Pathology of parenchymal lung disease Flashcards
Examples of mechanical defence mechanisms
Ciliated epithelium
Mucus
Cough (damaged by neuromuscular problem- strokes)
Examples of immunological defence mechanisms
IgA and antimicrobials in mucus
Resident alveolar macrophages and dendritic cells
Innate/ adaptive immune responses
Describe the gas exchange surface
Thin
Type 2 pneumocytes/ epithelium differentiate to type 1, produce surfactant
Type 1 pneumocytes- gas exchange
Vessels and cells
What is the parenchyma?
The parts of the lungs involved in gas transfer including the alveoli, interstitium, blood vessels, bronchi and bronchioles
- Respiratory bronchiole
- Terminal bronchiole
- Alveolar rings, ducts, septum
How might pneumonia present?
-Shortness of breath
-Cough
-Haemoptysis (coughing up blood)
-Pyrexia (temperature)
=Elevated neutrophils
=Right basal crepitations and consolidation
Describe pneumonia
- Greatest cause of deaths due to infection in the developed world
- 15% of all deaths of children under 5
- Caused by range of pathogens= bacteria, fungi, virus
What are the categories of pneumonia?
-Community acquired
-Hospital acquired
-Health care associated
-Aspiration associated
-Immunocompromised host
-Necrotising/ abscess formation
=Resistance
What pathogens are associated with Community acquired pneumonia?
- Streptococcal pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
- Staphylococcus aureus
- Klebsiella pneumoniae/ Pseudomonas aeruginosa
- Mycoplasma pneumoniae
What are the pathogens associated with hospital acquired/ health care associated pneumonia?
-Gram negative rods= Enterobacteriaceae, Pseudomonas
-Staph aureus (usually methicillin resistant)
=more immunosuppressed, at least 48 hours prior to symptom onset
What pathogens are associated with aspiration pneumonia?
Anaerobic oral flora mixed with aerobic bacteria
No control over larynx
What pathogens are associated with Pneumonia in the immunocompromised host?
- Cytomegalovirus (organ transplant-liver)
- Pneumocytis jiroveci (PCP)
- Mycobacterium avium-intracellulare
- Invasive aspergillosis
- Invasive candidiasis
- Unusual bacterial, virus and fungal organisms
What pathogens are associated with necrotising/ abscess formation?
Anaerobes, S. aureus, Klebsiella, S. pyogenes
Describe the cellular response to infection
- Neutrophils= chemotaxis, degranulation, reactive oxygen species, extracellular traps, phagocytosis
- Macrophages(alveolar resident recruit)= cytokine and chemokines, phagocytosis (bacteria and dead cells), antimicrobial peptides, resolution (also involves T cells, dendritic cells and epithelial cells)
What is the clinical presentation of pneumonia?
- Cough
- Sputum= stimulates goblet cells so production of mucus
- Pyrexia
- Pleuritic chest pain= irritated pleura (rubbing)
- Haemoptysis= vasodilation, rupture of small blood vessels
- Dyspnoea
- Hypoxia= not effective gas exchange, pus filled alveoli
What are the types of pneumonia?
- Bronchopneumonia
- Lobar pneumonia
Describe the appearance of bronchopneumonia
- Most common pattern
- Patchy consolidated areas of acute suppurative inflammation
- Often elderly with risk factors (cancer, heart failure, renal failure, stroke, COPD)
Describe the appearance of lobar pneumonia
- Rust coloured sputum
- S. pneumoniae
- Consolidation of a large portion of a lobe or of an entire lobe
What are the general risk factors for pneumonia?
- Chronic disease
- Immunologic deficiency
- Immunosuppressive agents
- Leukopenia
What are the local risk factors for pneumonia?
- Loss or suppression of the cough reflex (drugs)
- Injury to the mucociliary apparatus (viruses, gases)
- Accumulation of secretions (CF, obstruction- tumour)
- Impaired alveolar macrophages function (alcohol, tobacco)
- Pulmonary congestion and oedema
What are the complications of pneumonia?
Local:
-Abscess formation (poor blood supply)
-Parapneumonic effusion (aseptic oedema, visceral and pleura space)
-Empyema (same plus bacteria)- chronic= chest drain
Systemic:
-Sepsis (hyperdilation)
-ARDS (Acute respiratory distress syndrome)
Multi-organ failure
Not resolving- cancer?- allows stagnation behind tumour (6 week scan after pneumonia to check)
Describe Acute Respiratory Distress syndrome
- Incidence 10-14/100,000/yr
- Mortality rate= 40%
- Clinical diagnosis= hypoxia (PaO2/FiO2 <300mmHg), Non-cardiogenic pulmonary oedema
- Causes= direct (pneumonia, aspiration, hyperoxia, ventilation), indirect (sepsis, trauma/DAMPs, pancreatitis, acute hepatic failure)
What is Bronchiectasis?
- The permanent dilation of one r more large bronchi (chronic infection, altering bronchial defence= impaired)
- Typically affects the 2nd to 8th order of segmental bronchi (largest central airways more robust)
What are the causes of diffuse or multifocal bronchiectasis?
