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PBL COPD
1)

Mechanics of Respiration
Normal-> tengok PBL pneumothorax
Abnormal ???????

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2)

Histology of Respiratory Tract

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Tengok Lecture Notes and Practical

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3)

How sputum is produce and colour changes

The main function of the respiratory system is to draw air into the lungs to allow
the exchange of gases with blood circulating to the lungs. This blood supplies the
cells of the body with oxygen and removes the waste products of metabolism.
Tissues of the respiratory tract are thin and delicate, and become thinnest at the
surfaces of the aveoli, where gaseous exchange occurs. The body has a number of
mechanisms which protect these tissues and ensure that debris and bacteria do not
reach them.
Tiny hairs called cilia trap large pieces of debris and waft them out of the airways;
the reflexes of sneezing and coughing help to expel particles from the respiratory
system and the production of mucus keeps the tissues moist and helps to trap
small particles of foreign matter.
Mucus production in the airways is normal. Without it, airways become dry and
malfunction. But sometimes the mucus is produced in excess and changes in
nature. This results in the urge to cough and expectorate this mucus as sputum.
Sputum expectoration is not normal and there is always an underlying
pathological cause.

Mucus

Mucus is secreted from two distinct areas within the lung tissue. In the surface
epithelium, which is part of the tissue lining of the airways, there are mucus-producing
cells called goblet cells. The connective tissue layer beneath the mucosal epithelium
contains seromucous glands which also produce mucus.
The respiratory tract produce about two litres of mucus a day from these glands (Martini,
2003), and this is composed of water, carbohydrates, proteins and lipids. The high water
content helps to humidify the passing inspired air. Mucus contains glycoproteins (or
mucins) as well as proteins derived from plasma, and products of cell death such as
DNA.
Mucus is sticky and this helps to trap dust particles, bacteria and other inhaled debris.
Mucus also contains natural antibiotics, which help to destroy bacteria - the epithelial
cells secrete a substance called defensis. Mucus also contains lysozyme, which is an
antibacterial enzyme.

Movement of mucus
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Cilia in the nose move the mucus formed there towards the throat where it is swallowed
and digested in the stomach. In cold weather, this process slows and the mucus
sometimes gathers in the nose and drips or dribbles out - a winter runny nose.
Particles larger than 4mm in diameter usually become trapped in mucus in the nose and
rarely get any further down the airways. The nasal mucosa has many sensory nerve
endings and large particles irritate these nerves, stimulating a sneeze - a violent burst of
air - which expels the particles along with mucus.
Further down the airways, cilia in the trachea and bronchi also waft the mucus towards
the pharynx to be swallowed. This movement, against the force of gravity, is sometimes
called the mucus escalator. Normally, this upward movement is not noticeable, except
when we clear our throats. However, if larger quantities of mucus build up, the cough
receptors may be stimulated and air and mucus will be forcibly expelled from the
trachea.
Moving down the airway, the mucosal epithelium gets thinner and changes in nature.
There are only a few cilia and no mucus-producing cells in the bronchioles, so any
airborne debris is removed by macrophages in the alveoli or coughed out.

Sputum production

Irritation of the respiratory system causes both inflammation of the air passages and a
notable increase in mucus secretion. A person may become conscious of swallowing the
mucus or the inflammation may trigger a coughing reflex so that they expectorate
these secretions as sputum.
It seems that the inflammation of the mucosa is responsible for sputum production rather
than any of the other changes that occur in diseased lung tissue (Jeffrey Maestrelli et al,
2001).
Expectorated sputum contains lower respiratory tract secretions, as well as secretions
from the nose, mouth and pharynx, and cellular debris and micro-organisms (Rubin,
2002). In some disease processes, the sputum changes in nature and colour.

Airway disease and sputum

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Sputum production is associated with many lung disease processes and sputum may
become infected, stained with blood or contain abnormal cells.

Smoking - Smoking has many effects on the airways. Inhaled smoke destroys the cilia
that are important for moving mucus to the throat for swallowing. As a result, mucus
accumulates in the bronchioles and irritates the sensitive tissues there, causing a cough.
Coughing is vital as it is the only way smokers can remove mucus from their lungs and
keep the airways clean (Rubin, 2002). This is characterised by the smokers cough.

