Pathology lecture class for MBBS students on 'Respiratory Pathology'

1. Respiratory Pathology
Dr. Umme Kulsum Munmun
MBBS, MD (Pathology)
Assistant Professor
Department of Pathology
Cumilla Medical College

2. Anatomy of Lung
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3. Structure of lung
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4. Structure of lung
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5. Function of lung
• process of gas exchange called respiration
(or breathing).
• In respiration, oxygen from incoming air
enters the blood, and carbon dioxide, a
waste gas from the metabolism, leaves the
blood.
• A reduced lung function means that the
ability of lungs to exchange gases is
reduced.
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6. Respiratory Membrane
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7. 7

8. Diseases of lung
• Congenital Anomalies
• Atelectasis
• Pulmonary Oedema
• Acute lung Injury & ARDS
• Obstructive lung disease
• Restrictive lung disease
• Infectious lung disease
• Bronchogenic carcinoma
• Pleural disease 8
Structural
Disturbance in
inspiration
Disturbance in
expiration
Disturbance in lung
expansion

9. 9
Congenital Anomalies
• Agenesis or hypoplasia of lungs, one lung
or single lobe.
• Vascular anomalies
• Congenital lobar overinflation (congenital
emphysema)
• Congenital cysts
• Intralobar and extralobar pulmonary
sequestration.

10. 10
Atelectasis
Atelectasis refers either to incomplete
expansion of the lungs (neonatal
atelectasis) or to the collapse of previously
inflated lung, producing areas of relatively
airless pulmonary parenchyma.

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Types of Atelectasis
• Resorption atelectasis – due to airway
obstruction
• Compression atelectasis – accumulation
of fluid, tumour, or air in pleural cavity
• Contraction atelectasis – pulmonary or
pleural fibrosis prevents expansion

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13. Pulmonary Oedema
• Pulmonary edema is defined as an
abnormal accumulation of extravascular
fluid in the lung parenchyma
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14. Pulmonary Oedema
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Pulmonary Oedema
• Causes:
• Haemodynamic oedema
– Increased hydrostatic
pressure
• Left sided heart failure
• Volume overload
• Pulmonary vein obstruction
– Decreased oncotic pressure
• Hypoalbuminaemia
• Nephrotic syndrome
• Liver disease
• Protein-losing enteropathies
– Lymphatic obstruction
• Oedema due to Microvascular
injury
– Infection
• Bacterial pneumonia
– Inhaled gas
• Oxygen, smoke
– Liquid aspiration
• Gastric contents, near
drowning
– Drug and chemicals
– Shock, trauma and sepsis
– Radiation
– Miscellaneous
• Oedema of unknown origin
– High altitude
– Neurogenic

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Acute lung Injury &
Acute Respiratory Distress Syndrome
(Diffuse Alveolar Damage)
• Acute lung injury (ALI) is characterized
by the abrupt onset of significant
hypoxemia and bilateral pulmonary
infiltrates in the absence of cardiac failure.

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Acute respiratory distress
syndrome (ARDS)
• is a manifestation of severe ARI and is a
clinical syndrome of progressive
respiratory insufficiency caused by diffuse
alveolar damage in the setting of sepsis,
severe trauma or diffuse pulmonary
infection.

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Conditions Associated with ARDS
1. Infection
• Sepsis
• Diffuse pulmonary infections
• Gastric aspiration
2. Physical/Injury
• Mechanical trauma
• Pulmonary contusions
• Near-drowning
• Fracture with fat embolism
• Burns
• Ionising radiation
3. Inhaled Irritants
• Oxygen toxicity
• Smoke
• Irritant gases and chemicals
4. Chemical Injury
• Heroin or methadone overdose
• Acetylsalicylic acid
• Barbiturate overdose
• Paraquat
5. Haematological Conditions
• Transfusion associated lung
injury
• DIC
6. Pancreatitis
7. Uraemia
8. Cardiopulmonary Bypass
9. Hypersensitivity reactions

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Morphology:
• The lung become heavy, firm, red and
boggy.
• Exhibits congestion, oedema,
inflammation, fibrin deposition & diffuse
alveolar damage.
• Alveolar wall become lined with waxy
hyaline membrane.

