Lecture 17-18: Interstitial Lung Disease and Pathology Flashcards
PFT shows what in interstitial lung disease
Restrictive physiology and impaired gas exchange
ILD: acute or chronic?
Chronic typically
ILD: symptoms
Nonspecific: dyspnea, dry cough
ILD: FVC & TLC, DLCO, A-a gradient
Decreased FVC and TLC with PRESERVED FEV1 / FVC ratio, decreased DLCO, increased A-a gradient
ILD: hypoxemia?
Yes
ILD: imaging dx
High resolution CT scan to visualize fibrosis
Signs of fibrosis from early –> late
Increased reticular densities, traction bronchiectasis, honeycomb changes, cysts
What does reticular densities look like? Early or late?
Increased “lines” (thickened interalveolar septum); early fibrosis
What is traction bronchiectasis?
Dilated airways pulled apart (traction) by fibrosis
Honeycomb and cysts are evidence of what stage of firbrosis
Advanced
What is the histological pattern identified for idiopathic pulmonary fibrosis? Can this be associated with other disease?
Usual interstitial pneumonia (UIP); yes, known causes of pulmonary fibrosis can look like this
Is idiopathic pulmonary fibrosis deadly? Survival length?
YES: most deadly, median survival is 2.8 years
IPF: clinical features
Subacute, insidious dyspnea, cough, rales, CLUBBING, PFT’s restrictive, impaired gas exchange (DLCO, A-a gradient)
IPF: diagnostic blood test?
Nope
IPF: dx (2 findings from two different modalities)
CT scan: interstitial lung disease and biopsy: fibrotic changes –> fibroblast foci
IPF: gross
Dense, collagenous, dilated airways with large ares of scarring
IPF: pathogenesis
Alveolar epithelial cells injured (unidentified) with PERMANENT cell death and ABNORMAL cell growth = myofibroblast –> collagen and vascular remodeling
What is a myofibroblast
Both a SM cell (contractile properties) and a fibroblast cell that produces collagen
IPF: genetics (AD or AR?)
25% of IPF patients have a family member with interstitial lung disease; AD
If someone has family members with IPF and they get IPF, what is their course like?
More aggressive and occurs at a younger age
IPF: medical tx (2) and surgical tx
Pirfenidone (blocks pro-fibrotic cytokines) and nintedanib (trile tyorsine kinase inhibitor); lung transplant
Pirfenidone blocks what two factors?
TGF-beta and PDGF (platelet derived GF)
Nintedanib inhibits what three factors?
VEGF (vascular endothelial GF), FGF (fibroblast GF), PDGF
Lung transplant survival
5 year = 50%
Pulmonary manifestations of CT disease: systems that can be affected (5)
Parenchyma, airway, vasculature, serosal membranes (including effusion) and MSK
What is a drug-induced cause of interstitial lung disease?
Nitrofuranton (used to treat UTIs)
Describe sarcoidosis: main finding and organ systems
Noncaseating granulomas: delayed hypersensitivity reaction with unknown cause; multi-systemic disease (lungs in 80% of cases)
Sarcoidosis is a diagnosis of…
Exclusion (must rule out TB, fungal infections)
Sarcoidosis: radiological and histological finding
X-ray: enlarged lymph nodes in hilar areas; biopsy = large granulomas with multinucleated giant cells and NO NECROSIS
What is a typical outcome of ILD?
Honeycomb lung
Basics of ILD (4)
Decreased compliance, lung volumes, impaired diffusion/gas-exchange, development of pulmonary hypertension
One theory of ILD points to _________ as a possible cause
Abnormal wound healing
What components make up the interstitium
BM, fibroblasts, collagen fibers, elastic tissue
Describe UIP
Age: 50+; insidious onset; can be idiopathic, due to drug rxn, or collagen vascular/autoimmune disease
UIP pattern on histology plus idiopathic disease clinically =
IPF
UIP: pathoglogy (2 prime findings)
PATCHY fibrosis pronounced beneath pleura/interlobular septa; fibrosis exhibits TEMPORAL HETEROGENEITY (not all the same age)
What do we call the new region of temporal heterogeneity found on UIP?
Fibroblast focus (next to an area of dense, old fibrosis)
Two subtypes of non-specific interstitial pneumonia (NSIP). Worse/better than UIP?
Cellular and fibrosing; better (affects younger patients)
Cellular NSIP
Diffuse chronic inflammatory cell infiltrates without significant alveolar expansion; better prognosis than fibrosing
Fibrosing NSIP
Diffuse interstitial fibrosis with uniform appearance (temporally uniform), preserved lung architecture and chronic inflammation
How can we distinguish fibrosing NSIP from UIP
NSIP is not patchy and is all the same age
Describe lymphocytic interstitial pneumonia (LIP): who gets it, presentation, radiological finding
Rare: seen primarily in patient’s with Sjogren’s syndrome and HIV; presents as cough/dyspnea; radiology shows diffuse ground glass changes with cysts
LIP: histological finding
Small mature lymphocytes with variable numbers of plasma cells EXPANDING the alveolar septa
Interstitial lung diseases with graulomas: two
Sarcoidosis, hypersensitivity pneumonitis
Classic sarcoidosis findings (2)
Bilateraly hilar adenopathy and NON-NECROTIZING epithelioid granulomas
Who gets sarcoidosis?
20-40 years of age, F > M, black, rare in Asia
% sarcoidosis recovery, % with permanent pulmonary loss, rare outcome?
65%; 20%; small percentage progress to diffuse interstitial fibrosis
Describe sarcoid granulomas
Non-necrotizing epithelioid granulomas with tightly packed epithelioid cells, giant cells, lymphocytes; generally adjacent to bronchioles/vessels, etc
Dx of sarcoidosis requires…
Biopsy
Describe hypersensitivity pneumonitis
Lung disease due to an organic antigen, can be acute (within hours of exposure) or chronic (extended exposure, maybe with progressive fibrosis)
Hypersensitivity pneumonitis: classic triad
Chronic bronchiolotis, poorly-formed granulomas, organizing pneumonia
Hypersensitivity pneumonitis: long-standing disease may evolve into…
Diffuse fibrosis mimicking UIP or NSIP
Smoking-related interstitial lung disease (3)
Respiratory bronchiolitis associated interstitial lung diseae (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell histiocytosis
Describe RB-ILD
Clinical symptoms of an interstitial lung disease and only finding on biopsy is RB (the accumulation of macrophages with finely granular brown pigment ONLY around airways)
Describe Desquamative Interstitial Pneumonia (DIP)
Similar to RB-ILD but more diffuse and severe with insidious onset of SOB
DIP: histological findings
DIFFUSE collections of intraalveolar macrophages (as opposed to only around airways)
What is ABSENT in DIP
Minimal changes in alveolar septa and absent significant fibrosis
Describe Langerhans cell histiocytosis (on EM?)
Bronchiolocentric fibrosis with “stellate” scar formation and variable numbers of Langerhans cells (EM = Birbeck granule)
What does a Langerhans cell look like?
Polygonal with irregular nuclei with grooves
What do we call a macrophage filled with brown smoke material?
Smokers’ macrophages