- Infection (mycobacterial, childhood infection= pertussis bacterial/ Viral RSV/ adenovirus/ measles)
- Hereditary (Cystic fibrosis, primary ciliary dyskinesia, Alpha-1-antitrypsin deficiency)
- Congenital
- Immunodeficiency (hypogammaglobulinemia, HIV, Lung transplantation)
- Allergic bronchopulmonary aspergillosis
- Connective tissue disorders (rheumatoid, Sjogren’s Syndrome)
- Inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
- Chemical injury/ aspiration (Inhalation of SO2, NO5, H2S, gastric aspiration)
- Idiopathic
Describe Cystic Fibrosis
- Multi-system disorder affecting lungs, GI tract etc
- F508 (autosomal recessive) most common in CFTR
- Altered ion transportation
- Viscous mucoid secretions due to H20 resorption
Describe Tuberculosis
- Extremely common worldwide (more common in developing world)
- Immune response very important (11% of TB cases attributable to HIV 2000)
What are the predisposing factors of TB?
- Alcoholism
- Diabetes mellitus
- HIV/ AIDS
- Some ethnic groups
What is the treatment for TB?
- Socio-economic conditions
- Drugs- triple antibiotic therapy
- Prevention= BCG vaccination
What happens at 3-4 weeks in primary TB?
- M. TB multiples within alveolar macrophages (naïve, unable to kill)
- Bacterium resides in phagosomes and carried to regional lymph nodes, from there to circulation
What happens at 3-8 weeks in primary TB?
- Onset of cellular immunity and delayed hypersensitivity
- Activated lymphocytes further activate macrophages to kill
- Primary infection arrested in most immunocompetent people
- Few bacilli may survive dormant
What is a Ghon complex?
lesions consist of a Ghon focus along with pulmonary lymphadenopathy within a nearby pulmonary lymph node (hilar)
Subpleural lesion + hilar lymph node
Describe progressive primary TB
- Infection not arrested (minority: infants, children, immunocompromised)
- Tuberculosis bronchopneumonia (infection spreads via bronchi, results in diffuse bronchopneumonia, well developed granulomas do not form)
- Miliary TB (infection spreads via blood-stream, organisms scanty, multiple organs= liver, lungs, spleen, kidneys, meninges, brain)
Describe secondary TB
- Also termed post-primary TB
- Reactivation of old, often subclinical infection
- Occurs in 5-10% of cases of primary infection
- More damage due to hypersensitivity (apical region of lung/ tubercles develop locally, enlarge and merge/ erode into bronchus and cavities develop/ may progress to tuberculous bronchopneumonia)
What are other causes of granulomatous pulmonary inflammation?
- Other infection= fungi
- Sarcoidosis
- Rheumatoid arthritis
- Berrylosis
- Hypersensitivity pneumonitis
- Aspiration pneumonia
- Langerhans Cell Histiocytosis
Describe fibrosing diseases of the lung
- Restrictive chronic lung disease
- Dyspnoea, (cough), tachypnoea, crepitation, cyanosis (late stage)
- Pulmonary function tests= reduced transfer factor and total lung capacity
- Ground glass changes in lower zones on x-ray
Describe the pathogenesis of idiopathic pulmonary fibrosis
Unclear
- Cause unknown
- Persistent epithelial injury/ activation
- Innate and adaptive immune response
- Pro-fibro genic factors
- Abnormal intracellular signalling
- Proliferation and collagen production
- Fibrosis
Describe what IPF looks like under the microscope/ morphology
Usually interstitial pneumonia
- Subpleural accentuation
- Spatial and temporal heterogeneity
- Fibroblastic foci
- Mixed inflammatory infiltrate
- Excess alveolar macrophages
Describe asbestos
- Occupational lung disease= exposure in shipyards, building trade
- Several diseases= pleural plaques (benign), asbestosis (progressive fibrosis), mesothelioma, adenocarcinoma
- Issues surrounding compensation for patient and families
- Other occupational factors= silica, coal dust, berrylium
Describe hypersensitivity pneumonitis
- Type 3 hypersensitivity (Ab/Ag complex within the lung)
- Various causative agents= Farmer’s, Pigeon fancier’s, mushroom picker’s lung (and hot tub)
- Most resolve when agent of exposure removed but can be chronic
What are the local complications of Bronchiectasis?
- Distal airway damage/ loss and lung fibrosis
- Pneumonia
- Pulmonary abscess formation
- Haemoptysis
- Airway colonisation by aspergillus
- Aspergilloma
- Tumourlet formation
What are the physiological and systemic complications of bronchiectasis?
Physio= respiratory failure, cor pulmonale Systemic= metastatic abscess, amyloid deposition
Describe infection in bronchiectasis
Impaired bacterial clearance -Altered anatomy -Thickened mucus -Impaired immune cell function Colonisation -Pseudomonas Aeruginosa -Klebsiella, Moraxella -S. pneumoniae, H. influenzae
Describe the pathogenesis of bronchiectasis
- Airway injury
- Inflammation +/- infection
- Cough increases airway pressure/ destruction of airway wall, loss of elastic tissue and fibrosis
- Airway dilation
- Distal lung changes with fibrosis/ retained secretion and infection
What is traction bronchiectasis?
Dilation of airways due to parenchymal fibrosis
- Parenchymal inflammation
- New collagen formation
- Collagen contracts
- Loss of lung volume
- Pulling open of airways
- Airway dilation
What is the pattern of bronchiectasis?
Based on imaging appearances
- Cylindrical
- Sacular
- Varicose
- Cystic
What are the classifications of bronchiectasis
-More useful to think in terms of anatomical distribution of disease
-Closer linkage with aetiologies
=Localised bronchiectasis
=Diffuse/ multifocal bronchiectasis
Describe localised bronchiectasis
- Bronchial obstruction= neoplasm, foreign body, external compression (middle lobe syndrome), allergic bronchopulmonary aspergillosis
- Infection= TB, Necrotising bacterial/ viral infection
- Gastric acid aspiration
- Traction bronchiectasis
- Idiopathic
