AKSON COLLEGE OF PHARMACY

MIRPUR UNIVERSITY OF SCIENCE AND TECHNOLOGY (MUST), MIRPUR

 PHYSIOLOGY-A
PHARM 313

Lecture # 01:Chemical Composition Of The Body

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Atoms

4. Components of Atoms

5. Atomic Composition of the Body

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 Lecture Contents

6. Ions

7. Polar Molecules

8. Free Radicals

9. References

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 Learning Objectives

After this lecture, students will be able to:

• Describe the and location of the three major subatomic particles in an
atom.
• Describe is atomic composition of human body?
• Define ion , polar molecule.
• Explain the role free radical in body

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 Introduction

• The study of physiology requires some familiarity with the basic

concepts and terminology of chemistry.
• A knowledge of atomic and molecular structure, the nature of
chemical bonds, and the nature of pH and associated concepts
provides the foundation for much of human physiology.
• The structures and physiological processes of the body are based, to a
large degree, on the properties and interactions of atoms, ions, and
molecules.
• Water is the major constituent of the body. Dissolved in this water are
many organic molecules molecules such as carbohydrates, lipids,
proteins, and nucleic acids, as well as inorganic molecules and ions .

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 Molecules

• Two or more atoms bonded together make up a molecule.

• A molecule made up of two or more different elements is called a
compound.
• Molecules can be represented by their component atoms. In the two
examples just given, a molecule of oxygen can be represented as O2
and water as H2O.
• The atomic composition of glucose, a sugar, is C6H12O6, indicating
that the molecule contains 6 carbon atoms, 12 hydrogen atoms, and 6
oxygen atoms.

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 Atoms

• The units of matter that form all chemical substances are called atoms.
• Each type of atom—carbon, hydrogen, oxygen, and so on— is called a
chemical element.
• More than 100 elements occur naturally or have been synthesized in
the laboratory, only 24 have been clearly identified as essential for the
function of the human body and are therefore of particular interest to
physiologists.
• The chemical properties of atoms can be described in terms of three
subatomic particles—protons, neutrons, and electrons.

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 Atoms

• The protons and neutrons are confined to a very small volume at the
center of an atom called the atomic nucleus.
• The electrons revolve in orbitals at various distances from the
nucleus. Each orbital can hold up to two electrons and no more.
• An atom is most stable when all of the orbitals in its outermost shell
are filled with two electrons each.
• If one or more orbitals do not have their capacity of electrons, the
atom can react with other atoms and form molecules

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Atoms

10
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 Atoms

Atomic Composition of the Body

Major Elements: 99.3% of Total Atoms in the Body
• Hydrogen H (63%)
• Oxygen O (26%)
• Carbon C (9%)
• Nitrogen N (1%)

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 Atoms

• Mineral Elements: 0.7% of Total Atoms in the Body

• Calcium
• Phosphorus
• Potassium
• Sulfur
• Sodium
• Chlorine
• Magnesium

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 Atoms

• Trace Elements: Less than 0.01% of Total Atoms in the Body

• Iron
• Iodine
• Copper
• Zinc
• Manganese
• Cobalt
• Chromium

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 Atoms

• Selenium
• Molybdenum
• Fluorine
• Tin
• Silicon
• Vanadium

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 Ions

• Certain atoms may gain or lose one or more electrons, they will then
acquire a net electrical charge and become an ion.
• For example, when a sodium atom (Na), which has 11 electrons, loses
one electron, it becomes a sodium ion (Na+) with a net positive
charge; it still has 11 protons, but it now has only 10 electrons, two in
its first shell and a full complement of eight in its second, outer shell.
• A chlorine atom (Cl), which has 17 electrons, one electron shy of a
full outer shell. It can gain an electron and become a chloride ion (Cl−)
with a net negative charge—it now has 18 electrons but only 17
protons.
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Ions

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 Molecules

• Two or more atoms bonded together make up a molecule.

• A molecule made up of two or more different elements is called a
compound.
• Molecules can be represented by their component atoms. In the two
examples just given, a molecule of oxygen can be represented as O2
and water as H2O.
• The atomic composition of glucose, a sugar, is C6H12O6, indicating
that the molecule contains 6 carbon atoms, 12 hydrogen atoms, and 6
oxygen atoms.

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 Polar Molecules

• Atoms of oxygen, nitrogen, and sulfur, which have a relatively strong

attraction for electrons, form polar bonds with hydrogen atoms .
• One of the characteristics of polar bonds that is important in our
understanding of physiology is that molecules that contain such bonds
tend to be very soluble in water, these molecules—called polar
molecules.
• They readily dissolve in the blood, interstitial fluid, and intracellular
fluid.
• Water is the classic example of a polar molecule, with a partially
negatively charged oxygen atom and two partially positively charged
hydrogen atoms.
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Polar Molecules

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 Free Radicals

• An atom containing a single (unpaired) electron in an orbital of its

outer shell is known as a free radical.
• Free radicals are unstable molecules that can react with other atoms,
through the process known as oxidation.
• When a free radical oxidizes another atom, the free radical gains an
electron and the other atom usually becomes a new free radical.
• Free radicals are formed by the actions of certain enzymes in some
cells, such as types of white blood cells that destroy pathogens. The
free radicals are highly reactive, removing electrons from the outer
shells of atoms within molecules present in the pathogen cell wall or
membrane.
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 Free Radicals

• Free radicals can be produced in the body following exposure to

radiation or toxin ingestion. These free radicals can do considerable
harm to the cells of the body.
• For example, oxidation due to long-term buildup of free radicals has
been proposed as one cause of several different human diseases,
notably eye, cardiovascular, and neural diseases associated with aging.
• Free radicals be inactivated by molecules that can donate electrons to
free radicals without becoming dangerous free radicals themselves.

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 Free Radicals

• Examples of such protective molecules are the antioxidant vitamins C

and E.
• Examples of biologically important free radicals are superoxide anion,
O2 · −; hydroxyl radical, OH · ; and nitric oxide, NO · .
• A free radical configuration can occur in either an ionized (charged)
or a nonionized molecule.

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 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

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 PHYSIOLOGY-A
PHARM 313

Lecture # 02:Chemical Composition Of The Body

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 PHYSIOLOGY-A
PHARM 313

Lecture # 02: Chemical Composition Of The Body

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Objectives of the lecture

2. Solutions

3. Classes of Organic Molecules

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 Objectives Of The Lecture

After this lecture, students will be able to:

• Describe the structure and functions of major organic molecules in

body.

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 Solutions

• Substances dissolved in a liquid are known as solutes, and the liquid

in which they are dissolved is the solvent. Solutes dissolve in a solvent
to form a solution.
• Water is the most abundant solvent in the body, accounting for
approximately 60% of total body weight.
• Most of the chemical reactions that occur in the body involve
molecules that are dissolved in water, either in the intracellular or
extracellular fluid. However, not all molecules dissolve in water.

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 Solutions

• Molecular Solubility
• Molecules having a number of polar bonds and/or ionized groups will
dissolve in water. Such molecules are said to be hydrophilic, or
―water-loving.‖
• The presence of ionized groups such as carboxyl and amino groups or
of polar groups such as hydroxyl groups in a molecule promotes
solubility in water.
• Molecules composed predominantly of carbon and hydrogen are
poorly or almost completely insoluble in water because their
electrically neutral covalent bonds are not attracted to water
molecules. These molecules are hydrophobic, or ―water-fearing.‖

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 Classes Of Organic Molecules

• Most naturally occurring carbon-containing molecules are found in

living organisms, One of the properties of the carbon atom that makes
life possible is its ability to form four covalent bonds with other atoms,
including with other carbon atoms.
• Carbon atoms can also combine with hydrogen, oxygen, nitrogen, and
sulfur atoms, a vast number of compounds can form from relatively
few chemical elements.
• Some of these molecules are extremely large (macromolecules),
composed of thousands of atoms..

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 Classes Of Organic Molecules

• In some cases, such large molecules form when many identical

smaller molecules, called subunits or monomers (literally, ―one part‖),
link together.
• These large molecules are known as polymers (―many parts‖) . Most
of the organic molecules in the body can be classified into one of four
groups:
• carbohydrates,
• lipids,
• proteins, and
• nucleic acids

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 Classes Of Organic Molecules

Carbohydrates
• Carbohydrates account for only about 1% of body weight, they have a
central contribution in the chemical reactions that provide cells with
energy this energy can be released within cells when required and
stored in the bonds of another molecule called adenosine triphosphate
(ATP).
• The energy stored in the bonds in ATP is used to power many
different reactions in the body, including those necessary for cell
survival, muscle contraction, protein synthesis, and many others.

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 Classes Of Organic Molecules

• Carbohydrates are composed of carbon, hydrogen, and oxygen atoms.

Linked to most of the carbon atoms in a carbohydrate are a hydrogen
atom and a hydroxyl group
• When many monosaccharides are linked together to form polymers,
the molecules are known as polysaccharides. Starch, found in plant
cells, and glycogen, present in animal cells, are examples of
polysaccharides.
• Glycogen exists in the body as a reservoir of available energy that is
stored in the chemical bonds within individual glucose monomers.
• Hydrolysis of glycogen, as occurs during periods of fasting, leads to
release of the glucose monomers into the blood, thereby preventing
blood glucose from decreasing to dangerously low concentrations.

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 Classes Of Organic Molecules

Lipids
• Lipids are molecules composed predominantly of hydrogen and
carbon atoms. These atoms are linked by nonpolar covalent bonds;
therefore, lipids are nonpolar and have a very low solubility in water.
• Lipids, which account for about 40% of the organic matter in the
average body can be divided into four subclasses: fatty acids,
triglycerides, phospholipids, and steroids.
• Like carbohydrates, lipids are important in physiology partly because
some of them provide a valuable source of energy.
• Other lipids are a major component of all cellular membranes, and still
others are important signaling molecules.

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 Classes Of Organic Molecules

Fatty Acids
• A fatty acid consists of a chain of carbon and hydrogen atoms with an
acidic carboxyl group at one end.
• Fatty acids contain two oxygen atoms in addition to their complement
of carbon and hydrogen.
• Fatty acids are synthesized in cells by the covalent bonding together of
two-carbon fragments, resulting most commonly in fatty acids of 16 to
20 carbon atoms.
• When all the carbons in a fatty acid are linked by single covalent
bonds, the fatty acid is said to be a saturated fatty acid,

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 Classes Of Organic Molecules

Triglycerides
• Triglycerides constitute the majority of the lipids in the body; these
molecules are generally referred to simply as ―fats.‖
• Triglycerides form when glycerol, a three-carbon sugar-alcohol,
bonds to three fatty acids Triglycerides are present in the and can be
synthesized in the liver.
• They are stored in great quantities in adipose tissue, where they serve
as an energy reserve for the body, particularly during times when a
person is fasting or requires additional energy (exercise, for example).

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 Classes Of Organic Molecules

Phospholipids
• Phospholipids are amphipathic. In aqueous solution, they become
organized into clusters, with their polar ends attracted to the water
molecules.
• This property of phospholipids permits them to form the lipid bilayers
of cellular membranes.
Steroids
• Examples of steroids are cholesterol, cortisol from the adrenal glands,
and female and male sex hormones (estrogen and testosterone,
respectively) secreted by the gonads.

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 Classes Of Organic Molecules

Proteins
• Proteins, macromolecules composed primarily of carbon, hydrogen,
oxygen, and nitrogen, are polymers of 20 different amino acids.
• Amino acids have an amino (−NH2) and a carboxyl (−COOH) group
bound to their terminal carbon atom.
• Amino acids are bound together by peptide bonds between the
carboxyl group of one amino acid and the amino group of the next.
• The primary structure of a polypeptide chain is determined by
(1) the number of amino acids in sequence and
(2) the type of amino acid at each position.

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Classes Of Organic Molecules

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 Classes Of Organic Molecules

Nucleic Acids
• There are two classes of nucleic acids, deoxyribonucleic acid (DNA)
and ribonucleic acid (RNA).
• DNA molecules store genetic information coded in the sequence of
their genes.
• RNA molecules are involved in decoding this information into
instructions for linking together a specific sequence of amino acids to
form a specific polypeptide chain.
• Nucleic acids are polymers subunits, nucleotide, has three
components: a phosphate group, a sugar, and a ring of carbon and
nitrogen atoms known as a base because it can accept hydrogen ions
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 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

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 PHYSIOLOGY-A
PHARM 313

Lecture # 03:Cell Structure

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Microscopic Observation of Cell

4. Cell Organelles

5. Cytoskeleton

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 Learning Objectives

After this lecture, students should be able to:

• Describe the prominent cellular organelles and state their functions in
cells.
• Name the building blocks of the cellular cytoskeleton and state their
contributions to cell structure and function.

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 Introduction

• Cells are the structural and functional units of all living organisms and
make up the tissues and organs .
• Cells are the highly organized, living building blocks of the body. A
cell has three major parts: the plasma membrane, which encloses the
cell; the nucleus, which houses the cell’s genetic material; and the
cytoplasm.
• The cytoplasm consists of the cytosol, organelles, and cytoskeleton.
The cytosol is a gel-like liquid within which the organelles and
cytoskeleton are suspended.
• Organelles are discrete, well-organized structures that carry out
specialized functions. The cytoskeleton is protein scaffolding that
extends throughout the cell and serves as the cell’s ―bone and muscle.‖

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 Microscopic Observations Of Cells

• Cells are surrounded by a limiting barrier, the plasma membrane

(also called the cell membrane), which covers the cell surface.
• The cell interior is divided into a number of compartments surrounded
by membranes.
• These membrane-bound compartments, along with some particles and
filaments, are known as cell organelles.
• Each cell organelle performs specific functions that contribute to the
cell’s survival.

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Microscopic Observations Of Cells

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 Cell Organelles

Plasma Membrane
• The plasma membrane is a thin membranous structure that encloses
each cell and is composed mostly of lipid (fat) molecules and studded
with proteins.
• Functions of Plasma Membranes
• Regulate the passage of substances into and out of cells and between
cell organelles and cytosol.
• Detect chemical messengers arriving at the cell surface.
• Link adjacent cells together by membrane junctions.

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 Cell Organelles

1 )VANDER’S HUMAN PHYSIOLOGY: THE

MECHANISMS OF BODY FUNCTION, FIFTEENTH
EDITION , ERIC P. WIDMAIER , HERSHEL RAFF,
KE,STUART IRA FOX.

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 Cell Organelles

Nucleus
• Almost all cells contain a single nucleus, the largest of the membrane
bound cell organelles.
• A few specialized cells, such as skeletal muscle cells, contain multiple
nuclei, whereas mature red blood cells have none.
• The primary function of the nucleus is the storage and transmission of
genetic information to the next generation of cells.
• This information, coded in molecules of DNA, is also used to
synthesize the proteins that determine the structure and function of the
cell

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Cell Organelles

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 Cell Organelles

Golgi Apparatus
• The Golgi apparatus is a series of closely apposed, flattened
membranous sacs that are slightly curved, forming a cup-shaped
structure .
• Associated with this organelle, particularly near its concave
surface, are a number of roughly spherical, membrane-enclosed
vesicles.
• Proteins arriving at the Golgi apparatus from the rough endoplasmic
reticulum undergo a series of modifications as they pass from one
Golgi compartment to the next.

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Cell Organelles

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 Cell Organelles

Endosomes
• A number of membrane-bound vesicular and tubular structures called
endosomes lie between the plasma membrane and the Golgi
apparatus.
• Vesicles that pinch off the plasma membrane travel to and fuse with
endosomes.
• In turn, the endosome can pinch off vesicles that then move to other
cell organelles or return to the plasma membrane.
• Like the Golgi apparatus, endosomes are involved in sorting,
modifying, and directing vesicular traffic in cells.

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 Cell Organelles

Mitochondria
• Mitochondria (singular, mitochondrion) participate in the chemical
processes that transfer energy from the chemical bonds of nutrient
molecules to newly created adenosine triphosphate(ATP) molecules.
• Mitochondria are spherical or elongated, rodlike structures surrounded
by an inner and an outer membrane.
• Provide most of the energy required to power physiological events
such as muscle contraction, mitochondria also function in the synthesis
of certain lipids, such as the hormones estrogen and testosterone.

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Cell Organelles

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 Cell Organelles

Lysosomes
• Lysosomes are spherical or oval organelles surrounded by a single
Membrane The fluid within a lysosome is acidic and contains a variety
of digestive enzymes.
• Lysosomes act to break down bacteria and the debris from dead cells
that have been engulfed by a cell.
• They may also break down cell organelles that have been damaged and
no longer function normally.
• They have an especially important function in the various cells that
make up the defense systems of the body.

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 Cell Organelles

Peroxisomes
• Peroxisomes are moderately dense oval bodies enclosed by a single
membrane peroxisomes consume molecular oxygen, it undergoes
reactions that remove hydrogen from organic molecules including
lipids, alcohol, and potentially toxic ingested substances.
• Peroxisomes are also involved in the process by which fatty acids are
broken down into two-carbon fragments, which the cell can then use
as a source for generating ATP.

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 Cell Organelles

Vaults
• Vaults are cytoplasmic structures composed of protein and a type of
untranslated RNA called vault RNA (vRNA).
• These tiny structuresbhave been described as barrel-shaped . vaults are
important for transport of molecules between the cytosol and the
nucleus.
• One vault protein is believed to function in regulating a cell’s
sensitivity to certain drugs.

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 Cytoskeleton

• The cytoplasm of most cells contains a variety of protein filaments.

This filamentous network is referred to as the cell’s cytoskeleton. and,
like the bony skeleton of the body, it is associated with processes that
maintain and change cell shape and produce cell movements.
• The three classes of cytoskeletal filaments are based on their diameter
and the types of protein they contain. In order of size, starting with the
thinnest, they are
(1) actin filaments (also called microfilaments),
(2) intermediate filaments, and
(3) microtubules

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Cytoskeleton

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 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 62
 PHYSIOLOGY-A
PHARM 313

Lecture # 04 :Protein Activity

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

LECTURE CONTENTS

1. Introduction

2. Objectives of the lecture

3 Binding Site Characteristics

4. Regulation of Binding site Characteristics

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 Learning Objectives

After this lecture, students will be able to:

• Define ligand & binding site
• Describe the binding site Binding Site Characteristics.
• Understand the mechanisms of activation and inhibition of binding
site.

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 Introduction

• Proteins physically interact with each other and with other molecules
and ions.
• These interactions are fundamental to nearly all physiological
processes, clearly illustrating the general principle of physiology that
physiological processes are dictated by the laws of chemistry and
physics.
• The ability of various molecules and ions to bind to specific sites on
the surface of a protein forms the basis for the wide variety of protein
functions.

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 Binding Site Characteristics

Ligand
• A ligand is any molecule (including another protein) or ion that is
bound to a protein by one of the following physical forces:
• (1) electrical attractions between oppositely charged ionic or polarized
groups on the ligand and the protein, or
• (2) weaker attractions due to hydrophobic forces between nonpolar
regions on the two molecules.

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 Binding Site Characteristics

Binding Site
• The region of a protein to which a ligand binds is known as a binding
site or a ligand-binding site.
• A protein may contain several binding sites, each specific for a
particular ligand, or it may have multiple binding sites for the same
ligand.
• The binding of a ligand to a protein changes the conformation of the
protein. When this happens, the protein’s specific function may either
be activated or inhibited.

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Binding Site Characteristics

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 Binding Site Characteristics

• Chemical Specificity
• The binding between a ligand and a protein may be so specific that a
binding site can bind only one type of ligand and no other.
• Such selectivity allows a protein to identify (by binding) one particular
molecule in a solution containing hundreds of different molecules.
• This ability of a protein-binding site to bind specific ligands is known
as chemical specificity, because the binding site determines the type
of chemical that is bound.

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Binding Site Characteristics

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 Binding Site Characteristics

• Affinity
• The strength of ligand–protein binding is a property of the binding site
known as affinity.
• The affinity of a binding site for a ligand determines how likely it is
that a bound ligand will leave the protein surface and return to its
unbound state.
• Binding sites that tightly bind a ligand are called high-affinity binding
sites; those that weakly bind the ligand are low-affinity binding sites.

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 Binding Site Characteristics

• Saturation
• An equilibrium is rapidly reached between unbound ligands in
solution and their corresponding protein-binding sites.
• At any instant, some of the free ligands become bound to unoccupied
binding sites, and some of the bound ligands are released back into
solution. A single binding site is either occupied or unoccupied.
• The term saturation refers to the fraction of total binding sites
that are occupied at any given time.
• When all the binding sites are occupied, the population of binding sites
is 100% saturated.

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 Binding Site Characteristics

Competition
• More than one type of ligand can bind to certain binding sites. In such
cases, competition occurs between the ligands for the same binding
site.
• The presence of multiple ligands able to bind to the same binding site
affects the percentage of binding sites occupied by any one ligand.
• As a result of competition, the biological effects of one ligand may be
diminished by the presence of another.

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 Regulation Of Binding Site
Characteristics
There are two ways of controlling protein activity:
(1) changing protein shape, which alters the binding of ligands; and
(2) as described earlier in this chapter, regulating protein synthesis and
degradation, which determines the types and amounts of proteins in a
cell.
The two mechanisms found in cells that selectively alter protein shape
are known as allosteric modulation and covalent modulation, though
only certain proteins are regulated by modulation.

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 Regulation Of Binding Site
Characteristics
• Allosteric Modulation
• Whenever a ligand binds to a protein, the attracting forces betweenthe
ligand and the protein alter the protein’s shape.
• For example, as a ligand approaches a binding site, these attracting
forces can cause the surface of the binding site to bend into a shape
that more closely approximates the shape of the ligand’s surface.
• When a protein contains two binding sites, the noncovalent binding of
a ligand to one site can alter the shape of the second binding site and,
therefore, the binding characteristics of that site. This is termed
allosteric modulation

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 Regulation Of Binding Site
Characteristics
• Covalent Modulation
• The second way to alter the shape and therefore the activity of a
protein is by the covalent bonding of charged chemical groups to some
of the protein’s side chains. This is known as covalent modulation.
• In most cases, a phosphate group, which has a net negative charge, is
covalently attached by a chemical reaction called phosphorylation, in
which a phosphate group is transferred from one molecule to
another.

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Regulation Of Binding Site
Characteristics

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 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 79
 PHYSIOLOGY-A
PHARM 313

Lecture # 05:Cellular Metabolism

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3 Chemical Reactions

4 Enzymes

4. Regulation of Enzyme-Mediated Reactions

5. Multienzyme Reactions

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 Learning Objectives

After this lecture, students will be able to:

• Understand the mechanism of enzyme action.

• Describe the factors that effect the rate of chemical reactions.
• Describe the difference between cofactor and coenzyme .
• Describe the ways to alter the rate of an enzyme-mediated reaction
• Describe the end-product inhibition.

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 Introduction
• This section, include some of the major functionsof proteins,
specifically those that relate to facilitating chemical
reactions.Thousands of chemical reactions occur each
instantthroughout the body; this coordinated process of chemical
change is termed metabolism.
• Metabolism involves the synthesis and breakdown of organic
molecules required for cell structure and function and the release of
chemical energy used for cell functions.
• The synthesis of organic molecules by cells is called anabolism, and
their breakdown, catabolism.

Physiology-A 83
 Chemical Reactions

Chemical reactions involve

• (1) the breaking of chemical bonds in reactant molecules, followed by
• (2) the making of new chemical bond to form the product molecules.
• For example, a chemical reaction that occurs in the blood in the lungs,
which permits the lungs to rid the body of carbon dioxide.

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 Chemical Reactions

• Determinants of Reaction Rates

• The rate of a chemical reaction (in other words, how many molecules
of product formed per unit of time) can be determined by measuring
the change in the concentration of reactants or products per unit of
time.
• The lower the concentration of reactants, the slower the reaction
simply because there are fewer molecules available to react and the
likelihood of any two reactants encountering each other is low.

Physiology-A 85
 Chemical Reactions

• For a chemical reaction to occur, reactant molecules must acquire

enough energy—the activation energy—to overcome the mutual
repulsion of the electrons surrounding the atoms in each molecule.
• Temperature is the third factor influencing reaction rates.The higher
the temperature, the faster molecules move and the greater their
impact when they collide.One reason that increasing the temperature
increases a reaction rate is that reactants have a better chance of
acquiring sufficient activation energy.
• A catalyst is a substance or molecule that interacts with one or
more reactants , resulting in a decrease in the activation energy
required to transform the reactants into products.

Physiology-A 86
 Enzymes
• Enzymes are protein molecules, an enzyme can be defined as a
biological catalyst. ( some RNA molecules possess catalytic activity,
the number of reactions they catalyze is very small).
• To function, an enzyme must come into contact with reactants, which
are called substrates in the case of enzyme-mediated reactions.
• Two models have been proposed to describe the interaction of an
enzyme with its substrate(s). In one,
• the enzyme and substrate(s) fit together in a ―lock-and-key‖
configuration.
• In another model, the substrate itself induces a shape change in the
active site of the enzyme, which results in a highly specific binding
interaction (―induced-fit model‖)

Physiology-A 87
Enzymes

Physiology-A 88
 Enzymes

Cofactors
• Many enzymes are inactive without small amounts of other substances
known as cofactors.
• In some cases, the cofactor is a trace metal, such as magnesium,
iron, zinc, or copper. Binding of one of the metals to an enzyme alters
the enzyme’s conformation so that it can interact with the substrate;
this is a form of allosteric modulation.
• In other cases, the cofactor is an organic molecule that directly
participates as one of the substrates in the reaction, in which case the
cofactor is termed a coenzyme.

Physiology-A 89
 Enzymes

• Coenzymes are derived from several members of a special class of

nutrients known as vitamins. For example, the coenzymes NAD+

(nicotinamide adenine dinucleotide) and FAD (flavin adenine

dinucleotide) are derived from the B vitamins niacin and riboflavin,

respectively.

Physiology-A 90
 Regulation Of Enzyme-mediated Reaction

Substrate Concentration
• Substrate concentration may be altered as a result of factors that alter
the supply of a substrate from outside a cell.
• For example, there may be changes in its blood concentration due to
changes in diet .
• Intracellular substrate concentration can also be altered by cellular
reactions that either utilize the substrate, and thus decrease its
concentration, or synthesize the substrate, and thereby increase its
concentration.
• The rate of an enzyme-mediated reaction increases as the substrate
concentration increases.

Physiology-A 91
 Regulation Of Enzyme-mediated Reaction

• Enzyme Concentration
• At any substrate concentration, including saturating concentrations,
the rate of an enzyme-mediated reaction can be increased by
increasing the enzyme concentration.
• In most metabolic reactions, the substrate concentration is much
greater than the concentration of enzyme available to catalyze the
reaction.
• If the number of enzyme molecules is doubled, twice as many active
sites will be available to bind substrate and twice as many substrate
molecules will be converted to product

Physiology-A 92
 Regulation Of Enzyme-mediated Reaction

• Enzyme Activity
• A change in enzyme activity occurs when either allosteric or covalent
modulation alters the properties (for example, the structure) of the
enzyme’s active site.
• Such modulation alters the rate at which the binding site converts
substrate to product, the affinity of the binding site for substrate, or
both.
• The modulator molecules that allosterically alter enzyme activities
may be product molecules of other cellular reactions. The result is that
the overall rates of metabolism can adjust to meet various metabolic
demands.

Physiology-A 93
 Regulation Of Enzyme-mediated Reaction

• In covalent modulation, enzyme activity is mediated by protein kinase

enzymes that are themselves activated by various chemical signals the

cell receives from, for example, a hormone.

Physiology-A 94
 Multienzyme Reactions

• The sequence of enzyme-mediated reactions leading to the formation

of a particular product is known as a metabolic pathway.
• For example, the 19 reactions that break glucose down to carbon
dioxide and water constitute the metabolic pathway for glucose
catabolism.
• Because different enzymes have different concentrations and activities,
it would be extremely unlikely that the reaction rates of all these steps
would be exactly the same.
• Consequently, one step is likely to be slower than all the others. This
step is known as the rate limiting reaction in a metabolic pathway

Physiology-A 95
Multienzyme Reactions

Physiology-A 96
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 97
 PHYSIOLOGY-A
PHARM 313

Lecture # 06 :Cellular Metabolism

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3 ATP

4. Cellular Energy Transfer

5. Carbohydrate Metabolism

Physiology-A 99
 Learning Objectives

After this lecture, students will be able to:

• Describe the synthesis and function of ATP in body.
• Describe different processes involved in energy transfer.
• Describe the metabolism of carbohydrates.

Physiology-A 100
 Introduction

• Living organisms require the constant expenditure of energy to

maintain their complex structures and processes.
• Central to life processes are chemical reactions that are coupled, so
that the energy released by one reaction is incorporated into the
products of another reaction.
• Bioenergetics refers to the flow of energy in living systems.
Organisms maintain their highly ordered structure and life-sustaining
activities through the constant expenditure of energy obtained
ultimately from the environment.

Physiology-A 101
 ATP

• In the presence of oxygen, a cell breaks down glucose to yield carbon

dioxide and water, energy is released.
• Some of this energy is in the form of heat, but a cell cannot use heat
energy to perform its functions.
• The remainder of the energy is transferred to the nucleotide adenosine
triphosphate (ATP), comprised of an adenine molecule, a ribose
molecule, and three phosphate groups .
• ATP is the primary molecule that stores energy transferred from the
breakdown of carbohydrates, fats, and proteins.

Physiology-A 102
 ATP

• Energy released from organic molecules is used to add phosphate

groups to molecules of adenosine. This stored energy can then be
released upon hydrolysis:
• ATP + H2O ⎯ ⎯→ ADP + Pi + H+ + Energy
• The products of the reaction are adenosine diphosphate (ADP),
inorganic phosphate (Pi), and H+. Among other things, the energy
derived from the hydrolysis of ATP is used by cells for

Physiology-A 103
 ATP

Among other things, the energy derived from the hydrolysis of ATP is
used by cells for
(1) the production of force and movement, as in muscle contraction;
(2) active transport of molecules across membranes; and
(3) synthesis of the organic molecules used in cell structures and
functions.

