2. Diffuse pulmonary diseases
OBSTRUCTIVE VERSUS RESTRICTIVE
PULMONARY DISEASES
Diffuse pulmonary diseases can be classified in two categories:
obstructive disease (airway disease):
limitation of airflow usually resulting from an increase in
resistance caused by partial or complete obstruction at
any level
restrictive disease:
characterized by reduced expansion of lung parenchyma
accompanied by decreased total lung capacity
3. OBSTRUCTIVE PULMONARY
DISEASES
Limitation of airflow results from increased airflow resistance at
the level of bronchial passages.
Cause : expiratory obstruction:
i – anatomic airway narrowing (asthma)
ii- Loss of elastic recoil (emphysema)
Result : Normal Total Lung Capacity ( TLC )
Normal Forced Vital Capacity ( FVC )
Decreased Forced Expiratory Volume (FEV)
↓ FEV1 / FVC
Emphysema, Chronic bronchitis, and Bronchiectasis
4. RESTRICTIVE PULMONARY
DISEASES
FVC is reduced & expiratory flow rate is normal or reduced.
The ratio of FEV1 to FVC is near normal.
The restrictive defect occurs in two general conditions:
chest wall disorders in the presence of normal lungs such as
severe obesity,
diseases of the pleura,
neuromuscular disorders (Guillain-Barré syndrome; affect
respiratory muscles)
acute or chronic interstitial lung diseases.
ARDS,
Chronic restrictive diseases such as
pneumoconioses
interstitial fibrosis of unknown etiology,
infiltrative conditions (e.g., sarcoidosis)
6. Emphysema
Permanent enlargement of the air spaces distal to the terminal
bronchioles with destruction of their wall, but without fibrosis.
The anatomic distribution is restricted to the acinus
It is usually coexist with chronic bronchitis (smokers)
Clinically grouped together under chronic obstructive
pulmonary disease (COPD)
The primarily irreversible airflow obstruction of COPD
distinguishes it from asthma
COPD affects more than 10% of the US adult population and is
the fourth leading cause of death
9. Emphysema: Clinical Course
Patients with emphysema
Progressive dyspnea, weight loss, barrel chest, prolonged
expiration (a hunched-over position).
Airspace enlargement is severe and diffusing capacity is low.
Dyspnea and hyperventilation are prominent, gas exchange
(oxygenation of hemoglobin) is adequate and blood gas values are
relatively normal, these patients are sometimes called "pink puffers”.
Patients with emphysema and chronic bronchitis:
Cough and wheezing, hypercapnia, cyanosis, chronic
hypoxia, pulmonary hypertension, cor pulmonale (blue
bloaters)
11. Types of emphysema
Classified according to anatomic distribution within the lobule
There are four major types of emphysema:
centriacinar,
panacinar,
distal acinar, and
irregular.
Only the first two cause clinically significant airway
obstruction, with centriacinar emphysema being about 20-fold
more common than panacinar disease.
12. Types of Emphysema
Classified according to anatomic distribution within the lobule
Centriacinar (centrilobular) emphysema
Involves the central or proximal part of the acini
(respiratory bronchiole)
More common & severe in upper lobes (apical segments)
Inflammation around bronchi & bronchioles
More in male smokers & specially in patients with
chronic bronchitis
Panacinar (Panlobular) emphysema
The acini are uniformly enlarged from the level of the
respiratory bronchiole to the terminal blind alveoli
More severe in lower zones & bases
High association with α1 antitrypsin deficiency
13. Types of Emphysema
Classified according to anatomic distribution within the lobule
Distal (Paraseptal) emphysema
Mainly along pleura & connective tissue of septae (proximal
portion of the acinus is normal but the distal part is dominantly
involved).
More in upper half of the lung
Adjacent to areas of fibrosis, scarring, or atelectasis.
Bullae may be present.
Irregular Emphysema
The acinus is irregularly involved and associated with scarring
(healed inflammatory diseases).
This may be the most common form of emphysema.
