smaller, lighter ones)
5. Distance Travelled: Rate of diffusion is inversely proportional to distance
traveled.
6. Lipid Solubility: Rate of diffusion is directly proportional to the lipid
solubility of the substance.
7. Surface Membrane: Rate of Diffusion is directly proportional to the
surface area of the membrane.
8. Membrane Electrical Potential: Rate of diffusion is directly
proportional to the membrane electrical potential across the membrane.

29. Fick’s Law of Diffusion:
Rate of Diffusion (Q) =
∆ 𝒄𝒐𝒏𝒄. 𝑺𝒖𝒓𝒇𝒂𝒄𝒆 𝑨𝒓𝒆𝒂. 𝑳𝒊𝒑𝒊𝒅 𝑺𝒐𝒍𝒖𝒃𝒊𝒍𝒊𝒕𝒚
𝑴𝑾. ∆ 𝑿
Where∆ 𝑐𝑜𝑛𝑐. = concentration gradient
∆ 𝑋 = distance travelled (thickness of the membrane)
MW= Molecular weight

30. Diffusion
Simple Diffusion
Kinetic movement of
molecules/ ions
through membrane
opening or
intermolecular spaces
Facilitated Diffusion
A carrier protein
chemically binds with
the molecule/ ion and
aids in its passage
across the membrane

32. Simple Diffusion thru gated channels
• Protein channels are present all the way from
the ECF to the ICF, thus substances can move by
simple diffusion directly along these channels
from one side of the membrane to the other.
These channels are distinguished by 2 important
features:
1. Selective permeability of the channel
2. Presence of gates

33. Gated channels in
Simple Diffusion:
Sodium Channels:
• 0.3 by 0.5 nm in diameter
• Negatively charged on the
inside
• Because of the negative charges
they pull the positively charged
sodium ion inside, away from
the water molecule.
Potassium channel:
• 0.3 by 0.3 nm in diameter
• No negative charge on the
inside
• Pull the hydrated K ion inside.
As no negative charge on the
inside of the channel, no
attractive forces for the Na
ion… also, Na ions hydrated
form is far too big….

34. THINK!
How does water get through the
HYDROPHOBIC Plasma membrane?

35. How does water get through the HYDROPHOBIC
Plasma membrane?
Answer: Even though water is polar and so highly
insoluble in the membrane lipids, it readily passes through
the cell membrane thru 2 ways:
1. Water molecules are small enough to move through the
monetary spaces created between the phospholipid
molecules’ tails as they sway and move within the lipid
bilayer.
2. In many cells, membrane proteins form aquaporins,
which are channels specific for the passage of water.
About a billion water molecules can pass in single file
through an aquaporin channel in one second.

37. OSMOSIS

38. OSMOSIS
Definition:
The diffusion of water down its concentration gradient
(that is, an area of higher water concentration to an
area of lower water concentration) thru a semi-
permeable membrane is called Osmosis.
Concept: Because solutions are always referred to in
terms of concentration of solute, water moves by
osmosis to the area of higher solute concentration.
Despite the impression that the solutes are “pulling,”
or attracting, water, osmosis is nothing more than
diffusion of water down its own concentration gradient
across the membrane.

42. Osmotic pressure: is the pressure that is required to stop osmosis. It is
the pressure necessary to prevent osmosis into a given solution when the
solution is separated from the pure solvent by a semipermeable
membrane. The greater the solute conc. of a solution, the greater its
osmotic pressure.
(HYDROSTATIC PRESSURE = OSMOTIC PRESSURE)
An osmole is one mole of dissolved particles in a solution. E.g.
glucose when dissolved in solution does not dissociate, so 1 mole of
glucose is also 1 osmole of glucose. On the other hand, NaCl dissociates
into 2 ions (Na and Cl) so is taken as 2 moles.
Osmolarity is the number of osmoles of solute per liter of
solution. Simply put, osmolarity is a measure of total solute conc. given in
terms of number of particles of the solute in 1 liter of solution. The
osmolarity of body fluids is usually expressed in milliosmoles per liter
(mOsm/L). (The normal osmolarity of body fluid is 300 mOsm.) It is
usually employed in clinical settings.
Osmolality is the number of milliosmoles of solute per kg of
solvent. It is usually calculated in laboratories using an osmometer.

43. Key Concept!
Understand: Between Osmosis and Diffusion,
the difference is only in the terminology: we are
describing water instead of solute. The principles
are the same as those of diffusion of solute
molecules thru a membrane.
REVIEW: Compare Diffusion and Osmosis.

45. What is a carrier protein?
• A carrier protein spans the thickness of the plasma membrane
and change its conformation so that specific binding sites
within the carrier are alternately exposed to the ECF and ICF.
• Carrier-mediated transport systems display 3 characteristics:
1. Specificity: e.g. glucose cannot bind to amino acid carriers
and vice versa.
2. Saturation: A limited no. of carrier binding sites are
available within a particular plasma membrane for a specific
substance. Thus, there is a limit to the amount of substance a
carrier can transport across the membrane in a given time.
This is called Transport Maximum (Tm).
3. Competition: Several different substances are competing
for the same carrier site.

46. Facilitated Diffusion
Definition:
Facilitated diffusion is a mediated-transport that
moves molecules from higher to lower concentration
across a membrane by means of a transporter which is
a carrier protein. That is, the carrier facilitates the
diffusion of the substance to the other side.
Metabolic energy is NOT required for this process.
E.g: Glucose, amino acids
Changes in the conformation of the transporter move
the binding site to the opposite side of the membrane,
where the solute dissociates from the protein.

