1. Transport across the
cell membrane
Dr AnuPriya J
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2. • Transport of substances across the cell
membrane is necessary to maintain the
normal functioning of the cells in our body.
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Introduction

3. Transport across the
cell membrane
 Lipid soluble substances, water & urea can easily
pass through the lipid bilayer of the cell membrane
The lipid bilayer of the cell membrane is
impermeable to lipid insoluble substances such as
ions & charged or polar molecules like glucose
These substances pass through specialized protein
channels, carrier proteins & active pump
mechanisms
• Large macromolecules are transported through
vesicles.
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4. Types
• Passive transport
– Diffusion – simple, facilitated
– Osmosis
• Active transport
– Primary
– Secondary
• Vesicular transport
– Endocytosis
– Exocytosis
– Transcytosis
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5. NO ENERGY NEEDED:
Diffusion
Osmosis
Facilitated Diffusion
ENERGY NEEDED:
Active Transport
ANALOGY:
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6. NO ENERGY NEEDED:
Diffusion
Osmosis
Facilitated Diffusion
ENERGY NEEDED:
Active Transport
ANALOGY:
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7. PASSIVE TRANSPORT
Diffusion- Simple
Facilitated
Osmosis
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8. Diffusion-simple
• It is the movement of ions or molecules from
a region of their high concentration to a
region of their low concentration, without the
expenditure of energy
• Movement is towards the concentration
gradient until an equilibrium is achieved.
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9. 9/28/2018 msrmc 9

10. Distilled water
Potassium
manganate
(vii) crystals
a) The crystals starts to dissolve,
forming a region of high
concentration of solute
molecules.
b) The molecules
diffuse out along the
concentration
gradient in all
direction.
c) Eventually the molecules
spread throughout the
water uniformly.
Purple
solution
A sample experiment to illustrate the physical process of diffusion
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11. Factors affecting the rate of diffusion
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Factor Effect on the rate of simple diffusion
Diffusion gradient/
concentration difference
The steeper, the higher the rate
Size of molecules or ions/
Molecular weight
The smaller the size, the higher the rate
Indirectly proportional
Temperature The higher the temperature, the higher the
rate
Diffusion medium Rate in gas > rate in liquid > rate in solid
Surface area The larger the surface area, the higher the
rate

12. Factors affecting the rate of diffusion
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Factor Effect on the rate of simple diffusion
Solubility Directly proportional
Thickness of membrane Indirectly proportional
FICK’S LAW OF DIFFUSION

13. Simple diffusion
Diffusion through lipid matrix
• Lipophilic/hydrophobic/nonpolar/uncharged
substances such as O2,CO2,N2,fatty acids,
alcohol, steroid hormones, etc.,
• Water as it is a small molecule with high
kinetic energy
• Urea
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14. Simple diffusion
Ionic diffusion – through channel proteins
• Ions diffuse through the ion channels.
• They are either open or gated.
• Open/leak channels – ex: K+ channels
• Gated channels open when stimulus is given
– Voltage gated
– Ligand gated
– Mechano sensitive gated
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15. Inhaled and exhaled air
O2 CO2
Oxygenated bloodDeoxygenated
blood
Red blood cell
Capillary wall
Alveolus wall
Air sac
GASEOUS EXHANGE BY SIMPLE DIFFUSION
IN THE ALVEOLUS
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16. Facilitated diffusion
• Facilitated diffusion is the movement of specific
molecules (or ions) across the plasma membrane,
assisted by a carrier protein.
• The direction of movement is down the
concentration gradient of the molecules concerned.
• No energy required.
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17. Facilitated diffusion
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18. Difference between
carrier proteins & channel proteins
• Carrier proteins bind to larger molecules, and
change their shape so molecules can diffuse
through.
• Channel proteins provide water filled pores
for charged ions to pass through
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19. Difference between
simple and passive diffusion
Simple diffusion Facililated diffusion
Mechanism Concentration gradient Concentration gradient
Through carrier molecule
Rate of diffusion Increase with increase in
concentration gradient
Reaches plateau
(saturation of carrier
protein)
Example Ions through ion channels GLUT for glucose
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20. 0smosis
• Osmosis is the movement of water molecules
(solvent) through a selectively permeable
membrane/ semipermeable membrane like the
cell membrane.
• Water diffuses across a membrane from an
area of high concentration to an area of low
concentration.
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21. Osmosis
• Semi-permeable membrane is permeable
to water, but not to the solute i.e.,sugar
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23. Tonicity
• Osmolality of a solution relative to plasma
• Sodium ion is the major contributor to tonicity of ECF
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24. Hypertonic Solutions
•Contain a high concentration of solute relative to
another solution (e.g. the cell's cytoplasm).
•When a cell is placed in a hypertonic solution, the
water diffuses out of the cell, causing the cell to
shrivel.
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25. Hypotonic Solutions
• Contain a low concentration of solute relative
to another solution (e.g. the cell's cytoplasm).
• When a cell is placed in a hypotonic solution,
the water diffuses into the cell, causing the
cell to swell and possibly explode.
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26. Isotonic Solutions
• Contain the same concentration of solute as
another solution (e.g. the cell's cytoplasm).
• When a cell is placed in an isotonic solution, the
water diffuses into and out of the cell at the same
rate.
• The fluid that surrounds the body cells is isotonic.
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27. Click9/28/2018 msrmc 27

