INTRODUCTION TO PHYSIOLOGY

• Physiology: Is the study of biological

function of how the body works, from
molecular mechanisms within cells to the
actions of tissues, organs, and systems,
and how the organism as a whole
accomplishes particular tasks essential
for life.
 The goal of physiology

• To explain the physical and chemical factors

that are responsible for the origin,
development, and progression of life
• To understand and predict the body’s
responses to stimuli and to understand how
the body maintains conditions within a
narrow range of values in a constantly
changing environment.
 The goal of physiology cont’
• Medical physiology is concerned with
how a state of health and wellness is
maintained in a person and, therefore, it
takes a global view of how the body
systems function and how they are
controlled.
 HOMEOSTASIS

• It is the maintenance by the highly

coordinated, regulated actions of the
body systems of relatively stable
chemical and physical condition in the
internal fluid environment that bathes
the body’s cells.
 HOMEOSTASIS
• Homeostasis is not a rigid, fixed state but a
dynamic steady state in which the changes
that do occur are minimized by
compensatory physiological responses.
• The term dynamic refers to the fact that
each homeostatically regulated factor is
marked by continuous change, whereas
steady state implies that these changes do
not deviate far from a constant, or steady,
level.
 HOMEOSTASIS CONT’

• Homeostasis is a dynamic steady state of the

constituents in the internal fluid
environment that surrounds and exchanges
materials with the cells.
• As long as conditions are maintained within
the normal physiological range within the
internal environment, the cells of the body
continue to live and function properly.
 A feedback system

• A feedback system or feedback loop is a cycle of

events in which the status of a body condition is
monitored, evaluated, changed, remonitored, and
reevaluated, and so on.
• Each monitored variable, such as body temperature,
blood pressure, or blood glucose level, is termed a
controlled condition.
• Any disruption that changes a controlled condition is
called a stimulus.
• A feedback system includes three basic components:
a receptor, a control center, and an effector.
 A receptor

• A receptor is a body structure that monitors

changes in a controlled condition and sends input
to a control center.
• This pathway is called an afferent pathway, since
the information flows toward the control center.
• Typically, the input is in the form of nerve impulses
or chemical signals.
• For example, certain nerve endings in the skin
sense temperature and can detect changes, such
as a dramatic drop in temperature.
 A control center
• A control center in the body, e.g, the brain, sets the
range of values within which a controlled condition
should be maintained (set point), evaluates the input it
receives from receptors, and generates output
commands when they are needed.
• Output from the control center typically occurs as
nerve impulses, or hormones or other chemical signals.
• This pathway is called an efferent pathway, since the
information flows away from the control center.
• In our skin temperature example, the brain acts as the
control center, receiving nerve impulses from the skin
receptors and generating nerve impulses as output.
 An effector

• An effector is a body structure that receives

output from the control center and produces
a response or effect that changes the
controlled condition. Nearly every organ or
tissue in the body can behave as an effector.
When your body temperature drops sharply,
your brain (control center) sends nerve
impulses.
 A homeostatic control system

• is a functionally interconnected network of body

components that operate to maintain a given factor in
the internal environment relatively constant around an
optimal level. To maintain homeostasis, the control
system must be able to:
1. detect deviations from normal in the internal
environmental factor that needs to be held within
narrow limits
2. integrate this information with any other relevant
information
3. Make appropriate adjustments in the activity of the
body parts responsible for restoring this factor to its
desired value.
 FACTORS HOMEOSTATICALLY REGULATED
• Concentration of nutrients
• Concentration of O2 and CO2
• Concentration of waste products
• Changes in the pH
• Concentration of water, salt, and other
electrolytes
• Blood Volume and Pressure
• Temperature
 Components of a homeostatic system
• Regulated variable is a variable to be maintained
within a narrow normal range
• Set point is the desired value for the regulated
variable
• Sensors assess current status of the regulated variable
• Feedback controller compares current conditions with
the set point
• Effector brings current status of regulated variable into
line with the set point
 Characteristics of homeostasis
• Effectors may have opposing actions
• Negative feedback is the process that prevents change
• Positive feedback is the process that perpetuates
change
• Feedforward control is outside stimuli that alter the
normal feedback
• Adaptive control is a form of delayed negative
feedback control that favors survival in specific
environments.
 Important generalizations about homeostatic control systems