Physiology-A 104
 Cellular Energy Transfer

• Glycolysis
• Glycolysis (from the Greek glycos, “sugar,” and lysis,
“breakdown”) is a pathway that partially catabolizes carbohydrates,
primarily glucose.
• It consists of 10 enzymatic reactions that convert a six-carbon
molecule of glucose into two three-carbon molecules of pyruvate, the
ionized form of pyruvic acid

• Glucose + 2 ADP + 2 Pi + 2 NAD+ ______2 Pyruvate + 2 ATP + 2

NADH + 2 H+ + 2 H2O

Physiology-A 105
 Cellular Energy Transfer

• Krebs Cycle

• It utilizes molecular fragments formed during carbohydrate, protein, and fat

breakdown; it produces carbon dioxide, hydrogen atoms (half of which are

bound to coenzymes), and small amounts of ATP.

• The enzymes for this pathway are located in the inner mitochondrial

compartment, the matrix.

Physiology-A 106
 Cellular Energy Transfer

1 )VANDER’S HUMAN PHYSIOLOGY: THE MECHANISMS OF

BODY FUNCTION, FIFTEENTH EDITION , ERIC P. WIDMAIER ,
HERSHEL RAFF, KEVIN T. STRANG

2 )HUMAN PHYSIOLOGY , FIFTEENTH EDITION ,STUART IRA

FOX.

Physiology-A 107
 Cellular Energy Transfer

Oxidative Phosphorylation
• The energy transferred to ATP is derived from the energy released
when hydrogen ions combine with molecular oxygen to form water.
• The hydrogen comes from the NADH + H+ and FADH2 coenzymes
generated by the Krebs cycle, by the metabolism of fatty acids (see the
discussion that follows), and—to a much lesser extent—during
glycolysis. The net reaction is
• 1/2 O2 + NADH + H+___________ H2O + NAD+ + Energy

Physiology-A 108
Cellular Energy Transfer

Physiology-A 109
 Carbohydrate Metabolism

• The breakdown of glucose to pyruvate or lactate by way of the

glycolytic pathway, and the metabolism of pyruvate to carbon dioxide
and water by way of the Krebs cycle and oxidative phosphorylation.
• The amount of energy released during the catabolism of glucose to
carbon dioxide and water is 686 kcal/mol of glucose:
• C6H12O6 + 6 O2 ⎯→ 6 H2O + 6 CO2 + 686 kcal/mol
• The majority of ATP molecules glucose catabolism produces—up to
34 ATP per molecule—form during oxidative phosphorylation from
the hydrogens generated at various steps during glucose breakdown.
• In the absence of oxygen only two molecules of ATP can form from
the breakdown of glucose to lactate

Physiology-A 110
 Carbohydrate Metabolism

• Glycogen Storage
• A small amount of glucose can be stored in the body to provide a
reserve supply for use when glucose is not being absorbed into the
blood from the small intestine.
• Glucose Synthesis
Glucose can be synthesized in the liver and to a lesser extent the
kidneys from intermediates derived from the catabolism of glycerol (a
sugar alcohol) and some amino acids. This process of generating new
molecules of glucose from noncarbohydrate precursors is known as
gluconeogenesis.

Physiology-A 111
Carbohydrate Metabolism

Physiology-A 112
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 113
 PHYSIOLOGY-A
PHARM 313

Lecture # 07:Cellular Metabolism

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

2. Objectives of the lecture

3. Fat Metabolism

4. Protein and Amino Acid Metabolism

5. Essential Nutrients

Physiology-A 115
 Learning Objectives

After this lecture, students will be able to:

• Describe catabolism of triglycerides.
• Describe the synthesis of non-essential amino acids.
• Define essential nutrients and explain different types of essential
nutrients.

Physiology-A 116
 Fat Metabolism

• Fat Catabolism
• Triglyceride (fat) consists of three fatty acids bound to glycerol . Fat
typically accounts for approximately 80% of the energy stored in the
body .
• Under resting conditions, approximately half the energy used by
muscle, the liver, and the kidneys is derived from the catabolism of
fatty acids.
• The breakdown of a fatty acid is initiated by linking a molecule of
coenzyme A to the carboxyl end of the fatty acid. This initial step is
accompanied by the breakdown of ATP to AMP and two Pi.

Physiology-A 117
 Fat Metabolism

• The coenzyme-A derivative of the fatty acid then proceeds through a series

of reactions, collectively known as beta oxidation,

• Which splits off a molecule of acetyl coenzyme A from the end of the fatty

acid and transfers two pairs of hydrogen atoms to coenzymes (one pair to

FAD and the other to NAD+). The hydrogen atoms from the coenzymes

then enter the oxidative-phosphorylation pathway to form ATP.

Physiology-A 118
Fat Metabolism

Physiology-A 119
 Fat Metabolism

• Fat Synthesis
• The synthesis of fatty acids occurs by reactions that are almost the
reverse of those that degrade them.
• The enzymes in the synthetic pathway are in the cytosol, whereas the
enzymes catalyzing fatty acid breakdown are in the mitochondria.
• Once the fatty acids are formed, triglycerides can be synthesized by
linking fatty acids to each of the three hydroxyl groups in glycerol,
more specifically, to a phosphorylated form of glycerol called glycerol
3-phosphate.
• The synthesis of triglyceride is carried out by enzymes associated
with the membranes of the smooth endoplasmic reticulum.

Physiology-A 120
 Protein And Amino Acid Metabolism

• Protein catabolism requires only a few enzymes, collectively called

proteases, to break the peptide bonds between amino acids (a process
called proteolysis.
• Amino acids can be catabolized to provide energy for ATP synthesis,
and they can also provide intermediates for the synthesis of a number
of molecules other than proteins.
• Once the nitrogen-containing aminobgroup is removed, the remainder
of most amino acids can be metabolized to intermediates capable of
entering either the glycolytic pathway or the Krebs cycle.

Physiology-A 121
 Protein And Amino Acid Metabolism

• Oxidative Deamination
• If there are more amino acids than are needed for protein synthesis, the
amine group from glutamic acid may be removed and excreted as urea
in the urine . The metabolic pathway that removes amine groups from
amino acids—leaving a keto acid and ammonia (which is converted to
urea)—is known as oxidative deamination.
• Once the nitrogen-containing amino group is removed, the remainder
of most amino acids can be metabolized to intermediates capable of
entering either the glycolytic pathway or the Krebs cycle.

Physiology-A 122
 Protein And Amino Acid Metabolism

Transamination
• Keto acids can be converted to amino acids by the addition of an
amine (NH 2 ) group. This amine group is usually obtained by
―cannibalizing‖ another amino acid; in this process, a new amino acid
is formed as the one that was cannibalized is converted to a new keto
acid.
• This type of reaction, in which the amine group is transferred from one
amino acid to form another, is called transamination

Physiology-A 123
 Protein And Amino Acid Metabolism

• Each transamination reaction is catalyzed by a specific enzyme (a

transaminase) that requires vitamin B 6 (pyridoxine) as a coenzyme.
• The amine group from glutamic acid, for example, may be transferred
to either pyruvic acid or oxaloacetic acid. The former reaction is
catalyzed by the enzyme alanine transaminase (ALT). the latter
reaction is catalyzed by aspartate transaminase (AST).
• These enzyme names reflect the fact that the addition of an amine
group to pyruvic acid produces the amino acid alanine; the addition of
an amine group to oxaloacetic acid produces the amino acid known as
aspartic acid.

Physiology-A 124
Protein And Amino Acid Metabolism

Physiology-A 125
 Essential Nutrients

• About 50 substances required for normal or optimal body function

cannot be synthesized by the body or are synthesized in amounts

inadequate to keep pace with the rates at which they are broken down

or excreted. Such substances are known as essential nutrients.

Physiology-A 126
Essential Nutrients

Physiology-A 127
Essential Nutrients

Physiology-A 128
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 129
 PHYSIOLOGY-A
PHARM 313

Lecture # 08 :Genetic Information And Protein Synthesis

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Genetic Code

4. Protein Synthesis

5. Protein Degradation

Physiology-A 131
 Learning Objectives

After this lecture, students will be able to:

• Define genetic code.
• Explain how RNA is produced within the nucleus.
• Explain how RNA directs the synthesis of proteins in genetic
translation.
• Describe the role of ubiquitin and the proteasome in protein
degradation.

Physiology-A 132
 Introduction

• The importance of proteins in physiology cannot be overstated.

Proteins are involved in all physiological processes, from cell
signaling to tissue remodeling to organ function.
• This section describes how cells synthesize, degrade, and, in some
cases, secrete proteins .
• In order for a gene to be expressed, it first must be used as a guide, or
template, in the production of a complementary strand of messenger
RNA.
• This mRNA is then itself used as a guide to produce a particular type
of protein whose sequence of amino acids is determined by the
sequence of base triplets (codons) in the mRNA.

Physiology-A 133
 Genetic Code

• The genetic code is a universal language used by all living cells.

• For example, the triplets specifying the amino acid tryptophan are the same

in the DNA of a bacterium, an amoeba, a plant, and a human being.

• Although the same triplets are used by all living cells, the messages they

spell out—the sequences of triplets that encodes a specific protein—vary

from gene to gene in each organism.

Physiology-A 134
 Genetic Code

• Although the information coded in genes is always first transcribed into

RNA, there are several classes of RNA required for protein synthesis—

including messenger RNA, ribosomal RNA, and transfer RNA.

• Only messenger RNA directly codes for the amino acid sequences of

proteins, even though the other RNA classes participate in the overall

process of protein synthesis

Physiology-A 135
 Protein Synthesis

• Genetic information flows from DNA to RNA and then to protein. The
Process of transferring genetic information from DNA to RNA in the
nucleus is known as transcription.
• The process that uses the coded information in RNA to assemble a
protein in the cytoplasm is known as translation.
• Transcription: mRNA Synthesis
• the two polynucleotide chains in DNA are linked together by hydrogen
bonds between specific pairs of bases: A−T and C−G. To initiate RNA
synthesis, the two antiparallel strands of the DNA double helix must
separate so that the bases in the exposed DNA can pair with the bases
in free ribonucleotide triphosphates.

Physiology-A 136
 Protein Synthesis

• The ribonucleotides paired with this strand of DNA are linked by RNA
polymerase to form a primary RNA transcript containing a sequence of
bases complementary to the template strand of the DNA base
sequence.
• RNA splicing removes the intron-derived regions, which contain
noncoding sequences, in the primary RNA transcript and splices
together the exon-derived regions, which encode specific amino acids,
producing a molecule of mature mRNA.

Physiology-A 137
 Protein Synthesis

1 )VANDER’S HUMAN PHYSIOLOGY: THE MECHANISMS OF

BODY FUNCTION, FIFTEENTH EDITION , ERIC P. WIDMAIER ,
HERSHEL RAFF, KEVIN T. STRANG

2 )HUMAN PHYSIOLOGY , FIFTEENTH EDITION ,STUART IRA

FOX.

Physiology-A 138
 Protein Synthesis

• Translation: Polypeptide Synthesis

• The mRNA moves through the pores in the nuclear envelope into the
cytoplasm
• In the cytoplasm, mRNA binds to a ribosome, the cell organelle that
contains the enzymes and other components required for the
translation of mRNA into protein.
• Ribosomes
• A ribosome is a complex particle composed of about 70 to 80 different
proteins in association with a class of RNA molecules known as
ribosomal RNA (rRNA).

Physiology-A 139
 Protein Synthesis

Transfer RNA
• The key to tRNA’s function in protein synthesis is its ability to
combine with both a specific amino acid and a codon in ribosome-
bound mRNA specific for that amino acid.
• This permits tRNA to act as the link between an amino acid and the
mRNA codon for that amino acid.
• A three-nucleotide sequence at the end of one of the loops of tRNA
can base-pair with a complementary codon in mRNA. This tRNA
three-letter code sequence is appropriately known as an anticodon.

Physiology-A 140
 Protein Synthesis

Protein Assembly
• The process of assembling a polypeptide chain based on an mRNA
message involves three stages— initiation, elongation, and
termination. The initiation of synthesis occurs when a tRNA
containing the amino acid methionine binds to the small ribosomal
subunit.
• A number of proteins known as initiation factors are required to
establish an initiation complex . Following the initiation process, the
protein chain is elongated by the successive addition of amino acids .
A ribosome has two binding sites for tRNA.

Physiology-A 141
 Protein Synthesis

• Site 1 holds the tRNA linked to the portion of the protein chain that
has been assembled up to this point, and site 2 holds the tRNA
containing the next amino acid to be added to the chain
• Following the formation of the peptide bond, the tRNA at site 1 is
released from the ribosome, and the tRNA at site 2—now linked to the
peptide chain—is transferred to site 1.
• The ribosome moves down one codon along the mRNA, making room
for the binding of the next amino acid–tRNA molecule.
• This process is repeated over and over as amino acids are added to the
growing peptide chain .

Physiology-A 142
 Protein Synthesis

• When the ribosome reaches a termination sequence in mRNA (called a

stop codon) specifying the end of the protein, the link between the

polypeptide chain and the last tRNA is broken, and the completed

protein is released from the ribosome.

Physiology-A 143
Protein Synthesis

Physiology-A 144
Protein Synthesis

Physiology-A 145
 Protein Degradation

• The concentration of a particular protein in a cell at a particular time

depends upon not only its rate of synthesis but also its rates of
degradation and/or secretion.
• A denatured (unfolded) protein is more readily digested than a protein
with an intact conformation. Proteins can be targeted for degradation
by the attachment of a small peptide, ubiquitin, to the protein.
• This peptide directs the protein to a protein complex known as a
proteasome, which unfolds the protein and breaks it down into
small peptides.
• Degradation is an important mechanism for confining the activity of a
given protein to a precise window of time.

Physiology-A 146
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 147
 PHYSIOLOGY-A
PHARM 313

Lecture # 09 :Genetic Information And Protein Synthesis

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Objectives of the lecture

2. Protein Secretion

3. Replication of Genetic Information

4. Expression of Genetic Information

5. Cancer

6. Genetic Engineering

Physiology-A 149
 Learning Objectives

LAfter this lecture, students will be able to:

• Describe how proteins may be modified after genetic translation.
• Describe the functions of the Golgi complex.
• Explain the relationship between the genetic mutation and cancer
• Describe the role of Genetic Engineering in disease treatment.

Physiology-A 150
 Protein Secretion

• Proteins are large, charged molecules that cannot diffuse through the
lipid bilayer of plasma membranes.
• Special mechanisms are required to insert them into or move them
through membranes.
• Proteins destined to be secreted from a cell or to become integral
membrane proteins are recognized during the early stages of protein
synthesis.
• For such proteins, the first 15 to 30 amino acids that emerge from the
surface of the ribosome act as a recognition signal, known as the
signal sequence or signal peptide.

Physiology-A 151
 Protein Secretion

• The signal sequence binds to a complex of proteins known as a signal

recognition particle, which temporarily inhibits further growth of the
polypeptide chain on the ribosome.
• The signal recognition particle then binds to a specific membrane
protein on the surface of the rough endoplasmic reticulum.
• This binding restarts the process of protein assembly, and the growing
polypeptide chain is fed through a protein complex in the endoplasmic
reticulum membrane into the lumen of the reticulum

Physiology-A 152
 Protein Secretion

• Within the lumen of the endoplasmic reticulum, enzymes remove the

signal sequence from most proteins, so this portion is not present in
the final protein.
• In addition, carbohydrate groups are sometimes linked to various side
chains in the proteins.
• Following these modifications, portions of the reticulum membrane
bud off, forming vesicles that contain the newly synthesized proteins.
• These vesicles migrate to the Golgi apparatus and fuse with the Golgi
membranes

Physiology-A 153
 Protein Secretion

• Within the Golgi apparatus, the protein may undergo further

modifications.
• While in the Golgi apparatus, the many different proteins that have
been funneled into this organelle are sorted out according to their final
destinations.
• This sorting involves the binding of regions of a particular protein to
specific proteins in the Golgi membrane that are destined to form
vesicles targeted to a particular destination.
• The proteins are packaged into vesicles that bud off the surface of the
Golgi membrane.

Physiology-A 154
 Protein Secretion

• Some of the vesicles travel to the plasma membrane, where they fuse

with the membrane and release their contents to the extracellular fluid,

a process known as exocytosis.

• Other vesicles may dock and fuse with lysosome membranes

Physiology-A 155
Protein Secretion

Physiology-A 156
 Replication Of Genetic Information

• Replication of DNA is semiconservative; each DNA strand serves as

template for the production of a new strand.
• 1. The strands of the original DNA molecule gradually separate
along their entire length and, through complementary base pairing,
form a new complementary strand.
• 2. In this way, each DNA molecule consists of one old and one new
strand. During the G1 phase of the cell cycle, the DNA directs the
synthesis of RNA, and hence that of proteins. During the S phase of
the cycle, DNA directs the synthesis of new DNA and replicates
itself. After a brief time gap (G2), the cell begins mitosis (theM
stage of the cycle).

Physiology-A 157
 Replication Of Genetic Information

• 1. Mitosis consists of the following phases: interphase, prophase,

metaphase, anaphase, and telophase.
• 2. In mitosis, the homologous chromosomes line up single file and
are pulled by spindle fibers to opposite poles.
• 3. This results in the production of two daughter cells, each
containing 46 chromosomes, just like the parent cell.

Physiology-A 158
 Expression Of Genetic Information

• The primary structure of the protein (its amino acid sequence) is

determined by the sequence of bases in mRNA.
• The base sequence of mRNA has been previously determined by the
sequence of bases in the region of the DNA (the gene) that codes for
the mRNA.
• Genetic expression therefore occurs in two stages: first genetic
transcription (synthesis of RNA) and then genetic translation
(synthesis of protein).

Physiology-A 159
Expression Of Genetic Information

Physiology-A 160
 Cancer

• Tumors are described as benign when they are relatively slow growing
and limited to a specific location (warts, for example).
• Malignant tumors grow more rapidly and undergo metastasis, a term
that refers to the dispersion of tumor cells and the resultant seeding
of new tumors in different locations. The term cancer, as it is
generally applied, refers to malignant tumors.
• Cancer is now believed to result from altered expression of oncogenes
(genes that promote cancer), tumor-suppressor genes, and genes that
code for microRNA.
• Oncogenes are altered forms of normal proto-oncogenes, which code
for proteins that control cell division and apoptosis

Physiology-A 161
 Genetic Engineering

• Genetic engineering, also called Genetic modification or Genetic

manipulation, is the direct manipulation of an
organism's genes using biotechnology.
• It is a set of technologies used to change the genetic makeup of cells,
including the transfer of genes within and across species boundaries to
produce improved or novel organisms.
• By knocking out genes responsible for certain conditions it is possible
to create animal model organisms of human diseases.
• As well as producing hormones, vaccines and other drugs genetic
engineering has the potential to cure genetic diseases through gene
therapy.

Physiology-A 162
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 163
 PHYSIOLOGY-A
PHARM 313

Lecture # 10 :Movement of Molecules across Cell Membranes

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Diffusion

4. Mediated-Transport Systems

Physiology-A 165
 Learning Objectives

After this lecture, students will be able to:

• Define diffusion and describe the factors that influence the rate of
diffusion.
• Describe the characteristics of carrier-mediated transport, and
distinguish between simple diffusion, facilitated diffusion, and active
transport.

Physiology-A 166
 Introduction

• The movements of molecules and ions between the various cell

organelles and the cytosol, and between the cytosol and the
extracellular fluid, depend on the properties of these membranes.
• The rates at which different substances move through membranes vary
considerably and in some cases can be controlled—increased or
decreased—in response to various signals.
• This section focuses upon the transport functions of membranes, with
emphasis on the plasma membrane.
• The controlled movement of solutes such as ions, glucose, and gases,
as well as the movement of water across membranes, is of profound
importance in physiology.

Physiology-A 167
 Diffusion

• This movement of molecules from one location to another solely as a

result of their random thermal motion is known as simple diffusion.
• In living tissue, however, diffusion often occurs across cellular
membranes, including between intracellular and extracellular fluid
compartments.
• For example, cellular waste products of metabolism diffuse outward
from cells, whereas nutrients diffuse into cells; in both cases, the
solutes must cross the plasma membrane. most polar molecules diffuse
into cells very slowly .

Physiology-A 168
 Diffusion

• All, nonpolar molecules diffuse much more rapidly across plasma

membranes—that is, they have large permeability coefficients.
• The reason is that nonpolar molecules can dissolve in the nonpolar
regions of the membrane occupied by the fatty acid chains of the
membrane phospholipids.
• Oxygen, carbon dioxide, fatty acids, and steroid hormones are
examples of nonpolar molecules. proteins form ion channels that
allow ions to diffuse across the membrane.
• An important characteristic of ion channels is that they can show
selectivity for the type of ion or ions that can diffuse through them.

Physiology-A 169
 Mediated-transport Systems

• protein, a site exposed to the solute on one surface of the membrane .

A portion of the transporter then undergoes a change in shape,
exposing this same binding site to the solution on the opposite side of
the membrane. The dissociation of the substance from the transporter
binding site completes the process of moving the material through the
membrane.
• Four factors determine the magnitude of solute flux through a
mediated-transport system:
• (1) the solute concentration, (2) the affinity of the transporters for the
solute, (3) the number of transporters in the membrane, and (4) the
rate at which the conformational change in the transport protein
occurs.

Physiology-A 170
Mediated-transport Systems

Physiology-A 171
 Facilitated Diffusion

• In facilitated diffusion the net flux of a molecule across a membrane

always proceeds from higher to lower concentration, or ―downhill‖
across a membrane.
• The key difference between these two processes is that facilitated
diffusion uses a transporter to move solute, Neither simple diffusion
nor facilitated diffusion is directly coupled to energy (ATP) derived
from metabolism.
• Among the most important facilitated-diffusion systems in the body
are those that mediate the transport of glucose across plasma
membranes.

Physiology-A 172
Facilitated Diffusion

Physiology-A 173
 Active Transport

• Active transport differs from facilitated diffusion in that it uses

energy to move a substance uphill across a membrane—that is, against
the substance’s concentration gradient . As with facilitated diffusion,
active transport requires a substance to bind to the transporter in the
membrane.
• Primary Active Transport The hydrolysis of ATP by a transporter
provides the energy for primary active transport. The transporter itself
is an enzyme called ATPase that catalyzes the breakdown of ATP and,
in the process, phosphorylates itself. Phosphorylation of the
transporter protein is a type of covalent modulation that changes the
conformation of the transporter and the affinity of the transporter’s
solute binding site.

Physiology-A 174
 Active Transport

• One of the best-studied examples of primary active transport is the

movement of sodium and potassium ions across plasma membranes by
the Na+/K+-ATPase pump. This transporter, which is present in all
cells, moves Na+ from intracellular to extracellular fluid, and K+ in
the opposite direction. In both cases, the movements of the ions are
against their respective concentration gradients.
Secondary Active Transport In secondary active transport, the
movement of an ion down its electrochemical gradient is coupled to
the transport of another molecule, often an organic nutrient like
glucose or an amino acid. Thus, transporters that mediate secondary
active transport have two binding sites, one for an ion—typically but
not always Na+—and another for a second substance.

Physiology-A 175
 Active Transport

• In example, the electrochemical gradient for Na+ is directed into the

cell because of the higher concentration of Na+ in the extracellular
fluid and the excess negative charges inside the cell.
• The other solute to be transported, however, must move against its
concentration gradient, uphill into the cell.
• High-affinity binding sites for Na+ exist on the extracellular surface of
the transporter. Binding of Na+ increases the affinity of the binding
site for the transported solute.
• The transporter then undergoes a conformational change, which
exposes both binding sites to the intracellular side of the membrane

Physiology-A 176
Active Transport

Physiology-A 177
Active Transport

Physiology-A 178
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 179
 PHYSIOLOGY-A
PHARM 313

Lecture # 11 :Movement of Molecules across Cell Membranes

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Osmosis

4. Endocytosis

5. Exocytosis

6. Epithelial Transport

Physiology-A 181
 Learning Objectives

After this lecture, students will be able to:

• Define osmosis, describe the conditions required for it to occur.
• Explain the nature and significance of hypotonic, isotonic, and
hypertonic solutions.
• Explain bulk and epithelial transport.

Physiology-A 182
 Introduction

• The movements of molecules and ions between the various cell

organelles and the cytosol, and between the cytosol and the
extracellular fluid, depend on the properties of these membranes.
• The rates at which different substances move through membranes
vary considerably and in some cases can be controlled—increased or
decreased—in response to various signals.
• This section focuses upon the transport functions of membranes, with
emphasis on the plasma membrane.
• The controlled movement of solutes such as ions, glucose, and gases,
as well as the movement of water across membranes, is of profound
importance in physiology.

Physiology-A 183
 Osmosis

• Osmosis is the net diffusion of water (the solvent) across the

membrane. For osmosis to occur, the membrane must be selectively
permeable; that is, it must be more permeable to water molecules than
to at least one species of solute.
• There are thus two requirements for osmosis:
• (1) there must be a difference in the concentration of a solute on the
two sides of a selectively permeable membrane; and
• (2) the membrane must be relatively impermeable to the solute.
Solutes that cannot freely pass through the membrane can promote the
osmotic movement of water and are said to be osmotically active.

Physiology-A 184
Osmosis

Physiology-A 185
Osmosis

186
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 Endocytosis

• Three common types of endocytosis may occur in a cell. These are

pinocytosis (―cell drinking‖), phagocytosis (―cell eating‖), and receptor-
mediated endocytosis .
• Pinocytosis
• In pinocytosis, also known as fluid endocytosis, an endocytotic vesicle
encloses a small volume of extracellular fluid.
• This process is nonspecific because the vesicle simply engulfs the water in
the extracellular fluid along with whatever solutes are present.
• These solutes may include ions, nutrients, or any other small extracellular
molecule. Large macromolecules, other cells, and cell debris do not
normally enter a cell via this process.

Subject Name 187

Physiology-A 187
 Endocytosis

• Phagocytosis
• In phagocytosis, cells engulf bacteria or large particles such as
cell debris from damagssues.
• This form of endocytosis, extensions of the plasma membrane
called pseudopodia fold around the surface of the particle,
engulfing it entirely. The pseudopodia, with their engulfed
contents, then fuse into large vesicles called phagosomes that
are internalized into the cell. Phagosomes migrate to and fuse
with lysosomes in the cytoplasm, and the contents of the
phagosomes are then destroyed by lysosomal enzymes and other
molecules.
• Most cells undergo pinocytosis, only a few special types of cells,
such as those of the immune system , carry out phagocytosis.
Subject Name 188
Physiology-A 188
 Endocytosis

• Receptor-Mediated Endocytosis
• In contrast to pinocytosis and phagocytosis, most cells have the
capacity to specifically take up molecules that are important for
cellular function or structure.
• In receptor-mediated endocytosis, certain molecules in the
extracellular fluid bind to specific proteins on the outer surface of the
plasma membrane. These proteins are called receptors, and each one
recognizes one ligand with high affinity

Subject Name 189

Physiology-A 189
 Exocytosis

• Exocytosis performs two functions for cells:

• (1) It provides a way to replace portions of the plasma membrane that
endocytosis has removed and, in the process, a way to add new
membrane components as well; and
• (2) it provides a route by which membraneimpermeable molecules
(such as protein hormones) that the cell synthesizes can be secreted
into the extracellular fluid. From the Golgi apparatus, the proteins to
be secreted travel to the plasma membrane in vesicles from which they
can be released into the extracellular fluid by exocytosis.

Subject Name 190

Physiology-A 190
 Exocytosis

• The secretion of substances by exocytosis is triggered in most cells by

stimuli that lead to an increase in cytosolic Ca2+ concentration in the
cell.
• Exocytosis is the mechanism by which most neurons communicate
with each other through the release of neurotransmitters stored in
secretory vesicles that merge with the plasma membrane.
• It is also a major way in which many types of hormones are released
from endocrine cells into the extracellular fluid.
• Cells that actively undergo exocytosis recover bits of membrane via a
process called compensatory endocytosis.
Subject Name 191
Physiology-A 191
Endocytosis & Exocytosis

Subject Name 192

Physiology-A 192
 Epithelial Transport

• Epithelial cells line hollow organs or tubes and regulate the absorption or
secretion of substances across these surfaces.
• One surface of an epithelial cell generally faces a hollow or fluid-filled tube
or chamber, and the plasma membrane on this side is referred to as the
apical membrane (also known as the luminal membrane) .
• The plasma membrane on the opposite surface rests upon a basement
membrane and is usually adjacent to a network of blood vessels; it is
referred to as the basolateral membrane (also known as the serosal
membrane). The two pathways by which a substance can cross a layer of
epithelial cells are
• (1) the paracellular pathway, in which diffusion occurs between the
adjacent cells of the epithelium; and
Subject Name 193
Physiology-A 193
 Epithelial Transport

• (2) the transcellular pathway, in which a substance moves into an

epithelial cell across either the apical or basolateral membrane,
diffuses through the cytosol, and exits across the opposite membrane.
• During transcellular transport, the movement of molecules through the
plasma membranes of epithelial cells occurs via the pathways
(diffusion and mediated transport) already described for movement
across membranes.

Subject Name 194

Physiology-A 194
Epithelial Transport

Subject Name 195

Physiology-A 195
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 196
 PHYSIOLOGY-A
PHARM 313

Lecture # 12 :Homeostatic Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. General Characteristics of Homeostatic Control Systems

4. Components of Homeostatic Control System

Physiology-A 198
 Learning Objectives

After this lecture, students will be able to:

• Define homeostasis, and identify the components of negative feedback
loops.
• Explain the role of antagonistic effectors in maintaining homeostasis,
and the nature of positive feedback loops.

Physiology-A 199
 Introduction

• Most of the common physiological variables found in healthy

organisms such as humans—blood pressure; body temperature; and
blood-borne factors such as oxygen, glucose, and sodium ions, for
example—are maintained within a predictable range.
• This is true despite external environmental conditions that may be far
from constant Originally, homeostasis was defined as a state of
reasonably stable balance between physiological variables such as
those just described.
• There probably is no such thing as a physiological variable that is
constant over long periods of time. In fact, some variables undergo
fairly dramatic swings around an average value during the course of a
day, yet are still considered to be in balance.
Physiology-A 200
General Characteristics Of Homeostatic Control
Systems

• The activities of cells, tissues, and organs must be regulated and

integrated with each other so that any change in the extracellular fluid
initiates a reaction to correct the change. The compensating
mechanisms that mediate such responses are performed by
homeostatic control systems.
• Consider an example of the regulation of body temperature. subject is
a resting, lightly clad man in a room having a temperature of 20°C and
moderate humidity. His internal body temperature is 37°C, and he is
losing heat to the external environment

Subject Name 201

Physiology-A 187
General Characteristics of Homeostatic Control
Systems

• Because it is at a lower temperature. However, the chemical reactions

occurring within the cells of his body are producing heat at a rate
equal to the rate of heat loss.
• Under these conditions, the body undergoes no net gain or loss of
heat, and the body temperature remains constant. The system is in a
steady state, defined as a system in which a particular variable—
temperature, in this case— is not changing but in which energy—in
this case, heat—must be added continuously to maintain a stable,
homeostatic condition.
• The steady-state temperature in this example is known as the set point
of the thermoregulatory system.

