Acute Training Manual

RPG Life Sciences Limited
RESPIRATORY SYSTEM
What is Respiration?
Respiration is the act of breathing:
• Inhaling (inspiration) - Taking in oxygen
• Exhaling (expiration) - Giving off carbon dioxide
Fig. 1: Respiratory System

What makes up the Respiratory System?
The respiratory system is made up of the organs involved in breathing and
consists of the:
• Nose (nostrils and nasal cavity)
• Pharynx
• Larynx
• Trachea
• Bronchi
• Bronchioles
• Lungs
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What is the Respiratory passage?

The nostrils lead into the two nasal cavities. The nasal cavities are lined with
columnar ciliated mucous membrane which is highly vascular and secreting
mucus. The nasal cavities are continuous behind the nasopharynx, which leads
further to oropharynx and laryngopharynx (Parts of Pharynx).
Larynx (voice box)

Larynx is directly continuous with the trachea below. The upper opening of the
larynx is called ‘glottis’ and is guarded in front by a tongue-like projection of
cartilage known as ‘epiglottis’. Epiglottis prevents the entry of food into larynx.
The larynx contains the vocal cords which help in the production of voice by their
vibrations.
Trachea
The Trachea (Wind Pipe) is also lined by mucous membrane composed of
ciliated epithelium which secretes mucus. The cilia move in upward direction.
This help in preventing the particle from entering the lungs.
The Bronchi
The bronchi are two in number and are formed by the bifurcation of the trachea.
They are similar in structure to the trachea.
On entering the lung, each bronchus divides and sub-divides into a number of
small branches which go to the different lobes of the lung. These then sub-divide
into still smaller branches (similar to the branches of a tree) which are known as
Bronchioles. The bronchioles divide to form alveoli, which is basic functional unit
of lung.
Lungs
The lungs (right and left lung) are the principal organs of respiration.
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The lungs are divided into a number of lobes by fissures. Each of the lobe is in
turn composed of a number of small lobules. Each bronchiole ends in a small
dilated sac known as Alveoli (air sac of the lungs).
Where does gaseous exchange take place in the lungs?

The gaseous exchange takes place in the alveoli. The alveoli consist of a single
layer of flat epithelial cells and it is site for the exchange of gases. The oxygen
passes from the alveoli to the blood and the carbon dioxide diffuses from the
blood into the alveoli.
What are URT and LRT?

Conventionally, the portion of the respiratory passage till the larynx (i.e. Nasal
cavity, Pharynx and Larynx) is referred to as ‘Upper Respiratory Tract’ (URT) and
the portion below Larynx (i.e., Trachea, Bronchi and Lungs) is referred to as
‘Lower Respiratory Tract’ (LRT).
What is the Physiology (function) of Respiration?

The function of respiratory system is breathing. Where oxygen passes from the
air to the blood, carbon dioxide passes from the blood to the air.
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Internal Respiration:
The exchange of oxygen and carbon dioxide between the blood and the tissues
is known as ‘internal respiration’.
Fig 2: Internal respiration at the level of alveoli
External respiration:
The exchange of gases between the inspired air and blood flowing through the
lungs is known as ‘external respiration’.
How is the act of respiration regulated?

Respiration is regulated by two principal factors:
• The Nervous Control
• The Chemical Control
Nervous Control
Respiration is an automatic rhythmical act due to the influence of a ‘respiratory
centre’ situated in the brain.
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Chemical Control
The inspiratory centre is also directly controlled by the chemical composition of
blood. A rise in carbon dioxide content of the blood and a fall in oxygen content
of the blood stimulate the inspiratory centre.
What is Respiratory Tract Fluid?

The normal respiratory passages are kept moist by the respiratory tract fluid
which is secreted by the lining mucosa of the tract. This fluid also acts as a
natural demulcent (soothing agent). The secretion of this fluid is increased by the
action of expectorant drugs.
What is Surfactant?
It is fluid coating the respiratory membrane in alveoli, which decreases the
surface tension, hence maintains the shape & structure of alveoli. It prevents
alveoli from collapsing & sticking during ventilation.
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RESPIRATORY DISORDERS
Besides cough, there are also other changes taking place in the respiratory tract
as a result of the disorder due to infection, allergic reaction, etc. Infection to
‘tracheo-bronchial tree’ (trachea, bronchi, and bronchioles) causes inflammation
and this brings about congestion of the mucous membrane and increased
secretion of thick mucus. This also inhibits the normal ciliary movements of the
epithelial cells. The inflamed mucous membrane and the increased mucus
secretion cause local irritation and induce coughing. Moreover this condition
along with broncho-constriction causes obstruction to the flow of air and
produces difficulty in breathing i.e. ‘dyspnoea’.
Which are the common Upper Respiratory Tract Disorders

(URTIs)?
Influenza (flu)
Influenza (or flu) is a highly contagious viral respiratory tract infection. Influenza
is characterized by the abrupt onset of fever, muscle aches, sore throat, and dry
cough.
Pharyngitis and Tonsillitis

Pharyngitis and Tonsillitis are infections in the throat that cause inflammation. If
the tonsils are primarily affected, it is called tonsillitis. If the throat (pharynx) is
primarily affected, it is called Pharyngitis.
When there is inflammation and infection of both the tonsils and the throat, this
would be called pharyngotonsillitis.
The most common symptoms of pharyngitis and tonsillitis are sore throat, fever,
headache, and decrease in appetite, malaise (feeling of not being well), nausea,
and vomiting.
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Sinusitis
The sinuses are cavities, or air-filled pockets, that are found near the nasal
passage.
There are 4 types of sinuses. Sinusitis is an infection of the sinuses near the
nose. These infections usually occur after a cold or after an allergic inflammation.
The symptoms include the following:
• Running of nose or cold symptoms that last longer than seven to ten days
• Complaints of drip in the throat from the nose
• Headaches
• Facial discomfort
• Bad breath
• Cough
• Fever
• Sore throat
• Headache, worse in the morning
What is Acute Bronchitis?

Acute bronchitis is considered the lower respiratory tract infection. Its an acute
inflammation of the tracheo-bronchial tree. It may be:
• Acute Infective Bronchitis which is initially an upper respiratory tract
infection initiated commonly by bacteria or viruses.
• Acute irritative bronchitis due to fumes from strong acids, ammonia,
hydrogen sulfide, tobacco, smoke, pollution etc.
Initially the cough is unproductive but gradually develops into a productive cough
with abundant thick mucus which may be purulent.
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What is Chronic Bronchitis and Emphysema?

Also known as Chronic Obstructive Pulmonary Disease (COPD). These two
conditions often co-exist.
Chronic Bronchitis is a condition associated with prolonged exposure to

Bronchial irritants and accompanied by mucus hypersecretion and certain
structural alterations in bronchi. It is characterized by chronic productive cough
and is usually associated with cigarette smoking.
Emphysema is defined as enlargement of the air spaces distal to the terminal

bronchioles, accompanied by destructive changes of alveloar walls. Cough,
sputum, and wheezing vary in character and intensity. Chronic Bronchitis leads
to destruction of bronchi and damage to pulmonary tissues (alveoli) resulting in
Bronchiectasis and Emphysema.
What is Bronchiectasis?
It is an abnormal dilation of bronchi, which is associated with infection, airway
obstruction, persistent cough and sputum and occasional fever. Repeated
infections of the bronchi and bronchioles weaken their walls so that segments of
them undergo dilation, facilitate the accumulation of secretion and this leads to
the condition called bronchiectasis.
What is Pneumonia?
Infection of lungs by micro-organisms also results in inflammation of lung tissue
and other changes causing trouble in breathing and cough. The condition is
known as Pneumonia. If proper therapy is not initiated, the condition may be
fatal.
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What is Bronchial Asthma?

In this condition, due to allergy, the smooth muscles in the walls of trachea and
bronchi go into a spasm. These changes offer obstruction to the flow of air,
producing difficulty in breathing (dysnoea).
Three factors which collectively contribute to the narrowing in the airway are:
1. Excess mucus often with mucus plugs
2. Mucosal oedema and
3. Constriction of the bronchial muscles.
Ear Infections
Otitis
Inflammation of ear is known as Otitis.
• Otitis Externa: Infection of external ear (ear canal and ear pinna)
• Otitis Media: Infection of middle ear
• Otitis Interna: Infection of inner ear
Acute Otitis Media

Acute otitis media is an inflammation of the area behind the eardrum (tympanic
membrane) in the chamber called the middle ear.
The middle ear contains air and sits behind the eardrum. When the eardrum
vibrates, tiny bones within the middle ear transmit the sound signals to the inner
ear. In the inner ear, nerves are stimulated to relay the sound signals to the
brain.
Eustachian Tube
The eustachian tube, which connects the middle ear to the pharynx, normally
ventilates and equalizes pressure to the middle ear.
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Fig 3: Ear Anatomy
Causes
Viruses are an important cause of ear infections and often found along with
bacterial infections (Streptococcus pneumoniae, Hemophilus influenza, and
Moraxella catarhalis).
Sign and Symptoms

Acute otitis media frequently occur with respiratory infections as the nasal
membranes and eustachian tube become swollen and congested.
Common symptoms are:
Ear pain, Inflammation, pus, fluid, ear fullness, or hearing loss.
These symptoms are frequently associated with runny or stuffy nose or a cough.
Severe ear infections may cause the eardrum to rupture.
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COUGH
In all the respiratory disorders discussed here, it is noted that cough is the
common presenting symptom causing distress to the patients. So the mechanism
of cough has to be understood.
What is the mechanism of Cough?

Cough is a protective reflex which serves to remove the blockage & irritants from
respiratory tract.
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What are the types of cough?

Cough is of two types:
1. Non-productive or dry cough: this is encountered frequently due to
chemical or inflammatory stimuli in the upper respiratory tract. The dry
cough fails to produce expectoration because there is nothing to produce.
2. Productive cough: The productive cough is hallmark of inflammatory
conditions of lungs and lower respiratory tract. Cough can also be caused
as a result of inhalation of dust particles, fumes or allergic materials.
Sputum or phlegm is the secretion of the lower respiratory tract. It is mixed with
nasal, pharyngeal secretions and saliva. The character of sputum in productive
cough also gives clue to diagnosis.
What is the treatment of cough?

Definitive treatment of cough depends of determining its precise cause and then
initiating therapy for underlying cause e.g. antibiotics for infection of respiratory
tract. If the condition is not treatable or if no cause can be found, symptomatic
measures must be considered.
Two lines of approach are open – either suppress the cough or make the
expectoration easier. The drugs which act on the airways to soothe cough act
upon certain receptors.
E.g Adrenergic receptors
What are adrenergic receptors?

Adrenergic receptors are found in many different types of tissues and they
generate different cellular responses to the hormone, epinephrine. Epinephrine
is produced in the adrenal glands, and it is also known as adrenaline. These
receptors are classified according to their agonists and antagonists. They are
either α or β and these are further classified as type 1 or 2. So, there are four
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major types of adrenergic receptors: α1 α2 β1and β2. These receptors are

classified according to their agonists and antagonists.
What is an Agonist, and what is an Antagonist?

Agonist
A ligand that binds to a receptor and alters the receptor state resulting in a
biological response.
Antagonist
A ligand that binds to a receptor and alters the receptor state resulting in a
response, opposite to the agonist.
Where are these receptors located in the body and what are their
functions after stimulation?
Activation of these receptors through the administration of adrenergic agonists
will produce effects consistent with sympathetic flight or fight stimulation.
• Receptors are located in the eyes (Mydriasis/ dilation of the pupil), blood
vessels (constriction of the arterioles and veins), bladder (contraction).
• Receptors are found primarily in the heart (increased rate, increased force
of contraction, and the kidney (release of renin).
• Receptors are located in the arterioles of the heart, lung, and skeletal
muscles. They cause dilation in the bronchi (bronchodilation), skeletal
muscles (contraction).
What are Muscarinic receptors?

These are the receptors where another neurotransmitter called Acetylcholine
works. These are located in larger airway smooth muscles, and cause
bronchoconstriction. Anticholinergic agents block the muscarinic receptors
resulting in relief form bronchoconstriction (bronchodilation)
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ALLERGY
What is Allergy?
An allergy is an abnormal reaction or increased sensitivity to certain substances.
The allergic individual produces symptoms when exposed to these substances,
which are harmless to non-allergic people.
The main reason for this is that allergic people make a special type of antibody
called Immunoglobulin E (IgE), which can react with environmental substances in
a harmful way. These substances are called allergens. The reaction between
allergens and IgE antibodies causes the release of substances such as
histamine, which produce allergic symptoms in the skin, the nose, the eyes, the
chest, etc
Which are the common Allergens?

The common allergens are Dust, Smoke, Pollution, Grass, Weeds, Moulds,
Dander (animal fur), Feather, Pollen grains.
What is the mechanism of allergy?

Following the exposure to common environmental allergens, the allergic
individual produces a special type of antibody (produced in response to an
antigen which it neutralizes, thus producing an immune response), called
Immunoglobulin E, or IgE. The healthy individual has a very low level of IgE in
the blood, while those with certain allergic conditions such as hay fever, allergic
asthma and some forms of eczema have high IgE levels. People with eczema
have especially high blood levels of IgE. In the human body, certain cells called
mast cells and basophils are involved in allergic reactions. IgE, produced as a
result of repeated allergenic stimulation, attaches to the surface of these cells
and subsequent binding of the allergen stimulates the mast cells to release a
substance called histamine, leading to the symptoms of allergy.
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What are the symptoms of allergy in various organs?