• Stability of an internal environmental variable is achieved by balancing

inputs and outputs. It is not the absolute magnitudes of the inputs and
outputs that matter, but the balance between them
• In negative feedback, a change in the variable being regulated brings about
responses that tend to move the variable in the direction opposite the
original change-that is, back toward the initial value (set point)
• Homeostatic control systems cannot maintain complete constancy of any
given feature of the internal environment. Therefore any regulated variable
will have a more or less narrow range of normal values depending on the
external environmental conditions.
• The set point of some variables regulated by homeostatic control systems
can be reset-that is physiologically raised or lowered.
• It is not always possible for homeostatic control systems to maintain every
variable within a narrow normal range in response to an environmental
challenge. There is a hierarchy of importance, so that certain variables may
be altered markedly to maintain others within their normal range
 Negative Feedback Nature of Most Control Systems

• Most control systems of the body act by negative

feedback, which can best be explained by reviewing some
of the homeostatic control systems mentioned previously.
In the regulation of [CO2], a high concentration of carbon
dioxide in the ECF increases pulmonary ventilation.
• This, in turn, decreases the ECF CO2 because the lungs
expire greater amounts of CO2 from the body.
• In other words, the high concentration of CO2 initiates
events that decrease the concentration toward normal,
which is negative to the initiating stimulus.
• Conversely, if the CO2 concentration falls too low, this
causes feedback to increase the concentration. This
response is also negative to the initiating stimulus.
 A negative feedback

• A negative feedback control system contains the

following elements:
1. A set point value, which is at the center of the normal
range and is treated by the control system as the target
value.
2. Sensors that continuously monitor the controlled
variable.
3. A comparator, which interprets input from the sensors
to determine when deviations from the set point have
occurred. The comparator initiates a counter response.
4. Effectors are the mechanisms that restore the set
point to its normal level.
 Example

• A negative feedback system reverses a change in a

controlled condition. Consider the regulation of blood
pressure. Blood pressure (BP) is the force exerted by blood
as it presses against the walls of blood vessels.
1. If some internal or external stimulus causes blood
pressure (controlled variable) to rise, the following
sequence of events occurs.
2. Baroreceptors (the receptors), pressure-sensitive nerve
cells located in the walls of great blood vessels (carotid
sinus and aortic arch), detect the higher pressure.
3. The baroreceptors generate and send nerve impulses
(input) to the medulla oblongata of the brain (control
center), which interprets the impulses
 Example cont’

4. The control center compares the value of the variable against the set
point. The control center then responds by sending nerve impulses
(output) to the heart and blood vessels (the effectors).
5. Heart rate decreases and blood vessels dilate (widen), which cause BP
to decrease (response). This sequence of events quickly returns the
controlled condition—blood pressure—to normal and homeostasis is
restored. Notice that the activity of the effector causes BP to drop, a
result that negates the original stimulus (an increase in BP). This is
why it is called a negative feedback system.
6. If blood pressure increases slightly, receptors detect that change and
send the information to the control center in the brain. The control
center causes the heart rate to decrease, lowering blood pressure. If
blood pressure goes down slightly, the receptors inform the control
center, which elevates the heart rate, thereby producing an increase
in blood pressure. As a result, blood pressure constantly rises and falls
within a normal range of values.
 Positive feedback

• Positive-feedback mechanisms occur when a response

to the original stimulus results in the deviation from
the set point becoming even greater.
• The control center provides commands to an effector
which produces a physiological response that
reinforces the initial change in the controlled condition.
• The action of a positive feedback system continues
until it is interrupted by some mechanism (needs a cut-
off).
• Unlike a negative feedback system, a positive feedback
system tends to strengthen or reinforce a change in
one of the body’s controlled conditions.
 Positive feedback

