Lung Pathology Flashcards
Pathological Classification of Pneumonia: site, causative agents, inflammatory cells
Broncho-/Lobar pneumonia vs Interstitial pneumonia
Broncho-/Lobar Pneumonia
- inside alveolar space
- caused by bacteria and fungi
- polymorphs and then macrophages
Interstitial Pneumonia
- alveolar septa
- viruses, protozoa and mycoplasma
- lymphocytes, eosinophils and macrophages
Bronchopneumonia vs Lobar pneumonia
Spectrum that overlaps
Broncho = starts at bronchi/bronchioles and extends to alveolar spaces
- neutrophil-rich exudate
==> patchy distribution of acute suppurative inflammation usually multi lobar, bilateral and basal (secretions gravitate)
==> may become confluent and progress to lobar pneumonia
Lobar = consolidation of whole lobe (may become subtotal with effective treatment)
(consolidation = “solidification” of lung due to replacement of air by exudate in alveoli)
Natural Course of Lobar Pneumonia (4 stages)
24h: CONGESTION due to vascular response
- vascular engorgement, intra-alveolar fluid
- heavy and hyperemic lung
2-4 days: RED HEPATISATION from acute inflammation
- alveolar space filled with extravasated RBC, fibrin deposits and polymorphs (neutrophils)
4-8 days: GREY HEPATISATION from chronic inflammation
- red cells lysed by macrophages
- fibrinosuppurative exudate persists (i.e. fibrin and neutrophils)
> 8 days: RESOLUTION by fibrosis
- fibroblastic proliferation replace neutrophils
- digestion of exudate to granular debris –> ingested by macrophages (foamy histiocytes) or organised by fibroblasts
(there may be pleural fibrinous reaction - pleuritis - in early stages if consolidation extends to surface –> may resolve or leave fibrous thickening)
Complications of Lobar Pneumonia
Abscess (tissue destruction and necrosis forms pus in new cavity), Empyema (spread to pleural cavity, pus in pleura), Sepsis (dissemination to valves, pericardium, brain, kidneys, spleen…)
Lung abscess: definition, mechanism of infection, causative agents, presentations, complications
- localised area of suppurative necrosis forming one or more large cavities
Mechanism
- aspiration of infected materials e.g. periodontal disease
- aspiration of gastric contents
- complication of nectrotizing bacterial pneumonia (s. aureus, klebsiella)
- bronchial obstruction (e.g. CA, bronchiectasis; impair drainage, distal atelectasis, aspiration of blood/ tumour fragments)
- septic emboli (IE)
- haematogenous spread from pyogenic infection
(also increased risk in underlying lung disease and immunocompromised)
Causative agents:
- mixed infection (oropharyngeal flora, S. aureus, ANAEROBES e.g. bacteroides, prevotella, peptostreptococcus, GN org)
Presentations:
- fever, malaise, LOW, anaemia
- productive cough with foul-smelling purulent sputum
- air-fluid level on CXR (abscess rupture into airway)
Complications:
- bronchopleural fistulas (rupture of abscess into pleura) –> empyema/ pneumothorax
- brain abscess, meningitis (embolisation to brain)
Occurs in 10-15% of bronchogenic carcinoma – need to rule out!
Community-acquired pneumonia: types, causative agents, presentations
Acquired from normal environment: Typical and Atypical
- bacterial pneumonias often follow viral URTI
Typical:
- S. pneumoniae (MC), H. influenzae (MC in acute exacerbation of COPD; can be life-threatening in children), Moraxella catarrhalis
- S. aureus secondary to viral infection, IVDA, higher risk of complications
- Klebsiella pneumoniae (debilitated and malnourished patients, chronic alcoholics)
==> abrupt onset of HG fever, chills, productive cough with purulent sputum +/- pleuritic pain
==> CXR: consolidation of ALVEOLAR exudate; WBC increased
Atypical:
- Mycoplasma pneumoniae (MC), chlamydophila pneumoniae
- Legionella pneumophilia (rare) - artificial aquatic env, organ transplants
- Viruses e.g. SARS, H5N1, Influenza A/B, RSV etc.