Subject Name 202

Physiology-A 188
General Characteristics of Homeostatic Control
Systems

203
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Physiology 203
General Characteristics of Homeostatic Control
Systems

Subject Name 204

Physiology-A 204
 Feedback Systems

• The thermoregulatory system just described is an example of a

negative feedback system, in which an increase or decrease in the
variable being regulated brings about responses that tend to move the
variable in the direction opposite (―negative‖ to) the direction of the
original change. Thus, in example, a decrease in body temperature led
to responses that tended to increase the body temperature—that is,
move it toward its original value.
• Negative feedback has a vital part in the checks and balances on most
physiological variables. Negative feedback may occur at the organ,
cellular, or molecular level. For instance, negative feedback regulates
many enzymatic processes.

Subject Name 205

Physiology-A 205
Negative feedback system

Subject Name 206

Physiology-A 206
 Negative feedback system

• The production of adenosine triphosphate (ATP) within cells is a good

example of a chemical process regulated by feedback.
• Normally, glucose molecules are enzymatically broken down inside
cells to release some of the chemical energy that was contained in the
bonds of the molecule.
• This energy is then stored in the bonds of ATP. The energy from ATP
can later be tapped by cells to power such functions as muscle
contraction, cellular secretions, and transport of molecules across cell
membranes.
• As ATP accumulates in the cell, however, it inhibits the activity of
some of the enzymes involved in the breakdown of glucose.
Subject Name 207
Physiology-A 207
 Positive feedback system

Positive feedback accelerates a process, leading to an ―explosive‖ system.

This is counter to the general physiological principle of homeostasis,
because positive feedback has no obvious means of stopping. Positive
feedback is much less common in nature than negative feedback.
• When a blood vessel is ruptured, damaged cells in the vessel wall release
chemicals into the blood that attract platelets to the injury site and activate
them.
• Platelets are fragments of cells that stick together and form clots that seal a
wound. Once activated, moreover, platelets themselves then release
additional activating chemicals, which activate more platelets, and so on.
• The cycle finally stops once the wound is fully sealed with a clot.

Subject Name 208

Physiology-A 208
Positive feedback system

Subject Name 209

Physiology-A 209
Components of Homeostatic Control Systems

• The pathway mediating a reflex is known as the reflex arc, and its
components .
• A stimulus is defined as a detectable change in the internal or external
environment, such as a change in temperature, plasma potassium
concentration, or blood pressure.
• A receptor detects the environmental change. stimulus acts upon a
receptor to produce asignal that is relayed to an integrating center.
• The signal travels between the receptor and the integrating center along
the afferent pathway (the general term afferent means “to carry to,” in
this case, to the integrating center).
• An integrating center often receives signals from many receptors, some of
which may respond to quite different types of stimuli.

Subject Name 210

Physiology-A 210
Components of Homeostatic Control Systems

• The output of an integrating center reflects the net effect of the total
afferent input; that is, it represents an integration of numerous bits of
information.
• The output of an integrating center is sent to the last component of the
system, whose change in activity constitutes the overall response of the
system. This component is known as an effector.
• The information going from an integrating center to an effector is like a
command directing the effector to alter its activity. This information travels
along the efferent pathway (the general term efferent means ―to carry
away from,‖ in this case, away from the integrating center).
• Almost all body cells can act as effectors in homeostatic reflexes. Muscles
and glands, however, are the major effectors of biological control systems.
Subject Name 211
Physiology-A 211
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 212
 PHYSIOLOGY-A
PHARM 313

Lecture # 13 :Cellular Communication

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. The Role of Intercellular Chemical

Messengers in Homeostasis

4. Processes Related to Homeostasis

Physiology-A 214
 Learning Objectives

After this lecture, students will be able to:

• Distinguish between synaptic, endocrine, and paracrine regulation.
• Describe the conditions under which acclimatization occurs.
• Define circadian rhythm.
• Draw a figure illustrating the balance concept in homeostasis.

Physiology-A 215
 Introduction

• Essential to reflexes and local homeostatic responses—and therefore

to homeostasis—is the ability of cells to communicate with one
another.
• In this way, cells in the brain, for example, can be made aware of the
status of activities of structures outside the brain, such as the heart, and
help regulate those activities to meet new homeostatic challenges.
• In the majority of cases, intercellular communication is performed by
chemical messengers.
• There are four categories of such messengers: hormones,
neurotransmitters, paracrine, and autocrine substances

Physiology-A 216
The Role of Intercellular Chemical Messengers in
Homeostasis

• A hormone is a chemical messenger that enables the hormone-

secreting cell to communicate with other cells with the blood acting as
the delivery system.
• The cells on which hormones act are called the hormone’s target
cells.
• Hormones are produced in and secreted from endocrine glands or
in scattered cells. that are distributed throughout an organ. They have
important functions in essentially all physiological processes,
including growth, reproduction, metabolism, mineral balance, and
blood pressure, and several of them are produced whenever
homeostasis is threatened.
Subject Name 217
Physiology-A 202
The Role of Intercellular Chemical Messengers in
Homeostasis

• Neurotransmitters are chemical messengers that are released from

the endings of neurons onto other neurons, muscle cells, or gland cells.
• A neurotransmitter diffuses through the extracellular fluid separating
the neuron and its target cell; it is not released into the blood like a
hormone.
• They form the signaling basis of many reflexes, as well as having a
vital role in the compensatory responses to a wide variety of
challenges, such as the requirement for increased heart and lung
function during exercise.

Subject Name 218

Physiology-A 203
The Role of Intercellular Chemical Messengers in
Homeostasis

• Chemical messengers involved in local communication between cells

are known as paracrine substances (or agents).
• Paracrine substances are synthesized by cells and released, once given
the appropriate stimulus, into the extracellular fluid. They then diffuse
to neighboring cells, some of which are their target cells. Given this
broad definition, neurotransmitters could be classified as a subgroup of
paracrine substances, but by convention they are not.
• Once they have performed their functions, paracrine substances are
generally inactivated by locally existing enzymes and therefore they
do not enter the bloodstream in large quantities. Paracrine substances
are produced throughout the body;
219
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Physiology 219
The Role of Intercellular Chemical Messengers in
Homeostasis

• An example of their key role in homeostasis that is their ability to

fine-tune the amount of acid produced by cells of the stomach in
response to eating food.
• There is one category of local chemical messengers that are not
intercellular messengers—that is, they do not communicate between
cells.
• The chemical is secreted by a cell into the extracellular fluid and then
acts upon the very cell that secreted it. Such messengers are called
autocrine substances (or agents) .
• Frequently, a messenger may serve both paracrine and autocrine
functions simultaneously—that is,
Subject Name 220
Physiology-A 220
The Role of Intercellular Chemical Messengers in
Homeostasis

• Molecules of the messenger released by a cell may act locally on

adjacent cells as well as on the same cell that released the messenger.
• This type of signaling is commonly found in cells of the immune
system .
• A particular messenger may sometimes function as a neurotransmitter,
a hormone, or a paracrine or autocrine substance. Norepinephrine, for
example, is not only a neurotransmitter in the brain; it is also produced
as a hormone by cells of the adrenal glands.

Subject Name 221

Physiology-A 221
The Role of Intercellular Chemical Messengers in
Homeostasis

• There are two important types of chemical communication between

cells that do not require secretion of chemical messanger.
• The first type occurs via gap junctions, which are physical linkages
connecting the cytosol between two cells . Molecules can move
directly from one cell to an adjacent cell through gap junctions without
entering the extracellular fluid.

Subject Name 222

Physiology-A 222
The Role of Intercellular Chemical Messengers in
Homeostasis

• In the second type, the chemical messenger is not actually released from the
cell producing it but rather is located in the plasma membrane of that cell.
• For example, the messenger may be a plasma membrane protein with part
of its structure extending into the extracellular space. When the cell
encounters another cell type capable of responding to the message, the two
cells link up via the membranebound protein.
• This type of signaling, sometimes termed juxtacrine, is of particular
importance in the growth and differentiation of tissues as well as in the
functioning of cells that protect the body against pathogens . It is one way in
which similar types of cells ―recognize‖ each other and form tissues.

Subject Name 223

Physiology-A 223
 Processes Related to Homeostasis

• Adaptation and Acclimatization

• The term adaptation denotes a characteristic that favors survival
in specific environments.
• Common examples in humans include the ability of certain individuals
to digest lactose in milk, and the protection against the dangerous
effects of ultraviolet light conferred by dark skin.
• Homeostatic control systems are also inherited biological adaptations
and allow an individual to adapt to encountered environmental
changes. sweating in response to heat exposure as an example of an
adaptation
Subject Name 224
Physiology-A 224
 Processes Related to Homeostasis

• In some cases the effectiveness of such systems can be enhanced by

prolonged exposure to an environmental change. This type of
adaptation—the improved functioning of an already existing
homeostatic system—is known as acclimatization.

Subject Name 225

Physiology-A 225
 Processes Related to Homeostasis

• Biological Rhythms, a striking characteristic of many body functions is the

rhythmic changes they manifest.

• The most common type is the circadian rhythm, which cycles

approximately once every 24 h. Waking and sleeping, body temperature,

hormone concentrations in the blood, the excretion of ions into the urine,

and many other functions undergo circadian variation;

Subject Name 226

Physiology-A 226
Processes Related to Homeostasis

Subject Name 227

Physiology-A 227
Balance of Chemical Substances in the Body

Subject Name 228

Physiology-A 228
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 229
 PHYSIOLOGY-A
PHARM 313

Lecture # 14 :Cellular Communication

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Objectives of the lecture

2. Receptors

3. Types of Receptors

Physiology-A 231
 Learning Objectives

After this lecture, students will be able to:

• Identify the location of the receptor proteins for different regulatory
molecules.
• Classify plasma membrane receptors according to the signal
transduction pathways they initiate .

Physiology-A 232
 Receptors

• The first step in the action of any intercellular chemical messenger is

the binding of the messenger to specific target-cell proteins known as
receptors (or receptor proteins).
• a chemical messenger is a ligand, and the receptor has a binding site
for that ligand.

Subject Name 233

Physiology-A 217
 Types of Receptors

• They are proteins or glycoproteins located either in the cell’s plasma

membrane or inside the cell, either in the cytosol or the nucleus.
• The plasma membrane is the much more common location, because a
very large number of messengers are watersoluble and therefore
cannot diffuse across the lipid-rich (hydrophobic) plasma membrane.
• a much smaller number of lipid-soluble messengers diffuse through
membranes to bind to their receptors located inside the cell.

Subject Name 234

Physiology-A 218
 Plasma Membrane Receptors

• Plasma membrane receptors are transmembrane proteins; that is,

they span the entire membrane thickness.
• transmembrane proteins, a plasma membrane receptor has
hydrophobic segments within the membrane, one or more hydrophilic
segments extending out from the membrane into the extracellular
fluid, and other hydrophilic segments extending into the intracellular
fluid.
• Arriving chemical messengers bind to the extracellular parts of the
receptor; the intracellular regions of the receptor are involved in signal
transduction events.
235
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Physiology 235
 Intracellular Receptors

• intracellular receptors are not located in membranes but exist in either

the cytosol or the cell nucleus .e.g. receptor for such as cholesterol-
derived steroid hormones .
• Like plasma membrane receptors, they have a segment that binds the
messenger and other segments that act as regulatory sites.
• they have a segment that binds to DNA, unlike plasma membrane
receptors.
• plasma membrane receptors can transduce signals without interacting
with DNA, whereas all intracellular receptors transduce signals
through interactions with genes.
Subject Name 236
Physiology-A 236
Characteristics Of Receptors

Subject Name 237

Physiology-A 237
Characteristics Of Receptors

Subject Name 238

Physiology-A 238
Characteristics Of Receptors

Subject Name 239

Physiology-A 239
Characteristics Of Receptors

Subject Name 240

Physiology-A 240
Characteristics Of Receptors

Subject Name 241

Physiology-A 241
Types Of Receptors

Subject Name 242

Physiology-A 242
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 243
 PHYSIOLOGY-A
PHARM 313

Lecture # 15 :Cellular Communication

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Objectives of the lecture

2. Signal Transduction Pathways

Physiology-A 245
 Learning Objectives

After this lecture, students will be able to:

• Describe the signal transduction pathway that lipid-soluble messengers
use.
• Classify plasma membrane receptors according to the signal
transduction pathways they initiate
• Describe the function of plasma membrane G proteins.

Physiology-A 246
 Signal Transduction Pathways

• The binding of a messenger to a receptor changes the conformation

(tertiary structure; of the receptor, which activates it. This initiates a
sequence of events in the cell leading to the cell’s response to that
messenger, a process called signal transduction.
• The binding of a messenger to its receptor causes a change in the
conformation (tertiary structure) of the receptor. This event, known as
receptor activation, is the initial step leading to the cell’s responses
to the messenger.

Subject Name 247

Physiology-A 230
 Signal Transduction Pathways

These cellular responses can take the form of changes in

(1) the permeability, transport properties, or electrical state of the
plasma membrane;
(2) metabolism;
(3) secretory activity;
(4) rate of proliferation and differentiation; or
(5) contractile or other activities.

Subject Name 248

Physiology-A 231
 Signal Transduction Pathways

• Pathways Initiated by Lipid-Soluble Messengers

• Lipid-soluble messengers include hydrophobic substances such as
steroid hormones and thyroid hormone. Their receptors belong to a
large family of intracellular receptors called nuclear receptors.

249
Subject Name–A
Physiology 249
 Signal Transduction Pathways

• In a few cases, the inactive receptors are located in the cytosol and
move into the nucleus after binding their ligand.
• Most of the inactive receptors, however, already reside in the cell
nucleus, where they bind to and are activated by their respective
ligands.
• In both cases, receptor activation leads to altered rates of transcription
of one or more genes in a particular cell.

Subject Name 250

Physiology-A 250
 Signal Transduction Pathways

• The messenger diffuses out of capillaries from plasma to the

interstitial fluid (refer back to From there, the messenger diffuses
across the lipid bilayers of the plasma membrane and nuclear envelope
to enter the nucleus and bind to the receptor there.
• The activated receptor complex then functions in the nucleus as a
transcription factor.
• Cortisol, for example, inhibits transcription of several genes whose
protein products mediate inflammatory responses that occur following
injury or infection; for this reason, cortisol has important anti-
inflammatory effects.
Subject Name 251
Physiology-A 251
Signal Transduction Pathways

Subject Name 252

Physiology-A 252
Pathways Initiated by Water-Soluble Messengers

• Water-soluble messengers cannot readily enter cells by diffusion

through the lipid bilayer of the plasma membrane.

• they exert their actions on cells by binding to the extracellular portion

of receptor proteins embedded in the plasma membrane.

• Water-soluble messengers include most polypeptide hormones,

• neurotransmitters, and paracrine and autocrine compounds

Subject Name 253

Physiology-A 253
Pathways Initiated by Water-Soluble Messengers

• The extracellular chemical messengers (such as hormones or

neurotransmitters) that reach the cell and bind to their specific plasma
membrane receptors are often referred to as first messengers.

• Second messengers, then, are substances that enter or are generated

in the cytoplasm as a result of receptor activation by the first
messenger.

Subject Name 254

Physiology-A 254
Pathways Initiated by Water-Soluble Messengers

• Some water-soluble extracellular messengers open chemically gated

receptor-channels.

• Some water-soluble extracellular messengers activate receptor-

enzymes.

• water-soluble extracellular chemical messengers activate second-

messenger pathways via G-protein-coupled receptors.

Subject Name 255

Physiology-A 255
Pathways Initiated by Water-Soluble Messengers

Subject Name 256

Physiology-A 256
Pathways Initiated by Water-Soluble Messengers

Subject Name 257

Physiology-A 257
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 258
 PHYSIOLOGY-A
PHARM 313

Lecture # 16 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Structure and Maintenance of Neurons

4. References

Physiology-A 260
 Learning Objectives

After this lecture, students will be able to:

• Describe the Structure and Maintenance of Neurons

Physiology-A 261
 Introduction

• The functional unit of the nervous system is the individual cell, or

neuron. Neurons operate by generating electrical signals that move
from one part of the cell to another part of the same cell or to
neighboring cells. In most neurons, the electrical signal causes the
release of chemical messengers— neurotransmitters—to
communicate with other cells. Most neurons serve as integrators
because their output reflects the balance of inputs they receive from up
to hundreds of thousands of other neurons. The other major cell types
of the nervous system are nonneuronal cells called glial cells. These
cells generally do not participate directly in electrical
communication from cell to cell as do neurons, but they are very
important in various supportive functions for neurons.

Physiology-A 262
 Structure And Maintenance Of Neurons

• Most neurons contain a cell body and two types of processes—

dendrites and axons.

• A neuron’s cell body (or soma) contains the nucleus and ribosomes
and thus has the genetic information and machinery necessary for
protein synthesis.

Subject Name 263

Physiology-A 263
Structure and Maintenance of Neurons

Subject Name 264

Physiology-A 264
 Structure and Maintenance of Neurons

• The dendrites are a series of highly branched outgrowths of the cell

that receive incoming information from other neurons.

• Branching dendrites increase a cell’s surface area—Thus, the structure

of dendrites in the CNS increases a cell’s capacity to receive signals
from many other neurons.

265
Subject Name–A
Physiology 265
Structure and Maintenance of Neurons

Subject Name 266

Physiology-A 266
Structure and Maintenance of Neurons

Subject Name 267

Physiology-A 267
 Structure and Maintenance of Neurons

• The axons of many neurons are covered by sheaths of myelin which

usually consists of 20 to 200 layers of highly modified plasma
membrane wrapped around the axon by a nearby supporting cell.
• In the brain and spinal cord, these myelinforming cells are a type of
glial cell called oligodendrocytes.
• Each oligodendrocyte may branch to form myelin on as many as 40
axons.

Subject Name 268

Physiology-A 268
 Structure and Maintenance of Neurons

• In the PNS, glial cells called Schwann cells form individual myelin
sheaths surrounding 1- to 1.5-mm-long segments at regular intervals
along some axons.

• The spaces between adjacent sections of myelin where the axon’s

plasma membrane is exposed to extracellular fluid are called the nodes
of Ranvier.

Subject Name 269

Physiology-A 269
 Structure and Maintenance of Neurons

• To maintain the structure and function of the axon, various organelles

and other materials must move as far as 1 meter between the cell body
and the axon terminals.

• This movement, termed axonal transport, depends on a scaffolding

of microtubule ―rails‖ running the length of the axon and specialized
types of motor proteins known as kinesins and dyneins

Subject Name 270

Physiology-A 270
 Structure and Maintenance of Neurons

• At one end, these double-headed motor proteins bind to their cellular

cargo, and the other end uses energy derived from the hydrolysis of
ATP to ―walk‖ along the microtubules.

• Kinesin transport mainly occurs from the cell body toward the axon
terminals (anterograde) and is important in moving nutrient
molecules, enzymes, mitochondria, neurotransmitter-filled vesicles,
and other organelles.

Subject Name 271

Physiology-A 271
Structure and Maintenance of Neurons

Subject Name 272

Physiology-A 272
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 273
 PHYSIOLOGY-A
PHARM 313

Lecture # 17 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Functional Classes of Neuron

4. Glial Cells

5. REFERENCES

Physiology-A 275
 Learning Objectives

After this lecture, students will be able to:

• Describe the different types of neurons and supporting cells, and
identify their functions.

Physiology-A 276
 Introduction

• The functional unit of the nervous system is the individual cell, or

neuron. Neurons operate by generating electrical signals that move
from one part of the cell to another part of the same cell or to
neighboring cells. In most neurons, the electrical signal causes the
release of chemical messengers— neurotransmitters—to
communicate with other cells. Most neurons serve as integrators
because their output reflects the balance of inputs they receive from up
to hundreds of thousands of other neurons. The other major cell types
of the nervous system are nonneuronal cells called glial cells. These
cells generally do not participate directly in electrical
communication from cell to cell as do neurons, but they are very
important in various supportive functions for neurons.

Physiology-A 277
 Functional Classes of Neurons

• Neurons can be divided into three functional classes:

• afferent neurons,
• efferent neurons, and
• interneurons .
• Afferent neurons convey information from the tissues and organs
of the body toward the CNS.
• Efferent neurons convey information away from the CNS to effector
cells like muscle, gland, or other cell types.
• Interneurons connect neurons within the CNS.
Subject Name 278
Physiology-A 278
 Functional Classes of Neurons

• As a rough estimate, for each afferent neuron entering the CNS, there
are 10 efferent neurons and 200,000 interneurons. Thus, the great
majority of neurons are interneurons.
• At their peripheral ends (the ends farthest from the CNS), afferent
neurons have sensory receptors, which respond to Various physical
or chemical changes in their environment by generating electrical
signals in the neuron.

Subject Name 279

Physiology-A 279
 Functional Classes of Neurons

• Afferent neurons propagate electrical signals from their receptors into

the brain or spinal cord.
• Interneurons lie entirely within the CNS. They account for over 99%
of all neurons and have a wide range of physiological properties,
shapes, and functions.
• The number of interneurons interposed between specific afferent and
efferent neurons varies according to the complexity of the action they
control.

280
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Physiology 280
 Functional Classes of Neurons

• The anatomically specialized junction between two neurons where one

neuron alters the electrical and chemical activity of another is called a
synapse.

• At most synapses, the signal a term that also includes the chemicals
efferent neurons use to communicate with effector cells (e.g., a muscle
cell).

Subject Name 281

Physiology-A 281
 Functional Classes of Neurons

• The neurotransmitters released from one neuron alter the receiving

neuron by binding with specific protein receptors on the membrane of
the receiving neuron.

• Most synapses occur between an axon terminal of one neuron and a

dendrite or the cell body of a second neuron.

Subject Name 282

Physiology-A 282
Functional Classes of Neurons

Subject Name 283

Physiology-A 283
Functional Classes of Neurons

Subject Name 284

Physiology-A 284
 Glial Cells

• Neurons account for only about half of the cells in the human CNS.
the remainder are glial cells (glia, “glue”).
• Glial cells surround the axon and dendrites of neurons, and provide
them with physical and metabolic support.
glial cells retain the capacity to divide throughout life. Consequently,
many CNS tumors actually originate from glial cells rather than from
neurons.

Subject Name 285

Physiology-A 285
 Glial Cells

• There are several different types of glial cells found in the CNS .

• One type is the oligodendrocyte, which forms the myelin sheath of

CNS axons.

• A second type of CNS glial cell, the astrocyte, helps regulate the
composition of the extracellular fluid in the CNS by removing
potassium ions and neurotransmitters around synapses.

Subject Name 286

Physiology-A 286
 Glial Cells

• Astrocytes is to stimulate the formation of tight junctions between the

cells that make up the walls of capillaries found in the CNS.
• This forms the blood–brain barrier, which is a much more selective
filter for addition, astrocytes have many neuronlike characteristics.
• For example, they have ion channels, receptors for certain
neurotransmitters and the enzymes for processing them, and the
capability of generating weak electrical responses.

Subject Name 287

Physiology-A 287
 Glial Cells

• The microglia, a third type of CNS glial cell, are specialized,

macrophage-like cells that perform immune functions in the CNS, and

may also contribute to synapse remodeling and plasticity.

Subject Name 288

Physiology-A 288
 Glial Cells

• Ependymal cells line the fluid-filled cavities within the brain and
spinal cord and regulate the production and flow of cerebrospinal
fluid, which will be described later.

• Schwann cells, the glial cells of the PNS, have most of the properties
of the CNS glia. As mentioned earlier, Schwann cells produce the
myelin sheath of the axons of the peripheral neurons.

Subject Name 289

Physiology-A 289
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 290
 PHYSIOLOGY-A
PHARM 313

Lecture # 18 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Neural Growth and Regeneration

4. Basic Principles of Electricity

5. References

Physiology-A 292
 Learning Objectives

After this lecture, students will be able to:

• Describe the mechanism of neural growth and regeneration.

• Contrast the abilities of intracellular and extracellular fluids and
membrane lipids to conduct electrical current.
• Which two factors involving ion diffusion determine the magnitude of
the resting membrane potential?

Physiology-A 293
 Introduction

• The functional unit of the nervous system is the individual cell, or

neuron. Neurons operate by generating electrical signals that move
from one part of the cell to another part of the same cell or to
neighboring cells. In most neurons, the electrical signal causes the
release of chemical messengers— neurotransmitters—to
communicate with other cells. Most neurons serve as integrators
because their output reflects the balance of inputs they receive from up
to hundreds of thousands of other neurons. The other major cell types
of the nervous system are nonneuronal cells called glial cells. These
cells generally do not participate directly in electrical
communication from cell to cell as do neurons, but they are very
important in various supportive functions for neurons.

Physiology-A 294
 Neural Growth and Regeneration

• If axons are severed, they can repair themselves and restore significant
function provided that the damage occurs outside the CNS and does
not affect the neuron’s cell body.
• After such an injury, the axon segment that is separated from the cell
body degenerates. The part of the axon still attached to the cell body
then gives rise to a growth cone, which grows out to the effector organ
so that function can be restored.

Subject Name 295

Physiology-A 295
 Neural Growth and Regeneration

• Which route the axon follows depends largely on attracting,

supporting, deflecting, or inhibiting influences exerted by several
types of molecules.
• these molecules, such as cell adhesion molecules, reside on the
membranes of the glia and embryonic neurons.
• Others are soluble neurotrophic factors (growth factors for neural
tissue) in the extracellular fluid surrounding the growth cone or its
distant target.

Subject Name 296

Physiology-A 296
Neural Growth and Regeneration

297
Subject Name–A
Physiology 297
 Neural Growth and Regeneration

• Severed axons within the CNS may grow small new extensions, but no
significant regeneration of the axon occurs across the damaged site,
and there are no well-documented reports of significant return of
function. Functional regeneration is prevented either by some basic
difference of CNS neurons or some property of their environment,
such as inhibitory factors associated with nearby glia.
• Researchers are trying a variety of ways to provide an environment
that will support axonal regeneration in the CNS. They are creating
tubes to support regrowth of the severed axons

Subject Name 298

Physiology-A 298
 Neural Growth and Regeneration

• Medical researchers are also attempting to restore function to

or diseased spinal cords and brains by implanting undifferentiated
• stem cells that will develop into new neurons and replace missing
neurotransmitters or neurotrophic factors.
• Initial stem cell research focused on the use of embryonic and fetal
stem cells, which, while yielding promising results, raises ethical
concerns.

Subject Name 299

Physiology-A 299
 Basic Principles of Electricity

• The intracellular fluid contains high concentrations of potassium ions

and ionized nonpenetrating molecules, particularly phosphate
compounds and proteins with negatively charged side chains.
• Separated electrical charges of opposite sign have the potential to do
work if they are allowed to come together. This potential is called an
electrical potential or, because it is determined by the difference in
the amount of charge between two points, a potential difference.

Subject Name 300

Physiology-A 300
Basic Principles of Electricity

• The movement of electrical charge is called a current. The electrical

potential between charges tends to make them flow, producing a
current. the intracellular and extracellular fluids contain many ions and
can therefore carry current.
• Lipids, contain very few charged groups and cannot carry current.
Therefore, the lipid layers of the plasma membrane are regions of high
electrical resistance separating the intracellular fluid and the
extracellular fluid, two low-resistance aqueous compartments.

Subject Name 301

Physiology-A 301
Basic Principles of Electricity

Subject Name 302

Physiology-A 302
Basic Principles of Electricity

Subject Name 303

Physiology-A 303
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 304
 PHYSIOLOGY-A
PHARM 313

Lecture # 19 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. The Resting Membrane Potential

4. Graded Potentials

5. References

Physiology-A 306
 Learning Objectives

After this lecture, students will be able to:

• Which two factors involving ion diffusion determine the magnitude of
the resting membrane potential?
• How the magnitude and duration of a graded potential vary with the
magnitude and duration of a triggering event?

Physiology-A 307
 Introduction

• The functional unit of the nervous system is the individual cell, or

neuron. Neurons operate by generating electrical signals that move
from one part of the cell to another part of the same cell or to
neighboring cells. In most neurons, the electrical signal causes the
release of chemical messengers— neurotransmitters—to
communicate with other cells. Most neurons serve as integrators
because their output reflects the balance of inputs they receive from up
to hundreds of thousands of other neurons. The other major cell types
of the nervous system are nonneuronal cells called glial cells. These
cells generally do not participate directly in electrical
communication from cell to cell as do neurons, but they are very
important in various supportive functions for neurons.

Physiology-A 308
 The Resting Membrane Potential

• At rest, neurons have a potential difference across their plasma

membranes, with the inside of the cell negatively charged with respect
to the outside . This potential is the resting membrane potential
(abbreviated Vm).
• For example, if the inside of a cell has an excess of negative charge
and the potential difference across the membrane has a magnitude of
70 mV, that the membrane potential is −70 mV (inside relative to
outside).

Subject Name 309

Physiology-A 309
 The Resting Membrane Potential

• Nature and Magnitude of the Resting Membrane Potential

• The magnitude of the resting membrane potential in neurons is

generally in the range of −40 to −90 mV. The resting membrane
potential holds steady unless changes in electrical current alter The
magnitude of the resting membrane potential depends mainly on two
factors:

Subject Name 310

Physiology-A 310
 The Resting Membrane Potential

(1) differences in specific ion concentrations in the intracellular and

extracellular fluids; and

(2) differences in membrane permeabilities to the different ions, which

reflect the number of open channels for the different ions in the plasma
membrane.

311
Subject Name–A
Physiology 311
 The Resting Membrane Potential

• The resting membrane potential exists because of a tiny excess of

negative ions inside the cell and an excess of positive ions outside. The
excess negative charges inside are electrically attracted to the excess
positive charges outside the cell, and vice versa.

Subject Name 312

Physiology-A 312
• The leak of Na+ and K+ down their electrochemical gradients through
ion channels is the main factor in determining the resting membrane
potential, but the Na+/K+ -ATPase pump is essential to this process
because it maintains the concentration gradients.