• Positive feedback is inherently unstable, and requires

some mechanism to break the feedback loop and stop the
process, such as time-dependent inactivation of sodium
channels in the first example and the birth of the child in
the second.
• In positive feedback loop, the response reinforces the
stimulus rather than decreasing or removing it. In
positive feedback, the response sends the variable
being regulated even farther from its normal value
triggering a vicious cycle of ever-increasing response and
sending the system temporarily out of control. Because
positive feedback escalates the response, this type of
feedback requires some intervention or event outside the
loop to stop the response.
 Examples of positive feedback, 1

• Sex hormones normally inhibit gonadotropin

secretion by negative feedback.
• But one or two days before ovulation, high estrogen
levels actually increase the levels of luteinizing
hormone (LH) and follicle stimulating hormone
(FSH).
• The LH and FSH surge are essential for ovulation.
 Examples of positive feedback, 2

• During labor, uterine contractions push the fetus down

towards the cervix. Stretching of the cervix stimulates
uterine contraction by positive feedback.
• Uterine contractions push the fetus further down,
stretching the cervix still more, which in turn induces more
uterine contractions.
• Thus by positive feedback the uterine contractions keep
getting stronger till the baby is delivered.
• The cycle of stretching, hormone release, and ever-stronger
contractions is interrupted only by the birth of the baby.
• Then, stretching of the cervix ceases and oxytocin is no
longer released.
 Examples of positive feedback, 3

• Some blood coagulation reactions are

autocatalytic in nature.
• Once a small amount of thrombin is formed, it
acts on prothrombin to form still more
thrombin.
• Thus thrombin triggers the formation of still
more thrombin.
• Autocatalytic reactions are thus a form of
positive feedback.
 Examples of positive feedback, 4

• Under normal conditions, the heart pumps blood

under sufficient pressure to body cells to provide them
with oxygen and nutrients to maintain homeostasis.
• Upon severe blood loss, blood pressure drops and
body cells (including heart cells) receive less oxygen
and function less efficiently.
• If the blood loss continues, heart cells become weaker,
the pumping action of the heart decreases further, and
blood pressure continues to fall.
• This is an example of a positive feedback cycle that has
serious consequences and may even lead to death if
there is no medical intervention.
 Examples of positive feedback, 5

• During generation of nerve signals when the membrane of a

nerve fiber is stimulated, there is a slight leakage of sodium ions
through sodium channels in the nerve membrane to the fiber's
interior.
• The sodium ions entering the fiber then change the membrane
potential, which in turn causes more opening of channels, more
change of potential, still more opening of channels, and so forth.
• Thus, a slight leak becomes an explosion of sodium entering the
interior of the nerve fiber, which creates the nerve action
potential. This action potential in turn causes electrical current
to flow along both the outside and the inside of the fiber and
initiates additional action potentials.
• This process continues again and again until the nerve signal
goes all the way to the end of the fiber.
 Feedforward mechanisms
• Feedforward regulation anticipates changes in
regulated variables such as internal body
temperature or energy availability, improves the
speed of the body’s homeostatic responses and
minimizes fluctuations in the level of the variable
being regulated- that is, it reduces the amount of
deviation from the set point.
 E.g., salivation reflex
• The sight, smell, or even the thought of food is
enough to start our mouths watering in
expectation of the food to eat.
• This reflex extends even further, because the
same stimuli can start the secretion of HCl as
the stomach anticipates food on the way.
 Example

• when a meal is still in the digestive tract, a feedforward

mechanism increases secretion of a hormone (insulin)
that will promote the cellular uptake and storage of
ingested nutrients after they have been absorbed from
the digestive tract.
• This anticipatory response helps limit the rise in blood
nutrient concentration after nutrients have been
absorbed. In feedforward mechanism, the moment-to-
moment operation of the controller is “open loop”; that
is, the regulated variable itself is not sensed.
• Feedforward control mechanisms often sense a
disturbance and can, therefore, take corrective action
that anticipates change.
 Example

