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Transcript of General Physio
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GENERAL PHYSIOLOGY
~ CELL: THE BASIC STRUCTURAL AND FUNCTIONAL
UNIT OF THE BODY
The basic living unit of the body is the cell. Each
organ is an aggregate of many different cells held
together by intercellular supporting structures. Each type
of cell is specially adapted to perform one or a few
particular functions.
- Extracellular fluid: The internal environment
About 60 % of the adult human body is fluid. Of the
42 L fluid in the body, about 2/3rd (that is, 28 L) is
inside the cells and is called intracellular fluid.
The remaining 1/3rd (that is, 14 L) is in the spaces
outside the cells and is called extracellular fluid.
In the extracellular fluid are the ions and nutrients
needed by the cells to maintain cell life. Thus, all
cells live in essentially the same environment, that
is, the extracellular fluid. For this reason, the
extracellular fluid (ECF) is called the INTERNAL
ENVIRONMENT of the body, or the milieu int`erieur, a
term coined by the great 19th century French
physiologist Claude Bernard. Cells are capable of
living, growing, and performing their functions as
long as the proper concentrations of oxygen,
glucose, different ions, amino acids, fatty
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substances, and other constituents are available in
this environment.
The composition of the ECF is different from that of the
intracellular fluid (ICF). The ICF has potassium (K+),magnesium (Mg++), and phosphate ions in large
amounts, and sodium (Na+) and chloride (Cl-) ions are in
low concentrations. The ECF contains large amounts of
Na+, Cl-, bicarbonate (HCO3-), and low concentration of
potassium.
Intracellular fluid (ICF) Extracellular fluid (ECF)- Rich in potassium,
magnesium, andphosphate
- Low sodium andchloride
- Rich in sodium,chloride, andbicarbonate
- Low potassium
~ Homeostasis: constancy of the internal environment
(short note)
{When a human being is working in a relatively
constant environment, he/she will generally produce an
optimum output. Similarly, the environment surrounding
the cells also has to be kept constant.} The term
homeostasis is used to denote maintenance of constant
(or near-constant) conditions in the internal environment.
All of the organs and tissues of the body perform
functions that help to maintain these constant
conditions~
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(A)Transport of the extracellular fluid-The
circulatory system:
Nutrients, oxygen, and other substances are
circulated throughout the body by thecirculatory system. There is continual exchange
of material between plasma and the interstitial
fluid. Due to this, the environment surrounding
all cells is homogenous; and if there is a change
in the environment of cells in any part, it can be
normalized by either addition or removal of
material from the environment by the circulatorysystem.
(B)Origin of nutrients in the extracellular fluid:
(i) Respiratory system:
The circulating blood, when it passes
through the lungs, picks up oxygen in the
alveoli. This oxygen is needed by the cellsto produce energy.
(ii) Gastrointestinal tract:
The circulating blood passes through the
walls of the G.I.tract; here the nutrients
(carbohydrates, fatty acids, and amino
acids) are absorbed into the blood. Thenutrients are required to produce energy by
all cells of the body.
(iii) Musculoskeletal system:
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Musculoskeletal system moves the body so
as to obtain food for nutrition.
(C)Removal of metabolic end products:
(i) Removal of CO2 by the lungs:
CO2 is the end product of cell metabolism. It
diffuses from cells into blood, then blood
releases into the alveoli (lungs) from where
it is expelled out of the body by expiration.
(ii) Role of kidneys:
Apart from CO2, the other end products of
cellular metabolism (such as urea, uric acid)
are excreted by the kidneys, in the urine.
(D)Regulation of all the body systems:
Functioning of all the body systems is controlled
by two organ systems: the nervous system andthe endocrine system
The nervous system is a faster regulating
system; the endocrine system is (generally) a
slower regulating system. The nervous system is
composed of nerves that carry the appropriate
signals to all the organ systems. Endocrine
system is composed of ductless glands thatsecrete hormones that act at distant target
organs.
