TRANSPORT ACROSS CELL
MEMBRANES

•Cell membrane maintains
a constant and distinctive
intracellular environment
which is essential for
functioning of the
organelles

•There are several mechanisms of transport across cell
membranes.
•They may be grouped as under the headings:
1) Passive transport
2) Active transport
3) Vesicular transport
4) Transport across epithelia
5) Transport across capillaries

PASSIVE TRANSPORT
• It refers to the mechanism of transport of substances
along the gradient without expenditure of any energy.
• It depends on physical factors like concentration
gradient, electrical gradient and pressure gradient
• It is also called downhill movement

• Passive transport mechanism operating at cell
membrane level are
 Diffusion
 Osmosis

1. DIFFUSION
• Diffusion refers to passive transport of molecules
from areas of higher concentration to areas of lower
concentration
• Diffusion through cell membrane is divided into 2
subtypes
 Simple diffusion
Facilitated diffusion

Carrier
protein

SIMPLE DIFFUSION
 Movement of molecules or ions occurs through a
membrane due to their random movement.
 In this process, there occurs a net flux of molecules
from areas of high to areas of low concentration until
diffusional equilibrium is reached.
This can be expressed by Fick’s law of diffusion

Fick’s law of diffusion
J = D A (C1 - C2)
T
J  Rate of diffusion
D Diffusion co-efficient
A Area of membrane
T Thickness of membrane
C1-C2 Concentration gradient

• Simple diffusion can occur through 2 pathways
i. Direct passage without involvement of carrier
molecules
ii. Passage through protein channel molecules

i. Simple diffusion of lipid soluble substances
• Lipid soluble substances diffuse very rapidly through the
bilipid layer.
 O2, CO2, N2
 Fatty acids
 Alcohol
 Ketone bodies, Aldehydes
 Small uncharged molecules
• The rate of diffusion is directly proportional to the lipid
solubility of the substances and concentration gradient across
the membrane

ii. Simple diffusion through protein channels
•Water and other lipid insoluble substances pass
through cell membrane due to the presence of protein
channels
 Water
 Electrolytes or Ions
Eg: Sodium channels, Potassium channels, Chloride
channels, Calcium channels, Aquaporin channels

• Passage of substances through the protein channels is
regulated by selective permeability and gating of the
channels
• Permeability of such substances depends upon their
molecular size, shape and charge
• Some protein channels are continuously open (non
gated) while most are gated on either side of the
channel that can open or close as per requirement

• The opening and closing of gates are controlled by 3
principal ways
1. Voltage gated channels
Eg: Voltage gated sodium channels
2. Ligand gated channels
Eg: Acetyl choline channels
3. Mechanically gated channels
Eg: Stretch sensitive channels in ventricles, hair
cells

FACILITATED DIFFUSION
• Water soluble substances having larger molecular size
which cannot diffuse through protein channels
• They are transported across the cell membrane down their
concentration gradient with help of carrier proteins
without expenditure of energy.
• This type of diffusion is called facilitated or carrier
mediated diffusion
 Glucose
 Amino acids

•Mechanism of facilitated diffusion:
A conformational change occurs in the carrier
protein after the molecule to be transported is bound
at the receptor site.
As a result, the binding site is switched to the
opposite side of the cell membrane and the diffusing
molecule is released.

FACTORS AFFECTING NET RATE OF DIFFUSION
I. Concentration gradient
II. Electrical potential across the membrane
III. Permeability coefficient of the substance for the membrane
IV. Pressure difference across the membrane
V. Temperature
VI. Distance across which diffusion is occurring(thickness of
membrane)
VII. Area of membrane

2. OSMOSIS
• It refers to the diffusion of water or any other solvent
molecules through a semipermeable membrane from
a solution containing lower concentration of solutes
towards the solution containing higher concentration
of solutes.