Constant coughing to clear the sputum has an effect on the smooth muscle of the
bronchioles which becomes hypertrophied (enlarged or overgrown). This in turn causes
more mucus glands to develop.

Smoking also causes hyperplasia (excessive cell division and growth) of the mucusproducing goblet cells (Maestrelli et al, 2001). Because of the constant irritation, more
mucus is produced and collects in the alveoli, which can become overburdened and
collapse.
Another effect of smoking is the development of emphysema when the alveoli expand,
the capillary blood supply deteriorates and gaseous exchange is reduced. Smoking makes
other lung diseases worse and is a major cause of lung, and many other, cancers.
Smoking cessation improves lung health - bronchial tubes relax and the work of
breathing becomes easier, and cilia begin to regrow within a few months, so mucus and
debris can be cleared without the need for constant coughing. Also, the risk of cancers
reduces over time.

Sputum assessment

Sputum can provide a number of clues about a patients health. It is difficult to assess the
amount of sputum produced in a day (Law, 2000) but there are many terms to describe it mucoid, purulent, mucopurulent, frothy, viscous or bloodstained.

Mucus colour also varies considerably from white or opaque to grey, orange, green,
brown or, occasionally, black. Yellow, orange or green sputum is commonly associated
with bacterial infection. The more neutrophils that are present in sputum, the greener it
becomes and patients may require treatment with antibiotics.

However, people with asthma often have neutrophils in their sputum - the sputum may be
coloured but is free from infection. Red sputum indicates the presence of blood and may
suggest tuberculosis or cancer.

http://www.nursingtimes.net/clinical-subjects/respiratory/the-physiology-of-mucus-andsputum-production-in-the-respiratory-system/205397.fullarticle

Meaning of Different Sputum Colors

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As mentioned under the Types of Sputum, the discharge is a combination of mucus produced in
the respiratory tract and saliva from the mouth. It also contains microorganisms, immune cells,
cellular debris, dust and possibly even blood components or whole blood (plasma and blood cells).
Depending on the quantity of these components and disease process, the sputum color may vary
between :

Clear

White

Gray

Yellow

Green

Brown

Pink

Red

Rust-colored

Black

Clear, White, Gray Sputum

Clear sputum is considered as normal, however, there are many conditions that may cause
excessive sputum production. A profuse amount of clear sputum should therefore be considered as
abnormal.

Pulmonary edema (fluid in the lungs) clear, white or pink frothy sputum

Viral respiratory tract infections clear to white (acute)

Chronic bronchitis (COPD) clear to gray

Asthma white to yellow (thick)

Yellow Sputum
Yellow colored sputum is due to the presence of white blood cells, particularly neutrophils and
eosinphils. These cells are often present in chronic inflammation, allergic and infectious causes. With
infections, it is often in the acute setting that yellow sputum is evident due to the presence of
live neutrophils. With allergic conditions, particularly airway hypersensitivity, the yellowish
sputum is due to the presence of eosinophils.

Acute bronchitis white to yellow

Acute pneumonia white to yellow

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Asthma white to yellow (thick)

Green Sputum
Green mucus is indicative of a long-standing, possibly chronic, infection. The color is a result of
the breakdown of neutrophils and the release of verdoperioxidase / myeloperioxidase, an enzyme
that is present within these cells. It may also be seen in long standing non-infectious inflammatory
conditions. With infections, the green sputum will be more purulent (large amounts of pus) while
in non-infectious inflammatory conditions, the green sputum will be more mucoid (large amounts
of mucus).

Pneumonia white, yellow or green

Lung abscess green, sudden accumulation of large amount of sputum if the

abscess ruptures

Chronic bronchitis clear, grey to green (infection)

Bronchiectasis, cystic fibrosis green

Brown and Black Sputum

Brown or black sputum is an indication of old blood and the color may be due to the
breakdown of red blood cells thereby releasing hemosiderin (from hemoglobin). Certain organic
and non-organic dusts may also cause a brown to black discoloration of the sputum.

Chronic bronchitis green, yellow, brown (infection)

Chronic pneumonia white, yellow, green to brown

Coal workers pneumoconiosis brown to black

Tuberculosis red to brown or black

Lung cancer red to brown to black

Red, Pink and Rust-Colored Sputum

Red sputum is usually an indication of whole blood that is more profuse than bleeding in pink
colored sputum. It may completely discolor the mucus or appear as streaks or spots. Pink
sputum is also a sign of bleeding but usually of smaller quantities that may stain or streak the
sputum. Rust colored sputum is also due to the bleeding although the clotting process may have
commenced and the red blood cells may have broken down.