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The negative feedback mechanism : (short
note)
Most of the control mechanisms of the body operate
on the basis of negative feedback mechanism. Itcan be explained as follows:
If some factor in the body becomes excessive or
deficient, a control mechanism initiates negative
feedback, which consists of a series of changes that
return the factor toward a certain mean value, thus
maintaining homeostasis.
If there is a change in any factor of the cellular
environment, the control mechanisms come into
action to negate or cancel the change, so that the
factor returns toward its original level.
Therefore, negative feedback is the integral part of
maintaining the homeostasis.
- Examples of negative feedback mechanism:
(i) Regulation of arterial blood pressure- {the
baroreceptor system}
When the arterial B.P. is increased, the change is
sensed or detected by the receptors in the wallsof carotid artery and aorta. These receptors,
called the baroreceptors, increase their impulse
discharge frequency to vasomotor center in the
brain stem. Vasomotor center then sends the
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signals via autonomic nerves to the blood
vessels. The resultant vasodilatation decreases
the B.P. and brings it near normal/original value.
(ii) Regulation of the body temperature-
If the body temperature increases, temperature
of the blood is increased. When the blood
circulates through the brain, neurons in a
particular area of hypothalamus sense this
increased temperature. It then sends signals via
the autonomic neurons, to increase blood flow in
the skin and also to cause sweating. Heat will be
lost from the skin and the body temperature will
return to the original value.
~ Gain of a control mechanism-
The degree of effectiveness of a control system is
determined by the gain of the negative feedback.
Gain = Correction applied
residual error
HIGHER THE GAIN, MORE EFFEICIENT IS THE SYSTEM.
Example: Let us consider a baseline blood pressure of
100 mm Hg. After physical exercises it increases upto
150 mm Hg. Now the baroreceptor system will instantly
comes into action and returns the BP toward the original
value. It comes back to a level of 110 mm Hg. It means
correction applied in this instance is 40 mm Hg (from 150
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to 110), and the residual error is 10 mm Hg (because,
original BP was 100 and the correction came upto 110).
Thus, gain would be 40/10 = +4.
Higher gain would mean, correction applied is greaterand the error remaining is smaller.
Among the physiological control systems, temperature
regulating system has a very high gain (- 33); it is one of
the most efficient control systems of the body.
~ Positive feedback system:
In some instances, some control systems act in a
positive feedback manner.
Positive feedback is also known as vicious circle, as in
most instances it may be detrimental to body functioning
and even may lead to death.
If there is a change in the environment by a stimulus, this
initiating stimulus repeats itself cyclically. The events
occur in a cyclic fashion, to cause more and more of the
same. Thus, instead of the change getting nullified or
negated, it becomes consolidated or stronger and the
parameter moves away from its original/normal level.
Example: If there is sudden loss of blood (say, upto 2liters blood loss) from the body, the arterial blood
pressure falls. Blood flow to the heart muscle decreases,
there is weakening of the heart muscle. Pumping
effectiveness of heart is decreased, this further reduces
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blood pressure, blood flow into the heart muscle is
decreased further. There is further weakening of the
heart muscle and further decrease of blood pressure. The
cycle repeats itself again and again, and may eventuallylead to death.
Note that: If the positive feedback is of mild degree, it
can be overcome by the negative feedback control
mechanisms of the body, and a vicious circle fails to
develop. For instance, if there is blood loss of up to 1 liter
instead of 2 liters, the normal negative feedback
mechanisms for controlling cardiac output and arterialblood pressure would overbalance the positive feedback
and the person would recover.
~ Instances when positive feedback can be useful:
(1) Childbirth/parturition (delivery of baby):
At term (i.e. 9 months completed of a pregnancy),
uterine contractions cause the babys head to beginto push on the cervix. The signals will be set up, to
cause release of oxytocin from posterior pituitary.
Oxytocin causes uterine contractions that further
press down the babys head. Cervix dilates further,
again the signals are set up to cause oxytocin to
further cause uterine contractions. This cycle
continues till the baby is delivered.