Subject Name 313

Physiology-A 313
The Resting Membrane Potential

Subject Name 314

Physiology-A 314
 Graded Potentials

• Graded potentials are changes in membrane potential that are

confined to a relatively small region of the plasma membrane.

• They are produced when some specific change in the cell’s

environment acts on a specialized region of the membrane.

• They are called graded potentials simply because the magnitude of the
potential change can vary (is ―graded‖).
Subject Name 315
Physiology-A 315
 Graded Potentials

• Whenever a graded potential occurs, charge flows between the place

of origin of this potential and adjacent regions of the plasma
membrane, which are still at the resting potential.

• a small region of a membrane depolarized by transient application

of a chemical signal, briefly opening membrane cation channels and
producing a potential less negative than that of adjacent areas.

Subject Name 316

Physiology-A 316
Graded Potentials

Subject Name 317

Physiology-A 317
Graded Potentials

Subject Name 318

Physiology-A 318
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 319
 PHYSIOLOGY-A
PHARM 313

Lecture # 20 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. Action Potentials

4. Action Potential Mechanism

5. Functional Anatomy of Synapses

6. References

Physiology-A 321
 Learning Objectives

After this lecture, students will be able to:

• List the differences between graded potentials and action potentials.

• Step-by-step, explain how an action potential is produced.

Physiology-A 322
 Introduction

The functional unit of the nervous system is the individual cell, or

neuron. Neurons operate by generating electrical signals that move
from one part of the cell to another part of the same cell or to
neighboring cells. In most neurons, the electrical signal causes the
release of chemical messengers— neurotransmitters—to
communicate with other cells. Most neurons serve as integrators
because their output reflects the balance of inputs they receive from up
to hundreds of thousands of other neurons. The other major cell types
of the nervous system are nonneuronal cells called glial cells. These
cells generally do not participate directly in electrical
communication from cell to cell as do neurons, but they are very
important in various supportive functions for neurons.

Physiology-A 323
 Action Potentials

• Action potentials are very different from graded potentials. They

are large alterations in the membrane potential; the membrane
potential may change by as much as 100 mV.
• For example, a cell might depolarize from −70 to +30 mV, and then
repolarize to its resting potential.
• Action potentials are generally very rapid (as brief as 1–4
milliseconds) and may repeat at frequencies of several hundred per
second.
• The propagation of action potentials down the axon is the mechanism
the nervous system uses to communicate from cell to cell over long
distances.
Subject Name 324
Physiology-A 324
 Action Potentials

• Voltage-Gated Ion Channels

• it is voltage-gated ion channels that give a membrane the ability to
undergo action potentials.
• Ligand-gated ion channels open in response to the binding of
signaling molecules , and
• mechanically gated ion channels open in response to physical
deformation (stretching) of the plasma membranes.
• These types of channels often mediate graded potentials that can serve
as the initiating stimulus for an action potential,.

Subject Name 325

Physiology-A 325
 Action Potentials

• There are dozens of different types of voltage-gated ion channels,

varying by which ion they conduct (for example, Na+, K+, Ca2+, or
Cl−) and in how they behave as the membrane voltage changes.
• Na+ and K+ channels are similar in having sequences of charged
amino acid residues in their structure that make the channels reversibly
change shape in response to changes in membrane potential.
• When the membrane is at a negative potential (for example, at the
resting membrane potential), both types of channels tend to stay
closed, whereas membrane depolarization tends to open them. Two
key differences, however, allow these channels to make different
contributions to the production of action potentials.

326
Subject Name–A
Physiology 326
 Action Potentials

• First, voltage-gated Na+ channels respond faster to changes in

membrane voltage.
• When an area of a membrane is suddenly depolarized, local voltage-
gated Na+ channels open before the voltage-gated K+ channels do,
• and if the membrane is then repolarized to negative voltages, the
voltage-gated K+ channels are also slower to close.
• Na+ channels have an inactivation gate, limits the flux of Na+ by
blocking the channel shortly after depolarization opens it. When the
membrane repolarizes, the channel closes, forcing the inactivation gate
back out of the pore and allowing the channel to return to the closed
state.
Subject Name 327
Physiology-A 327
 Action Potential Mechanism

• During an action potential, transient changes in membrane

permeability allow Na+ and K+ to move down their electrochemical
gradients.
• when a neurotransmitter binds to a specific ligand-gated ion channel
and allows Na+ to enter the cell .
• This initial depolarization stimulates the opening of some voltage-
gated Na+ channels, and further entry of Na+ through those channels
adds to the local membrane depolarization. Na+ entry causes
depolarization, which opens more voltage-gated Na+ channels, which
causes more depolarization, and so on
Subject Name 328
Physiology-A 328
 Action Potential Mechanism

• This process is represented as a rapid depolarization of the membrane

potential (step 3), and it overshoots so that the membrane actually
becomes positive on the inside and negative on the outside.
• As the membrane potential reaches its peak value (step 4), the Na+
permeability abruptly declines as inactivation gates break the cycle of
positive feedback by blocking the open Na+ channels.
• Meanwhile, the depolarized state of the membrane has begun to open
the relatively sluggish voltage-gated K+ channels, and the resulting
increased K+ flux out of the cell rapidly repolarizes the membrane
toward its resting value (step 5)
Subject Name 329
Physiology-A 329
Action Potential Mechanism

Subject Name 330

Physiology-A 330
 Action Potential Mechanism

• The return of the membrane to a negative potential causes

voltagegated Na+ channels to go from their inactivated state back to
the closed state (without opening, as described earlier) and K+
channels to also return to the closed state.
• voltage-gated K+ channels close relatively slowly, immediately after
an action potential there is a period when K+ permeability remains
above resting levels and the membrane is transiently hyperpolarized.

Subject Name 331

Physiology-A 331
 Action Potential Mechanism

• Toward the K+ equilibrium potential (step 6). This portion of the

action potential is known as the afterhyperpolarization.
• Once the voltage-gated K+ channels finally close, , the resting
membrane potential is restored (step 7).
• voltage-gated Na+ channels operate in a positive feedback mode at the
beginning action potential to an end and induce their own closing
through anegative feedback process .

Subject Name 332

Physiology-A 332
Action Potential Mechanism

Subject Name 333

Physiology-A 333
 Functional Anatomy of Synapses

• There are two types of synapses: electrical and chemical.

• Electrical Synapses
• At electrical synapses, the plasma membranes of the presynaptic
and postsynaptic cells are joined by gap junctions . These allow the
local currents resulting from arriving action potentials to flow directly
across the junction through the connecting channels from one neuron
to the other.
• This depolarizes the membrane of the second neuron to threshold,
continuing the propagation of the action potential. One advantage of
electrical synapses is that communication between cells via these
synapses is extremely rapid.
Subject Name 334
Physiology-A 334
Functional Anatomy of Synapses

Subject Name 335

Physiology-A 335
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 336
 PHYSIOLOGY-A
PHARM 313

Lecture # 21 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Functional Anatomy Of Synapses

4. Mechanisms Of Neurotransmitter Release

5. Activation Of The Postsynaptic Cell

6. Synaptic Strength

7. References
Physiology-A 338
 Learning Objectives

After this lecture, students will be able to:

• Describe the structure and function of electrical and chemical
synapses.
• Identify the nature of excitatory and inhibitory postsynaptic potentials
• List ways in which the effectiveness of synapses may be altered

Physiology-A 339
 Introduction

• The functional unit of the nervous system is the individual cell, or

neuron. Neurons operate by generating electrical signals that move
from one part of the cell to another part of the same cell or to
neighboring cells. In most neurons, the electrical signal causes the
release of chemical messengers— neurotransmitters—to
communicate with other cells. Most neurons serve as integrators
because their output reflects the balance of inputs they receive from up
to hundreds of thousands of other neurons. The other major cell types
of the nervous system are nonneuronal cells called glial cells. These
cells generally do not participate directly in electrical
communication from cell to cell as do neurons, but they are very
important in various supportive functions for neurons.

Physiology-A 340
 Functional Anatomy of Synapses

Chemical Synapses
• The axon of the presynaptic neuron ends in slight swellings, the axon
terminals, which hold the synaptic vesicles that contain
neurotransmitter molecules.
• The postsynaptic membrane adjacent to an axon terminal has a high
density of membrane proteins that make up a specialized area called
the postsynaptic density.
• A 10 to 20 nm extracellular space, the synaptic cleft, separates the
presynaptic and postsynaptic neurons and prevents direct propagation
of the current from the presynaptic neuron to the postsynaptic cell.
Subject Name 341
Physiology-A 342
 Functional Anatomy of Synapses

• signals are transmitted across the synaptic cleft by means of a

chemical messenger—a transmitter—released from the presynaptic
axon terminal.
• more than one neurotransmitter may be simultaneously released from
an axon, in which case the additional neurotransmitter is called a
cotransmitter.
• These neurotransmitters have different receptors on the postsynaptic
cell. As we will see shortly, a major advantage of chemical synapses is
that they permit integration of multiple signals arriving at a given cell.

Subject Name 342

Physiology-A 343
Functional Anatomy of Synapses

343
Subject Name–A
Physiology 343
Mechanisms of Neurotransmitter Release

• Prior to activation,many vesicles are docked on the presynaptic

membrane at release regions known as active zones,
• Neurotransmitter release is initiated when an action potential reaches
the presynaptic terminal membrane.
• A key feature of neuron terminals at chemical synapses is that in
addition to the Na+ and K+ channels found in the neuron, they also
possess voltage-gated Ca2+ channels.
• Depolarization during the action potential opens these Ca2+ channels,
and because the electrochemical gradient favors Ca2+ influx, Ca2+
flows into the axon terminal. Calcium ions activate processes that lead
to the fusion of docked vesicles with the synaptic terminal membrane
Subject Name 344
Physiology-A 344
Mechanisms of Neurotransmitter Release

Subject Name 345

Physiology-A 345
Mechanisms of Neurotransmitter Release

• Removal of Neurotransmitter from the Synapse

• Unbound neurotransmitters are removed from the synaptic cleft when
they (1) are actively transported back into the presynaptic axon
terminal for reuse (in a process called reuptake);
• (2) are transported into nearby glial cells where they are degraded;
• (3) diffuse away from the receptor site; or
• (4) are enzymatically transformed into inactive substances, some of
which are transported back into the presynaptic axon terminal for
reuse. The enzymes involved in this last process may be located on the
postsynaptic or presynaptic membrane or within the synaptic cleft.

Subject Name 346

Physiology-A 346
 Activation of the Postsynaptic Cell

• Binding of Neurotransmitters to Receptors

• Neurotransmitters rapidly and reversibly bind to receptors on
theplasma membrane of the postsynaptic cell.
• The activated receptors themselves may be ion channels, which
designates them as ionotropic receptors .
• the receptors may indirectly influence ion channelsthrough a G
protein and/or a second messenger, the result of the binding of
neurotransmitter to receptor is the opening or closing of specific
ligand-gated ion channels in the postsynaptic plasma membrane,
which eventually leads to changes in the membrane potential in that
neuron.
Subject Name 347
Physiology-A 347
 Activation of the Postsynaptic Cell

• Excitatory Chemical Synapses

• The two kinds of chemical synapses—excitatory and inhibitory— are
differentiated by the effects of the neurotransmitter on the postsynaptic
cell. Whether the effect is excitatory or inhibitory depends on the type
of ion channel influenced by the neurotransmitter when it binds to its
receptor.
• At an excitatory chemical synapse, the postsynaptic response to the
neurotransmitter is a depolarization, bringing the membrane potential
closer to threshold. The usual effect of the activated receptor on the
postsynaptic membrane at such synapses is to open nonselective
channels that are permeable to Na+ and K+.

Subject Name 348

Physiology-A 348
 Activation of the Postsynaptic Cell

• These ions then are free to move according to the electrical and
concentration gradients across the membrane. Thus, the net movement
of positive ions is into the postsynaptic cell, causing a slight
depolarization. This membrane potential change is called an
excitatory postsynaptic potential (EPSP).
• Inhibitory Chemical Synapses
At inhibitory chemical synapses, the potential change in the
postsynaptic neuron is generally a hyperpolarizing graded potential
called an inhibitory postsynaptic potential (IPSP, ). Alternatively,
there may be no IPSP but rather stabilization of the membrane
potential at its existing value.

Subject Name 349

Physiology-A 349
 Synaptic Strength

• In either case, activation of an inhibitory synapse lessens the

likelihood that the postsynaptic cell will depolarize to threshold and
generate an action potential. At an inhibitory synapse, the activated
receptors on the postsynaptic membrane open Cl− or K+ channels;
Na+ permeability is not affected
• Synaptic Strength
• The effectiveness or strength of a given synapse is influenced by both
presynaptic and postsynaptic mechanisms.

Subject Name 350

Physiology-A 350
 Synaptic Strength

• Presynaptic Mechanisms
• A presynaptic terminal does not release a constant amount of
neurotransmitter every time it is activated.One reason for this variation
involves Ca2+ concentration.
• Calcium ions that have entered the terminal during previous action
potentials are pumped out of the cell or (temporarily) into intracellular
organelles.
• The greater the amount of neurotransmitter released, the greater the
number of ion channels opened in the postsynaptic membrane and the
larger the amplitude of the EPSP or IPSP in the postsynaptic cell
Subject Name 351
Physiology-A 351
 Synaptic Strength

• Axo–axonic synapses such as A in can alter the Ca2+ concentration in

axon terminal B or even affect neurotransmitter synthesis there.
• Some receptors on the presynaptic terminal are not associated with
axo–axonic synapses.
• they are activated by neurotransmitters or other chemical messengers
released by nearby neurons or glia or even by the axon terminal itself.
• autoreceptors provide an important feedback mechanism that the
neuron can use to regulate its own neurotransmitter output.

Subject Name 352

Physiology-A 352
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 353
 PHYSIOLOGY-A
PHARM 313

Lecture # 22 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Neurotransmitters And Neuromodulators

4. Neuroeffector Communication

5. Central Nervous System: Brain

6. Central Nervous System: Spinal Cord

7. References
Physiology-A 355
 Learning Objectives

After this lecture, students will be able to:

• Discuss differences between neurotransmitters and neuromodulators
• Make an organizational chart showing the brain.
• Draw a cross section of the spinal cord.

Physiology-A 356
 Introduction

• The central nervous system (CNS), consisting of the brain and

spinal cord , receives input from sensory neurons and directs the
activity of motor neurons that innervate muscles and glands. The
association neurons within the brain and spinal cord are in a position,
as their name implies, to associate appropriate motor responses with
sensory stimuli, and thus to maintain homeostasis in the internal
environment and the continued existence of the organism in a
changing external environment. Further, the central nervous systems
of all vertebrates (and most invertebrates) are capable of at least
rudimentary forms of learning and memory. This capability— most
highly developed in the human brain—permits behavior to be
modified by experience.

Physiology-A 357
 Neurotransmitters and Neuromodulators

• The word modulation is used for these complex responses, and the
messengers that cause them are called neuromodulators.
• Neuromodulators are often synthesized by the presynaptic cell and
coreleased with the neurotransmitter.
• Many hormones, paracrine factors, and messengers used by the
immune system serve as neuromodulators.
• Neuromodulators often modify the postsynaptic cell’s response to
specific neurotransmitters, amplifying or dampening the effectiveness
of ongoing synaptic activity , they may change the presynaptic cell’s
synthesis, release, reuptake, or metabolism of a transmitter.
Subject Name 358
Physiology-A 6
 Neurotransmitters and Neuromodulators

• The receptors for neurotransmitters influence ion channels that directly

affect excitation or inhibition of the postsynaptic cell.
• These mechanisms operate within milliseconds. Receptors for
neuromodulators, more often bring about changes in metabolic
processes in neurons, often via G proteins coupled to second-
messenger systems.
• Such changes, occur over minutes, hours, or even days, include
alterations in enzyme activity or, through influences on DNA
transcription. Thus, neurotransmitters are involved in rapid
communication, whereas neuromodulators tend to be associated with
slower events such as learning, development, and motivational states.

Subject Name 359

Physiology-A 7
Neurotransmitters and Neuromodulators

360
Subject Name–A
Physiology 360
 Neuroeffector Communication

• Many neurons of the PNS end, however, not at synapses on other

neurons but at neuroeffector junctions on muscle, gland, and other
cells.
• The neurotransmitters released by these efferent neurons’ terminals or
varicosities provide the link by which electrical activity of the nervous
system regulates effector cell activity.
• The events that occur at neuroeffector junctions are similar to those at
synapses between neurons. The neurotransmitter is released from the
efferent neuron upon the arrival of an action potential at the neuron’s
axon terminals or varicosities. The neurotransmitter
Subject Name 361
Physiology-A 361
 Neuroeffector Communication

• Then diffuses to the surface of the effector cell, where it binds to

receptors on that cell’s plasma membrane.
• The receptors may be directly under the axon terminal or varicosity, or
they may be some distance away so that the diffusion path the
neurotransmitter follows is long.
• The receptors on the effector cell may be either ionotropic or
metabotropic. The response (such as altered muscle contraction or
glandular secretion) of the effector cell.

Subject Name 362

Physiology-A 362
 Central Nervous System: Brain

• During development, the CNS forms from a long tube.

• As the anterior part of the tube, which becomes the brain, folds during
its continuing formation, initially three different regions become
apparent, identified as the forebrain, midbrain, and hindbrain .
• These regions continue to develop, forming subdivisions. The
forebrain develops into two major subdivisions, the cerebrum and the
diencephalon.
• The midbrain remains as a single major division.
• The hindbrain develops into three parts: the pons, medulla oblongata,
and the cerebellum.

Subject Name 363

Physiology-A 363
 Central Nervous System: Brain

• The pons, medulla oblongata, and the midbrain are heavily

interconnected and share many similar functions; for that reason and
their anatomical location, they are considered together as the
brainstem.
• The brain also contains four interconnected cavities, the cerebral
ventricles, which are filled with fluid and which provide support
for the brain

Subject Name 364

Physiology-A 364
Central Nervous System: Brain

Subject Name 365

Physiology-A 365
Central Nervous System: Brain

Subject Name 366

Physiology-A 366
Central Nervous System: Brain

Subject Name 367

Physiology-A 367
 Central Nervous System: Spinal Cord

• The central butterfly-shaped area (in cross section) of gray matter is

composed of interneurons, the cell bodies and dendrites of efferent
neurons, the entering axons of afferent neurons, and glial cells.
• The regions of gray matter projecting toward the back of the body are
called the dorsal horns, whereas those oriented toward the front are
the ventral horns.
• The gray matter is surrounded by white matter, which consists of
groups of myelinated axons. These tracts run longitudinally through
the cord, some descending to relay information from the brain to the
spinal cord, others ascending to transmit information to the brain. rd.
Subject Name 368
Physiology-A 368
Central Nervous System: Spinal Cord

Subject Name 369

Physiology-A 369
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 370
 PHYSIOLOGY-A
PHARM 313

Lecture # 23 :Neural Control Mechanisms

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Peripheral Nervous System

4. Protective Elements Associated With The Brain

5. Cerebrospinal Fluid

6. The Blood–brain Barrier

7. References
Physiology-A 372
 Learning Objectives

After this lecture, students will be able to:

• Describe the structure of the sympathetic and parasympathetic
divisions of the autonomic system.
• Explain the role of Cerebrospinal Fluid and The Blood–Brain Barrier
in CNS.

Physiology-A 373
 Introduction

• The central nervous system (CNS), consisting of the brain and

spinal cord , receives input from sensory neurons and directs the
activity of motor neurons that innervate muscles and glands. The
association neurons within the brain and spinal cord are in a position,
as their name implies, to associate appropriate motor responses with
sensory stimuli, and thus to maintain homeostasis in the internal
environment and the continued existence of the organism in a
changing external environment. Further, the central nervous systems
of all vertebrates (and most invertebrates) are capable of at least
rudimentary forms of learning and memory. This capability— most
highly developed in the human brain—permits behavior to be
modified by experience.

Physiology-A 374
 Peripheral Nervous System

• The PNS consists of 43 paired nerves—12 pairs of cranial nerves and

31 pairs of spinal nerves, as well as neurons found in the
gastrointestinal tract wall.
• Most nerves contain the axons of both afferent and efferent neurons.
• The efferent division of the PNS is divided into somatic and
autonomic parts.
• The somatic fibers innervate skeletal muscle cells and release the
neurotransmitter acetylcholine.

Subject Name 375

Physiology-A 375
Peripheral Nervous System

Subject Name 376

Physiology-A 376
 Peripheral Nervous System

• Autonomic Nervous System I. The autonomic nervous system

innervates cardiac and smooth muscle, glands, gastrointestinal tract
neurons, and other tissue cells.
• Each autonomic pathway consists of a preganglionic neuron with its
cell body in the CNS and a postganglionic neuron with its cell body in
an autonomic ganglion outside the CNS.
• II. The autonomic nervous system is divided into sympathetic and
parasympathetic components. Enteric neurons within the walls of the
GI tract are also sometimes considered as a separate subcategory of
the autonomic system.
377
Subject Name–A
Physiology 377
 Peripheral Nervous System

• Preganglionic neurons in both the sympathetic and parasympathetic

divisions release acetylcholine; the postganglionic parasympathetic
neurons release mainly acetylcholine; and the postganglionic
sympathetic neurons release mainly norepinephrine.
• III. The adrenal medulla is a hormone-secreting part of the
sympathetic nervous system and secretes mainly epinephrine.
• IV. Many effector organs that the autonomic nervous system
innervates receive dual innervation from the sympathetic and
parasympathetic divisions of the autonomic nervous system.

Subject Name 378

Physiology-A 378
Peripheral Nervous System

Subject Name 379

Physiology-A 379
Peripheral Nervous System

Subject Name 380

Physiology-A 380
Protective Elements Associated with the Brain

• Cerebrospinal Fluid
• Ependymal cells make up a specialized epithelial structure called the
choroid plexus, which produces CSF at a rate that completely
replenishes it about three times per day.
• It circulates through the brain’s interconnected ventricular system to
the brainstem, where it passes through small openings out to the
subarachnoid space surrounding the brain and spinal cord.
• Aided by circulatory, respiratory, and postural pressure changes, the
fluid ultimately flows to the top of the outer surface of the brain,
where most of it enters the bloodstream through one-way valves in
large veins.
Subject Name 381
Physiology-A 381
 Cerebrospinal Fluid

• CSF can provide important diagnostic information for diseases of the

nervous system, including meningitis.
• CSF samples are generally obtained by inserting a large needle into
the spinal canal below the level of the second lumbar vertebra, where
the spinal cord ends Thus, the CNS literally floats in a cushion of
cerebrospinal fluid.
• The brain and spinal cord are soft, delicate tissues, they are somewhat
protected from sudden and jarring movements by this shock-absorbing
fluid. If the outflow is obstructed, cerebrospinal fluid accumulates,
causing hydrocephalus (“water on the brain”).
Subject Name 382
Physiology-A 382
 Cerebrospinal Fluid

• Elevation of pressure in the ventricles causes compression of the

brain’s blood vessels, which may lead to inadequate blood flow to the
neurons, neuronal damage, and cognitive dysfunction.
• CSF may have some nutritive functions for the brain, the brain—like
all tissues—receives its nutrients from the blood. Under normal
conditions, glucose is the only substrate metabolized by the brain to
supply its energy requirements, and most of the energy from the
oxidative breakdown of glucose is transferred to ATP.
• The brain’s glycogen stores are negligible, so it depends upon a
continuous blood supply of glucose and oxygen.
Subject Name 383
Physiology-A 383
Cerebrospinal Fluid

Subject Name 384

Physiology-A 384
 The Blood–Brain Barrier

• The blood–brain barrier is formed by the cells that line the smallest
blood vessels in the brain.
• It has anatomical structures, such as tight junctions, and physiological
transport systems that handle different classes of substances in
different ways.
• Substances that dissolve readily in the lipid components of the plasma
membranes enter the brain quickly.
• The extracellular fluid of the brain and spinal cord is a product of—but
chemically different from—the blood. drugs that have rapid effects in
the CNS because of their high lipid solubility are barbiturates,
nicotine, caffeine, and alcohol
Subject Name 385
Physiology-A 385
 The Blood–Brain Barrier

• Many substances that do not dissolve readily in lipids, such as glucose

and other important substrates of brain metabolism, nonetheless enter
the brain quite rapidly, facilitated by membrane transport proteins in
the cells that line the smallest blood vessels of the brain.
• Transport systems also move substances out of the brain and into the
blood, preventing the buildup of molecules that could interfere with
brain function.

Subject Name 386

Physiology-A 386
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 387
 PHYSIOLOGY-A
PHARM 313

Lecture # 24 :The Sensory Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Sensory Receptors

4. The Receptor Potential

5. References

Physiology-A 389
 Learning Objectives

After this lecture, students will be able to:

• Describe the nature and significance of the receptor (generator)
potential
• Describe the general process of transduction in a receptor that is a cell
separate from the afferent neuron.

Physiology-A 390
 Introduction

• A sensory system is a part of the nervous system that consists of

sensory receptors that receive stimuli from the external or internal
environment, the neural pathways that conduct information from the
receptors to the brain or spinal cord, and those parts of the brain that
deal primarily with processing the information. The information that a
sensory system processes may or may not lead to conscious awareness
of the stimulus. For example,whereas you would immediately notice a
change when leaving an air-conditioned house on a hot summer day,
your blood pressure can fluctuate significantly without your
awareness. Regardless of whether the information reaches
consciousness, it is called sensory information. If the information
does reach consciousness,nit can also be called a sensation.

Physiology-A 391
 Sensory Receptors

• Information about the external world and about the body’s internal
environment exists in different forms—pressure, temperature, light,
odorants, sound waves, chemical concentrations.
• Sensory receptors at the peripheral ends of afferent neurons
change this information into graded potentials that can initiate action
potentials, which travel into the central nervous system.
• The receptors are either specialized endings of the primary afferent
neurons themselves or separate receptor cells (someof which are
actually specialized neurons) that signal the primary afferent neurons
by releasing neurotransmitters.
Subject Name 392
Physiology-A 392
Sensory Receptors

Subject Name 393

Physiology-A 393
 Sensory Receptors

• The energy or chemical that impinges upon and activates a sensory

receptor is known as a stimulus.
• There are many types of sensory receptors, each of which responds
much more readily to one form of stimulus than to others. The type of
stimulus to which a particular receptor responds in normal functioning
is known as its adequate stimulus.
• A particular receptor may respond best (i.e., at lowest threshold) to a
limited subset of stimuli. For example, different individual receptors in
the eye respond best to light (the adequate stimulus) of different
wavelengths.
394
Subject Name–A
Physiology 394
 Sensory Receptors

• Most sensory receptors are exquisitely sensitive to their specific

adequate stimulus. For example, some olfactory receptors respond to
as few as three or four odor molecules in the inspired air, and visual
receptors can respond to a single photon, the smallest quantity of light.
• Several general classes of receptors are characterized by the type of
stimulus to which they are sensitive. As the name indicates,
mechanoreceptors respond to mechanical stimuli, such as pressure
or stretch, and are responsible for many types of sensory information,
including touch, blood pressure, and muscle tension.

Subject Name 395

Physiology-A 395
 Sensory Receptors

• These stimuli alter the permeability of ion channels on the receptor

membrane, changing the membrane potential.
• Thermoreceptors detect sensations of cold or warmth, and
• photoreceptors respond to particular ranges of light wavelengths.
• Chemoreceptors respond to the binding of particular chemicals to the
receptor membrane. This type of receptor provides the senses of smell
and taste.
• Nociceptors tsense pain . They can be activated by a variety of stimuli
such as heat, mechanical stimuli like excess stretch, or chemical
substances in the extracellular fluid of damaged tissues.

Subject Name 396

Physiology-A 396
 The Receptor Potential

• The signal that activates sensory receptors, are translated into the
language of graded potentials or action potentials. The process by
which a stimulus—a photon of light, say, or the mechanical stretch of
a tissue—is transformed into an electrical response is known as
sensory transduction.
• The transduction process in all sensory receptors involves the opening
or closing of ion channels that receive information about the internal
and external world, either directly or through a second- messenger
system.

Subject Name 397

Physiology-A 397
 The Receptor Potential

• The ion channels are present in a specialized region of the receptor

membrane located at the distal tip of the cell’s single axon or on
associated specialized sensory cells .
• The gating of these ion channels allows a change in ion flux across the
receptor membrane, which in produces a change in the membrane
potential. This change is a graded potential called a receptor
potential.

Subject Name 398

Physiology-A 398
 The Receptor Potential

• If the receptor membrane is on a separate cell, the receptor potential

there alters the release of neurotransmitter from that cell.
• The neurotransmitter diffuses across the extracellular cleft between the
receptor cell and the afferent neuron and binds to receptor proteins on
the afferent neuron, this junction is a synapse.
• The combination of neurotransmitter with its binding sites generates a
graded potential in the afferent neuron analogous to either an
excitatory postsynaptic potential or, in some cases, an inhibitory
postsynaptic potential.

Subject Name 399

Physiology-A 399
 The Receptor Potential

• As long as the receptor potential keeps the afferent neuron depolarized

to a level at or above threshold, action potentials continue to fire and
propagate along the afferent neuron.
• An increase in the graded potential magnitude causes an increase in
the action potential frequency in the afferent neuron and an increase
in neurotransmitter release at the afferent neuron’s central axon
terminal .
• The magnitude of the receptor potential determines the frequency of
the action potentials,

Subject Name 400

Physiology-A 400
 The Receptor Potential

• Adaptation is a decrease in receptor sensitivity, which results in a

decrease in action potential frequency in an afferent neuron despite the
continuous presence of a stimulus.
• Degrees of adaptation vary widely among different types of sensory
receptors Slowly adapting receptors, maintain a persistent or slowly
decaying receptor potential during a constant stimulus, initiating
action potentials in afferent neurons for the duration of the stimulus.
• These receptors are common in systems sensing parameters that need
to be constantly monitored, such as joint and muscle receptors that
participate in the maintenance of steady postures.
Subject Name 401
Physiology-A 401
 The Receptor Potential

• Rapidly adapting receptors,generate a receptor potential and action

potentials at the onset of astimulus but very quickly cease responding.
Adaptation may be so rapid that only a single action potential is
generated.
• Some rapidly adapting receptors only initiate action potentials at the
onset of a stimulus—a so-called ―on response‖—whereas others
respond with a burst at the beginning of the stimulus and again upon
its removal—called ―on–off responses.‖
• Rapidly adapting receptors are important for monitoring sensory
stimuli that move or change quickly (like receptors in the skin that
sense vibration) and those that persist.