14. Centrilobular emphysema. Central areas show marked
emphysematous damage (E), surrounded by relatively spared
alveolar spaces. B. Panacinar emphysema involving the entire
pulmonary architecture.
15. Centrilobular emphysema of the upper lung fields.
The central lobular loss of tissue with intense black
anthracotic pigmentation (dirty holes) is apparent.
16. Pathogenesis:
Protease/ Antiprotease imbalance
and oxidant-antioxidant imbalance
Excess protease or elastase activity unopposed by appropriate
antiprotease regulation
Increase in protease occurs whenever there is increase in neutrophils
& macrophages e.g. in smokers
Decrease in antiprotease activity may be:
Genetic: α1 antitrypsin deficiency (Pi locus on Ch.14)
Acquired: Smoking inhibits enzyme activity
Result: Elastic tissue digestion & destruction → EMPHYSEMA
18. Morphology
Macroscopic:
- Large pale lungs, may obscure the heart
- Less severe in centriacinar where it is more in upper two
thirds
Microscopic :
- Destruction of alveolar walls → Confluent air spaces
- Collapse of adjacent spaces
- Diminished vessels in septae
- Chronic bronchitis may be seen
- Later pulmonary hypertension & cor pulmonale
20. Conditions related to emphysema
There is enlargement of air spaces without destruction of their
walls = Overinflation
They include:
Compensatory Emphysema (surgical removal of a diseased
lung or lobe)
Senile Emphysema
Obstructive Overinflation (tumor or foreign object)
Mediastinal (interstitial) Emphysema (sudden increase in
intra-alveolar pressure; as with vomiting or violent
coughing).
Bullous Emphysema: Any type with formation of sub- pleural
air filled cysts (0.5-2 cm.or more), more in paraseptal and
may lead to Pneumothorax
22. Chronic Bronchitis
Persistent chronic productive cough with large amount of
sputum for at least 3 months for at least 2 consecutive years .
COPD with hypercapnia, hypoxemia, ± cyanosis (Blue Bloater) → Cor
pulmonale. Dyspnea is RARE
Common among cigarette smokers and urban dwellers in
smog-ridden cities
It can occur in several forms:
Simple chronic bronchitis→ mucoid sputum
Chronic asthmatic bronchitis: intermittent bronchospasm
and wheezing (episodes of asthma)
Chronic obstructive bronchitis: outflow obstruction,
coexistant emphysema (heavy smokers)
23. Chronic Bronchitis: Pathogenesis
Chronic bronchitis represents reaction of the tracheobronchial tree to
inhaled irritants e.g. cigarette smoke, air pollutants (sulfur dioxide and
nitrogen dioxide)
This induces Hypersecretion of Mucus by:
Hyperplasia & hypertrophy of mucus glands
Increase in goblet cells by metaplasia
Recurrent infections
Inflammation with infiltration of CD8+ T cells, macrophages, and
neutrophils.
Airflow obstruction is more peripheral and results from
Small airway disease (chronic bronchiolitis): bronchiolar wall fibrosis &
above
Coexistent emphysema.
24. Morphology of chronic bronchitis
Macroscopically: Edematous congested bronchus
(hyperemic and swollen ) with luminal thick mucus.
Microscopically: Inflammatory cell infiltrate, enlarged mucus
gland layer, ↑number of glands, ↑ goblet cells down to small
passages, metaplastic changes (mucus & goblet ) ±
DYSPLASIA
Reid Index: Thickness of submucosal layer / bronchial wall
25. A bronchus with increased numbers of chronic
inflammatory cells in the submucosa. Chronic
bronchitis does not have characteristic
pathologic findings
26. Chronic bronchitis.
The lumen of the bronchus is above. Note the marked
thickening of the mucous gland layer (approximately twice
normal) and squamous metaplasia of lung epithelium.
27. Bronchiectasis
It is permanent dilation of bronchi and bronchioles caused by
destruction of the muscle and elastic supporting tissue, resulting from
or associated with chronic necrotizing infections .
