The document summarizes various pathologies of the respiratory system including pneumonias, pneumoconiosis, chronic obstructive pulmonary disease (COPD), and bronchogenic carcinoma. It describes the pathogenesis, classification, clinical features, and histopathology of conditions like lobar pneumonia, bronchopneumonia, acute respiratory distress syndrome, atelectasis, pneumoconiosis, chronic bronchitis, bronchial asthma, bronchiectasis, and lung cancer. Key points covered include the etiology and predisposing factors for pneumonias, different types of pneumoconiosis based on inhaled dust, components of COPD, and molecular pathogenesis involving oncogene mutations in lung cancer.

1. PATHOLOGY OF RESPIRATORY
SYSTEM

2. PNEUMONIAS
 Pneumonia is defined as acute inflammation of the
lung parenchyma distal to the terminal bronchioles
(consisting of the respiratory bronchiole, alveolar
ducts, alveolar sacs and alveoli).
 The terms ‘pneumonia’ and ‘pneumonitis’ are often
used synonymously for inflam mation of the lungs,
while ‘consolidation’ (mean ing solidification) is the
term used for gross and radiologic appearance of
the lungs in pneumonia.

3. PATHOGENESIS
 The microorganisms gain entry into the lungs by
one of the following four routes:
 1. Inhalation of the microbes present in the air.
 2. Aspiration of organisms from the nasopharynx or
oropharynx.
 3. Haematogenous spread from a distant focus of
infection.
 4. Direct spread from an adjoining site of infection.
 Failure of defense mecha nisms and presence of
certain predisposing factors result in pneumonias.

4. CONTD…
 These conditions are as under:
 1. Altered consciousness
 2. Depressed cough and glottic reflexes
 3. Impaired mucociliary transport
 4. Impaired alveolar macrophage function
 5. Endobronchial obstruction
 6. Immuno compromised states

5. CLASSIFICATION
 I. On the basis of the anatomic region of the lung
parenchyma involved, pneumonias are traditionally
classified into 3 main types:
 1. Lobar pneumonia
 2. Bronchopneumonia (or Lobular pneumonia)
 3. Interstitial pneumonia.

6. CONTD…
II. Based on the clinical settings in which infection
occurred, pneumonias are classified as under:
 1. Community-acquire pneumonia
 2. Health care-associated pneumonia (including
hospital-acquired pneumonia)
 3. Ventilator-associated pneumonia

7. CONTD…
 III. Based on etiology and pathogenesis,
pneumonias are classified as under:
 A. Bacterial pneumonia
 B. Viral pneumonia
 C. Pneumonias from other etiologies

8. LOBAR PNEUMONIA
 Lobar pneumonia is an acute bacterial infection of a
part of a lobe, the entire lobe, or even two lobes of
one or both the lungs.
 ETIOLOGY
 Pneumococcal pneumonia
 Staphylococcal pneumonia
 Streptococcal pneumonia

9. MORPHOLOGIC FEATURES
 Laennec’s original description divides lobar
pneumonia into 4 sequen tial pathologic phases:
 stage of congestion (initial phase),
 red hepatisation (early consolidation),
 grey hepatisation (late consolidation) and
 resolution

10. CLINICAL FEATURES
 Classically, the onset of lobar pneumonia is
sudden.
 The major symptoms are: shaking chills, fever,
malaise with pleuritic chest pain, dyspnoea and
cough with expectoration which may be mucoid,
purulent or even bloody.
 The common physical findings are fever,
tachycardia, and tachypnoea, and sometimes
cyanosis if the patient is severely hypoxaemic.
 There is generally a marked neutrophilic
leucocytosis. Blood cultures are positive in about
30% of cases. Chest radio graph may reveal
consolidation.

11. BRONCHOPNEUMONIA (LOBULAR
PNEUMONIA)
 Bronchopneumonia or lobular pneumonia is
infection of the terminal bronchioles that extends
into the surrounding alveoli resulting in patchy
consolidation of the lung.
 The condition is particularly frequent at the
extremes of life (i.e. in infancy and old age), as a
terminal event in chronic debilitating diseases and
as a secondary infection following viral respiratory
infec tions such as influenza, measles etc.

12. ETIOLOGY
 The common organisms responsible for
bronchopneumonia are staphylococci, streptococci,
pneumococci, Klebsiella pneumoniae, Haemophilus
influenzae, and gram-negative bacilli like
Pseudomonas and coliform bacteria

13. CLINICAL FEATURES
 The patients of broncho pneumonia are generally
infants or elderly individuals.
 There may be history of preceding bed-ridden
illness, chronic debility, aspiration of gastric
contents or upper respiratory infection.
 Chest radiograph shows mottled, focal opacities in
both the lungs, chiefly in the lower zones.

