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Human Biology
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Human Biology (BIO 102)
Academic Year 2013-2014
Credit Hours: (3 hrs / week theory & 2 Hour/ week Lab)

Human Biology II Course Outline
Week Professor / Lecturer / Instructor Topics/Skills Covered
Week 1 Prof. Dr. Ali, Dr. Nazia, Mrs. Asmaa
Skeletal system
Week 2
Muscular system
Week 3
Respiratory system
Week 4
Urinary system
Week 5
Human reproductive system
Week 6 Macromolecules and enzymes
Week 7
Pathogens and infectious diseases
Week 8
Pathogens and infectious diseases
Week 9 Molecular Biology
Week 10
Molecular Biology
Week 11
Chromosomes and genes
Week 12 Basics of genetics and genetic diseases
Week 13 Cancer Biology
Week 14
Cancer Biology
Week 15
Cancer Biology
Week 16 Questions and answers
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Teaching Staff:
Dr. Ali Mohamed Eldib: PhD & Professor of Biology-Head of FAST
Dr. Bibi Nazia Murtaza: PhD & Assistant Professor -Coordinator of Biology
Mrs. Rehana Imtiaz: M Phil & Biology Lab. Instructor
Mrs. Noreen Javed: M Sc & Biology Lab. Instructor
Mrs. Asmaa: M Sc & Biology Lecturer
Mrs. Wegdan Bokhari: M Sc & biology Lecturer


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Table of contents
Content Page No.
Skeletal system 05
Muscular system 13
Respiratory system 23
Urinary system 37
Human reproductive system 46
Macromolecules and Enzymes 62
Pathogens and infectious diseases 76
Molecular Biology 97
Chromosomes and genes 110
Basics of genetics and genetic diseases 119
Cancer Biology 129

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The Skeletal System
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The Skeletal System


Introduction:
The skeletal system includes
connective tissues such as bone,
cartilage, tendons, and ligaments.
These tissues are combined with
the various types of muscle tissue
to form the Musculoskeletal
System. Bones work together with
muscles as simple mechanical
lever systems to produce body
movement.
The primary organs of the skeletal
systems are the bones. They lie
buried within the muscles and
other soft tissue, providing a rigid
framework and support structure
for the whole body. Bones are
living organs that they can remodel
themselves and help the body
respond to a changing environment.
Bones contain more calcium than
any other organ. The intercellular
matrix of bone contains large
amounts of calcium salts, the most important being calcium phosphate.
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Functions of the skeletal system
1. Support: Bones form the bodys supporting framework.
2. Protection: The skull protects the brain, the breastbone and ribs protect vital organs
and vital tissue such as heart, lungs and red bone marrow.
3. Movement: Muscles are anchored firmly to bones. As muscles contract and shorten,
they pull on bones and thereby move them.
4. Storage: Bones play an important part in maintaining homeostasis of blood calcium,
(a vital substance for normal nerve and muscle function). When the amount of
calcium in blood increases above normal, calcium moves out of the blood and the
bones for storage.
5. Hemopoiesis: is the process of blood cell formation. Blood cell formation is a vital
process carried on in the red bone marrow. Red bone marrow is soft connective
tissue inside the hard walls of some bones.


Division of skeleton

The human has two divisions: The axial skeleton and the appendicular skeleton. The
bones of the center or axis of the body make up the axial skeleton. The bones of the
skull, spine (vertebral column), and chest and the hyoid bone in the neck are all in the
axial skeleton. The bones of the upper and lower extremities make up the
appendicular skeleton.

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Bones of the Human Body: This system has 206 bones and associated cartilage, tendons
and ligaments.

Because bone is rigid, it gives the body a framework, maintains its shape, and protects vital
organs.

Shape of Bones
There are 4 types of bones based on shape:
1. Long: e.g. humerus or upper arm bone.
2. Short: e.g. wrist bones
3. Flat: e.g. frontal or skull bone.
4. Irregular: e.g. vertebrae of spinal bones.
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Two basic types of bone tissue related to structure:
Compact bone, and Spongy bone.

The two types differ in density, or how tightly the tissue
is packed together.

Compact bone consists of closely packed osteons or
Haversian systems, while spongy bone is lighter and less
dense than compact bone.

The spongy bone has irregular cavities that contain bone
marrow.
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Cells of the bones: There are three types of cells that contribute to bone homeostasis.
Osteoblasts are bone-forming cells. They secrete bone matrix element and
help in depositing calcium in the bone
Osteoclasts are bone destroying cells. They resorb or break down bone.
Osteocytes are mature bone cells.
Equilibrium between osteoblasts and osteoclasts maintains bone tissue.

Structure of long bones:
The names of the main parts of a long bone:
Diaphysis: or shaft- a hollow tube made of hard,
compact bone.
Medullary cavity: the hollow area inside the diaphysis
of a bone contains soft yellow bone marrow.
Epiphysis: or the ends of the bone- red bone marrow
fills in small spaces in the spongy bone composing the
epiphyses
Articular cartilage: a thin layer of cartilage covering
each epiphysis; functions like a small rubber cushion
Periosteum: a strong fibrous membrane covering a long
bone except at joint surfaces. Endosteum: a fibrous
membrane that lines the medullary cavity.








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Microscopic structure of bone:
The skeletal system contains two
major types of connective tissue:
Bone and Cartilage.
The outer layer of bone is hard and
dense.
Bone of this type is called dense
or compact bone.
The porous bone in the end of
the long bone is called spongy bone.
Compact or dense bone does not
contain a network of open spaces.
Instead, the matrix is organized into numerous structural units called Osteons or
Haversian systems.

Each circular and tube like osteon is composed of calcified matrix arranged in multiple
layers resembling the rings of onion. Each ring is called a concentric lamella. The
lamellae surround the central canal, which contains a blood vessel.
Within the hard matrix of bones are many living bone cells called osteocytes.
Osteocytes lie between the hard layers of the lamellae in little spaces called lacunae.
Tiny passageways or canals called canaliculi connect the lacunae with one other and with
central canal in each Haversian system.
Nutrients pass from blood vessels in Haversian canal through the canaliculi to the
osteocytes.
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Most bones of the body are formed from cartilage. The laying down of calcium salts
in the gel- like matrix of the forming bones makes bones hard. Bones grow in length at
the epiphyseal plate. The cartilage in the region of the epiphyseal plate next to the
epiphysis continues to grow by mitosis. Osteoblasts move in and ossify the matrix to
form bone. This process continues throughout childhood and the adolescent years until
the cartilage growth slows and finally stops. When cartilage growth ceases, usually in the
early twenties, the epiphyseal plate completely ossifies so that only a thin epiphyseal
line remains and the bones can no longer grow in length.
Bone growth is under the influence of growth hormone from the anterior pituitary
gland and sex hormones from the ovaries and testes.

Joints (Articulations)
Every bone in the body (except one: the hyoid bone in the neck), connects to at least
one other bone. Joints hold our bones together securely and at the same time make it
possible for movement to occur between the bones.
Kinds of joints: joints are classified according to the degree of movement they allow:
(no movement like the joints between cranial bones, slight movement like the joints
between the bones of the vertebrae, and free movement like most joints in the
appendicular skeleton). Joints are also classified according to structure:
Fibrous joints (Generally immovable),
Cartilaginous joints (Immovable or slightly moveable),
Synovial joints (Freely moveable).
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The Muscular System

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The Muscular System

Introduction:

The muscular system moves the bony framework of the body.
The muscular system is often referred to as the musculoskeletal system
because without the muscles, the bones would not be able to move, and,
without the bones, the muscles would lack support.
Main organs of the muscular system are the muscles (Cardiac-smooth or
skeletal). Muscular system has connective tissue such as tendons and
connective sheaths, blood vessels and nerves.
Characteristics of muscle tissue:

There are four characteristics associated with muscle tissue:

1. Excitability: Muscle responds to electrical stimulation from nerve
impulses.

2. Contractility: Muscle responds to stimuli by contracting lengthwise, or shortening.

3. Extensibility: Muscle can be stretched up to 30% of its resting length.

4. Elasticity: After contracting or lengthening, tissue always can return to its resting state.

Functions of Skeletal Muscles:
Produce movement: The primary function of skeletal muscle in the body is movement. Muscle pulls tendons to move
the skeleton.
Maintain posture and body position: Skeletal muscles maintain posture, stabilize the joints and
support viscera.
Support soft tissue: Support weight of visceral organs.
Guard entrances and exits in internal organs: Muscles encircle the openings to digestive and
urinary tracts, called sphincters. They control swallowing, defecation and urination.
Maintain body temperature: Muscle metabolism produces. Energy from contraction is converted to
heat.






























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Types of Muscles:
Skeletal, Cardiac and Smooth Muscles

The body contains 3 types of muscle tissue. The differences in these types of muscle are due
to their microscopic structure, their location in the body and their function and how their
functions are controlled; either voluntary or involuntary.

a. Skeletal muscles:

Muscles attached to skeleton.
They provide the means by which
the body can move.
Skeletal muscles are voluntary
muscles that contract and relax in
response to conscious thought.
Skeletal Muscle cells or fibers are
striated (striped) with multiple
nuclei; are arranged as many, long, cylindrical cells bundled together.
They are responsible for voluntary movement, and are generally connected to
the bones via tendons.
b. Cardiac muscle:
It is found only in the wall of the
heart and has the unique property of
auto- rythmicity. It pumps blood
through the circulatory system.
(Makes up myocardium of heart)
Cardiac muscle fibers are also
striated and have intercalated discs
that help hold adjacent cells together
and transmit the force of
contraction from cell to cell. Their contraction is involuntary and has intrinsic
stimulation.

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c. Smooth muscles:

They make up walls of internal organs and blood vessels (tubular organs of the GI tract,
reproductive, urinary and
respiratory systems). The
smooth muscle fibers are
short, spindle shaped non-
striated and contain a single
nucleus. These muscles are
under automatic control, they
are involuntary.
Smooth muscles decrease the
diameter of blood vessels and
propel food through the
stomach and intestines, help
in respiration.


Skeletal muscles





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Anatomy of the skeletal Muscular System:
Each muscle is wrapped in fascia, a thin, connective tissue
that also joins to the tendon.


Muscle attachments:
Every muscle has at least one
point of origin on a
stationary bone and an insertion
on a bone that moves when the
muscle contracts.

Tendon: Is dense connective
tissue that attaches muscle to
bone.

Origin: The less movable
attachment of the muscle is
called the origin.

Insertion: The more movable bony
attachment of the muscle is called the
insertion.


Agonist: A muscle that contracts to create the
desired action is known as an agonist or prime
mover.

Synergist: A muscle that helps the agonist is a
synergist.

Antagonist: A muscle that opposes the action of the agonist, therefore undoing the desired action
is an antagonist.


Skeletal muscles work in opposition:
The biceps and triceps muscles of the arm work in opposition: to move the forelimb
up or down. Contraction of the biceps, together with relaxation of the triceps, pulls the
forelimb up. Contraction of the triceps and relaxation of the biceps pull it down.















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Functional Organization of Skeletal Muscle:































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Microanatomy of a skeletal Muscle Fiber (Cell)
Skeletal Muscle tissue consists of specialized contractile cells called muscle fibers.
Muscle tissue consists of specialized contractile cells called muscle fibers grouped into
bundles.
A muscle fiber is a single,
multinucleated muscle cell.

A muscle is made up of
hundreds or even thousands
of muscle fibers, depending
on the muscles size.

Although muscle fiber makes
up most of the muscle tissue,
a large amount of
connective tissue, blood
vessels, and nerves are also
present.

The health of muscle depends
on a sufficient nerve and
blood supply. Each skeletal
muscle has a nerve ending that
controls its activity
(innervation), and an
individual system to supply
and drain blood
(vascularization).

Connective tissue covers and
supports each muscle fiber
and reinforces the muscle
as a whole.


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Microscopic structure of skeletal muscle fiber
Skeletal muscle is surrounded by connective membrane called epimysium. Skeletal
muscle contains muscle fascicles which are bundles of muscle fibers.
Each muscle fascicle is surrounded by perimysium membrane and contains hundreds
of muscle fibers.








Muscle fiber is an elongated cell surrounded by Endomysium. Sarcolemma is the
plasma membrane of muscle fiber.
Muscle fiber has cylindrical organelles called myofibrils.
Myofibrils are bundles of filaments that run from one end of the cell to the other
and are attached to the cell surface membrane at each end.
The filaments of myofibrils consist of two types: thick and thin filaments.
Thin filaments consist of the protein actin. Thick filaments consist of the protein
myosin.
Interaction between thick and thin filaments causes contraction. When myofibrils
contracts, the whole cell contracts.



































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Sarcomere

Sarcomere: is the smallest functional unit of muscle fiber. Each myofibril contains
10,000 sarcomeres end to end. Sarcomere is made up of repeated units of myofilaments
arranged in parallel lines. Myosin and Actin myofilaments are arranged to form
overlapping patterns, which are responsible for the light and dark bands (striations) that
can be seen in skeletal muscle.

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Myosin pulls on actin, causing thin myofilaments to slide across thick
myofilaments, towards the center of the sarcomere (sliding filament theory).

Physiology of skeletal muscle contraction
Skeletal muscles require stimulation from nervous system in order to contract.
Motor neurons are the cells that cause muscle fibers to contract.






Motor neurons are the cells that cause muscle fibers to co



Once an action potential (AP) is generated at the motor end plate it will spread like an electrical
current along the sarcolemma of muscle fiber. The sarcoplasmic reticulum is a specialized
endoplasmic reticulum that stores and releases calcium ions needed for muscle contraction.
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The Respiratory System
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The Respiratory System
















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Respiratory System


Introduction
The respiratory system is the system that makes you breath in and out, resulting
in gas exchange. That means take oxygen from air into the body and remove
carbon dioxide from it.

Functions of respiratory systems
Breathing: is the movement of air in and out of the lungs. It includes the
mechanical processes of inhaling and exhaling.
o Inhalation (inspiration) draw gases into the lung.
o Exhalation (expiration) forces gases out of the lung.

Air conditioning: as air passes through the upper respiratory tract it get
warmed to body temperature, humidified, and cleaned of particulate matter.

Gas Exchange: it provides oxygen to the blood and removes carbon dioxide.

Production of sound: it enables sound production as expired air passes over
the vocal cords.

Site for olfactory sensation: the olfactory epithelium in the upper medial
portion of the nasal cavity is concerned with smell.

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Structure of respiratory system
The respiratory system includes
The conducting division which include all structures except pulmonary
alveoli
The respiratory division which includes the pulmonary alveoli where gas
exchange occur between air and blood capillary

1. Respiratory tract
a. Upper respiratory tract (nose, pharynx, and larynx)
b. Lower respiratory tract (trachea and lungs including bronchi,
bronchioles and pulmonary alveoli)

2. Accessory organs of respiration
a. Diaphragm
b. Intercostals muscle
Respiratory mucosa
Its the membrane that lines
most of the system. It is
mostly made of pseudo
stratified columnar
epithelium, containing goblet
cells. It secretes mucous to
clean all respiratory tubes
with the help of cilia. Any dust, insects, pollen etc enter that tract get caught by
the protective mucous secretion that cover large part of the membrane and
expelled by millions of cilia that covers respiratory mucosa.
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Respiratory Tract: Upper Respiratory Tract and lower respiratory tract

Upper respiratory tract: Nasal
cavity, pharynx and larynx


Function:
Passageway for respiration
Receptors for smell (Olfactory
epithelium)
Filters incoming air to remove larger foreign material
Moistens and warms incoming air
Resonating chambers for voice
1-Nose and nasal cavities
Air enters respiratory system through nostrils
(nasal opening) pass through 2 nasal cavities
where it gets filtered, warmed and humidified;
the 2 cavities are separated by nasal septum.
Conchae: shelf like protrusions on each side
of nasal cavities to increase surface area over
which air pass through.
Olfactory receptors: are the nerve ending responsible for sense of smell.
Paranasal sinuses: hollow spaces help to lighten the skull, together with the
nasal cavity they warm and moisten air, and serve as resonant chambers for the
production of sound there are 4 pairs of them located in the frontal, sphenoid,
ethmoid and maxillary bones

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2-Pharynx (throat)
It is the first passage that air and food
pass through to lungs and stomach
respectively. Air enters pharynx through
nose and leave it by the way of larynx.
Food enters it through mouth and leaves
through esophagus.
Eustachian tube opens in
nasopharynx serves to equalize pressure
between middle and external ear.
Tonsils are masses of lymphatic tissue embedded in the mucous
membrane of pharynx they serve as the first line of defense and provide
immunity to the respiratory system.

3-Larynx (voice box):
Located just below pharynx it is composed of several pieces of cartilages the
largest of this is thyroid cartilage, we call it
(Adams apple).
Two short fibrous bands (vocal cords) stretch
across the interior of the larynx can pull these
cords in a way they become tenser or relaxed
producing different voice tones while air
passes through them. The spaces between
cords is called glottis that is covered partially
by epiglottis that acts like a door closing the larynx during swallowing to prevent
food from entering trachea.