(2) Platelet plug formation / clot formation :
When a blood vessel ruptured and bleeding begins,
bleeding is stopped by a platelet plug that is formed
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in the injured part of vessel. A few platelets come in
the ruptured area, they are activated, adhere to the
injured vessel area and then release some chemicals.
This causes more platelets to come in that region,get activated, stick to the previous platelets, and
release more chemicals. This causes even more
platelets to be activated. Eventually, a platelet plug
is formed that stops the bleeding.
Or
In the injured area of the blood vessel, a clotting
factor is activated; it acts enzymatically to activate
next clotting factor. This factor then activates the
next clotting factor, and so on. Eventually a blood
clot is formed over the platelet plug.
(3) Depolarization upto threshold in an action potential
(AP):
When a nerve is stimulated, a few sodium channelsopen initially, to cause sodium influx into the nerve.
This causes membrane potential to become less
negative, which in turn, opens few more sodium
channels. Some more sodium enters the nerve;
membrane potential becomes even less negative.
This causes even more sodium channels to open.
Membrane potential eventually reaches a certainthreshold value to fire action potential.
{There are a few more examples of positive feedback,
such as, release ovulation release of ovum due to
midcycle LH surge; etc}
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Positive feedback mechanisms may be operating as a
part of larger negative feedback homeostasis. For
instance, childbirth is due to positive feedback
mechanism. However, the female has some physiologicalparameters before pregnancy, which got altered due to
pregnancy (e.g. blood volume, blood pressure). After
delivery, these parameters return to original levels; this is
negative feedback.
---------------------------------------------------------------------------------
--------------
TRANSPORT OF SUBSTANCES THROUGH /
ACROSS THE CELLMEMBRANE:
If a cell is to live and grow and reproduce, it must
obtain nutrients and other substances from the
surrounding fluids. Also, for various other reasons,
substances have to either enter a cell or have to be
extruded out of the cells. The transport mechanismsby which the substances enter or leave the cells are
as follows:
(1) Exocytosis
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(2) Endocytosis
(3) Passive transport, such as diffusion
(4) Active transport primary & secondaryAlso, there is movement of water through the cell
membrane by osmosis.
(1) Osmosis:
When there are two solutions of unequal
concentrations separated by a semi permeable
membrane, the solvent moves through themembrane from low solute concentration to high
solute concentration. For the body fluids, water is the
solvent mostly. Hence, we will consider movement of
water as osmosis.
Water moves through cell membranes, either
into or out of cells, depending on the solute
concentrations. Let us consider a red blood cell.Inside the red cell is NaCl of 0.9 % concentration in
water. The plasma that surrounds the RBCs also has
the NaCl 0.9% in plasma water. There will be no net
movement of water into or out of the cells.
If the red cells are placed in distilled water, water will
move into the red cells and the cells will swell. It can
be said that NaCl exerts a force or osmotic
pressure thatpulls watertowards it by osmosis.
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If the red cells are placed in a solution of 0.5% NaCl,
water will move into the cells. That is, from low
solute concentration to high solute concentration.
If the red cells are placed in a solution having morethan 0.9 % concentration of NaCl, water will move
out of the red cells and they will shrink.
A solution is said to be hypotonic if it has less
concentration of solutes compared to the solution
inside of cells. If the cells are placed in such
hypotonic solutions (less solutes, more water), cells
will swell because water will move into them.
If cells are placed in hypertonic solutions (more
solutes, less water), they shrink because water
moves out of the cells.
A solution is said to be isotonic if its solute
concentration is the same as that inside of cells. The
cell size does not change if the cell is placed inisotonic solution, as there is no net movement of
water into or out of the cell.
- Osmotic pressure: (or oncotic pressure)-
The osmotic pressure is exerted by particles in a
solution; it is determined by the number of
particles per unit volume of fluid. It is a force thatwill pull water (toward the particles) by osmosis.
