HistoPath - Respiratory disease Flashcards
Give examples of congenital lung disease
Lung agenesis or hypoplasia – LBW, impaired foetal respiratory movements
Tracheal and bronchial stenosis – associated with other malformations
Congenital cysts
Define asthma
widespread reversible narrowing of the airways (bronchi) that changes in severity over short periods of time
What are the causes/triggers of asthma
Recent RTI
Allergens/atopy
Pollution
Drugs (NSAIDs)
Occupational (gases)
Diet
Physical exertion
Intrinsic
Genetics
What is the pathogenesis of asthma
Immediate phase = mast cell degranulation → mediator release → increased vascular permeability → eosinophil + mast cell recruitment → bronchospasm
Late phase = tissue damage, increased mucous production, muscle hypertrophy
What are the histological features of asthma
Smooth muscle cell hyperplasia
Excess mucous → goblet cell hypertrophy
Inflammation
Whorls of shed epithelium (Cusrchmann spirals)
eosinophils
Charcot-Leyden crystals
Define Chronic bronchitis and what are the causes
Chronic bronchitis = type of COPD (other type = emphysema)
Dilatation of the airways (bronchi) and excess mucus production → Chronic cough productive of sputum; most days for ≥3 months over ≥2 consecutive years
Causes = smoking, air pollution, occupational exposures
What are the histological features of Chronic bronchitis
Dilatation of the airways
Goblet cell hyperplasia
Hypertrophy of mucous glands
What are the complications of COPD
Repeat infections
Chronic hypoxia
Reduced exercise tolerance, pulmonary HTN → RHF
Lung cancer risk
Define bronchiectasis and what are the histological features
Permanent abnormal dilatation of the terminal bronchi
Permanent fibrotic dilatation of the bronchi
What are the causes of bronchiectasis
Inflammatory
- Post-infectious
- Abnormal host defence (1º (hypogammaglobulinaemia) and 2º (chemotherapy, NG))
- Obstruction
- Post-inflammatory e.g. aspiration
- Secondary to bronchiolar disease and interstitial fibrosis (CFA, sarcoidosis)
- Systemic disease (connective tissue disorders)
- Asthma
Congenital
- Cystic fibrosis
- Primary ciliary dyskinesia (kartagener’s)
- Hypogammaglobulinaemia
- Young’s syndrome (rhinosinusitis, azoospermia and bronchiectasis)
What are the complications of bronchiectasis
Recurrent infections
Haemoptysis
Cor pulmonale
Amyloidosis
What is the cause of cystic fibrosis
Autosomal recessive
mutation in CFTR gene on Chr 7 (F508del) → defective Cl ion transfer → less water transfers to secretions → abnormally thick secretions
Allows growth of bacteria + frequent lung infections → bronchiectasis
What are the clinical features of cystic fibrosis
Lung → obstruction, recurrent infection → bronchiectasis → infection (pseudomonas, S. aureus, H. influenza, B. epacia)
Gi tract → meconium ileus, malabsorption
Pancreas → pancreatitis
Liver → cirrhosis
Male infertility
What is pulmonary oedema, its causes and its pathology
Parenchymal lung disease where fluid accumulation in alveolar spaces → poor gas exchange
Causes – LHF, alveolar injury, neurogenic, high altitude
- Intra-alveolar fluid on histology
- “Heart failure cells” = iron-laden macrophages
What is ARDS
Parenchymal disease of diffuse alveolar damage
Acute damage to endothelium ± alveolar epithelium leading to an exudative inflammatory reaction
What are the causes of ARDS in adults and neonates
Adults → acute respiratory distress syndrome / ARDS
- Infection
- Aspiration
- Trauma
- Inhaled irritant
- Shock
- Blood transfusion
- DIC
- Drug overdose
- Pancreatitis
Neonates = respiratory distress syndrome/ hyaline membrane disease of the newborn
- Insufficient surfactant in premature babies
What is the pathology of respiratory distress syndrome
Gross: fluffy white infiltrates in all lung fields, lungs expanded/firm, plum-coloured lungs, airless lungs, >1kg
Micro: capillary congestion, exudative phase, hyaline membranes, organising phase
What are the patterns of lung involvement in bacterial pneumonia
Bronchopneumonia
Lobar pneumonia
Abscess formation
Granulomatous inflammation
Describe the epidemiology, cause, and pathology of bronchopneumonia
Elderly
Low virulence organisms (staph, H. influenzae, strep, pneumococcus)
Pathology = patchy bronchial and peribronchial distribution, lower lobes, inflammation surrounding the airways themselves and is within the alveoli
What are the stages of lobar pneumonia
(1) Congestion: Hyperaemia, Intra-alveolar fluid
(2) Red hepatization: Hyperaemia, Intra-alveolar neutrophils (non-atypical)
(3) Grey hepatization: Intra-alveolar connective tissue
(4) Resolution: Restoration normal architecture
What are the causes and complications of lobar pneumonia
90-95% pneumococcus
Complications: abscess, pleuritis, effusion, empyema (infected effusion), fibrosis, sepsis
What are the features of atypical pneumonia
Mycoplasma, viruses (CMV, influenza), Coxiella, chlamydia, etc.
