Introduction to physiology

What do we mean by physiology???!

Physiology is the study of the functions of the human body. In other words, the
mechanisms by which the various organs and tissues carry out their specific activities are
considered. In order for the body to function optimally, conditions within the body, referred to
as the internal environment, must be very carefully regulated. Therefore, many important
variables, such as body temperature, blood pressure, blood glucose, oxygen and carbon
dioxide content of the blood, as well as electrolyte balance, are actively maintained within
narrow physiological limits.

The Human Body - A Complex

Society of Differentiated Cells

Cells : the basic structural and functional unit of the body (~ 100 trillion)
But there are differences between the cells through the body.
Tissues: (e.g. muscles, epithelial, nervous )
connection of cells => Tissues

Organs: (e.g. kidney, heart, liver, pancreas)

connection of tissues => Organs

Organ systems: (e.g. cardiovascular, urinary)

Connection of organs => the Body

Each part of the body maintain general homeostasis

The human physiology affected by environment.

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 Regulation and Integration

Exists at all levels of organization

Cells : e.g., genes, repressor proteins, transcription factors, membrane transport
Tissues
Organ systems: e.g., nervous and endocrine systems

Human physiology: is a science which analyzes the body functions and their
interaction with the environment.
Humans are influenced by the external environment in which they live.

Functional relationships of body

systems

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 Homeostasis

Defined as maintenance of a relatively stable internal environment.

Does not mean that composition, temperature, and other characteristics are absolutely
unchanging.
Homeostasis is essential for survival and function of all cells.
It is important because the cells and tissues of the body will survive and function efficiently
only when these internal conditions are properly maintained.
All of the organ systems in the body, except the reproductive system, contribute to the
maintenance of homeostasis.
Two regulatory systems in the body influence the activity of all the other organ systems so
that homeostasis is ultimately maintained:

Nervous system & Endocrine system.

Nervous system:
Controls and coordinates bodily activities that require rapid responses.
Detects and initiates reactions to changes in external environment.

Endocrine system:
Secreting glands of endocrine system regulate activities that require duration rather than
speed.
Carries out its effects by secreting hormones.
Controls concentration of nutrients and, by adjusting kidney function, controls internal
environments volume and electrolyte composition.

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Homeostatic Control Systems
Feedback: refers to responses made after change has been detected.

Consists of:

Receptor: structures that monitor a

controlled condition and detect changes.
Afferent pathway:
Control center: determines response
Efferent pathway:
Effector:
receives orders from the control center.
produces a response that restores the controlled condition.

In general, when a physiological variable becomes too high or too low, a control system elicits
a negative feedback response consisting of one or a series of changes that returns the variable
to within its normal physiological range.

Types of feedback (control) systems:

Negative
This is a response that causes the level of a variable to change in a direction opposite
to that of the initial change.
Used for conditions that need frequent adjustment.
Most of the bodys compensatory homeostatic mechanisms function by way of
negative feedback.
Example of Negative Feedback:
Blood Pressure Regulation:
o Baroreceptors in walls of blood vessels detect an increase in Blood Pressure.
o Brain receives inputs and send signals to the blood vessels and heart.
o Blood vessels dilate, HR decreases.
o So Blood Pressure decreases towards normal.

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 Positive
Change is driven further away from original set-point.
Seen during normal childbirth.
Example of Positive Feedback:
Positive Feedback during Childbirth
o Stretch receptors in walls of uterus send signals to the brain.
o Brain induces release of hormone (oxytocin) into bloodstream.
o Uterine smooth muscle contracts more forcefully.
o More stretch, more hormone, more contraction etc.
o Cycle ends with birth of the baby.

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 Basic Characteristics of Cells
- Smallest living subdivision of the human body.

- Diverse in structure and function.

- Each Cell Has Three Primary Regions

Plasma Membrane Cytoplasm Nucleus

Cell Membrane

The cell membrane produces the following functions:

Separates intracellular environment from the
extracellular environment.
Regulates movement of materials in and out of
cell.
A selective mechanical barrier.

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Structure of the cell membrane:
The cell membranes are composed of lipids, proteins and carbohydrate. Membrane lipids
include phospholipids and cholesterol.

