The respiratory system
The respiratory system
The respiratory system
Respiration is controlled by spontaneous
rhythmic discharges from R.C.
Many factors can affect the respiratory
center including :
Partial pressure of carbon dioxide
Partial pressure of oxygen
A moderate degree of voluntary control can
be superimposed on the automatic
regulation of breathing
Regulation of airway
muscle, blood vessels and
The parasympathetic nerves which mediates bronchial
constriction and mucus secretion through its action on M3
The sympathetic nerves which innervate blood vessels
(causing constriction) and glands (causing inhibition of its
secretion), with no sympathetic innervations of bronchial
Circulating adrenaline acts on β2-receptors in the alveoli
(relaxation), mast cells (inhibition of inflammatory mediators
release) and increase mucocilliary clearance.
The main neurotransmitter causing relaxation of airway smooth
muscles is the NANC inhibitory transmitter, though to be NO.
NANC excitatory transmitters are released from sensory fibers
when stimulated by inflammatory mediators and irritant
chemicals as substance P (which increase permeability and
mucus secretion) and neurokinin A (a potent spasmogen).
Irritant receptors (on vagal fibers in the
upper airway) and sensory nerve fibers (in
the lower airway) respond to exogenous
chemicals( e.g. ammonia, sulfur dioxide and
cigarette smoke), endogenous inflammatory
mediators and physical stimuli (e.g. cold air)
causing constriction of the bronchi and
mucus secretion through A.Ch. release in the
upper airway and release of excitatory
transmitters in the lower airway.
DISORDERS OF THE
It is a condition of recurrent reversible
bronchial obstruction leading to:
shortness of breath
Etiology of bronchial asthma
Externsic factors (mainly in
children -Allergic asthma ):
Pollen grains ,house dust,
cockroach detritus and
Cigarette smoke by the
Internsic factors (mainly in
Viral infection in respiratory
and mucosal inflammation
Exercise (water and heat
lose from airway
Drug induced (e.g.) NSAID especially aspirin.
The development of allergic
Upon exposure of genetically sensitive individuals to allergens,
this will cause an
Immediate phase of inflammation:
Stimulation of Th2-lymphocytes
cytokines that promote:
-differentiation and activation of eosinophiles.
-IgE production and release.
-expression of IgE receptors on mast cells and eosinophils.
The allergen interact with mast cell-fixed IgE
several spasmogen as :histamine, leukotrienes, prostaglandin and
Also mast cells release many chemotaxins and chemokines which
attract more WBCs.
The role of T lymphocytes in
The late phase of inflammation
This response occurs at a variable time after
exposure to the stimulus and includes:
Hypersecretion of mucus
Bronchospasm by the released
Different phases of asthmatic
Diagnosis of bronchial asthma
Patient usually suffers from cough with
difficulty in breathing out (dyspnoea) and
Full history of the patient (genetic
Lung function tests (after allergen
challenge) e.g. forced expiratory volume
Drugs used in treatment of
These medications relieve
the symptoms of asthma by
relaxing the muscle bands
that tighten around the
airways. This action rapidly
opens the airways, letting
more air come in and out of
the lungs. As a result,
Bronchodilators also help
clear mucus from the lungs.
As the airways open, the
mucus moves more freely
and can be coughed out
This is the most important
type of therapy for most
people with asthma because
these drugs prevent asthma
attacks on an ongoing basis.
These drugs reduce swelling
and mucus production in the
airways. As a result, airways
are less sensitive and less
likely to react to antigen.
They are first line drugs in treatment of asthma , they are used
by inhalation or IV( in status asthmaticus).
-Dilate the bronchi by direct action on β2-receptors.
-They inhibit mediators release from mast cells.
-They may increase mucus clearance by an action on cilia.
Short-acting beta 2-agonists :
are also called "quick acting," "reliever," or "rescue" medications because
they relieve asthma symptoms very quickly by opening the airways. These
inhalers are the best for treating sudden and severe or new asthma symptoms.
They work within 30 minutes and last four to six hours. They are also the
medications to use 15-20 minutes before exercise to prevent exercise-induced
E.g.:salbutamol and terbutaline
bambuterol (pro-drug of terbutaline).