Lower respiratory tract: trachea and lungs including bronchi, bronchioles and
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pulmonary alveoli .
1- Trachea
It is the only tube that extends between the larynx and bronchi through which air
can reach lungs warmed, and
humidified. Trachea is lined
with respiratory mucosa
membrane (ciliated
pseudostratified columnar
epithelium). If its closed, we will
choke, thats why it is made of
C shaped rings of cartilages
placed one above the other with only little soft tissue in between to secure
constant opening of its lumen and prevent its collapse.
2- Bronchial tree
It includes the conducting zone and the respiratory zone.
The conducting zone: extensively branching respiratory passage ways that
include the:
Primary bronchi (main bronchi)
Secondary bronchi
Tertiary bronchi
Bronchioles- little bronchi less than one mm in diameter
Terminal bronchioles- less than 0.5 mm in diameter
The tissue composition of the walls of the main bronchi mimics that of the
trachea, but as the conducting tubes become smaller, elastic fibers replace the
cartilage and the amount of smooth muscle in the tube walls increases. Cilia are
spares, and mucous producing cells are absent in the bronchiole.

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The respiratory zone: consist of air exchanging structures (Alveoli). The
respiratory bronchioles (branch from terminal bronchioles), which lead to
alveolar duct.

3. Alveolar ducts and
alveoli are the functional
units of respiratory system
which are responsible for gas
exchange between air and
blood. There are 300 million or so gas-filled alveoli in the lungs, each in contact
with blood vessels, so respiration takes place on that level.

Respiratory membrane
The membrane that separates the air in the
alveoli from the blood in surrounding
capillaries is made of capillaries basement,
alveolar basement membrane and the space in
between. Gas exchange occur by simple diffusion across the respiratory
membrane (O
2
passes from the alveolus into blood and CO
2
leaves the blood to
enter the gas filled alveolus)
Alveolar macrophages crawl freely along the internal alveolar surfaces to
remove air debris.
Surfactant: substance produced by alveolar cells to covers the respiratory
membrane. It lowers surface tension in alveoli and prevent them from
collapsing during respiration



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Lungs

The paired lungs occupy the entire
thoracic cavity except the mediastinum.
The two lungs differ slightly in shape
and size because the apex of the heart is
slightly to the left of the median plane.
The lung consist largely of air spaces.
These are mainly made up of elastic
connective tissue. As a result, the lung
are soft, spongy and elastic organs. On the mediastinal surface of each lung is an
indentation, the hilum, through which pulmonary and systemic blood vessels,
bronchi, lymphatic vessels, and nerves enter and leave the lungs.
Lungs provide the place where air and blood can exchange gases with air at
alveolar level.

The pleura: covers the outer surface of both
lungs and lines the inner surface of thoracic
cage. It is a thin moist serous membrane
that is composed of two parts: partial pleura
(lines thoracic cage) visceral pleura (covers
the lung). The inter pleural space lies
between the two membranes; it contains
little fluid to moist the two membranes making them slippery easily to glide on
each other.


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Main accessory organs of respiration: (respiratory muscles)
Diaphragm is the dome-shaped muscle separating thoracic cavity from
abdominal cavity. During inspiration, the
diaphragm contracts, it moves inferiorly and
flattens out. As a result, the superior-inferior
dimension of the thoracic cavity increases.
Intercostals muscles are located between
ribs. During inspiration, they contract and
increase the size of the chest by increasing the
antro-posterior diameter (from front to back), so lungs expand in width.

Abdominal muscles also help in the mechanism of respiration. The increase in
the thoracic volume, allows air to flow into lungs down its pressure gradient. Of
the two main types of inspiratory muscles, the diaphragm is far more important in
producing the volume changes that lead to normal inspiration.

Mechanism of respiration (Inhalation and Exhalation)

Respiration: means exchange
of gases (oxygen & carbon
dioxide) between living
organism and its environment
In humans, lungs are
responsible for this process as it
provides the place where air
and blood can come close
enough to each other for gas
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exchange.

Air enters nose then passes through pharynx, larynx then trachea, bronchi and
bronchioles where it gets filtered and humidified through the whole tract.
Then it passes through alveolar ducts to alveoli where O2 is delivered to the
blood and waste gases (CO2) are collected. This process takes place through the
extremely thin wall of alveoli and blood vessels

Breathing (pulmonary ventilation): movement of air into and out of lungs

Inspiration: Inhalation (taking in) air into the lungs is an active process occurs
when thoracic cage enlarges, lungs expand and air rushes into them down to the
alveoli. Dilatation of thoracic cage happens as result of contraction of respiratory
muscles (diaphragm moves down toward abdominal cavity increasing
longitudinal diameter and intercostals contracts increasing transverse diameter.)

Expiration: Exhalation (moving out) of air from the lungs is a passive process it
happens when the respiratory muscle relaxes, the thoracic cavity returns to its
original size, lungs recoil (decrease in size) as air leaves alveoli outward through
respiratory passages.


Types of respiration:

1. External respiration: gas exchange between air and blood at the level of
alveoli

2. Internal respiration: gas exchange between blood and tissues
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3. Cellular respiration: actual use of oxygen by the cell in the process of
metabolism to produce ATP, carbon dioxide and water as waste.


External respiration (exchange of gases in lungs)

Blood pumps from the heart into the
pulmonary artery then flows through
thousands of tiny lung capillaries
that are in proximity to lung alveoli
which provide the place where air
and blood exchange gases.
Oxygen has high concentration in alveolar air and low in capillaries. So by
diffusion it will pass from area of high
concentration (alveolar air) to the area of
low concentration (capillary blood)
where it will combine with hemoglobin
in red blood cells. Then the blood carries
it to the tissues where it is removed from
blood and used by the cells.
CO
2
diffuses from high concentration in
capillary blood to low concentration in alveolar air.


1. Internal respiration:
It is the gas exchange between blood and tissue. Also it occurs by diffusion
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2. Cellular respiration:
O
2
diffuse from the blood to the
tissue where it is used by the cells
then CO
2
that is produced from
cellular respiration diffuses back to
blood capillaries. Cellular
respiration occurs in the
mitochondria.



Binding of

hemoglobin with
oxygen
Hemoglobin (Hb) is a red pigment
in RBCs. It is composed of 4
polypeptide chains, each bound to
an iron containing heme group. The
name hemoglobin comes from the combination of Heme (iron part that unit with
O
2
) and globin (protein part). It units with O
2
and carries it to tissue, it can also
carry small amount of CO
2

returning it to alveoli.






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Regulation of respiration

Respiratory muscles are stimulated by respiratory control center located in
the medulla, this center produces
regular breathing pattern by
sending regular impulses to
muscles of respiration
(diaphragm, intercostals
muscles, muscles of the
abdomen) to contract and relax
accordingly.

This center is stimulated by
receptors that detect carbon
dioxide, hydrogen ions and oxygen levels to increase or decrease frequency of
respiration.

Conscious control of respiration: higher centers (cerebral cortex) can control
automatic respiration to increase its force (blowing balloon) or speed; make it
fast, slow or hold it ( swimming and scuba diving)






37


The Urinary System
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The Urinary System
The urinary system or renal system is the organ system that produces, stores, and eliminates urine.
It includes two kidneys, two ureters, the bladder and the urethra. The female and male urinary
systems are very similar, differing only in the length of the urethra.
In other words, the urinary system maintains the volume and composition of body fluids
(electrolyte, water, and acid-base balance) within normal limits. One aspect of this function is to
get rid the body of waste products that accumulate as a result of cellular metabolism so; it is
sometimes referred to as the excretory system.

T
T
T

The urinary system consists of the following structures:
Two kidneys: Filter blood to produce urine.
Two ureters: conduct urine from kidneys to the urinary
bladder.
The urinary bladder: where urine is collected and
temporarily stored.
The urethra: through which the urine is discharged from the
urinary bladder to outside the body.
Functions of the urinary system:
1. Excretion: Removal of metabolic waste products from the blood, such as nitrogen-containing
waste material (urea), excess salts and toxins.
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2. Maintenance of water balance: Although the amount of water gained and lost in a day can
vary, the kidneys can adapt to these variations, so that the volume of body water remains
remarkably stable.
3. Regulation of acid-base balance: If the body is to function normally, the pH of body fluids
must remain in the range of 7.35 to 7.45.
4. Regulation of blood pressure: The kidneys depend on blood pressure to filter blood. If blood
pressure falls too low for effective filtration, cells in the kidneys release renin; an enzyme that
activates angiotensin, a blood protein that causes blood vessels to constrict, thus raising blood
pressure.
5. Regulation of red blood cell production: When the kidneys do not get enough oxygen, they
produce the hormone erythropoietin (EPO), which stimulates the red cell production in the bone
marrow.
The kidneys:
GENERAL ROLE: The kidneys are organs that serve
several essential regulatory roles. They also serve the body
as a natural filter of the blood, and remove wastes which are
diverted to the urinary bladder. In producing urine, the
kidneys excrete wastes such as urea and ammonium, and
they are also responsible for the re-absorption
of water, glucose, and amino acids. The kidneys also
produce hormones including calcitriol, erythropoietin, and the enzyme renin.
SHAPE: Kidneys are bean-shaped organs. A sheath of fibro-elastic renal fascia encloses the
kidney. In the adult, each kidney is approximately 3 cm thick, 6 cm wide and 12 cm long. The
ureter and renal vein leave the kidney, and the renal artery enters the kidney at the hilum.
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LOCATION: The kidneys lie on the posterior abdominal wall, one on each side of the vertebral
column, behind the peritoneum and below the diaphragm. The right kidney is usually slightly
lower than the left.
Blood supply to the kidney:

Blood is brought to the kidney through a branch of the aorta called the renal artery, it subdivides
into smaller and smaller branches which make contact with the functional unit of the kidney, the
nephron. Filtered blood leaves the kidney through the renal vein.
External Anatomy of Kidneys:

Renal capsule: surrounds each kidney
Renal artery and nerves enter and renal vein and
ureter exit kidneys at the hilum.
Internal Anatomy of Kidneys:

Renal cortex: Outer area
Renal medulla: Inner area
Renal pyramids projecting into a funnel space
called renal pelvis.
Medulla pyramids consists of numerous uriniferous tubules or nephrons, sites where urine is
formed.
Renal papilla: innermost end of a pyramid.
Renal pelvis: the tube that drains urine into the bladder.
Calyces: Cup-like structures that converge to form renal pelvis. Minor calyces collects urine
from individual renal pyramid


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Anatomy of nephron (functional unit of kidney):
The Nephron is composed of two principle components: The renal corpuscle and the renal
tubule.

The renal corpuscle is subdivided into two parts:

Bowmans capsule: the cup- shaped top
of a nephron.

Glomerulus: network of blood capillaries. High pressure is required to filter wastes from the blood
The renal tubule has 4 regions:

Proximal convoluted tubule.
Loop of Henle: consists of descending
and ascending limbs.
Distal convoluted tubule.
Collecting tubule: distal tubules of
several nephrons join to form a single
collecting tubule or duct.

The functions of nephron:
1- Filtration:
Most filtration occurs in the glomerulus.
Blood pressure forces water, salt, glucose,
amino acids, and urea into Bowmans
capsule. Proteins and bloo cells are too large
to cross the membrane; they remain in the
42

blood. The fluid that enters the renal tubules is called the filtrate.
2- Re-absorption:
As the filtrate flows through the renal tubule, most of the water and nutrients are reabsorbed into the
blood.
3- Tubular secretion:
Before the filtrate leaves the body as urine,
the kidney makes final adjustments in
composition by the process of tubular
secretion. In this process, kidneys regulate
the acid-base (pH) balance of body fluid by
the active secretion of hydrogen ions.

Hormone secretion:
In addition to removing wastes, your kidneys release three important hormones:
Erythropoietin or EPO, stimulates the bone marrow to make red blood cells
Renin, which regulates blood pressure
Calcitriol, the hormonally active form of vitamin D (D3), which helps maintain
calcium for bones and for normal chemical balance in the body.
The kidneys act as osmoregulators (Control of urine volume):
The kidneys, by helping to regulate the water or the salt concentration in the blood, are called
osmoregulators. This is an example of homeostasis.
The water potential of the blood depends on the amount of water and salts in the plasma. The
water content of the blood is controlled by vasopressin or anti-diuretic hormone (ADH). It is
produced by the posterior pituitary gland and increases water reabsorption by the kidney tubules.

43

ADH from pituitary causes kidneys to retain water by increasing reabsorption of water. ADH
is water retaining hormone or urine decreasing hormone
Aldosterone, secreted by the adrenal cortex, and stimulated by renin secretion, promotes the
reabsorption of sodium ions, and water and the excretion of potassium ions therefore blood
volume and blood pressure increase.
Atrial natriuretic hormone (ANH), secreted from the hearts atrial wall, has the opposite
effect of aldosterone. ANH causes kidneys to excrete Sodium and water decreasing blood volume
and lowering blood pressure.
The Ureters:
Each ureter is a small tube, about 25 cm long that carries urine
from the renal pelvis to the urinary bladder. It descends from
the renal pelvis and enters the urinary bladder on the posterior
inferior surface.
The wall of the ureter consists of three layers:
1. The outer layer: the fibrous coat
2. The middle layer: the muscular coat. The main
function of this layer is peristalsis to propel the
urine.
3. The inner layer, the mucosa, is transitional
epithelium. This layer secretes mucus which coats
and protects the surface of the cells.

The Urinary bladder:
Urinary bladder temporarily stores urine prior to micturition. Bladder capacity is 700-800mL.
44

It is lined with mucosa of transitional epithelium with rugae. The triangular area formed by
openings of ureters and urethra is called trigone.
The muscularis layer of the urinary bladder has 3 layers of smooth muscle known as detrusor
muscle.










Urethra: Lowest part of the urinary
Urethra is fibro-muscular tube that exits the urinary bladder through the urethral opening
and conducts urine to the exterior of the body. The luminal lining of the urethra is a
protective mucous membrane. Bundles of primarily smooth muscle fibers surround the
mucosa and help propel urine to the outside of the body.






45


Urethra has two urethral sphincters: Inner urethral sphincter of smooth muscle;
external urethral sphincter of skeletal muscle. Sphincters restrict the release of urine until the
pressure within the urinary bladder is high enough and voluntary activities are needed to release
the urine. In a man, the urethra has two functions: it is the terminal portion of the urinary tract and
it is the passageway for the movement of the reproductive fluid (semen) from the male. In woman,
the urethra is a part of only the urinary tract.
Micturition (Urination)
Micturition is the expulsion of urine from the bladder. It is initiated by a complex sequence of
events called the micturition reflex.
Micturition reflex stretch receptors in wall of bladder stimulate smooth muscle (involuntary),
this causes stimulation of internal urethral sphincter (involuntary) and external urethral sphincter
of skeletal muscle (voluntary).


46



Human Reproductive System
47


The Human Reproductive System
Female Reproductive System
Introduction:
In human, gametes, called ova and sperm, come together during the process of fertilization to
produce a cell called the zygote, which ultimately develops into the new individual. Ability to
reproduce sexually is one of the main properties of human due to the presence of male and female
reproductive system.
Functions of Reproductive System:
The major function of the reproductive system is to ensure survival of the species. Within the
context of producing offspring, the reproductive system has four functions:
To produce egg and sperm cells (gametes)
To transport and sustain these cells
To nurture the developing offspring
To produce hormones mainly sex hormones

Sexual Reproduction
It involves the fusion of two types of haploid gametes, sperm and egg. The male and female
reproductive systems contribute to the events leading to fertilization. The male gonad called testes
produce the sex cell sperm cell and female gonad called ovaries produce the sex cell ova. The
gonads also produce hormones necessary for the proper development, maintenance, and functioning
of the organs of reproduction and other organs and tissues. Fusion of the gametes produces a
zygote, which develops into a new complete organism. Each zygote inherits 23 chromosomes from
48

the mother and 23 chromosomes from the father.


Female reproductive system

Functions of the female reproductive system: The female reproductive system is adapted to
produce a gamete called eggs, receive the sperm and incubate, protect and nourish the embryo
during and after pregnancy.
The processes of the female reproductive system are regulated by hormones secreted by the ovaries,
the hypothalamus and the anterior lobe of the
pituitary gland.

Main organs of the female reproductive system:

1. Ovaries: two female sex glands that produce
egg cells via oogenesis, and female sex hormones.
2. Fallopian Tubes or the oviducts: passage way of
ova from the ovaries and connected with the
muscular uterus. Egg travels through these 2 tubes to the uterus.
3. Uterus or Womb: a muscular pear-shaped organ, where baby develops. The uterus ends in the
cervix
4. Cervix: Opening between the uterus &vagina
5. Vagina: Muscular tunnel from cervix to
outside, opens to the vulva, the external female
organs
6. Accessory glands: the mammary glands.