1. Bilayer of phospholipids:
a. Hydrophilic heads: "water "loving" attracted to water on inner/outer parts of cell.
b. Hydrophobic tails: fatty acids "water" "fearing" attracted to each other on inside of
bilayer.
c. Glycolipids: some carbohydrates attached to outer lipids.
d. Cholesterol: regulates fluidity of membrane.

2. Membrane proteins have the following functions:

1- Carrier proteins.

2- Ion channels.

3- Pumps involved in active transport.

4- Receptors for hormones.

Cell organelles
1- Nucleus:
Cell's "control center".
Largest organelle.
Contains DNA and associated proteins.
2- Ribosomes:
Large protein-RNA complexes
Found free floating in cytosol or attached to endoplasmic reticulum
synthesize proteins based on sequences of messenger RNA (mRNA) molecules
3- Endoplasmic reticulum:
an intracellular transport network.
Two types are present (rough and smooth),
the rough endoplasmic reticulum contains ribosomes and is the site of protein synthesis.
The smooth endoplasmic reticulum is the site of lipid and steroid synthesis.
4- Golgi apparatus:
It modifies and distributes newly synthesized proteins and lipids from the endoplasmic
reticulum to the plasma membrane and secretory vesicles.

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5- Mitochondria:
The mitochondria are called the powerhouses of the cell.
 They are responsible for energy production needed for all cellular functions.

6-Lysozomes:
Small vesicles containing digestive enzymes.
The lysosomal enzymes digest the unwanted organelles inside the cell.

Transport through cell membrane

Substances are transported through the cell membranes which separate the intracellular
fluid from the extra cellular fluid by two major processes; passive diffusion and active
transport.

Illustration of Different Transport Mechanisms

I. Passive diffusion:
A solution is a mixture of water (solvent) and various molecules and ions dissolve in the
water (solutes)
Solute particles tend to diffuse more from regions of high concentration to regions of low
concentration.

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 Factors influencing rate of diffusion
1. concentration gradient
difference in concentration, diffusion rate
2. Permeability of the plasma membrane to that substance
permeability for the diffusing substance, diffusion rate
3. Temperature
solution temperature, diffusion rate
4. Membrane surface area: direct relation.

1- Simple diffusion:

Net diffusion of substance across the plasma membrane without use of a carrier protein.
o Diffusion directly across the lipid bilayer (nonpolar molecules).
o Diffusion through channel proteins (water and inorganic ions).
Channels are specific for particular ions.

Osmosis

Net diffusion of water across a semi-permeable membrane.

Driven by differences in solute concentration across a semi-permeable membrane
If there is a difference in solute concentration across a membrane and the solute cannot
diffuse along the gradient, water will diffuse from the more dilute solution into the more
concentrated solution to equalize the concentration of the two solutions.
clinical implications of osmosis:
Isotonic solution: the same osmolarity as
plasma.
Hypertonic solution: more than plasma.
Hypotonic solution: less than plasma.

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2- Facilitated diffusion or carrier mediated:
Diffusion of a molecule along its concentration
gradient through a carrier protein
Adding carriers or removing carriers increases or
decreases membrane permeability and rate of
diffusion.

II. Active transport:

It means transport of substances across the cell
membrane against a concentration (or electric)
gradient e.g. transport of ions, sugars, amino acids
etc.

Mechanism of active transport:

It depends upon presence of a carrier and it needs energy. The carrier combines with the
substance to be transported at the outer surface of the membrane, then diffuses through the
membrane to the inner surface where the substance is released from the carrier. This process
needs energy which is derived from ATP.

Na+/ K+ Pump
Active transport carrier that simultaneous pumps Na + out
of the cell and K+ into the cell 3 Na+ out per 2 K+ in for
each cycle of the pump.
Generates concentration gradients and electrical charge
differences between the inside and outside of the cell
Important for:
Generation of electrical impulses in nerves and
muscles.
Driving cotransport of other substances across the
plasma membrane

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Other forms of active transport:
Transport of proteins and other large molecules through the cell membrane occur by the
following:
A) Endocytosis: In this process substances of large molecules are transported inside the cell.
It has two types:
1- Phagocytosis: (cell eating )
It is the process by which bacteria and dead tissues are engulfed by cells The material makes
contact with the cell membrane, then invaginated into it.
The invaginated portion of the membrane breaks away from the surface of the cell, forming
phagocytic vesicle which then penetrates deep into the cytoplasm away from the cell
membrane.

