ICL 1.6: Pathology of Restrictive Lung Diseases Flashcards
hypertrophy of smooth muscles of bronchi and bronchioles
asthma
Curshman spirals
asthma
elastase
emphysema
cirrhosis and emphysema
alpha1-antitrypsin deficiency emphysema
PIZZ
alpha1-antitrypsin deficiency emphysema
productive cough for 3 months over 2 years
chronic bronchitis
spontaneous pneumothorax
paraseptal emphysema
Kartagener’s syndrome
bronchiectasis
situs inversus
increased IgE
atopic asthma
pink puffer
emphysema
blue bloater
chronic bronchitis
superimposed infection
chronic bronchitis
because of the accumulation of secretions you can get superimposed infections
chitinase
YKL40 asthma
leukotrienes
asthma
panacinar emphysema characteristics
lober lobes
alveolar wall destruction
emphysema
65 year old male with lung resection when he was 60. dies of acute MI. lung autopsy shows dilated alveoli. what kind of lung disease do you think he has?
overinflation because there’s no wall destruction
overinflation happens when the other lung is trying to compensate like his was since part of it was removed
what are the defining characteristics of restrictive lung diseases?
- reduced expansion of the lung
- reduced total lung capacity
- expiratory flow rate will be normal or proportionally reduced
they can breath in and out but they can’t expand all the way
what conditions can lead to restrictive lung diseases?
- chest wall disorders with normal lungs
ex. neuromuscular disorders, severe obesity, kyphoscoliosis, pleural effusions - acute interstitial and infiltrative diseases
ex. acute respiratory distress syndrome (ARDS) - chronic interstitial and infiltrative diseases
ex diffuse interstitial diseases
what are diffuse interstitial infiltrative restrictive diseases?
a heterogenous group of disorders characterized by:
- diffuse and chronic involvement of the pulmonary connective tissue; often bilateral – mainly alveolar interstitium
- restrictive clinical and pulmonary functional changes
- presents with dyspnea, tachypnea, and end inspiratory crackles WITHOUT wheezing
- they progress clinically to secondary pulmonary hypertension –> cor pulmone –> right sided heart failure
what will you see on a CXR of a patient with diffuse interstitial infiltrative restrictive diseases?
infiltrative changes on CXR
there’s a variety of things you can see early on like small nodules, irregular lines or ground glass shadows
however, end stage you’ll see honeycomb lung in all of them so you can’t differentiate them!
which diseases are diffuse interstitial infiltrative restrictive diseases?
- environmental diseases
- sarcoidosis
- idiopathic pulmonary fibrosis
- collagen vascular diseases (SLE, rheumatoid, scleroderma)
what is the pathogenesis of diffuse interstitial infiltrative restrictive diseases?
alveolitis!!!!**
this is characterized by accumulation of inflammatory and immune effector cells within the alveolar wall and within alveolar spaces
this causes:
1. distortion of the normal alveolar structure
- inflammatory cells releases chemokine that injure parenchymal cells and stimulate fibrosis
al the diffuse interstitial infiltrative restive diseases cause fibrosis, damage of type I pneumocytes and proliferation of type II pneumocytes
what are the 3 categories of diffuse interstitial infiltrative restrictive diseases?
- fibrosing diseases
- granulomatous diseases
- smoking related interstitial diseases
which diseases are part of the fibrosing class of diffuse interstitial infiltrative restrictive diseases?
- Idiopathic Pulmonary Fibrosis
- Cryptogenic Organizing Pneumonia
- Collagen Vascular Diseases with Pulmonary Involvement
- Pneumoconioses (CWP, Silicosis, Asbestosis)
- Complications of Therapies
which diseases are part of the granulomatous class of diffuse interstitial infiltrative restrictive diseases?
- sarcoidosis
2. hypersensitivity pneumonitis
which diseases are part of the smoking-related class of diffuse interstitial infiltrative restrictive diseases?
desquamatic interstitial pneumonitis
This forty-year-old white female presents to your office because of increasing shortness of breath over the past three months. She has otherwise been in perfect health. She is employed as a secretary for an insurance company. To the best of her knowledge she has never been exposed to anything unusual.