Usually secondary to predisposing conditions such as:
Bronchial Obstruction
Localized (foreign bodies, tumor, mucus)
Generalized (atopic asthma, bronchitis)
Congenital & hereditary conditions:
Cystic fibrosis, Immunodeficiency, Kartagener S.
Necrotizing or suppurative pneumonia (Staphylococcus aureus or
Klebsiella )
Post-tubercular bronchiectasis
28. Pathogenesis of Bronchiectasis
Obstruction + Infection → damage of the wall → weakening
& dilatation + accumulation of exudate → more infection
Morphology:
Localized or widespread, but more in lower lobes
Dilatation can be followed almost to pleural surface
Wall shows acute &chronic inflammatory cells, squamous
metaplasia of lining +fibrosis
Often mixed bacterial flora
Clinical Course: Chronic productive cough with purulent
sputum and hemoptysis from branches of bronchial artery
33. Diseases which interfere with lung
expansion
Chest wall defects
Pulmonary parenchymal diseases (Interstitial Lung Diseases)
Destruction of alveolar walls with FIBROSIS
34. Restrictive pulmonary diseases
Predominantly diffuse, more in peripheral areas
Decreased lung compliance (stiff lung) & Increase in effort to
breath → dyspnea
Decreased arterial O2 pressure due to abnormalities in ventilation-
perfusion ratio leading to hypoxemia (resistant to O2 therapy)
Usual cause is interstitial lung disease
Primary or secondary
Acute or chronic
Acute is represented by ARDS
Chronic involvement of the pulmonary connective tissue
Pulmonary Function Tests :
↓ Forced Vital Capacity ( FVC ), Air flow ( FEV1 ) is normal / ↓
FEV1 / FVC is near normal
36. Pathogenesis
Whatever the cause, the lesion is an alveolitis
Lymphocytes, macrophages & neutrophils infiltration
Macrophage activation→ chemoatractants
IL-8 & Leukotrine B4 → Recruit Neutrophils
Fibrogenic Cytokines (TFG-β & PDGF)
Activation of Fibroblasts
Destruction of type I pneumocytes & proliferation of type II
pneumocytes
37.
38. Fibrosing Reaction
1. Idiopathic Pulmonary Fibrosis (IPF) (Cryptogenic Fibrosing
Alveolitis)
Commonest type, M > F, most > 60, (diffuse interstitial fibrosis)
Diagnosed only after exclusion of all other causes
Gross: Cobblestone outer surface of lung
Microscopy: Histological pattern of Usual Interstitial Pneumonia (UIP)
Patchy interstitial fibrosis (varying in intensity & time) Temporal
Heterogeneity i.e. Fibroblastic foci + Collagenous foci
The dense fibrosis causes collapse of alveolar walls and formation
of cystic spaces lined by hyperplastic type II pneumocytes or
bronchiolar epithelium (honeycomb fibrosis).
Interstitial inflammation: patchy consists of an alveolar septal
infiltrate (mostly lymphocytes and occasional plasma cells, mast
cells, and eosinophils)
Lower lobe predominance, along pleura & septa
48. Pneumoconiosis
B- Silicosis
Commonest occupational lung disease in the world
inhalation of crystalline silica
Workers in sandblasting, ceramics , glass, and stone cutting,
construction….etc
Acute heavy exposure → ARDS
Chronic after 20-40 yrs exposure
Pathogenesis:
Silica in macrophages → cause activation and release of
mediators by pulmonary macrophages (IL-1, TNF,
fibronectin, lipid mediators, oxygen-derived free radicals
and fibrogenic cytokines)
49. Pathology
Silicotic nodules, in upper lobe & LNs
Small nodules → large nodules (1-10cm) of concentrically arranged
collagen fibers with polarizing crystalls in the center
Cavitation, pleural fibrosis.
