Lung Pathology

Pulmonary Infections

Pneumonia - infection and inflammation in the lung parenchyma

Bronchitis – inflammation in the bronchi

Factors predisposing to pulmonary infections:

  • General weakening of the organism

    • Chronic diseases

    • Immunosuppression / immunodeficiency

    • Hypoproteinemia

    • Leukopenia

  • Decreased local protection

    • Diminished cough reflex: coma, anaesthesia, chest pain

    • Decreased phagocytic and bactericidal activity of pulmonary macrophages: Alcohol, Smoking, High or low oxygen concentration

  • Damage of mucociliary clearance

    • Smoking

    • Inhalation of hot or corrosive gases

    • Viral infections - ARVI!!

    • Immotile cilia syndrome

  • Pulmonary blood congestion and oedema

  • Congestion of sections

    • Cystic fibrosis

    • Bronchial obstruction

Classification of pneumonias

  • By etiologic agent

  • By the clinical setting: pneumonia syndromes

    • Community – acquired acute pneumonia

    • Community – acquired atypical pneumonia

    • Hospital – acquired pneumonia

    • Aspiration pneumonia

    • Chronic focal inflammation

    • Necrotising pneumonia and lung abscess

    • Pneumonia in the immunocompromised host

  • By anatomic distribution:

    • Lobar: Lobar pneumonia s. pleuropneumonia

      Stages of Lobar pneumonia

      1. Congestion

      2. Red hepatisation: 2-3 days, fibrinous pleuritis

      3. Grey hepatisation: several days

      4. Resorption: 8th – 9th day, in pre-antibiotic era, resolution by crisis

    • Lobular: Lobular bronchopneumonia

      • Focus/ foci 3 - 4 cm

      • Acute purulent inflammation in the bronchi and alveoli

  • By clinical manifestations:

    • Classic

    • Atypical

Complications of pneumonia

  • Abscess

  • Purulent inflammation in the pleura

  • Purulent inflammation in the pleura

  • Bacteraemia

  • Metastatic abscesses in distant organs

  • Sepsis

  • Septic shock

  • Fibrosis

Sepsis

SIRS – systemic inflammatory reaction syndrome

Sepsis: SIRS + proved or possible infection

Severe sepsis: dysfunction of distant organs

Septic shock: sepsis + arterial hypotension + no reaction to fluid infusion

Obstructive lung diseases

Decreased air flow in the airways

Includes:

  • Chronic bronchitis

  • Lung emphysema

    • Chronic bronchitis + lung emphysema = COPD

  • Bronchectasis

  • Bronchial asthma

Bronchectasis

Permanent dilation of bronchi and bronchioles: Saccular, Cylindrical

Destruction of muscle and elastic tissue

Mechanisms:

  • Obstruction, e.g. by mucus in cystic fibrosis

  • Infections

Morphology:

  • Preferred location: lower lobes

  • Intense acute and chronic inflammation

  • Ulcers

  • Metaplasia

  • Fibrosis of bronchial walls and peribronchiolar tissues: subtotal or total bronchiolar obliteration

Clinical Course:

  • Severe, persistent cough

    • Triggered by change of body position

    • More severe in the morning

  • High amount of foul-smelling sputum

  • Sputum can be bloody

  • Life- threatening haemoptysis is occasionally possible

  • Later: respiratory insufficiency, amyloidosis etc.

Emphysema = destruction of alveolar walls

Lung Emphysema

Causes: Smoking, alpha 1 antitrypsin deficiency

Pathogenesis:

  • imbalance between proteases and antiproteases

    • Neu, mf // alpha-1-antitrypsin

  • imbalance between oxidants and antioxidants

    • ROS (Neu, smoking) // superoxide dismutase, glutathione


Chronic bronchitis = inflammation and hypersecretion in the bronchial walls

Chronic Bronchitis

Persistent cough with sputum production for at least 3 months in at least 2 consecutive years

Etiology:

  • Long-standing irritation by inhaled substances

    • Tobacco smoke

    • Dust (grain, cotton, silica)

  • Infections have secondary role:

    • Maintain chronic bronchitis

    • Responsible for exacerbations and +/- complications

Morphology

  • Mucus hypersecretion: Hypertrophy of submucosal glands Reid index exceed 0.4 Increase in goblet cell number

  • Inflammation: Hyperemia, swelling, oedema of bronhial mucous membranes Inflammatory infiltrate

  • Epithelial changes: metaplasia, dysplasia

  • Fibrosis, bronchial deformities

  • Bronchial obstruction

Complications of chronic bronchitis:

  • COPD

  • Respiratory failure

  • Pulmonary hypertension, cor pulmonale and heart failure

  • Metaplasia – dysplasia – cancer cascade

Restrictive lung diseases

Reduced expansion of lung parenchyma

Causes:

  • Chest wall disorders

  • Chronic interstitial and infiltrative lung diseases decreasing lung compliance and contribution to the loss of parenchyma

