B4.056 - Restrictive Lung Diseases: Interstitial Lung Disease Flashcards
Diseases affecting the pulmonary interstitium result in
Effective loss of lung tissue
decrease in lungs ability to expand
decrease in the lungs ability to transfer oxygen or CO2 within the blood
what are fibrosisng interstitial lung diseases
- idiopathic pulmonary fibrosis
- non specific interstitial pneumonia
- cryptogenic organizing pneumonia
- drugs
- connective tissue diseases
- pneumoconiosis
- radiation
what are granulomatous interstitial lung diseases
- sarcoidosis
- hypersensitivity penumonitis
what re smoking related interstitial lung diseases
desquamative interstitial pneumonia
what are other interstitial lung diseases
pulmonary alveolar proteinosis
langerhans cell histiocytosis/eosinophilic granulom
characterize idiopathic pulmonary fibrosis
chronic progressive fibrosing interstitial lung disease without an identifiable cause and with a high mortality rate
how do you diagnose idiopathic pulmonary fibrosis
progressive scarring of lung parenchyma and loss of lung function
characteristic clinical, pathologic and radiologic findings
typical histologic pattern is usual interstitial pneumonia (UIP)
how do you get IPF
environmental exposures
genetically predisposed prone to aberrant repair of recurrent alveolar epithelial cell injury
increased fibrogenic cytokines like TGFbeta
what is the epidemiology of idiopathic pulmonary fibrosis
older, smoker maybe
describe the presentation of idiopathic pulmonary fibrosis
insidious onset of worsening dyspnea and dry couhg
5th - 6th decade at presentation
fine bibasilar inspiratory crackles in >80% of patients, with progression upward as teh disease advances
subsequent hypoxemia, cyanosis and clubbing
cobblestoned pleural surface seen in idiopathic pulmonary fibrosis
due to fibrosis of interlobar septae
extensive fibrosis, accentuated subpleurally and in lower lobe
seen in idiopathic pulmonary fibrosis
what is this and what is the blue line pointing to
Usual interstitial pneumonia
Fibroblast focus (plump fibroblasts)
what is this and when is it seen
Left arrow - established (late) fibrosis
Right arrow - uninvolved, note subpleural area more affected
Usual interstitial pneumonia
seen in idiopathic pulmonary fibrosis
what is characteristic of the distribution of idiopathic pulmonary fibrosis
spatially and temporally hetoerogenous distribution: i.e. normal and abnormal areas, early fibrosis (fibroblast foci) and established fibrosis
UIP in IPF
end stage lung with honeycomb fibrosis
UIP in IPF
what is the differential for UIP microscopic pattern
Idiopathic pulmonary fibrosis
collagen vascular disease
drug
chronic hypersensitivity pneumonitis
asbestosis
course of IPF
chronic progressive, downhill course
may have acute exacerbations
progressive lung disease, end stage lung and/or pulmonary hypertension
increased risk of lung cancer
respiratory failure most frequent cause of death
what are the 2 drugs for treatment of IPF
pirfenidone - antifibrotic med
nintedanib - TKI inhibits fibrosis pathways
definitive treatment of IPF
transplant
post transplatn 5- yr survival about 50-60%
what is the etiology of cryptogenic organizing pneumonia
unknown!
