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Diffuse lung disease:
1- obstructive disease or airway disease
limitation of airflow resulting from an increase resistance due to partial or complete obstruction at any level(trachearespiratory bronchiole)
2- restrictive diseas:
reduced expansion of lung parenchyma + decreased total lung capacity.
Chronic obstructive pulmonary disease(COPD)
Definition
Anatomic
sites
-shared symptoms : dyspnea , chronic/recurrent obstructive to air flow within the lung.
Bronchial asthma
Chronic bronchitis
emphysema
COPD characterized by:
Clinically-Persistent productive
Abnormal permanent
1.Recurrent,episodic disabling
cough for at least 3 months in at enlargement/dilatation of
attack of severe dyspnea
least 2 consecutive years
air spaces distal to the
2. coughing
terminal bronchioles
3. expiratory wheezing
+destruction of their walls.
triggered by sudden episodes of
*Overinflation=
bronchospasm.
enlargement of air spaces
without destruction of their
walls.
bronchus
Bronchus
bronchioles
Acinus (structure distal to
terminal bronchioles and
includes the respiratory
bronchioles, alveolar ducts
and alveoli)
bronchiectasis
Permanent abnormal dilatation
of small bronchi and
bronchioles due to destruction
of their muscle and elastic
supporting tissue resulting
from or associated with chronic
necrotizing infections.
Bronchus
bronchioles
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Etiology/
pathogen
esis
Bronchial asthma
Chronic bronchitis
1.atopy-genetic predisposition
to mast cell igE type1
hypersensitivity reaction
1. chronic irritation by inhaled
substances.
(*cigarrete smoking
-SO2, N02)
>Stimulates hypersecretion of
mucus,
> hypertrophy of mucous glands
in trachea and bronchi,
>bronchioles
goblet cells metaplasia,
bronchiolitis “small airway
disease”
2. acute & chronic airway
inflammation
3. bronchial
hyperresponsiveness to any
irritants.
emphysema
A. centriacinar and
panacinar emphysema
Destruction of alveolar wall
is primary event.
Theory: protease
antiprotease mechanism
-imbalance between
proteases (elastase) and
anti proteases(a1 anti
trpsin) in lung=> proteolytic
destruction of elastic
tissue=>emphysema.
Eg:
2. microbiologic infection.
1.smokers
>maintaining inflammation and
Smoke particles in small
may cause acute exacerbation.
bronchi and bronchioles:
> stimulate neutrophils and
Net result of excessive mucous
macrophages proteolytic
secretion and infection:
activity in lung.
-accumulation of mucopurelent
>inhibit a1 antitrypsin
discharge in lumen of bronchi
activity ending in
and bronchioles. And
destruction of proximal part
-bronchiolitis , destruction of
of acinus and development
their walls ending in fibrosis. This of centriacinar emphysema.
will lead to airway obstruction.
2. a1 antitrypsin
deficiency=>unchecked
elastic tissue destruction by
elastase
enzyme=>panacinar
emphysema.
Bronchiectasis
Predisposing factors:
1. Bronchial
obstruction(tumour, foreign
body, impacted mucus, chronic
bronchitis or atopic asthma).
2. hereditary or congenital
conditions(cystic fibrosis of
lung, ig deficiency, structural
abnormality of cilia such as in
immotile cilia syndrome)
3. necrotizing or suppurative
pneumonia.
Pathogenesis:
In presence of
1.obstruction and
2. chronic persistence
infection.
Either of them may come 1st.
1.obstruction=>air
resorbedfrom airways distal to
the obstruction=>atelectasis in
alveoli, elastic forces within the
lobe disappear=>relaxation and
dilatation of those airways that
are patent.
Clearing mechanism is impaired
in these dilated
airways=>2ndry infection.
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B. irregular and distal
acinar
2ndry to fibrosis of
adjacent lung parenchyma.
How?
1. scarring and fibrosis
resulting from healing of
granulamatous
lesion(tb,sarcoidosis)=>incr
ease elastic pull of adjacent
alveoli=>destruction of their
walls.
2. fibrosis=>distortion of
bronchial and bronchiolar
walls=>narrowing esp in
expiration=>air trapped in
alveoli=>further destruction
of their walls.
So, bronchial narrowing acts
as “one way
valve”(permitting entrance
of air in alveoli during
inspiration and preventing
its exit during expiration).
2. infection=>
-bronchial wall inflammation
and weakening leading to
increse its dilatation.