==> more in children and young adults
==> gradual onset of LG fever, non-productive cough with non-purulent sputum
==> CXR: patchy infiltrates (INTERSTITIAL inflammation), no consolidation; normal WBC
==> respiratory distress out of proportion to clinical signs (as alveolar wall inflammation leads to ventilation-perfusion mismatch)
Severe acute respiratory distress syndrome (SARS): pathology
Endemic in 2003
SARS-CoV coronavirus
- lung disease and diarrhoea partly due to overactive immune response
Pathology:
- INTERSTITIAL inflammation (congestion, lymphocytes) –> DIFFUSE ALVEOLAR DAMAGE – pink hyaline membrane lining alveolar wall, intra-alveolar oedema and necrosis of type I pneumocytes
- Cytopathic effect: MULTINUCLEATED GIANT CELLS formed by reactive pneumocytes or macrophages
- Organisation: fibroblastic proliferation (fill air spaces) and macrophages
CXR ==> diffuse haziness
Progressive in 7-10 days
Can be seen by in situ hybridisation of viral genome, IHC with Ab against viral protein or EM
Avian flu (H5N1): adverse outcomes
Airborne
Most cases recovered but fatal cases seen in some children and fit adults
– overwhelming immune response - HAEMOPHAGOCYTIC SYNDROME
==> overactive lymphocytes and macrophage engulf blood cells in body including RBC, WBC, platelets
Nosocomial pneumonia: risk factors, causative agents
Hospital acquired
- usually severe underlying diseases, immunocompromised, invasive devices e.g. mechanical ventilator, prolonged antibiotics
Agents:
- pseudomonas aeruginosa (neutropenic, extensive burns, mechanical ventilation)
- enterbacteriaceae
- s. aureus
Pathology similar to typical/atypical pneumonia depending on microbes
P. aeruginosa can invade vessels with extra pulmonary spread (fulminant disease)
Aspiration pneumonia: risk factors, causative agents, common site, effects
Usually in elderly, debilitated, bedridden
Abnormal gag and swallowing reflex e.g. post-anaesthesia, unconscious, repeated vomiting, chronic alcoholism
Caused by anaerobic oral flora (e.g. bacteroides, prevotella) admixed with aerobic bacteria (typicals)
Commonly in right lung (bronchus more straight),
Acute onset, Fulminant course –> necrotising pneumonia and abscess formation
Effects of smoking and alcohol on lung infections
Smoking - impair mucociliary clearance and compromises macrophage activity
Alcohol - impairs neutrophil function and affects cough/ epiglottic reflexes
Pulmonary Tuberculosis: organism, presentations, pathophysiology, pathology
Mycobacterium tuberculosis
(can be caused by atypical species in immunocompromised patients e.g. MAI)
- AFB, ZN stain
Presentations:
- generally asymptomatic focus of pulmonary infection appears that is self-limited (evidence is tiny fibrocalcific nodule where viable org remains dormant - Ranke complex)
- fever, drenching night sweat, weight loss
Tuberculin (Mantoux test) - delayed cell-mediated hypersensitivity to tubercular antigens (can’t distinguish infection and disease; limitation of false negatives)
Pathophysiology
- first 3 weeks: bacteria enter alveolar macrophage (histiocytes) –> cord factor prevents fusion of lysosome and phagosome –> persist and proliferate –> bacteraemia +/- seeding to multiple organs in NRAMP1 polymorphism (but asymptomatic or “mild flu”
- after 3 weeks: type IV HSR - cell mediated immunity –> antigens reach LN and presented to CD4 T cells –> CD4 Th1 lymphocytes activated:
==> secrete IFN to activate macrophages –> secrete TNF: activate monocytes into epithelioid histiocytes; increase NO to kill MTB
==> formation of granulomas (halt infection before destruction and illness) and caseous necrosis –> GHON FOCUS –> cavitation
Pathology
- macroscopic: caseating granuloma, may resemble SQCC of lung but different locations (TB middle-zone and subpleural vs SQCC centrally located)
- microscopic: focal accumulation of epithelioid cells and Langhan’s giant cells with rim of surrounding lymphocytes and central caseous necrotic core
+ regional LN caseate = Ghon complex (fibrocalcification with scarring as infection contained)
TB disease course: primary and secondary
Primary TB
- sub pleural location
- ghon focus and ghon complex
- outcome
- -> resolve