49


1. Ovaries:
The two ovaries are the primary female reproductive organs or gonads. Ovaries are small, almond-
shaped organs located near lateral walls of pelvic cavity. The ovaries are held in place by various
ligaments which attached them to the uterus and the
pelvis.
Function of the ovaries
1. Production of female gametes (oocytes)
2. Secretion of female sex hormones (estrogens,
progestin)
3. Secretion of inhibin: feedback control of pituitary FSH
The ovary contains ovarian follicles, in which eggs develop.
Once a follicle is mature, it ruptures and the egg is ejected from the ovary into the fallopian tubes.
This is called ovulation.

OOGENESIS (results in one haploid ovum):

Female sex cells, or gametes, develop in the ovaries by a form of meiosis called oogenesis.
2. Oviduct (Follapian tube):

The fallopian tubes are about 10 cm long and begin as funnel-shaped structures next to the ovary.
They have a number of projections known as fimbriae on the end near the ovary.
The oviduct receives the secondary oocyte, which moves by peristalsis and ciliary beating down the
oviduct toward the uterus. A successful fertilization occurs in the oviduct.
Ovum is fertilized at the oviduct. Motile sperm meet the egg in the upper part of the oviduct and
fertilization happens.
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The fertilized ovum is carried to the uterus by the beating cilia on the inner wall of oviduct and the
contraction of muscles of the oviduct.
The newly formed zygote stays in the oviduct 3-4 days. This time is needed for the uterus to
prepare itself for implantation
3. Uterus:
The uterus is a muscular organ that receives
the fertilized oocyte and provides an
appropriate environment for the developing
fetus. The uterus incubates the embryo.
The main part of the uterus (which sits in the
pelvic cavity) is called the body of the uterus,
while the rounded part above the entrance of
the fallopian tubes is the fundus.

The thick wall and lining of the uterus is composed of 3 layers:
Endometrium, myometrium and perimetrium
Endometrium: is the inner layer which has stratified, squamous, non-keratinized epithelium. It has
numerous uterine glands and consists of:
Stratum functionalis: It undergoes cyclic changes in response to ovarian hormones and is shed
during menstruation
Stratum basalis: It forms a new functionalis layer after menstruation ends. It does not respond to
ovarian hormones.The endometrium thickens each month in preparation for pregnancy, and if that
does not occur, it sheds in menstruation. A fertilized egg implants in the endometrium
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Myometrium: a smooth muscle layer. The myometrium is the large middle layer of the uterus,
which is made up of groups of muscle. It plays an important role during the birth of a baby by
contracting to move the baby out of the body via the birth canal (vagina).

Perimetrium: outer layer of connective tissue.

Before the first pregnancy, the uterus is about the size and shape of a pear, with the narrow portion
directed inferiorly. After childbirth, the uterus is usually larger, and then regresses after menopause.
4. The cervix:
It is the neck of the uterus and is a common site of cancer. Cervical glands secrete mucus.
5. Vagina:
It is a fibro-muscular tube, about 10 cm long that extends from the cervix of the uterus to the
outside. Vagina is located between the rectum and the urinary bladder. The vagina serves as a
passageway for menstrual flow, and is the birth canal during childbirth.
Accessory organ: The mammary glands:
Each breast is composed of glandular tissue (mammary glands) surrounded by adipose tissue.
During pregnancy and after the delivery of baby, the hormone prolactin from the anterior pituitary
stimulates the production of milk; Oxytocin from posterior pituitary stimulates the release of milk
by a positive feedback mechanism.
Summary Reproductive Hormones in Female
The hypothalamus, pituitary, and ovaries interact to regulate female reproduction
Hypothalamus releases Gonadotropin Releasing Hormone (GRH) which binds with receptors
in Anterior Pituitary
Anterior Pituitary releases Follicle Stimulating Hormone (FSH) and Luteinizing Hormone
(LH) pass in blood to the site of action
52

FSH acts on receptors in ovaries to stimulate development of the egg follicles
LH causes rupture of egg follicles.
Rupture of egg triggers production of estrogens and progesterone from remaining tissues of
follicle, corpus luteum.
These hormones travel in blood to the brain
Hypothalamus senses levels, then may decrease release of G (negative feedback mechanism).

Fertilization:
Fertilization is the fusion of sperm and egg. The ovum remains fertile for only ~ 24 hrs
(postovulation); sperm remain alive in the womans reproductive tract for several days. Fertilization
is accompanied by an action potential in the egg
which stops further sperm entry. Further changes
occur on the outside of the egg to block further
sperm after fertilization. The ovum completes the
second meiotic division after sperm entry.

Implantation
If fertilization occurs, development begins as the
embryo is moved to the uterus.
After about 3-5 days the embryo implants in the
endometrium. Membranes that develop around the
embryo secrete hCG, human chorionic gonadotrophin.
hCG stimulates the corpus luteum to continue to
secrete progesterone. After ~ 3 months, uterine tissues
begin to form the placenta, the corpus luteum degrades
53

and the placenta takes over nourishment of the embryo.
The placenta itself secretes estrogen and progesterone
Structure of the placenta:

Placenta is a membranous vascular organ that develops in female during pregnancy, lining the
uterine wall and partially enveloping the fetus, to which it is attached by the umbilical cord. The
placenta grows during pregnancy and stays connected to the wall of the uterus where it provides the
fetus with nourishment. Following birth, the placenta is expelled.
Amniotic Sac:
Act as a shock absorber and prevent the fetus from getting shocks and germs.
Oxytocin receptors form in the uterus when released, the uterine wall contracts strongly Oxytocin
also stimulates prostaglandin production which can also powerfully stimulate uterine muscle
contraction.




54




MALE REPRODUCTIVE SYSTEM

The major function of the reproductive system is to ensure survival of the species. The male
reproductive system, like that of the female, consists of two groups of organs: primary and accessory
organs.
Functions of male reproductive system:

1. To produce, maintain and transport sperm (the male reproductive cells) and protective fluid
(semen)
2. To produce and secrete male sex hormones (Androgens mainly testosterone) responsible for
maintaining the male reproductive system, and male sex characteristics.
Male reproductive organs: Structure of the male reproductive system:
A. The primary reproductive organs called testes that produce gametes (reproductive cells) and
hormones. These hormones function in the maturation of the reproductive system, the development of
sexual characteristics, and have important roles in regulating the normal physiology of the
reproductive system.
B. The secondary reproductive organs: ducts that
transport gametes, accessory glands and organs that
secrete fluids (semen).

The organs and their functions:

1. SCROTUM: The sac enclosing the testes. It has role
in temperature regulation and protection of the testes.
2. TESTES: For sperms production and the secretion of
55

male sex hormones.
3. DUCTS: Store and transport sperms
4. ACCESSORY GLANDS: Secretion of the fluid part of the semen.
5. PENIS: Serve for discharge of both urine and semen.
TESTES:
The paired testes are the primary male sex
glands that produce gametes and hormones.
Testes are covered by a membrane of fibrous
connective tissue. Connective tissue septa
divide testis into ~ 250 lobules. Each lobule
contains 1-4 seminiferous tubules and interstitial connective tissue.
Seminiferous tubules produce sperm:
Seminiferous tubules lined with spermatogenic cells that develop to form sperms and supporting cells
for the sperms nourishment.
Interstitial cells or Leydig cells: Leydig cells or interstitial cells that secrete male sex hormones
called androgens after puberty. The testes hang below the body housed in the scrotum, maintains
testes at lowered temperature
Sperm are produced by spermatogenesis in the seminiferous tubules
Sperm are collected into the epididymis that lead to the vas deferens

56


Hormonal control of the testes:
Seminiferous tubules: Contain receptor for FSH (Follicle stimulating hormone) in Sertoli cells
(The Sertoli cells in the seminiferous tubules nourish and protect the developing spermatozoa).
FSH stimulates spermatogenesis to occur.

Leydig cells or interstitial cells:
Stimulated by LH (Luteinizing hormone) to secret testosterone.
FSH and LH are released and triggered by the hypothalamus GnRH. GnRH stimulates the pituitary to
secrete gonadotrohic hormones.
Functions of testosterone:
Promotes spermatogenesis/sperm production
Maintains accessory organs
Muscle growth
Secondary sexual characteristics
Feedback to Pituitary and hypothalamus secretions
Spermatogenesis: production of sperm cells
Spermatogenesis occurs within the testes, in the seminiferous tubules. Spermatogonia (germ cells)
divide by mitosis to form more spermatogonia. Some spermatogonia become primary spermatocytes
which undergo spermatogenesis (sperm production by meiosis). Primary spermatocytes produce
secondary spermatocytes, which produce spermatids. Four haploid spermatids are produced by one
diploid primary spermatocyte.
1st meiotic division produces 2 secondary spermatocytes.
2nd meiotic division produces 4 spermatids.
57


Development of Mature Sperm:
Spermatids differentiate into a mature sperm by developing a flagellum, an enzyme cap (the
acrosome).
The Sertoli cells supply nutrients to the sperm.
The mid-piece is located at the base of the flagellum, and is supplied with mitochondria (Tail
provides propulsion)
Testosterone required for completion of meiosis and spermatid maturation
Sperm develop at a temperature lower than the core body temperature in the scrotum

Pathway of spermatozoa:


Duct system:
After they leave the testes, the sperm passes through the epididymis, ductus deferens, ejaculatory
duct, and urethra. Sperm leave the seminiferous tubules and move into tubules of the epididymis,
where the sperm cells mature and stored. Sperm are then ejaculated from the epididymis into the vas
deferens, which passes into the pelvic cavity. The vas deferens leads to the ejaculatory duct, which
passes through the prostate gland and empties into the urethra. The urethra may carry urine or semen,
and passes out through the penis.

Ducts and Tubules Store and Transport Sperm
1. Epididymis
This is a long tube (about 6 meters) located along the superior
and posterior margins of the testes. Sperm that leave the testes
are immature. They complete their maturation process and
become fertile as they move through the epididymis. Mature
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sperm are stored in the lower portion, or tail, of the epididymis.
Spermatic cord
This contains the proximal ductus deferens, testicular artery and veins, lymph vessels, testicular
nerve, muscle and a connective tissue covering.
2. Ductus Deferens [vas deferens]
This is a fibro-muscular tube that is continuous with the epididymis.
Vas deferens enters the abdomino- pelvic cavity and passes along the lateral pelvic wall, behind
bladder and toward the prostate gland. Sperm are stored in the proximal portion of the ductus
deferens, near the epididymis.
3. Ejaculatory Duct
Each ductus deferens joins the duct from the adjacent seminal vesicle (one of the accessory glands) to
form a short ejaculatory duct. Each ejaculatory duct passes through the prostate gland and empties
into the urethra.

4. Urethra:
The penis contains the urethra tube that carries urine from the bladder to outside of the body and also
carries semen out of the body.
Accessory glands:
When sperm leaves the body, it will go up the
vas deferens, past the following glands:
1. Seminal vesicles
2. Prostate gland
3. Bulbourethral gland (cowpers gland)
The accessory glands produce the fluid portion
of semen. Semen is the sperm suspended in the fluid productions of the seminal vesicles. A single
ejaculate of about 3.5 mL of semen contains about 400 million sperm cells.
59

The paired seminal vesicles secrete a fluid rich in fructose.
The single prostate gland, located under the bladder, secretes an alkaline fluid that. It helps to
neutralize the acidic environment of the vagina. The alkaline environment is crucial to generate active
motility in sperm.
The paired bulbourethral glands produce a mucous secretion which lubricates the penis.
Seminal vesicles: (Paired, on back wall of urinary bladder) are active secretory gland. They contribute
~ 60% total volume of semen. Secretions contain fructose, prostaglandins and fibrinogen.
Activate sperm (leading to motility): Alkaline fluid containing fructose for sperms nutrition and
energy.
Prostate gland: (Single, doughnut-shaped). It contributes ~ 20 - 30% of seminal fluid.
Bulbourethral glands: (Cowpers glands) (Pea size, paired, at base of penis). They produce about
10% of semen.
The glands secretion functions to neutralize any acidic urine present in the urethra prior to
ejaculation.
Secrete alkaline mucus with lubricating properties
Semen: is a mixture of sperm and seminal fluid, a liquid that consists of the secretions of the
seminiferous tubules, seminal vesicles, prostate, and bulbourethral.
It is a milky white, sticky mixture of sperm and accessory gland secretions.
Semen provides a transport medium and nutrients (fructose), protects and activates sperm, and
facilitates their movement.

Main constituents:
1. Sperm - 20 - 100 million sperm/ ml. A very large number of sperm is required for successful
fertilization.
2. Seminal fluid Secreted from glands
3. Enzymes protease to break down clotting
60


Hormonal Regulation of Male Reproduction:
The entire male reproductive system is dependent on hormones. The primary hormones involved in
the male reproductive system are:
follicle-stimulating hormone (FSH)
luteinizing hormone (LH)
testosterone (Androgens)
The hypothalamus, pituitary, and testes interact to regulate male reproduction
At about age 10, the hypothalamus secretes gonadotropin-releasing hormone (GnRH)
GnRHstimulates the anterior pituitary to secrete the gonadotrophic hormones: follicle stimulating
hormone (FSH) and luteinizing hormone (LH)
Follicle-stimulating hormone (FSH):
FSH stimulates Sertoli cells that results in development of the seminiferous tubules and stimulates
spermatogenesis.
Luteinizing hormone (LH):
LH, also called interstitial cell stimulating hormone (ICSH), stimulates the interstitial cells to secrete
testosterone.
Inhibin:
Secreted by the Sertoli cells, inhibits FSH production (Negative feedback mechanism)
Testosterone (Main androgens):
Stimulates spermatogenesis, growth of the reproductive organs and development of the male primary
and secondary sexual characteristics including muscle mass , fat distribution, bone mass, facial and
body hair growth, voice change and sex drive.
In castration before puberty, the male remains childlike sex organs and develops no male
secondary sex characteristics
61

Castration after puberty causes increased secretion of male hormones by the adrenal glands
maintains masculine characteristics.
Male Infertility
Over the past 30 years, the sperm content of semen has dropped dramatically
In the 1970s sperm content of an average ejaculate was ~100 million / mL; now it is ~60 million /
mL
It is thought that low sperm count is attributable to drug usage, alcohol abuse, cigarette smoking
and possibly industrial and environmental toxins.



62







Macromolecules and Enzymes

63


Macromolecules

The structure and physiology of all living organisms is dependent mainly on large molecules known as
macromolecules (proteins, carbohydrates, lipids and DNA). In addition to these molecules water,
vitamins and micromolecules such as metal ions also play their important role in the maintenance of life
activities.

1. Amino acids and Proteins
Proteins are the most abundant and functionally diverse molecules in living systems. Every life process
depends on this class of molecules. For example, enzymes and polypeptide hormones direct and regulate
metabolism in the body, whereas contractile proteins in muscle permit movement.

Structure of the amino acids
Although more than 300 different amino acids have been
described in nature, only 20 are commonly found as
constituents of mammalian proteins.
Symbols or codes for amino acids
Each amino acid is given a three letters or single letter code.
Peptide bond
In proteins, amino acids are joined covalently by peptide
bonds, which are amide linkages between the -carboxyl group
of one amino acid and the -amino group of another.

Structure of proteins
The structure of proteins has been given 4 different stages i.e.
primary, secondary, tertiary and quaternary structures.



64

Primary structure of proteins
The sequence of amino acids in a polypeptide chain is known as primary structure of proteins. The
primary structure of proteins has only peptide bond between the amino acids as the binding force.
Secondary structure of proteins
The arrangement of amino acids in the
polypeptide chain into some regular
secondary structures like alpha-helices and
beta-pleated sheets or irregular structures
like random coils, turns and loops is known
as the secondary structure of proteins.
Tertiary structure of proteins
Three dimensional arrangements of
secondary structures is known as tertiary
structure of proteins. The proteins become
functionally active after having the tertiary
structure if they consist of single
polypeptide chain.
Quaternary structure of proteins
For those proteins which consist of more
than one polypeptide chains, these chains
interact with each other after achieving
tertiary structure to become a functional
unit. This combination of properly folded
two or more polypeptides for a physiological activity is known as quaternary structure of proteins.
65


Carbohydrates
Carbohydrates are molecules composed of carbon, hydrogen, and oxygen; the ratio of hydrogen atoms to
oxygen atoms is 2:1. Almost all organisms use carbohydrates as sources of energy. In addition, some
carbohydrates serve as structural materials.
On the basis of the number of forming units, three major classes of carbohydrates can be defined:
monosaccharides, oligosaccharides and polysaccharides. The term saccharide derives from the
greek word sakcharon, which means sugar.
Monosaccharides or simply sugars are formed by only one polyhydroxy aldehydeidic or ketonic
unit. The most abundant monosaccharide is D-glucose, also called dextrose.