On physical examination, she is a well-developed, well-nourished female who, at rest, demonstrates minimal shortness of breath. When asked to exercise, she becomes quite dyspneic and slightly cyanotic. On auscultation of the chest, occasional fine rales are heard, with no evidence of wheezing. On chest x-ray, a diffuse reticulonodular pattern is present throughout both lung fields.
diffuse reticulonodular pattern = honeycomb pattern –> so we know she has some kind of restrictive lung disease
hypersensitivity pneumonitis and pneumoconiosis is ruled out because she’s a secretary and hasn’t been exposed to anything
collagen vascular diseases are ruled out because she has no other conditions like SLE, RA, or scleroderma
sarcoidosis? idiopathic pulmonary fibrosis?
based on her history, she most likely has idiopathic pulmonary fibrosis but you need to rule out sarcoidosis since IPF is a diagnosis of exclusion –> check Ca+2 and ACE levels which will both be elevated in sarcoidosis
what is the common pathogenesis of the diffuse interstitial restrictive lung disease?
regardless of the type or specific cause of interstitial lung disease, the earliest common manifestation of most of these disorders is alveolitis**
alveolitis is the accumulation of inflammatory and immune effector cells in the alveolar wall and spaces
this accumulation has two main consequences:
1) it distorts the normal alveolar structure
2) cytokines are released that injure normal lung parenchyma and stimulate fibrosis
the end result is a fibrotic lung with multiple cystic spaces separated by thick bands of fibrous tissue
what is the pathogenesis of idiopathic pulmonary fibrosis?
Previously believed that some insult leads to chronic inflammation which consequently leads to fibrosis
however, anti-inflammatories do not provide much benefit for patients!
it’s now believed to be caused by repetitive cycles of acute injury (alveolitis) with “wound healing” –> excessive fibrosis
it begins with an alveolitis and damage to type I pneumocytes
then proliferation of type II pneumocytes – alveolar spaces lined by cuboidal cells
fibroblastic proliferation –> in septae and intraalveolar exudate –> intermixed normal & fibrotic lung –> end stage honey-comb lung
what is the clinical course of idiopathic pulmonary fibrosis?
insidious onset
40-70 year old
unpredictable course, with most gradually deteriorating despite treatment
mean survival 3 years or less
only definitive therapy = lung transplant
what is the pulmonary involvement in collagen vascular disorders?*** (SLE, RA, scleroderma)
SLE –> serositis –> sharp chest pain due to inflammated pleura
RA –> rheumatoid nodules
scleroderma –> fibrosis
what is the clinical presentation of scleroderma?
- tightening of the skin due to scarring that occurs everywhere in the body
- dysphagia
- Raynaud’s
- HTN due to fibrosis and scaring of blood vessels
- anti SCL-70 antibodies are high
also do an ANA and you’ll see a speckle pattern
what is pneumoconiosis?
includes diseases induced by organic as well as inorganic dusts and chemical fumes and vapors
most as a result of occupational exposure**
slow and insidious onset
particulate air population in urban areas also a risk
what is the pathogenesis of pneumoconiosis?**
it depends on:
- amount of dust retained in the lungs and airways
dust concentration in the ambient air, duration of exposure, effectiveness of clearance mechanisms
- size and shape of particle
most dangerous particles are 1-5 µm in diameter because they reach the terminal small airways and alveoli
- particle solubility and cytotoxicity
smaller particles tend to reach toxic levels rapidly and cause acute injury while larger particles are less likely to dissolve and may persist in the lung parenchyma for years causing chronic injury and fibrosis
- additional effects of other irritants (tobacco smoking)
what is coal worker’s pneumoconiosis?
CWP is a fibrosing restrictive lung disease caused by coal mining; either carbon dust alone or contaminated with silica
it’s usually benign but it can cross the line and cause problems:
1. asymptomatic anthracosis = we probably all have this just from city pollution
- simple CWP = no effect on pulmonary function
- complicated CWP = fibrosis + cor pulmoné
which other conditions is coal worker’s pneumoconiosis associated with?
increased incidence of:
1. tuberculosis
- chronic bronchitis
- emphysema
does NOT predispose you to cancer though
what is Caplan syndrome?
pneumoconiosis of any type + rheumatoid arthritis
patients will have nodular lesions similar to rheumatoid nodules in the lung- fibroblasts, macrophages and collagen surround an area of central necrosis
occurs with CWP, asbestosis and silicosis
why is tuberculosis associated with a lot of the pneumoconiosis conditions?
the dust inhibits the ability of macrophages to phagocytose and kill the TB organism
A 50-year-old man presents to your office for an annual check-up. He has worked as a sandblaster for the last 15 years. A routine chest x-ray shows a fine nodularity in the upper zones of the lung. The patient has no pulmonary symptoms.
diagnosis?
silicosis
this is the most prevalent chronic occupational disease
it occurs mostly in sandblasters and miners
generally a slowly progressive nodular fibrosis
macrophages release fibrogenic cytokines and to other mediators, such as TNF, IL-1, etc.
what are the gross morphological changes seen in silicosis?