Long-acting forms of beta 2-agonist :
are used to provide control -- NOT QUICK RELIEF -- of asthma. These drugs
take longer to begin to work, but their benefits last longer, even up to 12 hours.
They are used twice a day in conjunction with anti-inflammatory inhalers to
maintain open airways for long term-control.
E.g.salmeterol, formoterol, reprotelol (long- acting).
Side effects of β2-agonists
Side effects of beta 2-agonists include:
Nervous or shaky feeling
Overexcitement or hyperactivity
Increased heart rate
Trouble sleeping (rare)
They are second line drugs, they are used orally or intravenously.
It is a bronchodilator that is used to control asthma. It is
available as an oral (pill and liquid) or intravenous (slow IV
loading dose followed by infusion in acute attack) form.
Mechanisms of action:
-Inhibition of phosphodiestrase enzyme
-Competitive antagonism with adenosine at adenosine
-Improve diaphragmatic contraction.
Side effects of theophyline
Side effects include:
Nausea and/or vomiting
Nervous feeling, alertness ,tremor and interfere with sleep (CNS stimulant)
As it has narrow therapeutic index, regular blood analysis should be don
(especially if taken in high oral dose or when used IV in status asthmaticus)
These symptoms may be a sign of having taken too much medication,or due to
other certain medications, such as antibiotics containing erythromycin, oral
contraceptives and ulcer medicine (inhibitors of P450).
Seizure medicine as phenytoin,carbamazepine, Phenobarbital, antibiotics as
rifampicin and smoking can also interfere with the way theophylline works
(inducers of P450).
Also, other medical conditions as some diseases and illnesses can change
how the body responds to theophylline.
Muscarinic receptor antagonist
It is used to control asthma and is not a rescue or quickrelief drug. It is available in both a metered-dose inhaler
and a nebulizer solution. For asthma it works best when
used with a short-acting beta 2-agonist inhaler. It is a not
a quick-relief medication. It isn't commonly used alone
to treat asthma.
Side effects are minor; dry throat is the most common. If
the medication gets in the eyes, it may cause blurred
vision for a short period of time. It is not recommended
for elderly patients and glaucoma patients
- They are used orally
-These drugs competitively block leukotriene
-They are useful in aspirin- and exercise-induced
-They have a bronchodilator effect that is additive with
β2-agonist ,so used as add-on therapy for mild and
-E.g.: zafirlukast and montelukast.
-Side effects include:
GIT- disturbances (Nausea and/or vomiting).
Anti-inflammatory drugs are some of the most important treatment
options for people with asthma. They prevent asthma attacks and
work by reducing swelling and mucus production in the airway.
Inhaled corticosteroids are the most effective medications to reduce
airway inflammation and mucus production. The use of these
medicines leads to:
Better asthma control
Reduced need for hospitalization
Inhaled steroids prevent symptoms, they do not relieve symptoms.
E.g.: fluticasone propionate
Mechanism of action of
- Decrease the formation of Th2 cytokines.
- Inhibit the generation of both LTs and PGs by
inhibiting phospholipase enzyme (decrease
- Decrease the formation of LTB (chemotaxin) and
platelet-activating factor reduce antigen-induced
influx of eosinophils into lung).
- Upregulate β -receptors.
- Vasoconstricting effect( edema).
- Decrease the release of inflammatory mediators
from mast cells.
Inhaled corticosteroids have very few side
effects, especially at lower doses. It is rare, but if
you are taking higher doses, candidiasis (fungal
infection in the mouth) may occur. Rinsing the
mouth, gargling after each use will help prevent
such side effects. It is also easily treated with an
anti-fungal (e.g. nystatin) mouthwash.
Inhaled steroids are safe to give to both adults
Oral (and Intravenous)
Systemic corticosteroids are used to treat severe asthma episodes.
These drugs are used with other medications to either control
sudden and severe asthma attacks or to treat long-term, hard-tocontrol asthma.