Oligosaccharides are formed by short chains of monosaccharidic units (from 2 to 20) linked one to
the next by chemical bounds, called glycosidic bounds. The most abundant oligosaccharides are
disaccharides, formed by two monosaccharides, and especially in the human diet the most important
are sucrose (common table sugar), lactose and maltose. Within cells many oligosaccharides formed
by three or more units do not find themselves as free molecules but linked to other ones, lipids or
proteins, to form glycoconjugates.

Polysaccharides are polymers consisting of 20 to 10
7
monosaccharidic units; the difference is due to
the presence of monosaccharides recurring in the structure, for the length and the degree of branching
of chains or for the type of links between units. Polysaccharides are defined omopolysaccharides if
they contain only one type of monosaccharide as starch, glycogen and chitin; eteropolysaccharides,
instead, contain two or more different kinds (e.g. hyaluronic acid).

66


Lipids
Lipids are organic molecules composed of carbon, hydrogen, and oxygen atoms. The ratio of hydrogen
atoms to oxygen atoms is much higher in lipids than in carbohydrates. Lipids include steroids (the
material of which many hormones are composed), waxes, and fats.
Fats stored in cells usually form clear oil droplets called globules because fats do not dissolve in water.
The fats in adipose tissue contain much concentrated energy. Hence, they serve as a reserve energy
supply to the organism. The enzyme lipase breaks down fats into fatty acids and glycerol in the human
digestive system.















67

Louis Pasteur

Enzymes
Enzymes are proteins that control the speed of chemical reactions in your body. Without enzymes,
these reactions would take place too slowly to keep you alive. The branch of science concerned
with the study of enzymes is called enzymology.

Background
The history of enzymes and enzymology is as old as the history of human
beings. In the modern biochemistry, the first use of enzymes was made by
Louis Pasteur in 1850s when he was converting sugars to alcohols by the
help of yeast cells. The word enzyme means in yeast (en- in, zyme-
yeast).

Properties of enzymes
1. Enzymes are proteins in nature: A vast majority of enzymes are protein catalysts that
increase the velocity of a chemical reaction, and are not consumed during the reaction.
2. Active sites: Enzymes are larger molecules which contain a special pocket or cleft called the
active site. The active site contains amino acid side chains that participate in substrate binding and
catalysis. The substrate binds the enzyme, forming an enzymesubstrate (ES) complex.
E + S <==> ES <==> S + P

Where E stands for enzyme, S for substrate and for products.

Substrate: The material or substance on which an enzyme acts.
Product: The product is what you're left with when the enzyme binds with the substrate.





68


Enzyme nomenclature/classification
The enzymes are named according to different criteria.
They may be named after the name of substrate acted upon, after the name of product and the
name of reaction catalyzed. For example, enzymes acting upon lipids were named lipases, acting
on proteins were named proteinases and sucrose (acting upon sucrose) etc.
Similarly, the enzymes have also been named after the name of product of reaction catalyzed
with the addition of suffix ase after the name of product. For example, fumarase is the enzyme
which catalyzes the production of fumarate.
As the enzymes are reaction specific, they can also be named after the name of reaction
catalyzed. For example, hydrolase (catalyzing hydrolysis), Oxidase (catalyzing oxidation),
dehydrogenase (catalyzing dehydrogenation reaction).
In 1961, International Union of Biochemistry (I.U.B.) named the enzymes according to the
name of substrate and chemical reaction involved by adding suffix ase after the name of chemical
reactions. e.g. L-malate dehydrogenase.

Classification of enzymes
Enzymes are classified into 6 major classes and 13 sub classes on the basis of the type of reaction
they catalyze. The major classes and related reaction types are described in the table below:

Binding of an enzyme active site with the substrate
There are two basic concepts about the binding of an enzyme active site with the substrate.
Lock and key theory: The Lock and key theory was proposed by Emile Fischer in 1894.
69

According to this theory the enzyme is a larger and rigid molecule and the substrate fits into the
enzyme active site like a key fits into a lock.








Theory of induced fit: The theory of induced fit was proposed by Daniel Koshland in 1958.
According to this theory, the enzyme is a rigid larger molecule with minimum flexibility in the active
site. The binding of substrate with the enzyme active site causes a conformational change in the
enzyme (induced fit) that allows catalysis. ES is converted to an enzymeproduct (EP) complex that
subsequently dissociates to enzyme and product.

3. Catalytic efficiency: Enzyme
catalysed reactions are highly
efficient, proceeding from 10
3
10
8

times faster than uncatalyzed
reactions.

4. Specificity: Enzymes are highly
specific, interacting with one or a few
(Lock and key theory of ES-Complex) (Induced-fit theory of ES-Complex)
70

substrates and catalysing only one type of chemical reaction.
5. Apoenzymes and Holoenzymes: The term holoenzyme refers to the active enzyme with its
non-protein component, whereas the enzyme without its nonprotein moiety is termed an apoenzyme
and is inactive.
Cofactor: If the nonprotein part is a metal ion such as Zn
2+
or Fe
2+
, it is called a cofactor.
Coenzyme: If the nonprotein part is organic molecule, it is termed a coenzyme.
Cosubstrates: If the coenzyme is temporarily associate with the enzyme are called cosubstrates.
Prosthetic group: If the coenzyme is permanently associated with the enzyme and returned to its
original form, it is called a prosthetic group.
How enzymes work?
Every chemical reaction requires crossing a specific energy barrier to start. This energy barrier is
known as activation energy. More precisely, the activation energy is the amount of energy required to
bring a substrate from its ground state (stable) to transition state (highly unstable). The catalysts like
the enzymes lower the activation energy of a chemical reaction and consequently increase the rate of
reaction. The reaction coordinate diagram indicates the activation energy of an uncatalyzed reaction is
higher than that of an enzyme catalysed reaction. The increase in rate of reaction decreases the time to
achieve the reaction equilibrium.







71



However it does not change the equilibrium position of a chemical reaction.
Factors Affecting Enzyme Activity

Enzyme Concentration
Increase in the concentration of the enzyme increases the rate of reaction linearly. That is if the
concentration of enzyme is doubled, the rate doubles.

Substrate Concentration
At constant enzyme concentration, initially, the rate increases with increases in substrate
concentration, but at a certain level, the rate levels out and remains constant. So at some point,
increasing the substrate concentration does not increase the rate of reaction, because the excess
substrate cannot find any active sites to attach to.

Temperature
For enzyme-catalyzed reactions, like all chemical reactions, rate increases with temperature.
However, enzymes are proteins, and at higher temperatures proteins become denatured and inactive.
Thus, every enzyme has an optimum temperature.

Optimum temperature - the temperature at which enzyme activity is highest, usually about 25
o
C-
40
o
C.

Effect of pH
Small changes in pH can result in enzyme denaturation and loss of catalytic activity. Because the
charge on acidic and basic amino acid residues located at the active site depends on pH. Most
enzymes only exhibit maximum activity over a very narrow pH range.

Optimum pH - is the pH at which an enzyme has maximum activity.
Most enzymes have an optimum pH that falls within the physiological range of 7.0-7.5.

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Inhibition of enzyme activity
Enzyme inhibitors are molecules that
interact in some way with the enzyme to
prevent it from working in the normal
manner. These inhibitors can be specific and
nonspecific.
Nonspecific Inhibitors:
A nonspecific inhibitor effect all enzymes in
the same way. Non-specific methods of
inhibition include any physical or chemical
changes which ultimately denatures the
protein portion of the enzyme and are
therefore irreversible.

Specific Inhibitors:
A specific inhibitor effects upon a single enzyme. Most poisons
work by specific inhibition of enzymes. It can be irreversible and
reversible - competitive and noncompetitive. Poisons and drugs
are examples of enzyme inhibitors.
Competitive inhibition
This type of inhibition occurs when the inhibitor binds
reversibly to the same site that the substrate would normally
occupy and, therefore, competes with the substrate for that site.
Noncompetitive inhibition
Noncompetitive inhibition occurs when the inhibitor and
substrate bind at different sites on the enzyme. The non-
competitive inhibitor can bind either free enzyme or the ES
complex, thereby preventing the reaction from occurring.

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Applications of Enzymes
In daily life:
The enzymes have many applications in our daily life. Some important applications include
production of dairy products, wine manufacturing, candy making, fruit juices, tenderizing meat etc.
In medical sciences:
Diagnosis of diseases: Fluctuation in the standard amount of enzymes in human body sometimes
can be used as predictable markers for some diseases, for example: The activity of renin, a proteolytic
enzyme produced by kidneys is found associated with hypertension and is used as the indirect marker
of hypertension diagnosis.
Cancer Chemotherapy: Some enzymes are used in cancer chemotherapy.

Digestive Enzymes
Digestive Enzymes assist the body in the breakdown of food. Different enzymes with different
functions are produced in particular areas of the digestive tract. Digestive enzymes are primarily
responsible for the chemical breakdown of food and constitute a large portion of digestive secretions.
The human body makes approximately 22 different enzymes that are involved in digestion.
Mouth
Saliva contains the enzyme salivary amylase. This enzyme breaks starch into smaller sugars and is
stimulated by chewing. It is important to chew food thoroughly as this is the first stage of the
digestive process. Starch hydrolysed into maltose through the action of the enzyme amylase
Stomach
The stomach is responsible for the digestion of protein. Gastric juice is produced by the gastric glands
in the stomach wall.
It contains mucus, hydrochloric acid, the inactive enzyme precursor Pepsinogen. Pepsinogen is
activated by the hydrochloric acid, which converts it into pepsin. Pepsin converts proteins into
peptides.
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Small intestine
Enzymes produced by the wall of the small intestine are not secreted like the other enzymes of the
digestive tract. Instead, they remain attached to the plasma membrane of the cells lining the intestine,
with their active sites exposed to the food in the intestine. With this arrangement, the substrates can
be digested and then the products of digestion can immediately be absorbed into the body. Jejunum
absorbs water-soluble vitamins, protein and carbohydrates.
Maltose hydrolysed into glucose through the action of the enzyme maltase. Maltase breaks down
maltose into two glucose molecule. The ileum absorbs fat-soluble vitamins, fat, cholesterol and bile
salts. The small intestine also receives secretions and enzymes from the pancreas, liver and the
gallbladder.

Pancreas
The pancreas produces digestive enzymes that act in the small intestine. These enzymes play a major
role in digestion. The pancreas secretes about one and a half litters of pancreatic juice a day. The
enzymes produced by the pancreas include;
Amylases - Pancreatic amylase carries out the same reaction as salivary amylase. These break down
starch molecules into smaller sugars. Amylases also break down carbohydrates into maltose.
Lipases - Lipases function in the digestion of fats, oils and fat-soluble vitamins.
Proteases - are responsible for breaking down protein into smaller amino acids. Proteases include
trypsin, chymotrypsin and carboxypeptidase. A lack of proteases can cause incomplete digestion that
can lead to allergies and the formation of toxins.

Liver
The liver is the largest internal organ of the human body. The liver produces bile that is either stored
by the gallbladder or secreted into the small intestine. Bile emulsifies fats and fat-soluble vitamins. It
also helps keep the small intestine free from parasites. The liver metabolizes proteins, carbohydrates
and cholesterol and is responsible for the detoxification of toxins, drugs and hormones.

Large intestine
The large intestine absorbs water, electrolytes and some of the final products of digestion.

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Digestive Enzymes

Digestive juices and enzymes Substance
digested
Product formed
Saliva
Amylase
Starch Maltose
Gastric juice
Protease (pepsin) and
hydrochloric acid
Proteins Partly digested proteins
Pancreatic juice
Proteases (trypsin)
Lipases
Amylase
Proteins
Fats emulsified
by bile
Starch
Peptides and amino acids
Fatty acids and glycerol
Maltose
Intestinal enzymes
Peptidases
Sucrase
Lactase
Maltase
Peptides
Sucrose (sugar)
Lactose (milk
sugar)
Maltose
Amino acids
Glucose and fructose
Glucose and galactose
Glucose
Bile from the liver
Bile salts
Fats globules Fat droplets





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Pathogens and infectious diseases
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Pathogens
A pathogen is a biological agent that causes disease or illness to its host.
Pathogens include the disease causing microorganisms, such as bacteria, fungi , protozoans and
viruses, found commonly in sewage, hospital waste and anywhere in the environment. Most pathogens
are parasites (live off the host) and the diseases they cause are indirect result of their obtaining food
and introducing toxic or harmful materials into the host. Larger parasites (such as worms) are not
called pathogens.
Viruses
Viruses are small infectious agents that
replicate only inside the living cells of host
organisms. Viruses can infect all types of life
forms, from animals and plants to bacteria
and Achaea.
Viruses were first of all reported in the leaves
of infected tobacco plant by Dmitri
Ivanovsky's in 1892.
Virion: In its infective form, outside the
cell, a virus particle is called a virion. Each
virion contains at least one unique protein
synthesized by specific genes in its nucleic acid.
Structure: A virus particle consists of a DNA or RNA core which serves as the viral genome. The
genome remains protected in a protein coat. The protein coat or capsid consists of a head region, a tail,
an end plate and tail fibers.

Capsid - The capsid is the protein shell that encloses the nucleic acid; with its enclosed nucleic acid, it
is called the nucleocapsid.

Envelope - Many types of virus have a glycoprotein envelope surrounding the nucleocapsid. The
envelope is composed of two lipid layers interspersed with protein molecules (lipoprotein bilayer) and
may contain material from the membrane of a host cell as well as that of viral origin.
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Nucleic Acid - The genetic material within virus particles, and the method by which the material is
replicated, varies considerably between different types of viruses.
DNA viruses
The genome replication of most DNA viruses takes place in the cell's nucleus. If the cell has the
appropriate receptor on its surface, these viruses enter the cell sometimes by direct fusion with the cell
membrane (e.g., herpesviruses) or more usually by receptor-mediated endocytosis. Most DNA
viruses are entirely dependent on the host cell's DNA and RNA synthesising machinery, and RNA
processing machinery; however, viruses with larger genomes may encode much of this machinery
themselves. In eukaryotes the viral genome must cross the cell's nuclear membrane to access this
machinery, while in bacteria it need only enter the cell.
RNA viruses
Replication usually takes place in the cytoplasm. RNA viruses can be placed into four different groups
depending on their modes of replication. The polarity (whether or not it can be used directly by
ribosomes to make proteins) of single-stranded RNA viruses largely determines the replicative
mechanism; the other major criterion is whether the genetic material is single-stranded or double-
stranded. All RNA viruses use their own RNA replicase enzymes to create copies of their genome
Mode of action/ mechanism of viral pathogenesis
Generally viral pathogenic mechanisms include implantation of the virus at a body site (the portal of
entry), replication at that site, and then spread to and multiplication within sites (target organs) where
disease or shedding of virus into the environment occurs.










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Viral populations do not grow through cell division, because they are acellular. Instead, they use the
machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble
in the cell.











A typical virus replication cycle


The life cycle of viruses differs greatly between species but there are six basic stages in the life
cycle of viruses:
Attachment is a specific binding between viral capsid proteins and specific receptors on the host
cellular surface. Attachment to the receptor can induce the viral envelope protein to undergo changes
that results in the fusion of viral and cellular membranes, or changes of non-enveloped virus surface
proteins that allow the virus to enter.
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Penetration or viral entry follows attachment: Virions enter the host cell through receptor-
mediated direct penetration, endocytosis or membrane fusion. This is often called viral entry.
Uncoating is a process in which the viral capsid is removed: This may be by degradation by viral
enzymes or host enzymes or by simple dissociation; the end-result is the releasing of the viral genomic
nucleic acid.
Replication of viruses involves primarily multiplication of the genome. Replication involves
synthesis of viral messenger RNA (mRNA), viral protein synthesis, possible assembly of viral
proteins, then viral genome replication mediated by early or regulatory protein expression. Following
the structure-mediated self-assembly of the virus particles, some modification of the proteins often
occurs.

Release of Viruses from host cell can occur by lysis, a process that kills the cell by bursting its
membrane.
Some viruses undergo a lysogenic cycle where the viral genome is incorporated by genetic
recombination into a specific place in the host's chromosome. Whenever the host divides, the viral
genome is also replicated.
The viral genome is mostly silent within the host; however, at some point, it may give rise to active
virus, which may lyse the host cells.



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82


Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this
process the virus acquires its envelope, which is a modified piece of the host's plasma or other, internal
membrane.


















Effects on the host cell
Most virus infections eventually result in the death of the host cell. The causes of death include cell
lysis, alterations to the cell's surface membrane and apoptosis. Some viruses cause no apparent
changes to the infected cell. Cells in which the virus is latent and inactive show few signs of infection
and often function normally.
In humans, smallpox, the common cold, chickenpox, influenza, shingles, herpes, polio, rabies and
AIDS are examples of viral diseases.