-may cause extensive
bronchiolar
damage=>endobronchiolar
obliteration=>
atelactasis distal to
obliteration+ bronchiectatic
dilatation around atelactatic
area.
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Types
Gross
Bronchial asthma
1~pathophysiology of asthma:
-extrinsic
-intrinsic
-mixed patterns
Chronic bronchitis
~clinically:
1. simple chronic bronchitis
2. chronic mucopurulent
bronchitis
3. chronic asthmatic
bronchitis
4. chronic obstructive
bronchitis
2~agents/events that trigger
bronchospasm:
-seasonal
-Exercise induced
-drug induced : aspirin-sensitive
asthma
-occupational:triggered by
fumes,organic and chemical
dust , gases and other chemicals
-asthmatic bronchitis in smokers
-Lungs are: voluminous due to
-Mucous membrane of larger
everinflation and air trapping.
airways is swollen , edematous ,
-Fill entire chest wall
hyperaemic and covered by
mucinous,mucopurelent or
Small and medium sized
purelent secretions.
bronchi:
-Occluded with thick , tough ,
-Smaller bronchi and bronchioles
tenacious mucus plugs formad
filled with same secretions.
of whorls of shed
epithelium(curschmann spirals)
and charcot leyden crystals
emphysema
Bronchiectasis
~anatomic distribution in
acinus:
1 .centriacinar (entrilobular)
emphysema
2. panacinar (panlobular)
emphysema
3.distal acinar (periacinar ,
paraseptal , superficial)
emphysema
4. irregular emphysema
Other types:
-compensatory emphysema
-senile emphysema
-intersitial emphysema.
Depends on types and
severity.
1.panacinar
Lungs-voluminous,
overlapping the heart and
hiding it.
Pulmonary tissuehypercrepitant(+++ air)
Emphysematous lobes-pale
due to compression of
blood vessels.
2. centriacinar
Macroscopic feature not
evident unless condition is
-May be Bilateral , unilateral ,
or segmental.
-Usually affect lower lobes
-Small bronchi and bronchioles
dilated(4× its normal sizes) and
can be traced to the pleural
surface.
-Dilatation- saccular, fusiform
,cylindroids , or cystic with
honey comb appearance.
-Lumen of dilated part filled
with suppurative, yellowish
green to hemorrhagic
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severe and advanced.
Upper 2/3 of lung more
affected.
Microsco
pic
1.Bronchi and bronchioles
obliterated by mucus
plug+whorls of shed
epithelium(curschmann spirals)
1. Chronic inflammation of
airways with cellular infiltrate
predominantly lymphocytes.
3. irregular and distal
*Presence of large apical
bullae:
-Subpleural
-Cyst like spaces
-Wall-thin and formed of
fibrous tissue.
-Contents-air
-Naked eye-translucent
1.Overdistension of alveoli.
exudates.
-Removal of exudates reveal an
edematous reddish green or
necrotic black ulcerated
mucosa. squamous metaplasia
can be seen.
1. Lining epitheliumdesquamation , ulceration , or
squamous metaplasia.
2.Complete destruction of
septal wall leaving only a
2. enlargement of mucous
strand of residual tissue
2. Lumen-obliterated with
2.Numerous eosinophils-charcot secreting glands of trachea and
with
mucopurulent exudates.
leyden crystals(made of protein large bronchi.
Very small compressed
of eosinophil membrane )
Reid index(ratio of mucous gland blood vessels appear as free 3. Wall- inflamed.
layer to the thickness of wall
floating island of tissue.
3.Airway remodeling:
between epithelium and
4. in more chronic cases-thickening of basement
cartilage) normally 0.4 but it
3. Respiratory bronchioleshealing by fibrosis occurs,
membrane of bronchial
increase in chronic bronchitis.
distorted, evidence of
associated with peribronchial
epithelium.
bronchitis and bronchiolitis fibrosis and atelactasis.
-edema and inflammatory
3. slight increase in goblet cells + may be present.
infiltrate(eosinophils, mast cells) loss of ciliated epithelial cells.
5. Severe cases-necrotizing
-Increase size of submucosal
Squamous metaplasia occurs and
reaction destroys the walls and
mucous glands.
ay be followed by dysplasia.
forms lung abscess.
-Hypertrophy of bronchial wall
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smooth muscle cells.