2- Pinocytosis: (cell drinking)

In this process the substance ingested is present in solution e.g. proteins. The process is
almost identical with that of phagocytosis.

B) Exocytosis: (cell vomiting)

It is the process by which proteins and peptides are secreted from the cells e.g. secretion of
hormones protein in nature from endocrine cells. In this process the membrane around the
secretion granules fuses with the cell membrane and the region of fusion breaks down, leaving
the contents of the secretion granule outside.

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 The body fluids

Total body water (TBW ): (42 liters).

It constitutes about 60 % of the body weight in young men, and 50% of the body weight in
young women.
The lower percentage of TBW in women is largely due to the greater amounts of fat in
women (30%) than in men (15 %), because fat is relatively free of water.
In newborn infants, the TBW is as high as 70 % of the body weight.
In men and women the percentages of the TBW tends to decrease with advance of age.

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The total body water is divided into:
A) Intracellular fluid (ICF): (28 liters).

It is the fluid present inside the whole body cells. It represents about 40 % of the body
weight.

B) Extracellular fluid (ECF): (14 liters)

It is the fluid present outside the cells and separated from the ICF by the cell membranes. It
represents about 20 % of the body weight. The ECF is divided into:

1. Blood plasma: (3 liters)

It is the part of the extracellular fluid which is present in the circulatory system.

2. Interstitial fluid: (11 liters)

It is the part of the extracellular fluid which surrounds all cells (except blood cells). It is
separated from plasma by the capillary membranes and from the intracellular fluid by the
cell membranes.

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 Physiology Of Excitable Tissues
Excitable tissues
All tissues in our body are living cells and can maintain resting membrane potential.
Excitability, however, is shown only by specialized cells, nerve and muscle. An excitable cell is
able to respond to a stimulus and generate electrical changes.

Neurons
Nerve cells, called neurons, are responsible for conducting impulses from one part of
the body to another. They are the structural and functional units of the nervous system.

A neuron consists of 3 portions.

1) cell body. 2) dendrites. 3) axon.

Parts Character
The cell body Contains a well-defined nucleus surrounded by a cytoplasm.
Within the cytoplasm are typical organelles such as mitochondria,
lysosomes and golgi complex.
Dendrites Are branched, extensions of the cell body.
Their function is to conduct impulses toward the cell body.
Axon It is a single, long, thin process that conduct impulses way from
the cell body to another neuron.
This axon formed of initial sagment and terminal branches called
synaptic knobes which contain synaptic vesicles.
When the impulse reaches the synaptic terminals leading to
release of neurotransmitter which excite or inhibit nearby neurons
It may be myelinated or unmyelinated.
This myelin contain gaps called nodes of Ranvier.
This myelin is protective and electrical insulator, it also incease
the speed of transmission of nerve impulse.

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Properties of nerves
1- Excitability: it the ability of nerve to respond to stimulus.
2- Conductivity: it the ability of nerve to conduct nerve impulse.
3- Infatiguibility: nerves not liable to fatigue by repeated stimulation.
4- All or none law:
If a single nerve fiber is stimulated with a threshold or
suprathershold stimulus, an action potential will result, which
always have the same characteristic amplitude regardless the
strength of stimulation.
Subthreshold stimulus ; no action potential.
Threshold stimulus; action potential.
Suprathreshold stimulus; same action potential.

Stimulus
Def: It is a change in the surrounding environment.
Types: electrical, thermal, chemical or mechanical.
Electrical stimuli are used to study the function of nerve or muscle. It is preferred because
intensity and duration can be easily controlled.

Effects of stimulation of the nerve

A given stimulus will cause its effect by altering the permeability to one or more ions. The
involved ions will then diffuse into or out of the cell according to their concentration and
electrical gradients, causing a change in the membrane potential.

Depolarization occurs when the membrane potential becomes less negative,

moving toward zero. Depolarization makes the neuron more excitable.

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Hyperpolarization occurs when the membrane potential becomes more negative, moving
away from zero. Hyperpolarization makes the neuron less excitable.