- tiny collagenous nodules especially in upper zones of lungs, enlarge and coalesce to form readily visible hard collagenous scars
- lymph nodes can become calcified –seen radiographically as “eggshell calcifications”***
silicosis can continue to progressive massive fibrosis
what are the microscopic morphological changes seen in silicosis?
hyalinized, rounded, collagenous nodules
collagen is laid down in concentric layers
polarizing light demonstrates the presence of silica particles
what is the clinical course of silicosis?
generally asymptomatic because the nodules are usually pretty small
but you can see eggshell calcifications in the lymph nodes and detect it by CXR where you’ll see fine nodularity in the upper zones of the lungs –> pulmonary function tests are normal or moderately effects
symptoms usually develop after progressive massive fibrosis is present
the disease will continue to progress even when exposure to silica stops!!!*** this is because the silica particles are stuck in the lungs stimulating the fibrosis and scaring
it’s associated with an increased susceptibility to tuberculosis because it inhibits macrophage ability to phagocytose TB
silica possible carcinogen
what is asbestos?
asbestos is the general name applied to a group of crystalline hydrated silicates that form fibers
heaviest exposure occurs in miners, fabrication, installation and removal of asbestos containing products, such as insulation in old homes
unlike CWP and silicosis, asbestos begins in lower lobes subpleurally so the pathology will be different
what are the 2 fibers associated with asbestos?
- serpentine
- amphibole
BOTH are fibroblastic because they cause macrophage activation and cause asbestos related disease –> macrophage activation causes fibrosis because it stimulates the production of growth factors such as fibroblast growth factor which leads to scar!
only amphiboles cause mesotheliomas (disease of the pleura)
what are serpentine asbestos fibers?
- more prevalent
- less pathogenic
- curly, flexible, don’t fragment
- more soluble
- retained in the upper airway
what are amphibole asbestos fibers?
- less prevalent
- more pathogenic
- straight, stiff, brittle
- less soluble
- delivered deep into the lungs
which diseases are related to asbestos exposure?
- diffuse interstitial fibrosis (asbestosis)
- localized fibrous pleural plaques
- pleural effusions
- lung cancer
- mesotheliomas (pleural & peritoneal)
- laryngeal and possibly other extra-pulmonary tumors, including colon cancer
what are pleural plaques?
they are the most common manifestation of asbestos exposure
they’re well-circumscribed dense collagenous plaques
they do NOT cause chest pain because they’re chronic scars; acute inflammation of the pleural is what causes chest pain
they most commonly defect the anterior and posterolateral aspects of the parietal pleura and diaphragm dome
the size and number of pleural plaques does not correlate with the level or length of time of asbestos exposure
how is lung cancer associated with asbestos exposure?
- increased risk of mesothelioma 1000X
- increased risk of lung cancer:
with asbestos alone = 5X
with asbestos and smoker = 55X
increased risk with smoking due to adsorption of cigarette smoke carcinogens onto asbestos fibers; you’re specifically worried about the amphiboles fiber because they’re brittle, break and go deep into the lungs
what is the clinical course of asbestosis?
it’s similar to other diffuse interstitial lung diseases
symptoms usually appear 10 -20 yrs after exposure and may be debilitating proceeding to cor pulmonale and death
pleural plaques are generally asymptomatic because it’s not an acute inflammation
asbestosis complicated by lung cancer or mesothelioma has a poor prognosis
which drugs/therapies can cause damage to the lungs?
- drugs can cause a variety of acute and chronic pulmonary changes
- cytotoxic drugs (ex. bleomycin) lead to pulmonary fibrosis by direct toxicity
- amiodorone leads to pneumonitis from preferential concentration in the lung - acute Radiation Pneumonitis occurs in 10-20% of thorax-radiated patients, 1-6 mos. post-radiation
- radiation causes alveolitis or hypersensitivity pneumonitis that can lead to fibrosis
which drugs cause drug-induced pulmonary disease? which pulmonary disease is associated with each?
- bleomycin –> pneumonia and fibrosis
- methotraxate –> hypersensitivity and pneumonitis
- amiodarone –> pneumonitis and fibrosis
- nitrofurantoin –> hypersensitivity pneumonitis
- aspirin –> bronchospasm (asthma)
- B-antagonists –> bronchospasm
what toxic side effects does amiodarone cause?
pneumonitis and fibrosis
hypothyroidism
microvascular fatty infiltration in the liver
what is the triad associated with aspirin induced asthma?