14. ACUTE RESPIRATORY DISTRESS SYNDROME
(HYALINE MEMBRANE DISEASE)
 Acute respiratory distress syndrome (ARDS) is a
severe, at times lifethreatening, form of progressive
respiratory insufficiency which involves pulmonary
tissues diffusely i.e. involvement of the alveolar
epithelium, alveolar lumina and interstitial tissue

15. CLINICAL FEATURES AND
CONSEQUENCES
 These are different in children and adults: ”
 Neonatal ARDS occurring in newborn infants
begins with dyspnoea within a few hours after birth
with tachypnoea, hypoxia and cyanosis; in severe
cases death may occur within a few hours. ”

16. CONTD…
 Adult ARDS is known by various synonyms such
as shock-lung syndrome, diffuse alveolar damage
(DAD), acute alveolar injury, traumatic wet lungs
and post-traumatic respiratory insufficiency.
 Adult ARDS also presents clinically by sudden and
severe respiratory distress, tachypnoea,
tachycardia, cyanosis and severe hypoxaemia

17. PATHOGENESIS
 NARDS - The basic defect in neonatal ARDS is a
deficiency of pulmonary surfactant, normally
synthesised by type II alveolar cells.
 The main function of alveolar surfactant being
lowering of alveolar surface tension, its deficiency
leads to increased alveolar surface tension which in
turn causes atelectasis

18. ADULT ARDS
 i) Activated pulmonary macrophages release
proinflammatory cytokines such as IL8, IL1, and
tumour necrosis factor (TNF), while macro phage
inhibitory factor (MIF) helps to sustain inflammation
in the alveoli.
 In either case, injury to the capillary endothelium
leads to increased vascular permeability while
injured pneumocytes, especially type 1, undergo
necrosis. The net effect of injury to both capillary
endothelium and alveolar epithelium is interstitial
and intra-alveolar

19. ATELECTASIS AND COLLAPSE
 Atelectasis in the newborn or primary atelectasis is
defined as incomplete expansion of a lung or
part of a lung, while
 pulmonary collapse or secondary atelectasis is the
term used for reduction in lung size of a
previously expanded and well-aerated lung.
Obviously, the former occurs in newborn whereas
the latter may occur at any age..

20. CONTD..
 ATELECTASIS Stillborn infants have total
atelectasis, while the newborn infants with weak
respiratory action develop incomplete expansion of
the lungs and clinical atelectasis. The common
causes are prematurity, cerebral birth injury, CNS
malformations and intrauterine hypoxia.
 COLLAPSE Pulmonary collapse or secondary
atelectasis in children and adults may occur from
various causes such as compression, obstruction,
contraction and lack of pulmonary surfactant

21. PNEUMOCONIOSES
 Pneumoconiosis is the term used for lung diseases
caused by inhalation of dust, mostly at work
(pneumo = lung; conis = dust in Greek).
 These diseases are, therefore, also called ‘dust
diseases’ or ‘occupational lung diseases’

22. ETIOLOGY
 The type of lung disease varies according to the
nature of inhaled dust. Some dusts are inert and
cause no reaction and no damage at all, while
others cause immunologic damage and predispose
to tuberculosis or to neoplasia.

23. FACTORS AFFECTING
 The factors which determine the extent of damage
caused by inhaled dusts are as under:
 1. size and shape of the particles;
 2. their solubility and physicochemical composition;
 3. the amount of dust retained in the lungs;
 4. the additional effect of other irritants such as
tobacco smoke; and
 5. host factors such as efficiency of clearance
mecha nism and immune status of the host.

24. REACTIONS
 The tissue response to inhaled dust may be one of
the following three types: ”
 Fibrous nodules e.g. in coal-workers’
pneumoconiosis and silicosis. ”
 Interstitial fibrosis e.g. in asbestosis. ”
 Hypersensitivity reaction e.g. in berylliosis.

25. TYPES
 COAL-WORKERS’ PNEUMOCONIOSIS
 SILICOSIS
 ASBESTOS DISEASE
 BERYLLIOSIS

26. CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(COPD)
 Chronic obstructive pulmonary disease (COPD) or
chronic obstructive airway disease (COAD) are com
monly used clinical terms for a group of
pathological conditions in which there is chronic,
partial or complete, obstruction to the airflow at any
level from trachea to the smallest airways resulting
in functional disability of the lungs i.e. these are
diffuse lung diseases.
 One etiologic factor which is a common
denominator in all forms of COPD is smoking.

27. CEB(2)S
 The following entities are included in COPD:
 I. Chronic bronchitis
 II. Emphysema
 III. Bronchial asthma
 IV. Bronchiectasis
 V. Small airways disease (bronchiolitis)

28. CHRONIC BRONCHITIS
 Chronic bronchitis is a common condition defined
clinically as persistent cough with expectoration
on most days for at least three months of the
year for two or more consecutive years. The
cough is caused by over secretion of mucus.

29. ETIOPATHOGENESIS
 The two most important etio logic factors
responsible for majority of cases of chronic
bronchitis are: cigarette smoking and atmospheric
pollution.
 Other contri butory factors are occupation,
infection, familial and genetic factors

30. CLINICAL FEATURES
 1. Persistent cough with copious expectoration of
long duration; initially beginning in a heavy smoker
with ‘morning catarrh’ or ‘throat clearing’ which
worsens in winter.
 2.Recurrent respiratory infections are common.
 3. Dyspnoea is generally not prominent at rest but
is more on exertion.