- -> progress to haematogenous dissemination and miliary TB (usually immunocompromised e.g. AIDS - can’t mount CD4 T cell response to contain org –> no granulomas; NRAMP1 polymorphism)
- -> latency (foci of scarring/ fibrosis/ calcification as infection is controlled by type IV HSR, with viable bacteria)
Secondary TB
- reactivation in immunocompromised or re-infection
- usually upper zone/ apical (highest ventilation)
- cavitation due to type IV HSR (erosion and dissemination into airways; produce sputum)
- heal with fibrosis
or - progressive pulmonary TB
(lesion enlarge, erode into bronchus, form irregular cavity lined by caseous material –> treatment can arrest process but pulmonary architecture distorted by fibrosis
–> if inadequate Tx or defences impaired then infection spreads by direct extension or through airways, blood and lymphatics) - miliary pulmonary TB = org reach blood through lymphatics and recirculate to lung via pulmonary arteries; systemic if disseminate through body e.g. liver, BM, kidneys, meningitis, osteomyelitis/ Pott disease, salpingitis
- pleural effusions, tuberculous empyema, obliterative pleuritis
- lymphadenitis is most frequent extra-pulmonary TB (cervical region)
Pneumonia in immunocompromised host
Fungal infections
- candida albicans (bilateral nodular infiltrates)
- pneumocystis jirovecii (reactivation, esp. in AIDS; interstitial pneumonitis, intralveolar foamy pink granular exudate, septa thickened with edema; Dx by BAL or induced sputum - Grocott’s/ Toluidine O blue – round/cup shaped cysts)
- cryptococcus (pigeon droppings; AIDS/ haematolymphoid malignancy; lung necrosis, congestion; India ink clear halo, latex agglutation assay)
- aspergillus (aspergilloma - non-invasive; allergic bronchopulmonary aspergillosis - Type 1 and 3 HSR, IgE, eosinophilia; invasive aspergillosis - necrotising, parenchymal and vessel invasion, systemic dissemination –> haemorrhage, vascular necrosis and infarction; sepated, acute angles)
- mucormycosis (zygomycetes; non septate; also invasive like aspergillus)
Viral infections
CMV
– congenital or perinatal infections
– mononucleosis in immunocompetent (fever, LN, hepatomegaly)
– disseminated life-threatening disease in immunocompromised (retinitis, pneumonitis, colitis)
– gigantic cells with nuclear (owls eye with clear halo) and cytoplasmic inclusion bodies
Lung Tumours epidemiology and facts
CA lung is 1st in mortality and 2nd in incidence in HK
- no guarantee of survival even in the mildest form
Hamartoma is the most common tumour (benign neoplasm) due to overgrowth of native tissues e.g. cartilage, respiratory epithelium, lung parenchyma
Clinical presentations of CA lung: risk factors, local, systemic and metastasis symptoms
Risk factors: smoking, asbestos
Usually present at late stage
Local symptoms:
- cough (MC), haemoptysis, obstructive pneumonia
- compression effect: SVCO, pancoast tumour
- pleural effusion
Systemic:
- constitutional symptoms e.g. fever, LOW, cachexia
- paraneoplastic conditions (more in SQCC and SCLC)
- neurological e.g. Lambert-eaton myasthenia syndrome (SCLC)
- endocrine e.g. hyperCa of malignancy (SQCC only), SIADH (SQCC, SCLC), Cushing’s (SCLC, ADC, Carcinoid), oncogenic osteomalacia
- rheumatological e.g. hypertrophic osteoarthropathy
Metastasis:
- bone (pathological fracture)
- brain (neurological manifestation e.g. seizure)
Pancoast tumour effects
Tumour at superior pulmonary sulcus with destruction at the thoracic inlet
- invasion of lower brachial plexus and cervical sympathetic chain
Symptoms:
- shoulder pain radiation to axilla and scapula, along ulnar nerve distribution up to hand
- Horner syndrome: anhidrosis, miosis, ptosis, enophthalmos
- compression of vessels due to oedema
Staging of lung cancers
T1 <3cm
T2 3-5 cm or involving main bronchus, visceral pleura or obstructive pneumonia
T3 5-7 cm or invading chest wall, phrenic nerve, parietal pericardium or separate tumour nodule in same lobe
T4 >7cm or invading diaphragm, trachea, carina, mediastinum or separate nodule in different ipsilateral lobe
Classification and types of lung tumours
Small cell carcinoma (part of neuroendrocine tumours)
vs.