I.E. CMV pneumonia in those immunosuppressed
Interstitial inflammation without the accumulation of intra-alveolar inflammatory cells
Chronic inflammatory cells within alveolar septa with oedema ± viral infections
Define emphysema and what is the histology/pathology
Parenchymal type of COPD
permanent loss of alveolar parenchyma distal to terminal bronchiole
Pathology = Airspace enlargement, wall destruction
What are the causes of emphysema
Damage to alveolar epithelium:
Smoking (centrilobular loss)
A1AT deficiency (panacinar loss)
Rare (IVDU, connective tissue disease)
What are the complications of emphysema
Bullae formation → pneumonthorax
Respiratory failure
Cor pulmonale
What is interstitial lung disease
Group of >200 diseases characterized by inflammation and fibrosis of the pulmonary connective tissue, accounting for 15% of respiratory disease burden
What are the features of interstitial lung disease on presentation and investigation
Chronic SOB
Fine end-inspiratory crackles
Cyanosis, pulmonary HTN and cor pulmonale
rRduced FEV1 and FVR but normal FEV1/FVC ratio i.e. >70%) - RESTRICTIVE picture
Decreased CO diffusion capacity
Decreased lung volume
Decreased compliance
Advanced → ground glass/honeycomb appearance on CT CAP
What are the categories of interstitial lung disease
- Fibrosing
- Cryptogenic Fibrosing Alveolitis/ Idiopathic pulmonary fibrosis
- Pneumoconiosis
- Cryptogenic organizing pneumonia
- Associated with connective tissue disease
- Drug-induced
- Radiation pneumonitis - Granulomatous
- Sarcoid
- Extrinsic allergic alveolitis
- Associated with vasculitides e.g. Wegener’s, Churg-Strauss, microscopic
polyangiitis - Eosinophilic
- Smoking related
What are the features of Cryptogenic Fibrosing Alveolitis/ Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis
>50yo, male
>50% die in 2-3 years
progressive SOB/cough
Diagnosed on HR-CT
What are the histological features of Cryptogenic Fibrosing Alveolitis/ Idiopathic pulmonary fibrosis
Usual Interstitial Pneumonia
Progressive patchy interstitial fibrosis with loss of normal lung architecture and honeycomb change, beginning at periphery of the lobule, usually sub-pleural
Hyperplasia of type II pneumocytes causing cyst formation – honeycomb fibrosis.
Give examples of pneumoconiasis causes
Occupational lung disease - inhalation of mineral dusts/inorganic particles
Industrial lung diseases: asbestosis, silicosis, coal-miner’s lung
- Asbestosis → fine sub-pleural fibrosis with asbestos bodies in tissues (typically lower lobe)→ increased risk of adenocarcinoma/mesothelioma
What are granulomas
collection of histiocytes, macrophages ± giant multinucleate cells
What are the causes of granulomatous disease of the lung
TB
Fungal (histoplasma, Cryptococcus, coccidioides, aspergillus, mucor)
Others (pneumocystis, parasites)
Sarcoidosis
Foreign body (aspiration, IVDU)
Drugs
Occupational lung disease
What is the pathophysiology of Extrinsic allergic alveolitis and its presentation
Immune-mediated lung disorders caused by intense/prolonged exposure to inhaled ORGANIC antigens → widespread alveolar inflammation
(pts. get better over weekend away from work)
Presents with productive cough/SOB/clubbing/severe weight loss
What are the histological features of Extrinsic allergic alveolitis
Polypoid plugs of loose connective tissue within the alveoli/bronchioles
Granuloma formation
organising pneumonia
Give examples of occupation causes of granulomatous lung disease
Farmer’s lung: mouldy hay/grain/silage – Saccharopolyspora rectivirgula)
Pigeon fancier’s lung: proteins in excreta/feathers
Humidifier’s lung: heated water reservoirs –
thermactinomyces spp.
Malt-worker’s: germinating barley – Aspergillus
clavatus/fumigatus
Cheese washer’s lung: mouldy cheese – Aspergillus
clavatus/penicillium casei
What is the pathogenesis of sarcoidosis
abnormal host immunological response to variety of commonly encountered antigens, probably environmental in origin
Affects lungs, skins, lymph nodes and eyes
Lungs: discrete epithelioid and giant cell granulomas (usually upper zones → peri-lymphatic and peri-bronchial) → advanced disease becomes fibrocystic
How is sarcoidosis diagnosed
Non-caseating granulomas
Elevated serum ACE
Hypercalcaemia (1a-hydroxylase)
What are the risk factors for pulmonary embolism
Female
Immobility
Cardiac disease
Cancer
Primary and secondary hypercoagulable states (Virchow’s triad = stasis + vessel wall injury + hypercoagulability).