48. Types of Active Transport
Active
Transport:
Primary
Active
Transport
Secondary
Active
Transport

49. Types of Active Transport:
Active transport is divided into 2 types depending on the source of
energy used:
In primary active transport, the energy is derived directly from breakdown
of adenosine triphosphate (ATP) or from some other high-energy phosphate
compound.
In secondary active transport, the energy is derived secondarily from
energy stored in the form of an ion concentration gradient between the two
sides of a cell membrane, created originally by primary active transport. Thus,
energy is used but it is “secondhand” energy and NOT directly derived from
ATP.
In both instances, transport depends on carrier proteins.
However, in active transport, the carrier protein functions differently from
the carrier in facilitated diffusion because it is capable of imparting energy to
the transported substance to move it against the electrochemical gradient by
acting as an enzyme and breaking down the ATP itself.

50. Primary Active Transport
• In primary active transport, energy in the form of ATP is required to
change the affinity of the carrier protein binding site when it is exposed
on opposite sides of plasma membrane.
• The carrier protein also acts as an enzyme that has ATPase activity,
which means it splits the terminal phosphate from an ATP molecule to
yield ADP and inorganic phosphate plus free energy.
Examples:
1. Sodium-Potassium Pump.
2. Transport of Hydrogen ions: occurs at 2 places in the human body:
- in the gastric glands of the stomach
- In the kidneys

52. Na-K PUMP:
• The carrier protein in the pump
has 2 subunits; a larger α
subunit and a smaller β subunit.
They perform the following
functions:
1. 3 receptor sites for binding
Na ions on the portion of the
protein that protrudes to the
inside of the cell.
2. 2 receptor sites for potassium
ions on the outside.
3. The inside portion of this
protein near the sodium
binding site has ATPase
activity.

53. FUNCTIONS OF SODIUM-POTASSIUM PUMP:
1. Control the Volume of each cell: It helps regulate cell
volume by controlling the concentrations of solutes inside
the cell and thus minimizing osmotic effect that would
induce swelling or shrinking of the cell. If the pump stops,
the increased Na concentrations within the cell will promote
the osmotic inflow of water, damaging the cells.
2. Electrogenic nature of the pump: It establishes Na and K
concentration gradients across the plasma membrane of all
cells; these gradients are critically important in the ability of
nerve and muscle cells to generate electrical signals essential
to their functioning.
3. Energy used for Secondary active transport: The steep Na
gradient is used to provide energy for secondary active
transport.

54. SECONDARY ACTIVE TRANSPORT
Secondary active transport: is also called coupled
transport. In secondary active transport, the downhill flow
of an ion is linked to the uphill movement of a second
solute either in the same direction as the ion (co-
transport) or in the opposite direction of the ion (co-
transporter).
The diffusion of Na+ down its concentration gradient into
the cell can then power the movement of a different ion or
molecule against its concentration gradient. If the other
molecule or ion is moved in the same direction as Na+ (that
is, into the cell), the coupled transport is called either
cotransport or symport. If the other molecule or ion is
moved in the opposite direction (out of the cell), the
process is called either countertransport or antiport.

55. Co-Transport/ Symport

56. CO-TRANSPORT OR SYMPORT:
• The carrier protein has two binding sites: one for the solute being moved against its
concentration gradient and one for Na.
• Sites: intestinal and kidney cells
• INTESTINAL CELLS: more Na+ is present in the ECF (in the intestinal lumen) than inside
the cells (because Na-K pump moves the Na out of the cell keeping its intracellular conc.
low).
• Because of this conc. difference, more Na binds to the carrier protein in the ECF.
• Binding of Na increases the affinity of the protein for Glucose which is present in low conc.
In the ECF.
• When both Na and Glucose are attached to the carrier protein, it undergoes a
conformational change and opens to the inside of the cell.
• Both Na & glucose are released to the inside of the cell: Na as there is low conc. & glucose
as carrier proteins affinity for it decreases as Na is released.
• The released Na is quickly pumped out by the Na-K pump, keeping the levels of
intracellular Na low.
• Thus, Na has been moved down its “downhill” while glucose is moved “uphill”.

57. COUNTER-TRANSPORT OR ANTI-PORT:
• . Sodium ions again attempt to diffuse to the interior
of the cell because of their large concentration
gradient. This time, the substance to be transported
is on the inside of the cell and must be transported to
the outside.
• The sodium ion binds to the carrier protein where it
projects to the exterior surface of the membrane,
while the substance to be counter-transported binds
to the interior projection of the carrier protein.
• Once both have bound, a conformational change
occurs, and energy released by the sodium ion
moving to the interior causes the other substance to
move to the exterior

59. SECONDARY ACTIVE TRANSPORT
CO-TRANSPORT COUNTER TRANSPORT
• Symport
• Na moves downhill
• Molecule to be co-transported
moved in the same direction as
Na, i.e. to the inside of the cell.
• E.g. Na with glucose and
amino acids.
• Site: intestinal lumen and
renal tubules of kidney.
• Anti-port
• Na moves downhill
• Molecule to be counter-
transported moves in the
opposite direction to Na, i.e. to
the outside of the cell.
• E.g. Na with Calcium and
Hydrogen ions.
• Site: Na-Ca counter transport
in almost all cells of the body
and Na-H+ in the proximal
tubules of the kidney.

62. MATCH:
• Diffusion
• Osmosis
• Carrier-mediated transport
• Facilitated Diffusion
• Primary active transport
• Secondary active transport
1. A passive transport process
which can be saturated at
high substrate conc.
2. Depends on a solute conc. to
drive the movement of
solvent across the plasma
membrane.
3. This uses ATP breakdown to
move the substance from low
to high conc.
4. This uses a conc. Gradient for
one substance to drive the
transport of another.

63. Questions:
• Give the Fick’s law of diffusion. Explain.
• What 2 properties of a particle influence
whether it can permeate the plasma membrane.
• State 3 important roles of Na-K Pump.