Subject Name 402

Physiology-A 402
The Receptor Potential

Subject Name 403

Physiology-A 403
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 404
 PHYSIOLOGY-A
PHARM 313

Lecture # 25 :The Sensory Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Primary Sensory Coding

4. References

Physiology-A 406
 Learning Objectives

After this lecture, students will be able to:

• How does the nervous system distinguish between stimuli of different
types?
• How does the nervous system code information about stimulus
intensity?
• Describe the general mechanism of lateral inhibition and explain its
importance in sensory processing.

Physiology-A 407
 Introduction

• A sensory system is a part of the nervous system that consists of

sensory receptors that receive stimuli from the external or internal
environment, the neural pathways that conduct information from the
receptors to the brain or spinal cord, and those parts of the brain that
deal primarily with processing the information. The information that a
sensory system processes may or may not lead to conscious awareness
of the stimulus. For example,whereas you would immediately notice a
change when leaving an air-conditioned house on a hot summer day,
your blood pressure can fluctuate significantly without your
awareness. Regardless of whether the information reaches
consciousness, it is called sensory information. If the information
does reach consciousness,nit can also be called a sensation.

Physiology-A 408
 Primary Sensory Coding

• Coding is the conversion of stimulus energy into a signal that

conveys the relevant sensory information to the central nervous
system.
• Characteristics of a stimulus include the type of input it represents, its
intensity, and the location of the body it affects.
• Coding begins at the receptive neurons in the peripheral nervous
system.

Subject Name 409

Physiology-A 409
 Primary Sensory Coding

• A single afferent neuron with all its receptor endings makes up a

sensory unit.
• In a few cases, the afferent neuron has a single receptor, but
generally the peripheral end of an afferent neuron divides into many
fine branches, each terminating with a receptor.
• The area of the body that leads to activity in a particular afferent
neuron when stimulated is called the receptive field for that neuron .
• Receptive fields of neighboring afferent neurons usually overlap so
that stimulation of a single point activates several sensory units,
activation of a single sensory unit almost never occurs.
Subject Name 410
Physiology-A 410
 Stimulus Type

• Another term for stimulus type (heat, cold, sound, or pressure, for
example) is stimulus modality.
• Modalities can be divided into submodalities. Cold and warm are
submodalities of temperature, whereas salty and sweet are
submodalities of taste.
• The type of sensory receptor a stimulus activates is the major factor in
coding the stimulus modality. a given receptor type is particularly
sensitive to one modality—the adequate stimulus—because of the
signal transduction mechanisms and ion channels incorporated in the
receptor’s plasma membrane.
411
Subject Name–A
Physiology 411
 Stimulus Type

• For example, receptors for vision contain pigment molecules whose

shapes are transformed by light, which in turn alters the activity of
membrane ion channels and generates a receptor potential.
• Receptors in the skin do not have light-sensitive pigment molecules,
so they cannot respond to light.
• All the receptors of a single afferent neuron are preferentially sensitive
to the same type of stimulus; for example, they are all sensitive to cold
or all to pressure. Adjacent sensory units may be sensitive to different
types of stimuli.

Subject Name 412

Physiology-A 412
Stimulus Type

Subject Name 413

Physiology-A 413
Stimulus Intensity

Subject Name 414

Physiology-A 414
 Stimulus Intensity

• The frequency of action potentials in a single afferent neuron is one

way, increased stimulus strength means a larger receptor potential,
and this in turn leads to more frequent action potentials .
• As the strength of a local stimulus increases, receptors on adjacent
branches of an afferent neuron are activated, resulting in a summation
of their local currents.
• An increased stimulus intensity to the receptors of a sensory unit is
reflected in increased action potential frequency in its afferent neuron.

Subject Name 415

Physiology-A 415
 Stimulus Intensity

• In addition to increasing the firing frequency in a single afferent

neuron, stronger stimuli usually affect a larger area and activate
similar receptors on the endings of other afferent neurons.
• For example, when touch a surface lightly with a finger, the area of
skin in contact with the surface is small, and only the receptors in that
skin area are stimulated.
• Pressing down firmly increases the area of skin stimulated. This
―calling in‖ of receptors on additional afferent neurons is known as
recruitment.

Subject Name 416

Physiology-A 416
 Stimulus Location

• A third feature of coding is the location of the stimulus—, where the

stimulus is being applied.

• In vision, hearing, and smell, stimulus location is interpreted as

arising from the site from which the stimulus originated rather than the
place on our body where the stimulus was actually applied.

Subject Name 417

Physiology-A 417
 Stimulus Location

• The precision, or acuity, with which locate and discern one stimulus
from an adjacent one depends upon the amount of convergence of
neuronal input in the specific ascending pathways.
• The greater the convergence, the less the acuity. Other factors affecting
acuity are the size of the receptive field covered by a single sensory
unit , the density of sensory units, and the amount of overlap in nearby
receptive fields.

Subject Name 418

Physiology-A 418
 Central Control of Afferent Information

• All sensory signals are subject to extensive modification at the various

synapses along the sensory pathways before they reach higher levels
of the central nervous system.
• Inhibition from collaterals from other ascending neurons (e.g., lateral
inhibition) reduces or even abolishes much of the incoming
information, as can inhibitory pathways descending from higher
centers in the brain
• In some cases, for example, in the pain pathways, the afferent input is
continuously inhibited to some degree. This provides the flexibility of
either removing the inhibition,
Subject Name 419
Physiology-A 419
Central Control of Afferent Information

Subject Name 420

Physiology-A 420
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 421
 PHYSIOLOGY-A
PHARM 313

Lecture # 26 :The Sensory Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Neural Pathways In Sensory Systems

4. Association Cortex And Perceptual Processing

5. Somatic Sensation

6. Vision

7. References
Physiology-A 423
 Learning Objectives

After this lecture, students will be able to:

• Explain the Neural Pathways in Sensory Systems
• Describe the relationship between sensory information processing in
the primary cortical sensory areas and in the cortical association areas.
• Describe the similarities between pain and the other
somaticsensations. Describe the differences

Physiology-A 424
 Introduction

• A sensory system is a part of the nervous system that consists of

sensory receptors that receive stimuli from the external or internal
environment, the neural pathways that conduct information from the
receptors to the brain or spinal cord, and those parts of the brain that
deal primarily with processing the information. The information that a
sensory system processes may or may not lead to conscious awareness
of the stimulus. For example,whereas you would immediately notice a
change when leaving an air-conditioned house on a hot summer day,
your blood pressure can fluctuate significantly without your
awareness. Regardless of whether the information reaches
consciousness, it is called sensory information. If the information
does reach consciousness it can also be called a sensation.

Physiology-A 425
 Neural Pathways in Sensory Systems

• Afferent sensory pathways are generally formed by chains of three

or more neurons connected by synapses.
• These chains of neurons travel in bundles of parallel pathways
carrying information into the central nervous system.
• Some pathways terminate in parts of the cerebral cortex responsible
for conscious recognition of the incoming information; others carry
information not consciously perceived.
• Sensory pathways are also called ascending pathways because they
project ―up‖ to the brain.

Subject Name 426

Physiology-A 426
 Neural Pathways in Sensory Systems

• The central processes of the afferent neurons enter the brain or spinal
cord and synapse upon interneurons there.
• The central processes may diverge to terminate on several, or many,
interneurons or converge so that the processes of many afferent
neurons terminate upon a single interneuron .
• The interneurons upon which the afferent neurons synapse are
called second-order neurons, and these in turn synapse with third-
order neurons, and so on, until the information (coded action
potentials) reaches the cerebral cortex.

Subject Name 427

Physiology-A 427
 Neural Pathways in Sensory Systems

• Most sensory pathways convey information about only a single type of

sensory information. For example, one pathway conveys information
only from mechanoreceptors, whereas another is influenced by
information only from thermoreceptors.
• This allows the brain to distinguish the different types of sensory
information even though all of it is being transmitted by essentially the
same signal, the action potential.
• The specific ascending pathways pass to the brainstem and thalamus,
and the final neurons in the pathways go from there to specific sensory
areas of the cerebral cortex
428
Subject Name–A
Physiology 428
 Neural Pathways in Sensory Systems

• The specific ascending pathways that transmit information from

somatic receptors project to the somatosensory cortex.
• Somatic receptors are those carrying information from the skin,
The specific ascending pathways from the eyes connect to a different
primary cortical receiving area, the visual cortex, which is in the
occipital lobe.
• Neurons in the nonspecific ascending pathways are activated by
sensory units of several different types and therefore signal general
information they indicate that something is happening, without
specifying just what or where.
Subject Name 429
Physiology-A 429
Association Cortex and Perceptual Processing

• Information from the primary sensory cortical areas is elaborated after

it is relayed to a cortical association area.
• a. The primary sensory cortical area and the region of association
cortex closest to it process the information in fairly simple ways and
serve basic sensory-related functions.
• b. Regions of association cortex farther from the primary sensory areas
process the sensory information in more complicated ways.
• c. Processing in the association cortex includes input from areas of the
brain serving other sensory modalities, arousal, attention, memory,
language, and emotions.
Subject Name 430
Physiology-A 430
 Somatic Sensation

• Sensation from the skin, skeletal muscles, bones, tendons, and joints—
somatic sensation—is initiated by a variety of sensory receptors
collectively called somatic receptors.
• Some of these receptors respond to mechanical stimulation of the
skin, hairs, and underlying tissues, whereas others respond to
temperature or chemical changes.
• Activation of somatic receptors gives rise to the sensations of touch,
pressure, awareness of the position of the body parts and their
movement, temperature, pain, and itch. Each sensation is associated
with a specific receptor type.
Subject Name 431
Physiology-A 431
 Somatic Sensation

• Rapidly adapting mechanoreceptors of the skin give rise to sensations

such as vibration, touch, and movement, whereas slowly adapting ones
give rise to the sensation of pressure.
• b. Skin receptors with small receptive fields are involved in fine
spatial discrimination, whereas receptors with larger receptive fields
signal less spatially precise touch or pressure sensations.
• c. A major receptor type responsible for the senses of posture is the
muscle-spindle stretch receptor.

Subject Name 432

Physiology-A 432
 Somatic Sensation

• d. Cold receptors are sensitive to decreasing temperature; warmth

receptors signal information about increasing temperature.
• e. Tissue damage and immune cells release chemical agents that
stimulate specific receptors that give rise to the sensation of pain.
• f. Stimulation-produced analgesia, transcutaneous electrical nerve
stimulation (TENS), and acupuncture control pain by blocking
transmission in the pain pathways.

Subject Name 433

Physiology-A 433
 Vision

• The color of light is defined by its wavelength or frequency.

• The light that falls on the retina is focused by the cornea and lens. a.
Lens shape changes (accommodation) to permit viewing near or
distant images so that they are focused on the retina.
• Stiffening of the lens with aging interferes with accommodation.
Cataracts decrease the amount of light transmitted through the lens.
• An eyeball too long or too short relative to the focusing power of the
lens and cornea causes nearsighted (myopic) or farsighted (hyperopic)
vision, respectively.

Subject Name 434

Physiology-A 434
 Vision

• The photopigments of the rods and cones are made up of a protein

component (opsin) and a chromophore (retinal).
• The rods and each of the three cone types have different opsins, which
make each of the fou receptor types sensitive to differentranges of
light wavelengths.
• When light strikes retinal, it changes shape, triggering a cascade of
events leading to hyperpolarization of photoreceptors and decreased
neurotransmitter release from them. When exposed to darkness, the
rods and cones are depolarized and therefore release more
neurotransmitter than in light.
Subject Name 435
Physiology-A 435
 Vision

• Due to differences in the synapse with bipolar cells,

photoreceptorhyperpolarization increases ganglion cell action
potentials in the ON-pathway and decreases ganglion cell action
potentials in the OFF-pathway. The rods and cones synapse on bipolar
cells, which synapse on ganglion cells.
• Ganglion cell axons form the optic nerves, which exit the eyeballs.
• The optic nerve fibers from the medial half of each retina cross to the
opposite side of the brain in the optic chiasm. The fibers from the optic
nerves terminate in the lateral geniculate nuclei of the thalamus, which
sends fibers to the visual cortex.
Subject Name 436
Physiology-A 436
 Vision

• Photoreceptors also send information to areas of the braindealing with

biological rhythms. Coding in the visual system occurs along parallel
pathways in which different aspects of visual information, such as
color, form, movement, and depth, are kept separate from each other.
The colors we perceive are related to the wavelength of light. The
three cone photopigments vary in the strength of their response to light
over differing ranges of wavelengths.
• Certain ganglion cells are excited by input from one type of cone cell
and inhibited by input from a different cone type.

Subject Name 437

Physiology-A 437
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 438
 PHYSIOLOGY-A
PHARM 313

Lecture # 27 :The Sensory Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Hearing

4. Vestibular System

5. Chemical Senses

6. References

Physiology-A 440
 Learning Objectives

After this lecture, students will be able to:

• List the sequence of events that occurs between the entry of a the entry
of a sound wave into the external auditory canal and the firing of
action potentials in the cochlear nerve.
• What is the relationship between head movement and cupula
movement in a semicircular canal?
• In what ways are the sensory systems for gustation and olfaction
similar?

Physiology-A 441
 Introduction

A sensory system is a part of the nervous system that consists of sensory

receptors that receive stimuli from the external or internal
environment, the neural pathways that conduct information from the
receptors to the brain or spinal cord, and those parts of the brain that
deal primarily with processing the information. The information that a
sensory system processes may or may not lead to conscious awareness
of the stimulus. For example,whereas you would immediately notice a
change when leaving an air-conditioned house on a hot summer day,
your blood pressure can fluctuate significantly without your
awareness. Regardless of whether the information reaches
consciousness, it is called sensory information.

Physiology-A 442
 Hearing

• The sense of audition (hearing) is based on the physics of sound

and the physiology of the external, middle, and inner ear.
• Sound energy is transmitted by movements of pressure waves.
• a. Sound wave frequency determines pitch.
• b. Sound wave amplitude determines loudness.
The sequence of sound transmission follows.
• a. Sound waves enter the external auditory canal and press against the
tympanic membrane, causing it to vibrate.

Subject Name 443

Physiology-A 443
 Hearing

• b. The vibrating membrane causes movement of the three small middle

ear bones; the stapes vibrates against the oval window membrane.
• c. Movements of the oval window membrane set up pressure waves in
the fluid-filled scala vestibuli, which cause vibrations in the cochlear
duct wall, setting up pressure waves in the fluid there.
• d. These pressure waves cause vibrations in the basilar membrane,
which is located on one side of the cochlear duct.
• e. As this membrane vibrates, the hair cells of the organ of Corti move
in relation to the tectorial membrane.

Subject Name 444

Physiology-A 444
 Hearing

• f. Movement of the hair cells’ stereocilia stimulates the hair cells to

release glutamate, which activates receptors on the peripheral ends of
the afferent nerve fibers.
• Separate parts of the basilar membrane vibrate maximally in response
to particular sound frequencies; high frequency is detected near the
oval window and low frequency toward the far end of the cochlear
duct.

445
Subject Name–A
Physiology 445
Hearing

Subject Name 446

Physiology-A 446
 Vestibular System

• I. A vestibular apparatus lies in the temporal bone on each side of the

head and consists of three semicircular canals, a utricle, and a saccule.
• II. The semicircular canals detect angular acceleration during rotation
of the head, which causes bending of the stereocilia on their hair cells.
• III. Otoliths in the gelatinous substance of the utricle and saccule
• (a) move in response to changes in linear acceleration and the position
of the head relative to gravity and
• (b) stimulate the stereocilia on the hair cells.

Subject Name 447

Physiology-A 447
Vestibular System

Subject Name 448

Physiology-A 448
Vestibular System

Subject Name 449

Physiology-A 449
 Chemical Senses

Gustation
• The specialized sense organs for gustation (taste) are the 10,000 or
so taste buds found in the mouth and throat, the vast majority on
the upper surface and sides of the tongue.
• Taste buds are small groups of cells arranged like orange slices around
a hollow taste pore and are found in the walls of visible structures
called lingual papillae .
• Some of the cells serve mainly as supporting cells, but others are
specialized epithelial cells that act as receptors for various chemicals
in the food we eat.
Subject Name 450
Physiology-A 450
 Gustation

• Small, hairlike microvilli increase the surface area of taste receptor

cells and contain integral membrane proteins that transduce the
presence of a given chemical into a receptor potential.
• At the bottom of taste buds are basal cells, which divide and
differentiate to continually replace taste receptor cells damaged in the
occasionally harsh environment of the mouth.
• To enter the pores of the taste buds and come into contact with taste
receptor cells, food molecules must be dissolved in liquid— either
ingested or provided by secretions of the salivary glands

Subject Name 451

Physiology-A 451
Gustation

Subject Name 452

Physiology-A 452
 Olfaction

• Olfactory receptors, which are part of the afferent olfactory neurons,

lie in the upper nasal cavity.
• a. Odorant molecules, once dissolved in the mucus that bathes the
olfactory receptors, bind to specific receptors (protein-binding sites).
Each olfactory receptor cell has one or at most a few of the 400
different receptor types.
• b. Olfactory pathways go directly to the olfactory cortex and limbic
system, rather than to the thalamus.

Subject Name 453

Physiology-A 453
Olfaction

Subject Name 454

Physiology-A 454
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 455
 PHYSIOLOGY-A
PHARM 313

Lecture # 28 :Principles of Hormonal Control Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Hormone Structures And Synthesis

4. References

Physiology-A 457
 Learning Objectives

After this lecture, students will be able to:

• Describe the chemical nature of hormones and define the terms
prehormone and prohormone

Physiology-A 458
 Introduction

• The endocrine system consists of all those ductless glands called

endocrine glands that secrete hormones, as well as hormone-
secreting cells located in various organs such as the brain, heart,
kidneys, liver, and stomach. Hormones are chemical messengers that
enter the blood, which carries them from their site of secretion to the
cells upon which they act. The cells a particular hormone influences
are known as the target cells for that hormone. Hormones functionally
link various organ systems together . This coordination is key to the
maintenance of homeostasis, which is important for health and
survival.

Physiology-A 459
 Hormone Structures and Synthesis

• Hormones fall into three major structural classes: (1) amines, (2)
peptides and proteins, and (3) steroids.
• Amine Hormones
• The amine hormones are derivatives of the amino acid tyrosine.
They include the thyroid hormones (produced by the thyroid ) and
the catecholamines epinephrine and norepinephrine (produced by
the adrenal medulla) and dopamine (produced by the hypothalamus).
The adrenal medulla secretes mainly two catecholamines, epinephrine
and norepinephrine. In humans, the adrenal medulla

Subject Name 460

Physiology-A 460
 Amine Hormones

• Secretes approximately four times more epinephrine than

norepinephrine. This is because the adrenal medulla expresses high
amounts of an enzyme called phenylethanolamine- N-
methyltransferase (PNMT), which catalyzes the reaction that converts
norepinephrine to epinephrine ..
• The other catecholamine hormone, dopamine, is synthesized by
neurons in the hypothalamus. Dopamine is released into a special
circulatory system called a portal system , which carries the hormone
to the pituitary gland; there, it acts to inhibit the activity of certain
endocrine cells.

Subject Name 461

Physiology-A 461
 Amine Hormones

• Synthesis of catecholamines begins with the uptake of tyrosine by the

axon terminals and its conversion to another precursor, L-
dihydroxyphenylalanine (L-dopa) by the rate-limiting enzyme in
the pathway, tyrosine hydroxylase.

462
Subject Name–A
Physiology 462
Amine Hormones

Subject Name 463

Physiology-A 463
 Peptide and Protein Hormones

• Most hormones are polypeptides.

• Short polypeptides with a known function are often referred to simply
as peptides;
• Longer polypeptides with tertiary structure and a known function are
called proteins.
• Hormones in this class range in size from small peptides having only
three amino acids to large proteins, some of which contain
carbohydrate and thus are glycoproteinsIn many cases, peptide
hormones are initially synthesized on the ribosomes of endocrine

Subject Name 464

Physiology-A 464
 Peptide and Protein Hormones

• Cells as larger molecules known as preprohormones, which are then

cleaved to prohormones by proteolytic enzymes in the rough
endoplasmic reticulum .

• The prohormone is then packaged into secretory vesicles by the Golgi

apparatus. Insulin is synthesized as a polypeptide preprohormone, then
processed to the prohormone.
Subject Name 465
Physiology-A 465
Peptide and Protein Hormones

Subject Name 466

Physiology-A 466
 Steroid Hormones

• Steroid hormones are primarily produced by the adrenal cortex and the
gonads (testes and ovaries), as well as by the placenta during
pregnancy.
• vitamin D is enzymatically converted in the body to an active steroid
hormone.
• In both the gonads and the adrenal cortex, the hormone-producing
cells are stimulated by the binding of an anterior pituitary gland
hormone to its plasma membrane receptor. These receptors are linked
to Gs proteins which activate adenylyl cyclase and cAMP production.

Subject Name 467

Physiology-A 467
 Steroid Hormones

• All of the steroid hormones are derived from cholesterol, which is

either taken up from the extracellular fluid by the cells or synthesized
by intracellular enzymes.
• The final steroid hormone product depends upon the cell type and the
types and amounts of the enzymes it expresses. Cells in the ovary, for
example, express large amounts of the enzyme needed to convert
testosterone to estradiol,
• Cells in the testes do not express significant amounts of this enzyme
and therefore make primarily testosterone.

Subject Name 468

Physiology-A 468
 Steroid Hormones

• Once formed, the steroid hormones are not stored in the cytosol in
membrane-bound vesicles, because the lipophilic nature of the steroids
allows them to freely diffuse across lipid bilayers

• Once they are synthesized, steroid hormones diffuse across the plasma
membrane into the circulation. Because of their lipid nature, steroid
hormones are not highly soluble in blood.

Subject Name 469

Physiology-A 469
Steroid Hormones

Subject Name 470

Physiology-A 470
Steroid Hormones

Subject Name 471

Physiology-A 471
Steroid Hormones

Subject Name 472

Physiology-A 472
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 473
 PHYSIOLOGY-A
PHARM 313

Lecture # 29 :Principles of Hormonal Control Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Hormone Transport In The Blood

4. Hormone Metabolism And Excretion

5. References

Physiology-A 475
 Learning Objectives

After this lecture, students will be able to:

• Which classes of hormones are carried in the blood mainly as
unbound, dissolved hormone? Mainly bound to plasma proteins?

Physiology-A 476
 Introduction

• The endocrine system consists of all those ductless glands called

endocrine glands that secrete hormones, as well as hormone-
secreting cells located in various organs such as the brain, heart,
kidneys, liver, and stomach. Hormones are chemical messengers that
enter the blood, which carries them from their site of secretion to the
cells upon which they act. The cells a particular hormone influences
are known as the target cells for that hormone. Hormones functionally
link various organ systems together . This coordination is key to the
maintenance of homeostasis, which is important for health and
survival.

Physiology-A 477
 Hormone Transport In The Blood

• Most peptide and all catecholamine hormones are water-soluble.

Therefore, with the exception of a few peptides, these hormones are
transported simply dissolved in plasma .

• Steroid hormones and thyroid hormones are poorly soluble;

consequently, they circulate in the blood largely bound to plasma
proteins.
Subject Name 478
Physiology-A 478
 Hormone Transport in the Blood

• The steroid and thyroid hormones exist in plasma mainly bound to

large proteins, small concentrations of these hormones do exist
dissolved in the plasma. The dissolved, or free, hormone is in
equilibrium with the bound hormone
• The total hormone concentration in plasma is the sum of the free and
bound hormones.
• Only the free hormone can diffuse out of capillaries and encounter its
target cells.

Subject Name 479

Physiology-A 479
 Hormone Transport in the Blood

• The concentration of the free hormone is what is biologically

important rather than the concentration of the total hormone, most of
which is bound.

• The degree of protein binding also influences the rate of metabolism

and the excretion of the hormone.

480
Subject Name–A
Physiology 480
 Hormone Metabolism and Excretion

• Once a hormone has been synthesized and secreted into the blood, has
acted on a target tissue, and its increased activity is no longer required,
the concentration of the hormone in the blood usually returns to
normal.

• This is necessary to prevent excessive, possibly harmful effects from

the prolonged exposure of target cells to hormones.
Subject Name 481
Physiology-A 481
 Hormone Metabolism and Excretion

• A hormone’s concentration in the plasma depends upon

(1) its rate of secretion by the endocrine gland and

(2) its rate of removal from the blood. Removal, or ―clearance,‖ of the
hormone occurs either by excretion or by metabolic transformation.

• The liver and the kidneys are the major organs that metabolize or
excrete hormones.
Subject Name 482
Physiology-A 482
 Hormone Metabolism and Excretion

• The liver and kidneys, are not the only routes for eliminating
hormones.
• Sometimes a hormone is metabolized by the cells upon which it acts.
• some peptide hormones, for example, endocytosis of hormone–
receptor complexes on plasma membranes enables cells to remove the
hormones rapidly from their surfaces and catabolize them
intracellularly.

Subject Name 483

Physiology-A 483
 Hormone Metabolism and Excretion

• The receptors are then often recycled to the plasma membrane.

• Enzymes in the blood and tissues rapidly break down catecholamine

and peptide hormones.

Subject Name 484

Physiology-A 484
 Hormone Metabolism and Excretion

• These hormones therefore tend to remain in the bloodstream for only

brief periods—minutes to an hour.

• Protein-bound hormones are protected from excretion or metabolism

by enzymes as long as they remain bound. Therefore, removal of the
circulating steroid and thyroid hormones generally takes longer, often
several hours to days.
Subject Name 485
Physiology-A 485
 Hormone Metabolism and Excretion

• In some cases, metabolism of a hormone activates the hormone rather

than inactivates it.

• The secreted hormone may be relatively inactive until metabolism

transforms it. One example is T4 produced by the thyroid gland, which
is convertedto the much more active hormone T3 inside the target cell.

Subject Name 486

Physiology-A 486
Hormone Metabolism and Excretion

Subject Name 487

Physiology-A 487
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 488
 PHYSIOLOGY-A
PHARM 313

Lecture # 30 :Principles of Hormonal Control Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Mechanisms Of Hormone Action

4. References

Physiology-A 490
 Learning Objectives

After this lecture, students will be able to:

• Explain the mechanisms of action of steroid and thyroid hormones
• Describe the mechanisms by which other hormones exert their effects
on target cells.

Physiology-A 491
 Introduction

• The endocrine system consists of all those ductless glands called

endocrine glands that secrete hormones, as well as hormone-
secreting cells located in various organs such as the brain, heart,
kidneys, liver, and stomach. Hormones are chemical messengers that
enter the blood, which carries them from their site of secretion to the
cells upon which they act. The cells a particular hormone influences
are known as the target cells for that hormone. Hormones functionally
link various organ systems together . This coordination is key to the
maintenance of homeostasis, which is important for health and
survival.

Physiology-A 492
 Mechanisms of Hormone Action

Hormone Receptors

• Because hormones are transported in the blood, they can reach all
tissues. The response to a hormone is highly specific, involving only
the target cells for that hormone.

• The ability to respond depends upon the presence of specific receptors

for those hormones on or in the target cells.

Subject Name 493

Physiology-A 493
 Mechanisms of Hormone Action

• The response of a target cell to a chemical messenger is the final event

in a sequence that begins when the messenger binds to specific cell
receptors.

• The receptors for water-soluble chemical messengers like peptide

hormones and catecholamines are proteins located in the plasma
membranes of the target cells.
Subject Name 494
Physiology-A 494
Mechanisms of Hormone Action

495
Subject Name–A
Physiology 495
 Mechanisms of Hormone Action

• The receptors for lipid-soluble chemical messengers like steroid and

thyroid hormones are proteins located mainly inside the target cells.

Subject Name 496

Physiology-A 496
 Mechanisms of Hormone Action

• Down-regulation is a decrease in receptor number, often from

exposure to high concentrations of the hormone.

• This temporarily decreases target-cell responsiveness to the hormone,

thereby preventing overstimulation.

Subject Name 497

Physiology-A 497
 Mechanisms of Hormone Action

• Up-regulation is an ncrease in the number of a hormone’s receptors

in a cell, often resulting from a prolonged exposure to a low
concentration of the hormone.

• This has the effect of increasing target-cell responsiveness to the

hormone.

Subject Name 498

Physiology-A 498
 Mechanisms of Hormone Action

• A hormone may induce an increase in the number of receptors for a

second hormone.

• One reason is that thyroid hormones stimulate the synthesis of beta-

adrenergic receptors for epinephrine in adipose tissue; as a result, the
tissue becomes much more sensitive to epinephrine.

Subject Name 499

Physiology-A 499
Events Elicited by Hormone–Receptor Binding

• The events initiated when a hormone binds to its receptor— that is, the
mechanisms by which the hormone elicits a cellular response—are one
or more of the signal transduction pathways that apply to all chemical
messengers

Subject Name 500

Physiology-A 500
Effects of Peptide Hormones and Catecholamine

• This location is important because these hormones are too hydrophilic

to diffuse through the plasma membrane.

• When activated by hormone binding, the receptors trigger one or more

of the signal transduction pathways for plasma membrane receptors .
That is, the activated receptors directly influence .

Subject Name 501

Physiology-A 501
Effects of Peptide Hormones and Catecholamine

(1) enzyme activity that is part of the receptor,

(2) activity of cytoplasmic janus kinases associated with the receptor, or

(3) G proteins coupled in the plasma membrane to effector proteins—

ion channels and enzymes—that generate second messengers such as
cAMP and Ca2.

Subject Name 502

Physiology-A 502
 Effects of Steroid and Thyroid Hormone

• The steroid hormones and thyroid hormone are lipophilic, and their
receptors, which are intracellular, are members of the nuclear receptor
superfamily.
• The binding of hormone to its receptor leads to the activation (or in
some cases, inhibition) of the transcription of particular genes, causing
a change in the synthesis rate of the proteins coded for by those genes.
• The ultimate result of changes in the concentrations of these proteins
is an enhancement or inhibition of particular processes the cell carries
out or a change in the cell’s rate of protein secretion.

Subject Name 503

Physiology-A 503
 Pharmacological Effects of Hormones

• These pharmacological effects can also occur in diseases involving

the secretion of excessive amounts of hormones.
• Pharmacological effects are of great importance in medicine because
hormones are often used in large doses as therapeutic agents.
• Most common example is that of very potent synthetic forms of
cortisol, such as prednisone, which is administered to suppress allergic
and inflammatory reactions. In such situations, a host of unwanted
effects may be observed.