• Heart rate and breathing increase even before a person has begun
to exercise.
• Respiratory and cardiovascular adjustments closely match muscular
activity, so that arterial blood O2 and CO2 tensions are kept within
normal range.
• One explanation for this remarkable behavior is that exercise
simultaneously produces a centrally generated feedforward signal
to the active muscles and the respiratory and cardiovascular
systems; feedforward control, together with feedback information
generated as a consequence of increased movement and muscle
activity, adjusts the heart, blood vessels, and respiratory muscles.
• In addition, control system function can adapt over a period of
time. Past experience and learning can change the control system’s
output so that it behaves more efficiently or appropriately.
 Adaptive control

• Cell adaptation refers to the changes taking place in

a cell in response to environmental changes.
• Normal functioning of the cell is always threatened
by various factors such as stress, chemical agents,
diseases and environmental hazards.
• Yet, the cell survives and continues the function by
means of adaptation.
• Only during extreme conditions, the cell fails to
withstand the hazardous factors which results in
destruction and death of the cell.
 Cellular adaptation occurs by any of the
following mechanisms
• Atrophy
• Hypertrophy
• Hyperplasia
• Dysplasia
• Metaplasia.
 ATROPHY

• Atrophy means decrease in size of a cell.

Atrophy of more number of cells results in
decreased size or wasting of the concerned
tissue, organ or part of the body.
 HYPERTROPHY

• Hypertrophy is the increase in the size of a

cell. Hypertrophy of many cells results in
enlargement or overgrowth of an organ or a
part of the body. Hypertrophy is of three
types.
 HYPERPLASIA

• Hyperplasia is the increase in number of cells

due to increased cell division (mitosis). It is
also defied as abnormal or unusual
proliferation (multiplication) of cells due to
constant cell division. Hyperplasia results in
gross enlargement of the organ. Hyperplasia
involves constant cell division of the normal
cells only.
 DYSPLASIA

• Dysplasia is the condition characterized by the

abnormal change in size, shape and
organization of the cell. Dysplasia is not
considered as true adaptation and it is
suggested as related to hyperplasia. It is
common in epithelial cells of cervix and
respiratory tract.
 METAPLASIA

• Metaplasia is the condition that involves replacement of one

type of cell with another type of cell. It is of two types.
1. Physiological Metaplasia
• Replacement of cells in normal conditions is called physiological
metaplasia. Examples are transformation of cartilage into bone
and transformation of monocytes into macrophages.
2. Pathological Metaplasia
• Pathological metaplasia is the irreversible replacement of cells
due to constant exposure to harmful stimuli. For example,
chronic smoking results in transformation of normal mucus
secreting ciliated columnar epithelial cells into non-ciliated
squamous epithelial cells, which are incapable of secreting
mucus. These transformed cells may become cancerous cells if
the stimulus (smoking) is prolonged.
 THE INTERNAL ENVIRONMENT
• The goal of homeostasis is to provide an optimal
fluid environment for cellular function. The body
fluids are divided into two major functional
compartments.
1. The fluid inside cells, taken collectively, is the
intracellular fluid (ICF) compartment.
2. The fluid outside cells is the extracellular fluid (ECF)
compartment, which is subdivided into the
interstitial fluid and the blood plasma
 THE INTERNAL ENVIRONMENT

• The concept of an internal environment in the body

correlates with the interstitial fluid bathing cells.
There is free exchange of water and small solutes in
the ECF between interstitial fluid and plasma across
the blood capillaries. In contrast, the exchange of
most substances between interstitial fluid and
intracellular fluid is highly regulated and occurs
across plasma cell membranes.
 Body fluids