Pneumococcal pneumonia rusty-red

Lung cancer pink to red (frothy) progressing to brown or black

Tuberculosis bright red streaks progressing to fully red sputum (hemoptysis)

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Pulmonary embolism bright red blood (acute)

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4)

Relationship between smoking and lung disease

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Cigarette smoke is divided into two phases: a tar phase and a gas phase. Cigarette
smoke that is drawn through the tobacco into an active smoker's mouth is known as
mainstream smoke. Sidestream cigarette smoke is the smoke emitted from the burning
ends of a cigarette.
Such changes include increased mucus production (as much as 7-fold); decreased
ciliary movement, beat frequency, and transport; increased WBC production and
movement to the airway lumen; and increased mucosal permeability to allergens,
associated with increased total and specific immunoglobulin E (IgE) levels and
increased blood eosinophil counts.
Smoking is associated with structural changes in the airways and pulmonary parenchyma,
including upper airway mucosal gland hypertrophy and hyperplasia. Changes have been
described in lung compliance and elasticity
Cigarette smoke contains many chemicals that interfere with the body's method of
filtering air and cleaning out the lungs. The smoke irritates the lungs and leads to
overproduction of mucus. It also paralyses the cilia - tiny hair-like structures that line
the airways and clean out dust and dirt. Paralysis of the cilia means mucus and toxic
substances accumulate, resulting in congestion of the lungs. This extra mucus means
smokers are more likely to suffer from chronic bronchitis and what is known as 'smoker's
cough'. As a result, mucus accumulates in the bronchioles and irritates the sensitive
tissues there, causing a cough. Coughing is vital as it is the only way smokers can
remove mucus from their lungs and keep the airways clean Constant coughing to clear
the sputum has an effect on the smooth muscle of the bronchioles which becomes
hypertrophied (enlarged or overgrown). This in turn causes more mucus glands to
develop.
Cigarette smoke is one of the best known triggers of asthma. When people suffer from
asthma their inflamed air passages, which are very sensitive, narrow when exposed to
cigarette smoke. This causes an asthma attack.
Long term exposure of the lungs to the irritants in tobacco smoke destroys the normal
lung structure. The elastic walls of the small airways within the lungs are broken down.
This reduces the amount of lung tissue available for the transfer of oxygen from the air to
the blood. This condition is called emphysema. Some degree of emphysema is found in
almost all people who are long-term smokers, however the severity will vary depending
on the amount of cigarettes smoked, and the number of years the individual smokes.

5)

What causes barrel chest

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6)
Differences between restrictive and obstructive lung
disease
Obstructive lung diseases (or airway diseases) are characterized by an increase in
resistance to airfolw due to partial or complete obstruction at any level from the trachea
and larger bronchi to the terminal and respiratory bronchioles. These are contrasted with
restrictive diseases, which are characterized by reduced expansion of lung parenchyma and
decreased total lung capacity.
The distinction between these chronic noninfectious diffuse pulmonary diseases is based
primarily on pulmonary function tests. In individuals with diffuse obstructive disorders,
pulmonary function tests show decreased maximal airflw rates during forced expiration, usually
expressed as the forced expiratory volume at 1 second (FEV1) over the forced ventilator capacity
(FVC). An FEV1/FVC ratio of less than 0.7 generally indicates airway obstruction.
Expiratory airflw obstruction may be caused by a variety of conditions (Table 15-3) that are
ideally distinguished by distinct pathologic changes and different mechanisms of airflw
obstruction. As discussed later, however, such neat distinctions are not always possible. In
contrast, restrictive diseases are associated with proportionate decreases in both total lung
capacity and FEV1, leading to normal FEV1/FVC ratio. Restrictive defects occur in two broad
kinds of conditions: (1) chest wall disorders (e.g., severe obesity, pleural diseases,
kyphoscoliosis, and neuromuscular diseases such as poliomyelitis) and (2) chronic interstitial
and infitrative diseases, such as pneumoconioses and interstitial firosis.