The symptoms of allergy are the result of the release of a chemical, called
histamine from mast cells after the activation of mast cells due to the contact with
antigen-antibody complex. Following symptoms are seen in nose, throat, and
eyes:
• Swelling (oedema)
• Inflammation
• Rhinitis (inflammation of nasal mucosa)
• Rhinorrhoea (running nose)
• Sneezing
• Itching
• Lacrimation (increase watery discharge from the eyes)
• Conjunctivitis (inflammation of the conjunctival tissue of the eye)
Which are the commonly encountered allergies?

Allergic Rhinitis
Rhinitis is defined as inflammation of the nasal membranes and is characterized
by a symptom complex that consists of any combination of the following:
sneezing, nasal congestion, nasal itching, and rhinorrhea. The eyes, ears,
sinuses, and throat can also be involved.
Allergic rhinitis is the most common cause of rhinitis. The pollens of grasses,
weeds and trees are the main causes of this type of allergy, although fungal
spores can also cause the symptoms. The lining of the nose becomes swollen
and exudes a runny discharge. Spells of sneezing and itching of the throat and
palate also occur and the eyes may be similarly affected.
Allergic Conjunctivitis
Allergic conjunctivitis is often associated with allergic rhinitis. A general complaint
is of itchiness of the eyes, which are rubbed frequently.
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Eczema
Eczema or dermatitis (inflammation of skin) presents with rashes that can be
either wet or dry and occasionally chapped. The reactions are often
accompanied by severe itching. The cause is often not clear, but is frequently
seen in children of families with a history of allergic diseases. It is possible for
eczema to become secondarily infected with skin bacteria, especially if there is
much broken skin due to scratching.
Urticaria Hives
Red inflamed rounded, raised, warm, reddish and itchy lesions on the skin. The
symptoms may last either for a couple of hours or up to a whole day. Blotches
may appear as raised wheals and vary in size from smaller than a mosquito bite
to several inches in diameter. In 95% of hives, the cause is unknown.
Contact Dermatitis
The symptoms of contact dermatitis are similar to those of the eczema, but this
reaction is of another type. The cause is direct contact with different substances,
such as:
• Nickel (in coins, stainless steel, clasps, jewelry)
• Rubber products (in gloves, boots, waistbands)
• Chromium (in cement, leather)
• Latex
• Preservatives (in creams, ointments and cosmetics)
Insect Allergy
Severe allergic reactions to bee and wasp stings are not uncommon. The local
toxic reaction and discomfort that usually occurs following an insect sting is not
generally considered to be allergic.
Ig E mediated (allergic) reactions induce symptoms such as urticaria or hives,
running nose and eyes, swelling of the throat, attacks of asthma and, in severe
cases, fainting.
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HISTAMINE AND ANTIHISTAMINES
What is Histamine?
Histamine is a main chemical substance which is involved in the mechanism of
allergy. Release of histamine is associated with allergic reactions, as it causes
both an inflammatory response and a contraction of smooth muscle tissue.
Histamine is released by mast cells primarily when they degranulate due to IgE
antibodies.
A mast cell (or mastocyte) is a resident cell of connective tissue that contains
many granules rich in histamine and heparin. When antigen and andibody
complex attaches to it, mast cell gets stimulated and the granules inside them
release histamine.
Histamine
Histamine binds to the specific histamine receptors and produces various effects.
Histamine leads to the contraction of smooth muscle cells, activates endothelium
and irritates nerve endings (leading to itching or pain). Cutaneous signs of
histamine release are the “flare and wheal” - reaction. This occurs seconds after
challenge of the mast cell by an allergen.
Which are the various receptors of histamine?

Histamine mediates its effects via histamine receptors, which are classified into
following types:
1. H1 histamine receptor – Widely expressed throughout the body, present in
brain, smooth muscles, endothelial cells, adrenal medulla and heart. The
functions are vasodilation (dialatations of blood vessels);
bronchoconstriction (constriction the smooth muscles of bronchi); smooth
muscle activation; separation of endothelial cells, responsible for hives;
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pain and itching due to insect stings; primary receptors involved in allergic
rhinitis symptoms and motion sickness.
2. H2 histamine receptor – Stimulate gastric acid secretion
3. H3 histamine receptor – Predominantly found in brain, they control
neurotransmitter release.
What are Antihistamines?

Antihistamines have been categorized over the years as first, second or third-
generation classes.
First-generation antihistamines include: Diphenhydramine, chlorpheniramine,
hydroxyzine or triprolidine. Although very effective all these drugs do cause
marked sedation.
Second-generation antihistamines include: Astemizole, terfenadine,
loratadine, cetirizine (levocetirizine), and fexofenadine, have been known as the
“nonsedating antihistamines,” were developed to minimize these side effects.
The newest antihistamine agent, desloratadine, an active metabolite of
loratadine has been categorized under the third-generation antihistamines and is
currently the only agent in this class.
These agents have been used clinically to treat various allergic disorders such as
seasonal or perennial allergic rhinitis and chronic urticaria. Antihistamines
antagonize the action of histamine by blocking H1 receptors. Blockade of H1
receptors inhibits nasal secretion promptly & facilitate passage for air and
provides symptomatic relief in allergic states.
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DIGESTIVE SYSTEM
What is digestive system or gastrointestinal tract?
Digestive System consists of an alimentary canal, which is muscular tube starting
from the mouth & ends at the anus.
Which are the various parts of gastrointestinal tract?

Digestive system or gastrointestinal tract consists of the following parts:-
• Mouth
• Oesophagus
• Stomach
• Small intestine (duodenum, jejunum and ileum)
• Caecum ( junction between the small intestine and large intestine)
• Large intestine (ascending colon, transverse colon and descending colon,
sigmoid colon, rectum)
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• Anus
• Fig 1: The Gastrointestinal Tract
The Liver, gall bladder, salivary glands and pancreas are major accessory
organs that have a role in digestion. These organs secrete fluids into the
digestive tract. (Fig.1).
What is the process of digestion and how does it progress?

Food undergoes three types of processes in the body:
• Digestion
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• Absorption
• Elimination
Digestion and absorption occur in the digestive tract. After the nutrients are
absorbed, they are available to all cells in the body and are utilized by the body
cells in metabolism. The waste is finally eliminated from the body.
What are Peristaltic movements?

After ingestion and mastication (chewing), the food particles move from the
mouth into the pharynx, then into the esophagus. This movement is deglutition,
or swallowing. Mixing movements occur in the stomach as a result of smooth
muscle contraction. These repetitive contractions usually occur in small
segments of the digestive tract and mix the food particles with enzymes and
other fluids.
The movements that propel the food particles through the digestive tract are
called peristalsis (Fig 2:). These are rhythmic waves of contractions that move
the food particles through the various regions (including oesophagus, stomach
and intestines) in which mechanical and chemical digestion takes place.
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Fig. 2: Peristaltic movements in stomach
ABSORPTION
The simple molecules that result from chemical digestion pass through cell
membranes of the lining in the small intestine into the blood or lymph capillaries.
This process is called absorption.
ELIMINATION
The food molecules that cannot be digested or absorbed need to be eliminated
from the body. The removal of indigestible wastes through the anus, in the form
of feces, is defecation or elimination.
What is the anatomy of stomach?

The stomach is a J-shaped organ that connects the esophagus to the duodenum
(the first part of the small intestine). The wall of the stomach is composed of 4
basic layers (from inside out): Mucosa, Submucosa, Muscularis & Serosa (Fig 3).
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• Mucosa - Inner lining of G.I. tract & has direct contact with G.I. contents.
• Submucosa – Next to mucosa, and is made up of loose connective tissue.
Important in controlling secretions of G.I. tract.
• Muscularis - Consists of smooth muscles whose contractions help in
breakdown & mixing of food with gastric juices. Also controls G.I. motility.
• Serosa - Outer most layer.
Fig 3: Layers of gastric wall
What are the two sphincter mechanisms in the stomach?

Stomach is divided into four areas; Cardia, Fundus, Body & Pylorus.
The stomach has two valve-like sphincters. One is at the upper end (cardiac end)
and is termed as LES, while the other is at the lower end (pyloric end) and is
called pyloric sphincter. These sphincters regulate the entry and exit of food from
the stomach.
Which are the specific sites in the stomach which produce

gastric secretion?
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The surface of the mucosa has many openings called as ‘gastric pits’. The
gastric pits are the openings of the gastric glands within the mucosa. These
gastric glands secrete various substances into the stomach. Mucous cells in the
gastric pits secrete mucus. In the deeper part of the gland, parietal cells secrete
hydrochloric acid. G cells, which are present predominantly only in the antrum of
the stomach, secrete gastrin, and chief cells secrete pepsinogen (an inactive
form of the pepsin-digesting enzyme pepsin). Intrinsic factor, needed for the
absorption of vitamin B12, is also secreted by the gastric mucosa.
Fig. 4: The Gastric gland
How does regulation of acid secretion take place?

Parietal cells belong to gastric glands and secrete hydrochloric acid, which is
needed for digestion.
The parietal cells have 3 kinds of receptors on their surface. These include:
• Histamine (H2) receptor
• Gastrin receptor
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• Muscarinic receptor
Stimulation by any one of these receptors causes stimulation of HCl secretion
from the parietal cells.
Fig. 5: Parietal cell with the receptor
How does stimulation of these receptors cause acid secretion?

When these receptors are stimulated, they increase the intracellular levels of
calcium and adenyl cyclase (enzyme acting on c-AMP), which in turn activates
the H, K ATPase enzyme. The inactive enzyme now gets activated and is
inserted into the apical end of the parietal cell. It then starts
exchanging H+ ions in the parietal cells for K+ ions leading to acid secretion.
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What is the proton pump inside parietal cells?

The H+, K+ ATPase enzyme is also termed as the proton pump. It is in an
inactive state inside the parietal cells. It gets activated when stimulated by
signals from the histamine, acetylcholine or gastrin receptor. Once activated, it
moves to the border of the cell and sends out H+ ions in exchange for K+ ions.
Since H+ and K+ ions are both protons, this enzyme is called as the ‘proton’
pump.
Fig. 6: Steps of Acid release
What are the steps in the formation of hydrochloric acid?

A stimulated cell begins the formation of hydrochloric acid from CO2 and H2O
which combine to form carbonic acid. Chemical reactions take place within the
cell, and as a result Cl- ions move to the outside of the cell along with K+ ions. As
a final step, K+ moves inside the cell, and in exchange H+ ion moves out of the
cell. This final exchange of K+ and H+ is carried out by the H+, K+ ATPase
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enzyme. Since both H+ and Cl- ions are outside the cell, they can combine
together to form HCl in the presence of H2O.
Which are the factors required to maintain normal mucosal

integrity?
• Mucus
• Bicarbonate
• Mucosal blood flow
• Cell renewal
• Endogenous prostaglandins
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GASTROINTESTINAL DISORDERS
What are ulcers?
An ulcer is a break (wound, sore or erosion) in the skin or mucus membrane. It is
usually caused by an injury of some kind.
What are Peptic ulcers?

Peptic ulcers are ulcers in the inner lining (mucosa) of the stomach, duodenum or
esophagus. Earlier these ulcers were thought to be caused by excessive acid
and pepsin activity in the upper GIT. Hence, they were termed as ‘peptic ulcers’.
What is Peptic Ulcer Disease (PUD)?

The term PUD generally refers to spectrum of disorders that includes often
esophageal ulcers, gastric ulcer (GU), pyloric channel ulcer, and duodenal ulcer
(DU).
What are the commonest sites of ulcer formation?

The commonest sites are the stomach and proximal duodenum.
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Fig 7: Commonest positions for Peptic Ulcers
What are the causes of peptic ulcer?

Recent research has shown that there are 2 main causes of ulcers:
1. Infection with H. pylori bacteria (H. pylori-associated ulcers)
2. NSAID drugs like ibuprofen, aspirin and others (NSAID-associated ulcers).
Others are:
• Hyperacidity
• Bile reflux
Fig. 8: Peptic Ulcers
It is now believed that most ulcers result from a complex interplay of acid and
chronic inflammation induced by H. pylori infection even though the exact
mechanism has not been found.
Which are the risk factors associated with the development of

Duodenal or Gastric Ulcers?
Two types of factor are seen:
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Endogenous Factors
• Genetic Predisposition
• Abnormalities in Secretion of Acid & Pepsin
• Reflux of Bile & Pancreatic Juice
• Abnormalities of Mucosal Defense (blood flow, bicarbonate secretion,
Prostaglandins)
• Emotional Stress
• Delayed Gastric Emptying
Exogenous Factors
• Cigarette Smoking
• Non-steroidal Anti-inflammatory Drugs (NSAIDs)
• Systemic Corticosteroid Therapy
• Alcohol or Caffeine - Containing Beverages
What are the symptoms of peptic ulcers?

A gastric ulcer typically causes a sharp pain in the stomach soon after eating,
whereas the pain of a duodenal ulcer is typically relieved by eating, or by drinking
milk. Other symptoms may include:
• Belching
• General discomfort in the stomach
• Loss of appetite or, rarely, increased appetite
• Nausea
• Vomiting
• Loss of weight
What are the complications of peptic ulcers?