28. Hypertonic solution Isotonic solution Hypotonic solution Remains of cell
surface membrane
Crenation: Red blood
cell shrinks and turns
’spiky’
Red blood cell Swells up Haemolysis: Red blood
cell finally burst
CRENATION AND HAEMOLYSIS OF RED BLOOD CELL
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29. • Isotonic solution – 0.9% NaCl, 5% dextrose in
water
• Hypotonic solution – treat dehydration
• Hypertonic solution – mannitol – treat
cerebral edema
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31. ACTIVE TRANSPORT
Primary
secondary
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32. Active Transport
• Molecules move against the
concentration gradient (low to high)
• Energy must be provided
• Exhibit saturation kinetics
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33. 9/28/2018 36Dr.Anu Priya J

34. • Active transport is divided into two types
according to the source of the energy used to
cause the transport:
• 1. Primary active transport
• 2. Secondary active transport.
Active Transport
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35. Primary active transport
• They use the energy directly from the
hydrolysis of ATP.
Sodium potassium Pump
Calcium pump
Hydrogen Potassium pump
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36. Sodium potassium pump
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37. 9/28/2018 40Dr.Anu Priya J

38. Sodium potassium pump
- present in all eukaryotic cells
Functions:
1. Maintains sodium potassium concentration difference across the
cell membrane.
2. Maintains volume of the cell.
3. Causes negative electrical charge inside the cell – electrogenic
pump
4. Essential for oxygen utilization by the kidneys
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39. Calcium pump
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40. Secondary active transport
• Energy utilised in the transport of one substance helps
in the movement of the other substance.
• Energy is derived secondarily, from energy that has
been stored in the form of ionic concentration
differences of secondary molecular or ionic substances
between the two sides of a cell membrane, created
originally by primary active transport.
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41. Co-transport-symport
• The transport of Na+ via its concentration gradient is
coupled to the transport of other substances in the
same direction
• Carrier protein
• E.g SGLT
• Sodium glucose Co-transport
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43. 9/28/2018 46Dr.Anu Priya J

44. Counter transport
• The transport of Na+ via its concentration gradient is
coupled to the transport of other substance in the
opposite direction
Sodium-Hydrogen counter transport in the proximal
tubule of the kidneys
Sodium-Calcium exchanger in the cardiac cells
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45. Counter transport
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46. • Cardiac glycosides -Digitalis & Ouabain –
management of heart failure
• Inhibits Na+-K+ pump
• Accumulation of Na+ inside the cell & prevention of
K+ influx
• Intracellular accumulation of Na+ , decreases Na+
gradient from outside to inside.
Applied aspects
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47. • Calcium efflux through sodium-calcium exchanger in
the membrane utilizes sodium gradient.
• Decreased sodium gradient decreases calcium efflux
causing increase in cytosolic calcium concentration,
that promotes myocardial contractility.
Applied aspects
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49. Applied aspects
• Activation of Na+-K+ pump:
Thyroxine, Insulin, Aldosterone
• Inhibition of Na+-K+ pump:
Dopamine, Digitalis, Hypoxia, Hypothermia
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50. Difference between Facilitated diffusion
and Active transport
• In both instances, transport depends on carrier
proteins that penetrate through the cell membrane,
as is true for facilitated diffusion. 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.
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51. VESICULAR TRANSPORT
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52. 9/28/2018 msrmc 55