Non-small cell carcinoma: ADC, SQCC, LCLC, (Adenosquamous carcinoma)
Neuroendocrine tumours - carcinoid/ atypical carcinoid, large cell neuroendocrine carcinoma, SCLC
Lung adenocarcinoma (ADC): a/w smoking?, location, pathology, IHC
Most common primary lung cancer
- least a/w smoking; can be see in young female non-smokers
- location: peripheral or central (P>C)
Pathology:
- Architecturally: glandular differentiation, desmoplastic stroma; forming infiltrative, irregular and complex glands (but may have multiple patterns including lepidic, solid, papillary, micro-papillary)
- Cytogically: malignant characteristics, mucin
IHC - mucin stain, TTF-1, Napsin A
a/w scar due to desmoplastic reaction
Pathogenesis of ADC from precursor lesions
ADC in situ
- previously bronchioloalveolar CA
- single or multiple lesions <3 cm, without invasion
- ill defined greyish soft lesion, consolidation
- CXR: ground-glass appearance
- excellent prognosis
Minimally invasive ADC
- single lesion <3 cm and maximum stromal invasion of 5mm
- no lymphovascular or pleural invasion
- lepidic pattern predominant
- CXR: ground glass with central opacity
- excellent prognosis
Progression:
- atypical adenomatous hyperplasia (<5mm) –> ADC in situ –> invasive ADC
Squamous cell carcinoma (SQCC): a/w smoking?, location, pathology, IHC, pathogenesis (course)
Strongest association with smoking (male-predominant)
Location: central (main airways, hilar region)
Pathology
- architecturally: squamous differentiation, keratinisation/ keratin pearls, forming infiltrative sheets and nests
- cytologically: malignant characteristics, intercellular bridges
IHC: CK5/6, p63
Pathogenesis:
- squamous metaplasia of bronchial epithelium –> dysplasia –> carcinoma
Others: obstruction of central airways may cause pneumonia in distal parenchyma
Large cell carcinoma (LCLC): diagnosis
Diagnosis by exclusion (NSCLC lacking ADC or SQCC differentiation)
Not a single entity
Small cell carcinoma (SCLC): a/w smoking?, location, prognosis, pathology, IHC, EM
Old age, aggressive NE tumour, a/w smoking
Location: central
Widespread metastasis usually presenting at advanced stage
- treat with chemo - good initial response by recur quickly
- poor prognosis overall
Pathology:
- small cells = scanty cytoplasm
- oat cells = crushing and “moulding” nuclei
- hyperchromatic nuclei, fine chromatin, indistinct nucleoli
- frequent mitotic figures and apoptotic bodies
- azzopardi effect: hematoxyphilic vascular walls due to chromatin diffusion secondary to tumour cell necrosis
IHC: NE markers e.g. chromogranin, synaptophysin
EM: electron dense granules
Carcinoid tumour: types, pathology, IHC
10% of all carcinoid, 1% of lung tumours
- most benign (typical)
- may be malignant (atypical; TP53 mutations)
Pathology:
- “organoid” pattern
- uniform cytology with regular round nuclei in typical carcinoid; atypical cytology with mitotic activities and small foci of necrosis in atypical carcinoid
- NE features e.g. NE markers, neuro-secretory granules in EM
Lung as a common site for metastasis: common primaries, routes of spread and gross morphology, differentiation of primary and metastasis
Breast > colon > RCC (and many more)
Haematological spread: multiple diffuse cannon-ball lesions in lung parenchyma
Lymphatic spread: lymphangitis carcinomatosis; peripheral at interlobular septum/ pleural surface and central at bronchovascular interstitium
Clinical, pathological and radiological evidence needed to differentiate synchronous (multiple primaries within 6 mths) tumours vs intra-pulmonary metastasis and metachronous (secondary primary after 6 mths) tumours vs metastasis
Pleural mesothelioma: risk factors, course of progression, manifestations, metastasis, histology
Malignant neoplasms of the pleura
- Risk factors: asbestos exposure
- latent 25-40 years (delayed presentation)