Fibrotic calcified nodules in hilar lymph nodes → X ray : Eggshell
calcification
Progressive Massive Fibrosis & Honey comb
Clinical picture
Many patients are asymptomatic, some with shortening of breath
Progressive Massive Fibrosis (PMF) late with abnormal pulmonary
function, pulmonary hypertension & cor pulmonale
Patients more susceptible to T.B.
↑ risk lung cancer with crystalline silica
Pneumoconiosis
B- Silicosis
57. Granulomatous Reaction
2. Hypersensitivity Pneumonitis (Allergic
Alveolitis)
Syndrome caused by a variety of inhaled organic dust or chemicals
Inflammatory response is in alveoli & terminal bronchiols with systemic
symptoms
Type III & type IV reactions with specific AB in serum
Presentation depends on duration & intensity of exposure:
Acute or Chronic
Antigens include fungal or bacterial spores, animal protein --- etc
Farmer’s Lung - moldy hay with fungal spores
Pigeon fancier’s lung - Bird droppings
Coffee worker’s lung - Coffee been dust
Sugar cane workers
Ventilation related
Many others
58. Phases of Hypersensitivity Pneumonitis :
Acute: direct irritant effect→ cough with dyspnea, fever (4-
8hr. after exposure)
Chronic: insidious onset cough, dyspnea, ↓weight.
Morphology:
Patchy peribronchiolar interstitial inflammatory infiltrate
& alveolar walls
75% show interstitial noncaseating granuloma →
FIBROSIS
60. Smoking –Related Interstitial Diseases
Desquamative Interstitial Pneumonia(DIP)
Interstitial inflammation + pigmented macrophages in
alveolar spaces
Respond to steroids
Bronchiolocentric respiratory bronchiolitis with
peribrochial fibrosis
61. Desquamative interstitial pneumonia: medium-power detail of lung to
demonstrate the accumulation of large numbers of mononuclear cells
within the alveolar spaces with only mild fibrous thickening of the alveolar
walls.
64. Definition of Pneumonia
Pneumonia is infection of lung parenchyma, distal to the
terminal bronchioles. It may present as:
Acute disease
Chronic disease
Acute bacterial pneumonias can present as one of two
anatomic and radiographic patterns,
Bronchopneumonia
Lobar pneumonia:
65. Bronchopneumonia
Patchy distribution of
inflammation that
generally involves more
than one lobe.
This pattern results from
an initial infection of the
bronchi and bronchioles
with extension into the
adjacent alveoli.
67. Lobar Pneumonia
Part or all of a lobe are
homogeneously filled with
an exudate, which can be
visualized on radiographs
as a lobar or segmental
consolidation.
71. Classification of pneumonias
Community-Acquired Acute Pneumonia
Community-Acquired Atypical Pneumonia
Nosocomial Pneumonia
Aspiration Pneumonia
Chronic Pneumonia
Necrotizing Pneumonia and Lung Abscess
Pneumonia in the Immunocompromised Host
There is an important table in your text book for causative agents
72. Community-Acquired Acute Pneumonias
The onset is abrupt, (fever, shaking chills, chest pain, cough,
sputum and occasionally hemoptysis).
Bacterial in origin, follows a viral upper respiratory tract
infection.
Streptococcus pneumoniae (or pneumococcus) is the most
common cause
Pneumococcal infections occur in patients with:
chronic diseases (congestive heart failure, COPD, diabetes)
congenital or acquired immunoglobulin defects (AIDS)
decreased or absent splenic function (e.g., sickle cell
disease or post splenectomy).
73. Morphology
It may occur in either pattern of pneumonia, lobar or
bronchopneumonia which is more prevalent in elderly.
The lower lobes or the right middle lobe are most frequently
involved.
Pneumococcal pneumonia involved entire or almost entire
lobes and evolved through four stages:
congestion,
red hepatization,
gray hepatization,
resolution.
74. Morphology
1- Congestion (1-2 days)
* Heavy red and boggy lungs, Severe vascular congestion, Intra alveolar
exudate with few neutrophils, and Bacteria
2- Red hepatization (2-4 days)
* Firm airless , liverlike lung
* Pleura demonstrates a fibrinous or fibrinopurulent exudate
* Alveolar spaces packed with neutrophils, red cells, and fibrin.