• Osmotic pressure refers to the minimum pressure
which when applied on the side of higher solute
concentration prevents the osmosis
• The osmotic pressure exerted by the colloidal
substances in the body is called colloidal osmotic
pressure
• The colloidal osmotic pressure due to plasma proteins
is called oncotic pressure

• Osmole is the unit to express the concentration of osmotically active
particles in a given solution (Osm)
• One osmole = Molecular weight (g)
Number of freely moving particles that each mol liberates in
solution.
• Osmolality of a solution refers to the number of osmotically active
particles per kilogram of a solution (Osm/kg)
• Osmolarity refers to number of osmoles per litre of a solution
(Osm/L)

Plasma Osmolality(mOsm/L)
=2[Na+ (mEq/L) ]+0.055[Glucose (mg/dL) ] + 0.36[BUN(mg/dL)]
• Normal plasma osmolality is 290 mOsm/kg
270 mOsm is contributed by Na+, Cl-, HCO3-
20 mOsm is contributed by glucose and urea
Plasma proteins contribute only 2 mOsm due to large
molecular weight and lesser number of particles

• Tonicity refers to the osmolality of a solution in relation plasma(290
mOsm)
• Isotonic fluids – solutions having osmolality similar to plasma
Eg: 0.9 % NaCl solution, 5% Glucose solution
• Hypertonic fluids - solutions having osmolality higher than plasma
• Hypotonic fluids - solutions having osmolality lower than plasma
• It is the RBC membrane across which the tonicity is tested
In Isotonic solution In Hypotonic solution In Hypertonic solution
RBCs do not change
the shape or size
Cells swell due to
endosmosis
Cells shrink due to
exosmosis

ACTIVE TRANSPORT
• Active transport is also carrier mediated like facilitated
diffusion
• It refers to the mechanism of transport of substances
against the chemical or electrical gradient
• It is also called uphill movement
• It involves expenditure of energy which is liberated by
breakdown of high energy compounds like ATP

Mechanism of active transport
• The substance to be transported combines with a
specific carrier protein on the cell membrane
• The complex undergoes conformational change and is
actively pumped towards the inner/outer surface of
the cell membrane
• Hence, it is also called as active pump mechanism
• The carrier protein then moves back to its original
position

• Active transport is of two types
Primary active transport
Secondary active transport

PRIMARY ACTIVE TRANSPORT
• Energy derived directly from breakdown of ATP or
some other high energy phosphate compound
Eg: Na⁺-K⁺ ATPase pump
H⁺-K⁺ ATPase pump
Calcium ATPase pump

SECONDARY ACTIVE TRANSPORT
• Energy is derived secondarily from the ionic
differences created by primary active transport
• At many areas in body, transport of some other
substances such as glucose, amino acid, chloride,
iodine is coupled with active transport of sodium
• It may occur as:
 Co-transport
 Counter transport

CO-TRANSPORT
• Examples :
Sodium- Glucose co-transport in intestine and
renal tubule
Sodium-Glucose-Amino acid cotransport
Sodium-Potassium-Chloride cotransport in renal
tubule

CO-TRANSPORT

COUNTER TRANSPORT
• Examples:
Sodium-Calcium counter transport in all cell membranes
Sodium-Hydrogen counter transport seen in Proximal
tubule in kidney
Anion exchangers: Chloride bicarbonate exchanger

VESICULAR TRANSPORT
• It involves the transport of macromolecules which can
neither pass through the cell membrane by diffusion nor by
active transport mechanisms
• In vesicular transport, formation and transport of vesicles are
facilitated by
 Clathrin
 Coating proteins
 Dynamin
 Docking proteins

Eg: Neurotransmitters, Hormones, Waste products of
metabolism
• Vesicular transport is of three types
Endocytosis
Exocytosis
Transcytosis

ENDOCYTOSIS
• It is the process in which substance to be transported
into the cell by in-folding of the cell membrane
around the substance and internalizing it in the form
of endocytic vesicle.
• The vesicle may contain fluid and dissolved solutes or
particulate material

• This includes:
 Pinocytosis(cell drinking)
 Phagocytosis(cell eating)
 Receptor mediated endocytosis
Constitutive endocytosis (Non clathrin/non caveolae)
Clathrin mediated endocytosis
Caveolae mediated endocytosis