Once the stimulus has been removed, the membrane potential returns to its resting state.
Following depolarization, the membrane is said to undergo repolarization, returning to its
resting potential.

Resting membrane potential

Definition:
It is the difference in potential under resting conditions between the outer surface and
inner surface of the membranes of excitable tissues with the inside of the membrane
negatively charged with respect to the outside.
The positivity of the outer surface is due to Na+ ions; while the negativity of inner surface
is due to intracellular protein anions.

RMP is normally 70 mv in nerves and 90 mv in muscles

Causes of resting membrane potential

1) Selective permeability of the nerve membrane: 16
 * permeability of membrane to K+ is more than that Na+ at rest.
* Passive K+ efflux is more than passive Na+ influx.
* K+ efflux is not accompanied by equal efllux of anions (-ve).
* The net result is that the membrane is maintained in a polarized state with the outside
positive relative to the inside.

2) Sodium-potassium pump:
*The Na+K+ pump also plays a vital role in this process.
*For each molecule of ATP expended, three Na+ ions are
pumped out of the cell into the ECF and two K+ ions are
pumped into the cell into the ICF.
*The result is the unequal transport of positively
charged ions across the membrane such that the outside of
the cell becomes more positive compared to its inside; in
other words, the inside of the cell is more negative compared to the outside.

Action potential

Definition:
It is a sudden change in the membrane potential of an excitable cells of the nerve in
response to stimulus.

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 Phases
1) Depolarization stage
At the beginning of A.P, depolarization is slow for 15 mv till it reaches the firing threshold then
the rate of depolarization increases markedly.
2) Then the membrane potential overshoots and becomes + 35 mv.
3) Repolarization stage
At the end of depolarization, the change in membrane potential then reverses and falls
rapidly towards the resting level.

Ionic basis
1- At the beginning of action potential, voltage gated
Na channeles start to open, so the membrane
potential reach to 15 mv (firing level).
2- At the firing level, of the action potential,
sodium channels open (activation state)
increasing permeability to Na+ several hundreds fold.
Na+ rushes into the membrane.
3- Positive feedback cycle develops:
i) Depolarization opens Na+ channels.
ii) Na+ diffuses into the cell due to increased
Na+permeability.
iii) Addition of +ve charges into the cell further
depolarizes the membrane.

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 iv) This in turn produces a still greater increase in Na+ permeability which inturn causes
and so on.
4- In the repolarization phase what causes the
membrane potential to return so rapidly to its resting level
- It is due to opening of K+ channels & closure of Na
channel.

5- Due to to delayed closure of K+ channels, the

membrane potential undershoot resulting in hyperpolarization.

6- The membrane potential returns to the resting state by activation of sodium potassium
pump.

Firing Level

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Excitability changes during action potential

1) Absolute Refractory Period

During depolarization and early repolarization, there is no response to any stimulus whtever
its strength. The excitability is zero.

2) Relative refractory period

During the lower 2/3 of repolarization, a stimulus stronger than threshold can stimulate the
nerve.

Propagation of the nerve impulse

a) Conduction in unmyelinated
fibers
The (+) charges in the region of the action
potential are attracted to the negative
charges in the immediately adjacent

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 region of the axonal membrane.
This current flow depolarizes the new region, causing an increase in the permeability of
the membrane to Na+ ions. The subsequent influx of Na+ ions further depolarizes the
membrane so that it reaches threshold and a new action potential is generated in this
region.
At the same time, the original site of action potential generation repolarizes due to the
efflux of K+ ions.

b) Conduction in myelinated fibers

Action potentials cannot be
generated in the regions
covered with myelin. Instead,
they occur only at nodes of
Ranvier. The flow of current
from an active node skips
down the axon to the adjacent node to cause
depolarization and generation of a new action
potential.
This transmission of the impulse from node to node is referred to as saltatory conduction.
(The term saltatory means jumping ).

Saltatory conduction is of value for two reasons

First it increases the velocity of nerve transmission.
Second it conserves energy, since depolarization occurs only at the node.

Factors Affecting Conduction Velocity

1. Types of nerve fibers:
I- Type A (alpha, Beta, Gamma, Delta).
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 It has the largest diameter (3-20 microns) and the highest Speeds of conduction (15-120
meters/sec).
II- Type B
It has a diameters (1.3-3 microns) and speed of conduction (3-15 metes/second).
III- Type C
It has the diameter of 0.3-1.3 microns and speed of conduction 0.5-3 meters/sec.(smallest
diameter & slowest conduction).