• Haematemesis (vomiting of blood)
• Melena (black faeces containing blood)
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• Iron deficiency anaemia

• Perforation
• Peritonitis (inflammation of peritonium)
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HELICOBACTER PYLORI
What is Helicobacter pylori?

It is a spiral, gram -ve bacillus with multiple flagella. It has preference for
microaerophillic environment (carbon dioxide required for its growth). It resides in
mucus gel coating epithelial cells with a minor proportion directly adherent to
epithelial cells. It produces abundant quantities of urease enzyme that produces
ammonia (a strong base that damages stomach tissues). It survives in acid as it
secretes enzymes to neutralise acid. May be contracted through food or water &
is present even in infected person’s saliva
Fig. 9: Helicobacter pylori
How does H. pylori damage the gastric lining?

The bacteria continue to survive in the acid environment of the stomach due to
several unique features: it burrows below the mucus protective layer, and is
therefore safe from the killing action of hydrochloric acid. It forms a layer of
alkaline ammonia by converting urea to ammonia using its urease enzyme. It
starts attacking the mucosal cells by forming potent enzymes that kill mucosal
cells. Finally, it may also disrupt the mucus layer so that acid can get in contact
with damaged mucosal area and damage it further.
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Fig. 10: H. pylori eroding mucosal layer
How is infection with H. pylori diagnosed?

Diagnosis is done with the help of a procedure called as ‘biopsy’, which is
performed while doing an endoscopy. The results indicate whether there is
infection or not. There are other tests like breath-tests and antibody titer tests but
these are not done routinely.
• Blood test.
• Urea Breath test.
• Fecal Antigen test.
• Tissue test.
• Histology test (biopsy sample removed by endoscope)
• Rapid urease test (to detect enzyme urease)
• Culture test
Which are the drugs used to treat H. pylori Peptic ulcer?
Antibiotics
• Metronidazole
• Tetracycline
• Clarithromycin
• Amoxicillin
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H2 Antagonist
• Cimetidine
• Ranitidine
• Famotidine
Proton Pump Inhibitors

• Omeprazole
• Lansoprazole
• Esomeprazole
• Rabeprazole
Coating Agents
• Colloidal bismuth compounds
• Sucralfate
34
REFLUX OESOPHAGITIS OR GASTROESOPHAGEAL

REFLUX DISEASE (GERD)
What is Reflux Oesophagitis or Gastroesophageal Reflux

Disease (GERD)?
GERD is also known as Heart burn in general terminology. If the LES remains
open at inappropriate times, the acid contents of the stomach are pushed into the
esophagus causing damage to the esophageal lining. This process is called
‘esophagealreflux’ or ‘acid reflux’. The disease caused by this process is termed
as ‘Gastro-Esophageal Reflux Disease’ or GERD.
Fig. 11: Acid reflux causing GERD. Fig. 12: Defect in LES
What can contribute to GERD?

The cause of GERD is not known. A hiatal hernia may cause GERD.
Other factors that may contribute to GERD include
• Alcohol overuse
• Overweight
• Pregnancy
• Smoking
35
Also, certain foods can be associated with reflux events, including

• Citrus fruits
• Chocolate
• Drinks with caffeine
• Fatty and fried foods
• Garlic and onions
• Mint flavorings
• Spicy foods
• Tomato-based foods, like spaghetti sauce, chili, and pizza
Which factors can contribute to GERD?

Lifestyle factors can also cause increased risk of reflux. Smoking, large
meals,fatty foods, caffeine, pregnancy, obesity, sleeping immediately after meals,
tight fitting clothes, drugs (Calcium channel blockers, anti-cholinergic, beta &
alpha-adrenergic agonist, dopamine, sedatives, pain relievers), and hormones
may all exacerbate GERD. Hiatus hernia is an important surgical condition
resulting in GERD symptoms and esophageal damage.
A hiatal hernia occurs when the upper part of the stomach is above the
diaphragm (the muscle wall that separates the stomach from the chest). The
diaphragm helps the LES keep acid from coming up into the esophagus. When a
hiatal hernia is present, it is easier for the acid to come up.
What are the common symptoms of GERD?

Clinical presentation
The classic symptoms are heartburn and regurgitation, which may also include
dysphagia.
Other symptoms that may be caused by GERD are:
• Atypical chest pain
36
• Hoarseness
• Nausea
• Cough
• Odynophagia (pain during swallowing)
• Asthma
What are the complications of chronic GERD?

Pathologic conditions associated with GERD include:
Deep ulcers, bleeding, esophageal stricture, and replacement of normal
esophageal epithelium with abnormal (Barrett’s) epithelium, cancer of
oesophagus, and reflux laryngitis.
What is Gastritis?
Gastritis means inflammation of the stomach. It means that white blood cells
move into the wall of the stomach as a response to some type of injury. Gastritis
does not mean that there is an ulcer or cancer. It is simply inflammation–either
acute (present for a short period) or chronic (for a longer duration).
What are the causes of Gastritis?

Chronic infection - Helicobacter pylori
Immunologic - associated with pernicious anemia
Chemical - NSAID’s bile reflux
Others - post-surgical, radiation
What are the symptoms of Gastritis?

The symptoms of gastritis depend on how acute it is and how long it has been
present. In the acute phase, there may be pain or gnawing in the upper
abdomen, nausea and vomiting. In the chronic phase, the pain may be dull and
there may be loss of appetite with a feeling of fullness after several bites of food.
37
Very often, there are no symptoms at all. If the pain is severe, there may be an
ulcer as well as gastritis.
What is Duodenitis?
Duodenitis is basically inflammation and irritation of the wall of the first part of the
small intestine.
Symptoms are similar to Peptic Ulcer Disease or duodenal ulcers. There can be
stomach pain, bleeding from the intestine, nausea, vomiting, loss of appetite,
and, rarely, intestinal obstruction.
It is similar to ulcers but less severe. Treatment is similar to ulcers.
38
DYSPEPSIA
What is Dyspepsia?
Dyspepsia means bad digestion and is commonly known as indigestion.
What are the symptoms of Dyspepsia?

The symptoms include epigastric discomfort, bloating, nausea, acid regurgitation,
heart-burn & a feeling of fullness that occurs soon after eating. In some patients,
symptoms usually develop after meals (post-prandial dyspepsia).
What are the types of Dyspepsia?

The following are the types of dyspepsia:
• Ulcer-like dyspepsia - Primary symptom is pain.
• Motility-like dyspepsia - Primary symptoms may be bloating, fullness &
gas distention of abdomen.
• Reflux-like dyspepsia - Primary symptom is similar to that of heartburn.
• Functional or non-ulcer dyspepsia - When clear cause of symptoms
cannot be identified.
What is the treatment of Dyspepsia?

The drugs used for the treatment of Dyspepsia include antisecretory drugs,
prokinetic drugs, cytoprotective agents & antacids.
39
EMESIS (VOMITING)
What is Nausea and Vomiting?

Nausea is defined as a sensation or desire to vomit, whereas vomiting is the act
of expelling the contents of the stomach. Vomiting is often the end result of a
period of nausea.
What is the physiology of nausea & vomiting?

Coordination of nausea and vomiting is performed by the vomiting centre, located
in the brainstem.
The vomiting centre receives information from 4 main areas within the body.
• Chemoreceptor Trigger Zone (CTZ) eg. Drugs and toxins stimulate it.
• Vestibular Centre (brainstem) eg. sea sickness, motion sickness
• Cerebral Cortex (memory of unpleasant stimulus/ anticipatory nausea) eg.
drug previously causing nausea-chemotherapy
• Gut (GIT) via the vagus nerve eg. gastric irritation by drugs, dyspepsia
What is chemoreceptor trigger zone and which are the factors

which stimulate it?
The CTZ comprises a bundle of nerve fibres in the brainstem which are able to
sense changes that occur in the chemical composition within the bloodstream.
Abnormal chemical states (hypocalcemia), drugs (morphine), stimulate CTZ
which in turn stimulates vomiting centre to produce nausea (DIRECT).
Further, vestibular disturbances also send impulses to the CTZ and hence, to
vomiting centre, to produce nausea & vomiting (INDIRECT).
Specifically, activation of dopamine receptors (D2) in the CTZ can stimulate
nausea and vomiting.
40
Which are the commonly used antiemetic drugs?

ANTIEMETIC DRUGS
• Dopamine antagonists: e.g Metoclopramide, Domperidone. They inhibit
Activation of dopamine receptors in CTZ and thereby, prevent nausea and
vomiting. These are useful for gastric-mediated nausea and vomiting
(gastric irritation, dyspepsia).
• 5HT3 Antagonists: e.g. Ondansetron, Granisetron, etc. These are useful
for cortex-mediated nausea/ vomiting as 5HT3 receptors are involved in
this type of vomiting (chemotherapy induced vomiting).
• Antihistaminics: As histamine & acetylcholine are involved in vestibular
nausea (motion sickness), antihistaminics with anti-emetic action
(Promethazine) are useful.
41
42
GASTROENTERITIS
What is Gastroenteritis?
Gastroenteritis is the irritation and inflammation of the digestive tract.
What are the causes of Gastroenteritis?

Food poisoning, stress, excessive alcohol or tobacco use, viral infections, food
allergies, improper diet, certain drugs, food consumed in foreign countries and
intestinal parasites are all possible causes for this condition.
How does Gastroenteritis spread?

Gastroenteritis caused by viral infection or bacteria is easily passed from one
person to another. Care should always be taken to wash the hands often,
especially when preparing food after bowel movements. Hand washing after
bowel movements is important since the organism that causes this condition lives
in the digestive tract, is passed in the stool and due to lack of hygiene of hands
can infect the food.
What are the symptoms of Gastroenteritis?

The symptoms of gastroenteritis can include:
• Abdominal cramps
• Nausea and vomiting
• Diarrhea
• Loss of appetite
• Weakness
• Fever or chills
• Dehydration
43
What is the general treatment for Gastroenteritis?

In cases of dehydration, fluid replacement is the primary factor in treatment. If
signs of dehydration (wrinkled skin, dry mouth, excess thirst or absence of
urination for over six hours) appear, a doctor should be consulted as soon as
possible. A doctor should also be consulted if the any of the following occur:
• Symptoms persisting for more than 48 hours

• Mucus or blood in stools
• Fever over 1010 F
• Severe abdominal or rectal pain
• Vomiting and diarrhea after being treated
In severe cases where vomiting is prolonged, a doctor may prescribe an anti-

emetic suppository or give medication by injection. Prolonged diarrhea is often
treated with medications that harden stools and reduce bowel activity. As soon
as bowels resume normal function, this medication is stopped.
44
AMOEBIASIS
What is Amoebiasis?
Amoebiasis, a type of gastroenteritis, is a cause of diarrhoea among travelers. It
is caused by a parasite known as Entamoeba histolytica that infects the bowel.
Amoebiasis most commonly affects young to middle-aged adults.
What are the symptoms of Amoebiasis?

Diarrhoea is one of the most common symptoms. In addition to diarrhoea (which
may contain blood) signs and symptoms include:
• Stomach cramps and
• Fever
How does Amoebiasis spread?

Amoebiasis occurs when the parasites are taken in by mouth. People with
amoebiasis have Entamoeba hisolytica parasites in their faeces. The infection
can spread when infected people do not dispose of their faeces in a sanitary
manner or do not wash their hands properly after going to the toilet.
Contaminated hands can then spread the parasites to food that may be eaten by
other people and surfaces that may be touched by other people. Hands can also
become contaminated when changing the nappies of an infected infant.
Amoebiasis can also be spread by:

• Drinking contaminated water
• Eating contaminated raw vegetables and fruit
• Unprotected oral-anal sexual contact
45
What are Carriers?

Some people carry the parasite in their faeces without having symptoms, but
they can still pass the disease on to other people. These people are known as
carriers.
What are the symptoms of Amoebiasis?

Diarrhoea is one of the most common symptoms. In addition to diarrhoea (which
may contain blood) signs and symptoms include:
• Stomach cramps and
• Fever
46
DIAGNOSIS AND MANAGEMENT OF VARIOUS

GI DISORDERS
Diagnosis
Diagnosis is made with help of barium meal, X-Ray examination or endoscopy.
Barium swallow - This involves swallowing a drink containing barium, which

shows up white on X-rays. The barium coats the lining of the stomach and
duodenum, and X-rays are taken to show an outline. These may show an ulcer.
Gastroscopy - A tube (endoscope) containing a fibre-optic tube is passed through

the mouth and into the stomach. The doctor can see the lining of the stomach
through the tube, and can take a sample of the stomach lining with an instrument
that is passed down through the tube. This sample is tested for H. pylori and
examined under a microscope to check whether cancer is present.
How is GERD diagnosed?

In the great majority of cases, a diagnosis of gastro-esophageal reflux disease is
straightforward, particularly if heartburn and acid regurgitation are present and
are lessened by taking antacids for short periods.
What is the treatment of GERD?