Course: extensive pleural fibrosis –> plaque –> mesothelioma
Manifestations:
- pleural effusion
- compression e.g. SVCO, pancoast tumour
- relentless local spread (diffuse) but metastasis is rare
Histology:
- epithelial or sarcomatoid or biphasic pattern
- characteristic gross morphology
Pathological diagnosis methods (conventional and auxiliary)
Conventional
- histology: biopsy, excision
- cytology: BAL, sputum, pleural fluid, FNA
Auxiliary techniques
- IHC
- molecular/ biomarkers (PCR, FISH)
- EM (ultrastructure)
–> diagnostic, prognostic, predictive
Molecular classifications of ADC: purpose, common mutations in HK, pathogenesis, potential therapies
Identification of “driver genetic mutations” associated with cancer proliferation and survival
–> potential targeted therapy (anti-cancer effects with minimal adverse effects on host)
HK: EGFR > KRAS > ALK
EGFR in 40-60% asians with ADENOCARCINOMA
- constitutive activation of EGFR downstream signalling leading to cell proliferation, migration, invasion, inhibition of apoptosis etc
- more resistant to traditional chemo, higher metastatic potential, worse prognosis
ALK fusion gene resulting in activation of RAS and PI3K-AKT (translocation upregulates expression in lungs)
EGFR TKI: erlotinib, gefitinib
KRAS: mutually exclusive with EGFR, no drug available
ALK TKI: crizotinib (but may not all respond well/ eventually develop resistance)
PD-1 immune checkpoint: tumour cells produce PD-L1 to suppress T cell response –> Anti-PD1 Ab e.g. pembrolizumab or Anti-PD-L1 Ab e.g. atezolizumab
Molecular testing and targeted therapy of colorectal ADC vs lung ADC (genetic defect, therapy, molecular test)
Colorectal ADC
- EGFR overexpression in 80%
- therapy: anti-EGFR monoclonal Ab e.g. cetuximab, panitumumab
- molecular test: KRAS/NRAS mutation which predicts ineffecive targeted therapy
Lung ADC
- EGFR activation mutation in 40-60%
- therapy: EGFR TKI e.g. erlotinib, gefitinib
- molecular test: EGFR mutation predicts effective targeted therapy
Functional anatomy of airway: definition of lobule and acini
Lobule = pre-terminal bronchiole + 3-30 acini
Acini = functional unit of lung; respiratory bronchiole and associated alveolar ducts and sacs
Obstructive vs Restrictive Lung Diseases: definition, mechanism, FEV1/FVC, examples
Obstructive = progressive largely irreversible obstruction of airflow out of lung
- mechanism: increased resistance to outflow
- FEV1/FVC <0.8
- narrowed airways e.g. asthma, chronic bronchitis, bronchiectasis
- loss of elastic recoil e.g. emphysema
Restrictive = reduced total lung capacity
- mechanism: decreased expansion of lung parenchyma
- FEV1/FVC normal
- chest wall disorders e.g. obesity, kyphoscoliosis, pleural disease, GBS
- acute interstitial disease e.g. ARDS
- chronic interstitial disease e.g. idiopathic pulmonary fibrosis, pneumoconiosis, sarcoidosis (infiltrative)
Chronic obstructive airway diseases: examples and complications
Common
- majority have mixed emphysema and chronic bronchitis (as both caused by smoking) - COPD (IRREVERSIBLE airway obstruction)
Emphysema, chronic bronchitis, asthma, bronchiectasis, small airway disease (bronchiolitis)
Complications:
- acute exacerbation of COPD
- pulmonary HT, cor pulmonale
- pneumothorax (bullous emphysema)
- secondary polycythaemia (chronic bronchitis)
- respiratory failure (+ respiratory acidosis)
Emphysema (acinus): definition, types and pathology (site, V/Q, ABG, cause)
Histopathological definition (not clinical): permanent ENLARGEMENT of airspaces distal to terminal bronchioles, accompanied by DESTRUCTION of their walls without obvious fibrosis
Pathology: - Centriacinar and panacinar most common Centriacinar - at respiratory bronchioles, upper lobes, more central? - V/Q decreases (decreased ventilation without decreased perfusion) - severe change in ABG - caused by smoking and pneumoconiosis - more common than panacinar