What is the pathophysiology of pulmonary embolism
95% originate from DVTs
Large emboli impact in the main pulmonary arteries → acute cor pulmonale, cardiogenic shock and death if >60% of pulmonary bed occluded
(N.B. occluding pulmonary trunk = saddle embolus)
Small emboli may can be silent or cause peripheral wedge infarctions
Repeated infarctions → pulmonary HTN
Give examples of non-thrombotic emboli
Bone marrow
Amniotic fluid
Trophoblast
tumour
Foreign body
Air
Fat
What is the definition of pulmonary hypertension
Mean pulmonary arterial pressure of >25mmHg at rest
N.B. normal response of lungs to hypoxia is to reduce blood supply to hypoxic areas of lungs and divert it to aerated zones → chronic hypoxia results in chronic vasoconstriction to pulmonary arterioles (COPD, fibrosing lung disease)
What is the pathophysiology of pulmonary hypertension
Pre-capillary (chronic hypoxia/embolus)
Capillary (Pulmonary Fibrosis)
Post-capillary (left heart disease/ veno-occlusive disease)
Pulmonary vasoconstriction of arterioles – intimal fibrosis, thickened walls
What are the complications of pulmonary hypertension
Right heart failure → venous congestion of organs (nutmeg liver), peripheral oedema
Describe pulmonary vasculitis
Uncommon
Present as life threatening haemorrhage, chronic haemoptysis, mass lesion, interstitial lung disease
Variety of patterns from granulomatous vasculitis involving small-medium sized vessels (GPA) through to a leukocytoclastic vasculitis involving capillaries (e.g with Rheumatoid arthritis)
Describe squamous cell carcinomas of the lung (representation, RFs, site, response to chemo, subtypes)
30-50%
RF: Men, smoking, p53/c-myc mutations
Proximal bronchi →local spread → late mets
Less responsive to chemo
There are a variety of subtypes e.g. papillary, basaloid
Associated with cavitation and hypercalcaemia due to paraneoplastic syndrome (PTHrp secretion).
Describe the histology and cytology of squamous cell carcinomas of the lung + progression
Histology: Keratinisation, intercellular prickles (desmosomes).
Cytology: Squamous cells
Describe the progression of squamous cell carcinomas
Progression: Epithelium → hyperplasia →squamous metaplasia→angiosquamous dysplasia→carcinoma in situ→invasive carcinoma
What are the features of adenocarcinoma of the lung (representation, definition, RF, site)
20-25%
Malignant epithelial tumour with glandular differentiation or mucin production
RF: women, non-smokers
In peripheral alveolar spaces → early mets
Describe the histology and cytology of adenocarcinomas of the lung
Histology: Glandular differentiation (gland formation and mucin production).
Cytology – cells containing mucin vacuoles. Molecular – EGFR mutations (non-smokers), K-rase (smokers)
Describe the progression of adenocarcinomas of the lung
Atypical adenomatous hyperplasia→non-mucinous BAC→mixed pattern adenocarcinoma
What are the features of small cell carcinomas (representation, RFs, site, prognosis, association)
10-15%
RF: smoking, p53, RB1
Occurs centrally, proximal bronchi
Highly malignant, metastasize early, usually by diagnosis commonly to bone, adrenal, liver and brain
Poor prognosis
Arises for neuroendocrine cells
→ ectopic ACTH secretion
→ Lamber-Eaton
→ SIADH
Describe the cytology and histology of small carcinomas
Cytology: small cells, ciliated normal resp. cell
Histology: Small, poorly differentiated “oat cells”
Describe large cell carcinomas and its histology
Poorly differentiated malignant epithelial tumour – large cells, large nuclei, prominent nucleoli.
Poor prognosis
Histology: No evidence of glandular or squamous differentiation
Give examples of paraneoplastic syndromes
ADH → SIADH (Small cell)
ACTH → Cushing’s syndrome (Small cell)
PTH/ PTHrP → primary hyperparathyroidism, hypercalcaemia and bone pain (Squamous cell)
Calcitonin → hypocalcaemia
Serotonin → carcinoid syndrome (flushing + diarrhoea + bronchoconstriction)
Bradykinin → cough
What are the molecular associations with lung cancers
ERCC1 – NSCLC = poorer response to cisplatinEGFR – adeno (usually) = target for Anti-EGFR (usually tyrosine kinase inhibitor (TKI)) therapy
Kras – adeno/squamous = poor prognosis, non-response to TKI
EML4-ALK – adeno (usually) = no benefit from TKI
How are lung cancers staged
TNM staging
Tumour (T1-4) – based on size and invasion of pleura, pericardium
Node metastasis (N0-2) -
- N0: lymph node not involved by tumour
- N1 or N2: lymph nodes involved (1 vs 2 depends on extent of involvement)
Distant metastasis (M0 or 1) - M1 – tumour has spread to distant sites.
Describe mesotheliomas
Malignant tumour of the pleura (parietal or visceral), associated with asbestos exposure
Extensive pleural effusion, chest pain and dyspnoea
Long latent (lag) period of 25-45 years for development
Poor prognosis