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7)
7)
7)
What is moderate obstructive pulmonary disease and how it
cause right ventricular hypertrophy
8)
Same
Cor pulmonale is defined as an alteration in the structure and function of the right
ventricle caused by a primary disorder of the respiratory system. Pulmonary hypertension
is the common link between lung dysfunction and the heart in cor pulmonale. Although
cor pulmonale commonly has a chronic and slowly progressive course, acute onset or
worsening cor pulmonale with life-threatening complications can occur.

Lung disorders cause pulmonary hypertension by several mechanisms:

Loss of capillary beds (eg, due to bullous changes in COPD or thrombosis in pulmonary
embolism)

Vasoconstriction caused by hypoxia, hypercapnia, or both

Increased alveolar pressure (eg, in COPD, during mechanical ventilation)

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Medial hypertrophy in arterioles (often a response to pulmonary hypertension due to

other mechanisms)

The pulmonary vasculature of patients with COPD associated PH is markedly abnormal and
shows increased intimal and medial thickening that cause luminal narrowing and vascular
obstruction of the small pulmonary arteries (Wright et al 1992). These vascular changes lead to
an increase in pulmonary vascular resistance (PVR) and elevation of pulmonary artery pressures
(PAP). PH leads to pressure overload of the right ventricle (RV). RV muscular hypertrophy
occurs in response to the increased pulmonary pressures (Dias et al 2002) and occurs in up to
40%70% of patients with COPD at autopsy (11,62). Hypertrophy is followed by contractile
dysfunction of the RV (Voelkel et al 2006). The contractile dysfunction leads to RV dilation, a
decrease in cardiac output, and an increase in right sided filling pressures (Voelkel et al 2006).
The dilation and pressure overload of the RV causes left ventricular (LV) diastolic dysfunction
(Louie et al 1995). Eventually, the ability of the RV to compensate is overwhelmed and RV
failure ensues

9) COPD

(Emphysema and Chronic Bronchitis) !!!!!

Intro

Common obstructive lung diseases include emphysema, chronic bronchitis,

asthma, and bronchiectasis.

Chronic obstructive pulmonary disease (COPD) is a group of lung diseases
characterized by increased airway resistance resulting from narrowing of the
lumen of the lower airways. When airway resistance increases, a larger pressure
gradient must be established to maintain even a normal airfow rate. For example,
if resistance is doubled by narowing of airway lumens, P must be doubled through
increased respiratory muscle exertion to induce the same flow rate of air in and
out of the lungs as a healthy person accomplishe during quiet breathing.
Accordingly, patients with COPD must work harder to breathe. Chronic

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obstructive pulmonary disease encompasses three chronic (long-term) diseases:

chronic bronchitis, asthma, and emphysema.

Emphysema and chronic bronchitis are often clinically grouped together and
referred as chronic obstructive pulmonary disease (COPD), sincethe majority of
patients have features of both, almost certainly because they share a major trigger
cigarette smoking
DIFFICULTY IN EXPIRING

When COPD of any type increases airway resistance, expiration is more diffiult than inspiration.
The smaller airways, lacking the cartilaginous rings that hold the larger airways open, are held
open by the same transmural pressure gradient that distends the alveoli. Expansion of the
thoracic cavity during inspiration indirectly dilates the airways even further than their expiratory
dimensions, like alveolar expansion, so airway resistance is lower during inspiration than during
expiration.
In a healthy individual, the airway resistance is always so low that the slight variation between
inspiration and expiration is not noticeable.

When airway resistance has substantially increased, however, as during an asthmatic attack,the
diference is quite noticeable. Thus, a person with asthma has more dif iulty expiring than
inspiring, giving rise to the characteristic wheeze as air is forced out through the narrowed
airways.
Normally the smaller airways stay open during quiet breathing and even during active expiration
when intrapleural pressure is elevated, as during exercise ( Figure 13-15a and b). In people
without chronic obstructive pulmonary disease, the smaller airways collapse and further outf ow
of air is halted only at very low lung volumes during maximal forced expiration ( Figure 1315c). Because of this airway collapse, the lungs can never be emptied completely.
By contrast, in people who have COPD, especially emphysema, the smaller airways may
routinely collapse during expiration, preventing further outf ow of air through these passageways
( Figure 13-15d). Because of the extra air trapped behind these collapsed airways, people with
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emphysema have enlarged lungs and tend to appear barrel-chested. Compared to normal, those
with pronounced emphysema suf er an ironic twist of having more air in the lungs but less gas
exchange (because of the loss of surface area resulting from the breakdown of alveolar walls)
and decreased ability to bring in fresh air (because the chest wall cannot expand as much from its
larger-than-normal resting position to reduce the intra-alveolar pressure enough to accomplish
adequate inspiration).