Subject Name 504

Physiology-A 504
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 505
 PHYSIOLOGY-A
PHARM 313

Lecture # 31 :Principles of Hormonal Control Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Inputs That Control Hormone Secretion

4. References

Physiology-A 507
 Learning Objectives

After this lecture, students will be able to:

• What are the direct inputs to endocrine glands controlling hormone
secretion?
• How does control of hormone secretion by plasma mineral ions and
nutrients achieve negative feedback control of these substances?

Physiology-A 508
 Introduction

• The endocrine system consists of all those ductless glands called

endocrine glands that secrete hormones, as well as hormone-
secreting cells located in various organs such as the brain, heart,
kidneys, liver, and stomach. Hormones are chemical messengers that
enter the blood, which carries them from their site of secretion to the
cells upon which they act. The cells a particular hormone influences
are known as the target cells for that hormone. Hormones functionally
link various organ systems together . This coordination is key to the
maintenance of homeostasis, which is important for health and
survival.

Physiology-A 509
 Inputs That Control Hormone Secretion

• Hormone secretion is mainly under the control of three types of inputs

to endocrine cells :
• (1) changes in the plasma concentrations of mineral ions or organic
nutrients,
• (2) Neurotransmitters released from neurons ending on the endocrine
cell, and
• (3) Another hormone (or, in some cases, a paracrine substance) acting
on the endocrine cell. For example, insulin secretion is stimulated by
the extracellular concentrations of glucose and other nutrients, and is
either stimulated or inhibited by the different branches of the
autonomic nervous system.
Subject Name 510
Physiology-A 510
 Inputs That Control Hormone Secretion

• The control of endocrine cells illustrates the general principleof

physiology that most physiological functions are controlled by
multiple regulatory systems, often working in opposition.
• The resulting output—the rate of hormone secretion—depends upon
the relative amounts of stimulatory and inhibitory inputs The term
secretion applied to a hormone denotes its release by exocytosis from
the cell.
• Hormones such as steroid hormones are not secreted, per se, but
instead diffuse through the cell’s plasma membrane into the
extracellular space. Secretion or release by diffusion is sometimes
accompanied by increased synthesis of the hormone.

Subject Name 511

Physiology-A 511
Control by Plasma Concentrations of Mineral
Ions or Organic Nutrients

• The secretion of several hormones is directly controlled—at least in

part—by the plasma concentrations of specific mineral ions or organic
nutrients.
• A major function of the hormone is to regulate through negative
feedback the plasma concentration of the ion or nutrient controlling its
secretion. For example, insulin secretion is stimulated by an increase
in plasma glucose concentration.
• Insulin, in turn, acts on skeletal muscle and adipose tissue to promote
facilitated diffusion of glucose across the plasma membranes into the
cytosol. Consequently, the action of insulin restores plasma glucose
concentration to normal

512
Subject Name–A
Physiology 512
Control by Plasma Concentrations of Mineral Ions
or Organic Nutrients

• Another example is the regulation of calcium ion homeostasis by

parathyroid hormone (PTH), .
• This hormone is produced by cells of the parathyroid glands, which, as
their name implies, are located in close proximity to the thyroid gland.
A decrease in the plasma Ca2+ concentration directly stimulates PTH
secretion.
• PTH then exerts several actions on bone and other tissue that increase
calcium release into the blood, thereby restoring plasma Ca2+ to
normal.

Subject Name 513

Physiology-A 513
Control by Plasma Concentrations of Mineral
Ions or Organic Nutrients

Subject Name 514

Physiology-A 514
 Control by Neurons

• In addition to controlling the adrenal medulla, the autonomic nervous

system influences other endocrine glands .

• Both parasympathetic and sympathetic inputs to these other glands

may occur, some inhibitory and some stimulatory.

Subject Name 515

Physiology-A 515
 Control by Neurons

• Examples are the secretions of insulin and the gastrointestinal

hormones, which are stimulated by neurons of the parasympathetic
nervous system and inhibited by sympathetic neurons.

• One large group of hormones—those secreted by the hypothalamus

and the posterior pituitary—is under the direct control of neurons in
the brain itself.
Subject Name 516
Physiology-A 516
 Control by Other Hormones

• The secretion of a particular hormone is directly controlled by the

blood concentration of another hormone.

• The only function of the first hormone in a sequence is to stimulate the

secretion of the next. A hormone that stimulates the secretion of
another hormone is often referred to as a tropic hormone.

Subject Name 517

Physiology-A 517
 Control by Other Hormones

• The tropic hormones usually stimulate not only secretion but also the
growth of the stimulated gland.

• In addition to stimulatory actions, some hormones such as those in a

multihormone sequence inhibit secretion of other hormones.

Subject Name 518

Physiology-A 518
Control by Other Hormones

Subject Name 519

Physiology-A 519
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 520
 PHYSIOLOGY-A
PHARM 313

Lecture # 32 :Principles of Hormonal Control Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Control Systems Involving The Hypothalamus And Pituitary Gland

4. References

Physiology-A 522
 Learning Objectives

After this lecture, students will be able to:

• Describe the anatomical relationships between the hypothalamus and
the pituitary gland.
• Name the two posterior pituitary hormones and describe the site of
synthesis and mechanism of release of each.
• List all six well-established anterior pituitary gland hormones and their
major functions.

Physiology-A 523
 Introduction

• The endocrine system consists of all those ductless glands called

endocrine glands that secrete hormones, as well as hormone-
secreting cells located in various organs such as the brain, heart,
kidneys, liver, and stomach. Hormones are chemical messengers that
enter the blood, which carries them from their site of secretion to the
cells upon which they act. The cells a particular hormone influences
are known as the target cells for that hormone. Hormones functionally
link various organ systems together . This coordination is key to the
maintenance of homeostasis, which is important for health and
survival.

Physiology-A 524
Control Systems Involving the Hypothalamus and
Pituitary Gland

• The pituitary gland, or hypophysis (from a Greek term meaning

―to grow underneath‖), lies in a pocket (called the sella turcica) of the
sphenoid bone at the base of the brain just below the hypothalamus.
• The pituitary gland is connected to the hypothalamus by the
infundibulum, or pituitary stalk, containing axons from neurons in
the hypothalamus and small blood vessels.
• In humans, the pituitary gland is primarily composed of two adjacent
lobes called the anterior lobe—usually referred to as the anterior
pituitary gland or adenohypophysis

Subject Name 525

Physiology-A 525
Control Systems Involving the Hypothalamus and
Pituitary Gland

• and the posterior lobe—usually called the posterior pituitary or

neurohypophysis.
• anterior pituitary gland arises embryologically from an invagination of
the pharynx called Rathke’s pouch, whereas the posterior pituitary is
not actually a gland but, rather, an extension of the neural components
of the hypothalamus .
• The axons of two well-defined clusters of hypothalamic neurons (the
supraoptic and paraventricular nuclei) pass down the infundibulum
and end within the posterior pituitary in close proximity to capillaries
(small blood vessels where exchange of solutes occurs between the
blood and interstiti.

Subject Name 526

Physiology-A 526
Control Systems Involving the Hypothalamus and
Pituitary Gland

• Therefore, these neurons do not form a synapse with other neurons.

Instead, their terminals end directly on capillaries. The terminals
release hormones into these capillaries, which then drain into veins
and the general circulation.
• Posterior Pituitary Hormones
• The hormones are synthesized not in the posterior pituitary itself but in
the hypothalamus—specifically, in the cell bodies of the supraoptic
and paraventricular nuclei, whose axons pass down the infundibulum
and terminate in the posterior pituitary.
• Enclosed in small vesicles, the hormone is transported down the
axons to accumulate at the axon terminals in the posterior pituitary.
527
Subject Name–A
Physiology 527
 Posterior Pituitary Hormones

• Various stimuli activate inputs to these neurons, causing action

potentials that propagate to the axon terminals and trigger the release
of the stored hormone by exocytosis.
• The hormone then enters capillaries to be carried away by the blood
returning to the heart. In this way, the brain can receive stimuli and
respond as if it were an endocrine organ.
• By releasing its hormones into the general circulation, the posterior
pituitary can modify the functions of distant organs.

Subject Name 528

Physiology-A 528
 Posterior Pituitary Hormones

• The two posterior pituitary hormones are the peptides oxytocin and
vasopressin.
• Oxytocin is involved in two reflexes related to reproduction. In one
case, oxytocin stimulates contraction of smooth muscle cells in the
breasts, which results in milk ejection during lactation.
• This occurs in response to stimulation of the nipples of the breast
during nursing of the infant.
• Sensory cells within the nipples send stimulatory neural signals to the
brain that terminate on the hypothalamic cells that make oxytocin,
causing their activation and thus release of the hormone.
Subject Name 529
Physiology-A 529
 Posterior Pituitary Hormones

• In a second reflex, one that occurs during labor in a pregnant woman,

stretch receptors in the cervix send neural signals back to the
hypothalamus, which releases oxytocin in response.
• Oxytocin then stimulates contraction of uterine smooth muscle cells,
until eventually the baby is born .
• Oxytocin is also present in males. Oxytocin may be involved in
various aspects of memory and behavior in male and female
mammals, possibly including humans.
• These include such things as pair bonding, maternal behavior, and
emotions such as love.
Subject Name 530
Physiology-A 530
 Posterior Pituitary Hormones

• The other posterior pituitary hormone, vasopressin, acts on smooth

muscle cells around blood vessels to cause their contraction, which
constricts the blood vessels and thereby increases blood pressure.
• This may occur, for example, in response to a decrease in blood
pressure that resulted from a loss of blood due to an injury.
• Vasopressin also acts within the kidneys to decrease water excretion in
the urine, thereby retaining fluid in the body and helping to maintain
blood volume.

Subject Name 531

Physiology-A 531
Posterior Pituitary Hormones

Subject Name 532

Physiology-A 532
 Anterior Pituitary Gland Hormones and the
Hypothalamus

• Other nuclei of hypothalamic neurons secrete hormones that control

the secretion of all the anterior pituitary gland hormones.
• The hypothalamic hormones that regulate anterior pituitary gland
function are collectively termed hypophysiotropic hormones . With
one exception (dopamine), each of the hypophysiotropic hormones is
the first in a three-hormone sequence:
(1) A hypophysiotropic hormone controls the secretion of
(2) an anterior pituitary gland hormone, which controls the secretion of
(3) a hormone from some other endocrine gland

Subject Name 533

Physiology-A 533
Anterior Pituitary Gland Hormones and the
Hypothalamus

Subject Name 534

Physiology-A 534
Anterior Pituitary Gland Hormones and the
Hypothalamus

Subject Name 535

Physiology-A 535
Anterior Pituitary Gland Hormones and the
Hypothalamus

Subject Name 536

Physiology-A 536
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 537
 PHYSIOLOGY-A
PHARM 313

Lecture # 33 :Principles of Hormonal Control Systems

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Types Of Endocrine Disorders

4. References

Physiology-A 539
 Learning Objectives

After this lecture, students will be able to:

• Distinguish between primary and secondary hyposecretion of a
hormone. Between hyposecretion and hyporesponsiveness.

Physiology-A 540
 Introduction

• The endocrine system consists of all those ductless glands called

endocrine glands that secrete hormones, as well as hormone-
secreting cells located in various organs such as the brain, heart,
kidneys, liver, and stomach. Hormones are chemical messengers that
enter the blood, which carries them from their site of secretion to the
cells upon which they act. The cells a particular hormone influences
are known as the target cells for that hormone. Hormones functionally
link various organ systems together . This coordination is key to the
maintenance of homeostasis, which is important for health and
survival.

Physiology-A 541
 Types of Endocrine Disorders

• There is such a wide variety of hormones and endocrine glands, the

features of disorders of the endocrine system may vary considerably.
• For example, endocrine disease may manifest as an imbalance in
metabolism, leading to weight gain or loss; as a failure to grow or
develop normally in early life; as an abnormally high or low blood
pressure; as a loss of reproductive fertility; or as mental and emotional
changes, to name a few.

Subject Name 542

Physiology-A 542
 Types of Endocrine Disorders

• All endocrine diseases can be categorized in one of four ways.

(1) Too little hormone (hyposecretion),
(2) Too much hormone (hypersecretion),
(3) Decreased responsiveness of the target cells to hormone
(hyporesponsiveness), and
(4) Increased responsiveness of the target cells to hormone
(hyperresponsiveness)

Subject Name 543

Physiology-A 543
 Types of Endocrine Disorders

Hyposecretion
• An endocrine gland may be secreting too little hormone because the
gland is not functioning normally, a condition termed primary
hyposecretion. Examples include
• (1) partial destruction of a gland, leading to decreased hormone
secretion;
• (2) an enzyme deficiency resulting in decreased synthesis of the
hormone;

544
Subject Name–A
Physiology 544
 Hyposecretion

• (3) Dietary deficiency of iodine, specifically leading to decreased

secretion of thyroid hormones.

• Many other causes, such as infections and exposure to toxic chemicals,

have the common denominator of damaging the endocrine gland or
reducing its ability to synthesize or secrete the hormone.

Subject Name 545

Physiology-A 545
 Hyposecretion

• Secondary hyposecretion. In this case, the endocrine gland is not

damaged (at least at first) but is receiving too little stimulation by its
tropic hormone.

Subject Name 546

Physiology-A 546
 Hypersecretion

• A hormone can also undergo either primary hypersecretion (the gland

is secreting too much of the hormone on its own) or secondary
hypersecretion (excessive stimulation of the gland by its tropic
hormone).

• One cause of primary or secondary hypersecretion is the presence of a

hormone-secreting, endocrine-cell tumor.
Subject Name 547
Physiology-A 547
 Hyporesponsiveness

• The tumor can be removed surgically or destroyed with radiation if it

is confined to a small area.

• Drugs that inhibit a hormone’s synthesis can block hypersecretion.

Alternatively,

• Drugs that do not alter the hormone’s secretion but instead block the
hormone’s actions on its target cells (receptor antagonists).

Subject Name 548

Physiology-A 548
 Hyporesponsiveness

• A component of the endocrine system may not be functioning

normally, even though there is nothing wrong with hormone secretion.
The target cells do not respond normally to the hormone, a condition
termed hyporesponsiveness, or hormone resistance.
• An important example of a disease resulting from hyporesponsiveness
is the most common form of diabetes mellitus (called type 2 diabetes
mellitus), in which the target cells of the hormone insulin are
hyporesponsive to this hormone.

Subject Name 549

Physiology-A 549
 Hyporesponsiveness

• The receptors for a hormone may be normal but some signaling event
that occurs within the cell after the hormone binds to its receptors may
be defective.
• There may be a deficiency of the enzymes that catalyze the activation.
For example, some men secrete testosterone (the major circulating
androgen) normally and have normal receptors for androgens.
• Missing the intracellular enzyme that converts testosterone to
dihydrotestosterone, a potent metabolite of testosterone that binds to
androgen receptors.

Subject Name 550

Physiology-A 550
 Hyperresponsiveness

• Thyroid hormone causes an up-regulation of beta-adrenergic receptors

for epinephrine; therefore, hypersecretion of thyroid hormone causes,
in turn, a hyperresponsiveness of target cells to epinephrine.

• One result of this is the increased heart rate typical of people with
increased plasma concentrations of thyroid hormone.

Subject Name 551

Physiology-A 551
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 552
 PHYSIOLOGY-A
PHARM 313

Lecture # 34 :Muscle

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Skeletal Muscle Structure

4. References

Physiology-A 554
 Learning Objectives

After this lecture, students will be able to:

• Diagram the arrangement of thick and thin filaments in a striated
muscle sarcomere, and label the major bands that give rise to the
striated pattern.
• Describe the organization of myosin, actin, tropomyosin, and troponin
molecules in the thick and thin filaments.

Physiology-A 555
 Introduction

• Muscle is one of the four tissue types that make up the human body.
The ability to harness chemical energy to produce force and movement
is present to a limited extent in most cells, but in muscle cells it has
become dominant. Muscles generate force and movements used to
regulate the internal environment, and they also produce movements
of the body in relation to the external environment. Most skeletal
muscle, as the name implies, is attached to bone, and its contraction is
responsible for supporting and moving the skeleton contraction of
skeletal muscle is initiated by action potentials in neurons of the
somatic motor division of the peripheral nervous system and is usually
under voluntary control.

Physiology-A 556
 Skeletal Muscle Structure

• The most striking feature seen when viewing skeletal muscle through
a microscope is a distinct series of alternating light and dark bands
perpendicular to the long axis.
• Cellular Structure
• Due to its elongated shape and the presence of multiple nuclei, a
skeletal muscle cell is also referred to as a muscle fiber.
• Each muscle fiber is formed during development by the fusion of a
number of undifferentiated, mononucleated cells known as myoblasts
into a single, cylindrical, multinucleated cell.

Subject Name 557

Physiology-A 557
 Cellular Structure

• Compared to other cell types, skeletal muscle fibers are extremely

large. Adult skeletal muscle fibers have diameters between 10 and 100
μm and lengths that may extend up to 20 cm.
• Key to the maintenance and function of such large cells is the retention
of the nuclei from the original myoblasts.
• Spread throughout the length of the muscle fiber, each participates in
regulation of gene expression and protein synthesis within its local
domain.
• If damaged or destroyed after birth as a result of injury, they undergo
a repair process involving a population of undifferentiated stem cells
known as satellite cells.
Subject Name 558
Physiology-A 558
 Cellular Structure

• In response to strain or injury, they become active and undergo mitotic

proliferation.
• Daughter cells then differentiate into myoblasts that can either fuse
together to form new fibers or fuse with stressed or damaged muscle
fibers to reinforce and repair them.
• The capacity for forming new skeletal muscle fibers is considerable
but may not restore a severely damaged muscle to the original number
of muscle fibers.
• Some of the compensation for a loss of muscle tissue also occurs
through a satellite cell-mediated hypertrophy (increase in size) of the
remaining muscle fibers.
559
Subject Name–A
Physiology 559
 Cellular Structure

• Muscle hypertrophy also occurs in response to heavy exercise.

• This occurs through a combination of hypertrophy of existing fibers,
splitting of existing fibers, and satellite cell proliferation,
differentiation, and fusion.
• Many hormones and growth factors are involved in regulating these
processes, such as growth hormone, insulin-like growth factor, and sex
hormones.

Subject Name 560

Physiology-A 560
 Connective Tissue Structure

• The term muscle refers to a number of skeletal muscle fibers bound

together by connective tissue .
• Skeletal muscles are usually attached to bones by bundles of
connective tissue consisting of collagen fibers known as tendons.
• In some muscles, the individual fibers extend the entire length of the
muscle, but in most, the fibers are shorter, often oriented at an angle to
the longitudinal axis of the muscle.
• The transmission of force from muscle to bone is like a number of
people pulling on a rope, each person corresponding to a single muscle
fiber and the rope corresponding to the connective tissue and tendons.
Subject Name 561
Physiology-A 561
 Connective Tissue Structure

• Some tendons are very long, with the site where the tendon attaches to
the bone far removed from the end of the muscle.

• For example, some of the muscles that move the fingers are in the
forearm (wiggle your fingers and feel the movement of the muscles
just below your elbow).

• These muscles are connected to the fingers by long tendons.

Subject Name 562

Physiology-A 562
 Filament Structure

• The striated pattern in skeletal muscle results from the arrangement of

cytosolic proteins organized into two types of filaments distinguished
by their size and protein composition.
• The larger are thick filaments and the smaller are thin filaments.
These filaments are arranged in cylindrical bundles called myofibrils,
• Most of the cytoplasm of a fiber is filled with myofibrils, each
extending from one end of the fiber to the other and linked to the
tendons at the ends of the fiber.
• The thick filaments are composed mainly of the protein myosin. The
myosin molecule is composed of two large polypeptide heavy chains
and four smaller light chains.
Subject Name 563
Physiology-A 563
 Filament Structure

• These polypeptides combine to form a molecule that consists of two

globular heads (containing heavy and light chains) and a long tail
formed by the two intertwined heavy chains.
• The tail of each myosin molecule lies along the axis of the thick
filament, and the two globular heads extend out to the sides, forming
cross- bridges, which make contact with the thin filament and
exert force during muscle contraction.
• Each globular head contains two binding sites, one for attaching to the
thin filament and one for ATP. The ATP binding site also functions as
an enzyme (called myosin- ATPase) that hydrolyzes the bound ATP,
harnessing its energy for contraction.

Subject Name 564

Physiology-A 564
 Filament Structure

• The thin filaments (which are about half the diameter of the thick
filaments) are principally composed of the protein actin, as well as a
protein called nebulin that is thought to play a role in thin filament
assembly, and two other proteins— troponin and tropomyosin—that
have important functions in regulating contraction.
• An actin molecule is a globular protein composed of a single
polypeptide (a monomer) that polymerizes with other actin monomers
to form a polymer made up of two intertwined, helical chains.
• These chains make up the core of a thin filament.
• Each actin molecule contains a binding site for myosin.
Subject Name 565
Physiology-A 565
Filament Structure

Subject Name 566

Physiology-A 566
Filament Structure

Subject Name 567

Physiology-A 567
Sarcomere Structure

Subject Name 568

Physiology-A 568
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 569
 PHYSIOLOGY-A
PHARM 313

Lecture # 35 :Muscle

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Molecular Mechanisms Of Skeletal Muscle Contraction

4. References

Physiology-A 571
 Learning Objectives

After this lecture, students will be able to:

• Define motor unit and describe its structure

• Describe the sequence of events by which an action potential in a
motor neuron produces an action potential in the plasma membrane of
a skeletal muscle fiber
• Describe the four steps of one cross-bridge cycle..

Physiology-A 572
 Introduction

• Muscle is one of the four tissue types that make up the human body.
The ability to harness chemical energy to produce force and movement
is present to a limited extent in most cells, but in muscle cells it has
become dominant. Muscles generate force and movements used to
regulate the internal environment, and they also produce movements
of the body in relation to the external environment. Most skeletal
muscle, as the name implies, is attached to bone, and its contraction is
responsible for supporting and moving the skeleton contraction of
skeletal muscle is initiated by action potentials in neurons of the
somatic motor division of the peripheral nervous system and is usually
under voluntary control.

Physiology-A 573
Molecular Mechanisms of Skeletal Muscle
Contraction

• Membrane Excitation: The Neuromuscular Junction

• Stimulation of the neurons to a skeletal muscle is the only mechanism
by which action potentials are initiated in this type of muscle.
• The neurons whose axons innervate skeletal muscle fibers are known
as alpha motor neurons (or simply as motor neurons), and their cell
bodies are located in the brainstem and the spinal cord.
• The axons of motor neurons are myelinated and are the largest-
diameter axons in the body.
• They are able to propagate action potentials at high velocities,
allowing signals from the central nervous system to travel to skeletal
muscle fibers with minimal delay.Subject Name 574
Physiology-A 574
Molecular Mechanisms of Skeletal Muscle
Contraction

• Upon reaching a muscle, the axon of a motor neuron divides into

many branches, each branch forming a single synapse with a muscle
fiber.
• A single motor neuron innervates many muscle fibers, but each muscle
fiber is controlled by a branch from only one motor neuron.
• Together, a motor neuron and the muscle fibers it innervates are called
a motor unit . The muscle fibers in a single motor unit are located in
one muscle, but they are distributed throughout the muscle and are not
necessarily adjacent to each other .
• When an action potential occurs in a motor neuron, all the muscle
fibers in its motor unit are stimulated to contract.
Subject Name 575
Physiology-A 575
Molecular Mechanisms of Skeletal Muscle
Contraction

• The axon terminals of a motor neuron contain vesicles similar to

those found at synaptic junctions between two neurons. The vesicles
contain the neurotransmitter acetylcholine (ACh).
• The region of the muscle fiber plasma membrane that lies directly
under the terminal portion of the axon is known as the motor end
plate.
• The junction of an axon terminal with the motor end plate is known
as a neuromuscular junction .

576
Subject Name–A
Physiology 576
Molecular Mechanisms Of Skeletal Muscle
Contraction

• When an action potential in a motor neuron arrives at the axon

terminal, it depolarizes the plasma membrane, opening voltage-
sensitive Ca2+ channels and allowing calcium ions to diffuse into the
axon terminal from the extracellular fluid.
• This Ca2+ binds to proteins that enable the membranes of ACh-
containing vesicles to fuse with the neuronal plasma membrane ,
thereby releasing ACh into the extracellular cleft separating the axon
terminal and the motor end plate.
• ACh diffuses from the axon terminal to the motor end plate where it
binds to ionotropic receptors of the nicotinic type . The binding of
ACh opens an ion channel.

Subject Name 577

Physiology-A 577
Molecular Mechanisms of Skeletal Muscle
Contraction

• In each receptor protein; both sodium and potassium ions can pass
through these channels. Because of the differences in electrochemical
gradients across the plasma membrane more Na+ moves in than K+
out, producing a local depolarization of the motor end plate known as
an end-plate potential (EPP).
• This action potential is then propagated over the surface of the muscle
fiber and into the T-tubules.
• Every action potential in a motor neuron normally produces an action
potential in each muscle fiber in its motor unit

Subject Name 578

Physiology-A 578
Molecular Mechanisms of Skeletal Muscle
Contraction

Subject Name 579

Physiology-A 579
Molecular Mechanisms of Skeletal Muscle
Contraction

Subject Name 580

Physiology-A 580
Molecular Mechanisms of Skeletal Muscle
Contraction

Subject Name 581

Physiology-A 581
 Disruption of Neuromuscular Signaling

• There are many ways by which disease or drugs can modify events at
the neuromuscular junction.
• For example, curare, a deadly arrowhead poison still used by some
indigenous peoples of South America, binds strongly to nicotinic ACh
receptors.
• It does not open their ion channels, however, and is resistant to
destruction by acetylcholinesterase. When a receptor is occupied by
curare, Ach cannot bind to the receptor.
• There is no resulting EPP in the motor end plate and no contraction.

Subject Name 582

Physiology-A 582
 Excitation–Contraction Coupling

• In a resting muscle, tropomyosin molecules that are in contact with the

actin subunits of the thin filaments block the attachment of cross-
bridges to actin.
• Contraction is initiated by an increase in cytosolic Ca2+ concentration.
The calcium ions bind to troponin, producing a change in its shape that
is transmitted via tropomyosin to uncover the binding sites on actin,
allowing the cross-bridges to bind to the thin filaments.
• a. The increase in cytosolic Ca2+ concentration is triggered by an
action potential in the plasma membrane. The action potential is
propagated into the interior of the fiber along the transverse tubules to
the region of the sarcoplasmic reticulum,

Subject Name 583

Physiology-A 583
 Excitation–Contraction Coupling

• b. Relaxation of a contracting muscle fiber occurs as a result of the

active transport of cytosolic calcium ions back into the sarcoplasmic
reticulum.
• When a skeletal muscle fiber actively shortens, the thin filaments are
propelled toward the center of their sarcomere by movements of the
myosin cross-bridges that bind to actin.
• The cross-bridges undergo repeated cycles during a contraction, each
cycle producing only a small increment of movement.

Subject Name 584

Physiology-A 584
Excitation–Contraction Coupling

Subject Name 585

Physiology-A 585
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 586
 PHYSIOLOGY-A
PHARM 313

Lecture # 36 :Muscle

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Mechanics Of Single-fiber Contraction

4. Skeletal Muscle Energy Metabolism

5. References

Physiology-A 588
 Learning Objectives

After this lecture, students will be able to:

• Describe isometric, concentric, and eccentric contractions.

• What is the function of creatine phosphate in skeletal muscle
contraction?
• What fuel molecules are metabolized to produce ATP during skeletal
muscle activity?
• List the factors responsible for skeletal muscle fatigue.

Physiology-A 589
 Introduction

• Muscle is one of the four tissue types that make up the human body.
The ability to harness chemical energy to produce force and movement
is present to a limited extent in most cells, but in muscle cells it has
become dominant. Muscles generate force and movements used to
regulate the internal environment, and they also produce movements
of the body in relation to the external environment. Most skeletal
muscle, as the name implies, is attached to bone, and its contraction is
responsible for supporting and moving the skeleton contraction of
skeletal muscle is initiated by action potentials in neurons of the
somatic motor division of the peripheral nervous system and is usually
under voluntary control.

Physiology-A 590
 Mechanics of Single-Fiber Contraction

• The force exerted on an object by a contracting muscle is known as

muscle tension, and the force exerted on the muscle by an object
(usually its weight) is the load.
• Muscle tension and load are opposing forces. Whether a fiber
shortens depends on the relative magnitudes of the tension and the
load.
• For muscle fibers to shorten and thereby move a load, muscle tension
must be greater than the opposing load.

Subject Name 591

Physiology-A 591
 Isometric (Constant Length) Contraction

• When a muscle develops tension but does not shorten or lengthen, the
contraction is said to be an isometric (constant length) contraction.

• Such contractions occur when the muscle supports a load in a

constant position or attempts to move an otherwise supported load that
is greater than the tension developed by the muscle.

Subject Name 592

Physiology-A 592
 Concentric ( Shortening ) Contraction.

• A contraction in which the muscle changes length while the load on

the muscle remains constant is an isotonic (constant tension)
contraction.
• If the muscle tension is greater than the load, the muscle shortens
when it contracts.
• This may be an isotonic contraction, but can be described more
generally as a concentric (or shortening ) contraction.

593
Subject Name–A
Physiology 593
 Eccentric ( Lengthening ) Contraction

• When a force exerted on a muscle to stretch it is greater than the force

of muscle contraction, the muscle will be stretched by that force, the
muscle will lengthen despite its contraction. This is known as an
eccentric (or lengthening ) contraction.
• For example, when you do a ―curl‖ with a dumbbell, your biceps
brachii muscle produces a concentric contraction as you flex your
forearm. When gently lower the dumbbell back to the resting position,
biceps produces an eccentric contraction.
• The force of contraction of biceps in this example allows the dumbbell
to be lowered gently against the force of gravity as your biceps
lengthens.

Subject Name 594

Physiology-A 594
 Skeletal Muscle Energy Metabolism

• In no other cell type does the rate of ATP breakdown increase so much
from one moment to the next as in a skeletal muscle fiber when it goes
from rest to a state of contractile activity.

• The rate of ATP breakdown may change 20- to several-hundred-fold

depending on the type of muscle fiber.