what are characterstics of cryptogenic organizing pneumonia
polypoid plugs of loose organizing connective tissue within small airways, alveolar ducts, and the surrounding alveoli
cryptogenic organizing pneumonia
note: polypoid plugs
cryptogenic organizing pneumonia
what are the symptoms of cryptogenic organizing pneumonia
variable onset
cough
dyspnea
may sponteneously resolve
treatment for cryptogenic organizing pneumonia
steroid treatment for most patients for complete recovery
what is the differential for organizing pneumonia pattern
viral and bacterial
inhaled toxins
drugs
collagen vascular diseases
GVHD
what is pneumonconiosis
non neoplastic reaction of teh lung to inhaled mineral dust, organic particles or chemical vapros
what size of inspired particles can affect pneumonconiosis
1-5 microns they can go further down past escalator
what does solubility of particles affect in pneumonconiosis
if theyre soluble they may be able to be taken care of by other cells but if not then they may cause problems
what leads to disease in pneumonconiosis
the particles inhaled stimulate an immune resonse that leads to disease
what are types of pneumonconiosis
aspestosis
silicosis
coal workers pneumonconiosis
what jobs are associated with asbestos related diseases
minin, milling, fabrication, insulation
what is asbestos
crystalline hydrated silicates that form fibers
what are the asbestos amphiboles
all but chrysotile
anthrophyllite
crocidolite
amosite
what are amphibole asbestos fibers
less prevalent but more potent for causing diseases, especially mesothelioma
what is the most common asbestos fiber
chrysotile
chrysotile asbestos
what happens in asbestos related disease
asbestos fibers are phagocytosed by macrophages acivate the inflammasone and stimulate the release of proinflammatory and fibrogenic factors
pleural plaques associated with aspestos related pleural disease
usually asymptomatic
recurrent pleural effusions in patients with asbestos exposrue
not common, think mesothelioma
extensive interstitial fibrosis associated with asbestos exposure
asbestos body
brown indicates iron from macrophage ferritin
describe how asbestos relates to malignancy
tumor initiator and promoter
asbestos fibers generate reactive free radicals in distal lung, close to mesothelium. toxic chemicals absorbed into asbestos fibers
does smoking increase risk for mesothelioma
no just like mathey said
lung cancer related to asbestos malignancy
risk for lung cancer related to asbestos
5x
55x if also a smoker
where does malignant mesothelioma arise
in pleura
latent period and lifetime risk for mesothelioma with asbestos exposure
latent period 25-45 yrs
lifetime risk - 7-10%
presentation of mesothelioma
chest pain, dyspnea, pleural effusions
grow extensively in pleural cavity, invade lungs and spread to lymph nodes, liver, distant metastatic sites
epitheliod type malignant mesothelioma
mixed type malignant mesothelioma
describe the genetics of malignant mesothelioma
homozygous deletion of tumor suppressor gene CDKN2A/INK4a on chromosome 9p
prognosis for mesothelioma and treatment
50% die in 12 months of Dx
chemo, radiaton, extrapleural pneumonectomy may help
what is silicosis
a lung disease caused by inhalation of proinflammatory crystalline silicon dioxide (silica)
usually decades of exposure, rarely rapid
most prevalent chronic occupational disease
silicosis
presentation of silicosis
slowly progessing, nodular, fibrosing pneumoconiosis
epidemiology of silicosis
african americans
foundry work, sandblasting, hardrock mining, stone cutting
what is the most common causative inhalant in silicosis
crystalline quartz (more fibrogenic)
what does silicosis lead to an increased risk of
TB, lung cancer
silicosis
silicosis
silicosis
Silica particles seen under polarized light
what is coal workers pneumoconiosis
parnchymal lung disease that results from the inhalation of, retention of and host respose to coal dust
what is an anthracosis
innocuous coal induced pulmonary lesion in coal miners, all urban dwellers and tobacco smokers
what happens when coal is inhaled
inhaled carbon pigment is engulfed by alveolar or intesrtitial macrophages, which then accumulate in connective tissue along lymphatics or in lympoid tissue
complicated CWP
progressive massive fibrosis
CWP
dense scars with collagen and pigment
what is sarcoidosis
a multisystem disease of unkown cause
causes non necrotizing granulomas
describe the way sarcoidosis looks on imagin
bilateral hilar lymphadenopathy or lung involvement is visible on chest imaging
what other lesions are associated with sarcoidosis
eye and skin lesions
pathogenesis of sarcoidosis
cell mediated immune response to an unidentified antigen
CD4 helper T cells
increased cytokines (TNF)
HLA-A1, HLA-B8
sarcoidosis
sarcoidosis
sarcoidosis
sarcoidosis
note: multinucleated giant cells
epitheliod histiocytes
epidemiology of sarcoidosis
african americans more common
women more common
lung/hilar lymph nodes involved usually
sarcoidosis
asteroid body
sarcoidosis
Schaumann body
lab values in sarcoidosis
elevated serum ACE
hypercalcemia or hypercalciuria leading to nephrolithiasis and renal dysfunction can occur
enzyme 1a - hydroxylase in activated macrophages that convert 25-hydroxyvitamin D to 1,26 -mdihydroxyvitamin D, the active form of the vitamin. this results in increased gut absorption
course and treatment of sarcoidosis
variable
treatment: steroids for progressive/dangerous disease
65-79% of patients recover
20% have impaired eye or lung function
hypersensitivity pneumonitis
a spectrum of immunologically mediated, predominantly interstitial, lung disorders caused by intense, often prolonged exposure to inhlaed organin antigens.