Pathophysio of COPD

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Chronic Bronchitis.

Chronic bronchitis is defied clinically as persistent cough with sputum production for at
least 3 months in at
least 2 consecutive years, in the absence of any other identifible cause.
Common in habitual smokers and inhabitants of smog-laden cities, chronic bronchitis is one end
of the spectrum of COPD, with emphysema being the other. Most patients lie somewhere in
between, having features of both.
When chronic bronchitis persists for years, it may accelerate decline in lung function, lead to cor
pulmonale and heart failure, or cause atypical metaplasia and dysplasia of the respiratory
epithelium, providing a rich soil for cancerous transformation.

Pathogenesis/ Causes.
The primary or initiating factor in the genesis of chronic bronchitis is exposure to noxious or
irritating inhaled substances such as tobacco smoke (90% of patients are smokers) and dust
from grain, cotton, andsilica. Many other inhaled irritants (for example, smog, industrial
pollutants, and solvents) can also result in chronic bronchitis.Viral and bacterial infections that
result in acute bronchitis may lead to chronic bronchitis if people have repeated bouts with
infectious agents. The principal pathologic features are inflammation of airways,
particularly small airways, and hypertrophy of large airway mucous glands, with increased
mucus secretion and accompanying mucus obstruction of airways

Mucus hypersecretion. The earliest feature of chronic bronchitis is hypersecretion of mucus in

the largeairways, associated with hypertrophy of the submucosal glands in the trachea and
bronchi. The basis for

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mucus hypersecretion is incompletely understood, but it appears to involve inflammatory

mediators such as histamine and IL-13.
With time, there is also a marked increase in goblet cells in small airwayssmall bronchi and
bronchiolesleading to excessive mucus production that contributes to airway obstruction. It is
thought that both the submucosal gland hypertrophy and the increase in goblet cells are
protective reactions against tobacco smoke or other pollutants (e.g., sulfur dioxide and nitrogen
dioxide).
Airway narrowing that leads to prolonged expiratory time produces hyperinflation.
Ventilation/perfusion relationships are altered with increased areas of low VV/QV ratios. These low
VV/QV mismatches are largely responsible for the more significant resting hypoxemia seen in
chronic bronchitis, compared with that seen in emphysema.
Inflmmation. Inhalants that induce chronic bronchitis cause cellular damage, eliciting both
acute and chronic inflmmatory responses involving neutrophils, lymphocytes, and macrophages.
Long-standing inflmmation and accompanying firosis involving small airways (small bronchi
and bronchioles, less than 2 to 3 mm in diameter) can also lead to chronic airway obstruction.
The airway mucosa is variably infiltrated with inflammatory cells, including polymorphonuclear
leukocytes and lymphocytes. Mucosal inflammation can substantially narrow the bronchial
lumen. As a consequence of the chronic inflammation, the normal ciliated pseudostratified
columnar epithelium is frequently replaced by patchy squamous metaplasia. In the absence of
normal ciliated bronchial epithelium, mucociliary clearance function is severely diminished or
completely abolished
Infection. Infection does not initiate chronic bronchitis, but is probably signifiant in
maintaining it and may be
critical in producing acute exacerbations. It should be recognized that cigarette smoke
predisposes to chronic bronchitis in several ways. Not only does it damage airway lining cells,
leading to chronic inflmmation, but it also interferes with the ciliary action of the respiratory
epithelium, preventing the clearance of mucus and increasing the risk of infection

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Sign and Symptoms/ Complication

The cardinal symptom of chronic bronchitis is a persistent cough productive of sparse sputum.
For many years no other respiratory functional impairmentis present, but eventually dyspnea on
exertion develops.
With the passage of time, and usually with continued smoking, other elements of COPD may
appear, includinghypercapnia, hypoxemia, and mild cyanosis (blue bloaters).
Differentiation of pure chronic bronchitis from that associated with emphysema can be made in
the classic case
(Table 15-4), but, as has been mentioned, many patients with COPD have both conditions.
Long-standing severe chronic bronchitis commonly leads to cor pulmonale and cardiac failure.
Death may also result from further impairment of respiratory function due to superimposed
acute infections. A collapsed lung (pneumothorax). COPD can damage the lung's structure
and allow air to leak into the chest cavity. Sleep problems because you are not getting enough
oxygen into your lungs.