Subject Name 595

Physiology-A 595
 Skeletal Muscle Energy Metabolism

• There are three ways a muscle fiber can form ATP

(1) phosphorylation of ADP by creatine phosphate (a small molecule
produced from three amino acids and capable of functioning as a
phosphate donor),
(2) oxidative phosphorylation of ADP in the mitochondria, and
(3) phosphorylation of ADP by the glycolytic pathway in the cytosol.

Subject Name 596

Physiology-A 596
 Skeletal Muscle Energy Metabolism

• Creatine Phosphate
• Phosphorylation of ADP by creatine phosphate (CP) provides a very
rapid means of forming ATP at the onset of contractile activity.
• When the chemical bond between creatine (C) and phosphate is
broken, the amount of energy released is about the same as that
released when the terminal phosphate bond in ATP is broken.
• This energy, along with the phosphate group, can be transferred to
ADP to form ATP in a reversible reaction catalyzed by the enzyme
creatine kinase:

Subject Name 597

Physiology-A 597
 Skeletal Muscle Energy Metabolism

• Oxidative Phosphorylation
• At moderate levels of muscular activity, most of the ATP used for
muscle contraction is formed by oxidative phosphorylation .
• During the first 5 to 10 min of moderate exercise, breakdown of
muscle glycogen to glucose provides the major fuel contributing to
oxidative phosphorylation.
• For the next 30 min or so, blood-borne fuels become dominant, blood
glucose and fatty acids contributing approximately equally.

Subject Name 598

Physiology-A 598
 Skeletal Muscle Energy Metabolism

• Glycolysis
• If the intensity of exercise exceeds about 70% of the maximal rate of
ATP breakdown, glycolysis contributes an increasingly significant
fraction of the total ATP generated by the muscle.
• The glycolytic pathway, although producing only small quantities of
ATP from each molecule of glucose metabolized, can produce ATP
quite rapidly when enough enzymes and substrate are available, and it
can do so in the absence of oxygen (anaerobic conditions).
• This is associated with a corresponding increase in the production of
lactic acid.
Subject Name 599
Physiology-A 599
Skeletal Muscle Energy Metabolism

Subject Name 600

Physiology-A 600
 Muscle Fatigue

• When a skeletal muscle fiber is repeatedly stimulated, the tension the

fiber develops eventually decreases even though the stimulation
continues . This decline in muscle tension as a result of previous
contractile activity is known as muscle fatigue.
• The onset of fatigue and its rate of development depend on the type of
skeletal muscle fiber that is active, the intensity and duration of
contractile activity, and the degree of an individual’s fitness.

Subject Name 601

Physiology-A 601
 Muscle Fatigue

• Muscle fatigue that occurs during other types of exercise appears to

have different causes.
• Chiefly, there is depletion of muscle glycogen and a reduced ability of
the sarcoplasmic reticulum to release Ca 2 + , leading to failure of
excitation-contraction coupling.
• Increases in the concentrations of ADP, Pi, Mg2+, H+ (from lactic
acid), and oxygen free radicals.

Subject Name 602

Physiology-A 602
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 603
 PHYSIOLOGY-A
PHARM 313

Lecture # 37 :Muscle

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Types Of Skeletal Muscle Fibers

4. Whole-muscle Contraction

5. Control Of Muscle Tension

6. References

Physiology-A 605
 Learning Objectives

After this lecture, students will be able to:

• Summarize the characteristics of the three types of skeletal muscle
fibers.
• Upon what factors does the amount of tension developed by a whole
skeletal muscle depend?

Physiology-A 606
 Introduction

• Muscle is one of the four tissue types that make up the human body.
The ability to harness chemical energy to produce force and movement
is present to a limited extent in most cells, but in muscle cells it has
become dominant. Muscles generate force and movements used to
regulate the internal environment, and they also produce movements
of the body in relation to the external environment. Most skeletal
muscle, as the name implies, is attached to bone, and its contraction is
responsible for supporting and moving the skeleton contraction of
skeletal muscle is initiated by action potentials in neurons of the
somatic motor division of the peripheral nervous system and is usually
under voluntary control.

Physiology-A 607
 Types of Skeletal Muscle Fibers

• Different types of fibers can be classified on the basis of

(1) their maximal velocities of shortening— fast or slow-twitch—and
(2) the major pathway they use to form ATP—oxidative or glycolytic.
• Fast and slow fibers contain forms of myosin that differ in the
maximal rates at which they use ATP, and corresponding differences in
proteins that affect the speed of membrane excitation, excitation–
contraction coupling, and ATP-production mechanisms.
• The myosin subtype in each fiber determines the maximal rate of
cross-bridge cycling and thus the maximal shortening velocity.

Subject Name 608

Physiology-A 608
 Types of Skeletal Muscle Fibers

• Slow-twitch fibers (also referred to as type 1 fibers) contain myosin

with low ATPase activity. Fasttwitch fibers (or type 2 fibers) contain
myosin with ATPase activity that is about four times higher.
• The extraocular muscles thatposition the eyes, for example, have a
high proportion of fast-twitch fibers The soleus muscle in the leg, by
contrast, has a high proportion of slow twitch fibers.
• The second means of classifying skeletal muscle fibers is according to
the abundance of the different types of enzymatic machinery available
for synthesizing ATP. Some fibers contain numerous mitochondria and
thus have a high capacity for oxidative phosphorylation.
Subject Name 609
Physiology-A 609
 Types of Skeletal Muscle Fibers

• These fibers are classified as oxidative fibers. Most of the ATP such
fibers produce is dependent upon blood flow to deliver oxygen and
fuel molecules to the muscle. Not surprisingly, therefore, these fibers
are surrounded by many small blood vessels.
• They also contain large amounts of an oxygen-binding protein known
as myoglobin, which increases the rate of oxygen diffusion into the
fiber and provides a small store of oxygen. The large amounts of
myoglobin present in oxidative fibers give the fibers a dark red color;
thus, oxidative fibers are often referred to as red muscle fibers.

610
Subject Name–A
Physiology 610
 Types of Skeletal Muscle Fibers

• glycolytic fibers have few mitochondria but possess a high

concentration of glycolytic enzymes and a large store of glycogen.
• Corresponding to their limited use of oxygen, these fibers are
surrounded by relatively few blood vessels and contain little
myoglobin.
• The lack of myoglobin is responsible for the pale color of glycolytic
fibers and their designation as white muscle fibers.

Subject Name 611

Physiology-A 611
Types of Skeletal Muscle Fibers

Subject Name 612

Physiology-A 612
 Whole-Muscle Contraction

• whole muscles are made up of many muscle fibers organized into

motor units.

• All the muscle fibers in a single motor unit are of the same fiber type.
Thus, apply the fiber designation to the motor unit and refer to slow-
oxidative motor units, fast-oxidative-glycolytic motor units, and fast-
glycolytic motor units.

Subject Name 613

Physiology-A 613
 Whole-Muscle Contraction

• Most skeletal muscles are composed of all three motor unit types
interspersed with each other .
• No muscle has only a single fiber type. Depending on the proportions
of the fiber types present, muscles can differ considerably in their
maximal contraction speed, strength, and fatigability.
• For example, the muscles of the back, which must be able to maintain
their activity for long periods of time without fatigue while supporting
an upright posture, contain large numbers of slow-oxidative fibers.

Subject Name 614

Physiology-A 614
 Whole-Muscle Contraction

• In contrast, muscles in the arms that are called upon to produce large
amounts of tension over a short time period, as when a boxer throws a
punch, have a greater proportion of fast-glycolytic fibers.
• Leg muscles used for fast running over intermediate distances
typically have a high proportion of fast-oxidative-glycolytic fibers.
Significant variation occurs between individuals.
• For example, elite distance runners on average have greater than 75%
slow-twitch fibers in the gastrocnemius muscle of the lower leg,
• In elite sprinters the same muscle has 75% fast-twitch fibers.

Subject Name 615

Physiology-A 615
 Control of Muscle Tension

The total tension a muscle can develop depends upon two factors:
(1) the amount of tension developed by each fiber, and
(2) the number of fibers contracting at any time. By controlling these
two factors, the nervous system controls whole-muscle tension as well
as shortening velocity.
The number of fibers contracting at any time depends on
(1) the number of fibers in each motor unit (motor unit size), and
(2) the number of active motor units.

Subject Name 616

Physiology-A 616
 Control of Muscle Tension

• Motor unit size varies considerably from one muscle to another.

• The muscles in the hand and eye, which produce very delicate
movements, contain small motor units.
• For example, one motor neuron innervates only about 13 fibers in an
eye muscle.
• In the more coarsely controlled muscles of the legs, each motor unit is
large, containing hundreds and in some cases several thousand fibers.
• When a muscle is composed of small motor units, the total tension the
muscle produces can be increased in small steps by activating
additional motor units.

Subject Name 617

Physiology-A 617
 Control of Muscle Tension

• If the motor units are large, large increases in tension will occur as
each additional motor unit is activated.
• Thus, finer control of muscle tension is possible in muscles with small
motor units.
• The process of increasing the number of motor units that are active in
a muscle at any given time is called recruitment. It is achieved by
activating excitatory synaptic inputs to more motor neurons.
• The greater the number of active motor neurons, the more motor units
recruited and the greater the muscle tension.

Subject Name 618

Physiology-A 618
Control of Muscle Tension

Subject Name 619

Physiology-A 619
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 620
 PHYSIOLOGY-A
PHARM 313

Lecture # 38 :Control of Body Movement

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Motor Control Hierarchy

4. References

Physiology-A 622
 LEARNING OBJECTIVES

After this lecture, students will be able to:

• Describe motor control in terms of the conceptual motor control
hierarchy.
• List the characteristics of voluntary actions.

Subject Name 623

Physiology-A 623
 Introduction

• The building blocks for these movements—as for all movements—are

motor units, each comprising one motor neuron together with all the
skeletal muscle fibers innervated by that neuron. The motor neurons
are the final common pathway out of the central nervous system
because all neural influences on skeletal muscle converge on the motor
neurons and can only affect skeletal muscle through them. All the
motor neurons that supply a given muscle make up the motor neuron
pool for the muscle. The cell bodies of the Within the brainstem or
spinal cord, the axon terminals of many neurons synapse on a motor
neuron to control its activity.

Physiology-A 624
 Introduction

The precision and speed of normally coordinated actions are produced

by a balance of excitatory and inhibitory inputs onto motor neurons.
For example, if inhibitory synaptic input to a given motor neuron is
removed, the excitatory input to that neuron will be unopposed and the
motor neuron firing will increase, leading to increased contraction. It
is important to realize that movements—even simple movements such
as flexing a finger—are rarely achieved by just one muscle. Body
movements are achieved by activation, in a precise sequence, of many
motor units in various muscles.

Physiology-A 625
 Motor Control Hierarchy

• The neurons involved in controlling skeletal muscles can be thought of

as being organized in a hierarchical fashion, with each level of the
hierarchy having a certain task in motor control .
• To begin a consciously planned movement, a general intention such
as ―pick up sweater‖ or ―write signature‖ or answer telephone‖ is
generated at the highest level of the motor control hierarchy.
• These higher centers include many regions of the brain (described in
detail later), including cortical and subcortical areas involved in
memory, emotions, and motivation.

Subject Name 626

Physiology-A 626
 Motor Control Hierarchy

• Information is relayed from these higher-center ―command‖ neurons

to parts of the brain that make up the middle level of the motor control
hierarchy.
• The middle-level structures specify the individual postures and
movements needed to carry out the intended action.
• In example of picking up a sweater, structures of the middle
hierarchical level coordinate the commands that tilt the body and
extend the arm and hand toward the sweater and shift the body’s
weight to maintain balance.
627
Subject Name–A
Physiology 627
 Motor Control Hierarchy

• The middle-level hierarchical structures are located in sensory and

motor regions of the cerebral cortex as well as in the cerebellum,
subcortical nuclei, and brainstem. These structures have extensive
interconnections.
• As the neurons in the middle level of the hierarchy receive input from
the command neurons, they simultaneously receive afferent
information from receptors in the muscles, tendons, joints, and skin, as
well as from the vestibular apparatus and eyes.
• Utilizing this afferent input, middle-level neurons build an internal
model of the pattern of neural activity that will be required to perform
a movement (sometimes referred to as a motor program).

Subject Name 628

Physiology-A 628
 Motor Control Hierarchy

• The model integrates information about the starting position of body

parts, the nature of the space they will move through, and
environmental elements with which they will interact (such as the
properties ofa diving board).
• The importance of sensory pathways in planning movements is
demonstrated by the fact that when these pathways are impaired, a
person has not only sensory deficits but also slow and uncoordinated
voluntary movement.
• The information determined by the motor program is transmitted via
descending pathways to the local level of the motor control
hierarchy

Subject Name 629

Physiology-A 629
 Motor Control Hierarchy

•There, the axons of the motor neurons projecting to the

muscles exit the brainstem or spinal cord.
•The local level of the hierarchy includes afferent neurons,
motor neurons, and interneurons.
•Local-level neurons determine exactly which motor neurons
will be activated to achieve the desired action and when this
will happen.

Subject Name 630

Physiology-A 630
 Motor Control Hierarchy

• The term sensorimotor cortex is used to describe the widespread

regions of the frontal and parietal lobes that act together to control
muscle movement.
• Other brain areas, notably the basal nuclei (also referred to as the basal
ganglia), thalamus, and cerebellum, exert their effects on the local
level only indirectly via the descending pathways from the cerebral
cortex and brainstem.
• The motor programs are continuously adjusted during the course of
most movements. As the initial motor program begins and the action
gets underway, brain regions at the middle level of the hierarchy
continue to

Subject Name 631

Physiology-A 631
 Motor Control Hierarchy

receive a constant stream of updatedafferent information about the

movements taking place.
• Afferent information about the position of the body and its parts in
space is called proprioception.
• For example, that the sweater you are picking up is wet and heavier
than you expected so that the initially determined strength of muscle
contraction is not sufficient to lift it.
• Any discrepancies between the intended and actual movements are
detected, program corrections are determined, and the corrections are
relayed to the local level of the hierarchy and the motor neurons.
Subject Name 632
Physiology-A 632
Motor Control Hierarchy

Subject Name 633

Physiology-A 633
Motor Control Hierarchy

Subject Name 634

Physiology-A 634
 .Voluntary and Involuntary Actions

• .Voluntary refer to actions that have the following characteristics: (

1) The movement is accompanied by a conscious awareness of what we
are doing and why we are doing it, and
2) our attention is directed toward the action or its purpose.
• The term involuntary, on the other hand, describes actions that do not
have these characteristics.
• Almost all motor behavior involves both components,
• For example, some highly conscious acts with a repetitive nature,
such as walking, are initiated by preprogrammed pattern-generating
circuits in the brain and spinal cord.

Subject Name 635

Physiology-A 635
 Voluntary and Involuntary Actions

• The alternating pattern of contraction of muscles activated by those

circuits is then subconsciously varied in response to unique situations,
as might occur when you encounter obstacles or uneven terrain while
walking.
• Moreover, actions shift along this continuum according to the
frequency with which they are performed. When a person first learns
to drive a car with a manual transmission, for example, shifting gears
requires a great deal of conscious attention. With practice, those same
actions become automatic.
• Reflex behaviors that are generally involuntary can, with special
effort, sometimes be voluntarily modified or even prevented.

Subject Name 636

Physiology-A 636
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 637
 PHYSIOLOGY-A
PHARM 313

Lecture # 39 :Control of Body Movement

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Local Control Of Motor Neurons

4. References

Physiology-A 639
 Learning Objectives

After this lecture, students will be able to:

• List the inputs that can converge on the interneurons active in local
motor control.
• Draw a muscle spindle within a muscle, labeling the spindle,

Subject Name 640

Physiology-A 640
 Introduction

• The building blocks for these movements—as for all movements—are

motor units, each comprising one motor neuron together with all the
skeletal muscle fibers innervated by that neuron. The motor neurons
are the final common pathway out of the central nervous system
because all neural influences on skeletal muscle converge on the motor
neurons and can only affect skeletal muscle through them. All the
motor neurons that supply a given muscle make up the motor neuron
pool for the muscle. The cell bodies of the Within the brainstem or
spinal cord, the axon terminals of many neurons synapse on a motor
neuron to control its activity.

Physiology-A 641
 Introduction

. The precision and speed of normally coordinated actions are produced

by a balance of excitatory and inhibitory inputs onto motor neurons.
For example, if inhibitory synaptic input to a given motor neuron is
removed, the excitatory input to that neuron will be unopposed and the
motor neuron firing will increase, leading to increased contraction. It
is important to realize that movements—even simple movements such
as flexing a finger—are rarely achieved by just one muscle. Body
movements are achieved by activation, in a precise sequence, of many
motor units in various muscles.

Physiology-A 642
 Local Control of Motor Neurons

• The local control systems are the relay points for instructions to the
motor neurons from centers higher in the motor control hierarchy.
• In addition, the local control systems are very important in adjusting
motor unit activity to unexpected obstacles to movement and to
painful stimuli in the surrounding environment.
• To carry out these adjustments, the local control systems use
information carried by afferent fibers from sensory receptors in the
muscles, tendons, joints, and skin of the body parts to be moved.

Subject Name 643

Physiology-A 643
 Interneurons

• Most of the synaptic input to motor neurons from the descending

pathways and afferent neurons does not go directly to motor neurons
but, rather, goes to interneurons that synapse with the motor neurons.
• Interneurons comprise 90% of spinal cord neurons, and they are of
several types. Some are near the motor neuron they synapse upon and
thus are called local interneurons.
• Others have processes that extend up or down short distances in the
spinal cord

644
Subject Name–A
Physiology 644
 Interneurons

and brainstem, or even throughout much of the length of the central

nervous system.
• The interneurons with longer processes are important for integrating
complex movements such as stepping forward with your left foot as
you throw a baseball with your right arm.
• The interneurons are important elements of the local level of the motor
control hierarchy, integrating inputs not only from higher centers and
peripheral receptors but from other interneurons as well .
• They are crucial in determining which muscles are activated and
when.
Subject Name 645
Physiology-A 645
 Interneurons

• This is especially important in coordinating repetitive, rhythmic

activities like walking or running, for which spinal cord interneurons
encode pattern generator circuits responsible for activating and
inhibiting limb movements in an alternating sequence.
• Interneurons can act as ―switches‖ that enable a movement to be
turned on or off under the command of higher motor centers.
• For example, if you pick up a hot plate, a local reflex arc will be
initiated by pain receptors in the skin of your hands, normally causing
you to drop the plate.

Subject Name 646

Physiology-A 646
 Interneurons

• If it contains your dinner, however, descending commands

can inhibit the local activity and you can hold onto the plate
until you reach a location where you can put it down safely.
• The integration of various inputs by local interneurons is a
prime example of the general principle of physiology that most
physiological functions are controlled by multiple regulatory
systems, often working in opposition.
Subject Name 647
Physiology-A 647
 Local Afferent Input

Afferent fibers sometimes impinge on the local interneurons.

The afferent fibers carry information from sensory receptors located in
three places:
(1) in the skeletal muscles controlled by the motor neurons;
(2) in other muscles, such as those with antagonistic actions; and
(3) in the tendons, joints, and skin of body parts affected by the action
of the muscle. Voluntary and Involuntary Actions

Subject Name 648

Physiology-A 648
 Local Afferent Input

• These receptors monitor the length and tension of the muscles,

movement of the joints, and the effect of movements on the overlying
skin.
• The movements themselves give rise to afferent input that, in turn,
influences how the movement proceeds.
• Their input sometimes provides negative feedback control over the
muscles and also contributes to the conscious awareness of limb and
body position.

Subject Name 649

Physiology-A 649
Local Afferent Input

Subject Name 650

Physiology-A 650
 Length-Monitoring Systems

• Stretch receptors embedded within muscles monitor muscle length and

the rate of change in muscle length.
• These receptors consist of peripheral endings of afferent nerve fibers
wrapped around modified muscle fibers, several of which are enclosed
in a connective-tissue capsule.
• The entire apparatus is collectively called a muscle spindle .
• The modified muscle fibers within the spindle are known as
intrafusal fibers. The skeletal muscle fibers that form the bulk of
the muscle and generate its force and movement (which were the
focus of are the extrafusal fibers.
Subject Name 651
Physiology-A 651
 The Stretch Reflex

• When the afferent fibers from the muscle spindle enter the central
nervous system, they divide into branches that take different paths.
• Path A makes excitatory synapses directly onto motor neurons that
return to the muscle that was stretched, thereby completing a reflex arc
known as the stretch reflex.
• This reflex is important in maintaining balance and posture, and is
probably most familiar in the form of the knee-jerk reflex, part of a
routine medical examination.

Subject Name 652

Physiology-A 652
 The Withdrawal Reflex

• In addition to the afferent information from the spindle stretch

receptors and Golgi tendon organs of activated muscles, other input is
transmitted to the local motor control systems.
• For example, painful stimulation of the skin, as occurs from stepping
on a tack, activates the flexor muscles and inhibits the extensor
muscles of the ipsilateral leg (on the same side of the body).
• The resulting action moves the affected limb away from the harmful
stimulus and is thus known as a withdrawal reflex.

Subject Name 653

Physiology-A 653
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 654
 PHYSIOLOGY-A
PHARM 313

Lecture # 40 :Control of Body Movement

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives of the lecture

3. The Brain Motor Centers (Cerebral Cortex , Subcortical and

Brainstem Nuclei , Cerebellum)

4. Descending Pathways (Corticospinal Pathway , Brainstem Pathways

5. References

Physiology-A 656
 Learning Objectives

After this lecture, students will be able to:

• Distinguish among the following areas of the cerebral cortex:
sensorimotor, primary motor, premotor, and supplementary motor
• Describe the functions that the basal nuclei and cerebellum have in
motor control.
• Contrast the two major types of descending motor pathways in terms
of structure and function.

Subject Name 657

Physiology-A 657
 Introduction

• The building blocks for these movements—as for all movements—are

motor units, each comprising one motor neuron together with all the
skeletal muscle fibers innervated by that neuron. The motor neurons
are the final common pathway out of the central nervous system
because all neural influences on skeletal muscle converge on the motor
neurons and can only affect skeletal muscle through them. All the
motor neurons that supply a given muscle make up the motor neuron
pool for the muscle. The cell bodies of the Within the brainstem or
spinal cord, the axon terminals of many neurons synapse on a motor
neuron to control its activity.

Physiology-A 658
 Introduction

. The precision and speed of normally coordinated actions are produced

by a balance of excitatory and inhibitory inputs onto motor neurons.
For example, if inhibitory synaptic input to a given motor neuron is
removed, the excitatory input to that neuron will be unopposed and the
motor neuron firing will increase, leading to increased contraction. It
is important to realize that movements—even simple movements such
as flexing a finger—are rarely achieved by just one muscle. Body
movements are achieved by activation, in a precise sequence, of many
motor units in various muscles.

Physiology-A 659
The Brain Motor Centersand the Descending
PathwaysThey Control

Cerebral Cortex
• A network of connected neurons in the frontal and parietal lobes of the
cerebral cortex has a critical function in both the planning and ongoing
control of voluntary movements, functioning in both the highest and
middle levels of the motor control hierarchy.
• A large number of neurons that give rise to descending pathways for
motor control come from two areas of sensorimotor cortex on the
posterior part of the frontal lobe: the primary motor cortex
(sometimes called simply the motor cortex) and the premotor area .

Subject Name 660

Physiology-A 7
Cerebral Cortex

661
Subject Name–A
Physiology 661
 Subcortical and Brainstem Nuclei

• Numerous highly interconnected structures lie in the brainstem and

within the cerebrum beneath the cortex, where they interact with the
cortex to control movements.

• Their influence is transmitted indirectly to the motor neurons both by

pathways that ascend to the cerebral cortex and by pathways that
descend from some of the brainstem nuclei.
Subject Name 662
Physiology-A 662
 Parkinson’s Disease

• In Parkinson’s disease, the input to the basal nuclei is diminished, the

interplay of the facilitatory and inhibitory circuits is unbalanced, and
activation of the motor cortex (via the basal nuclei–thalamus limb of
the circuit just mentioned) is reduced. Clinically, Parkinson’s disease
is characterized by a reduced amount of movement (akinesia), slow
movements (bradykinesia), muscular rigidity, and a tremor at rest.
• A major part of the initial defect arises in neurons of the substantia
nigra These neurons normally project to the basal nuclei, where they
release dopamine from their axon terminals.

Subject Name 663

Physiology-A 663
 Cerebellum

• The cerebellum receives information from the sensorimotor cortex

and also from the vestibular system, eyes, skin, muscles, joints, and
tendons—that is, from some of the very receptors that movement
affects.
• One role of the cerebellum in motor functioning is to provide timing
signals to the cerebral cortex and spinal cord for precise execution of
the different phases of a motor program.
• It also helps coordinate movements that involve several joints and
stores the memories of these movements.

Subject Name 664

Physiology-A 664
 Cerebellum

• The cerebellum also participates in planning movements— integrating

information about the nature of an intended movement with
information about the surrounding space.

• Unstable posture and awkward gait are two other symptoms

characteristic of cerebellar disease.

Subject Name 665

Physiology-A 665
 Descending Pathways

• The influence exerted by the various brain regions on posture and

movement occurs via descending pathways to the motor neurons and
the interneurons that affect them.
• The pathways are of two types: the corticospinal pathways, which,
as their name implies, originate in the cerebral cortex; and
• a second group we will refer to as the brainstem pathways, which
originate in the brainstem.

Subject Name 666

Physiology-A 666
 Corticospinal Pathway

• The nerve fibers of the corticospinal pathways have their cell bodies
in the sensorimotor cortex and terminate in the spinal cord. The
corticospinal pathways are also called the pyramidal tracts or
pyramidal system because of their triangular shape as they pass
along the ventral surface of the medulla oblongata.
• Corticospinal pathways control rapid, fine movements of the distal
extremities, such as those you make when you manipulate an object
with your fingers.
• After damage occurs to the corticospinal pathways, movements are
slower and weaker, individual finger movements are absent, and it is
difficult to release a grip.

Subject Name 667

Physiology-A 667
 Brainstem Pathways

• Axons from neurons in the brainstem also form pathways that descend
into the spinal cord to influence motor neurons.

• These pathways are sometimes referred to as the extrapyramidal

system, or indirect pathways, to distinguish them from the
corticospinal (pyramidal) pathways.

Subject Name 668

Physiology-A 668
 Brainstem Pathways

• The brainstem descending pathways, in contrast, are involved more

with coordination of the large muscle groups of the trunk and proximal
portions of the limbs used in the maintenance of upright posture, in
locomotion, and in head and body movements when turning toward a
specific stimulus.
• The distinctions between the corticospinal and brainstem descending
pathways are not clear-cut.
• All movements, whethervautomatic or voluntary, require the
continuous coordinated interaction of both types of pathways.

Subject Name 669

Physiology-A 669
Brainstem Pathways

Subject Name 670

Physiology-A 670
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 671
 PHYSIOLOGY-A
PHARM 313

Lecture # 41 :Control of Body Movement

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Learning Objectives

3. Muscle Tone

4. REFERENCES

Physiology-A 673
 Learning Objectives

After this lecture, students will be able to:

• Explain how hypertonia may result from disease of the descending
pathways.
• Explain how hypotonia may result from lower motor neuron disease.

Subject Name 674

Physiology-A 6
 Introduction

• The building blocks for these movements—as for all movements—are

motor units, each comprising one motor neuron together with all the
skeletal muscle fibers innervated by that neuron. The motor neurons
are the final common pathway out of the central nervous system
because all neural influences on skeletal muscle converge on the motor
neurons and can only affect skeletal muscle through them. All the
motor neurons that supply a given muscle make up the motor neuron
pool for the muscle. The cell bodies of the Within the brainstem or
spinal cord, the axon terminals of many neurons synapse on a motor
neuron to control its activity.

Physiology-A 675
 Introduction

. The precision and speed of normally coordinated actions are produced

by a balance of excitatory and inhibitory inputs onto motor neurons.
For example, if inhibitory synaptic input to a given motor neuron is
removed, the excitatory input to that neuron will be unopposed and the
motor neuron firing will increase, leading to increased contraction. It
is important to realize that movements—even simple movements such
as flexing a finger—are rarely achieved by just one muscle. Body
movements are achieved by activation, in a precise sequence, of many
motor units in various muscles.

Physiology-A 676
 Muscle Tone

• Even when a skeletal muscle is relaxed, there is a slight and uniform

resistance when it is stretched by an external force.

• This resistance is known as muscle tone, and it can be an important

diagnostic tool for clinicians assessing a patient’s neuromuscular
function.

Subject Name 677

Physiology-A 7
 Muscle Tone

• Intrinsic muscle tone in smooth muscle is due to a baseline level of

Ca2+ in the cytosol that causes low-level activity of tension-
generating cross-bridges.

• By contrast, muscle tone in skeletal muscles is due both to the passive

elastic properties of the muscles and joints and to the degree of
ongoing alpha motor neuron activity.

678
Subject Name–A
Physiology 678
 Abnormal Muscle Tone

• Abnormally high muscle tone, called hypertonia.

• The increased resistance is due to an increased level of alpha motor

neuron activity , Hypertonia usually occurs with disorders of the
descending pathways that normally inhibit the motor neurons.

Subject Name 679

Physiology-A 679
 Abnormal Muscle Tone

• Spasticity is a form of hypertonia in which the muscles do not

develop increased tone until they are stretched a bit; after a brief
increase in tone, the contraction subsides for a short time.

• Spasticity may be accompanied by increased responses of motor

reflexes such as the knee jerk and by decreased coordination and
strength of voluntary actions.
Subject Name 680
Physiology-A 680
 Abnormal Muscle Tone

• Rigidity is a form of hypertonia in which the increased muscle

contraction is continual and the resistance to passive stretch is constant
(as occurs in the disease tetanus,)
• Two other forms of hypertonia that can occur suddenly in individual or
multiple muscles may originate as problems either in muscle cells or
neuronal pathways:
• Muscle spasms are brief, involuntary contractions that may or may
not be painful, and
• muscle cramps are prolonged, involuntary, and painful contractions.

Subject Name 681

Physiology-A 681
 Abnormal Muscle Tone

• Hypotonia is a condition of abnormally low muscle tone

accompanied by weakness, atrophy (a decrease in muscle bulk), and
decreased or absent reflex responses.