Panacinar
- whole acini, lower lobe, more peripheral/ subpleural
- V/Q normal (both affected)
- less drastic ABG change
- caused by alpha-1 antitrypsin deficiency
- if very severe, can form bulla
(more pale and voluminous lung)
Other types that don’t cause obstruction
- paraseptal: distal part of acinus – form bullae –> pneumothorax
- irregular: localised disease associated with scar tissue
Emphysema pathogenesis and manifestations, CXR
Protease-antiprotease imbalance:
- alpha-1 antitrypsin is major inhibitor of protease produced by neutrophils, which degrades elastin in lungs
- deficiency = loss of connective tissue support
(PiZZ defect)
Oxidant - antioxidant imbalance:
- reactive oxygen species from tobacco
- ->inactivates AAT causing functional deficiency
- -> depletes antioxidant mechanisms
==> loss of elastic recoil/ connective tissue –> airway collapse during EXPIRATION
Manifestations:
- older and thin patients
- “pink” (hyperventilation to compensate for less O2
- “puffer” - early severe dyspnea
==> adequate gas exchange until late disease
- late hypoxaemia, respiratory alkalosis, quiet chest
- CXR: hyperinflated lung, flattened diaphragm
Chronic bronchitis (bronchus): definition, pathology, pathogenesis, aetiology, manifestations, severe complications
Clinical definition = peristent productive cough for >3 months in a year for >2 consecutive years
Pathology:
- MUCUS HYPERSECRETION beginning at the large airways then small airways
- due to goblet cell metaplasia and gland hyperplasia
- airway INFLAMMATION (oedema) and FIBROSIS
- increased REID INDEX (>0.4) i.e. enlargement of mucus secreting glands
Pathogenesis:
==> airway obstruction due to MUCUS PLUGS in SMALL AIRWAYS and inflammation/FIBROSIS (bronchiolitis) – complete obstruction in severe cases = bronchiolitis obliterans
==> due to coexisting emphysema
Aetiology:
- smoking
- air pollutants
Manifestations:
- obese and cyanotic
- “blue bloater” (elevate Hb to compensate low O2 – less ventilation and oxygenation)
- early hypoxaemia (absence of increased respiratory drive with retention of CO2)
- late dyspnea, respiratory acidosis
- productive cough
- wheezing and rhonchi
- progressive disease can lead to pulmonary HT and cardiac failure; recurrent infections; resp failure
Asthma (bronchus): definition, pathology, airway remodelling, presentations
Chronic inflammatory disorder of airways with episodic and reversible (bronchodilator/ steroids) airway obstruction
Pathology:
- gross: hyperinflated lungs, mucus plugs
- microscopic:
- bronchi - smooth muscle HYPERTROPHY, thickened basement membrane, oedema
- bronchiole - Curschmann spirals, Charcot-leyden crystals
Airway remodelling
- smooth muscle hypertrophy, thickened basement membrane, oedema, increase submucosal glands and vascularity, increase eosinophils and mast cells
Presentations
- recurrent wheezing (bronchoconstriction), nocturnal cough, chest tightness and dyspnea
- respiratory alkalosis (acidosis indicating severe case needing intubation)
- prolonged severe attacks: status asthmaticus
Asthma: causes and pathogenesis
Extrinsic / Atopic (70%)
- immunological sensitivity to environmental antigens
- Type I HSR stimulating CD4 Th2 cells which produce:
- IL4 –> increase IgE – stimulate mast cells in early phase (vascular permeability, vasodilation, mucous, bronchoconstriction)
- IL5 –> activate eosinophils – late phase (major basic proteins cause airway damage)
- IL13 –> increase mucus secretion
(+ve family hx of atopic illness, prev hx of allergic rhinitis/ eczema, present in childhood, wheal and flare skin test)
Intrinsic (30%)
- mechanisms not clear (possible viral inflammation lowering threshold of sub epithelial receptors to irritants)
- common mediators of reaction (eosinophils; no IgE!)