Systemic steroids include:
Side effects of systemic steroids tend to occur after years of use and
include: acne, weight gain, mood or behavior changes, upset
stomach, bone loss, eye changes, and slowing of growth. These
side effects rarely occur with short-term use, as is used for an acute
asthma episode .
Mast Cell Stabilizers
Mechanism of action
This is inhaled asthma medication that work by preventing the release of
irritating and inflammatory substances from immune cells called mast cells.
They effectively prevent asthma symptoms, especially in children with allergies
and asthma and in exercise-induced asthma.
It also depress the exaggerated neuronal reflexes which are caused by
stimulation of irritant receptors or sensory fibers.
This drug need to be taken two to four times a day, and take three to four
weeks to start working (prophylacting drug).
This medication is very safe and have few side effects. Upper airway irritation is
the main S.E. Also, hypersensitivity reactions as urticaria may occur.
Stopping the Asthma Attack
These medicines are used to provide prompt relief of asthma attack
symptoms (cough, chest tightness and wheezing -- all signs of
Short acting beta-agonists (bronchodilators that are the drug of
choice to relieve asthma attacks and prevent exercise-induced
asthma symptoms) .
Anticholinergics (bronchodilators used in addition to short-acting
beta-agonists when needed).
Systemic corticosteroids (an anti-inflammatory drug used in an
emergency to get rapid control of the disease while initiating other
treatments and to speed recovery)
Long Term Control Medications:
Treating the Inflammation
Research has shown that reducing and preventing
further inflammation is the key to prevent asthma
attacks, hospitalizations and death from asthma.
Long-term control medications are taken daily over
an extended period of time to achieve and maintain
control of persistent asthma (asthma that causes
symptoms more than twice a week and frequent
attacks that affect activity).
The most effective long-term control medications are
those that stop airway inflammation (antiinflammatory drugs), but there are others that are
often used along with anti-inflammatory drugs to
enhance their effect.
Long Term Control Medications:
Treating the Inflammation
Long-term control medications include:
Corticosteroids (The inhaled form is the antiinflammatory drug of choice for persistent asthma).
Mast cell stabilizers (anti-inflammatory drugs).
Long acting beta-agonists (bronchodilators often
used along with an anti-inflammatory drug) .
Theophylline (a bronchodilator used along with an
anti-inflammatory drug to prevent nighttime
Chronic obstructive pulmonary
COPD is a group of lung diseases that
reduce the ability of the lungs to
oxygenate the blood.
Emphysema and chronic bronchitis are the
main diseases that make up COPD.
What is chronic bronchitis?
Chronic bronchitis is inflammation and irritation
of the airways of the bronchial tubes ,which is
characterized by thickening of the muscular wall
of the large airways and an increase in size and
activity of mucous glands.
This leads to airway narrowing and blockage by
thick, tenacious secretions result in productive
cough that is present for a period of 3 months in
each of 2 consecutive years .
The symptoms include:
-Mucus production (sputum)
-Shortness of breath
-fever due to infection)
-and chest pain.
Pathogenesis of Bronchitis
1-Susceptible individual exposed to trigger (e.g.
cigarette smoke) initiate an inflammatory processes
and several mediators are released as well as
increased mucus secretion.
2-Risk of infection increase.
3-In sever cases ,mucus plug the lung
difficulty in expiration
elasticity of alveoli decrease (+infection)
destruction of alveoli walls
Emphysema develops over many years.
It is an inflammation (edema) which is
usually induced by cigarette smoke.
The tiny air sacs within the lungs (alveoli)
are gradually destroyed.
As a result, the alveoli are not able to pick
up enough oxygen (more and more short
Pathogenesis of emphysema
The exposure of a susceptible individual to noxious particles and gases
(Cigarette smoke as well as other gases and particles)
The predominant inflammatory cell is the neutrophil ,macrophages and Tlymphocytes are increased in the various parts of the lungs, and several
mediators are released, including leukotriene B4, interleukin 8, and TNF α
leading to sever inflammatory process and edema.
Altered protease/antiprotease balance, at least in individuals with severe
deficiency of alpha1-antitrypsin, has been shown to predispose to
emphysema. Individuals with severe deficiency of alpha1-antitrypsin may
develop emphysema at an early age (fourth decade), in contrast to the
"usual" emphysema, which typically begins in the sixth decade.