53. Vesicular transport
• Endocytosis
• Exocytosis
• Transcytosis
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54. Endocytosis/Exocytosis
• For substances the cell needs to take in
(endo = in) or expel (exo = out), that are too
large for passive or active transport
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56. Endocytosis
• The material makes contact with the cell
membrane
• Cell membrane then invaginates
• Invagination is then pinched off leaving the
cell membrane intact
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57. Types of Endocytosis
1. receptor mediated endocytosis
2. phagocytosis (solids)
3. pinocytosis (liquids)
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58. 9/28/2018 msrmc 61
Types of Endocytosis

59. Ex:
• White Blood Cells surround and engulf bacteria by
Phagocytosis.
• Pinocytosis – amino acids, fatty acids
• Receptor mediated endocytosis – LDL, Nerve growth
factor, vitamins, hormones, HIV virus entering the T
cell etc.,
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60. Exocytosis
• The process of release of macromolecules from
the cells to the exterior.
• Vesicles containing material to be exposed, bind
to the cell membrane
• Area of fusion breaks down leaving the contents
of the vesicle outside & the cell membrane intact
• Reverse pinocytosis or emeiocytosis
• Requires calcium & energy
• Secretory granules, hormones
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61. 9/28/2018 msrmc 64
Exocytosis

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Exocytosis

63. • Vesicles endocytosed on one side of the cell;
exocytosed on the opposite side.
• Caveolin mediated (Rafts & Caveolae)
• Also known as cytopempsis
• Transport of substances across the endothelial
cells of blood vessels to interstitial fluid
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Transcytosis

64. Transcytosis
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65. Thank you
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66. 9/28/2018 69Dr.Anu Priya J

67. 9/28/2018 Dr.Anu Priya J 70
Hydrogen Potassium pump
H+-K+ ATPase

68. Hydrogen Potassium pump
H+-K+ ATPase
• Gastric glands - parietal cells - hydrochloric acid
secretion
• Renal tubules - intercalated cells in the late distal
tubules and cortical collecting ducts.
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69. • Present in lysosome and endoplasmic
reticulum
• Pumps proton from cytosol into these
organelles.
Proton pump
H+ ATPase
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71. • In counter-transport, sodium ions again attempt to diffuse
to the interior of the cell because of their
• large concentration gradient. However, this time, the
substance to be transported is on the inside of the
• cell and must be transported to the outside. Therefore, the
sodium ion binds to the carrier protein
• where it projects to the exterior surface of the membrane,
while the substance to be countertransported
• 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.
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72. • Different substances that are actively
transported through at least some cell
membranes include sodium ions, potassium
ions, calcium ions, iron ions, hydrogen ions,
chloride ions, iodide ions, urate ions, several
different sugars, and most of the amino acids.
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73. • At times, a large concentration of a substance is required in the intracellular fluid
even though the
• extracellular fluid contains only a small concentration. This is true, for instance, for
potassium ions.
• Conversely, it is important to keep the concentrations of other ions very low inside
the cell even though
• their concentrations in the extracellular fluid are great. This is especially true for
sodium ions. Neither
• of these two effects could occur by simple diffusion because simple diffusion
eventually equilibrates
• concentrations on the two sides of the membrane. Instead, some energy source
must cause excess
• movement of potassium ions to the inside of cells and excess movement of sodium
ions to the outside
• of cells. When a cell membrane moves molecules or ions "uphill" against a
concentration gradient (or
• "uphill" against an electrical or pressure gradient), the process is called active
transport.
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74. ACTIVE TRANSPORT
• A process in which molecules move against
the concentration gradient across the cell
membrane with expenditure of energy.
• This energy is provided
by ATP.
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75. Sodium potassium pump
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76. Sodium potassium pump
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77. 9/28/2018 81Dr.Anu Priya J