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84



Bacteria
Bacteria are microscopic unicellular prokaryotic organisms characterized by the lack of a membrane-
bound nucleus and membrane-bound organelles. They were first observed by Antony van
Leeuwenhoek in the 17th century. However,
bacteriology as an applied science began to develop
in the late 19th century as a result of research in
medicine and in fermentation processes by Louis
Pasteur and Robert Koch.

Structure
In most bacteria, a cell wall is present on the outside
of the cytoplasmic membrane. A common bacterial
cell wall material is peptidoglycan. The plasma
membrane and cell wall comprise the cell envelope.
Plasma membrane encloses the contents of the cell and acts as a barrier to hold nutrients, proteins and
other essential components of the cytoplasm within the cell. Bacteria do not usually have membrane-
bound organelles in their cytoplasm and their genetic material is typically a single circular
chromosome located in the cytoplasm in an irregularly shaped body called the nucleoid. The nucleoid
contains the chromosome with its associated proteins and RNA.
Bacteria are divided into several types on the basis of their shape and structure. Bacteria cause
diseases in man including tuberculosis, cholera, typhoid fever and tetanus.








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How bacteria cause diseases in human
Pathogenic bacteria can be grouped into three categories on the basis of their invasive properties for
eukaryotic cells.
Extracellular bacteria
Intracellular bacteria

Extracellular bacteria: Extracellular bacterial pathogens do not invade cells and proliferate instead in
the extracellular environment which is enriched with body fluids. Some of extracellular bacteria even
dont penetrate body tissues (e.g. V. cholerae) but adhere to epithelial surfaces and cause disease by
secreting potent toxins. Extracellular bacteria do not
have the capacity to survive the intracellular
environment or to induce their own uptake by most
host cells.

Intracellular Bacteria:
Intracellular bacteria can enter and survive within
eukaryotic cells are shielded from humoral antibodies
and can be eliminated only by a cellular immune
response. However these bacteria must possess specialized mechanisms to protect them from the harsh
environment of the lysosomal enzymes encountered within the cells.
Steps in the intracellular life cycles of the bacterial pathogens. (1) internalization of bacteria into host
cells, (2) destruction of phagosomes and access of bacteria to the host cytosol, (3) replication in the
cytosol, (4) entrance in the adjacent cell, (5) formation of bacterial protrusions, (6) engulfment of
protrusions and (7) dissolution of the double membranous vacuole. The process of cellcell spread
comprises steps 47.
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Two broad qualities of pathogenic bacteria underlie the means by which they cause disease;
1. Invasiveness is the ability to invade tissues. It encompasses
mechanisms for colonization (adherence and initial multiplication),
production of extracellular substances which facilitate invasion
(invasins) and ability to bypass or overcome host defense mechanisms.
2. Toxigenesis is the ability to produce toxins. Bacteria may produce
two types of toxins called exotoxins and endotoxins. Exotoxins are
released from bacterial cells and may act at tissue sites removed from
the site of bacterial growth. Endotoxins are cell-associated substance.
Some bacterial toxins may also act at the site of colonization and play
a role in invasion.

Binary fission: Bacteria grow to a fixed size and then reproduce through
binary fission, a form of asexual reproduction. Under optimal conditions,
bacteria can grow and divide extremely rapidly, and bacterial populations
can double as quickly as every 9.8 minutes.
Treatment: Bacterial infections may be treated with antibiotics, which are
classified as bactericidal if they kill bacteria or bacteriostatic if they just prevent bacterial growth.

Fungi
Fungi cause diseases because they have toxins called mycotoxins, which can cause serious illness if
ingested. The spores may also cause allergic reactions and diseases to susceptible humans and animals,
such as bronchitis. Fungi may also cause infections but this only affects people with a very low
immune system. Fungal diseases are called mycoses and those affecting humans can be divided into
four groups based on the level of penetration into the body tissues.
Superficial mycoses are caused by fungi that grow on the surface of the skin or hair.
Cutaneous mycoses or dermatomycoses include such infections as athlete's foot and ringworm,
where growth occurs only in the superficial layers of skin, nails, or hair.
Subcutaneous mycoses penetrate below the skin to involve the subcutaneous, connective, and
bone tissue.

87

Athletes foot
diseases



Systemic or deep mycoses are able to infect internal organs and become widely disseminated
throughout the body. This type is often fatal.

Disease mechanisms of Fungi:
Entry: Fungi infect the body through several portals of entry. The first
exposure to fungi that most humans experience occurs during birth, when they
encounter the yeast C. Albicans.

Multiplication: Although most fungal diseases are the result of accidental
encounters with the agent, many fungi have developed mechanisms that
facilitate their multiplication within the host. For example, the dermatophytes that colonize skin, hairs,
and nails elaborate enzymes that digest keratin. Fungal growth is discouraged by the intact skin and
factors such as naturally occurring long-chain unsaturated fatty acids, pH competition with the normal
bacteria, epithelial turnover rate of stratum corneaum. In humans, fungi can cause ringworms and
athlete's foot diseases.









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Infectious diseases
Infectious diseases are caused by pathogenic microorganisms, such as bacteria, viruses, protozoans
and fungi. The diseases can be spread, directly or indirectly, from one person to another. Major
infectious diseases are Influenza, pneumonia, cholera, malaria, measles, tuberculosis, dengue and
hepatitis.

Influenza
Influenza is an acute viral infection
that spreads easily from person to
person. Influenza circulates
worldwide and can affect anybody in
any age group.

Causative agent
Seasonal influenza is caused by an
influenza virus. There are three types of seasonal influenza A, B and C.

Signs and symptoms
Seasonal influenza is characterized by a
sudden onset of high fever, cough (usually
dry), headache, muscle and joint pain,
severe malaise (feeling unwell), sore throat
and runny nose. Most people recover from
fever and other symptoms within a week
without requiring medical attention. But
influenza can cause severe illness or death
in people at high risk. The time from
infection to illness, known as the incubation
period, is about two days.


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Risk factors
The highest risk of complications occur among children younger than age two, adults age 65 or older,
and people of any age with certain medical conditions, such as chronic heart, lung, kidney, liver,
blood or metabolic diseases (such as diabetes), or weakened immune systems
.
Transmission
Seasonal influenza spreads easily and can sweep through
schools, nursing homes or businesses and towns. When
an infected person coughs, infected droplets get into the
air and another person can breath them in and be exposed.
The virus can also be spread by hands infected with the
virus. To prevent transmission, people should cover their
mouth and nose with a tissue when coughing, and wash
their hands regularly.

Treatment
Antiviral drugs for influenza are available in some countries and effectively prevent and treat the
illness.
Prevention
The most effective way to prevent the disease or severe outcomes from the illness is vaccination. Safe
and effective vaccines have been available and used for more than 60 years.
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Measles
Measles is one of the leading causes of death among young children even though a safe and cost-
effective vaccine is available. Measles is a highly contagious, serious disease caused by a virus.

Causative agent
Measles is caused by Rubeola virus
(paramyxovirus family). The measles
virus normally grows in the cells that
line the back of the throat and lungs.
Measles is a human disease and is not
known to occur in animals.

Symptoms
The first sign of measles is usually a
high fever, which begins about 10 to
12 days after exposure to the virus, and lasts four to seven days. A runny nose, a cough, red and
watery eyes, and small white spots inside the cheeks can develop in the initial stage. After several
days, a rash erupts, usually on the face and upper neck. Over about three days, the rash spreads,
eventually reaching the hands and feet. The rash lasts for five to six days, and then fades. On average,
the rash occurs 14 days after exposure to the virus (within a range of seven to 18 days). Most
measles-related deaths are caused by complications associated with the disease. Complications are
more common in children under the age of five, or adults over the age of 20.

Mode of transmission
The highly contagious virus is spread by coughing and sneezing, close personal contact or direct
contact with infected nasal or throat secretions. It can be transmitted by an infected person from four
days prior to the onset of the rash to four days after the rash erupts.

Treatment
No specific antiviral treatment exists for measles virus. Severe complications from measles can be
avoided though supportive care that ensures good nutrition, adequate fluid intake and treatment of
dehydration with WHO-recommended oral rehydration solution. This solution replaces fluids and
91

other essential elements that are lost through diarrhoea or vomiting. Antibiotics should be prescribed
to treat eye and ear infections, and pneumonia.






















Prevention
Routine measles vaccine has been in use for over 40 years. It is safe, effective and inexpensive.


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Pneumonia
Pneumonia is an infection of the lungs caused by bacteria, viruses or fungi. It is characterized
primarily by inflammation of the alveoli in the lungs or by alveoli that are filled with fluid (alveoli
are microscopic sacs in the lungs that absorb oxygen). In severe condition, pneumonia can make a
person very sick or even cause death. Although the disease can occur in young and healthy people, it
is most dangerous for older adults, babies, and people with other diseases or impaired immune
systems.
Bacteria and viruses are the primary causes of pneumonia. When a person breathes pneumonia-
causing germs into his lungs and his body's immune system cannot otherwise prevent entry, the
organisms settle in small air sacs called alveoli and continue multiplying. As the body sends white
blood cells to attack the infection, the sacs become filed with fluid and pus causing pneumonia.

Bacterial Pneumonia
Streptococcus pneumoniae is the most common cause of bacterial pneumonia. Atypical pneumonia, a
type of pneumonia that typically occurs during the summer and fall months, is caused by the bacteria
Mycoplasma pneumoniae.

Viral Pneumonia
Viral pneumonias do not typically
respond to antibiotic treatment (in
contrast to bacterial pneumonias).
Adenoviruses, rhinovirus, influenza
virus (flu), respiratory syncytial virus
(RSV), and parainfluenza virus are all
potential causes of viral pneumonia.

Fungal Pneumonia
Histoplasmosis, coccidiomycosis,
blastomycosis, aspergillosis, and
cryptococcosis are fungal infections
that can lead to fungal pneumonia.
93

These types of pneumonias are relatively infrequent in the United States.

Other types of Pneumonia
Organisms that have been exposed to strong antibiotics and have developed resistance are called
nosocomial organisms. If they enter the lungs, a person may develop nosocomial pneumonia.
Resistant bacteria are often found in nursing homes and hospitals. An example is MRSA, or
methicillin-resistant Staph aureus, which can cause skin infections as well as pneumonia. Similarly,
outbreaks of the H5N1 influenza (bird flu) virus and severe acute respiratory syndrome (SARS) have
resulted in serious pneumonia infections.
Risk factors
Some people are more likely than others to develop pneumonia. Individuals at higher risk include
those who smoke, abuse alcohol, have other medical conditions like HIV/AIDS or recently recovered
from a cold or influenza infection or malnourished.
Symptoms of pneumonia
Common symptoms include: Cough
Rusty or green mucus (sputum)
coughed up from lungs, Fever, Fast
breathing and shortness of breath,
Chest pain, Nausea and vomiting and
Headache etc

Diagnosis of pneumonia
A pneumonia diagnosis usually
begins with a physical exam and a
discussion about your symptoms and
medical history. Chest x-rays,
analysis of sputum and blood tests
are usually recommended.
94

Treatment of Pneumonia
Pneumonia treatments depend on the type of pneumonia and the severity of symptoms. Bacterial
pneumonias are usually treated with antibiotics, whereas viral pneumonias are treated with rest and
plenty of fluids. Fungal pneumonias are usually treated with antifungal medications. Over-the-counter
medications are also commonly prescribed to better manage pneumonia symptoms. These include
treatments for reducing fever, reducing aches and pains, and suppressing coughs. In addition, it is
important to get plenty of rest and sleep and drink lots of fluids.
Prevention of Pneumonia
In addition to vaccinations, physicians recommend that people wash hands, refrain from smoking, eat
healthfully, exercise, and stay away from sputum or cough particles from others with pneumonia.
The pneumonia vaccine may not completely prevent older adults from getting pneumonia, but it can
reduce the severity of a future pneumonia.


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Tuberculosis

Tuberculosis (TB) is second only to HIV/AIDS as the greatest killer
worldwide due to a single infectious agent.

Causative agent
Tuberculosis (TB) is caused by bacteria (Mycobacterium tuberculosis)
that most often affect the lungs. Tuberculosis is curable and
preventable.

Mode of transmission
TB is spread from person to person through
the air. When people with lung TB cough,
sneeze or spit, they propel the TB germs into
the air. A person needs to inhale only a few of
these germs to become infected. Tuberculosis
mostly affects young adults, in their most
productive years. However, all age groups are
at risk.

Symptoms and diagnosis
Common symptoms of active lung TB are cough with sputum and blood at times, chest pains,
weakness, weight loss, fever and night sweats. Generally Sputum smear microscopy is used to
diagnose TB.

Treatment
TB is a treatable and curable disease. Active, drug-sensitive TB disease is treated with a standard six-
month course of four antimicrobial drugs that are provided with information, supervision and support
to the patient by a health worker or trained volunteer.
96

97









Molecular Biology

98


Molecular Biology
Genetic information, stored in the chromosomes and transmitted to daughter cells through DNA
replication, is expressed through transcription to RNA and, in the case of messenger RNA
(mRNA), subsequent translation into proteins (polypeptide chains).



















STRUCTURE OF DNA
DNA is a polymer of deoxyribonucleoside monophosphates covalently linked by 3'5'
phosphodiester bonds. With the exception of a few viruses that contain single-stranded (ss) DNA,
DNA exists as a double stranded (ds) molecule, in which the two strands wind around each other,
forming a double helix.
In eukaryotic cells, DNA is found associated with various types of proteins (known collectively as
nucleoprotein) present in the nucleus, whereas in prokaryotes, the proteinDNA complex is present in
a non-membrane-bound region known as the nucleoid.
99



Phosphodiester bonds
A nucleotide is composed of three parts: a nitrogen
containing (nitrogenous) base, a five-carbon sugar (a
pentose), and one or more phosphate groups. To
distinguish the numbers of the sugar carbons from
those used for the ring atoms of the attached
nitrogenous base, the sugar carbon numbers of a
nucleoside or nucleotide have a prime () after them.
Phosphodiester bonds join the 3'-hydroxyl group of
the deoxy pentose of one nucleotide to the 5'-hydroxyl
group of the deoxy pentose of an adjacent nucleotide
through a phosphate group. The resulting long,
unbranched chain has polarity, with both a 5'-end (the
end with the free phosphate) and a 3'-end (the end
with the free hydroxyl) that is not attached to other
nucleotides. In the double helix, the two chains are
coiled around a common axis called the axis of
symmetry. The chains are paired in an anti-parallel
manner, that is, the 5'-end of one strand is paired with
the 3'-end of the other strand.

In the DNA helix, the hydrophilic deoxyribosephosphate backbone of each chain is on the outside of
the molecule, whereas the hydrophobic bases are stacked inside. The overall structure resembles a
twisted ladder. The bases of one strand of DNA are
paired with the bases of the second strand, so that an
adenine is always paired with a thymine and a
cytosine is always paired with a guanine. The two
strands of the double helix separate when hydrogen
bonds between the paired bases are disrupted.
Disruption can occur in the laboratory if the pH of the
100

DNA solution is altered so that the nucleotide bases ionize, or if the solution is heated.

Eukaryotes have closed circular DNA molecules in their mitochondria, as do plant chloroplasts. A
prokaryotic organism typically contains a single, double-stranded, supercoiled, circular chromosome.
Each prokaryotic chromosome is associated with non-histone proteins that can condense the DNA to
form a nucleoid.












101


DNA Replication or Synthesis of DNA
When the two strands of the DNA double helix are separated, each can serve as a template for the
replication of a new complementary strand. This produces two daughter molecules, each of which
contains two DNA strands with an antiparallel orientation. This process is called replication of DNA.
The enzymes involved in the DNA replication process are template-directed polymerases that can
synthesize the complementary sequence of each strand with extraordinary fidelity. Overall replication
process involves following steps:

Separation of the two complementary DNA strands
Two strands of the parental double helical DNA separate
over a small region, because the polymerases use only
ssDNA as a template. DNA replication begins at unique
nucleotide sequencea site called the origin of replication
This site includes a short sequence composed almost
exclusively of AT base pairs that facilitate melting. In
eukaryotes, replication begins at multiple sites along the
DNA helix whereas in prokaryotes there is a single site for DNA replication origin.

Formation of the replication fork
As the two strands unwind and separate,
they form a V where active synthesis
occurs. This region is called the
replication fork. It moves along the DNA
molecule as synthesis occurs. Replication
of dsDNA is bidirectionalthat is, the
replication forks move in opposite
directions from the origin.

102


Initiation of DNA replication requires the recognition of the origin of replication by a group of
proteins that form the pre-priming complex. These proteins are responsible for maintaining the
separation of the parental strands, and for unwinding the double helix ahead of the advancing
replication fork.