Pathogenesis of emphysema
What does the alpha1 antitrypsin
do in the body?
Alpha-1 antitrypsin is a major protein in the
blood. It is produced mainly in the liver cells. It
protects the lung by blocking the effects of a
powerful enzyme called elastase.
Elastase is normally carried in white blood cells
and protects the delicate tissue of the lung by
killing bacteria and neutralizing tiny particles
inhaled into the lung.
Alpha-1 antitrypsin inactivates elastase once it
has finished its job. Without alpha1 antitrypsin,
elastase can destroy the air sacs of the lung.
Symptoms of emphysema
Initial symptoms include:
- Chronic coughing, which may be worse upon awakening.
- Increased production of mucus (which is actually a symptom of chronic
- Shortness of breath.
- Fatigue easily even with little physical exercise (stair climbing, walking).
As the disease progresses:
-Shortness of breath may be present at rest.
-Some people with emphysema develop body changes; their chest begins to
take on a "barrel-like" appearance as the lungs compensate for the loss of
functioning tissue by expanding.
-Others develop a bluish color of the lips and nail beds, resulting from
chronically low levels of oxygen in the blood.
-Some people with emphysema will develop heart failure that may lead to
swelling in the lower extremities and increased fluid in the lungs.
Etiology of COPD :
1-The most important cause is tobacco smoke.
2- It can also develop after exposure to chemicals
or air pollution.
3-Deficiency of alpha1-antitrypsin, has been
shown to predispose to emphysema.
4-Bronchitis is also can be caused by infection with
a virus (less commonly with a bacteria or
To diagnose COPD :
Detailed medical history
including family history of lung
Breathing tests and X-rays
Special blood tests used for
diagnosis of inherited
emphysema. The test
measures the concentration of
alpha-1 antitrypsin in the
Bronchodilators include ß-adrenergic agonists, anticholinergics, and
Corticosteroids: used along with bronchodilators.
Prophylactic immunization with the influenza vaccine yearly and with
the 23-polyvalent pneumococcal vaccine every 5-10 years is
Mucolytic drugs (eg, ambroxol, erdosteine, carbocysteine, iodinated
glycerol, etc) are beneficial and are recommended.
In the specific case of alpha 1-antitrypsin deficiency, intravenous
augmentation therapy with pooled human plasma antiprotease can
raise serum levels of alpha 1-antitrypsin above a protective threshold
In addition to medicines, the management of COPD includes:
Exercise and a healthy lifestyle
Avoidance of infection
Giving Up Smoking
Giving up smoking and avoiding secondhand smoke is very
important. Smoking can accelerate or speed the development of the
disease and shorten the lifespan.
Lung transplants may be an option for people severely affected by
Coughing is the body's way of removing foreign material or mucus from the lungs and upper
airway passages or of reacting to an irritated airway.. A cough is only a symptom, not a disease,
and often the importance of your cough can be determined only when other symptoms are
There are many causes of a productive cough, such as:
Viral illnesses: It is normal to have a productive cough when you have a common cold.
An infection :of the lungs or upper airway passages can cause a cough. A productive cough may
be a symptom of pneumonia, bronchitis, sinusitis, or tuberculosis.
Chronic lung disease: A productive cough could be a sign that a disease such as chronic
obstructive pulmonary disease (COPD) is getting worse.
Stomach acid backing up into the esophagus : This type of coughing may be a symptom of
gastroesophageal reflux disease (GERD) and may awaken you from sleep.
Nasal discharge: draining down the back of the throat (postnasal drip syndrome).
Smoking: or other tobacco use. Here, productive coughs is often a sign of lung damage or
Drugs used for treatment of cough
-Less addiction liability
-Effective cough suppressant
-Decrease secretions in the bronchioles
-S.E.: Constipating effect & cilliary clearance
-It is a synthetic narcotic analgesic
-Its antitussive effect = that of codeine
-Less Constipating effect & less inhibition on cilliary clearance