20. 20
Obstructive & restrictive lung diseases
• Obstructive lung diseases are characterized by
an increase in resistance to airflow due to partial
or complete obstruction at any level from the
trachea and larger bronchi to the terminal and
respiratory bronchioles. FEV1 is reduced, FVC
normal
• Restrictive diseases are characterizes by
reduced expansion of the lung parenchyma and
decreased total lung capacity. Both FEV1 & FVC
reduced

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Obstructive lung diseases
• Emphysema
• Chronic bronchitis
• Asthma
• Bronchiectasis

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Chronic Obstructive Pulmonary
Disease (COPD)
Def: COPD refers to a group of conditions
that share a major symptom – dyspnoea
and are accompanied by chronic or
recurrent obstruction to air flow within the
lung.

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Clinical Conditions Associated with
COPD
– Emphysema
– Chronic Bronchitis

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Chronic Bronchitis
• Def: Persistent cough with sputum
production for at least 3 months in at least
2 consecutive years, in the absence of any
other identifiable cause.
• Common among habitual smokers and
inhabitants of smog-laden cities.

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Pathogenesis:
• The primary or initiating factor is exposure to noxious or
irritating inhaled substances such as tobacco smoke
(90%), dust from grain, cotton and silica.
• Mucus hypersecretion : Inflammation : Both acute &
chronic inflammation
• Infection:
Cigarette smoke predisposes the infection
Complications: Cor pulmonale with cardiac failure
(benign mesothelioma)

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27. 27
Bronchiectasis
• Def: Bronchiectasis is a disorder in which
destruction of smooth muscle and elastic
tissue by chronic necrotising infection
leads to permanent dilatation of bronchi
and bronchioles.

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Associated conditions:
• Congenital or hereditary conditions such as
cystic fibrosis, intralobar sequestration of lung,
immunodeficiency states, immotile cilia and
kartegener’s syndrome.
• Infection including necrotising pneumonia
caused by bacteria, viruses or fungus.
• Bronchial obstruction due to tumour, foreign
body, mucous impaction etc.
• Other conditions including rheumatoid arthritis,
SLE, COPD.
• Idiopathic

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30. Bronchiectasis
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31. 31
Emphysema:
Def: Emphysema is irreversible enlargement
of the airspaces distal to the terminal
bronchiole, accompanied by destructions
of their walls without obvious fibrosis.
Types of Emphysema:
• Centriacinar
• Panacinar
• Paraseptal
• Irregular

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• Centriacinar:
– Central or proximal parts of acini are affected,
whereas distal alveoli are spared.
– Occurs in heavy smoker associated with
chronic bronchitis.
• Panacinar:
– Acini are uniformly enlarged from the level of
the respiratory bronchioles to the terminal
blind alveoli.
– Associated with α1-antitrypsin deficiency.

33. 33
• Paraseptal:
– Proximal portion of acini is normal but the
distal part is dominantly involved.
– Occurs adjacent to areas of fibrosis, scarring
or atelectasis.
• Irregular:
– The acinus is irregularly involved.
– Associated with scarring.

34. 34
Pathogenesis of Emphysema:
• Emphysema results from the destructive effects
of high protease activity in subjects with low
antiprotease activity.
• Both increased elastase availability and
decreased antielastase activity occurs in
smokers.
• increased elastase and decreased -1antitrypsin
activity causes the centriacinar emphysema
seen in smoker.
• (Functional Obstruction)

35. 35

36. 36

37. 37
Asthma:
• Def: Asthma is a chronic disorder of the
conducting airways, usually caused by an
immunological reaction, which is marked
by episodic bronchoconstriction due to
increased airway sensitivity to a variety of
stimuli; inflammation of the bronchial walls;
and increased mucus secretion.