Emphysema

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Emphysema is characterized by irreversible

enlargement of the airspaces distal to the terminal
bronchiole, accompanied by destruction of their walls
without obvious firosis. Small airway firosis (distinct from
chronic bronchitis) has recently been to shown to be
present in patientswith emphysema; it is a signifiant
contributor to airflwobstruction.
Emphysema is classifid according to its anatomic
distribution within the lobule. Recall that the lobule
is a cluster of acini, the terminal respiratory units. Basedon
the segments of the respiratory units that are involved,
emphysema is classifid into four major types: (1)
centriacinar, (2) panacinar, (3) paraseptal, and (4)
irregular. Of these,only the fist two cause clinically
signifiant airflw
obstruction (Fig. 15-6).

Types.
Centriacinar emphysema is the most common form, constituting more than 95% of clinically
signifiant cases.
Centriacinar (centrilobular) emphysema. In this type of emphysema the central or proximal
parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are
spared (Figs. 15-6B and 15-7A). Thus, both emphysematous and normal airspaces exist within
the same acinus and lobule. The lesions are more common and usually more severe in the upper
lobes, particularly in the apical segments. Inflmmation around bronchi and bronchioles is
common. In severe centriacinar emphysema, the distal acinus may also be involved, making
differentiation from panacinar emphysema diffiult. Centriacinar emphysema occurs
predominantly in heavy smokers, often in association with chronic bronchitis (COPD).
Panacinar (panlobular) emphysema. In this type, the acini are uniformly enlarged from the
level of the respiratory bronchiole to the terminal blind alveoli (Figs.15-6C and 15-7B). The prefi
pan refers to the entire acinus, not the entire lung. In contrast to centriacinar emphysema,
panacinar emphysema tends to occur more commonly in the lower zones and in the anterior

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margins of the lung, and it is usually most severe at the bases. This type of emphysema is
associated with 1-antitrypsin defiiency (Chapter 17).
Distal acinar (paraseptal) emphysema. In this type, the proximal portion of the acinus is
normal, and the distal part is predominantly involved. The emphysema is more striking adjacent
to the pleura, along the lobular connective tissue septa, and at the margins of the lobules. It
occurs adjacent to areas of firosis, scarring, or atelectasis and is usually more severe in the upper
half of the lungs. The characteristic fidings are of multiple, continuous, enlarged airspaces from
less than 0.5 cm to more than 2.0 cm in diameter, sometimes forming cystlike structures. This
type of emphysema probably underlies many cases of spontaneous pneumothorax in young
adults.
Airspace enlargement with firosis (irregular emphysema). Irregular emphysema, so named
because the
acinus is irregularly involved, is almost invariably associated with scarring. In most instances it
occurs in small
foci and is clinically insignificant.
Pathogenesis/ Causes.