Treatment of GERD is divided into Non-Pharmacological and Pharmacological.
Non Pharmacologic Treatment

Dietary
• Eat regularly, have nutritious meals & avoid food that bothers.
• Avoid alcohol, nicotine, & tobacco.
• Other dietary factors to be avoided may include tomatoes, citrus, spicy
foods, chocolate & mint
47
Pharmacologic Treatment
Following classes of drugs are included in the treatment of Acid-peptic disorders:
• Antacids (Aluminum & Magnesium salts)
• H2 receptor antagonists (Ranitidine, Cimetidine, Famotidine)
• Proton Pump Inhibitors (Omeprazole, Rabeprazole, Pantoprazole &
Esomeprazole)
• Coating agents (Sucralfate, Colloidal Bismuth Compounds)
What are Antacids?

• Basic compounds which neutralizes gastric acid
• Used in symptomatic management of acid disorders
• Do not reduce volume of HCl secreted
• Most commonly used antacids are Aluminium & Magnesium salts
• Most common side effect of magnesium salts is diarrhea and with
aluminum salts is constipation
What are H2 receptors antagonists?

• Blocks H2 receptors on parietal cells, and antagonize normal stimulatory
effect of histamine on acid secretion e.g. Ranitidine, Cimetidine,
Famotidine
• Inhibit acid secretion for 6 to 24 hrs and are very useful for people who
need persistent acid suppression.
Shortcoming of H2 receptor antagonists

• Not effective in meal-stimulated acid secretion which is required for
management of Erosive oesophagitis & for relief of reflux symptoms.
• Rapid development of tolerance.
• Rebound acid hypersecretion after withdrawal
48
What are the Proton pump inhibitors?

• Acts by blocking enzyme system i.e. H+, K+ - ATPase, which is found at
acid secretory surface of parietal cells that mediates final transport of H+
ions in exchange of K+ into gastric lumen.
• These drugs inhibit H+, K+ - ATPase which activate proton pump.
• More potent & long acting than H2 receptor antagonists
• E.g are Omeprazole, lansoprazole and pentoprazole
Advantages of PPIs
• Remains the mainstay of treatment in suppression of gastric acid
secretion.
• Very effective for suppressing gastric acidity to all known stimuli.
• Drug of choice in serious or refractory acid related diseases (GERD)
• Once-daily dosing in the morning is more effective.
What are the Prokinetic agents?

Prokinetic Agents: Rather than neutralizing acid, prokinetic agents increase both
gastric emptying and lower esophageal sphincter pressure. These agents are
used when esophagus is not injured.
E.g Cisapride and mosapride
Cisapride acts by increasing acetylcholine concentrations in the myenteric

plexus. Because of the cholinergic side effects associated with these older
prokinetic agents are no longer frequently prescribed.
The side effects of cisapride are generally limited to abdominal cramping and
diarrhea. Cisapride should not be used in conjunction with antibiotics,
antifungals, protease inhibitors, antiallergics, angina, arrhythmias, depression
and psychosis.
49
What are Coating agents?

They act neither by adhering to an ulcer crater and protecting it from further
damage by the stomach acid and pepsin e.g Sucralfate, DGL (Deglycerrhizinated
Licorice)
Which are the cases, where surgery is required?

Surgery may be considered in patients who fail medical therapy or develop
complications of GERD. Patients can fail medical therapy because of
noncompliance, inability to afford medications, relapse of symptoms soon after
medication is stopped or relapse of symptoms despite continuous use of
medication. Possible complicating factors include large hiatal hernia, Barrett’s
esophagus, severe esophagitis, recurrent esophageal strictures and severe
pulmonary symptoms.
Surgical intervention has been shown to provide long-term relief of symptoms in
patients with GERD.
50
MUSCULOSKELETAL SYSTEM
What are the components of the Musculo-skeletal System?

Body movements are carried out by the interaction of the (skeletal) muscular and
skeletal (bone) systems. For this reason, they are often grouped together as the
musculoskeletal system.
Fig. 1: The skeleton
51
What are the functions of skeletal system?

The skeletal system serves many important functions:
• It provides the shape and form to the body in addition to support
• Protects delicate organs (for instance, the skull protects the brain)
• Allows body movements through the joints
• Produces blood for the body (using the bone marrow)
• Stores minerals like calcium and phosphorus
What is a joint?
A joint can be defined simply as the union of two or more bones. In other words,
it is the site at which two or more bones come together.
What are the main components of a synovial joint?

The main components of a synovial joint include:
1. Bones
2. Joint capsule: Covers the joint from outside
3. Synovial membrane: Lining of the capsule
4. Synovial fluid: Fluid present in the synovial cavity
5. Articular cartilage: Covering the ends of the two bones inside the bones.
Fig. 2: Typical Synovial Joint
52
What is Synovium and Synovial fluid?

The synovial membrane or synovium is a thin, delicate membrane that lines the
inner surface of the fibrous capsule and also covers the areas of the joint that is
not covered by the articular cartilage. The cells of synovium secrete a fluid called
‘synovial fluid’. The synovial fluid provides lubrication for smooth and painless
movements and also serves to absorb strong shocks to the joint structures during
physical activities such as walking and running. Lastly, it provides nutrition and
oxygen to the articular cartilage, as the cartilage does not have a blood supply of
its own.
What is an articular cartilage?
The articular cartilage is a smooth and slippery connective tissue that covers the
ends of the bones which form a joint. It is formed by cells called chondrocytes.
Chondrocytes also replicate (divide) poorly, therefore once damaged, they are
very rarely replaced. Hence articular damage is considered more or less
permanent, as repair and healing of cartilage is minimal.
What are the other supporting structures in a joint?

There are other structures found outside the capsule like joint ligaments, muscles
and tendons as well as bursae which support the joint structure. They are called
as ‘extra-articular structures’ or ‘extra-capsular structures’.
Fig. 3: Extra articular structures
53
SKELETAL MUSCLES
What are muscles?
Muscle is another type of tissue. Muscles are bundles of fibers that can contract.
Skeletal muscles, which are responsible for posture and movement, are attached
to bones, so are called skeletal muscles.
What are the different types of muscles?
There are 3 kinds of muscle tissues:
1. Skeletal muscles: Skeletal muscles are of the voluntary type. Contraction
of these muscles generates sufficient force to move the bones of the joints
so that various movements can occur at a joint.
2. Smooth muscles: Smooth muscles are muscles found in the internal
organs like the lungs, digestive system and urinary system. They are
involuntary and are controlled by the autonomic nervous system.
3. Cardiac muscles: Cardiac or myocardial muscles are found only in heart.
What is a tendon?
Tendon is a part of the skeletal muscle that joins the bone. It is composed mainly
of very strong fibrous tissue.
What is a ligament?
A joint capable of a wide range of movements needs more supporting tissues in
order to remain stable. Assisting the capsule are several strong, fibrous tissues
that bind the two bones of the joint, called joint ligaments.
54
PAIN AND INFLAMMATION
What is the role of pain and inflammation?

Pain and inflammation are protective processes in the body. Pain alerts a person
of some disorder within the body that needs treatment. Inflammation is also
protective. During the process of inflammation, immune cells surround the
pathogen from all sides and create a ‘wall of immune cells’. This prevents the
further spread of pathogens away from the site of entry. Without inflammation,
the spread of pathogen will go unchecked causing even more harm to the body.
What is Pain?
Pain is defined as an unpleasant sensory ,emotional experience to tissue
damage.
What is Inflammation?
Inflammation is the response of living tissue to any kind of damage. The common
causes include physical agents, chemical agents and microbial pathogens.
Inflammation is classified into 2 types based on duration: acute inflammation
(lasting for few days) and chronic inflammation (lasting for weeks to months). It
can also be classified according to the cause of inflammation into infective
inflammation, allergic inflammation and traumatic inflammation etc.
What are the signs of inflammation?
The signs of inflammation are given below:
55
How does inflammation occur?

The process of inflammation begins with tissue damage. The cell membrane is
rich in phospholipids, and these phospholipid molecules are released during cell
damage. Phospholipids are then converted to arachidonic acid by an enzyme,
phospholipase A2 (PLA).
What are the pathways of metabolism of arachidonic acid?
Arachidonic Acid (AA) is further metabolized via two pathways, involving two
different enzymes – cyclooxygenase enzyme (COX) and lipooxygenase enzyme
(LOX). These two pathways are called cyclooxygenase and lipooxygenase
pathway respectively. The end-products of these two metabolic pathways
ultimately cause inflammation.
What are the end products of the cyclooxygenase pathway?
56
Arachidonic is converted to a thromboxane A2 (TXA2) and a group of

compounds called prostaglandins (PGG2, PGH2, PGI2, PGE2, and PGF2) by COX
enzyme.
What are the end products of the lipooxygenase pathway?
In the LOX enzyme pathway, arachidonic acid is converted to a group of
products called leukotrienes (LTB4, LTC4, LTD4, and LTE4).
What are mediators of inflammation?
Mediators of inflammation are a large family of substances that are collectively
responsible for different aspects of inflammatory process. Some are released by
damaged and dying tissue cells, while some are released by immune cells.
Some of the substances responsible for inflammation are given below:
• Prostaglandin family (PG I2, PGD2, PG E2, PGF2)
• Leukotriene family (LTC4, LTD4, LTE4)
• Interleukin family (IL1 to IL14)
• Interferons
• Tumor Necrosis Factor (TNF-á)
• Bradykinin
• Neurokinins
• Substance P
What is the significance of cyclooxygenase enzyme?

Cyclooxygenase or COX is an enzyme which converts arachidonic acid into
prostaglandins and thromboxane. Two kinds of COX enzymes have been
discovered - COX-1 and COX-2. There are several structural and functional
differences between the two enzymes.
COX-1 is found in almost all tissues of the body, therefore is called ‘constitutive’
enzyme. But, it is especially required to provide useful prostaglandins in certain
tissues like stomach mucosa, kidneys, uterus and blood platelets. The function of
these tissues is affected when prostaglandins and TXA are not available to them.
57
What is the significance of COX-2 enzyme?

COX-2 enzyme is found in most tissues in very small amounts, but is largely
formed during injuries and inflammation in whichever tissue or cells that may be
involved in inflammation. Therefore it is called ‘inducible’ enzyme as the
formation is induced by inflammation. The prostaglandins thus formed by COX-2
promote inflammation and pain. However, very small amounts of prostaglandins
formed using COX-2, are needed by kidney & brain.
58
Cox-1
Thromboxane
(causes vasoconstriction
& have thrombotic
property
Prostaglandin which
Offers GI cytoprotection 59
MUSCULOSKELETAL DISORDERS
Following are the commonly seen musculoskeletal disorder:
What is Rheumatoid Arthritis (RA)?

Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory
disorder of unknown origin characterized by symmetric (both sides of the body is
involved) synovitis (inflammation of synovial membrane) and joint destruction,
leading to swelling, pain, stiffness, and the possible loss of function of the joints.
Apart from joints, RA can also affect other organs, and therefore is termed as a
‘systemic disorder’. It affects around 1% of the adult population and its
prevalence is 3 times more in women than in men. Rarely children may be
affected (Juvenile RA).
What is the basic pathology in RA?

RA is an autoimmune disease in which the body’s immune system attacks joint
tissue of the body itself, leading to pain, inflammation, deformity and disability
that can be permanent. While the cause of rheumatoid arthritis is not yet known,
genetic predisposition plays a role as well as possible environmental factors such
as a bacterial or viral infection.
Fig. 1: Arthritic joint
60
As the disease progresses, due to destruction of the bone tissue deformity

develops which ultimately leads to disability.
RA—Pathophysiology
• Synovitis: inflammation re
• Pannus formation: granula
over articular capsule
Which joints are commonly affected in RA?
– Pannus releases enzyme

Common joints affected in RA
which destroy the cartila

• Fibrosis
– Pannus between bone e
movement
• Cartilage erosion
– By enzymes frompannu
• Ankylosis
61
What are the common symptoms of RA?

The symptoms of rheumatoid arthritis vary a lot from person to person. The
common symptoms include the following:
62
How is RA diagnosed?
There is no single physical sign or laboratory finding that is 100% specific for a
diagnosis of RA, but a number of features are highly suggestive, including the
finding of symmetrical peripheral synovitis and subcutaneous nodules.
Laboratory & X ray findings:
• Elevation of erythrocytes sedimentation rate (ESR) and C reactive protein
(CRP) for acute inflammation.
• Rheumatoid factor: Are autoantibodies directed against the body and are
found in 75-80% of patients with RA.
• Joint x-rays: As the disease progresses x-rays can show bony erosions
typical of rheumatoid arthritis in the joints.
What are the aims of the treatment of RA?

RA is a progressive disorder and has no cure. Extensive joint damage can occur
within 2-3 years after the disease commences, so it needs to be managed
aggressively. The aims of the treatment should be directed towards the following:
• Reduction of joint inflammation and pain
• Maximize joint function
• Prevention of joint destruction
• Preventing deformity.
What is the management of RA?