38. Pathophysiology of Asthma:
• inflammation and airway remodeling,
which include
• goblet cell hyperplasia
• subepithelial fibrosis, collagen deposition
• mucosal gland hyperplasia
• smooth muscle hypertrophy and changes
in the extracellular matrix.
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40. 40
Normal airway vs. bronchial asthma

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Types Precipitating factor Mechanism or immunologic reaction
Extrinsic:
Atopic (allergic) Specific allergens Type 1 (IgE) immune reaction
Occupational Chemical challenge Type 1 immune reaction
Allergic bronchopulmonary
aspergillosis
Antigens (spore) challenge Type 1 and III immune reaction
Intrinsic:
Non-reaginic Respiratory tract infection Unknown; hyperactive airways.
Pharmacological (e.g. aspirin sensitive) Aspirin Decreased prostaglandin, increased
leukotrienes.
Types of Asthma:

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43. Restrictive Lung disease
• Occurs in two general conditions-
1. Chronic interstitial and infiltrative
diseases
2. Chest wall disorders
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44. Chronic interstitial and
infiltrative diseases
• Idiopathic pulmonary fibrosis
• Nonspecific interstitial pneumonia
• Pneumoconiosis
• Sarcoidosis
• Drug reactions
• Langerhans cell histiocytosis
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46. 46
Pnemoconiosis:
Non-neoplastic lung reaction to
inhalation of mineral dusts.
Mineral Dusts Diseases
Coal dust Anthracosis
Silica Silicosis
Asbestose Asbestosis
Beryllium Berillosis

47. Pulmonary Hypertension
• Chronic obstructive or interstitial lung
disease
• Congenital or acquired heart disease (eg.
Mitral stenosis)
• Recurrent thromboemboli
• Autoimmune diseases
• Obstructive sleep apnea
47

48. 48
Pulmonary Infection
Pneumonia:
• Inflammation of lung parenchyma with
solidification or consolidation is called
pneumonia.

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Classification:
• On anatomical distribution
• Lobular bronchopneumonia
• Lobar pneumonia
• On distinct clinical setting
• Community-Acquired Acute Pneumonia
• Health Care-Associated Pneumonia
• Hospital-Acquired Pneumonia
• Aspiration Pneumonia
• Chronic Pneumonia
• Necrotizing Pneumonia & Lung Abscess
• Pneumonia in the Immunocompromised Host

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Bronchopneumonia:
• Patchy consolidation
• Parenchymal infection, usually represent
an extension of a pre-existing bronchitis or
bronchiolitis
• Occurs in infancy and old age.
Lobar Pneumonia:
• Consolidation of large portion of lobe or of
an entire lobe is called lobar pneumonia.

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52. 52

53. 53
• The clearing mechanisms can be
interfered by many factors such as
– Loss or suppression of cough reflex
– Injury to the mucocilliary apparatus
– Interference with phagocytic or bactericidal
action of alveolar macrophages
– Pulmonary congestion and oedema
– Accumulation of secretion

54. 54
Aetiology
• Community-acquired
• Streptococcus
pneumonae
• Mycoplasma
pneomonae
• Haemophilous
influenza
• Staphylococcus aureus
• Legionella pneumonae
• Klebsiella pneumonae
• Chlamydae spp.
• Viruses- Influenza,
Parainfluenza, Measles
Health care associated
• Staphylococcus aureus
• Pseudomonas
• Streptococcus
pnumoniae

55. Pneumonic lung
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56. Normal vs pneumonia lung
histology
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57. 57
Morphology:
Lobar pneumonia:
• There is widespread fibrinosuppurative
consolidation of large areas and even
whole lobes of the lungs. There are four
stages
• Stages of congestion
• Stage of red hepatisation
• Stage of grey hepatisation
• Stage of resolution

58. 58
• Stage of congestion: The lung is heavy, boggy
and red. Vascular engorgement and intra-
alveolar fluid with few neutrophils and often
presence of numerous bacteria.
• Stage of red hepatisation: Massive confluent
exudation with red cells, neutrophils and fibrin fill
alveolar spaces. The lobe appears red, firm and
airless with a liver-like consistency hence the
term hepatization.

