Lung Pathology Flashcards
Acute vs chronic pattern of lung injury
Acute
• Inflammation (neutrophils)
• Edema/Pleural effusion
• Acute lung injury (ARDS/DAD = Diffuse alveolar damage)
• Pulmonary hemorrhage (infarct/vasculitis)
Chronic
• Inflammation (lymphocytes/macrophages)
• Fibrosis
• Emphysema
Describe the different types of pulmonary inflammation
Acute
• Polys
• Infection (bacterial)
Pattern of infection:
• Bronchopneumonia = patchy, distributed around airway
• Lobar pneumonia = diffuse
Also from infarct, abscess, DAD, any necrosis
Pulmonary abscess
o Localized suppurative process
o Walled off
o Oral anaerobes (60%), Staph, Gram-negative
o From aspiration, septic embolus, traumatic
Chronic
• Lymphocytes
• Infection (viral or chronic)
• Also from any chronic lung disease
Granulomatous • See macrophages/giant cells and lymphocytes Two types: (both appear similar) • Foreign body granulomas • Immune granulomas
Eosinophilic
• Infection (parasitic)
• Also from asthma, allergy, Eosinophilic syndromes
Causes of granulomas in lungs
TB infection Fungal infection Sarcoid Foreign body Wegeners Granulomatosis Hypersensitivity pneumonitis
Fungal pneumonia
Causes: Histoplasma capsulatum: -round to oval small yeast (2-5 microns) -darkly staining foci -narrow based budding
Coccidioides immitis:
- thick-walled, non-budding spherules (20-60 microns)
- often filled with small endospores
Blastomyces dermatitidis:
- round to oval large yeast (5-15 microns)
- Broad based budding
Aspergillis:
- 45 degree (acute) angle branching
- septated hyphae
Mucor:
- 90 degree (right) angle branching
- non-septated hyphae
So when see pulmonary granulomas in specimen
o Perform Acid-Fast and Fungal (GMS –Silver) stains
o Rules out mycobacterial and fungal infections
Granulomas from TB
caseating granulomas (necrosis)
Granulomas from sarcoid
o “Naked” bland granulomas (well-defined)
o Non-caseating
o Not associated with acute inflammation, necrosis, foreign material or demonstrable infectious agents
o See prominent hilar lymphadenopathy
Foreign body granulomas
o Has foreign material
o From IVDA/aspiration
Granulomas from Hypersensitivity pneumonitis
o Immune response to inhaled antigen
o Loose granuloma (not sarcoid)
o Without necrosis (not TB)
o No foreign material (not foreign body)
o Negative on AFB/GMS stain
o Suggests Type IV hypersensitivity reaction
o Also complement and Ig in vessels (Type III)
Other types:
• Farmer’s lung: thermophilic actinomyces in hay
• Pigeon Breeders Lung (Bird Fancier’s disease)
• Humidifier (or air-conditioner) lung = bacteria
Emphysema
- Irreversible enlargement of airspaces distal to terminal bronchioles
- Destruction of alveolar walls without obvious fibrosis
- Apical and subpleural bullae (“blebs”)
Types:
Centriacinar (centrilobular)
o Affects respiratory bronchioles (proximal acinus)
o Smoking
Panacinar (panlobular)
o Affects entire acinus (RB, AD, alveolus)
o Alpha-1-antitrypsin
BOTH: protease (elastin) and antiprotease (alpha-1-antitrypsin imbalance
Chronic bronchitis
- Persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in absence of any other identifiable cause
- Mucus gland hyperplasia
- Chronic inflammation
- Mucinous metaplasia of epithelium
Asthma
- Pulmonary hyperplasia
- Mucus plugs with eosinophils
- Sub-basement membrane thickened (type I and II collagen under type IV)
- Curschmann spirals (whorls of shed epithelium in mucus plugs) and Charlot-Leyden crystals (derived from eosinophils)
Bronchiectasis
• Permanent dilation of bronchi/bronchioles
• Destruction of muscle and elastic tissue
Associated with chronic necrotizing infection:
• Hereditary: CF, Kartageners (mucus/cilia)
• Infectious: necrotizing (TB, Staph, Aspergillus)
• Obstruction: tumor, foreign body
Pulmonary eosinophilia (IL-5)
Asthma, allergies, and parasites (secondary)
Loffler Syndrome = simple pulmonary eosinophilia
• Transient pulmonary lesions, peripheral (blood) eosinophilia, benign course
Acute eosinophilic pneumonia with respiratory failure
• Rapid onset acute illness of unknown cause
• Fever, dyspnea, hypoxemic repiratory failure
• BAL > 25% eosinophils
• Chest x-ray = diffuse infiltrates
• Prompt response to corticosteroids
Primary Ciliary Dyskinesia
- Autosomal recessive defect in dynein arms in cilia
- Retention of secretions → infection → bronchiectasis
Half of patients have Kartageners Syndrome:
• Triad: bronchiectasis, sinusitis, situs inversus
• Males = infertility
Cystic Fibrosis
CF in lungs = abnormal transport of Chloride and sodium
o Results in thickened viscous airway secretions
o Chronic infections
o Progressive respiratory failure