Management is multidisciplinary and incorporates drug therapy, physical therapy,
dietary therapy, patient education and counseling and aids for activities of daily
living.
Drug Therapy
Therapeutic approaches to RA include glucocorticoids, NSAIDs (Non steroidal
anti-inflammatory drugs) and DMARDs.
63
1. Analgesics are essential. Analgesics such as paracetamol are commonly

combined with NSAIDs including the newer COX-2 inhibitors.
2. Oral and intra-articular corticosteroids show a dramatic effect in patients
with RA.
3. DMARDs (Disease Modifying Anti-Rheumatic Drugs)
They are used to delay or arrest joint progression. DMARDs or slow acting
anti-rheumatic drugs belong to different classes of the drug but they all
modify the disease process. The most commonly used DMARDs are:
Methotrexate, Sulphasalazine, Chloroquine and Hydroxychloroquine etc.
Surgery
Despite therapy with DMARDs, joint destruction and erosive changes occur over
time in many patients. Several types of surgery are available to patients with
severe joint damage.
64
OSTEOARTHRITIS
What is Osteoarthritis?
Osteoarthritis (OA), also known as degenerative joint disease, is considered the
most prevalent chronic joint disorder worldwide.
What is the basic pathology of Osteoarthritis?
Osteoarthritis symptoms are considered to be due to an imbalance between the
synthesis and degradation of articular cartilage. In this disorder, an affected joint
experiences a progressive loss of cartilage. Degradation in the smooth,
lubricating property of the articular cartilage is followed by changes in the
underlying bone that lead to bony overgrowth. There are secondary inflammatory
changes in the synovial tissue and weakening of ligaments and associated
muscles.
Fig. 5: Osteoarthritic joint

The process continues until all of the cartilage is lost, leading to bone exposure.
65
What happens once the cartilage is destroyed?

Articular cartilage functions as the body’s shock absorbers. Once they degrade
and are destroyed, they can no longer perform their function. Without proper
cushioning effect, bones grind against one another and the increased friction can
cause pain, stiffness, decreased range of motion and swollen joints.
Which joints are commonly affected?

The weight bearing joints such as hips, knees and spine
are most commonly affected in osteoarthritis. OA only
occasionally affects the wrist, elbows, shoulders, and
jaw.
What are the common symptoms of OA?

The common symptoms include the following:
• Aching pain in one or more joints, stiffness, and
loss of mobility
• Inflammation may or may not be present
66
• Stiffness tends to follow periods of inactivity, such as sleep or sitting, and

can be eased by stretching and exercise
• The pain may increase for some days followed by periods of relative relief
It often worsens after extensive use of the joint and is more likely to occur
at night than in the morning.
What are the risk factors of OA?

There are several factors that make a person prone to developing osteoarthritis:
• Aging
OA is very common in people past age 65, in whom 85% show some
evidence of osteoarthritis on x-ray, and about 50% experience symptoms.
• Gender
Before age 45, osteoarthritis occurs more frequently in males, while after
55 years of age, it develops more often in females. Apart from this
ethnicity, genetic Inheritance, and obesity also play a role in OA.
How is OA diagnosed?
The best way to diagnose osteoarthritis is through x-rays of the affected joint
which reveal evidence of cartilage damage.
What are the aims of the treatment of OA?

OA treatment has following general goals:
• Improve joint care through rest and exercise
• Maintain an acceptable body weight
• Control pain with medical and other measure
• Achieve a healthy life style
67
What is the treatment for OA?

Osteoarthritis is a progressive disorder and only symptomatic treatments are
given to the patients. The following types of medicines are commonly used in
treating OA.
• Acetaminophen
• NSAIDs (amongst COX 2 inhibitors, valdecoxib and celecoxib are
commonly used for OA
• Corticosteroids
68
BACK PAIN
What is back pain and what are the causes of it?

Back pain can develop anywhere from the neck to the lower spine. The low back
is the region that lies between the thorax and the pelvis at the rear of the body.
Low back pain (also called Lumbago) is a symptom caused by various disorders.
The pain can be localized or spread across a wide area and radiate from a
central point. Most back pains are caused by muscle strain, trauma, spinal
deformity and poor posture. It also includes, degeneration of vertebrae, infection,
or tumor. Certain sports, such as prolonged vehicle driving are also associated
with back pain. Diseases such as spinal osteoarthritis, spondylitis and
compression fractures can also cause pain.
What is the treatment for back pain?

• Over-the-counter pain relievers, such as aspirin, acetaminophen and non-
steroidal anti¬inflammatory drugs, are often the only treatment necessary
for back pain.
• Patients should avoid any activity that increases the pain.
• For persistent pain, assistance from a rheumatologist should be obtained.
Treatment should be directed at the specific cause of pain.
• Surgery can be very helpful when nonoperative therapy fails.
69
GOUT & GOUTY ARTHRITIS
What is Gout?
Gout is a painful and potentially disabling form of arthritis, which is caused by an
excess of uric acid in the body.
With time, elevated levels of uric acid in the blood may lead to deposits around
joints leading to gouty arthritis. Uric acid may also collect under the skin, which is
known as tophi, or in the urinary tract as kidney stones.
What is the treatment of gout?

Treatment
1. NSAIDs: Because of the unpleasant side effects of colchicine, non-
steroidal anti-inflammatory drugs (NSAIDs) have become the treatment of
choice for most acute attacks of gout. The NSAID that is most widely used
to treat acute gout is indomethacin.
2. Corticosteorid are also used to treat gout attacks and they can be given in
pills or by injection.
3. Probenecid, a drug that helps the kidneys eliminate uric acid, and
allopurinol, a drug that blocks production of uric acid by the body are also
available.
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CERVICAL SPONDYLITIS
Cervical spondylitis is a very common disorder, normally seen in the elderly from
the age of 55 onwards, cervical spondylitis today is increasingly frequent in the
younger age group from 35 to 45 years of age.
What is Cervical Spondylitis?

Essentially, the pathology consists of:
• Narrowing of the cervical vertebrae with disc space reduction.
• Friction between two vertebral bodies created by this narrowing, with an
osteophyte (bony spur) formation.
• Loss of normal concavity (bend) in the cervical region, i.e., loss of lordosis.
What are the common symptoms of this condition?

This problem causes pain, stiffness and numbness in the neck - often running
down the arms. Other symptoms include:
• Chronic neck pain, particularly while moving.
• Numbness and tingling sensation in the hands or feet due to the
compression of the cervical nerve roots.
• Tenderness and swelling in the neck
The problems of vascular insufficiency consist of vertigo (spinning of head),

giddiness, occasional tinnitus (a ringing sensation in the inner ear), a sense of
unsteadiness, etc. In a severe case, there is transient loss of consciousness.
What are the causes of Cervical Spondylitis?

Cervical spondylitis can be caused by inflammation of one or more vertebrae.
Stiff muscles in the cervical region can occur due to:
• Bad posture and lack of exercise
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• Lying in bed with several pillows propping the neck

• Hunching over the computer for many hours
• Positioning the body on the same side during sleep
• Ill-designed chairs
What is the treatment of Cervical Spodylitis?

Cervical spondylitis is considered as a normal degenerative aging change. As
treatment non¬steroidal anti-inflammatory medication such as aspirin,
acetaminophen or ibuprofen may be recommended to decrease swelling and
relieve pain. The best way to get rid of the pain can be by massaging the
muscles, and performing gentle neck exercises. Improvement in the posture also
minimizes the symptoms of cervical spondylitis.
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ANKYLOSING SPONDYLITIS
What is Ankylosing Spondylitis?

Ankylosing spondylitis is a form of chronic inflammation of the spine and the
sacroiliac joints. The sacroiliac joints are located in the low back where the
sacrum (the bone directly above the tailbone) meets the iliac bones (bones on
either side of the upper buttocks). Chronic inflammation in these areas causes
pain and stiffness in and around the spine. Over time, chronic spinal
inflammation (spondylitis) can lead to a complete cementing together (fusion) of
the vertebrae, a process called ankylosis. Ankylosis causes total loss of mobility
of the spine.
Ankylosing spondylitis is 2-3 times more common in males than in females.
Ankylosing spondylitis affects all age groups, including children. The most
common age of onset of symptoms is in the second and third decades of life.
What causes Ankylosing Spondylitis?

The tendency for developing ankylosing spondylitis is believed to be genetically
inherited. The initial inflammation may be a result of an activation of body’s
immune system by a bacterial infection. Once activated, the body’s immune
system becomes unable to turn itself off, even though the initial bacterial infection
may have long subsided. Chronic tissue inflammation resulting from the
continued activation of the body’s own immune system in the absence of active
infection is the hallmark of an autoimmune disease.
What are the symptoms of Ankylosing Spondylitis?

The symptoms of ankylosing spondylitis are related to inflammation of the spine,
joints, and other organs. Inflammation of the spine causes pain and stiffness in
the low back, upper buttock area, neck, and the remainder of the spine. The
73
onset of pain and stiffness is usually gradual and progressively worsens over
months.
Patients who have chronic, severe inflammation of the spine can develop a
complete bony fusion of the spine (ankylosis). Once fused, the pain in the spine
disappears, but the patient has a complete loss of spine mobility. These fused
spines are particularly brittle and vulnerable to breakage (fracture).
Ankylosing spondylitis can cause inflammation and scarring of the lungs, causing
coughing and shortness of breath, especially with exercise and infections.
Other areas of the body affected by ankylosing spondylitis include the eyes,
heart, and kidneys. Advanced spondylitis can lead to deposits of protein material
called amyloid into the kidneys and result in kidney failure.
How is Ankylosing Spondylitis diagnosed?

The diagnosis of ankylosing spondylitis is based on evaluating the patient’s
symptoms, a physical examination, x-ray findings, and blood tests
What are treatment options for Ankylosing Spondylitis?

• Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) are
commonly used to decrease pain and stiffness of the spine and other
joints. Commonly used NSAIDs include indomethacin, tolmetin , sulindac,
naproxen, and diclofenac.
• Oral or injectable corticosteroids (cortisone) are potent anti-inflammatory
agents and can effectively control spondylitis and other inflammations in
the body. Unfortunately, corticosteroids can have serious side effects
when used on a long-term basis. Inflammation and diseases in other
organs are treated separately.
• Cigarette smoking is strongly discouraged in patients with ankylosing
spondylitis, as it can accelerate lung scarring and seriously aggravate
breathing difficulties. Finally, patients who have severe disease of the hip
joints and spine may require orthopedic surgery.
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ANALGESICS AND ANTI-INFLAMMATORY DRUGS
What are Analgesics?

Drugs, which are used to relieve pain without loss of consciousness, are called
analgesics. They selectively relieve pain by acting in the CNS or on peripheral
pain mechanisms, without affecting its cause.
How are the analgesics classified?

1. Opioids
2. Non-opioids i.e. NSAIDs
What are Opioids ?

The term ‘opioid’ is used to denote all drugs which has morphine (opium) like
action: relief from pain and depression of the CNS.
The opioids produce their pharmacological effects by interacting with the opioid
receptors which are widely distributed in the CNS and other tissues. These drugs
act on the cortex and subcortical level and not only raise the pain threshold but
also modify the pain processing phenomenon.
Morphine is a natural opioid which is a potent analgesic but has severe side-
effects like drowsiness, respiratory depression, cardiovascular depression,
physical dependence (addiction), tolerance, and constipation.
What are non-opioids?

• In contrast to opioids, the non-opioids analgesics have following functions:
Relieve pain without interacting with the opioid receptors.
• Possess anti-inflammatory property and are known as NSAIDs (Non
Steroidal Anti-Inflammatory Drugs)
• Reduce elevated body temperature (antipyretic effect)
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• Non-addicting.
• No significant depression of the CNS.
Which are the common anti-inflammatory drugs?
Corticosteroids
These are the most potent immunosuppressant and anti-inflammatory drugs.
They are believed to exert their anti-inflammatory actions by inhibiting the
production of Prostaglandins. While they produce remarkable results in
inflammatory conditions, long term use may precipitate numerous side effects,
therefore, used judiciously and cautiously and their use is limited to patients who
fail to respond to other forms of therapy. The examples are Prednisolone,
Dexamethasone etc.
Non-steroidal Anti-inflammatory drugs (NSAIDs)

These have Analgesic & Anti-inflammatory & Antipyretic properties. These inhibit
Cox-1 & Cox-2 non selectively. Eg. are Aspirin, Indomethacin, Ibuprofen,
Naproxen, Mefenamic Acid, Diclofenac, Piroxicam, Meloxicam, Nimesulide,
Paracetamol.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

They are generally termed as NSAIDs. They possess analgesic, antipyretic and
anti-inflammatory properties. Blocking the release of prostaglandins is now
considered to be the major mechanism of NSAIDs. Most NSAIDs inhibit COX-1
and COX-2 non-selectively, but some highly selective COX-2 inhibitors have
been produced.
Problems Associated with NSAIDs use in Orthopedic Surgery
• Bleeding, particularly during perioperative period, when combined with
warfarin or low molecular weight heparin.
• Risk of epidural hematoma* (epidural-outer side of the dura mater [(a
tough, fibrous membrane forming the outer covering of the central nervous
system.)] with spinal anesthesia.
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• Cumulative GI effects when combined with other medications.

• Enhanced renal toxicity particularly with dehydration, which may occur
postoperatively.
Which are the nonselective COX-2 drugs?

All the conventional NSAID’s like Aspirin, Ibuprofen, Diclofenac, Piroxicam, or
Indomethacin inhibits both COX-1 & COX-2 thus provides powerful anti-
inflammatory and analgesic action.
Which are the selective COX 2 enzyme inhibitors?