    • Pneumo-fibrosis

    • Interstitial lung disease: alveolitis

    • Pneumo-conioses

Alveolitis: chronic course with deformation of pulmonary architecture

Granulomatous lung diseases

  • Tuberculosis

  • Sarcoidosis

  • Exogenic allergic alveolitis

  • Foreign body granulomas

Sarcoidosis

Systemic disease of unknown etiology

The most frequent involvement:

  • Lymph nodes: bilateral hilar lymphadenopathy

  • Lungs

  • Other affected sites: skin, eyes, heart

Exogenous allergic alveolitis s. hypersensitivity pneumonitis

Immunologically mediated, mostly interstitial inflammatory reaction to prolonged exposure to inhaled organic antigens

Morphology:

  • Interstitial inflammation s. interstitial pneumonitis (ly, pc, mf)

  • Non-caseating granulomas

  • Interstitial fibrosis can develop

Foreign body granulomas

Occupational lung diseases

Pneumoconioses: restrictive pathologies

  • Asbestosis

  • Silicosis

  • Anthracosis

  • Berilliosis

  • Hard metal pneumoconiosis

Occupational bronchial asthma: obstructive lung disease

Vascular lung diseases

Vascular lung diseases

  • Lung oedema

  • Pulmonary hypertension

  • Thrombembolism

Pulmonary Oedema

Classification

By localisation:

  • Interstitial

  • Alveolar

By cause and pathogenesis:

  • Hemodynamic oedema; Causes: Increased hydrostatic pressure, Decreased oncotic pressure, Lymphatic obstruction

  • Oedema due to microvascular and alveolar injury; Causes: Infections: pneumonia, sepsis  Inhaled gases: oxygen, SO2  Aspiration: gastric contents, near-drowning  Drugs: bleomycin  Shock  Radiation

  • Oedema of undetermined origin; Causes: High altitude  Neurogenic: central nervous system trauma

Non-cardiogenic lung oedema

Related terms:

  • diffuse alveolar damage (DAD),

  • acute respiratory distress syndrome (ARDS)

Basic pathogenetic event: damage of endothelium or pulmonary epithelium

ARDS / DAD: the pathogenetic events

  • Endothelial damage: increased capillary permeability, formation of microthrombi, ischemic injury

  • Alveolar cell death

    • Hyaline membranes

    • Decreased lung compliance

  • Ventilation – perfusion mismatch

  • Imbalance of anti-inflammatory and inflammatory mediators:

    • Nuclear factor kappa B

    • 30 min.: IL-8

    • Pulmonary microvascular sequestration and activation of neutrophils

  • Problems associated with the underlying disease

  • Dyspnoea, tachypnoea

  • Hypoxemia, resistant to O2 inhalation

  • Respiratory failure

  • Diffuse bilateral infiltrates  Mortality rate (USA) 60% - 40%

Secondary pulmonary hypertension

  • Chronic obstructive and interstitial lung diseases

    • Hypoxia

    • Destruction of lung parenchyma and capillaries

  • Congenital or acquired heart disease: mitral stenosis

  • Recurrent thrombemboli

  • Connective tissue diseases / vasculitis

  • Obstructive sleep apnoea

Primary pulmonary hypertension (PPH)

  • Primary changes in pulmonary blood vessel structure

  • Loss of BMPR2 (bone morphogenetic protein receptor 2) function

  • N: BMPR2 inhibits proliferation and favours apoptosis in vascular smooth muscle

  • PPH: Medial hypertrophy Plexiform lesions

Prognosis and treatment

  • Prognosis: death from decompensated cor pulmonale in 2-5 years: 80%

  • Limited treatment effect:

    • O2 , Calcium channel blockers, diuretics, digoxin

  • Specific treatment:

    • prostacyclin analogues,

    • endothelial receptor antagonists,

    • inhaled NO

  • Lung transplantation

Lung Cancer

Importance of the problem:

  • Frequent

  • Potentially preventable

  • 5-year survival 10 – 15 – 18%

The etiological factors of lung cancer

  • Smoking

  • Passive smoking

  • Occupational factors

  • Chronic lung diseases: tuberculosis, alveolitis

  • Outdoor air pollution

  • Hereditary factors:

    • AR

    • AD

The pathogenesis of the main clinical symptoms of lung cancer

  • Systemic manifestations: Non – specific  Weight loss  Lack of appetite  Fever  Weakness

  • Local manifestations: Genesis [ central / peripheral cancer ]  Cough, dyspnoea, lung bleeding, chest pain  Pleural exudation

  • Mediastinal damage:

  • Metastatic manifestations

  • Paraneoplastic syndromes

WHO classification of lung cancer: the main groups

  • Squamous cancer

  • Small cell cancer

  • Adenocarcinoma

  • Large cell cancer

  • Sarcomatoid carcinoma

  • Carcinoid

  • Other type

TNM of Lung Cancer

Squamous cell cancer

Small cell cancer

Lung adenocarcinoma

Colloid cancer

Bronchioloalveolar carcinoma

Carcinoid tumour

Chondroid hamartoma

Types of metastatic spread within lungs

Immunohistochemistry in the diagnostics of lung cancer

To lazy to do notes for all these - go through variants 😬