Clinical
features
-Attacks of dyspnea,
-Cough,
-Wheezing(a soft whistling
sound during expiration)
-Attacks are triggered by sudden
episode of bronchospasm
-Usually relieve spontaneously
or with
treatment(bronchodilators,
costicosteroids)
-In between attacks-patients
free from respiratory difficulty
but occasionally attacks are
severe, fail to respond to
therapy, persist for days or
weeks(“status asmathicus”)
4. chronoic bronchiolitis- goblet
cells metaplasia, inflammation,
fibrosis of wall, smooth muscle
hypertrophy, marked narrowing
of lumen and in severe cases
completely obliteration of
lumen.
5.hypersecretion
1.Simple chronic bronchitis
-Productive cough(mucous in
nature) , air flow not obstructed
2.Chronic mucopurulent
bronchitis
-Chronic cough+mucopurulent
sputum
3.Chronic asthmatic bronchitis
-Chronic cough , productive
sputum, intermittent episodes of
bronchial asthma.
4.Chronic obstructive bronchitis
Marked outflow obstruction.
-Dyspnea and chronic
cough=>barrel shaped
chest.
-Dyspnea and orthopnea in
severe cases.
-Cough with foul odour sputum
Hypoxaemia=>polycythemia esp in morning.
.
-Fever
-Clubbing of fingers
-Chronic
-Lung abscess , gangrene of
hypoxaemia=>pulmonary
lung, sometimes associated
vascular spasm, pulmonary with hemoptysis(destruction of
hypertension and cor
blood vessesl)
pulmonale.
-Emphysema, bronchopleural
fistula, and pyopneumothorax.
-Rupture of
-Metastatic brain abscess and
bullae=>pneumothorax=>
meningitis.
colllapse of lung.
-Squamous metaplasia=>sq cell
carcinoma.
-Amyloidosis( increase
proteinatious material in
intersitial spaces).
-Rarely cor pulmonale.
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Incidence
Bronchial asthma
Chronic bronchitis
emphysema
5% adults
7-10% children
Most frequent- middle aged men Ventillatory disability- 5th
esp in heavy smokers
decade of life but with air
pollution it occurs earlier.
Males>females. Esp heavy
smokers.
Bronchiectasis
Rarely primary disease of lung
but it develops as sequel to:
-persistent infection of lung
-or to previous obstructive
airway disease.
All ages and both sexes.
Genetic and familial
incidence.
complicati 1.Superadded
ons
infection=>chronic
bronchitis, bronchiectasis,
bronchopneumonia.
1. Precanacerous
conditions(squamous metaplasia
and dysplasia)=>bronchogenic
carcinoma.
2.obstruction=>emphysema,atel 2. emphysema in areas with
actasis
incomplete obstruction.
3. cor pulmonale
3. atelactasis in the areas where
obstruction is complete.
4. right side heart failure, cor
pulmonale.
5. death due to:
-recurrent bacterial infection
-respiratory failure
-right side heart failure.
1.Same to clinical pictures
above.
2. die due to:
-pulmonary failure with
respiratory acidosis
-hypoxia
-coma
-right side heart failure
Same as clinical features above.
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Types of emphysema
Affected part
Incidence
Associated with
Centriacinar
(centilobular)
Proximal or central parts of acini(respiratory
bronchioles),
Distal parts not affected.
Upper lobes particularly apical segments
Males esp
heavy
smokers.
Chronic bronchitis
Panacinar
(panlobular)
Acini uniformly dilated from terminal bronchioles to
terminal blind alveolar spaces.
Affects lower zones , anterior margins of lungs and
most severe in bases of lobes.
-Distal part is dominantly enlarged and destroyed.
-proximal part is normal.
-Occurs adjacent to pleura and at margins of lobules
along connective tissue septa and adjacent to areas
of fibrosis, scarring , or atelactasis.
Acinus irregularly involved
Distal acinar
(periacinar, paraseptal,
superficial)
Irregular
Walls of
emphymatous
spaces
-Contain large
amount of
pigmented alveolar
macrophages.
-Inflammation is
common around
bronchi and
bronchioles and in
septa
A1 antitrypsin
deficiency
Most
common
Scarring of lung.
Eg: tb, sarcoidosis.
Asymptomatic in
most cases.
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Restrictive lung disease
Definition: group of disease identified by a reduced total lung capacity while expiratory flow rate is normal or slightly
reduced.
May be due to:
1. extrapulmonary chest wall disorders, lungs are normal.
Eg: poliomyelitis, obesity, scoliosis, kyphosis etc.
2. parenchymal causes(lung itself).