The examples are Nimesulide, Meloxicam, Celecoxib, Rofecoxib & Valdecoxib
etc. These NSAID’s selectively inhibit COX-2 enzyme and do not inhibit COX -1
enzyme.
They can be further be classified into two categories.
1. Preferential COX-2 Inhibitors: Nimesulide, Meloxicam (Meloxicam &
Nimesulide may have some COX-1 inhibition, Hence such drugs are NOT
COX specific)
2. Highly Selective COX-2 Inhibitors: Rofecoxib, Celecoxib, Valdecoxib
etc.
What are the advantages of inhibiting COX-2 enzymes?

As discussed earlier, COX-1 is needed for maintaining the function of several
tissues like stomach, kidneys and platelets. If a drug blocks both COX-1 and
COX-2, it will achieve anti-inflammatory effects along with a higher percentage of
gastrointestinal side effects. If only COX-2 is blocked by a drug, it will achieve
anti-inflammatory effects with much lesser risks of gastrointestinal side effects.
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What is the role of COX-2 enzymes in kidneys and stomach?

In Kidneys
Both COX-1 and COX-2 are required in small amounts in the kidneys. COX-1 is
needed to form useful prostaglandins to maintain renal blood flow and GFR
(glomerular filtration rate). Similarly, COX-2 is required to form useful
prostaglandins to maintain the sodium and water excretion from the kidneys. If a
drug blocks both COX-1 and COX-2 enzymes for a long time, it can have harmful
effects on the kidneys. However, a drug that blocks only COX-2 will have lesser
renal side effects.
In Stomach
COX-1 is needed to form prostaglandins that maintain gastric mucosal blood
flow, mucosal cell integrity and mucus formation. These functions are essential to
prevent gastric erosions and gastric ulcers. Drugs that block COX-1 and COX-2
will therefore carry a higher risk of causing
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gastric ulcers (breech in the continuity of the mucosal layer of the stomach). In
fact, such NSAIDs are a leading cause of upper gastrointestinal ulcerations and
bleeding complications. On the same lines, a drug that specifically blocks only
COX-2 will have very small risk of gastrointestinal side effects, as it does not
interfere with COX-1 functions in the stomach and duodenum.
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PYREXIA
What is Pyrexia?
Pyrexia means fever. Fever is a natural response of the body that helps in
fighting off foreign substances, such as microorganisms (e.g bacteria, and virus),
toxins, etc.
How is the normal temperature of the body controlled?

Body temperature is set by the thermoregulatory center, located in an area in the
brain called hypothalamus. Body temperature is not constant all day, but actually
is lowest at 6 A.M. and highest around 4-6 P.M. In addition, temperature varies in
different regions of the body; for example, rectal and urine temperatures are
about one degree Fahrenheit higher than oral temperature and rectal
temperature is higher than urine.
It is also important to realize that certain normal conditions can effect body
temperature, such as pregnancy, food ingestion, age, and certain hormonal
changes.
What are the substances, which bring about change in body temperature?
Substances that cause fever are known as “pyrogens.” There are two types of
pyrogens; exogenous and endogenous.
• Those that originate outside the body, such as bacterial toxins, are called
“exogenous” pyrogens.
• Pyrogens formed by the body’s own cells in response to an outside
stimulus (such as a bacterial toxin) are called “endogenous” pyrogens.
Researchers have discovered that there are several “endogenous” pyrogens.

These are made up of small groups of amino acids, the building blocks of
proteins. These natural pyrogens have other functions in addition to inducing
fever; they have been named “cytokines”.
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How do these pyrogens produce fever?

The production of fever is a very complex process; somehow, these cytokines
cause the thermoregulatory center in the hypothalamus to reset the normal
temperature level. The body’s initial response is to conserve heat by
vasoconstriction, a process in which blood vessels narrow and prevent heat loss
from the skin and elsewhere. This alone will raise temperature by two to three
degrees. Certain behavioral activities also occur, such as adding more clothes,
seeking a warmer environment, etc. If the hypothalamus requires more heat,
then shivering occurs.
What are the effects of raised body temperature on body?

Fever is a body defense mechanism. It has been shown that one of the effects of
temperature increase is to slow bacterial growth. However, fever also has some
downsides; the body’s metabolic rate is increased and with it, oxygen
consumption. This can have a devastating effect on those with poor circulation.
In addition, fever can lead to seizures in the very young children (febrile
convulsions).
What is Pyrexia of Unknown Origin (PUO)?

Pyrexia of unknown origin has been defined as temperature greater than 101°F
(38.3°C), for at least three weeks, and inability to find a cause after one week of
basic investigations in hospital.
There are many possible causes of FUO; generally though, a diagnosis can be
found. About 10% of patients will wind up without a definite cause, and about the
same percentage have “factitious fevers” (either self induced or no fever at all).
Within the past decade, a revision has been proposed that categorizes FUO into
classic, hospital acquired FUO, FUO associated with low white blood counts, and
HIV associated FUO (AIDS related).
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Which are the common ailments which produce fever?

Some general symptoms tend to occur along with fever; these are called
constitutional symptoms and consist of myalgias (muscle aches), chills, and
headache.
The most frequent cause of FUO is still infection, though the percentage has
decreased in recent years.
Tuberculosis remains an important cause, especially when it occurs outside the
lungs. Others are typhoid fever, paratyphois fever, viral infections, UTI (Urinary
Tract Infection), respiratory tract infections etc. Allergies to medications can also
cause prolonged fever; sometimes patients will have other symptoms suggesting
an allergic reaction, such as a rash.
What are the steps to reach a Diagnosis for fever?

Usually the first step is to search for an infectious cause.
• Skin and other screening tests for diseases such as tuberculosis, and
examination of blood, urine, and stool, are generally indicated.
• Antibody levels to a number of infectious agents can be measured; if
these are rising, they may point to an active infection.
• Various x-ray studies are also of value.
• In addition to the above mentioned examinations, ultrasound, computed
tomography scan (CT scan) and magnetic resonance imaging (MRI)
scans are now available.
• Furthermore, new studies using radioactive materials (nuclear medicine),
can detect areas of infection and inflammation previously almost
impossible to find, even with surgery.
• Biopsies of any suspicious areas found on an x-ray exam can be
performed. Evidence of infection, tumor or other diseases can be found in
this way.
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What is Typhoid fever and paratyphoid fever?

• Typhoid fever (also known as enteric fever) is caused by an infection with
the bacterium Salmonella typhi, which is only found in humans and may
lead to serious illness.
• When the bacterium passes down to the bowel, it penetrates through the
intestinal mucosa (lining) to the underlying tissue. If the immune system is
unable to stop the infection here, the bacterium will multiply and then
spread to the bloodstream.
• Paratyphoid fever is caused by Salmonella paratyphi, a similar and
generally milder disease.
What are the symptoms of typhoid fever?

The incubation period (period between the entry of bacteria in the body and
manifestation of the symptoms of the disease) is 10 to 20 days.
In the mild disease, the bacterium is eliminated very early in the course of the
disease and there are perhaps only mild symptoms. It is possible to become a
healthy carrier of infection.
There are two phases of classic typhoid fever:
• 1st phase: the patient’s temperature rises gradually to 40ºC and the
general condition becomes very poor with bouts of sweating, no appetite,
coughing and headache and Constipation. Children often vomit and have
diarrhoea. The first phase lasts a week and towards the end the patient
shows increasing listlessness and clouding of consciousness.
• 2nd phase: in the second to third weeks of the disease, symptoms of
intestinal infection are manifested and the fever remains very high and the
pulse becomes weak and rapid. In the third week the constipation is
replaced by severe pea-soup-like diarrhoea. The faeces may also contain
blood. It is not until the fourth or fifth week that the fever drops and the
general condition slowly improves.
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Complications
Intestinal perforation or profuse bleeding from the intestinal mucosa may occur if
typhoid fever is left untreated.
How is Typhoid fever treated?

Treatment requires antibiotics and loss of fluid and salt is treated with fluid
therapy as appropriate.
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GLOSSARY
• Pain: A symptom of some physical hurt or disorder.
• Fever: A rise in the temperature of the body; frequently a symptom of

infection.
• Inflammation: A response of body tissues to injury or irritation;

characterized by pain, swelling, redness and heat.
• Prostaglandins: A class of naturally occurring chemicals that are made in

many tissues of the body. They (among other chemicals) contribute to
proper functioning of the stomach and intestinal lining, the platelets, and
the kidneys.
• Arthritis: Inflammation of the joints.
• Osteoarthritis: Also called OSTEOARTHROSIS, OR DEGENERATIVE

JOINT DISEASE, a disorder of the joints, characterized by progressive
deterioration of the articular cartilage. It is the most common joint disease,
affecting more than 80 percent of those who reach the age of 70. Although
its suffix indicates otherwise, osteoarthritis is not characterized by
excessive joint inflammation, as is the case with rheumatoid arthritis. The
disease may be asymptomatic, especially in the early years of its onset.
As it progresses, however, pain, stiffness, and a limitation in movement
may develop. Common sites of discomfort are the vertebrae, knees, and
hips—joints that bear much of the weight of the body.
• Rheumatoid arthritis: An inflammatory disease that involves the lining of

the joint (synovium). The inflammation often affects the joints of the hands
and the feet and tends to occur equally on both sides of the body.
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• Cervical spondylitis: Degenerative process of the spine in the neck. A

combination of disc deterioration and osteoarthritis.
• Ankylosing spondylitis: A type of arthritis that affects the spine.
• Tendonitis: Inflammation of a tendon.
• Tendon: Tough tissue that connects a muscle with a bone.
• Fibrositis: Pain arising from damaged tendons or muscles.
• Myositis: Inflammation of a muscle.
• Bursitis: Inflammation of a bursa.
• Bursa: A sac filled with fluid located between a bone and a tendon or
muscle.
• Capsulitis: Inflammation of the capsule (cover) of the joint, if you can’t

move your shoulder around like you used to, you could have adhesive
capsulitis When it hurts to move your shoulder or you don’t have as much
movement in your shoulder as before, your shoulder may become
“frozen.” Because of this, doctors sometimes refer to this problem as
“frozen shoulder.”
• Tonsillitis: An inflammation of the tonsil.
• Pharyngitis: Inflammation of the pharynx; sore throat.
• Otitis: Inflammation of the ear.
• Otitis media: Inflammation of the middle ear.
• Otitis externa: Inflammation of the external ear.
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• Sprains: An injury to a ligament when the joint is carried through a range

of motion greater than normal, but without dislocation or fracture.
• Strains: Injury to a muscle (often caused by overuse); results in swelling

and pain.
• Alveolar abscess or apical abscess: An apical abscess of a tooth is

characterized by rapid onset, acute pain, and tenderness of the tooth to
touch, pus formation, and swelling of tissues in a later stage.
• Periodontitis: Inflammation of the supporting structures of the tooth,

including the gum, the periodontal ligament, and the jawbone.
• Maxillofacial: Relating to the upper jaw and face (particularly with

reference to specialized surgery of the maxilla); “maxillofacial surgery”.
• Dysmenorrhoea: Difficult or painful menstruation (e.g., cramps).
87
MICROBIOLOGY
What is Microbiology?
Microbiology is a science / study of microorganisms.
What is a Microorganism?
Microorganisms are a group of several distinct classes of living beings, which can
not be seen with naked eyes and can only be seen under the microscope.
Types of Microorganisms
1. Bacteria
2. Viruses
3. Protozoa
4. Fungi
What are Bacteria?

Bacteria are microorganisms, which lack nucleus, nuclear membrane,
mitochondria and several other cell organelles.
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Fig. 1: Structure of a Bacterial cell
Certain terms to understand the Bacterial anatomy

• Capsule - a protein & carbohydrate outer wall of the bacteria
• Pili (fimbriae) - a fine hair like structure, seem to mediate bacterial
conjugation (union of two unicellular organisms during sexual
reproduction.)
• Ribosomes - submicroscopic structure and is useful to receive genetic
information and functions to synthesize protein from amino acids.
• DNA - (deoxyribonucleic acid) contains chromosomes and genetic
materials.
• Flagella - a whiplike locomotory organ, makes the bacteria motile.
• Mesosome - a coiled membranous body, it functions in cellular respiration
and cell division.
• Cytoplasmic membrane - membrane covering the cytoplasm.
• Peptidoglycan - a compound containing amino acids (or peptides) &
sugar.
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• Plasmids - circular genetic material present outside the chromosomes

(DNA) also reffered as extrachromosomal genetic material.
What is the classification of bacteria according to shapes?
Bacteria exist in different shapes and sizes, and are accordingly classified.
Fig. 2: Shapes of bacteria

Classification of Bacteria based on their shapes
1. Cocci are rounded or oval bacteria. E.g Staphylococcus aureus,
Streptococcus pyogenes.
2. Bacilli (bacillus meaning rod) are rod shaped. e.g.Clostridium welchi,
Clostridium tetani.
Other bacteria are Vibrio (comma shaped), Spirilla (rigid spiral forms),
Spirochaetes (coil shaped), Actinomycetes (filamentous forms), Mycoplasma (do
not contain cell wall)
What is Gram staining?
90
Bacteria are transparent and colourless and therefore almost invisible. Therefore,
certain dyes (acidic and basic) are used to stain the bacteria so that their
morphology can be studied.
The two most widely used stains are:

a) Gram’s Stain.
The Gram stain differentiates bacteria into two broad groups, Gram- positive
bacteria are those that retain the stain and appearing violet or blue, and Gram -
negative bacteria, which appear red or pink.
b) Ziehl-Neelsen Stain.
This staining technique is used to identify Acid -fast bacteria known to cause
Tuberculosis and Leprosy e.g. Mycobacterium tuberculosis and Mycobacterium
leprae.
How are bacteria classified based on gram staining?