abnormal sensitivity to antigen, affecting primarily the alveoli
prevention of hypersensitivity pneumonitis
removal of environmental agent
BAL of hypersenstivity pneumonitis
increased CD4 and CD8 T lymphocytes
specific antibodies against the causative antigen in serum
complement and immunoglobulins
noncaseating granulomas in 2/3rd of patients: T cell mediated (type 4) HS againts antigens
loose granulomas in HS pneumonitis
granuloma and chronic inflammation in HS pneumonitis
clinical syndrome of HS pneumonitis
bird fanciers disease, (protein in serum, feathers, droppings)
Farmers lung (thermophilic actinomycetes in moldy hay)
Bagassosis (moldy sugar cane)
Humidifier lung (thermophilic bacteria in heated water reservoirs)
clinicla presentation of HS pneumonities
acute episodes follow inhalation of antigenic dust in a previously sensitized patient usually 4-6 hrs after exposure. Recurrent episodes of dyspnea, fevver, cough and increased white cells
management of HS pneumonitis
steroids
remove anitgen
transplant if it goes on a long time and you get fibrosis
drug associated interstitial disease
Belomycin
Methotrexate
amiodarone
nitrofurantoin
aspirin
beta antagonists
what is pulmonary langerhans cell histocytosis/eosinophilic granuloma and who is it seen in
interstitial lung disease with proliferation of langerhans cells (immature dendritic cells)
adults
smoking
nodules or nodules with cystic change
classic complication of langerhans histocytosis
pneumothorax bc its right up next to pleural space
pulmonary langerhans cell histocytosis
pulmonary langerhans histocytosis
pulmonary langerhans histiocytosis
birbeck granules tennis racket shape
langerhans histocytosis
treatment for pulmonary langerhans histiocytosis
cessation of tobacco smoking, steroids, cyclophosphamide, lung transplant
pulmonary alveolar proteinosis
rare
characterized by bilateral patchy asymmetric pulmonary opacification on imaging
accumulation of acellular surfactant in the intra alveolar and bronchiolar spaces
pulmonary alveolar proteinosis commonest type
autoimmune aquired
anti GM-CSF signaling
loss of GM CSF signaling blocks terminal differentition of alveolar macrophages impairing their ability to catabolize surfactant
alveolar proteinosis
alveolar proteinsois
granular material and histiocytes within alveolar spaces
lamellar bodies
alveolar proteinosis
clinical presentation of alveolar proetinosis and management
pulmonary hypertension
honeycomb lung
a 55 yo man originally from metsova area, northwest greece presents with dyspnea, cough, fever and chest pain. Medial occupational history were unremarkable. Physical exam unremarkable. X ray showed irregular linear densities, particularly in the lower lungs, pleural effusion and pleural thickening. PFTs revealed restrictive lung function. Dx?
asbestosis
60 yo with 3 year history of cough and progressive dyspnea. His PMH of cough and progressive dyspnea. Heavy smoker. Not taking any drugs, non occupational exposures. Gradual appearance of dyspnea on exertion which worsened with time and was associated with a dry cough, no pain, fever or other symptoms. Elevarted RR and bibasilar velcro rales. Cyanosis and clubbing.
IPF
fibroblast foci
IPF
HS PF
most likey microscopic finding of HS P?
granuloma
24 to African American woman presents with fatigue, ahces and pains, blurry vision, dry eyes and SOB. Small cutaneous bumps, uveitis and enlarged liver. Abnormal X rays restrictiv lung findings, increased ACE and 24 hr Ca++ excretion. Bronchioloalveolar lavage revealed CD4/8 ratio of >5
sacroidosis