- Osmolality:
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To express the concentration of a solution in terms of
numbers of particles, the unit osmole is used. One
osmole is 1 gram molecular weight of undissociated
solute. Thus, 180 grams of glucose, which is 1 grammolecular weight of glucose, is equal to 1 osmole of
glucose.
A solution that has 1 osmole of solute dissolved in
each Kg of water is said to have an osmolality of 1
osm/kg.
{The normal osmolality of plasma, and other
body fluids, is about 300 milli osmoles/Kg of
water; or simply, 300 mosm.}
In simple terms, it is concentration of solute
particles relative to water. If in a particular
solution (say, plasma), amount of water is increased,
solute concentration will become relatively less. This
solution has now become hypo-osmolar or hypotonic.On the other hand, if the water is removed from a
particular solution, solute concentration will become
relatively more. This will be called a hyper-osmolar or
hypertonic solution.
~ Endocytosis: (macromolecules taken into the cell)
(short note)
{It may be considered to be a transport mechanism
across the cell membrane as the substances move from
one side of membrane to the other. The other processes,
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such as diffusion and active transport, are transport
through the membrane.}
- Very large particles or macromolecules enter the
cell by a specialized function of the cell membranecalled endocytosis.
- There are two types of endocytosis: (i)
phagocytosis (cell eating) is the process by
which bacteria, dead tissue, or other bits of material
visible under the microscope are engulfed by WBCs
and macrophages. (ii) pinocytosis (cell
drinking) is the same process, but the substances
ingested are in solution and not visible under the
microscope.
- The molecules that are ingested by the cell, first
attach to the specialized receptors on the surface of
the membrane. These receptors are specific for the
particle that is to be ingested. The receptors aregenerally concentrated in small pits on the outer
surface of the cell membrane. These are called
coated pits.
- Below these pits, on the inside of the cell membrane
there is a fibrillar protein called clathrin.
- Once the particle combines with the receptors, the
clathrin causes the pit to invaginate inward. It
becomes deeper and deeper. The edges of the
membrane come closer. And finally, a collar is
formed around the neck-like portion of the
membrane. The part of the membrane now pinches
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off into the cell. This breaking off creates a vesicle
with the particle inside the vesicle. This is called
phagocytic vesicle.
- Thus, the particle has gone into the cell, inside avesicle. Now this vesicle will fuse with lysosomes
within the cell; lysosomes have enzymes that can kill
/ degrade the particle.
- Apart from bacteria ingested in this way, other
examples of clathrin-mediated endocytosis include:
LDL uptake by cells.
{Now, before we discuss the other transport mechanisms
through the cell membrane, let us understand the
structure of the cell membrane.
- All cells have a cell membrane made up of a lipid
bilayer. There are two rows of lipid moleculesthat constitute the membrane.
- Interspersed in the lipid bilayer are the protein
molecules. These protein molecules are basically of
two types: (i) integral proteins, and (ii) peripheral
proteins.
- The peripheral proteins are attached on the outside
of the membrane. They may act as receptors.
- The integral proteins span the entire membrane;
they protrude all the way through the membrane.
These integral proteins act as transport proteins.
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Different transport proteins cause movement of
particles through the membrane in different ways.
a. Channel proteins: they have watery spaces which
allow water and water soluble substances to movethrough.
b. Carrier proteins: molecules and ions can bind to
these proteins; this binding causes conformational
change in the carrier and the bound molecule/ion
crosses the membrane.
~ Diffusion v/s active transport:
Transport through the cell membrane may be: (i)
passive transport diffusion; and (ii) active transport.
Diffusion is said to be a passive transport because it
does not require energy / ATP. Active transport is said to
be active because it requires metabolic energy / ATP.
~ Diffusion:
Molecules and ions in liquids and gases move
continuously among one another. This continual
movement of molecules and ions is due to their kinetic
energy. This random movement is called diffusion.
Diffusion never stops, except at absolute zero
temperature.
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Diffusion through a cell membrane would occur in both
directions, that is, from inside to outside and vice versa.