Helicases are the enzymes which bind to ssDNA near the replication fork, and then move into the
neighboring double stranded region, forcing the
strands apartin effect, unwinding the double
helix. Helicases require energy provided by ATP.

DNA topoisomerases are the enzymes which
remove the supercoiling of parent DNA strand and
help in unwinding of DNA. The DNA
polymerases responsible for copying the DNA
templates are only able to read the parental
nucleotide sequences in the 3'5' direction, and they synthesize the new DNA strands only in the
5'3' (antiparallel) direction. Therefore, beginning with one parental double helix, the two newly
synthesized stretches of nucleotide chains must grow in opposite directionsone in the 5'3'
direction toward the replication fork and one in the 5'3' direction away from the replication fork.

Leading and Lagging strands
The strand that is being copied in the direction of the advancing replication fork is called the leading
strand and is synthesized continuously. The strand that is being copied in the direction away from the
replication fork is synthesized discontinuously, with small fragments of DNA being copied near the
replication fork. These short stretches of discontinuous DNA, termed Okazaki fragments, are
eventually joined (ligated) to become a single, continuous strand. The new strand of DNA produced
by this mechanism is termed the lagging strand.





103


Transcription-Synthesis of RNA from DNA
The process of transcription of a typical gene can be divided into three phases: initiation, elongation,
and termination.

Initiation
Transcription begins with the binding of the RNA
polymerase holoenzyme to a region of the DNA known as
the promoter, which is not transcribed. The holoenzyme
moves to the site of initial DNA melting (unwinding).
Melting of a short stretch (about 14 bases) converts the
closed complex to an open one known as a transcription
bubble.

Elongation
Once the promoter region has been recognized and bound by the holoenzyme, local unwinding of the
DNA helix continues, mediated by the polymerase. RNA polymerase begins to synthesize a transcript
of the DNA sequence, and several short pieces of RNA are made and discarded. The elongation phase
is said to begin when the transcript (typically starting with a purine) exceeds ten nucleotides in length.
As with replication, transcription is always in the
5'3' direction. In contrast to DNA polymerase,
RNA polymerase does not require a primer and
does not appear to have proofreading activity.

Termination
The elongation of the single-stranded RNA chain
continues until a termination signal is reached.
Termination can be intrinsic (spontaneous) or
dependent upon the participation of a protein
known as the (rho) factor.



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Types of RNA molecules produced by transcription
There are three major types of RNA that differ from each other in size, function, and special
structural modifications:
Ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA.
The mRNA carries genetic information from the nuclear DNA to the cytosol, where it is used as the
template for protein synthesis.
Prokaryotic DNA transcription produces messenger RNA, which is necessary for transfer from
the cell nucleus to the cytoplasm where translation occurs.
In contrast, eukaryotic DNA transcription takes place in a cell's nucleus and produces what is
called a primary RNA transcript or pre-messenger RNA.
Before eukaryotic products of transcription can be moved into the cytoplasm, they must undergo
modifications that allow them to become mature messenger RNA. In eukaryotes, introns are the
intervening sequences which do not code for protein from the primary transcript while exons are the
coding sequences. Maturation of eukaryotic mRNA usually involves the removal of intron sequences.
Exons are joined together to form the mature mRNA.

Post-transcriptional changes in
mRNA molecule
Splicing: The process of
removing introns and joining exons is
called splicing. The molecular
complex that accomplishes these
tasks is known as the spliceosome.

Special structural characteristics of eukaryotic (but not prokaryotic) mRNA include a long
sequence of adenine nucleotides (a poly-A tail) on the 3'-end of the RNA chain, plus a cap on the
5'-end consisting of a molecule of 7-methylguanosine.






Post-transcriptional changes in mRNA molecule in eukaryotes
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Translation of mRNA or Protein synthesis
The pathway of protein synthesis is called translation
because the language of the nucleotide sequence on the mRNA is translated into the language of
an amino acid sequence. The process of translation requires a genetic code, through which the
information contained in the nucleic acid sequence is expressed to produce a specific sequence of
amino acids. Any alteration in the nucleic acid sequence may result in an incorrect amino acid being
inserted into the polypeptide chain, potentially causing disease or even death of the organism. Newly
made proteins undergo a number of processes to achieve their functional form. They must fold
properly, and misfolding can result in degradation of the protein. Finally, proteins are targeted to their
final intra- or extracellular destinations by signals present in the proteins themselves.

The genetic code
The genetic code is a dictionary that identifies the correspondence between a sequence of nucleotide
bases and a sequence of amino acids. Each individual word in the code is composed of three bases.
These genetic words are called codons. There are 4 different nucleotides and 64 codons which
determine the amino acids in a protein in a sequence. For example, the codon 5'-AUG-3' codes for
methionine.
Sixty-one of the 64 codons code for the 20 common amino acids. Three of the codons, UAG, UGA,
and UAA, do not code for amino acids, but rather are termination codons. When one of these codons
appears in an mRNA sequence, synthesis of the polypeptide coded for by that mRNA stops.













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Components required for translation
A large number of components are required for the synthesis of a protein. These include all the amino
acids that are found in the finished product, the mRNA to be translated, transfer RNA (tRNA) for
each of the amino acids, functional ribosomes, energy sources, and enzymes, as well as protein
factors needed for initiation, elongation, and termination steps of polypeptide chain synthesis.
1. Amino acids
All the amino acids that eventually appear in the finished protein must be present at the time of
protein synthesis. This demonstrates the importance of having all the essential amino acids in
sufficient quantities in the diet to ensure continued protein synthesis.
2. Transfer RNA
At least one specific type of tRNA is required for each amino acid. In humans, there are at least 50
species of tRNA, whereas bacteria contain 3040 species. Because there are only 20 different amino
acids commonly carried by tRNA, some amino acids have more than one specific tRNA molecule.
This is particularly true of those amino acids that are coded for by several codons.
3. Aminoacyl-tRNA synthetases
This family of enzymes is required for attachment of amino acids to their corresponding tRNAs. Each
member of this family recognizes a specific amino acid and all the tRNAs that correspond to that
amino acid. Aminoacyl-tRNA synthetases catalyze a two-step reaction that results in the covalent
attachment of the carboxyl group of an amino acid to the 3'-end of its corresponding tRNA.
4. Messenger RNA
The specific mRNA required as a template for the synthesis of the desired polypeptide chain must be
present.
5. Functionally competent ribosomes
Ribosomes are large complexes of protein and ribosomal RNA.
Structure:
Riosomes consist of two subunitsone large and one smallwhose relative sizes are given in terms
of their sedimentation coefficients, or S (Svedberg) values.
The prokaryotic 50S and 30S ribosomal subunits together form a 70S ribosome.
The eukaryotic 60S and 40S subunits form an 80S ribosome.

Function of small sub unit: The small ribosomal subunit binds mRNA and is responsible for the
accuracy of translation by ensuring correct base-pairing between the codon in the mRNA and the
anticodon of the tRNA.
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Function of large sub unit: The large ribosomal subunit catalyzes formation of the peptide bonds
that link amino acid residues in a protein.

Binding sites: The ribosome has three binding sites for tRNA moleculesthe A, P, and E sites
each of which extends over both subunits. Together, they cover three neighboring codons.
During translation, the A site binds an incoming aminoacyl-tRNA as directed by the codon
currently occupying this site. This codon specifies the next amino acid to be added to the growing
peptide chain.
The P-site codon is occupied by peptidyl-tRNA. This tRNA carries the chain of amino acids that
has already been synthesized.
The E site is occupied by the empty tRNA as it is about to exit the ribosome. In eukaryotic cells,
the ribosomes are either free in the cytosol or are in close association with the endoplasmic
reticulum (which is then known as the rough endoplasmic reticulum, or RER).











Structure of ribosomal assembly


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Steps in protein synthesis
1. Initiation
Initiation of protein synthesis involves the assembly of the components of the translation system
before peptide bond formation occurs. These components include the two ribosomal subunits, the
mRNA to be translated, the aminoacyl-tRNA specified by the first codon in the message, and
initiation factors that facilitate the assembly of this initiation complex.
Initiation codon
The initiating AUG is recognized by a special initiator tRNA. The charged initiator tRNA enters the P
site on the small subunit. The large ribosomal subunit then joins the complex, and a functional
ribosome is formed with the charged initiating tRNA in the P site, and the A site empty.
2. Elongation
Elongation of the polypeptide chain involves the addition of amino acids to the carboxyl end of the
growing chain. During elongation, the ribosome moves from the 5' -end to the 3'-end of the mRNA
that is being translated. The formation of the peptide bond is catalyzed by peptidyl transferase, an
activity intrinsic to the 23S rRNA found in the large (50S) ribosomal subunit. [Note: Because this
rRNA catalyzes the reaction, it is referred to as a ribozyme.] After the peptide bond has been formed,
what was attached to the tRNA at the P site is now linked to the amino acid on the tRNA at the A site.
The ribosome then advances three nucleotides toward the 3'-end of the mRNA.





Polypeptide chain elongation



3. Termination

109
















Termination occurs when one of the three termination codons moves into the A site. These codons are
UAA and UAG, and UGA. The binding of these release factors results in hydrolysis of the bond
linking the peptide to the tRNA at the P site, causing the nascent protein to be released from the
ribosome.
Translation begins at the 5'-end of the mRNA, with the ribosome proceeding along the RNA
molecule. Because of the length of most mRNAs, more than one ribosome at a time can translate a
message. Such a complex of one mRNA and a number of ribosomes is called a polysome or
polyribosome.
110






Chromosomes and Genes

111


Chromosomes and Genes
Chromosomes
In the nucleus of each cell, the DNA molecule is packaged into rod-shaped structures called
chromosomes.
A chromosome is a long, stringy aggregate of genes that carries heredity information (DNA),
which is tightly coiled many times around proteins called histones that support its structure.
Chromosomes are the essential unit for cellular division and must be replicated, divided, and
passed successfully to their daughter cells so as to ensure the genetic diversity and survival of
their progeny.

The normal human chromosome complement consists of 46 chromosomes comprising 22
morphologically different pairs or homologs of autosomes and one pair of sex chromosomes
Somatic cells called diploid. (2n) (23*2)
Sex Cells - also known as gametes contain half the number of chromosomes as body cells and
are called haploid.
Sex chromosomes, are called X and Y. Females have two X chromosomes, while males have one
X and one (smaller) Y chromosome. This fact means that sperm are of two different types: half
will have an X chromosome and half a Y chromosome. But eggs all carry X chromosomes.

Chromatid
Nuclear chromosomes are packaged by proteins into a
condensed structure called chromatin. Each Chromosome
has two symmetrical chromatid joined at a centromere;
Chromatids are either sister chromatids or non-sister
chromatids. Out of these sister chromatids originate from
single (only one) chromosome while non-sister
chromatids are derived from homologous chromosomes.
Karyotype
A karyotype is a picture of a person's (or fetus) chromosomes. A karyotype is often done to
determine if the offspring has the correct number of chromosomes.
112


















Alterations in chromosomes
Alterations in either structural or in the number of the chromosomes frequently results in
significant mental and/or clinical abnormalities. And may involve more than one chromosome.
Numerical abnormalities
Ideally, chromosomes distributes to daughter cells during cell division without error. But there is
an occasional accident, called a nondisjunction; the failure of chromosomes to disjoin from each
other during cell division,
During meiosis I the members of a pair of homologous chromosomes do not move apart
properly.
During meiosis II sister chromatids fail to separate.
In these cases, one gamete receives two of the same type of chromosome and another gamete
receives no copy. If either of the aberrant gametes unites with a normal one at fertilization, the
offspring will have an abnormal number of a particular chromosome, a condition known as
aneuploidy. If the organism survives, it usually has a set of symptoms
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o If a chromosome is present in triplicate in the fertilized egg (so that the cell has a total of 2n + 1
chromosomes), the aneuploid cell is said to be trisomic for that chromosome.
o If a chromosome is missing (so that the cell has 2n 1 chromosomes), the aneuploid cell is
monosomic for that chromosome.
Nondisjunction can also occur during mitosis. Then the aneuploid condition is passed along by
mitosis to a large number of cells and is likely to have a substantial effect on the organism. The
general term for this chromosomal alteration is polyploidy, with the specific terms triploidy (3n)
and tetraploidy (4n) indicating three or four chromosomal sets, respectively. One way a triploid
cell may be produced is by the fertilization of an abnormal diploid egg produced by
nondisjunction of all its chromosomes. Polyploidy is fairly common in the plant kingdom. In
general, polyploids are more nearly normal in appearance than aneuploids.


Disorders due to aneuploidy
Down syndrome is usually the result of an extra chromosome 21, so that each body cell has a
total of 47 chromosomes. Because the cells are trisomic
for chromosome 21, Down syndrome is often called
trisomy 21. Down syndrome includes characteristic
facial features, short stature, heart defects, susceptibility
to respiratory infection, and mental retardation.
Although people with Down syndrome, on average, have
a life span shorter than normal, some live to middle age
or beyond. Most are sexually underdeveloped and
sterile. The frequency of Down syndrome increases with
the age of the mother, the correlation of Down syndrome
with maternal age has not yet been explained. Most
cases result from nondisjunction during meiosis I, and some research points to an agedependent
abnormality in a meiosis.

Nondisjunction of sex chromosomes
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o An extra X chromosome in a male, producing XXY, occurs approximately once in every 2,000
live births. People with this disorder, called Klinefelter syndrome, have male sex organs, but the
testes are abnormally small and the man is sterile. Some breast enlargement and other female
body characteristics are common. The affected individual is usually infertile and have mild mental
retardation.

o Males with an extra Y chromosome (XYY) do not exhibit any welldefined syndrome, but they
tend to be somewhat taller than average.

o Females with trisomy X (XXX), which occurs once in approximately 1,000 live births, are
healthy and cannot be distinguished from XX females except by karyotype.

o Monosomy X, called Turner syndrome, occurs about once in every 5,000 births and is the only
known viable monosomy in humans. Although these X0 individuals are phenotypically female,
they are sterile because their sex organs do not mature. Most have normal intelligence

Structural abnormalities
Errors in meiosis or damaging agents such as radiation can cause breakage of a chromosome,
which can lead to four types of changes in chromosome structure called structural aberrations
(breaks) which frequently alter chromosome morphology.
Deletions result in loss of chromosome fragment from a single chromosome. The affected
chromosome is then missing certain genes. Many deletions in human chromosomes cause severe
problems.

Duplication: a deleted
fragment may become attached
as an extra segment to a sister
chromatid, alternatively, a
detached fragment could attach
to a nonsister chromatid of a
homologous chromosome.

115

In that case, though, the duplicated segments might not be identical because the homologues
could carry different alleles of certain genes.
I nversion: chromosomal fragment may also reattach to the original chromosome but in the
reverse orientation.
Translocation: fragment join a nonhomologous chromosome, Chromosomal translocations have
been implicated in certain cancers, including chronic myelogenous leukemia (CML). Leukemia is
a cancer affecting the cells that give rise to white blood cells. In these cells, the exchange of a
large portion of chromosome 22 with a small fragment from a tip of chromosome 9 produces a
much shortened, easily recognized chromosome 22, called the Philadelphia chromosome.










Genes
Genes are segments of DNA located on chromosomes. They are the basic physical and functional
units of heredity that has been defined as the unit of genetic information that controls a specific
aspect of the phenotype.
Locus is a genes specific location along the length of a chromosome the genes (plural,
loci; from the Latin, meaning place).
An alleleis an alternative form of gene (one member of a pair) different forms of a gene at
one chromosome.
Phenotype, The physical appearance (observable) or biochemical characteristic of an
organism, for example, skin color, height, etc.
Genotype: The specific pair of alleles present at a single locus. This are features seen
genetically but may or may not have phenotypic (observable) characteristics.
Homozygous: individual with two identical alleles.
116

Heterozygous: individual that possesses two different alleles of one gene.

Mutation
A gene mutation is a permanent change in the DNA sequence that makes up a gene they are a
main cause of diversity among organisms. Mutations range in size from a single DNA base to a
large segment of a chromosome.

Causes of mutation
Mutations may be caused
Spontaneously by mistakes that occur during cell division,
By exposure to DNA-damaging agents in the environment.
Mutations can be harmful, beneficial, or have no effect. All mutations are changes in the normal
base sequence of DNA. Many mutations are silent and have no effect.

There are two types of mutations
Hereditary mutations: mutations passed on to us by our parents and present in all of our cells
from birth.
Somatic mutations: are caused randomly during a lifetime of regenerating cells by: Cell cycle
errors - Copy errors during DNA replication - Environmental agents such as chemicals, smoking
or pesticides Radiation - Certain viruses - Other life style exposures.

Polymorphism
Some genetic changes are very rare; others are common in the population. Genetic changes that
occur in more than 1 percent of the population are called polymorphisms. They are common
enough to be considered a normal variation in the DNA. Polymorphisms are responsible for many
of the normal differences between people such as eye color, hair color, and blood type.