A & 8 fibers are myelinated, while C fibers are unmyelinated.

The greater the nerve diameter, the greater is the speed of conduction. Therefore,
conduction velocity of the myelinated nerve fiber is faster than the unmyelinated one.
Normal propagation along an non-myelinated axon is typically in the range of 1-2
m/sec. In myelinated axon, this ranges from 15 to 150 m/sec.

2. Body temperature:
One degree fall in body temperature decreases nerve conduction velocity by 3%. At 3 - 7
C, nerve conduction is completely blocked. This physiologic observation is applied in many
beneficial surgical procedures (cryosurgery).

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 Local potential

DeFinition
The local potential is the depolarization of a cell below threshold. After the cell is
sufficiently depolarized (and reaches threshold), it fires an action potential down the axon.

Characteristic features of the local potential

Its magnitude is proportionate to the strength of the stimulus = graded response
(amplitude-modulated).
It is localized to the area of stimulation = not propagated.
it could be summated.
Local potentials could be induced by sub-threshold stimulation of the excitable
membranes of the nerve and muscle fibers.
Local potentials are important in short distance signaling function.

Neuromuscular Transmission
Motor end plate (neuromuscular junction) MEP
It is the area of contact between motor nerve fiber and muscle fibers.

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Mechanism of neuromuscular transmission
a) Development of end-plate potential
-Action potentials in the motor neuron cause release of the neurotransmitter
acetylcholine.
-Binding of acetylcholine to its receptors on the muscle fiber causes an increase in the
permeability to Na+ and K+ ions.
-The ensuing depolarization generates an action potential that travels along the surface of
the muscle fiber in either direction that is referred to as a propagated action potential.
-This action potential elicits the intracellular events that lead to muscle contraction.

b) Destruction of acetylcholine by choline esterase

The released acetylcholine is rapidly hydrolysed by choline-esterase enzyme. This prevents
re-excitation of the muscle.

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 Properties of NM

transmission
a) Unidirectional:
from the nerve to the
muscle.
b) NM delay: 0.5
msec passed from
the action potential
in the motor nerve
terminals to the start
of the muscle
contraction (Ca
influx, release of
ach, binding of
acetylcholine to the
receptors and
deveelopment of
muscle action potential).
c) NM fatigue: decrease in the NM transmission upon repeated stimulation of the nerve
terminals due to depletion of acetylcholine.

d) Drugs affecting neuro-muscular transmission

A) Drugs block transmission
1) Curare (d-tubocuraine) acting as competitive antagonist of acetylcholine at motor end plate.
2) Botulinum toxins: by inhibiting the release of acetylcholine.

B) Drugs stimulate transmission

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1) Acetylholine-like drugs e.g. metacholine, carbachol and nicotine.
2) Anticholine esterase drugs e.g. prostigmine, eserine and DFP.

Anticholine-esterases
Short acting
- eserine (physostigmine). - prostigmine (neostigmine).
These drugs increase the availability of acetylcholine by preventing its rapid breakdown by the
choinestrase.

Long acting
- Parathion (isecticides) - Di-isopropyl fluorophosphates (war poison).
They produce irriversible inhibition of cholinestrae enzyme, resulting in persistnt depolarization
and muscle paralysis. Death may follow due to failure of respiration.

Myasthenia gravis
It is characterized by marked weakness and easy fatigueability of muscles. It may be due to:
Autoimmune disease caused by the formation of circulating antibodies
destroying the acetylcholine receptors. It is treated by anti-cholinestrases

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The Dr mentioned that lectures are very
important sources that Summarize the main ideas
in the topic, and he will give information which
you cant find in the book so you have to follow
him and write down notes.

Note:

The doctor concentrated on Time respecting

issue, so you should come on time,
well be doctors and the time is a holy thing in
your life.
The doctor Said:

Respect me I will respect you, be in the lecture

in the proper time, and listen carefully to my
lectures.

Respect me I will respect you, be in the lecture in the

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proper time, and listen carefully to my lectures.