Inhaled cigarette smoke and other noxious

particles cause lung damage and
inflmmation, which results in parenchymal
destruction (emphysema) and airway
disease (bronchiolitis and chronic
bronchitis).
The main cause of emphysema is long-term exposure to airborne irritants, including:
Tobacco smoke, Marijuana smoke, Air pollution, Manufacturing fumes
Rarely, emphysema is caused by an inherited deficiency of a protein that protects the elastic
structures in the lungs. It's called alpha-1-antitrypsin deficiency emphysema.
Factors that inflence the development of emphysema include the following (Fig. 15-8):
Inflmmatory mediators and leukocytes. A wide variety of mediators have been shown to be
increased in the
affected parts (including leukotriene B4, IL-8, TNF, and others) These mediators are released by
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resident epithelial cells and macrophages, and attract inflammatory cells from the circulation
(chemotactic factors), amplify
the inflmmatory process (proinflmmatory cytokines) and induce structural changes (growth
factors).
Protease-antiprotease imbalance. Several proteases are released from the inflmmatory cells
and epithelial
cells that break down connective tissue components. In patients who develop emphysema, there
is a relative defiiency of protective antiproteases, which in some instances has a genetic basis
(further discussed later). Emphysema is characterized by (1) collapse of the smaller airways and
(2) breakdown of alveolar walls. T is irreversible condition can arise in two dif erent ways. Most
commonly, emphysema results from excessive release of proteindigesting enzymes such as
trypsin from alveolar macrophages as a defense mechanism in response to chronic exposure to
inhaled cigarette smoke or other irritants. T e lungs are normally protected from damage by these
enzymes by 1-antitrypsin, a protein that inhibits trypsin. The lung is protected from elastolytic
damage by 1-protease inhibitor and 2-macroglobulin. Bronchial mucus inhibitor protects the
airways. Excessive secretion of these destructive enzymes in response to chronic irritation,
however, can overwhelm the protective capability of 1-antitrypsin so that these enzymes destroy
not only foreign materials but lung tissue as well. Loss of lung tissue leads to the breakdown of
alveolar walls and collapse of small airways, which characterize emphysema. The unprotected
lung tissue gradually disintegrates under the influence of even small amounts of macrophagereleased enzymes, in the absence of chronic exposure to inhaled irritants.
Oxidative stress. Substances in tobacco smoke, alveolar damage, and inflmmatory cells all
produce oxidants, which may beget more tissue damage and inflmmation.
The role of oxidants is supported by mouse models in which the NRF2 gene is inactivated. NRF2
encodes a transcription factor that serves as a sensor for oxidants in alveolar epithelial cells and
many other cells types. Intracellular oxidants activate NRF2, which upregulates the expression of
multiple genes that protect cells from oxidant damage. Mice without NRF2 are significantly
more sensitive to tobacco smoke than normal mice, and genetic variants in NRF2, NRF2
regulators, and NRF2 target genes are all associated with smoking-related lung disease in
humans
Infection. Although infection is not thought to play a role in the initiation of tissue destruction,
bacterial and/or
viral infections may exacerbate the associated inflmmation and chronic bronchitis.
The idea that proteases are important is based in part on the observation that patients with
a genetic defciency of the antiprotease 1-antitrypsin have a markedly enhanced tendency
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to develop pulmonary emphysema,which is compounded by smoking. About 1% of all

patients with emphysema have this defect. 1-antitrypsin, normally present in serum, tissue flids,
and macrophages, is a major inhibitor of proteases (particularly elastase) secreted by neutrophils
during inflmmation. 1-antitrypsin is encoded by the proteinase inhibitor (Pi) locus on
chromosome 14. The Pi locus is polymorphic, and approximately 0.012% of the US population
is homozygous for the Z allele, a genotype that is associated with markedly decreased serum
levels of 1-antitrypsin.
More than 80% of these individuals develop symptomatic panacinar emphysema, which occurs
at an earlier age and is of greater severity if the individual smokes. It is postulated that any injury
(e.g., that induced by smoking) that increases the activation and inflx of neutrophils into the lung
leads to local release of proteases, which in the absence of 1- antitrypsin activity result in
excessive digestion of elastic tissue and emphysema. Several other genetic variants have been
linked to risk of emphysema. Among these are variants associated with the nicotinic
acetylcholine receptor, which are hypothesized to inflence the addictiveness of tobacco smoke
and thus the behavior of smokers. Not surprisingly, the same variants are also linked to lung
cancer risk, emphasizing the importance of smoking in both of these diseases. A number of
factors contribute to airway obstruction in emphysema. Small airways are normally held open by
the elastic recoil of the lung parenchyma, and the loss of elastic tissue in the walls of alveoli that
surround respiratory bronchioles reduces radial traction and thus causes the respiratory
bronchioles to collapse during expiration. This leads to functional airflw obstruction despite the
absence
of mechanical obstruction

Sign and Symptoms/ Complication

Symptoms do not appear until at least one third of the functioning pulmonary parenchyma is
damaged. Dyspnea usually appears fist, beginning insidiously but progressing steadily. In
some patients, cough or wheezing is the chief complaint, easily confused with asthma. Cough
and expectoration are extremely variable and depend on the extent of the associated bronchitis.
Weight loss is common and can be so severe as to suggest an occult cancer. Classically, the
patient with severe emphysema is barrel-chested and dyspneic, with obviously prolonged
expiration, sits forward in a hunched-over
position, and breathes through pursed lips.
Impaired expiratory airflw, best measured through spirometry, is the key to diagnosis. In
individuals with severe emphysema, cough is often slight, overdistention is severe, diffusion
capacity is low, and blood gas values are relatively normal at rest. Such patients may

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overventilate and remain well oxygenated, and therefore are somewhat ingloriously designated
pink puffers (Table 15-4).
Development of cor pulmonale and eventually congestive heart failure, related to secondary
pulmonary hypertension, is associated with a poor prognosis. Death in most patients with
emphysema is due to (1) coronary artery disease, (2) respiratory failure, (3) right sided heart
failure, or (4) massive collapse of the lungs secondary to pneumothorax.