- rhinitis
- nasal polyps
- asthma
25 year old African American female presents with watery eyes and tender red nodules on her shin for the last 2 months on further question she reports dry cough for 4 weeks
CXR show hilar lymphadenopathy
lab tests show elevated calcium
sarcoidosis
tender red nodules on the shin = erythema nodosum = panniculitis
mediastinum lymph nodes are enlarged
also should run an ACE test because it will probably be elevated
what are granulomatous diseases?
a multisystem disease of unknown cause characterized by noncaseating granulomas
females > males
age 20 -40 yrs; 2/3 cases occur <40 yrs
disease is a diagnosis of exclusion
what is the pathogenesis of granulomatous diseases?
we don’t know….
what is the morphology of granulomatous diseases?
non-caseating granulomas found in:
- lungs
- lymph nodes
- liver
- spleen
caseating granulomas are see in TB
what are the symptoms of sarcoidosis?
- cough
- erythema nodosum
- dyspnea
- neurologic manifestations
what are the lab findings associated with sarcoidosis?
↑ serum Ca
↑ ACE
↓ CD4
decreased CD4 makes you more prone to infections and they’re decreased because they’re consumed in the granulomas!
what is the course of sarcoidosis?
it can have a chronic or remitting spontaneously or with steroids
65-70% - recover with minimal or no residual effects
20% - permanent lung deficit or visual impairment
10-15% - die, usually due to progressive fibrosis of the lung or cor pulmonale
what is hypersensitivity pneumonitis?
caused by intense and often prolonged exposure to inhaled organic dusts containing bacterial spores or products, fungi, or animal proteins
individuals have abnormal sensitivity to a certain antigen which may progress to chronic fibrotic lung disease
early recognition and removal of precipitating cause may prevent progression
ex. farmers lung
ex. pigeon breeders lung
ex. humidifier or air conditioner lung
what is farmer’s lung?
a type of hypersensitivity pneumonitis
it’s caused by spores of thermophilic actinomycetes in moldy hay
what is pigeon breeder’s lung?
a type of hypersensitivity pneumonitis
it’s caused by proteins from serum, excreta or feathers of birds
what is humidifier/air conditioner lung?
a type of hypersensitivity pneumonitis
it’s caused by thermophilic bacteria in heated water reservoirs
what is the pathogenesis of hypersensitivity pneumonitis?
there is evidence of both immune complex (type III) and T-cell mediated delayed (type IV) hypersensitivity
what are the histologic changes seen with hypersensitivity pneumonitis?
histologic changes occur in bronchioles:
1. interstitial pneumonitis
- noncaseating granulomas
- interstitial fibrosis
- intraalveolar infiltrate
- obliterative bronchiolitis
what is the clinical course of hypersensitivity pneumonitis?
it’s variable
if it’s acute, inhalation of due in a previously sensitized individual can lead to fever, dyspnea, cough 4-6 hours after exposure
chronically from repeated exposure could lead to chronic interstitial lung disease
what is pulmonary alveolar proteinosis?
there is accumulation of acellular surfactant in alveoli and bronchioles
then there’s impaired surfactant clearance by pulmonary macrophages
CXR will show bilateral opacification
what leads to impaired surfactant clearance by pulmonary macrophages in pulmonary alveolar proteinosis?
- acquired autoimmune anti-GM-CSF against macrophages
- secondary from silicosis, tumors, immunodeficiency which inhibit macrophages
- congenital genetic mutations of GM-CSF = no macrophages
what is the clinical presentation of pulmonary alveolar proteinosis?
- SOB
- thick gelatinous sputum = jelly like
this is because their alveoli are filled with surfactant!
what is the summary of restrictive lung diseases?
lung injury –> alveolitis –> cellular and connective tissue alterations –> fibrosis –> end stage honeycomb lung
RA + pneumoconiosis
Caplan syndrome
jelly like sputum
pulmonary alveolar proteinosis
GM-CSF
pulmonary alveolar proteinosis
egg shell appearance on CXR
silicosis
amphibole
asbestos
honey cob lung
restrictive lung diseases
failure to clear surfactant
pulmonary alveolar proteinosis?
erythema nodosum + elevated ACE + constipation
sarcoidosis
high calcium = constipation because of decreased intestinal motility
why is there hypercalcemia in sarcoidosis?
increased vitamin D
macrophages/histiocytes in the granulomas convert the vitamin D from its inactive to it’s active form which increases intestinal absorption of calcium leading to hypercalcemia
65 year old female with a history of RA develops dyspnea after retiring from a glass factory
CXR reveals nodular lesions in both lungs
DD?
what’s she at risk for developing?
silicosis
final diagnosis because of h/o RA is Caplan syndrome
she’s at risk for developing TB
70 year old male presents with dyspnea for 6 months
PE crackles no wheezing in both lungs
what will CXR show ?
DD?
pathogenesis?
crackles = alveolar problems
alveolar problems means you’ll see reticular nodular pattern on the CXR but no honeycomb because he’s only had it for 6 months, not years = restrictive lung disease
most likely idiopathic pulmonary fibrosis
pathogenesis is alveolitis! and fibrosis eventually