59. 59
• Stage of grey hepatisation: The lung lobes are
greyish-brown with due to progressive
disintegration of red cells and persistence of
fibrinosuppurative exudates.
• Stage of resolution: Consolidated exudates
within the alveolar spaces undergo progressive
enzymatic digestion to produce granular,
semifluid debris that is resorbed; ingested by
macrophages, coughed up or organized by
fibroblast growth.

60. Stages of Pneumonia
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61. X ray pneumonia
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Bronchopneumonia:
• There are foci of consolidated areas,
usually of 3 to 4 cm diameter, slightly
elevated, dry, granular, grey-red to yellow
and poorly delimited at their margin.
• Histologicaly the inflammatory reaction
usually comprises suppurative neutrophil-
rich exudates that fill the bronchi,
bronchioles, and adjacent alveolar spaces.

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Complication of pneumonia:
1. Abscess formation,
2. Empyema,
3. Retention of sputum causing lobar collapse
4. Deep vein thrombosis & pulmonary embolism
5. Pneumothorax
6. ARDS, renal failure, multiorgan failure
7. Ectopic abscess formation
8. Hepatitis, pericarditis, myocartitis,
meningoencephalitis

64. 64
Lung Abscess:
• Def: Local suppurative process that
causes necrosis of lung tissue.
• Aetiology: Common organisms -
Aerobic & anaerobic streptococcus
Staphylococcus aureus
Gram-negative bacilli
Anaerobic organism (Bacteroides,
Fusobacterium, Peptostreptococcus)

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The causative agents are introduced by
the following mechanisms:
• Aspiration of infective material
• Antecedent primary lung infection
• Septic embolism
• Neoplasia
• Miscellaneous.

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67. 67
Morphology:
• Lung abscess vary in diameter from few
mm to large cavity of 5 to 6 cm. The cavity
may or may not be filled with suppurative
debris.
• Cardinal histologic change is suppurative
destruction of the lung parenchyma within
the central area of cavitations. In chronic
case fibroblastic proliferation produces a
fibrous wall.

68. Lung Abscess
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69. Lung Abscess
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Complication of lung abscess
• Extension of infection into pleural cavity
• Hemorrhage
• Brain abscess
• Meningitis
• Secondary amyloidosis

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Pulmonary Tuberculosis:
Primary Pulmonary Tuberculosis: refers to the
infection of a previously uninfected (tuberculin-
negative) individual.
• Lungs are the usual location of primary infection. Lower
part of upper lobe or upper part of lower lobe, subpleural.
• The primary lesion is called Ghon focus.
• Enlarged lymph nodes draining the
parenchymal focus .
• This combination of Ghon focus, draining
lymphatics and nodal involvement is called
Ghon complex.

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• The course and fate of this initial infection
are variable. Most cases are
asymptomatic and the undergo fibrosis
and calcification.
• In infants and in children or
immunodeficient adults progressive
spread with cavitation, tuberculous
pneumonia or miliarry tuberculosis may
follow primary infection.

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Secondary or post primary tuberculosis
• Secondary tuberculosis refers to all form of
active infection in a person who has been
sensitised by earlier exposure.
It may occur by :
• Reactivation (endogenous) of an old, possibly
subclinical infection of primary tuberculosis.
• Reinfection (exogenous)

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Progressive Pulmonary Tuberculosis:
• A variable number of lesions continue to
progress over a period of months or years,
causing further pulmonary and even
distant organ involvement.
– Cavitary fibrocaseous tuberculosis
– Miliary tuberculosis and
– Tuberculous bronchopneumonia.

