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