However, when there are unequal concentrations of a
substance on inside and outside, NET DIFFUSION wouldoccur from higher concentration of the substance
tothe lower concentration.
Hence, net diffusion is said to be a downhill
process; it occurs fromhigh to low concentration of
a substance. That is, ALONG THE CONCENTRATION
GRADIENT.
~ Diffusion through the cell membrane:
It is of two types: (i) simple diffusion, and (ii)
facilitated diffusion.
Simple diffusion occurs by virtue of kinetic energy of the
particles.
Facilitated diffusion is a carrier-mediated transport. Aspecific carrier causes the substance to move to other
side of the membrane.
Simple diffusion occurs in two ways-
(i) Through lipid bilayer : The lipid soluble
substances diffuse through the lipid bilayer of
the membrane. E.g. diffusion of oxygen andcarbon dioxide through cell membranes
(ii) Through protein channels : The water soluble
substances are not soluble in lipids. They diffuse
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through the protein channels in the membrane.
E.g. diffusion of Na+, K+, and other ions.
- Factors that affect the net rate of diffusion:
I. Lipid solubility: The lipid soluble substances
dissolve in the lipid molecules of the bilayer and
then diffuse. The rate of this diffusion would
depend on the lipid solubility of the substance.
Greater the lipid solubility, more will be the rate
of diffusion. {directly proportional}
II. Number of protein channels available fordiffusion:
For the water soluble substances, more the
number of channels available for diffusion,
greater will be the rate of diffusion. {directly
proportional}
III. Temperature: More the temperature, more isthe kinetic energy. Hence, diffusion rate is
directly proportional to the temperature.
{directly proportional}
IV. Surface area: if there is more surface area
available for diffusion, more ions will diffuse per
unit time, and the diffusion rate will be higher.
{directly proportional}
V. Size/molecular weight of the diffusing
substance: diffusion rate is inversely
proportional to the size or molecular weight of
the diffusing substance. Larger the size, lesser
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will be the rate of diffusion. {inversely
proportional}
VI. Thickness of the membrane/diffusion
distance: if the membrane has greaterthickness, the molecules will have to travel more
distance to cross the membrane; rate of
diffusion would be less. {inversely proportional}
VII. Concentration gradient: diffusion occurs from
high to low concentration. Its rate is directly
proportional to the concentration gradient.
Larger the gradient, greater will be the rate of
diffusion. {If there are 50 ions on one side of the
membrane and 5 on the other side, there will be
diffusion of ions. If there are 150 ions on one
side and 5 on the other side, diffusion rate will
be higher because of larger gradient}
VIII. Pressure gradient: gases exert pressures. And,gases diffuse through the membrane from high
pressure to lower pressure. Larger this gradient,
higher will be the rate of diffusion.
IX. Electrical/electrochemical gradient: for
example, Na+ ions are positively charged. They
will diffuse through the membrane from the area
of higher number of positive charges to the areahaving lower number of positive charges. And,
larger this gradient, more will be the rate of
diffusion.
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Facilitated diffusion-
It is a carrier-mediated diffusion. That is, a
specific carrier mediates or facilitates the diffusion of
a particular substance from one side of membrane tothe other side.
Example: glucose entry in almost all cells of the
body occurs by facilitated diffusion. There are carrier
proteins called GLUTS (glucose transporters) that
facilitate glucose entry into the cells. {There are only
two places where glucose transport does not occur
by facilitated diffusion: G.I.T. and kidney.}
Mechanism of facilitated diffusion-
The particle binds to its specific carrier
in the membrane
Conformational change in the carrier protein
the particle is delivered to the other side of the
membrane
Note that: because the particle binds to the carrier only if
it is highly concentrated, the particle can only move from
its high to low concentration with the help of carrier.
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Characteristics of facilitated diffusion:
(i)
Specificity:Only a specific molecule or ion can be transported
through a particular membrane which has the
specific carrier protein. {Compare this with simple
diffusion in which, any lipid soluble substance can
cross the membrane through the lipid bilayer.}
(ii) Saturation:
The rate of diffusion increases as the concentration
gradient increases. This is true of simple diffusion.