Organisms can be classified as:
Table 1: Classification of bacteria as per gram staining
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Gram (+)ve
Staphylococcus on the s
Aureus Nasoph
Staphylococcus On skin
Epidermis
Gram (+)veOn skin
Streptococcus
Pyogenes In fema
Corenybacterium Mainly i
Diptheriae predom
Nasoph
Sreptococcus in Naso
Clostridium
Pneumoniaewelchi Large in 92
Gram (-)ve
Neisseria meningitidis Nasoph
Neisseria gonorrhoeae- urinary

Gram (-)ve
E.coli Large in
Klebsiella intestin
Salmonella Intestin
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Gram (-)ve
Haemophilus ducreyi Vagina
How the bacteria are classified on the basis of oxygen
Brodetella
requirement?
Respira
Microorganisms may be divided into several groups with respect to their
requirement of oxygen.
• Strictly Aerobic: require the presence of oxygen for their growth, e.g.
Vibrio cholerae.
• Strictly Anaerobic: require the absence of oxygen for their growth, e.g.
Bacteroides fragilis, Clostridia.
• Facultative Anaerobes: are ordinarily aerobic, but can grow also in the
Pseudomonas Man, wa
absence of oxygen, though less abundantly, e.g. Staphylococcus aureus.
Aeruginosa
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AEROBES
Staphylococcus Aureus  P
 Staphylococcus Epidermis  S
 Streptococcus Pyogenes  S
 Sreptococcus Pneumoniae
V
ANAEROBES
 Corenybacterium Diptheriae

 B
 Neisseria meningitidis
 P
 Klebsiella
A
 Clostridium
 E.coli welchi
 M
 Clostridium botulinum
What are atypical bacteria?
Atypical bacteria do not contain a cell wall. Thus, they can assume multiple t
shapes including round, pear shaped and even filamentous.
 Clostridium tetani
E.g. Legionella pneumophila, Mycoplasma pneumoniae or hominis, Chlamydia  M
pneumoniae or trachomatis
 Clostridium difficile
What are the methods for Identification of Bacteria?
 Haemophilus influenzae
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 Haemophilus ducreyi
1. Smear test Bacteria are stained using different (acidic and basic) dyes to
differentially identify them.
2. Culture: Culture helps to isolate and grow the micro-organisms on
suitable growth media. It usually takes about 24 to 48 hours for these
colonies to become visible.
3. Test for Biochemical Properties: e.g. Sugar fermentation test, Methyl
red test, Urease test etc. These tests are done to confirm the identification
of bacteria.
What is the process of protein synthesis in Bacteria?
Which are the steps of bacterial protein synthesis?

Step 1 : DNA polymerase replicates DNA strand
Step 2 : RNA polymerase attaches to DNA and begins to transcribe mRNA.
Step 3 : Ribosome subunits attach to mRNA 30S & 50S
Step 4 : Formation of 70S ribosome
Step 5 : With the help of tRNA leads to the growth of polypeptide chain
Step 6 : After completion of polypeptide chain RNA polymerase & mRNA is
released
Step 7 : Ribosome subunits 30S & 50S separates from mRNA & completed
polypeptide chain is released from mRNA
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INFECTIONS AND ANTIBACTERIALS
What are Infections?

The lodging and multiplication of a parasite in or on the tissue of a living host
constitutes infection. It does not invariably result in disease.
The development of infectious disease takes place in five stages.
1. Infection: Introduction of microorganisms into the tissues.
2. Incubation: Period in which bacteria multiply without causing signs or
symptoms of disease.
3. Prodrome: Phase in which non-specific signs and symptoms of disease
begin to appear.
4. Clinical Illness: Period in which characteristic signs and symptoms of the
disease begin to be specific and identifiable.
5. Resolution: Period in which host’s defense mechanisms overcome and
eliminate bacteria from the tissues, and the host recovers.
Which are the terms used for various Infections?

1. Primary infection: Initial infection or infection for the first time with a
parasite in a host.
2. Reinfection: Subsequent infections by the same parasite after initiating the
infection in the host.
3. Secondary infection: When in a host whose resistance is lowered by a
pre-existing disease, a new parasite sets up an infection (usually
complicates the disease).
4. Cross infection: When in a patient already suffering from a disease, a new
infection is set up from another host or another external source.
5. Nosocomial infection: Cross infection occurring in hospitals.
6. Iatrogenic infection: Physician induced infections resulting from
investigative, therapeutic or other procedures.
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7. Subclinical infection: This is one where clinical effects are not apparent or
presence of a disease without manifesting symptoms; may be an early
stage in the evolution of a disease. (synonym - Inapparent infections.)
8. Atypical infection: This is one where the typical or characteristic clinical
manifestations of the particular infectious disease are not apparent.
9. Latent infection: Some parasites, following infection, may remain in the
tissues in a latent or hidden form and produce a disease when the host
resistance is lowered (Opportunistic infection).
Pathogens most lik

specific organs and
Newborn Infants :
 E .coli
 Listeria
monocytogenes
 Staph.aureus
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Pathogens most like

specific organs and
Adults :
 E .coli
 Staph.aureus
Pathogens most
 Strep.pneumoniae
like
specific organs
 Bacteroides
and
 Strep.pyogenes
Skin infection :
 Staph.epidermidis
 Staph.aureus
 Neisseria gonorrhoea
 Sterp.pyogenes
 Candida albicans
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 Neisseria meningitidis
Pathogens most like

specific organs and
Lungs :
 Mycoplasma pneumo
 Sterp.pneumoniae
Pathogens
 H .influenzaemost like
 Bacteroids
specific organs
 Staph.aureus
and
 Klebsiella
Urinary tractpneumoph
 Legionella :
 E .coli
 Chlamydia pneumoni
 Rickettsia
 Staph.aureus
 Myco.tuberculosis
Neisseria gonorrh
100

 Pneumocystis carini
Respiratory Tract Inf
Upper Respiratory T
- Sinusitis, pharyngitis
URTI
Lower Respiratory T
- AECB, Tuberculosis
Sinusitis
Inflammation of sinu
101
URTI
Pharyngitis - is an inflammat
Tonsillitis - is an inflamma
the back of the mouth/top o
Lower
Otitis Respiratory
media - is an inflammT
Causative organism :
Haemophilus influen
Tuberculosis - it is
Streptococcus pneum
Mycobacterium tuberculo
Bronchitis - it is an infl 102

ACEB - Acute Exace
Symptoms - Increased
thickness, increased sput
and breathlessness.
Pneumonia
Causative organisms
Is an Streptococcus
infection of pnth
can be causedpneu
Mycoplasma b
viruses, fungi etc.
Moraxella catarrh
Causative agents
Chlamydia :
pneum 103
H. influenza
Urinary Tract Infectio
Upper urinary tract

Pyelonephritis - inflamm
Nephritis - inflammation
Lower urinary tract
Gynaecological infec
Ureteritis - inflammatio
Cystitis - inflammation
Prostatitis - inflammatio
Pelvic inflammator
Urethritis - inflammatio
This refers to infection t
Causative organism
involve endometrium and
E.coli in 80%
Cervicitis, cases, ProteS
Endometritis,
104
Skin and soft Tissue
These occurs due to

Cellulitis - Staphylococ
Erysepales - S.pyogen
Bone and Joint Infec
Folliculitis - S.aureus, P
Osteomyelitis - It isse
Carbuncle - is deep a
Furuncle - is a type
Septic arthritis - It of
is a
Impetigo - superficial p
inflammation.
105
GI Tract Infections
Enteric fever - caused

Salmonella paraty
Shigellosis - caused by
Cholangitis - Inflamma
Cholecystitis - Inflamm
Peritonitis - It is an intra
peritonium causa
E.coli, enterobact
106
SKIN AND SOFT TISSUE INFECTIONS
Acne
Topical benzoyl peroxide (Acnidazil, Benoxyl, Panoxyl, Quinoderm), tretinoin
(Retin-A, Airol) or topical clindamycin. Systemic doxycycline and/or isotretinoin
(Roaccutane) should be considered for severely inflamed or cystic cases.
Bite wounds
Pasteurella multocida (cats and dogs), Eikenella corrodens (humans),
Staphylococcus aureus, Streptococcus spp., and/or oral anaerobes may be
involved.
Amoxycillin/clavulanate OR ampicillin PLUS cloxacillin OR cefoxitin are
appropriate empirical treatment and the duration should be clinically determined.
Doses:
• Ampicillin 500 mg 6 hourly (75 - 100 mg/kg/day in children)
• Amoxycillin-clavulanate 500 mg 8 hourly (13.3 mg/kg 8 hourly in children)
• Cloxacillin 1 - 2 gram 6 hourly (50 - 100 mg/kg/day in children)
• Cefoxitin 1 - 2 g 8 hourly (80 - 160 mg/kg/day in children)
Breast abscess/Mastitis: Inflammation of the breast

Lactating : Usually due to Staphylococcus aureus: cloxacillin is first choice.
Nonlactating: Anaerobes and/or Staphylococcus aureus: amoxycillin-clavu-
lanate is recommended.
Erysipelas: Is a contagious disease of the skin & sub cutaneous tissue due to
infection with S.pyogenes with redness & swelling of affected areas
,constitutional symptoms & sometimes vesicular & bullous lesions. Usually due to
Streptococcus pyogenes. Treat with benzylpenicillin initially IV and continue
treatment with oral penicillin VK for 10 days.
Cellulitis:
107
Inflammation of the soft or connective tissue, in which a thin, watery exudate

spreads through the cleavage planes of interstitial & tissue spaces ; it may lead
to ulceration & abscess.
Usually due to Streptococcus pyogenes, but Staphylococcus aureus is often also
involved. When cellulitis is associated with an open wound, there is usually an
exudate that can be obtained for culture. In the setting of cellulitis with unbroken
skin, a needle aspiration from the advancing edge can sometimes yield a positive
diagnosis. Blood cultures are also of diagnostic value.
Treat with amoxycillin-clavulanate OR a 1st-generation cephalosporin
(cephalothin or cephalexin or cefazolin). In young children with facial cellulitis,
consider Haemophilus influenzae. In diabetics and debilitated patients, consider
Staphylococcus aureus, Enterobactericeae and anaerobes.
Erythrasma:
Caused by the bacterium Corynebacterium minutissimum. Treat with oral
erythromycin 250 mg 6 hourly. A 5-day course is usually sufficient but
occasionally 2 - 3 weeks treatment is required.
Furunculosis
Is the persistent sequential occurrence of furuncles over a period of weeks or
months or the simultaneous occurrence of a number of furuncles(a boil; a painful
nodule formed in the skin by circumscribed inflammation of corium(dermis) &
subcutaneous tissue enclosing a central slough or “core”; due to staphylococci
entering the skin through hair follicle.
Usually due to Staphylococcus aureus. No antibiotic therapy is necessary. The
treatment of choice is surgical drainage.
In most persons with recurrent furunculosis (boils), the nares and the perineum
are usually the sites of Staphylococcus aureus carriage. In such patients,
diabetes mellitus should be excluded.
Therapeutic regimes which are effective for recurrent furunculosis include:
108
Mupirocin ointment or cream applied topically to the nares, axillae, and perineum
for a 5 day period with or without one of the following oral antibiotics:
Oral clindamycin 150 mg daily (in adults) for a 3-month period
OR
Oral rifampicin 600 mg daily (in adults) for 7 - 10 days
OR
Oral cloxacillin 500 mg 6 hourly for 7 -10 days.
Necrotising cellulitis or fasciitis

Urgent surgical debridement in addition to broad spectrum antibiotics to cover
Enterobacteriaceae, anaerobes, Streptococcus spp., Staphylococcus aureus,
e.g. amoxycillin-clavulanate OR clindamycin PLUS amikacin, until culture results
become available.
Impetigo
Usual pathogens are Streptococcus pyogenes with or without Staphylococcus
aureus.
Treat with amoxycillin-clavulanate OR a 1st-generation-cephalosporin OR
penicillin (ampicillin) PLUS cloxacillin. Topical mupirocin also results in high rates
of cure.
Infected wounds
Treat according to the clinical condition , and the results of culture and sensitivity
tests from representative specimens. It is important to distinguish between
superficial wound colonization and true infection, as antimicrobial therapy is
generally not indicated for colonization.
The need for tetanus prophylaxis should be evaluated in the case of traumatic
wounds (see under bite wounds).
109
ANTIINFECTIVES/ ANTIBIOTICS / ANTIMICROBIAL AGENT
Chemical substances produced by one type of micro-organisms that are capable

of suppressing the growth/ killing the other microorganisms, are called antibiotics.
Natural antibiotics are those chemicals isolated from various species of
microorganisms. In many cases, synthetic analogues of natural agents have also
been developed; these drugs are referred to as Semi-synthetic antibiotics
(Substitution of a chemical group or moiety to the structure of the natural
anbiotic). Both natural and semi-synthetic antibiotics have anti-infective
properties, while antibacterials derived from chemical substances are referred as
Synthetic antibacterials.
How can the Anti -bacterial agents be classified?