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Miliary Tuberculosis:
• Lymphohaematogenous dissemination may give
rise to miliary tuberculosis, confined only to the
lungs or involving other organs also.
• Individual lesions are 1-2 mm in diameter foci of
yellow-white consolidation scattered throughout
the lung field. (The term miliary is derived from
the resemblance of these foci to millet seeds).

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77. 77

78. Cavitary tuberculosis
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Bronchogenic Carcinoma:
• Most common visceral malignancy in male
• Accounts for one-third of all cancer death
in male and even 7% of all death in both
sexes.
• Occurs most often between ages 40 and
70 years with peak incidence in the 50s or
60s.
• 2% appears before the age of 40 years.

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Aetiological factors:
• Tobacco smoking
• Industrial hazards
– Radiation
– Uranium
– Asbestos
• Air pollution
• Molecular genetic

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Histologic Classification of Bronchogenic carcinoma:
1. Squamous cell carcinoma
2. Adenocarcinoma
– Bronchial derived
• Acinar
• Papillary
• Solid
– Bronchioloalveolar adenocarcinoma
3. Small cell carcinoma
– Oat cell carcinoma (lymphocyte-like)
– Intermediate cell carcinoma (polygonal)
4. Large cell carcinoma
5. Adenosquamous carcinoma
6. Carcinoma with pleomorphic or sarcomatoid or
sarcomatous element
7. Carcinoid tumour
8. Carcinoma of salivary gland type

82. Effects of Lung cancer
• A chronic cough that does not go away or
gets worse
• Coughing up bloody spit or mucus
• Chest pain (or discomfort) that worsens
with laughing, deep breaths or coughing
• Hoarse voice
• Loss of appetite
• Unexplained weight loss
82

83. Effects of Lung cancer
• Shortness of breath
• Fatigue or weakness
• Lung infections that don’t go away or keep
coming back (i.e., bronchitis or
pneumonia)
• Wheezing
• Difficulty swallowing
• Swelling in veins of face or neck
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84. Diagnosis of lung cancer
84
•Imaging tests. X-ray , CT scan
•Cytology. presence of lung cancer cells
in sputum
bronchial brushing sample
• X-ray or CT guided FNAC
•Tissue sample (biopsy).
Bronchoscopy
Mediastinoscopy

85. Bronchogenic carcinoma
85

86. Tests to determine the extent
of the cancer
86
• CT
• MRI
• positron emission tomography (PET)
• bone scans.

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Key point
• Most common form of carcinoma is
adenocarcinoma and arises in peripheral lung.
• Squamous cell carcinoma arises in central/hilar
region. Most commonly found in men and
strongly associated with smoking.
• Small cell carcinoma is highly malignant tumor
and strongly related with cigarette smoking.

88. 88
Metastatic Tumours:
• Both carcinoma and sarcoma arising
anywhere in the body may spread to the
lungs via the blood or lymphatic or by
direct continuity.

89. Pleural effusion
• Accumulation of serous fluid in pleural
cavity
89

90. Causes of Pleural effusion
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91. Few terminology
• Empyema: Purulent fluid in pleural cavity
• In case of hemorrhagic pleural fluid,
careful search for presence of exfoliated
tumor cells shold be made
• Hemothorax
• Hydrothorax
• Chylothorax
• Pneumothorax
91

92. 92
Pleural Tumour:
• Primary
– Pleural fibroma
– Solitary fibrous tumour
– Malignant mesothelioma
• Secondary tumour

93. Pleural fluid examination
• Appearance: clear/turbid/milky
• Biochemical: pH, LDH, protein, glucose level,
ADA (> 50 u/L indicates TB), Pleural fluid
amylase ( Pancreatitis )
• Microbiological: gram staining, AFB staining and
culture
• Autoantibody: ANA (rheumatoid pleurisy, lupus
pleuritis)
• Cell count with differentials
• Cytology: to see presence of malignant cells
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94. 94
Thank You