However, facilitated diffusion occurs due to a
carrier protein; this carrier has certain number of
binding sites. In this case, as the concentration
gradient increases, more and more particles will
bind with the carrier and the rate of diffusion willalso increase. At some points, all the binding sites
of the carrier will get occupied with these particles.
Now the rate of diffusion cannot increase any
further with increasing particle concentration. This
is called saturation of the carrier, or, Michaelis-
Menten Kinetics. The rate of transport is called
Vmax
when it reaches maximum.
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simple
diffusion
rate
of Vmax
diffusion facilitated diffusion
Concentration gradient
(iii)Competitive inhibition:
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Structurally related compounds compete for the
same binding sites on the carrier molecule. If a
substance [A] is diffusing by binding with carrier,
another structurally similar substance [B] cancompete for the binding sites. This will reduce the
rate or may even inhibit the diffusion of [A]. This is
called competitive inhibition.
Thus, facilitated diffusion can be distinguished from
simple diffusion by certain characteristics:
(1) Facilitated diffusion allows for a very high rate
of solute transport, as compared to that of
simple diffusion.
(2) Facilitated diffusion is a saturable process; it may get
limited beyond a certain saturation point. Simple
diffusion rate will go on increasing without limitation
if the concentration of the solute increases.
(3) Facilitated diffusion is a highly specific process.Simple diffusion is not so specific.
(4) Facilitated diffusion can be blocked by
competitive inhibition. Simple diffusion is not
inhibited by such mechanism.
{Non-ionic diffusion: diffusion trapping- (weak acids
and weak bases)
This type of diffusion is seen in the transport of weak
acids and weak bases. The neutral form of a weak acid or
a weak base can diffuse across a cell membrane, but the
charged form cannot diffuse. This is called non-ionic
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diffusion or diffusion trapping. For example, ammonia is a
weak base that is produced by renal tubular cells. It
diffuses easily into the lumen of the tubule. If there are
acids in the tubules, ammonia gains a proton to formammonium ion. Ammonia was lipid-soluble, ammonium is
not. So this ammonium cannot diffuse back into the cell.
It is trapped in the lumen and excreted in the urine. Thus,
acids can be removed from the body by diffusion
trapping.}
~ Active transport: {an uphill process}
- Active transport process is said to be an uphill
process, because in this process, substances move
from their low concentrations to their high
concentrations. That is, AGAINST THE
CONCENTRATIONGRADIENT.
- This is made possible by a specific carrier proteinin the cell membrane.
- Active transport requires metabolic energy ATP.
Hence, the term active.
There are two general types of the active transport
process; depending on whether the movement of solute
is linked directly or indirectly to energy-yielding reactions.
1. Primary active transport: when the movement of
solute is directly coupled with ATP breakdown.
E.g. Na+ - K+ ATPase (pump). It utilizes a pump or
ATPase in the membrane, to cause ATP breakdown
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directly and energize the transport of ions. (Na+-K+
pump described later.)
2. Secondary active transport:
It is a carrier-mediated active transport in which, the
energy stored in the Na+ concentration gradient is
utilized for the transport of other molecules or ions.
Hence, it uses energyindirectly.
Energy / ATP is required to establish the Na+
concentration gradient so that Na+ concentration is
higher in the ECF as compared to Na+
in the ICF.Energy in this concentration gradient is then utilized
for the movement of other substances. Thus, it is
indirect energy utilization by other substances.
Examples: transport of glucose against its
concentration gradient in G.I. cells and renal tubules;
transport of amino acids, etc.
Secondary active transport is of two types: (i) co-
transport or symport, and (ii) counter-transport or
antiport.
(i) Co-transport or symport:
When sodium is transported out of cells by
primary active transport, a large concentration
gradient of sodium develops very high sodium
outside the cell and very low inside. This
gradient represents a storehouse of energy
because sodium now attempts to diffuse
inward. This diffusion energy of sodium pulls
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other substance, such as glucose, along with it
into the cell. Since glucose moves in the same
direction as that of the sodium diffusion pull, this
is called co-transport or symport (sym =together).