• Pinocytosis – refers to the process of engulfing liquid
substances by the enfolding of the cell membrane
Eg: Reabsorption by renal tubular epithelial cells

• Phagocytosis – is the process of engulfing solid
particles consisting of 3 steps – attachment,
engulfment and killing
Eg: Bacteria, dead tissue and foreign particles

• Receptor mediated endocytosis – the substance to be
transported binds with a special receptor protein
present on the cell surface and the complex is
engulfed
Eg: Transport of iron, cholesterol into the cells

• Endocytosis takes place by 2 mechanisms:
1. Constitutive endocytosis
The substance first makes contact with the
cell membrane, the cell membrane invaginates to form
endocytic vesicle and is pinched off
2. Clathrin mediated endocytosis
It occurs at the specific sites(coated pits)
on the cell membrane where clathrin accumulates
Eg: Uptake of nerve growth factor , low density
lipoprotein

• In Caveolar mediated endocytosis, caveolae bud off
from the plasma membrane and fuse back with the
plasma membrane

EXOCYTOSIS
• It is reverse of endocytosis and by this process the
substances are expelled from the cell without passing
through cell membrane.
• The substances which are to be extruded are collected in the
form of vesicles which move towards the cell membrane,
fuses with cell membrane.

• The area of fusion breaks down releasing the contents to
the exterior
• The process of exocytosis requires Ca2+ and energy along
with docking proteins.
• Substances like digestive enzymes, hormones,
neurotransmitters, mucus are secreted out of the cell

• Exocytosis occurs by 2 pathways:
1. Non constitutive or regulated pathway
Proteins secreted initially enters the
secretory granules where processing occur before
exocytosis
2. Constitutive pathway
Prompt transport of proteins to the cell
membrane in vesicle with little or no processing

TRANSCYTOSIS
• Vesicular transport within the cell is called transcytosis
or cytopempsis
• Vesicles are formed within the cell and transported in
the cytoplasm
• It involves 3 steps – vesicle formation, vesicle
transportation, docking in the cell

TRANSPORT ACROSS EPITHELIA
• There are two mechanisms
a. Transcellular transport or transport through the cell
Substance enters the cell from one side and exit through
other side
Eg: Reabsorption of sodium and glucose in kidney tubule
and in intestine
b. Paracellular transport
Transport through the tight junctions
Eg: Movement of sodium chloride in epithelia of small
intestine, gall bladder, proximal renal tubule

TRANSPORT ACROSS THE CAPILLARY WALL
• Capillary wall acts like impermeable membrane to colloids &
exert an osmotic pressure.
• Filtration:
Fluid is forced through a membrane or barrier because of a
difference in pressure on the two sides.
Eg: Ultrafiltration through glomerular capillary endothelium
and Bowman’s capsule epithelium

APPLIED PHYSIOLOGY
• Channelopathies:
-Single ion channel mutations resulting in various
diseases
-Affects both excitable & non excitable cells

Example for excitable cells
• Periodic paralysis due to defective one subunit of K+ channel
• Long QT syndrome due to defect in both Na+ & K+ channel
subunit
• Myasthenia occurs due to defective nicotinic acetylcholine
receptor
• Malignant hyperthermia due to defect in ryanodine receptor
of Ca2+ channel

Examples for non excitable cells:
• Cystic fibrosis due to defect in Chloride channel
• Bartter’s syndrome due to defect in K⁺ channel subunit

Plasma osmolality & diseases
• The total plasma osmolality may increase in patients having
severe dehydration
• In diabetes, Increased plasma glucose concentration
Increased Plasma osmolality
Shrinkage of cells mainly brain cells
Hyperosmolar coma
• In renal disease, raised plasma levels of urea causes
hyperosmolality

REFERENCES
• William F. Ganong - Review of Medical Physiology - Twenty
sixth edition
• Guyton & Hall - Textbook of Medical Physiology -Thirteenth
edition
• G K Pal – Comprehensive textbook of Medical Physiology –
First edition
• Indu Khurana – Textbook of Medical Physiology –Third
edition