Depending on their mechanism of action and concentration in the body, anti-
infectives may be classified as Bacteriostatic or Bactericidal.
Bacteriostatic agents inhibit the growth and reproduction of bacteria;
(e.g.Tetracyclines, Sulphonamides, etc.) Bactericidal agents, on the other hand,
actively destroy the pathogenic bacteria. (Beta-lactam antibiotics,
Aminoglycosides, etc).
• The distinction between bacteriostatic and bactericidal action is a relative
one; at high enough concentrations, most bacteriostatic agents can
become bactericidal. This is referred to as concentration-dependent killing.
• Some anti-infective agents are only bactericidal, if an organism is exposed
to them for prolonged periods of time, then this is referred to as time-
dependent killing.
Penicillins, cephalosporins, vancomycin, aminoglycosides, quinolones, and
polymyxins are generally considered bactericidal (ie, they kill bacteria).
Erythromycin, tetracyclines, chloramphenicol, clindamycin, clarithromycin,
azithromycin, and sulfonamides are generally bacteriostatic (ie, they slow
bacterial growth).
110
However, bactericidal drugs may be bacteriostatic against certain

microorganisms and vice versa.
Which are the parameters used to judge the activity of an

antibiotic?
Following are the important parameters:
• MIC (Minimum Inhibitory Concentration): This is minimum concentration of
the drug required to inhibit the growth of micro-organisms
o MIC90 means if it inhibits 90% of the strain of micro-organisms.
• MBC (Minimum Bacterial Concentration): This is minimum concentration
of the drug required to kill micro-organisms.
• PAE (Post Antibiotic Effect): The sustained antibacterial effect of an
antibiotic even after the drug levels fall below MIC for the bacteria.
• Spectrum of coverage: If the drug has activity against gram +ve, gram-ve
or atypical pathogens, it has wider spectrum of coverage as compared to
the one which has coverage against only one of them.
• Peak serum concentration: the highest concentration of the drug achieved
with standard dosage of the drugs.
• Tissue concentration: It signifies the concentration of the drug which
reaches the tissues, It signifies the ability of an antibiotic to combat the
intracellular pathogens.
How are antibacterials classified on the basis of the mechanism

of action?
In most common pharmacologic classification systems, anti-infective agents with
a similar chemical structure and /or similar mechanism of action are usually
grouped together.
There are five main mechanisms of anti-infective action:
1. Interference with bacterial cell wall synthesis
111
2. Interference with genetic replication (e.g., DNA gyrase)

3. Interference with bacterial protein synthesis
4. Interference with bacterial folic acid synthesis
5. Destruction of bacterial cell membrane/ or by increasing the cell
membrane permeability
Fig. 3: Action of various classes of antimicrobials
Mechanism of action of anti-infectives with examples

1. Agents that inhibit synthesis of bacterial cell wall e.g Penicillins,
Cephalosporins, (Glycopeptides-Vancomycin), Bacitracin, etc.
2. Agents that act directly on the cell membrane of the microorganism,
affecting permeability and leading to leakage of intracellular compounds
e.g Polymyxin, Colistimethane (Colistin), etc.
112
3. Agents that affect the function of 30S or 50S ribosomal subunits to cause
a reversible inhibition of protein synthesis e.g Chloramphenicol,
Tetracycline, Erythromycin, etc.
4. Agents that bind to the 30S ribosomal subunit and alter protein synthesis,
which eventually leads to cell death e.g Aminoglycosides (Streptomycin,
Gentamicin, Tobramycin, Amikacin etc.)
5. Agents that affect nucleic acid metabolism and interfere with DNA / RNA
synthesis. e.g Rifampicin, Quinolones (Ciprofloxacin, Norfloxacin,
Ofloxacin, Sparfloxacin, Levofloxacin etc.)
6. Agents that block specific metabolic steps (bacterial folic acid synthesis),
that are essential to microorganisms- e.g Sulfonamides, Trimethoprim etc.
Which are the main classes of antibiotics?

ß -Lactam antibiotics
The ß-lactam antibiotics can be classified into several groups according to their
structural characteristics, but their unique structural feature is the presence of the
four-membered ß-lactam (2-azetidinone) ring.
Penicillins, monobactams, carbapenems, imipenems, and cephalosporins are
known chemically as beta-lactam antibiotics because as part of their chemical
structure they contain what is know as a beta-lactam ring.
The beta-lactam antibiotics exert their effect by interfering with the structural
crosslinking of peptidoglycans in bacterial cell walls. Because many of these
drugs are well absorbed after oral administration, they are clinically useful in the
outpatient setting.
113
Fig. 4: Basic structure of penicillin, cephalosporin, imipenem, and clavulanate.

“R” represents sites where different chemical side chains attach, depending on
the particular antibiotic.
Penicillins
The penicillins are a large group of bactericidal antibiotics, all of which have a 6-
aminopenicillanic acid nucleus. Their antibacterial action seems to reside in their
ability to inhibit metabolic functions vital to bacterial cell wall synthesis and to
activate enzymes that destroy the cell wall. Thus, penicillins affect only actively
multiplying bacteria.
Among the structural analogs of the ß-lactam antibiotics the group of ß-
lactamase enzyme inhibitors.
ß-Lactamases are bacterial enzymes that catalyze the hydrolysis of the ß-lactam
ring, thus, they inactivate the antibiotics. The ß-lactamase inhibitors are weak
antibiotics per se, but they protect a real antibiotical agent from the bacterial
hydrolysis. Therefore they are used in combination. E.g. Amoxycillin with
sulbactam.
114
Cephalosporins
They also belong to B lactam antibiotics. They are classified into generations on
the basis of general features of antimicrobial activity (Table).
1. The first generation cephalosporins have good activity against gram
positive bacteria and relatively modest activity against gram negative
bacteria.
2. The second generation cephalosporins have somewhat increased activity
against gram negative bacteria.
3. The third generation cephalosporins less active against gram positive
bacteria as compared to first generation agents but are much more active
against enterobacteriacae, including B lactamase producing strains.
Cefoparazone and ceftazidime are also active against Pseudomonas.
4. The fourth generation cephalosporins have an extended spectrum of
activity compared to third generation agents and show activity against
aerobic gram negative bacilli resistant to third generation cephalosporins
Table 2: Generation of Cephalosporins
115
Pharmacology
The cephalosporins are bactericidal drugs with both gram-positive and gram-
negative activity. They inhibit bacterial cell wall synthesis in a way similar to the
penicillins.
Macrolides
The macrolides are a group of drugs (typically antibiotics) whose activity stems
from the presence of a macrolide ring, a large lactone ring to which one or more
deoxy sugars, usually cladinose and desosamine, are attached. The lactone ring
can be either 14, 15 or 16-membered.
Members
The most commonly-prescribed macrolide antibiotics are:
1. Erythromycin
2. Clarithromycin
3. Azithromycin
4. Roxithromycin
Uses
Macrolides are used to treat infections such as respiratory tract infections and
soft tissue infections.
Spectrum of activity
The antimicrobial spectrum of macrolides is slightly wider than that of penicillin.
Beta-hemolytic streptococci, pneumococci, staphylococci and enterococci are
usually susceptible to macrolides. Unlike penicillin, macrolides have shown
effective against mycoplasma, mycobacteria, and chlamydia.
Mechanism of action
The mechanism of action of the macrolides is inhibition of bacterial protein
synthesis by binding reversibly to the subunit 50S of the bacterial ribosome,
116
thereby inhibiting translocation of peptidyl¬tRNA. This action is mainly

bacteriostatic, but can also be bactericidal in high concentrations.
Macrolides tend to accumulate within leucocytes, and are therefore actually
transported into the site of infection
Quinolones and Fluoroquinolones

The first quinolone, nalidixic acid, was introduced in the 1960s. The next one,
norfloxacin, the first clinical fluoroquinolone, came in 1986.
Quinolones are composed of a bicyclic aromatic core — a dual-ring chemical
structure.
Fluoroquinolones
Fluoroquinolones are synthetic quinolone derivatives that have a fluorine atom in
the 6 position. The addition of the fluorine atom improves potency; enhances
antimicrobial activity; and alters pharmacokinetic properties, which provide
tremendous therapeutic advantages over nalidixic acid.
Table 3:
117
Mechanism of Action
DNA gyrase and topoisomerase IV are required for bacterial DNA replication.
Fluoroquinolones inhibit these enzymes thereby inhibit the DNA replication.
DNA gyrase enzyme is responsible for introducing and removing DNA supercoils
and for unlinking (decatenating) interlocked DNA circles.This action proceeds
118
ahead of the actively moving replication fork. DNA gyrase safeguards against the
occurrence of replication-induced structural changes before advancement of the
replication fork.
Topoisomerase IV acts in a manner similar to that of DNA gyrase. The major
actions of topoisomerase IV are removal of DNA supercoils and separation of
newly built daughter DNA after replication is complete. These actions occur
primarily behind the advancing replication fork.The pair of type II topoisomerases
thus work both before and behind the replication fork to provide a properly
supercoiled environment for DNA synthesis and to release newly replicated DNA.
Quinolones inhibit the action of DNA gyrase and topoisomerase IV and kill
bacteria by binding to these enzyme-DNA complexes, thereby disrupting DNA
replication
119
BACTERIAL RESISTANCE
What is Drug Resistance?

Drug resistance is a state of insensitivity or decreased sensitivity to drugs that
ordinarily cause growth inhibition or cell death.
What are the types of resistance?

Microorganisms show two types of resistance. Intrinsic resistance (i.e. the
microorganism is inherently insensitive to a drug. e.g.-bacteria responding to
antifungal agents) and Acquired resistance. (i.e .the microorganism acquires
resistance over a period of time.)
What are the mechanisms of drug resistance?

The mechanisms by which bacteria resist antibiotics reflect the mechanisms by
which antibiotics work.
The four general mechanisms of resistance center around a bacterium’s ability to
inactivate an antibiotic, reduce the intracellular concentration of the antibiotic,
modify the target site of the antibiotic, and eliminate the target site of the
antibiotic.
Which is the commonest mechanism of resistance?

The most common mechanism of resistance is the production of enzymes that
modify the antibiotic, rendering it inactive. Resistance to penicillin results largely
from the production of enzymes by bacteria known as ß-lactamases. These
enzymes hydrolyze the antibiotic’s ß-lactam ring, a structure essential for
antibiotic activity. Another enzyme-induced mechanism of resistance is
production of acetyltransferases—which are known to inhibit aminoglycosides,
antibiotics that are effective against gram-negative bacteria.
120
What are the implications of bacterial resistance?

• Repeated infections
• Increasing concentration of drug
• Longer duration of therapy
• Antibiotic failure
• Increased cost of therapy
• Increased morbidity
• Increased mortality
________________
121

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Fig. 1: Respiratory System

What is the Respiratory passage?

Larynx (voice box)

Where does gaseous exchange take place in the lungs?

What are URT and LRT?

What is the Physiology (function) of Respiration?

Fig 2: Internal respiration at the level of alveoli

How is the act of respiration regulated?

What is Respiratory Tract Fluid?

Which are the common Upper Respiratory Tract Disorders

Pharyngitis and Tonsillitis

What is Acute Bronchitis?

What is Chronic Bronchitis and Emphysema?

Chronic Bronchitis is a condition associated with prolonged exposure to

Emphysema is defined as enlargement of the air spaces distal to the terminal

What is Bronchial Asthma?

Acute Otitis Media

Fig 3: Ear Anatomy

Sign and Symptoms

What is the mechanism of Cough?

What are the types of cough?

What is the treatment of cough?

What are adrenergic receptors?

major types of adrenergic receptors: α1 α2 β1and β2. These receptors are

What is an Agonist, and what is an Antagonist?

What are Muscarinic receptors?

Which are the common Allergens?

What is the mechanism of allergy?

What are the symptoms of allergy in various organs?

Which are the commonly encountered allergies?

HISTAMINE AND ANTIHISTAMINES

Which are the various receptors of histamine?

What are Antihistamines?

Which are the various parts of gastrointestinal tract?

• Fig 1: The Gastrointestinal Tract

What is the process of digestion and how does it progress?

What are Peristaltic movements?

Fig. 2: Peristaltic movements in stomach

What is the anatomy of stomach?

Fig 3: Layers of gastric wall

What are the two sphincter mechanisms in the stomach?

Which are the specific sites in the stomach which produce

Fig. 4: The Gastric gland

How does regulation of acid secretion take place?

Fig. 5: Parietal cell with the receptor

How does stimulation of these receptors cause acid secretion?

What is the proton pump inside parietal cells?

Fig. 6: Steps of Acid release

What are the steps in the formation of hydrochloric acid?

Which are the factors required to maintain normal mucosal

What are Peptic ulcers?

What is Peptic Ulcer Disease (PUD)?

What are the commonest sites of ulcer formation?

Fig 7: Commonest positions for Peptic Ulcers

What are the causes of peptic ulcer?

Fig. 8: Peptic Ulcers

Which are the risk factors associated with the development of

What are the symptoms of peptic ulcers?

What are the complications of peptic ulcers?

• Iron deficiency anaemia

What is Helicobacter pylori?

Fig. 9: Helicobacter pylori