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Lab investigation

Lung function tests show evidence of airflow limitation The FEV1 : FVC ratio is
reduced. In many patients the airflow limitation is reversible to some extent (usually a
change in FEV1 of < 15%), and it can be difficult to distinguish between asthma and
COPD. Lung volumes may be normal or increased, and the gas transfer coefficient of
carbon monoxide is low when significant emphysema is present.

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Chest X-ray is often normal, even when the disease is advanced. The classic features are
overinflation of the lungs with low, flattened diaphragms, and sometimesthe presence of
large bullae. Blood vessels may be pruned with large proximal vessels and relatively
littleb lood visible in the peripheral lung fields.
High resolution CT scans are used, particularly to show emphysematous bullae.
Haemoglobin level and PCV can be elevated as a result of persistent hypoxaemia
(secondary polycythaemia, see p. 420). The CRP is raised.
Sputum examination is not useful in ordinary cases as Strep. pneumoniae and H.
influenzae are the only common organisms to produce acute exacerbations. Occasionally
Moraxella catarrhalis may cause infective exacerbations.
Electrocardiogram. In advanced cor pulmonale the P wave is taller (P pulmonale) and
there may be right bundle branch block (RSR complex) and the changes of right
ventricular hypertrophy (see p. 784)..
1-Antitrypsin levels and genotype, especially inpremature disease or non-smokers.

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Treatment and management

The goal of COPD management is to improve a patients functional status and quality of life by
preserving optimal lung function, improving symptoms, and preventing the recurrence of
exacerbations. Currently, no treatments aside from lung transplantation have been shown to
significantly improve lung function or decrease mortality.
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Once the diagnosis of COPD is established, it is important to educate the patient about the
disease and to encourage his or her active participation in therapy.

Smoking cessation continues to be the most important therapeutic intervention for

COPD. Most patients with COPD have a history of smoking or are currently smoking
tobacco products. Smoking intervention programs include self-help, group, health care
provider delivered,workplace, and community programs.

Drug therapy. This is used both for the short-term management of exacerbations and for
the long-term relief of symptoms and with an FEV1 of < 60% predicted. Many of the
drugs used are similar to those used in asthma (see p. 854).

Bronchodilators Many patients with mild COPD feel less breathless after inhaling a adrenergic agonist such as salbutamol (200 g every 46 hours). In more severe airway
limitation (moderate and severe COPD), a long-acting 2 agonist should be used, e.g.
formoterol 12 g powder inhaled twice daily or salmeterol 50 g twice daily. More
prolonged and greater bronchodilatation is achieved with antimuscarinic agents:
tiotropium (long-acting) (18 g daily), ipratropium (40 g four times daily) or oxitropium
(200 g twice daily). Tiotropium has been shown to improve function and quality of life
but the decline in FEV1 is unaffected.

Corticosteroids In symptomatic patients with moderate/severe COPD, a trial of

corticosteroids is always indicated, since a proportion of patients have a large,
unsuspected, reversible element to their disease and airway function may improve
considerably. Prednisolone 30 mg daily should be given for 2 weeks, with measurements
of lung function before and after the treatment period. Combination of a corticosteroid
with a long-acting 2 agonist has been shown in a trial to protect against a decline in lung
function but there was no reduction in overall mortality.
Antibiotics Prompt antibiotic treatment shortens exacerbations and should always be
given in acute episodes as it may prevent hospital admission and further lung damage.
Patients can be given a supply of antibiotics to keep at home to start as soon as their
sputum turns yellow or green

.Antimucolytic agents These reduce sputum viscosity and can reduce the number of
acute exacerbations. A 4-week trial of carbocisteine 2.25 g daily can be tried.

Diuretic therapy (see p. 657) This is necessary for all oedematous patients. Daily weight
should be recorded during acute inpatient episodes.

Oxygen therapy
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