3- Grey hepatization :
Lung is dry grey and firm
Fibrinous exudate persists within the alveoli with increased fibrin &
macrophages.
4- Resolution :
* Enzymatic digestion of exudate → resorption, phagocytosis, sometimes
with residual adhesion
76. The histopathologic hallmark of acute pneumonia is the presence of
neutrophils within the alveolar spaces. This is accompanied by septal
capillary congestion and fibrinous exudates, resulting from increased
capillary permeability. The term fibrinopurulent is applied to the
combination of fibrin and neutrophils (pus) within the alveolar spaces.
77. Gross view of lobar pneumonia with gray hepatization.
The lower lobe is uniformly consolidated.
78. Morphology
In the bronchopneumonic pattern, patches of inflammatory
consolidation throughout one or several lobes, most
frequently bilateral and basal.
In severe cases, confluence of these foci may occur producing
the appearance of a lobar consolidation.
Surrounding areas of consolidation is usually hyperemic and
edematous, but the rest is normal.
Pleural involvement is less common than in lobar pneumonia.
Histologically, focal suppurative exudate fills the bronchi,
bronchioles, and adjacent alveolar spaces.
79. Complications
Abscess
Empyema
Organization of the intra-alveolar exudate may convert areas
of the lung into solid fibrous tissue
Bacteremic dissemination may lead to meningitis, arthritis,
or infective endocarditis.
Complications are much more likely with serotype 3
pneumococci.
80. Other organisms commonly implicated in
community-acquired acute pneumonias
Haemophilus influenzae
Individuals at risk include those with chronic bronchitis, cystic
fibrosis, and bronchiectasis.
In children, bronchopneumonia, often follows viral infection, (mild).
Moraxella catarrhalis cause pneumonia in COPD patients and
elderly
Klebsiella pneumoniae
It is the most frequent cause of gram-negative bacterial pneumonia.
Affects debilitated and malnourished persons, alcoholics and COPD.
Thick and gelatinous sputum is characteristic, which the patient may
have difficulty coughing up.
bronchopneumonia or lobar
81. Staphylococcus aureus
It is an important cause in
children and healthy adults following viral respiratory
illnesses (e.g., measles in children and influenza in
children and adults).
intravenous drug abusers (staphylococcal pneumonia in
association with right-sided endocarditis).
Staphylococcal pneumonia is associated with a high
incidence of complications (lung abscess and empyema).
82. Pseudomonas aeruginosa
Pseudomonas pneumonia is common in
neutropenic cancer patients, usually secondary to
chemotherapy
patients with extensive burns;
patients requiring mechanical ventilation.
Histologic examination reveals
coagulation necrosis of the pulmonary parenchyma
organisms invading the walls of necrotic blood vessels
(Pseudomonas vasculitis).
Pseudomonas bacteremia is a fulminant disease, causing
death within a matter of days.
83. Legionella pneumophila
It may cause epidemic and sporadic forms of pneumonia.
Acquired through contaminated water, air conditions.
common in adults with predisposing conditions such as
cardiac, renal, immunologic, or hematologic disease and
organ transplant recipients.
It can be quite severe, bronchopneumonia with
fibrinopurulent exudate & microabscesses, empyema and
fibrosis
Immunosuppressed individuals may have a fatality rate of
30% to 50%.
Diagnosis by culture & Legionella antigen in urine
84. Community-Acquired Atypical Pneumonias
The most common cause is upper respiratory infection by one of
following causative agents:
Mycoplasma pneumoniae: is the most common cause
(children and young adults),
Chlamydia pneumoniae
Rickettsiae
Viruses
Influenza viruses A and B (adults)
Parainfluenza,
Respiratory syncytial viruses (infants and children),
Adenovirus pneumonias are particularly common in
young army recruits.
