General Physio

8/8/2019 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.

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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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General Physio