- commonly caused by viral infections, air pollutants, (aspirin, stress, cold)
- no family hx
Bronchiectasis (bronchus): definition, pathology, pathogenesis, aetiology, presentations
Histolopathological definition = SECONDARY permanent dilation of bronchi and bronchiole
Pathology:
- MC in lower lobes and vertical airways
- ABNORMAL DILATED airways (up to 4x) that extend almost to pleural surface
- acute and chronic inflammation, ulceration, desquamation and scarring (fibrosis)
Pathogenesis:
- CHRONIC PERSISTENT infection –> damage elastic tissues and smooth muscle –> weakening and dilation of airways
- Bronchial obstruction –> decrease clearance
Aetiology:
- infection e.g. TB, necrotising pneumonia (s. aureus, klebsiella higher virulence)
- bronchial obstruction e.g. tumour, foreign bodies, mucous impaction
- congenital e.g. CF, Ig immunodeficiency, Kartagener syndrome
Presentation:
- cough with copious amounts of purulent sputum
- haemoptysis
Small airway diseases (chronic bronchiolitis): definition, pathology, pathogenesis, aetiology, presentations
Definition: airway obstruction of NON-CARTILAGINOUS airway with internal diameter of <2mm (up to and including respiratory bronchioles)
Pathology:
- inflammatory scarring (peribronchiolar fibrosis) and cellular bronchiolitis (lymphocytes)
- mucous plugging due to goblet cell hyperplasia
- -> bronchiolitis obliterans
Pathogenesis:
- CONSEQUENCE of disease
- a/w chronic bronchitis, infections, COAD etc.
Aetiology
- smoking, air pollutants
Presentation
- cough, dyspnea (+ other specific to primary disease)
Chronic diffuse interstitial diseases: general pathology, pathogenesis, presentations, CXR, outcome
RESTRICTIVE lung disease
General pathology:
- inflammation and fibrosis of connective tissues –> scarring, contraction of fibrous tissue and gross destruction of normal architecture with enlarged spaces
==> HONEYCOMB LUNG
- bronchiolisation (epithelium of alveoli replaced by bronchiole type ciliated columnar epithelium)
Pathogenesis:
- many unknown
- alveolitis –> damage to type I/II pneumocytes (activate macrophages and release fibrogenic cytokines) –> decrease compliance but increase elasticity –> decrease FEV1 similar to FVC
Presentations:
- dyspnea, tachypnea, end-respiratory crackles, dry cough
==> eventually cyanosis WITHOUT WHEEZING (non-obstructive)
CXR: bilateral infiltrative lesions, reticulonodular pattern
Outcome:
- secondary pulmonary HT, RHF with cor pulmonale
Different types of chronic interstitial lung disease
Fibrosing
- usual interstitial pneumonia/ idiopathic pulmonary fibrosis
- bronchiolitis obliterans organising pneumonia (BOOP)
- pneumoconiosis
Granulomatous
- sarcoidosis
- granulomatous
Smoking
- desquamative interstitial fibrosis
Autoimmune
- pulmonary alveolar proteinosis
Idiopathic pulmonary fibrosis: pathology, pathogenesis, prognosis, treatment
Primary
Pathology: Usual interstitial pneumonia
- fibrosing
- affect mainly lower lobes/ sub pleural/ interlobular septa
- both EARLY and LATE lesions present
- “fibroblastic foci” of young granulation tissue at sub pleural areas
- PATCHY INTERSTITIAL FIBROSIS
Pathogenesis:
- repeated cycles of epithelial activation and repair/ injury by unknown agents
- driven by TGF-beta1 ==> FIBROBLASTIC PROLIFERATION
Prognosis:
- poor
- mean survival 3 years (rapidly declining course)
Treatment:
- lung transplant
- nintedanib (GFR inhib), pirfenidone (TGF inhib)
Bronchiolitis obliterans organising pneumonia: pathology, CXR, pathogenesis, treatment
Primary