Gross Pathology: o Mucus plugging o Bronchiectasis o Consolidation o Green discoloration from pseudomonas infection
Histology:
o Dilated airways filled with mucous and pus (inflammation)
Idiopathic pulmonary fibrosis (IPF)
Histologic pattern = usual interstitial pneumonia (UIP)
o Repeated cycles of alveolar epithelial injury
o TGF-beta1 released from injured Type I alveolar epithelial cells → stimulates fibroblasts → fibrosis
o Temporal heterogeneity: key feature of UIP
• New/active fibrosis = “Fibroblastic foci”
• Old/collagenized dense fibrosis
o Progressive disease
• 3 year survival
Asbetosis
Two geometric forms: Amphibole • Aerodynamic = travel deeper/more distally • Less soluble (lasts longer) • More pathogenic • Fibrogenic • Causes mesothelioma Serpentine • Curly shaped (filtered out earlier) • Less pathogenic • More soluble • Fibrogenic
Complications: Pleural plaques • On diaphragm or chest wall • Most common manifestation of exposure • Dense fibrosis with dystrophic calcification
Pleural effusions Pulmonary fibrosis Malignancy Mesothelioma • Pleural based tumor encasing lung • Often grows along septae • Histology: TTF-1 marker to see if primary lung cancer Lung carcinoma
Histology
• Prussion blue (iron staining) → Ferruginous bodies
Silicosis
o Most prevalent chronic occupational disease
• Sand blasters mine workers
• Crystalline silacon dioxide (silica)-quartz
o Nodular fibrosing pneumoconiosis
o “Eggshell” calcifications on x-ray (double rim)
o Fibrotic nodules may polarize under light
o Increased susceptibility to TB
Pulmonary Thromboembolus
- 95% from Deep vein thrombosis of legs
- Large or saddle emboli lethal quickly
- Non-perfused lung → Respiratory compromise
- Hemodynamic compromise → acute cor pulmonale
- Loss of pulmonary venous return → decreased CO
- Electromechanical dissociated (rhythm on EKG, no pulses)
Histology = Lines of Zahn
• Layering effect due to thrombus forming in vessel with blood flow
• From alternating platelets, fibrin, and RBCs
• Allows identification of ante-mortem (true) thrombus vs. post-mortem clot
Smaller/peripheral emboli may infarct lung
o Cause pleuritic chest pain, hemoptysis, cough, dyspnea
o Wedge-shaped appearance
o In lungs = dual blood supply → red
Pulmonary HT
Occurs when mean pulmonary BP reaches ¼ of systemic levels (normally is 1/8th of systemic)
Causes:
o Increased pulmonary blood flow/pressure
o Increased pulmonary vascular resistance
o Left heart resistance to blood flow (CHF)
Diseases:
o COPD/ILD = hypoxia and loss of capillaries
o Congenital (shunts) or acquired heart disease
o Recurrent small thromboemboli → obstruct → increased PVR
o CT disease (ex: systemic sclerosis)
o Obstructive sleep apnea (with obesity)
Familial
Primary pulmonary HT (common in 20-40 yr old females)
Bone morphogenetic protein receptor type 2 (BMPR2)
• Normally BMPR2 → decreased proliferation and increased apoptosis
• If lose/defective BMPR2 → increased smooth muscle cells in vessels → pulmonary HT
Morphologic changes in Pulmonary HT
o Atherosclerosis of pulmonary artery
• Normally not seen in pulmonary vessels due to low pressures
o Medial hypertrophy (smooth muscle proliferation)
o Plexiform lesion: in advanced and severe Pulmonary HT
Pulmonary alveolar proteinosis (PAP)
o Like edema but acellular (only fluid), granular precipitate of surfactant
Acquired: (90%) anti-GM-CSF antibody (autoimmune)
• Decreased GM-CSF activity → reduced surfactant clearance → accumulation
Congenital: inherited GM-CSF or surfactant defects
Secondary: hematopoietic disease, malignancy
Diffuse alveolar damage (DAD)
o What we see in lungs/the histologic manifestation of ALI and ARDS
o Hyaline membranes = histologic hallmark
• Line alveoli
• Fibrin-rich edema fluid mixed with cytoplasmic and lipid remnants of necrotic cells
Pulmonary hemorrhage syndromes
Goodpasture syndrome
o Antibody against type IV collagen
o Basement membrane damage in lung and kidney
o Type II (Ab mediated) reaction
o Linear deposition of Ab along basement membrane
• Vs: SLE = granular pattern due to immune complex deposition in Type III reactions
o Most common cause of death = uremia
o Treat with plasmapheresis to remove antibody
Wegener granulomatosis
o Necrotizing granulomatous vasculitis
o Involves airways and kidneys
o Upper (sinus/pharynx) and lower (lungs) airways
o cANCA (anti-proteinase-3) in 95% patients
o Granulomas (necrotizing) and vasculitis
• Often infectious (fungal/TB/abscess) or neoplastic (necrotic tumor)
Histologically:
• Granulomatous inflammation with giant cells and vasculitis
• Need AFB/GNS stains (would be negative)
• Serum c-ANCA (anti-PR3) would be positive