117


Types of mutations
A. Point mutations
Point mutations involving changes in one or a few nucleotide in which only a single base pair is
changed into another base pair these include:
Substitution
Is the replacement of one nucleotide and its partner with another pair of nucleotides.
a. Transition, a purine nucleotide is replaced with a purine nucleotide, or a pyrimidine nucleotide is
replaced with a pyrimidine nucleotide.

b. Transversion, the chemical class of the base changes, i.e. a purine nucleotide is replaced with a
pyrimidine nucleotide or a pyrimidine nucleotide is replaced with a purine nucleotide.

Effects of substitution
Change a codon to one that encodes a different amino acid and cause a small change in the protein
produced.
Change in a nucleotide pair may transform one codon into another that is translated into the same
amino acid. Such a change called of a silent mutation
Substitutions that change one amino acid to another one are called missensemutations. Such a
mutation may have little effect on the protein.
Change an amino-acid-coding codon to a single "stop" codon and cause termination of protein
synthesis. This can have serious effects since the incomplete protein probably won't function. This
is called a nonsensemutation.







118



I nsertion
Insertions are mutations in which extra base pairs are inserted into a new place in the DNA.
Deletion
Deletions are mutations in which a section of DNA is lost, or deleted.

B. Frameshift mutation
Insertion or deletion of nucleotides may alter the
reading frame of the genetic message, the triplet
grouping of nucleotides on the mRNA that is read
during translation. Such a mutation, called a
frameshift mutation, will occur whenever the number
of nucleotides inserted or deleted is not a multiple of
three.








119

Basics of Genetics and genetic diseases

120


Basics of Genetics and genetic diseases

The Work of Gregor Mendel and two laws of heredity
Gregor Mendel (born in 1822) developed his theory of inheritance several decades (before
chromosomes were observed under the microscope) by breeding peas in carefully planned
experiments. He documented a particulate mechanism for inheritance.
A character is heritable feature that varies among individuals, such as flower color.
A trait is a variant for a character, such as purple or white color for flower.
True-breeding or monohybrid crosses plants are over many generations of self-pollination, had
produced only the same variety as the parent plant.
Dihybrid cross: crossing plants that differed in two traits.
P generation The plants involved in the original cross also caledl the parental.
First filial or F1 generation The offspring from cross.
Second filial generation or F2 the individuals resulting resulting from mating or genetically
crossing two members of first filial generation.

The Law of Segregation
In cross-pollinating plants between true-breeding peas strains that differed in one trait, that either
produce round or wrinkled pea seeds exclusively, Mendel found that the first offspring generation
(f1) always has round seeds. However, the following generation (f2) consistently has a 3:1 ratio of
round to wrinkle.






He concluded that the wrinkled trait seemed to be masked or dominated by the round trait in the
F1 seeds. Mendel called the round trait dominant and the wrinkled trait recessive, for the second
121

generation he found that both round and wrinkled seeds appeared in the F2 generation in a ratio of
three round (dominant trait) to one wrinkled (recessive trait).
Mendel continued with the F3 generation discovered that F2 individuals with the recessive trait
always produced progeny with the recessive trait. Some F2 individuals with the dominant trait
produced only offspring with dominant, while other F2 individuals with the dominant trait had
offspring with both dominant and recessive traits.
A genetic locus is actually represented twice in a diploid cell, once on each homologue of a
specific pair of chromosomes.
Homozygous an individual with two identical alleles at corresponding chromosomal loci that code
for the same trait.
Heterozygous an individual that
possesses two different alleles of one
gene.
The genotypeof an individual is
symbolized by letters.
Uppercase or capital letters
indicate a dominant allele, and
lowercase or small letters
indicate a recessive allele.
The genotype of a trait in an
individual is either

Homozygous Dominant AA
Heterozygous Dominant Aa
Homozygous recessive aa
The two members of a gene pair (alleles) segregate (separate) from each other in the formation of
gametes. Half the gametes carry one allele, and the other half carries the other allele. Mendel
formulated his first rule of genetics, the Rule of Segregation. This rule states that pairs of factors
alleles segregate or separate during the formation of gametes.

122


The Law of Independent Assortment
Rule of I ndependent Assortment: It states that alleles for different characteristics are distributed
to gametes independently.
Mendel crossed plants that were homozygous true-breeding strains for the dominant (RRYY round
yellow) and recessive (rryy wrinkled green) alleles.











From these experiments, Mendel concluded that seed shape and color were not inherited as a unit.
Mendel hypothesized that in order to produce the four different phenotypes, the alleles from these
genes must segregate independently.







123


Probability of Inheritance and Punnett Squares
Recombination of gametes during fertilization can be easily visualized by constructing a Punnett
square, named after the person who first devised this approach Reginald C. Punnett.
Each of the possible gametes is assigned to a column or a row; the vertical column represents those
of the female parent, and the horizontal row represents those of the male parent.


124

The new generation is predicted by combining the male and female
gametic information by entering the resulting genotypes in the boxes. This
process thus lists all possible random fertilization events. The genotypes
and phenotypes of all potential offspring are ascertained by reading the
entries in the boxes.
Traits controlled by many genes
The inheritance of characters determined by a single gene deviates from
simple Mendelian patterns
I ncomplete dominance, phenomenon for some traits, the F1 hybrids have
an appearance somewhat in between the phenotypes of the 2 parental
varieties

When red snapdragons are crossed with white snapdragons: All the F1
hybrids have pink flowers.
Codominance; A condition in which the alleles of a gene pair in a heterozygote are fully expressed thereby
resulting in offspring with a
phenotype that is neither dominant
nor recessive.
A typical example showing
codominance is the AB blood
group. For instance, a person
having A allele and B allele will
have a blood type AB because both
the A and B alleles are codominant
with each other.

Pleiotropy

Pleiotropy is the impact of a single
gene on 2 or more traits is (have
multiple phenotypic effects).
125

Example of pleiotropy in humans is phenylketonuria (PKU).

This disorder is caused by a deficiency of the enzyme phenylalanine hydroxylase, which is
necessary to convert the essential amino acid phenylalanine to tyrosine. A defect in the single gene
that codes for this enzyme therefore results in the multiple phenotypes associated with PKU,
including mental retardation, eczema, and pigment defects that make affected individuals lighter
skinned

Epistasis (from the Greek for standing upon), the phenotypic expression of a gene at one locus
alters that of a gene at a second locus.

Polygenic inheritancean additive effect of two or more genes on a single phenotypic character;
characters that vary in the population. Such as human skin color and height, these are called
quantitative characters



































126



Sex Determination

Sex is determined by specific chromosomes called the sex chromosome, designated X and Y


Males XY
Females XX


Human sex determination depends on the presence of
the Y chromosome in the fertilized egg

o Sperm with X chromosome fertilizes an egg
XX offspring = Female
o Sperm with Y chromosome fertilizes an egg
XY offspring = Male



Sex linked genes:

A gene located on either sex chromosome is called a sex linked gene; those located on the Y
chromosome are called Y-linked genes. The human X chromosome contains approximately 1,100
genes, which are X-linked genes.


Linkage
Two genes are said to be linked if they are located on the same chromosome. Genes in the same
chromosome are passed on together as a unit during meiosis. Linked genes most likely account for
such phenomena as red hair being strongly associated with light complexioned skin among
humans. If you inherit one of these traits, you will most likely inherit the other.

Genetic Diseases
Defective genes are often inherited from the parents. In this case, the genetic disorder is known as a
hereditary or genetic disease.
Autosomal dominant: Affected individuals are heterozygous, with one normal and one
mutated gene that is dominant. Homozygosity is generally fatal. A common feature of autosomal
dominant disorders is that they are structural disorders. They can have variable expression; this
means that some people have milder or more severe symptoms than others. Most families know that
127

there is a dominant trait or disorder in their family. Examples include Autosomal dominant
cerebellar ataxia (ADCA) that causes deterioration of the nervous system leading to disorder and a
decrease or loss of function to regions of the body.

Autosomal recessive the
affected person has two copies of the
altered gene one from each of the
parents. The person is called
affected because she or he has the
disorder
Common recessive disorders
include:
o Sickle cell disease: A group of
genetic disorders caused by the
substitution of a single amino acid in
the hemoglobin protein of red blood
cells; causes the red blood cells to take
on a crescent, or "sickle" shape. These
abnormal cells tend to get stuck in the
blood vessels. This cuts off oxygen to
tissues and causes pain.

X-linked dominant X linked diseases where defective genes are carried on the X chromosome.
Expression of the disorder in both sexes, but with a greater incidence in females due to the greater
number of X chromosomes the female. may be homozygous or heterozygous for the affected gene
while the male can only be heterozygous. An example of an X-linked dominant genetic disorder is a
rare form of rickets known as hypophosphataemic or vitamin D resistant rickets; metabolic disorder
decreased reabsorpion of phosphate by the renal tubule (causing hypophosphatemia) decreased
absorption of calcium and phosphorous from the GI tract.
128



X-linked recessive: this type of disorder is more common in males. It is caused by an alteration in
a gene on the X chromosome. Since a male has one X and one Y (XY), he does not have a second
healthy copy of the gene. Example of X-linked recessive genetic disorders Color blindness, (also
known as Dyschromatopsia) or color vision deficiency, in humans is the inability to perceive
differences between some or all colors that other people can distinguish

Multifactorial and polygenic disorders
Genetic disorders may be complex, multifactorial or polygenic, this means that they are likely
associated with the effects of multiple genes in combination with lifestyle and environmental
factors. Multifactoral disorders include heart disease and diabetes.

129

Cancer Biology
130


Basics of Cancer Biology
Introduction
Cancer is a broad group of diseases involving unregulated cell
growth. In cancer, cells divide and grow uncontrollably, forming
malignant tumors, and invading nearby parts of the body. The
cancer may also spread to more distant parts of the body
through the lymphatic system or bloodstream. Not all tumors
are cancerous; benign tumors do not invade neighboring
tissues and do not spread throughout the body. There are over
100 different known cancers that affect humans.
The causes of cancer are diverse, complex, and only partially
understood. Many things are known to increase the risk of
cancer, including tobacco use, dietary factors, certain
infections, exposure to radiation, lack of physical activity, obesity, and environmental pollutants.
These factors can directly damage genes or combine with existing genetic faults within cells to
cause cancerous mutations. Approximately 510% of cancers can be traced directly to inherited
genetic defects. Many cancers could be prevented by not smoking, eating more vegetables, fruits
and whole grains, eating less meat and refined carbohydrates, maintaining a healthy weight,
exercising, minimizing sunlight exposure, and being vaccinated against some infectious diseases.
Cancer can be detected in a number of ways, including the presence of certain signs and symptoms,
screening tests, or medical imaging. Once a possible cancer is detected it is diagnosed by
microscopic examination of a tissue sample. Cancer is usually treated with surgery, chemotherapy,
radiation therapy and recently immunotherapy.
Cancer, general information:
Cancer is a group of more than 100 diseases that develop across time and involve uncontrolled cells
division. Although cancer can develop in virtually any of the body's tissues, and each type of cancer
131

has its unique features, the basic processes that produce cancer are quite similar in all forms of the
disease.
Cancer starts when a cell begins to follow its own agenda for proliferation (Figure). All of the cells
produced by division of this first, ancestral cell also display inappropriate proliferation. A tumor,
formed of these abnormal cells may remain within the tissue in which it originated (a condition
called in situ cancer), or it may invade nearby tissues (a condition called invasive cancer). An
invasive tumor is said to be malignant, and cells shed into the blood or lymph from a malignant
tumor are likely to establish new tumors (metastases) throughout the body.










Stages of tumorigenesis
a a. . T Th he e t tu um mo or r b be eg gi in ns s t to o d de ev ve el lo op p w wh he en n a a c ce el ll l e ex xp pe er ri ie en nc ce es s a a m mu ut ta at ti io on n t th ha at t m ma ak ke es s t th he e c ce el ll l m mo or re e l li ik ke el ly y
t to o d di iv vi id de e a ab bn no or rm ma al ll ly y. .
b b. . Hyperplasia, T Th he e a al lt te er re ed d c ce el ll l a an nd d i it ts s d de es sc ce en nd da an nt t cells resulting from uncontrolled cell division,
g gr ro ow w a an nd d d di iv vi id de e t to oo o o of ft te en n ( (h hy yp pe er rp pl la as si ia a) ). A At t s so om me e p po oi in nt t, , o on ne e o of f t th he es se e c ce el ll ls s e ex xp pe er ri ie en nc ce es s a an no ot th he er r
m mu ut ta at ti io on n t th ha at t f fu ur rt th he er r i in nc cr re ea as se es s i it ts s t te en nd de en nc cy y t to o d di iv vi id de e. .
c c. . Dysplasia, T Th he e c ce el ll l' 's s d de es sc ce en nd da an nt ts s d di iv vi id de e e ex xc ce es ss si iv ve el ly y w wi it th h a ab bn no or rm ma al l changes ( (d dy ys sp pl la as si ia a) ). . B By y t ti im me e, ,
o on ne e o of f t th he e c ce el ll ls s e ex xp pe er ri ie en nc ce es s a an no ot th he er r m mu ut ta at ti io on n. .



132




d d. . A An na ap pl la as st ti ic c c ce el ll l f fo or rm ma at ti io on n requires additional changes, which result in cells that are even more
abnormal and can now spread over a wider area of tissue.
These cells begin to lose their original function. Because the
tumor is still contained within its original location (called in
situ cancer).
e e. . I If f s so om me e c ce el ll ls s e ex xp pe er ri ie en nc ce e a ad dd di it ti io on na al l m mu ut ta at ti io on ns s t th ha at t a al ll lo ow w
t th he e t tu um mo or r t to o i in nv va ad de e n ne ei ig gh hb bo or ri in ng g t ti is ss su ue es s a an nd d s sh he ed d c ce el ll ls s i in nt to o
t th he e b bl lo oo od d o or r l ly ym mp ph h, , t th he e t tu um mo or r i is s s sa ai id d t to o b be e m ma al li ig gn na an nt t. . The
last step occurs when the cells in the tumor metastasize, this
is the most serious type of tumor, but not all tumors progress
to this point. Non-invasive tumors are said to be benign.
A An ng gi io og ge en ne es si is s, as tumors enlarge, the cells in the center no
longer receive nutrients from the normal blood vessels. To
provide a blood supply for all the cells in the tumor, tumor
cells are induced for formation of new capillary blood
vessels.
Understanding Cancer
Cancer, then, is a disease in which a single normal body cell undergoes a genetic transformation
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into a cancer cell. This cell and its descendants, proliferating across many years, produce the
population of cells that we recognize as a tumor, and tumors produce the symptoms that an
individual experiences as cancer.