78. • As with other enzymes, the Na+-K+ ATPase pump can run in reverse. If the electrochemical
gradients
• for Na+ and K+ are experimentally increased enough so that the energy stored in their gradients is
• greater than the chemical energy of ATP hydrolysis, these ions will move down their concentration
• gradients and the Na+-K+ pump will synthesize ATP from ADP and phosphate. The phosphorylated
• form of the Na+-K+ pump, therefore, can either donate its phosphate to ADP to produce ATP or use
the
• energy to change its conformation and pump Na+ out of the cell and K+ into the cell. The relative
• concentrations of ATP, ADP, and phosphate, as well as the electrochemical gradients for Na+ and K+,
• determine the direction of the enzyme reaction. For some cells, such as electrically active nerve
cells,
• 60 to 70 percent of the cells' energy requirement may be devoted to pumping Na+ out of the cell
and
• K+ into the cell.
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79. • The Na+-K+ Pump Is Important For Controlling Cell Volume
• One of the most important functions of the Na+-K+ pump is to control the volume of each cell. Without
• function of this pump, most cells of the body would swell until they burst. The mechanism for controlling
• the volume is as follows: Inside the cell are large numbers of proteins and other organic molecules that
• cannot escape from the cell. Most of these are negatively charged and therefore attract large numbers
• of potassium, sodium, and other positive ions as well. All these molecules and ions then cause osmosis
• of water to the interior of the cell. Unless this is checked, the cell will swell indefinitely until it bursts.
• The normal mechanism for preventing this is the Na+-K+ pump. Note again that this device pumps
• three Na+ ions to the outside of the cell for every two K+ ions pumped to the interior. Also, the
• Guyton & Hall: Textbook of Medical Physiology, 12e [Vish'aAlc] tive Transport' of Substances Through Membranes
• 93 / 1921
• membrane is far less permeable to sodium ions than to potassium ions, so once the sodium ions are on
• the outside, they have a strong tendency to stay there. Thus, this represents a net loss of ions out of
• the cell, which initiates osmosis of water out of the cell as well.
• If a cell begins to swell for any reason, this automatically activates the Na+-K+ pump, moving still more
• ions to the exterior and carrying water with them. Therefore, the Na+-K+ pump performs a continual
• surveillance role in maintaining normal cell volume.
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80. • Electrogenic Nature of the Na+-K+ Pump
• page 53
• page 54
• The fact that the Na+-K+ pump moves three Na+ ions to the exterior for every two
K+ ions to the
• interior means that a net of one positive charge is moved from the interior of the
cell to the exterior for
• each cycle of the pump. This creates positivity outside the cell but leaves a deficit
of positive ions
• inside the cell; that is, it causes negativity on the inside. Therefore, the Na+-K+
pump is said to be
• electrogenic because it creates an electrical potential across the cell membrane. As
discussed in
• Chapter 5, this electrical potential is a basic requirement in nerve and muscle
fibers for transmitting
• nerve and muscle signals.
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81. Primary Active Transport of Hydrogen Ions
• At two places in the body, primary active transport of hydrogen ions is important:
(1) in the gastric glands of the stomach and (2) in the late distal tubules and
cortical collecting ducts of the kidneys.
• In the gastric glands, the deep-lying parietal cells have the most potent primary
active mechanism for transporting hydrogen ions of any part of the body. This is
the basis for secreting hydrochloric acid in the stomach digestive secretions. At the
secretory ends of the gastric gland parietal cells, the hydrogen ion concentration is
increased as much as a millionfold and then released into the stomach along with
chloride ions to form hydrochloric acid.
• In the renal tubules are special intercalated cells in the late distal tubules and
cortical collecting ducts that also transport hydrogen ions by primary active
transport. In this case, large amounts of hydrogen ions are secreted from the
blood into the urine for the purpose of eliminating excess hydrogen ions from the
body fluids. The hydrogen ions can be secreted into the urine against a
concentration gradient of about 900-fold.
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82. Secondary active transport
• Energy utilised in the transport of one
substance helps in the movement of the other
substance.
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83. • Secondary Active Transport-Co-Transport
• When sodium ions are transported out of cells by primary active transport, a large concentration gradient
of sodium ions across the cell membrane usually develops-high concentration outside the cell and low
concentration inside.
• This gradient represents a storehouse of energy because the excess sodium outside the cell membrane is
always attempting to diffuse to the interior.
• Under appropriate conditions, this diffusion energy of sodium can pull other substances along with the
sodium through the cell membrane. This phenomenon is called co-transport; it is one form of secondary
active transport.
• For sodium to pull another substance along with it, a coupling mechanism is required. This is achieved by
means of still another carrier protein in the cell membrane. The carrier in this instance serves as an
attachment point for both the sodium ion and the substance to be co-transported.
• Once they both are attached, the energy gradient of the sodium ion causes both the sodium ion and the
other substance to be transported together to the interior of the cell.
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84. Proton pump
H+ ATPase
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