• The volume of total body water is approximately

60% of body weight in men and 50% in women.
• About 60% of total body water is ICF and 40% is ECF.
Approximately 80% of ECF is interstitial fluid and the
remaining 20% is blood plasma, which is contained
inside the vascular system.
• ECF is high in NaCl and low in K+, whereas ICF is
high in K+ and low in NaCl.
• Interstitial fluid is similar in composition to plasma,
except that interstitial fluid has almost no protein.
Osmolarity is the same in all compartments.
 Blood Volume
• Blood contains both ECF (the fluid in plasma) and
intracellular fluid (the fluid in the red blood cells). Blood is
plasma with cells suspended in it.
• They are: (i) RBC, (ii) WBC, (iii) platelets. Blood is present in
separate fluid compartments of its own.
• Therefore, considered as separate fluid compartment.
• It contains ECF and ICF both. Average blood volume of
normal adult is about 7 percent of body weight, or about 5
liters. Out of which 55-60% is plasma and 40-45% is blood
cells. Volume occupied by blood cells is known as packed cell
volume or hematocrit.
• It is determined by centrifuging blood in a hematocrit tube
until the blood cells become tightly packed in the bottom.
 Explain why the effects of positive feedback would
be disastrous
• If a disturbance increases the value of the controlled
variable, in a positive feedback system the controller
will respond to the disturbance by increasing the value
of the controlled variable still further. Now the
feedback signal gets still stronger resulting in a still
stronger response. Thus the control system actually
increases the rate at which the disturbance would
produce its effect and also increases the magnitude of
the effect. For example, if a person is exposed to heat,
a small rise in body temperature, in a positive feedback
system, would raise the temperature still further, giving
rise to fever which will keep rising higher and higher.
 What is feedforward control ?

• is the same as anticipatory control. It is

so called because it depends on being
fed information that does not still exist.
In other words, it operates on the basis
of information that is forward in time.
 If we have homeostatic mechanisms for regulating blood pressure, why do
some people get hypertension?

• For regulation of blood pressure, there are short-term

as well as long-term homeostatic mechanisms.
Hypertension represents the failure of long-term
mechanisms. There are also reports of reduced
sensitivity of baroreceptors, a short-term mechanism,
in hypertensive patients. But this reduction may be
an effect rather than the cause of the hypertension.
Sustained hypertension possibly leads to an
adaptation of baroreceptors, which manifests as
reduced sensitivity (in the same way as staying in a
stinking area for some time leads to reduced
sensitivity to the smell).
 Can a single effector work in both directions: stepping up, or stepping
down, a function?

• Yes, it can. E.g., if increased activity of a nerve increases the heart

rate, decreased activity of the same nerve will decrease the heart
rate. Of course, this is possible only if there is some basal activity
in the nerve all the time.
• But having two effectors makes the control system more efficient.
E.g., the body has two sets of nerves for regulation of heart rate:
sympathetic and parasympathetic.
• Sympathetic activity increases the heart rate while
parasympathetic activity decreases the heart rate.
• The two together act like the accelerator and brake in a car.
Although a car can be slowed down by using only the accelerator,
even the best driver sometimes has to use the brake to make
slowing down more efficient in order to avoid an accident.
 Why is extracellular fluid referred to as the body’s internal environment?

• Most of the body’s cells are not able to exchange materials directly
with the external environment because they are not in direct contact
with it. Instead, cells receive O2 and nutrients from the bloodstream,
which also carries CO2 and waste products away from cells.
• Moreover, most cells are not in direct contact with the blood, but
instead are surrounded by a separate fluid that exchanges materials
with the blood. Because this fluid constitutes the immediate
environment of most of the body’s cells, it is called the internal
environment. Internal environment in the body is the ECF in which
the cells live.
• It is the fluid outside the cell and it constantly moves throughout the
body. It includes blood, which circulates in the vascular system and
fluid present in between the cells called interstitial fluid. ECF contains
nutrients, ions and all other substances necessary for the survival of
the cells.
 By giving a suitable example, explain why sometimes in homeostasis variables
do not remain within the same narrow range of values at all times.

• Although homeostasis is the maintenance of a normal range of

values, this does not mean that all variables remain within the same
narrow range of values at all times. Sometimes a deviation from the
usual range of values can be beneficial.
• E.g., during exercise the normal range for blood pressure differs from
the range under resting conditions and the blood pressure is
significantly elevated.
• Muscle cells require increased oxygen and nutrients and increased
removal of waste products to support their heightened level of
activity during exercise.
• Elevated blood pressure increases delivery of blood to muscles
during exercise, thereby increasing the delivery of oxygen and
nutrients and the removal of waste products—ultimately maintaining
muscle cell homeostasis.