Example of co-transport: transport of glucose
and amino acids into the epithelial cells of
G.I.tract and the kidneytubules. Glucose co-
transport with sodium is carried out by carrier
proteins called SGLTs {sodium glucose
transporters}.
{Mechanism: Na+ binds to the carrier SGLT on
the outside of the cell where the Na+
concentration is high. After Na+ binds to the
carrier, the carriers affinity for glucose
increases, now glucose binds to it. Carrier
undergoes conformational change. Glucose and
sodium now face the intracellular aspect.
Because sodium concentration inside is low,
sodium dissociates from the carrier. This reduces
the affinity of glucose to the carrier, and glucose
is delivered into the cell.}
(ii) Counter transport or antiport: {antiporters
are also called exchangers}Example: Na+ - Ca++ exchange.
Calcium is transported out of the cell against its
concentration gradient, with the help of a carrier
protein called Na+ - Ca++ exchanger. Three
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sodium ions are transported into the cell for
each calcium ion transported out of the cell.
~ Na+ - K+ ATPase or Na+ - K+ pump:
- Sodium-potassium pump is an example of primary
active transport. Na+ and K+ ions move against
their concentration gradients due to this pump.
- This pump is a carrier protein with ATPase activity. It
breaks down ATP to energize the movement of Na+
and K+ ions against their concentration gradients.
Sodium concentration is more on the outside of cells
compared to inside. The pump causes sodium to
move from inside to outside. Potassium
concentration is more on the inside of cells compared
to outside. The pump causes potassium to move
from outside to inside.
- This ATPase/pump is present in membranes of
almost all cellsthroughout the body. It has a very
important function to perform in the nerves and
muscles.
Mechanism of action:
This is a carrier protein which has two subunits:and . The subunit is a supporting subunit;
subunit is responsible for the transport mechanism.
The pump has 3 binding sites facing the intracellular
side of the membrane. 3 Na+ ions from the
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intracellular fluid bind to these sites. These ions are
transported to outside of the cell.
It has 2 binding sites facing the extracellular side of
the membrane. 2 K+ ions from the extracellular fluidbind to these sites and are transported into the cell.
It has a site for ATP binding. ATP hydrolysis will
provide the energy necessary for the transport.
~ Functional significance of the Na+ - K+
ATPase/pump:
(1) The pump regulates the cell volume. It causes
sodium to extrude out of the cells. This decreases
sodium concentration inside the cells. Sodium is an
osmotically active ion. If it remains high
intracellularly, it will pull water into the cells by
osmosis; cells will swell and may even burst. Sodium
prevents this osmotic lysis.
(2) The pump contributes in the BMR/basal energy
expenditure: The pump is continually active all the
time, in all cells, even under resting conditions. Since
this is an ATPase, it causes ATP breakdown
continually. Of the total basal energy expenditure of
the body, about 40 % is spent by this pump alone. In
nerves, this share of energy expenditure is upto 70%.
(3) The pump is electrogenic. 3 sodium (positive) ions
leave the cell but only 2 potassium (positive) ions
come in. Thus, with the activity of this pump, there is
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a deficit of positive charges on the inside of the
membrane. It means excess of negative charges
inside. This produces a charge of 4 mV on the inner
side of the membrane. The membranes have anegative charge of 70 mV, out of which, - 4 mV is
contributed directly by this pump.
(4) Maintenance of RMP: The pump creates unequal
concentrations of sodium and potassium ions, due to
their continual movement. (Sodium more on the
outside compared to inside; potassium more on the
inside compared to outside.) It causes these ions todiffuse, which creates a charge on the membrane.
{Note that: diffusion occurs down the
concentration gradient (high-to-low). Hence, it will
reduce the concentration gradient. Active
transport occurs against the concentration (low-to-high), and it will further increase this gradient.}
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