NOT bronchiolitis obliterans! (chronic diseases, no sig. X ray)
Pathology:
- fibrosing
- polypoid plugs of loose organising connective tissue (granulation tissue) within alveolar ducts and alveoli, often with bronchiolitis
- ALL AT SAME STAGE
- NO INTERSTITIAL FIBROSIS NOR HONEYCOMB
CXR: subpleural or peribronchial patchy consolidation
Pathogenesis:
- usually caused by acute infection, connective tissue disease or autoimmune disease
Treatment:
- recover spontaneously
- most need steroids for months to recover (good response)
Pneumoconiosis: pathogenesis, general pathology, asbestosis features and specific pathology, silicosis features, risk of CA and mesothelioma
Occupational
Reaction to inhalation of INORGANIC mineral dusts 1-5 micrometer ( + organic and inorganic particulates, chemical fumes and vapours)
General pathology:
- FERRUGINOUS BODIES (golden brown beaded rods, fusiform shape with translucent centre; inorganic particulates coated with iron containing proteinaceous material when macrophages phagocytose them)
- Fibrosing
Asbestosis:
- serpentine chrysotile (more common, less pathogenic; more flexible and soluble)
- amphibole (less common, more pathogenic for mesothelioma; stiff and less soluble, go deeper into lung and penetrate epithelial cells)
==> both fibrogenic
- pathology: more common in lower lobes; ASBESTOS BODIES, diffuse fibrosis subpleurally first then spread to middle and upper lobes, PLEURAL PLAQUES from fibrosis (parietal pleura/ dome of diaphragm)
- Lung CA (5x), Mesothelioma (1000x)
Silicosis:
- more common upper lobe
- risk of TB but not CA
- quartz stimulates alveolar macrophages to release cytokines for fibrogenesis
- concentrically arranged hyalinised collagen fibres around amorphous centre (“whorled appearance”)
- weakly birefringent silica
Sarcoidosis: pathology, organ effects
Primary
Granulomatous
Systemic disease
NON-CASEATING granulomas (collection of epithelioid histiocytes without many lymphocytes)
Hilar LN, lung, eye, skin, viscera (liver, spleen)
Hypersensitivity pneumonitis: pathology, pathogenesis
Occupational
Farmer’s lung/ bird fancier’s lung
Granulomatous
- allergic alveolitis a/w known inhaled ORGANIC antigen
- peribronchiolar location; chronic inflammation; “loose”, poorly formed granulomas without necrosis
Desquamative interstitial pneumonia: cause, risk groups, presentation, pathology, treatment and prognosis
All smokers
- 4th - 5th decade, M>F
- insidious onset of dyspnea, dry cough for weeks or months, clubbing of digits
Pathology:
- alveoli filled with pigment-laden macrophages
Treatment:
- cessation of smoking and steroids (100% response)
Pulmonary alveolar proteinosis: pathogenesis, pathology
Rare autoimmune
Pathogenesis:
- acquired anti-GM-CSF Ab, congenital (rare), secondary to haematopoietic disorders, malignancies…
Pathology:
bilateral patchy asymmetric opacifications
–> accumulation of acellular surfactant in intra-alveolar and bronchiolar spaces
- Homogenous PAS+ve granular precipitar, minimal inflammation
Pulmonary Hypertension pathology
Medial hypertrophy of pulmonary muscular and elastic arteries
Pulmonary arterial atherosclerosis
Right ventricular hypertrophy
(plexiform lesion in advanced cases)
Goodpasture syndrome pathology
Lung injury due to circulating antibodies against certain domains of type IV collagen
==> necrotising haemorrhagic interstitial pneumonitis
- diffuse alveolar haemorrhage and focal necrosis of alveolar walls
- abundant haemosiderin (previous haemorrhage)
- linear pattern of Ig deposition in renal biopsy