85. Pathogenetic mechanism
Organisms Attach to the epithelium followed by necrosis of the
cells and an inflammatory response which extends to alveoli,
causing interstitial inflammation.
Damage to and denudation of the epithelium inhibits
mucociliary clearance and predisposes to secondary bacterial
infections.
86. Morphology
The process may be patchy, or it may involve whole lobes
bilaterally or unilaterally.
Macroscopically:
The affected areas are red-blue, congested.
Histologically:
The inflammatory reaction is confined within the walls of
the alveoli.
The septa are widened and edematous; containing
(lymphocytes, histiocytes, and plasma cells).
Alveolar spaces are remarkably free of cellular exudate.
In severe cases, diffuse alveolar damage with hyaline
membranes may develop.
88. Clinical Course
Atypical pneumonias extremely varied range from mild to
severe depends on the resistance of the host
Typically, acute, nonspecific febrile illness
fever, headache, and malaise,
later, cough with minimal sputum.
Chest radiographs usually reveal transient, ill-defined
patches, mainly in the lower lobes.
No lobar consolidations (but it may occur).
In uncomplicated cases, the disease is followed by
reconstitution of the native architecture.
89. Nosocomial Pneumonia
(Hospital-Acquired Pneumonias)
It is a pulmonary infections acquired in hospital.
Common in
patients with severe underlying disease
immunosuppression
prolonged antibiotic therapy
invasive access devices (intravascular catheters).
patients on mechanical ventilation (ventilator-associated
pneumonia).
The most common causative agents
Gram-negative rods (Enterobacteriaceae and
Pseudomonas species)
Staphylococcus aureus.
90. Nosocomial Pseudomonas pneumonia
There is extensive destruction of pulmonary parenchyma
(arrowhead), with full-thickness fibrinoid necrosis of the
arterial wall in the upper portion of the field (arrow).
92. Aspiration Pneumonia
It occurs in
debilitated patients
unconscious patients aspirate gastric contents (e.g., after a
stroke)
during repeated vomiting.
Aspiration pneumonia is partly chemical (irritating effects of
the gastric acid), and partly bacterial.
Aerobic bacteria > anaerobes
This type of pneumonia is often necrotizing, and is a frequent
cause of death
Abscess formation is a common complication.
93. Lung Abscess
and necrotizing pneumonia
Lung Abscess is localized area of suppurative necrosis within
the pulmonary parenchyma, resulting in the formation of one
or more large cavities.
Necrotizing pneumonia has been used for a similar process
resulting in multiple small cavitations; necrotizing pneumonia
often coexists or evolves into lung abscess,
94. Pathogenesis
Aspiration of infective material (infected sinuses or tonsils)
Aspiration of gastric contents, usually accompanied by infectious
organisms from the oropharynx
Post pneumonic as complication of necrotizing bacterial pneumonias
Staphylococcus aureus, Streptococcus pyogenes, K. pneumoniae,
Pseudomonas
Mycotic infections
bronchiectasis
Bronchial obstruction (bronchogenic carcinoma obstructing a bronchus or
bronchiole)
Infection in existing cavities or cysts
Septic embolism (thrombophlebitis or from infective endocarditis)
hematogenous spread of bacteria (staphylococcal bacteremia)
96. Morphology of abscess
Variable size , may be single or multiple , depending on mode
of development.
Aspiration - Usually solitary , more in RL
Postpneumonic - usually multiple, more basal
Hematogenous - usually multiple at any site
Culture of pus - often mixed aerobic / anaerobic
Histology - focus of suppuration (neutrophils) surrounded by
fibrous scarring and mixed chronic inflammatory cells
Healing by fibrosis leaving a sterile cavity
97. Complications of lung abscess
Rupture with partial drainage of material
*Radiological picture → Air- Fluid level
*Rupture into pleura → Empyema
*Rupture into bronchus →Bronchopneumonia
Formation bronchopleural fistula → Pneumothorax
Septic emboli
Lung hemorrhage from vessels in fibrous wall