A series of changes leads to tumor formation. Tumor formation occurs as a result of successive
clonal expansions (production of daughter cells all arising originally from a single cell)
As a tumor develops, the cells of which it is composed become different from one another and form
distinct subpopulations of cells within the tumor. As shown in Figure, The development of cancer
occurs as a result of a series of clonal expansions from a single ancestral cell.
Differences between normal cells and cancer cells
Cancer cells are genetically unstable and prone to rearrangements, duplications, and deletions of
their chromosomes. Thus, although a tumor as a whole is monoclonal in origin, it may contain a
large number of cells with diverse characteristics.
Cancerous cells also look and act differently from normal cells. In most normal cells, the nucleus is
only about one-fifth the size of the cell; in cancerous cells, the nucleus may occupy most of the
cell's volume.
Whereas normal secretary cells produce and release mucus, cancers derived from these cells may
have lost this characteristic. Likewise, epithelial cells usually contain large amounts of keratin, but
the cells that make up skin cancer may no longer accumulate this protein in their cytoplasm.
The key difference between normal and cancerous cells, however, is that cancer cells have lost the
restraints on growth that characterize normal cells. Significantly, a large number of cells in a tumor
are engaged in mitosis, whereas mitosis is a relatively rare event in most normal tissues.
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Causes of cancer
Cancers are primarily an environmental disease with 9095% of cases attributed to environmental
factors (e.g. carcinogens) and 510% due to genetics. Common environmental factors that
contribute to cancer death include tobacco (2530%), diet and obesity (3035%), infections (15
20%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity, and
environmental pollutants.
Heredity and Cancer:
In some cases cancer is caused by an abnormal gene that is being passed along from generation to
generation. Although this is often referred to as inherited cancer, what is inherited is the abnormal
gene that can lead to cancer, not the cancer itself. Only about 5% to 10% of all cancers are inherited
resulting directly from gene defects (called mutations) inherited from a parent.
Carcinogens:
Carcinogens are a class of substances that are directly responsible for damaging DNA, promoting or
aiding cancer. Tobacco, asbestos, arsenic, radiation such as gamma and x-rays, the sun, and
compounds in car exhaust fumes are all examples of carcinogens. When our bodies are exposed to
carcinogens, free radicals are formed; theses free radicals damage cells and affect their ability to
function normally.
Other medical factors:
As we age, there is an increase in the number of possible cancer-causing mutations in our DNA.
This makes age an important risk factor for cancer. Several viruses have also been linked to cancer
such as: human papillomavirus (a cause of cervical cancer), hepatitis B and C (causes of liver
cancer), and Epstein-Barr virus (a cause of some childhood cancers). Human immunodeficiency
virus (HIV) - and anything else that suppresses or weakens the immune system - inhibits the body's
ability to fight infections and increases the chance of developing cancer.
Malignancy is the tendency of a medical condition, especially tumors, to become progressively
worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia,
invasiveness, and metastasis.
Malignancy is most familiar as a characterization of cancer. A malignant tumor contrasts with a
non-cancerous benign tumor in that a malignancy is not self-limited in its growth, is capable of
invading into adjacent tissues, and may be capable of spreading to distant tissues. A benign tumor
has none of those properties.
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Neoplasm or tumor is an abnormal mass of tissue as a result of abnormal growth or division of
cells. Prior to abnormal growth (known as neoplasia), cells often undergo an abnormal pattern of
growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress
to neoplasia. The growth of neoplastic cells exceeds, and is not coordinated with, that of the normal
tissues around it. The growth persists in the same excessive manner even after cessation of the
stimuli. It usually causes a lump or tumor. Neoplasms may be benign, pre-malignant (carcinoma in
situ) or malignant (cancer).
A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissue or
metastasize. These characteristics are required for a tumor to be defined as cancerous and therefore
benign tumors are non-cancerous. Also, benign tumors generally have a slower growth rate than
malignant tumors and the tumor cells are usually more differentiated (cells have normal features).
Benign tumors are typically surrounded by an outer surface (fibrous sheath of connective tissue) or
remain with the epithelium. Common examples of benign tumors include moles (nevi) and uterine
fibroids.
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Nomenclature
Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or
Greek word for the organ or tissue of origin as the root. For example, cancers of the liver
parenchyma arising from malignant epithelial cells is called hepatocarcinoma, while a malignancy
arising from primitive liver precursor cells is called a hepatoblastoma, and a cancer arising from fat
cells is called a liposarcoma. For some common cancers, the English organ name is used. For
example, the most common type of breast cancer is called ductal carcinoma of the breast. Here, the
adjective ductal refers to the appearance of the cancer under the microscope, which suggests that it
has originated in the milk ducts.
Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the
root. For example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name
of this frequently occurring benign tumor in the uterus is fibroid). Confusingly, some types of
cancer use the -noma suffix, examples including melanoma and seminoma.
Some types of cancer are named for the size and shape of the cells under a microscope, such as
giant cell carcinoma, spindle cell carcinoma, and small-cell carcinoma.
Stages of carcinogenesis








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Cancer develops through four definable stages: initiation, promotion, progression and malignant
conversion. These stages may progress over many years.
The first stage, initiation, involves a change in the genetic makeup of a cell. This may occur
randomly or when a carcinogen interacts with DNA causing damage. This initial damage rarely
results in cancer because the cell has in place many mechanisms to repair damaged DNA. However,
if repair does not occur and the damage to DNA is in the location of a gene that regulates cell
growth and proliferation, DNA repair, or a function of the immune system, then the cell is more
prone to becoming cancerous.
During promotion, the mutated cell is stimulated to grow and divide faster and becomes a
population of cells. Eventually a benign tumor becomes evident. In human cancers, hormones,
cigarette smoke, or bile acids are substances that are involved in promotion. This stage is usually
reversible as evidenced by the fact that lung damage can often be reversed after smoking stops.
The progression phase is less well understood. During progression, there is further growth and
expansion of the tumor cells over normal cells. The genetic material of the tumor is more fragile
and prone to additional mutations. These mutations occur in genes that regulate growth and cell
function such as oncogenes, tumor suppressor genes, and DNA mismatch-repair genes.
These changes contribute to tumor growth until conversion occurs, when the growing tumor
becomes malignant and possibly metastatic. Many of these genetic changes have been identified in
the development of colon cancer and thus it has become a model for studying multi-stage
carcinogenesis.
Cancer as a Multistep Process
A central feature of today's molecular view of cancer is that cancer does not develop all at once, but
across time, as a long and complex succession of genetic
changes. It develops step-by-step as an accumulation of many
molecular changes, each contributing some of the
characteristics that eventually produce the malignant state.
The number of cell divisions that occur during this process can
be astronomically largehuman tumors often become
apparent only after they have grown to a size of 10 billion to
100 billion cells, the time frame involved also is very long it
normally takes years to accumulate enough mutations to reach
a malignant state. Understanding the development of cancer as
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a multistep process also explains the lag time that often separates exposure to a cancer-causing
agent and the development of cancer.
Cancer as a Multistep Process, description:
A sound body depends on the continuous interplay of thousands of proteins, acting together in just
the right amounts and in just the right places. Each properly functioning protein is the product of an
intact gene.
Many, if not most, diseases have their roots in our genes. Common disorders such as heart disease
and most cancers arise from a complex interplay among multiple genes and between genes and
factors in the environment. Cancer may begin because of the accumulation of multiple mutations.
1. Cancer-associated mutations, whether somatic or germ line alter key proteins and their functions
in the human bio-system.
2. A wide variety of mutations seem to be involved.
3. Even mutations in non-coding regions can result in under or over expression of proteins needed
for normalcy.
4. Collectively, these mutations conspire to change a genome from normal to cancerous.
5. It is important to note that genes themselves do not cause disease. Genetic disorders are caused
by mutations that make a gene function improperly.

This explains, for example, the observation that severe sunburns in children can lead to the
development of skin cancer decades later. It also explains the 20-to-25-year lag between the onset
of widespread cigarette smoking among women after World War II and the massive increase in
lung cancer that occurred among women in the 1970s.

The Human Face of Cancer
Who are these people who develop cancer and what are their chances for surviving it? Scientists
measure the impact of cancer in a population by looking at a combination of three elements:
(1) The number of new cases per year per 100,000 persons (incidence rate).
(2) The number of deaths per 100,000 persons per year (mortality rate).
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(3) The proportion of patients alive at some point after their diagnosis of cancer (survival rate).
Everyone is at some risk of developing cancer. Cancer researchers use the term lifetime risk to
indicate the probability that a person will develop cancer over the course of a lifetime.
For a specific individual, however, the risk of developing a particular type of cancer may be quite
different from his or her lifetime risk of developing any type of cancer. Relative risk compares the
risk of developing cancer between persons with a certain exposure or characteristic and persons
who do not have this exposure or characteristic. For example, a person who smokes has a 10-to-20-
fold-higher relative risk of developing lung cancer compared with a person who does not smoke.
This means that a smoker is 10 to 20 times more likely to develop lung cancer than a nonsmoker.

Genetic basis of cancer
(proto-oncogenes and tumor-suppressor genes)











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Two categories of genes play major roles in triggering cancer, in their normal forms, these genes
control the cell cycle, the sequence of events by which cells enlarge and divide. One category of
genes, called proto-oncogenes, encourages cell division. The other category, called tumor-
suppressor genes, inhibits it.
Together, proto-oncogenes and tumor-suppressor genes coordinate the regulated growth that
normally ensures that each tissue and organ in the body maintains a size and structure that meets the
body's needs.
What happens when proto-oncogenes or tumor-suppressor genes are mutated? Mutated proto-
oncogenes become oncogenes, genes that stimulate excessive division. And mutations in tumor-
suppressor genes inactivate these genes, eliminating the critical inhibition of cell division that
normally prevents excessive growth.
Collectively, mutations in these two categories of genes account for much of the uncontrolled cell
division that occurs in human cancers.

Mutations are errors in DNA structure that alter genetic information. To function correctly, each
cell depends on thousands of proteins to do their jobs in the right places at the right times.
Sometimes, gene mutations prevent one or more of these proteins from working properly. By
changing a gene's instructions for making a protein, a mutation can cause the protein to malfunction
or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it
can disrupt normal development or cause a medical condition.

The Six Hallmarks of Cancer

Six characteristics of malignancies have been
proposed to most, if not all, cancers that are
essential for carcinogenesis, or cancer
formation. The behavior of that cancer is
incorporating all six of these characteristics, if
it is missing one of these characteristics, then
its very likely that you don't have cancer.
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These six hallmarks are:
1- Growth signal autonomy, which means the cell grows even when its not getting a message to
grow; not paying attention to the stop signs, which means the cell ignores messages telling it to stop
growing;
2- Evasion of apoptosis, which means a cell, avoids all the messages that tell it to die.
3- Angiogenesis, which means the ability to grow new blood vessels;
4- Unlimited replicative potential, which means that a cell keeps replicating no matter how many
times it has already done so.
5- Invasion, the spread of malignant cells to new sites in the body (surrounding structures).
6- Metastasis, which means the cells, are moving into areas where they should not be.
Effects, Signs and symptoms
Local effects
Local symptoms may occur due to the mass of the tumor or its
ulceration.
For example, mass effects from lung cancer can cause
blockage of the bronchus resulting in cough or pneumonia.
Esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow.
Colorectal cancer may lead to narrowing or blockages in the bowel, resulting in changes in bowel
habits.
Masses in breasts or testicles may be easily felt.
Ulceration can cause bleeding which, if it occurs in the lung, will lead to coughing up blood.
Although localized pain may occur in advanced cancer, the initial swelling is usually painless.
Some cancers can cause build up of fluid within the chest or abdomen.
Systemic symptoms
General symptoms occur due to distant effects of the cancer that are not related to direct or
metastatic spread. These may include: unintentional weight loss, fever, being excessively tired, and
changes to the skin. Hodgkin disease, leukemias, and cancers of the liver or kidney can cause a
persistent fever of unknown origin. Specific constellations of systemic symptoms, termed
paraneoplastic phenomena, may occur with some cancers.
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Metastasis
Symptoms of metastasis are due to the spread of cancer to other locations in the body. They can
include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically
hard), hepatomegaly (enlarged liver) or splenomegaly (enlarged spleen) which can be felt in the
abdomen, pain or fracture of affected bones, and neurological symptoms. Most cancer deaths are
due to cancer that has spread from its primary site to other organs (metastasized).
Classification
Cancers are classified by the type of cell that the tumor cells resemble and are therefore presumed
to be the origin of the tumor. These types include:
Carcinoma: Cancers derived from epithelial cells. This group includes many of the most common
cancers, particularly in the aged, and include nearly all those developing in the breast, prostate,
lung, pancreas, and colon.
Sarcoma: Cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve), each of which
develop from cells originating in mesenchymal cells outside the bone marrow.
Lymphoma and leukemia: These two classes of cancer arise from hematopoietic (blood-forming)
cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively.
Leukemia is the most common type of cancer in children accounting for about 30%.
Germ cell tumor: Cancers derived from pluripotent cells, most often presenting in the testicle or
the ovary (seminoma and dysgerminoma, respectively).
Blastoma: Cancers derived from immature "precursor" cells or embryonic tissue. Blastomas are
more common in children than in older adults.
Pathology
The tissue diagnosis indicates the type of cell that is proliferating, its histological grade, genetic
abnormalities, and other features of the tumor. Together, this information is useful to evaluate the
prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry
are other types of testing that the pathologist may perform on the tissue specimen. These tests may
provide information about the molecular changes (such as mutations, fusion genes, and numerical
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chromosome changes) that has happened in the cancer cells, and may thus also indicate the future
behavior of the cancer (prognosis) and best treatment.
Grading (tumors)
In pathology, grading is a measure of the cell appearance in tumors and other neoplasms. Some
pathology grading systems apply only to malignant neoplasms (cancer); others apply also to benign
neoplasms. The neoplastic grading is a measure of cell anaplasia (reversion of differentiation) in
the sampled tumor and is based on the resemblance of the tumor to the tissue of origin. Grading in
cancer is distinguished from staging, which is a measure of the extent to which the cancer has
spread.
Pathology grading systems classify the microscopic cell appearance abnormality and deviations in
their rate of growth with the goal of predicting developments at tissue level.
The histologic tumor grade score along with the metastatic (whole-body-level cancer-spread)
staging are used to evaluate each specific cancer patient, develop their individual treatment strategy
and to predict their prognosis. A cancer that is very poorly differentiated is called anaplastic.
Overall stage grouping
Overall Stage Grouping is also referred to as Roman Numeral Staging. This system uses numerals I,
II, III, and IV (plus the 0) to describe the progression of cancer.
Stage 0: carcinoma in situ.
Stage I: cancers are localized to one part of the body. Stage I cancer can be surgically removed if
small enough.
Stage II: cancers are locally advanced. Stage II cancer can be treated by chemo, radiation, or
surgery.
Stage III: cancers are also locally advanced. Whether a cancer is designated as Stage II or Stage III
can depend on the specific type of cancer; for example, in Hodgkin's disease, Stage II indicates
affected lymph nodes on only one side of the diaphragm, whereas Stage III indicates affected lymph
nodes above and below the diaphragm. The specific criteria for Stages II and III therefore differ
according to diagnosis. Stage III can be treated by chemo, radiation, or surgery.
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Stage IV: cancers have often metastasized, or spread to other organs or throughout the body. Stage
IV cancer can be treated by chemo, radiation, or surgery.









Prevention
Cancer prevention is defined as active measures to decrease the risk of cancer. The vast majority of
cancer cases are due to environmental risk factors, and many, but not all, of these environmental
factors are controllable lifestyle choices. Thus, cancer is considered a largely preventable disease.
Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco,
overweight / obesity, an insufficient diet, physical inactivity, alcohol, sexually transmitted
infections, and air pollution. Not all environmental causes are controllable, such as naturally
occurring background radiation, and other cases of cancer are caused through hereditary genetic
disorders, and thus it is not possible to prevent all cases of cancer.
How the Immune System Prevents Cancer
The immune system has three key responsibilities when it comes to preventing cancer:
Suppression of viral infections, which when unchecked can induce certain kinds of tumors
Timely elimination of pathogens, to reduce the extent and duration of inflammation, which often
promotes tumorigenesis.
Immunosurveillance, in which transformed cells are identified and destroyed before they can
establish malignancy.
The immunoediting of cancer can be seen as a dynamic process with three distinct phases:
Elimination, when innate and adaptive immune cells work together to identify and destroy tumor
cells before a malignancy can form.
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Equilibrium, a phase when the immune system contains tumor outgrowth but does not eliminate
transformed cells entirely.
Escape, in which tumor cells grow unrestricted by the immune system, and develop into clinically
apparent disease.
Both elimination and equilibrium might be considered satisfactory clinical endpoints for a patient,
because tumor cells are either destroyed entirely or held in check to prevent outgrowth of disease.

Cancer Treatment:
Surgery
Surgery is the primary method of treatment of most isolated solid cancers and may play a role in
palliation and prolongation of survival. It is typically an important part of making the definitive
diagnosis and staging the tumor as biopsies are usually required. In localized cancer surgery
typically attempts to remove the entire mass along with, in certain cases, the lymph nodes in the
area. For some types of cancer this is all that is needed to eliminate the cancer.
Chemotherapy
Chemotherapy in addition to surgery has proven useful in a number of different cancer types
including: breast cancer, colorectal cancer, pancreatic cancer, osteogenic sarcoma, testicular cancer,
ovarian cancer, and certain lung cancers. The effectiveness of chemotherapy is often limited by
toxicity to other tissues in the body.
Radiation
Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve the
symptoms of cancer. Radiation is typically used in addition to surgery and or chemotherapy but for
certain types of cancer such as early head and neck cancer may be used alone. For painful bone
metastasis it has been found to be effective in about 70% of people.
Immunotherapy
Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors. The
active agents of immunotherapy are collectively called immunomodulators. They are a diverse
array of recombinant, synthetic and natural preparations, often Cytokines. Local immunotherapy
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injects a treatment into an affected area, for example, to cause inflammation that causes a tumor to
shrink. Systemic immunotherapy treats the whole body by administering an agent such as the
protein interferon alpha that can shrink tumors. Immunotherapy can also be considered non-specific
if it improves cancer-fighting abilities by stimulating the entire immune system, and it can be
considered targeted if the treatment specifically tells the immune system to destroy cancer cells.
Bone marrow transplantation (hematopoetic stem cell transplantation) can also be considered
immunotherapy because the donor's immune cells will often attack the tumor or cancer cells that are
present in the host.
Alternative treatments
Complementary and alternative cancer treatments are a diverse group of health care systems,
practices, and products that are not part of conventional medicine. "Complementary medicine"
refers to methods and substances used along with conventional medicine, while "alternative
medicine" refers to compounds used instead of conventional medicine. Most complementary and
alternative medicines for cancer have not been rigorously studied or tested. Some alternative
treatments have been investigated and shown to be ineffective but still continue to be marketed and
promoted.