Parenchymal restrictive lung diseases
*acute restrictive lung disease
*chronic interstitial (restrictive ) lung disease
There is: reduction in o2 diffusion capacity, lung compliance, and lung volume.
acute
Eg: ARDS-Acute respiratory distress syndrome(diffuse
alveolar damage)
types
-
Causes
Infection,Physical injury,
Inhaled irritants,Chemical injury,Trauma.
chronic
Definition: heterogenous group of disorders
characterized by diffuse and usually chronic
involvement of pulmonary connective tissue in
intersitium of alveolar walls.
They have similar clinical signs, symptoms, radiologic
alterations, pathologic changes.
~characteristic histologic features:
1.fibrosing
2.granulamatous –pneumoconiosis
3. eosinophilic
4. Smoking related
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pathogenesis
More than 50% of ARDS associated with:
Sepsis, diffuse pulmonary infection, gastric aspiration
,trauma including head injury.
Primary lesion:
-diffuse damage of endothelial cells of capillary,
Epithelial cells of alveoli.
Injury is mediated by neutrophils and macrophages.



morphology
Earliest common manifestation is alveolitis(
interstitial pneumonitis) characterized by
accumulation of inflammatory cells and immune
effector cells in alveolar wall and intersitium.
Release of chemical mediators lead to:
-injury of endothelial cells of capillaries and flat
epithelial cells of alveoli
-stimulates fibrosis.
Final result: end stage fibrotic lung aka “stiff
lung”:
-alveoli replaced by cystic spaces separated by
thick bands of connective tissue containing
inflammatory cells
“honey comb lung”
-function of alveolocapillary membrane is lost.
Consistent feature of all cases irrespective to causative
agents is diffuse alveolar damage.
Microscopically: distended alveolar ducts lined with a
hyaline membrane (protein rich fluid exudates +
remnants of necrotic epithelial cells.
Clinical
features and
complications
fate
Dyspnea, tachypnea, cyanosis without wheezing or any
evidence of airway obstruction.
x-ray- diffuse infiltration by small nodules , irregular
lines “ground glass shadow”
Severe hypoxia , respiratory failure associated with
pulmonary hypertension , cor pulmonale(right side
heart failure)
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Pneumoconiosis
Due to
anthracosis
silicosis
asbestosis
berylliosis
Carbon deposition in lung.
-Coal miners disease
Prolonged inhalation
of silica
=>scattered
interstitial
pneumonitis=>fibrosis
and formation of
grayish black silicotic
nodules
Prolonged
heavy
exposure to
asbestos.
*also lead to
bronchogenic
carcinoma of
lung,
mesothelioma
of pleura,
carcinoma of
larynx.
Low dose
exposure to
beryllium for
many
years=>non
caseating
granulmatous
lesions.=>heal
by fibrosis(xray: fine
nodular
densities)
Hypersensitivity
pneomonitis
Hypersensitivity
to inhaled ag in
form of organic
dust.
-non caseating
granulama
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BRONCHIAL ASTHMA
Initiated by
Triggered by
incidence
severity
Extrinsic (allergic ,atopic) bronchial
asthma.
Ig e type 1 hypersensitivity
reaction(atopy)
exposure to extrinsic antigen
Eg: environmental ag(pollens, animal
dander, dusts, foods etc)
-50% of cases of asthma is exrtinsic
-Starts in children and young adults
-Most of patients have family history
Less severe and easily managed.
Attacks diminish in later years
Drug
No drug hypersensitivity
hypersensitivity
Signs and
 Asthmatic attacks are often
symptoms
preceded by allergic rhinitis,
urticaria, or eczema
 Serum ig e levels are raised in
about 60% patients
complications
Rarely:
-development of chronic bronchitis.
-emphysema
Intrinsic(non allergic, non atopic)
bronchial asthma
Diverse non immune mechanisms
Ingestion of aspirin,
Respiratory tract infection esp viral ,
cold, inhaled irritants, stress and
exercise.
(inflammation causes hyperirritability
of bronchial tree through abnormal
autonomic regulation).
Starts in adult life.
No family history
Attacks increase in severity with
passage of time.
May develop(aspirin,penicillin)
No other associated allergy.
Serum ig e levels-normal.
Commonly:
-development of chronic bronchitis
-Emphysema.
Mixed pattern
Both extrinsic and intrinsic factors
operate together.
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Rebutlah 5 perkara sebelum dating 5 perkara:
1.
2.
3.
4.
5.
Masa muda sebelum tua
Masa Sihat sebelum sakit
Masa Kaya sebelum miskin
Masa Lapang sebelum sibuk
Masa hidup sebelum MATI.