31. BRONCHIAL ASTHMA
 Asthma is a disease of airways that is characterised
by increased responsiveness of the
tracheobronchial tree to a variety of stimuli resulting
in widespread spas modic narrowing of the air
passages which may be relieved spontaneously
or by therapy.
 Asthma is an episodic disease manifested clinically
by paroxysms of dyspnoea, cough and wheezing.
However, a severe and unremitting form of the
disease termed status asthma ticus may prove
fatal.

32. ETIOPATHOGENESIS AND TYPES
 1. Extrinsic (atopic, allergic) asthma
 This is the most common type of asthma. It usually
begins in childhood or in early adult life. Most
patients of this type of asthma have personal and/or
family history of preceding allergic diseases such
as rhinitis, urticaria or infantile eczema.

33. CONTD…
 Hyper sensitivity to various extrinsic antigenic
substances or ‘allergens’ is usually present in these
cases. There is increased level of IgE in the serum
and positive skin test with the specific offending
inhaled antigen representing an IgEmediated type I
hypersensi tivity reaction which includes an ‘acute
immediate response’ and a ‘late phase reaction’.

34. 2. INTRINSIC (IDIOSYNCRATIC, NON-ATOPIC)
ASTHMA
 This type of asthma develops later in adult life with
negative personal or family history of allergy,
negative skin test and normal serum levels of IgE.
 Most of these patients develop typical symptom-
complex after an upper respiratory tract infection by
viruses

35. FEATURES
 G/A The lungs are overdistended due to over-
inflation. The cut surface shows characteristic
occlusion of the bronchi and bronchioles by viscid
mucus plugs.
 M/E 1. The mucus plugs contain normal or
degenerated respiratory epithelium forming twisted
strips called Curschmann’s spirals.

36. CONTD…
 2. The sputum usually contains numerous eosino
phils and diamond-shaped crystals derived from
eosino phils called Charcot-Leyden crystals.
 3. The bronchial wall shows thickened basement
membrane of the bronchial epithelium, submucosal
oedema and inflammatory infiltrate consisting of
lymphocytes and plasma cells with prominence of
eosino phils

37. BRONCHIECTASIS
 Bronchiectasis is defined as abnormal and irreversible
dilatation of the bronchi and bronchioles (greater
than 2 mm in diameter) developing secondary to inflam
matory weakening of the bronchial walls.
 The most characteristic clinical manifestation of
bronchiectasis is persistent cough with
expectoration of copious amounts of foul-smelling,
purulent sputum.

38. ETIOPATHOGENESIS
 The origin of inflammatory destruc tive process of
bronchial walls is nearly always a result of two
basic mechanisms: endobronchial obstruction and
infection.
 1. Hereditary and congenital factors
 2. Obstruction
 3. As secondary complication

39. FEATURES
 G/A
 The dilated airways, depending upon their gross or
broncho graphic appearance, have been
subclassified into the following different types:
 i) Cylindrical
 ii) Fusiform
 iii) Saccular
 iv) Varicose

40. CONTD…
 M/E :
 i) The bronchial epithelium may be normal,
ulcerated or may show squamous metaplasia.
 ii) The bronchial wall shows infiltration by acute and
chronic inflammatory cells and destruction of
normal muscle and elastic tissue with replacement
by fibrosis.
 iii) The intervening lung parenchyma shows fibrosis,
while the surrounding lung tissue shows changes of
interstitial pneumonia.

41. CLINICAL FEATURES
 The clinical manifestations of bronchiectasis
typically consist of chronic cough with foul-
smelling sputum production, haemoptysis and
recurrent pneumonia.
 Sinusitis is a common accompaniment of diffuse
bronchiectasis.
 Late complications occurring in cases uncontrolled
for years include development of clubbing of the
fingers, metastatic abscesses (often to the brain),
amyloidosis and cor pulmonale

42. BRONCHOGENIC CARCINOMA
 The term bronchogenic carcinoma is commonly
used for cancer of the lungs which includes
carcinomas arising from the respiratory epithelium
lining the bronchi, bronchioles and alveoli.

43. INCIDENCE
 Lung cancer is the most common primary malignant
tumour in men and accounts for nearly 30% of all
cancer deaths in both sexes in developing
countries.
 Currently, the incidence of lung cancer in females in
the United States has already exceeded breast
cancer as a cause of death in women

44. MOLECULAR PATHOGENESIS
 Molecular studies have revealed that there are
several genetic alterations in cancer stem cells
which produce clones of malignant cells to form
tumour mass.
 1. Activation of growth-promoting oncogenes
Mutation in K-RAS oncogene has been seen as the
dominant change in lung cancer. Besides, there is
mutation in tyrosine kinase domain of EGFR
oncogene in cases of adenocarcinoma lung in non-
smokers