• Hypotonia may develop after cerebellar disease, it more frequently

accompanies disorders of the alpha motor neurons (lower motor
neurons), neuromuscular junctions, or the muscles themselves.
Subject Name 682
Physiology-A 682
 Abnormal Muscle Tone

• Amyotrophic Lateral Sclerosis Amyotrophic lateral sclerosis

(ALS) is a lower motor neuron condition in which progressive
degeneration of alpha motor neurons causes hypotonia and atrophy
of skeletal muscles.
•It is often first detected as weakness of limb and trun muscles, but
involvement of muscles used in respiration and swallowing is
generally what makes the condition fatal.

Subject Name 683

Physiology-A 683
 Abnormal Muscle Tone

•There is currently no cure for ALS; treatment consists of

medications and respiratory, occupational, and physical therapies
that provide relief from symptoms and maintain comfort and
independence as long as possible.

Subject Name 684

Physiology-A 684
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 685
 PHYSIOLOGY-A
PHARM 313

Lecture # 42 :Control of Body Movement

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Learning Objectives

3. Maintenance Of Upright Posture And Balance

4. Walking

5. References

Physiology-A 687
 Learning Objectives

After this lecture, students will be able to:

• Explain the function of the crossed-extensor reflex in postural stability.
• Explain the function of the inter neuronal networks in walking,
incorporating in your discussion the following terms

Subject Name 688

Physiology-A 6
 Introduction

• The building blocks for these movements—as for all movements—are

motor units, each comprising one motor neuron together with all the
skeletal muscle fibers innervated by that neuron. The motor neurons
are the final common pathway out of the central nervous system
because all neural influences on skeletal muscle converge on the motor
neurons and can only affect skeletal muscle through them. All the
motor neurons that supply a given muscle make up the motor neuron
pool for the muscle. The cell bodies of the Within the brainstem or
spinal cord, the axon terminals of many neurons synapse on a motor
neuron to control its activity.

Physiology-A 689
 Introduction

. The precision and speed of normally coordinated actions are produced

by a balance of excitatory and inhibitory inputs onto motor neurons.
For example, if inhibitory synaptic input to a given motor neuron is
removed, the excitatory input to that neuron will be unopposed and the
motor neuron firing will increase, leading to increased contraction. It
is important to realize that movements—even simple movements such
as flexing a finger—are rarely achieved by just one muscle. Body
movements are achieved by activation, in a precise sequence, of many
motor units in various muscles.

Physiology-A 690
Maintenance of Upright Posture and Balance

•The skeleton supporting the body is a system of long bones and a many-
jointed spine that cannot stand erect against the forces of gravity without
the support provided through coordinated muscle activity.

Subject Name 691

Physiology-A 7
Maintenance of Upright Posture and Balance

•The muscles that maintain upright posture—that is, support the

body’s weight against gravity—are controlled by the brain and by
reflex mechanisms ―wired into‖ the neural networks of the
brainstem and spinal cord.
•Many of the reflex pathways previously introduced (for example,
the stretch and crossed-extensor reflexes) are active in posture
control.

692
Subject Name–A
Physiology 692
Maintenance of Upright Posture and Balance

• For stability, the center of gravity must be kept within the base of
•support the feet provide .

• Once the center of gravity has moved beyond this base, the body
will fall unless one foot is shifted to broaden the base of support.
• People can operate under conditions of unstable equilibrium because
complex interacting postural reflexes maintain their balance.

Subject Name 693

Physiology-A 693
Maintenance of Upright Posture and Balance

• The afferent pathways of the postural reflexes come from three

sources: the eyes, the vestibular apparatus, and the receptors involved
in proprioception (joint, muscle, and touch receptors, for example).
• The efferent pathways are the alpha motor neurons to the skeletal
muscles, and the integrating centers are neuron networks in the
brainstem and spinal cord.

Subject Name 694

Physiology-A 694
Maintenance of Upright Posture and Balance

• In addition to these integrating centers, there are centers in the brain

that form an internal model of the body’s geometry, its support
conditions, and its orientation with respect to vertical.

• There are many familiar examples of using reflexes to maintain

upright posture; one is the crossed-extensor reflex.

Subject Name 695

Physiology-A 695
Maintenance of Upright Posture and Balance

• As one leg is flexed and lifted off the ground, the other is extended
more strongly to support the weight of the body, and the positions of
various parts of the body are shifted to move the center of Gravity
over the single, weight-bearing leg.

• This shift in the center of gravity, demonstrates, is an important

component in the stepping mechanism of locomotion.

Subject Name 696

Physiology-A 696
 Maintenance of Upright Posture and Balance

•Afferent inputs from the eyes, vestibular apparatus, and somatic

receptors of proprioception are integrated for optimal postural
adjustments.
•The loss of vision or vestibular inputs alone does not cause a person to
topple over.
• Blind people maintain their balance quite well with only a slight loss of
precision.

Subject Name 697

Physiology-A 697
 Walking

• Walking requires the coordination of many muscles, each activated to

a precise degree at a precise time.
• We initiate walking by allowing the body to fall forward to an unstable
position and then moving one leg forward to provide support.
• When the extensor muscles are activated on the supported side of the
body to bear the body’s weight, the contralateral extensors are
inhibited to allow the nonsupporting limb to flex and swing forward.
• The cyclical, alternating movements of walking are brought about
largely by central pattern-generating networks of interneurons in the
spinal cord at the local level.
Physiology-A 698
 Walking

• The interneuron networks coordinate the output of the various motor

neuron pools that control the appropriate muscles of the arms,
shoulders, trunk, hips, legs, and feet

• These pattern generators are controlled by corticospinal and brainstem

descending pathways and affected by feedback and motor programs.

Physiology-A 699
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 700
 PHYSIOLOGY-A
PHARM 313

Lecture # 43 :Consciousness and Behavior

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. States Of Consciousness

4. References

Physiology-A 702
 Learning Objectives

After this lecture, students will be able to:

• State the two criteria used to define one’s state of consciousness.

•Distinguish NREM sleep from REM sleep.

Physiology-A 703
 Introduction

• The limbic system is not a separate structure but a functional

system consisting of a ring of forebrain structures that surround the
brain stem and are interconnected by intricate neuron pathways It
includes portions of each of the following: the lobes of the cerebral
cortex (especially the limbic association cortex), the basal nuclei, the
thalamus, and the hypothalamus. This complex interacting network is
associated with emotions, basic behavioral patterns, motivation,
learning, and memory.

Physiology-A 704
 States of Consciousness

• The term consciousness includes two distinct concepts: states of

consciousness and conscious experiences.
• The first concept refers to levels of alertness such as being awake,
drowsy, or asleep.
• The second refers to experiences a person is aware of—thoughts,
feelings, perceptions, ideas, dreams, reasoning—during any of the
states of consciousness.

Subject Name 705

Physiology-A 705
 States of Consciousness

• A person’s state of consciousness is defined in two ways:

(1) by behavior, covering the spectrum from maximum attentiveness to
comatose; and
(2) by the pattern of brain activity that can be recorded electrically. This
record, known as the electroencephalogram (EEG),

Subject Name 706

Physiology-A 706
 Electroencephalogram

• Neural activity is manifested by the electrical signals known as graded

potentials and action potentials .

• It is possible to record the electrical activity in the brain’s neurons—

particularly those in the cortex near the surface of the brain—from the
outside of the head, EEG patterns are largely due to synchronous
graded potentials
707
Subject Name–A
Physiology 707
 Electroencephalogram

• The EEG is useful clinically to monitor cerebral activity of surgical

patients under anesthesia, in the diagnosis of neurological diseases,
and in the diagnosis of coma and brain death.

• It was formerly also used in the detection of brain areas damaged by

tumors, blood clots, or hemorrhage.

Subject Name 708

Physiology-A 708
 The Waking State

• Behaviorally, the waking state is far from homogeneous, reflecting the

wide variety of activities you may be engaged in at any given moment.

• The most prominent EEG wave pattern of an awake, relaxed adult

whose eyes are closed is an oscillation of 8 to 12 Hz, known as the
alpha rhythm.

Subject Name 709

Physiology-A 709
 The Waking State

• When people are attentive to an external stimulus or are thinking hard

about something, the alpha rhythm is replaced by smaller-amplitude,
higher-frequency (>12 Hz) oscillations, the beta rhythm .

• This transformation, known as the EEG arousal, is associated with

the act of paying attention to a stimulus rather than with the act of
perception itself.
Subject Name 710
Physiology-A 710
 Sleep

• The EEG pattern changes profoundly in sleep. As a person becomes

increasingly drowsy, his or her wave pattern transitions from a beta
rhythm to a predominantly alpha rhythm.

• When sleep actually occurs, the EEG shifts toward lower-frequency,

larger-amplitude wave patterns known as the theta rhythm (4–8 Hz)
and the delta rhythm (slower than 4 Hz).
Subject Name 711
Physiology-A 711
Sleep

Subject Name 712

Physiology-A 712
Neural Substrates of States of Consciousness

• Periods of sleep and wakefulness alternate about once a day; that is,
they manifest a circadian rhythm consisting on average of 8 h asleep
and 16 h awake.
• Within the sleep portion of this circadian cycle, NREM sleep and
REM sleep alternate, as we have seen. As we shift from the waking
state through NREM sleep to REM sleep, attention shifts to internally
generated stimuli (dreams) so that we are largely insensitive to
external stimuli.

Subject Name 713

Physiology-A 713
Neural Substrates of States of Consciousnes

• The brainstem reticular formation and all other components involved

in regulating consciousness are sometimes referred to as the reticular
activating system (RAS).

• This system consists of clusters of neurons and neural pathways

originating in the brainstem and hypothalamus, distinguished by both
their anatomical distribution and the neurotransmitters they release.
Subject Name 714
Physiology-A 714
Neural Substrates of States of Consciousnes

• Wakefulness is stimulated or regulated by groups of neurons

originating in the brainstem and hypothalamus that activate cortical
arousal by releasing orexins, norepinephrine, serotonin, histamine, and
acetylcholine.

• A sleep center in the hypothalamus releases GABA and inhibits these

activating centers.
Subject Name 715
Physiology-A 715
 Coma and Brain Death

• The term coma describes an extreme decrease in mental function due

to structural, physiological, or metabolic impairment of the brain.
• A person in a coma exhibits a sustained loss of the capacity for arousal
even in response to vigorous stimulation.
• Experiments using high-density EEG arrays in some coma patients
suggest that even though they exhibit no outward behaviors or
responses, they may have some level of consciousness.

Subject Name 716

Physiology-A 716
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 717
 PHYSIOLOGY-A
PHARM 313

Lecture # 44 :Consciousness and Behavior

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Conscious Experiences

4. References

Physiology-A 719
 Learning Objectives

After this lecture, students will be able to:

• Describe the orienting response as a form of directed attention

Physiology-A 720
 Introduction

• The limbic system is not a separate structure but a functional

system consisting of a ring of forebrain structures that surround the
brain stem and are interconnected by intricate neuron pathways It
includes portions of each of the following: the lobes of the cerebral
cortex (especially the limbic association cortex), the basal nuclei, the
thalamus, and the hypothalamus. This complex interacting network is
associated with emotions, basic behavioral patterns, motivation,
learning, and memory.

Physiology-A 721
 Conscious Experiences

• Conscious experiences are those things we are aware of—either

internal, such as an idea, or external, such as an object or event.
• The most obvious aspect of this phenomenon is sensory awareness,
but we are also aware of inner states such as fatigue, thirst, and
happiness.
• We are aware of the passing of time, of what we are presently thinking
about, and of consciously recalling a fact learned in the past.

Subject Name 722

Physiology-A 722
 Selective Attention

• The term selective attention means avoiding the distraction of

irrelevant stimuli while seeking out and focusing on stimuli that are
momentarily important.
• Both voluntary and reflex mechanisms affect selective attention.
• An example of voluntary control of selective attention familiar to
students is ignoring distracting events in a busy library while studying
there.

Subject Name 723

Physiology-A 723
 Selective Attention

• If the stimulus has meaning for the individual, behavioral changes also
occur.

• The person stops what he or she is doing, listens intently, and turns
toward the stimulus source, a behavior called the orienting response.

724
Subject Name–A
Physiology 724
 Selective Attention

• If a stimulus is repeated but is found to be irrelevant, the behavioral

response to the stimulus progressively decreases, a process known as
habituation.
• For example, when a loud bell is sounded for the first time, it may
evoke an orienting response because the person may be frightened by
or curious about the novel stimulus.
• After several rings, however, the individual has a progressively
smaller response and eventually may ignore the bell altogether.

Subject Name 725

Physiology-A 725
 Selective Attention

• Habituation involves a depression of synaptic transmission in the

involved pathway, possibly related to a prolonged inactivation of Ca2+
channels in presynaptic axon terminals.
• Such inactivation results in a decreased Ca2+ influx during
depolarization and, therefore, a decrease in the amount of
neurotransmitter released by a terminal in response to action potential.

Subject Name 726

Physiology-A 726
Neural Mechanisms for Selective Attention

• Directing our attention to an object involves several distinct

neurological processes.
• First, our attention must be disengaged from its present focus.
• Then, attention must be moved to the new focus.
• Attention must then be engaged at the new focus.
• Finally, there must be an increased level of arousal that produces
prolonged attention to the new focus.

Subject Name 727

Physiology-A 727
 Neural Mechanisms for Selective Attention

• An area that has an important function in orienting and selective

attention is in the brainstem, where the interaction of various sensory
modalities in single cells can be detected experimentally. The receptive
fields of the different modalities overlap.
• The thalamus is another brain region involved in selective attention.
Inputs from regions of the cerebral cortex and brainstem can modulate
synaptic activity in the thalamus, making it a filter that can selectively
influence the transmission of sensory information.

Subject Name 728

Physiology-A 728
Neural Mechanisms of Conscious Experiences

• A further assumption is that the neural activity that corresponds to a

conscious experience resides not in a single anatomical cluster of
―consciousness neurons‖ but rather in a set of neurons that are
temporarily functioning together in a specific way.

Subject Name 729

Physiology-A 729
Neural Mechanisms of Conscious Experiences

• Consider the visual perception of an object. Different aspects of

something we see are processed by different areas of the visual
cortex—the object’s color by one part, its motion by another, its
location in the visual field by another, and its shape by still another—
but we see one object.

Subject Name 730

Physiology-A 730
Neural Mechanisms of Conscious Experiences

• Neurons from the various parts of the brain that simultaneously

process different aspects of the information related to the object we see
are said to form a ―temporary set‖ of neurons.

• It is suggested that the synchronous activity of the neurons in the

temporary set leads to conscious awareness of the object we are
seeing.
Subject Name 731
Physiology-A 731
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 732
 PHYSIOLOGY-A
PHARM 313

Lecture # 45 :Consciousness and Behavior

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Motivation

4. Emotion

5. References

Physiology-A 734
 Learning Objectives

After this lecture, students will be able to:

• Distinguish primary from secondary motivated behavior.

• Name the primary neurotransmitter that mediates the brain reward
systems.

Physiology-A 735
 Introduction

• The limbic system is not a separate structure but a functional

system consisting of a ring of forebrain structures that surround the
brain stem and are interconnected by intricate neuron pathways It
includes portions of each of the following: the lobes of the cerebral
cortex (especially the limbic association cortex), the basal nuclei, the
thalamus, and the hypothalamus. This complex interacting network is
associated with emotions, basic behavioral patterns, motivation,
learning, and memory.

Physiology-A 736
 Motivation And Emotion

• Motivation is a factor in most, if not all, behaviors, and emotions

accompany many of our conscious experiences.
• Motivation
• Those processes responsible for the goal-directed quality of behavior
are the motivations, or ―drives,‖ for that behavior.
• Motivation can lead to hormonal, autonomic, and behavioral
responses.
• Primary motivated behavior is behavior related directly to
homeostasis—that is, the maintenance of a relatively stable internal
environment, such as getting something to drink when you are thirsty.
Subject Name 737
Physiology-A 737
 Motivation

• In such homeostatic goal-directed behavior, specific body ―needs‖ are

satisfied.
• In many kinds of behavior, however, the relation between the behavior
and the primary goal is indirect.
• For example, the selection of a particular flavor of beverage has little
if any apparent relation to homeostasis.
• The motivation in this case is secondary. Much of human behavior fits
into this latter category and is influenced by habit, learning, intellect,
and emotions—factors that can be lumped together under the term
―incentives.
Subject Name 738
Physiology-A 738
 Motivation

• The concepts of reward and punishment are inseparable from

motivation. Rewards are things that organisms work for or things that
make the behavior that leads to them occur more often—in other
words, positive reinforcement. Punishments are the opposite.

739
Subject Name–A
Physiology 739
 Motivation

Neural Pathways
• The mesolimbic and mesocortical dopamine pathways originate in
the midbrain and consist of neuronal pathways that release
dopamine in brain regions that process emotions, including the
prefrontal cortex and parts of the limbic system such as the nucleus
accumbens .
• These pathways are implicated in evaluating the availability of
incentives and reinforcers (asking, Is it worth it? for example) and
translating the evaluation into action.

Subject Name 740

Physiology-A 740
 Motivation

• Scientists expected the hypothalamus to have a function in motivation

because the neural centers for the regulation of eating, drinking,
temperature control, and sexual behavior are there.

• Indeed, it was found that brain self-stimulation of the lateral regions

of the hypothalamus serves as a positive reward.

Subject Name 741

Physiology-A 741
 Motivation

Chemical Mediators
• Dopamine is a major neurotransmitter in the pathway that mediates the
brain reward systems and motivation.
• For this reason, drugs that increase synaptic activity in the dopamine
pathways increase selfstimulation rates—that is, they provide positive
reinforcement.
• Amphetamines are an example of such a drug because they increase
the presynaptic release of dopamine.

Subject Name 742

Physiology-A 742
 Emotion

• Emotion can be considered in terms of a relation between an

individual and the environment based on the individual’s evaluation of
the environment.
• Emotional behavior includes such complex behaviors as the
passionate defense of a political ideology and such simple actions as
laughing, sweating, crying, or blushing.
• Emotional behavior is achieved by the autonomic and somatic nervous
systems under the influence of integrating centers such as those we
just mentioned and provides an outward sign that the brain’s ―emotion
systems‖ are activated.
Subject Name 743
Physiology-A 743
 Emotion

• The cerebral cortex has a major function in directing many of the

motor responses during emotional behavior (for example, whether you
approach or avoid a situation).

• Moreover, forebrain structures, including the cerebral cortex, account

for the modulation, direction, understanding, or even inhibition of
emotional behaviors.
Subject Name 744
Physiology-A 744
 Emotion

• Although limbic areas of the brain seem to handle inner emotions,

there is no single ―emotional system.‖

• The amygdala and the region of association cortex on the lower

surface of the frontal lobe, however, are central to most emotional
states.

Subject Name 745

Physiology-A 745
Emotion

Subject Name 746

Physiology-A 746
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 747
 PHYSIOLOGY-A
PHARM 313

Lecture # 46 :Consciousness and Behavior

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Altered States Of Consciousness

4. References

Physiology-A 749
 Learning Objectives

After this lecture, students will be able to:

• Distinguish inner emotions from emotional behavior. Name the brain
areas involved in each.
• Name the major neurotransmitters involved in schizophrenia and the
mood disorders.

Physiology-A 750
 Introduction

• The limbic system is not a separate structure but a functional

system consisting of a ring of forebrain structures that surround the
brain stem and are interconnected by intricate neuron pathways It
includes portions of each of the following: the lobes of the cerebral
cortex (especially the limbic association cortex), the basal nuclei, the
thalamus, and the hypothalamus. This complex interacting network is
associated with emotions, basic behavioral patterns, motivation,
learning, and memory.

Physiology-A 751
 Altered States of Consciousness

• Unusual sensations, such as those occurring with hypnosis,

mindaltering drugs, and certain diseases, are referred to as altered
states of consciousness.
• These altered states are also characteristic of psychiatric illnesses.

Subject Name 752

Physiology-A 752
 Schizophrenia

• In this information is not properly regulated in the brain.

• The amazingly diverse symptoms of schizophrenia include
hallucinations, especially ―hearing‖ voices, and delusions, such as the
belief that one has been chosen for a special mission or is being
persecuted by others.
• Schizophrenics become withdrawn, are emotionally unresponsive, and
experience inappropriate moods.
• They may also experience abnormal motor behavior, which can
include total immobilization (catatonia).

Subject Name 753

Physiology-A 753
 Schizophrenia

• The causes of schizophrenia remain unclear. Studies suggest that it

reflects a developmental disorder in which neurons migrate or mature
abnormally during brain formation.
• The abnormality may be due to a genetic predisposition or multiple
environmental factors such as viral infections and malnutrition during
fetal life or early childhood.
• The brain abnormalities involve diverse neural circuits and
neurotransmitter systems that regulate basic cognitive processes.
• A widely accepted explanation for schizophrenia suggests that certain
mesocortical dopamine pathways are overactive.
754
Subject Name–A
Physiology 754
 Schizophrenia

This hypothesis is supported by the fact that amphetamine-like drugs,

which enhance dopamine signaling, make the symptoms worse, as
well as by the fact that the most therapeutically beneficial drugs used
in treating schizophrenia act at least in part to block dopamine
receptors.

Subject Name 755

Physiology-A 755
 Schizophrenia

• Schizophrenia affects approximately 1% of people over the age of 18,

with the typical age of onset in the late teens or early 20s just as brain
development nears completion.

• Currently, there is no prevention or cure for the disease, although

drugs can often control the symptoms. and the region of association
cortex on the
Subject Name 756
Physiology-A 756
 The Mood Disorders

• The term mood refers to a pervasive and sustained inner emotion

that affects a person’s perception of the world.
• In healthy people, moods can be normal, elevated, or depressed, and
people generally feel that they have some degree of control over their
moods. That sense of control is lost, however, in the mood disorders,
which include depressive disorders and bipolar disorders.
• Along with schizophrenia, the mood disorders represent the major
psychiatric illnesses.

Subject Name 757

Physiology-A 757
 Depression

• Some of the prominent features of depressive disorder (depression)

are a pervasive feeling of emptiness or sadness; a loss of energy,
interest, or pleasure; anxiety; irritability; an increase or decrease in
appetite; disturbed sleep; and thoughts of death or suicide.

Subject Name 758

Physiology-A 758
 Depression

• The major biogenic amine neurotransmitters

• (norepinephrine,
• dopamine, and
• serotonin) and
• acetylcholine have all been implicated

Subject Name 759

Physiology-A 759
 Depression

• Current treatment of the depressive disorders emphasizes drugs and

psychotherapy. The classical antidepressant drugs are of three types.
• The tricyclic antidepressant drugs.
• The monoamine oxidase (MAO) inhibitors interfere with the enzyme
responsible for the breakdown of these same two neurotransmitters.
• A third class of antidepressant drugs, the serotonin-specific reuptake
inhibitors (SSRIs), includes the most widely used antidepressant
drugs.
• In all three classes, the result is an increased concentration of serotonin
.

Subject Name 760

Physiology-A 760
 Depression

• Many psychoactive drugs, which are often chemically related to

neurotransmitters, result in substance use disorders, withdrawal, and
tolerance.
• The mesolimbic dopamine pathway is implicated in substance abuse.

Subject Name 761

Physiology-A 761
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 762
 PHYSIOLOGY-A
PHARM 313

Lecture # 47 :Consciousness and Behavior

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Learning And Memory

4. References

Physiology-A 764
 Learning Objectives

After this lecture, students will be able to:

• Distinguish the types of memory.

Physiology-A 765
 Introduction

• The limbic system is not a separate structure but a functional

system consisting of a ring of forebrain structures that surround the
brain stem and are interconnected by intricate neuron pathways It
includes portions of each of the following: the lobes of the cerebral
cortex (especially the limbic association cortex), the basal nuclei, the
thalamus, and the hypothalamus. This complex interacting network is
associated with emotions, basic behavioral patterns, motivation,
learning, and memory.

Physiology-A 766
 Learning and Memory

• Learning is the acquisition and storage of information as a

consequence of experience.

• Rewards or punishments are crucial ingredients of learning, as are

contact with and manipulation of the environment.

Subject Name 767

Physiology-A 767
 Memory

• Memory is the relatively permanent storage form of learned

information.
• The brain processes, stores, and retrieves information in different ways
to suit different needs.
• Memory can be viewed in two broad categories called declarative and
procedural memory.

Subject Name 768

Physiology-A 768
 Memory

• Declarative memory (sometimes also referred to as ―explicit‖

memory) is the retention and recall of conscious experiences that can
be put into words (declared).
• One example is the memory of having perceived an object or event
and, therefore, recognizing it as familiar and maybe even knowing the
specific time and place the memory originated.
• A second example would be the general knowledge of the world, such
as names and facts.

769
Subject Name–A
Physiology 769
 Memory

• The hippocampus, amygdala, and other parts of the limbic system are
required for the formation of declarative memories.
• Procedural memory, can be defined as the memory of how to do
things (sometimes this is also called ―implicit‖ or ―reflexive‖
memory).
• This is the memory for skilled behaviors independent of conscious
understanding, as, for example, riding a bicycle.

Subject Name 770

Physiology-A 770
 Memory

• Individuals can suffer severe deficits in declarative memory but have

intact procedural memory.

• The primary areas of the brain involved in procedural memory are

regions of sensorimotor cortex, the basal nuclei, and the cerebellum.

Subject Name 771

Physiology-A 771
 Memory

• Short-term memory registers and retains incoming information for a

short time—a matter of seconds to minutes—after its input.
• In other words, it is the memory that we use when we keep
information consciously ―in mind.‖
• For example, you may hear a telephone number in a radio
advertisement and remember it only long enough to reach for your
phone and enter the number.

Subject Name 772

Physiology-A 772
 Memory

• Short-term memories may be converted into long-term memories,

which may be stored for days to years and recalled at a later time.
• The process by which short-term memories become long-term
memories is called consolidation.
• Focusing attention is essential for many memory-based skills.
• The longer the span of attention in short-term memory, the better the
chess player, the greater the ability to reason, and the better a student
is at understanding complicated sentences and drawing inferences
from texts.

Subject Name 773

Physiology-A 773
The Neural Basis of Learning and Memory

Subject Name 774

Physiology-A 774
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 775
 PHYSIOLOGY-A
PHARM 313

Lecture # 48 :Consciousness and Behavior

Faisal Razzaq
(Lecturer)

Date: April 23 , 2020

 Lecture Contents

1. Introduction

2. Objectives Of The Lecture

3. Cerebral Dominance And Language Conclusion.

4. References

Physiology-A 777
 Learning Objectives

After this lecture, students will be able to:

• Describe the major brain regions involved in comprehension and
motor aspects of language.

Physiology-A 778
 Introduction

• The limbic system is not a separate structure but a functional

system consisting of a ring of forebrain structures that surround the
brain stem and are interconnected by intricate neuron pathways It
includes portions of each of the following: the lobes of the cerebral
cortex (especially the limbic association cortex), the basal nuclei, the
thalamus, and the hypothalamus. This complex interacting network is
associated with emotions, basic behavioral patterns, motivation,
learning, and memory.

Physiology-A 779
 Cerebral Dominance and Language

• The two cerebral hemispheres appear to be nearly symmetrical, but

each has anatomical, chemical, and functional specializations.

• The left hemisphere deals with the somatosensory and motor

functions of the right side of the body, and vice versa. specific aspects
of language use tend to be controlled by predominantly one cerebral
hemisphere or the other.

Subject Name 780

Physiology-A 780
 Cerebral Dominance and Language

• In 90% of the population, the left hemisphere is specialized to handle

specific tasks involved in producing and comprehending language—
the conceptualization of the words you want to say or write, the neural
control of the act of speaking or writing, and recent verbal memory.
• This is even true of the sign language used by some deaf people.
Conversely, the right cerebral hemisphere in most people tends to have
dominance in determining the ability to understand and express
affective, or emotional, aspects of language.

Subject Name 781

Physiology-A 781
 Cerebral Dominance and Language

• Language is a complex code that includes the acts of listening, seeing,

reading, speaking, and expressing emotion.
• The major centers for the technical aspects of language function are in
the left hemisphere in the temporal, parietal, and frontal cortex next to
the Sylvian fissure, which separates the temporal lobe from the frontal
and parietal lobes.
• Each of the various regions deals with a separate aspect of language.

782
Subject Name–A
Physiology 782
 Cerebral Dominance and Language

• For example, distinct areas are specialized for hearing, seeing,

speaking, and generating words .
• There are even distinct brain networks for different categories of
things, such as ―animals‖ and ―tools.

Subject Name 783

Physiology-A 783
 Cerebral Dominance and Language

• The specific defects that occur vary according to the region of the
brain that is damaged.
• For example, damage to the left temporal region known as Wernicke’s
area generally results in aphasias that are more closely related to
comprehension—the individuals have difficulty understanding spoken
or written language even though their hearing and vision are
unimpaired.

Subject Name 784

Physiology-A 784
 Cerebral Dominance and Language

• Damage to Broca’s area, the language area in the frontal cortex

responsible for the articulation of speech, can cause expressive
aphasias.
• Individuals with this condition have difficulty carrying out the
coordinated respiratory and oral movements necessary for language
even though they can move their lips and tongues.
• They understand spoken language and know what they want to say but
have trouble forming words and sentences.

Subject Name 785

Physiology-A 785
 Cerebral Dominance and Language

• The potential for the development of language-specific mechanisms in

the two hemispheres is present at birth, but the assignment of language
functions to specific brain areas is fairly flexible in the early years of
life.
• For example, damage to the language areas of the left hemisphere
during infancy or early childhood causes temporary, minor language
impairment until the right hemisphere can take over.
• Similar damage acquired during adulthood typically causes permanent,
devastating language deficits.
Subject Name 786
Physiology-A 786
 Cerebral Dominance and Language

• By puberty, the brain’s ability to transfer language functions between

hemispheres is less successful, and often language skills are lost
permanently.

• After damage to the dominant hemisphere, the opposite hemisphere

can acquire some language function—the younger the patient, the
greater the transfer of function.
Subject Name 787
Physiology-A 787
Cerebral Dominance and Language

Subject Name 788

Physiology-A 788
Cerebral Dominance and Language

Subject Name 789

Physiology-A 789
 References

1. Guyton AC. Text Books of Medical Physiology. 9th Ed. W B

Saunders Company; 2011.
2. Stuart Ira. Human Physiology. 11th Ed. Fox; 2008.
3. Widmaier E, Raff H, Strang K. Vander's Human Physiology. 12th
Ed. McGraw Hill; 2010.

Physiology-A 790
THANKS