Flashcards in L67 – Diffuse Interstitial Lung Diseases Deck (65):
Describe Diffuse Intersitital Lung Disease?
group of heterogeneous diseases
caused by a number of etiology (known or unknown)
causes Diffuse damage to pulmonary interstitium
What are the 3 components of pulmonary interstitium?
tissues of gas-exchange unit
Name the MILD Acute interstitial lung disease and give an example of its cause?
e.g. caused by mild viral infectiuon
In acute interstitial lung disease, describe the interstitial tissue?
Interstitial tissue infiltrated by lymphocytes, macrophages, plasma cells
Name the SEVERE Acute ILD ?
diffuse alveolar damage (DAD)
Name some COMMON causes of LUNG injuries in DAD (Severe Acute ILD)?
- Gastric aspiration (vomit, acid enters lungs)
- Infections from inhaling infectious agents (e.g. Virus, bacteria)
Name some UNCOMMON causes of LUNG injuries in DAD?
Toxic fume inhalation,
post-lung transplant immune reaction
Name some COMMON causes of GENERAL injuries in DAD (Severe Acute ILD)?
Severe trauma (caused by hypoxic blood, low BP)
Name some UNCOMMON causes of GENERAL injuries in DAD (Severe Acute ILD)?
What is the pathogenesis of DAD?
Severe injury to epithelium and/or endothelium
> Release inflammatory cytokines for WBC
> Causes necrosis of alveolar wall (damage endothelium and pneumocytes)
What are the consequences of necrosis of alveolar wall in DAD?
Alveolar wall necrosis:
1. Damage endothelium, interstitial cells >>> capillary leak
2. Lose alveolar pneumocytes >>> lose alveolar surfactant
What are the physiological effects of DAD?
Lose alveolar surfactant >> decrease lung compliance due to increase surface tension >> alveolar airspace collapse
>> not ventilated but perfused
>> ventilation/perfusion (VQ) mismatch
What replaces the necrotic alveolar wall? What is the result?
Type II pneumocytes try to regenerate and
differentiate into type I
>> result in cuboidal, hyperplasia of type II pneumocytes
Explain the formation of Hyaline membrane in DAD?
Alveolar wall necrosis > damaged endohelium and pneumocytes
>> Escaped RBC, serum protein + fibrinous exudate, cell debris accumulation
INSPIRATION pushes exudates to outer airspace
>> Hyaline membrane form
What is the effect of hyaline membrane?
Lower diffusion capacity
Summarize all the structural changes to alveolar wall in DAD?
Congested and dilated capillaries
Form Hyaline membrane
Type II pneumocyte hyperplasia
Interstitial edema + mononuclear exudate
What is the effect of V/Q mismatch in DAD?
Severely impaired gas exchange
What is the clinical term for Severe acute Interstitial lung disease/ DAD?
Acute Respiratory Distress Syndrome (ARDS)
What is the mortality of acute respiratory distress syndrome (ARDS)?
30-40% (surviving patients may develop lung fibrosis due to repair)
DAD, interstitial pneumonitis belong to Acute ILD. Descibe Chronic ILD?
Group of heterogenous diseases that causes diffuse injury to lung interstitium
** caused by chronic inflammation and lung fibrosis
What causes Chronic ILD? *think what type of injury*
Recurrent/ continuous/ severe lung damage
Initial injury may be asymptomatic
Could a viral infection lead to Chronic ILD?
If the infection is mild/ transient, then no
What are the 4 major causes of Chronic ILD?
Mineral dust deposition
Others (allergy, sarcoidosis...etc)
List some Toxic damages that can lead to Chronic ILD?
Irradiation (e.g. radiotherapy)
Prolonged treatment with hyperbaric O2
What is the name of the condition caused by mineral dust deposition in lungs?
What autoimmune diseases can lead to chronic ILD?
Systemic sclerosis (aka scleroderma)
Systemic lupus erythematosus (SLE)
What type of hypersensitivity reaction is Sarcoidosis?
type IV: delayed-type hypersensitivity (DTH)
What type of allergic condition can lead to chronic ILD?
extrinsic allergic alveolitis
Give 2 examples of Chronic ILD
1) Idiopathic pulmonary fibrosis**
(** No longer called cryptogenic fibrosing alveolitis**)
What is the progression of Idiopathic pulmonary fibrosis (chronic ILD) dependent on?
Disease progression = slow, insidious
depends on individuals, severity of injury
What gender is more affected by Idiopathic pulmonary fibrosis ?
What is the signature histological feature of advanced stage Idiopathic pulmonary fibrosis ?
What is the initial injury for Idiopathic pulmonary fibrosis ? What type of injury is caused?
Unknown agent, hence idiopathic
persistent, chronic, diffuse lung injury on tissue**
**not in airspace or airway
What is the pathology of Idiopathic pulmonary fibrosis?
Unknown agent cause persistent, chronic, diffuse lung tissue injury/ damage
>> B and T lymphocyte activation > Production of cytokines and Antibodies
>> Activate macrophage
>> recruit neutrophils, induce fibroblast proliferaton + release oxidants and proteases
>> Damage to type I pneumocytes
What is the pathological result of idiopathic pulmonary fibrosis at distal airways?
Fibroblast proliferation causes fibrosis**
Bronchiolar epithelium grows in / extends to line airspaces
Overall: distal airway is “amputated", reduce SA
Explain the end stage manifestation of idiopathic pulmonary fibrosis?
Distal airways become "amputated"
>> Acini "simplified" to become cystic spaces
>> Bronchiolar epithelium grows into cystic spaces
>> Honeycomb lung
Summarize the pathological features of Idiopathic pulmonary fibrosis?
Interstitial fibrosis >> "amputated" distal airways and honeycomb lungs
Obliteration or Cystic dilatation of air spaces
May associate with chronic inflammatory cells
Summarize the macroscopic appearance of Restrictive pattern lung damage in Acute ILD?
Thickened alveolar wall
Rigid, shrunken lungs
>>Type I respiratory failure
Summarize the macroscopic appearance of End-stage lung damage in Chronic ILD?
Dense interstitial fibrosis
Amputated airways and honeycomb lungs
Oliterated or cystic air spaces
What are the affected lung functions due to interstitial fibrosis?
Decrease compliance / increase elastic recoil
What are the gross results of interstitial fibrosis?
Stiff, rigid lungs
Restictive lung function
What are the affected lung functions due to congested/ damaged alveolar capillaries?
Imparied perfusion, ths gas exchange
What are the affected lung functions due to Alveolar wall fibrosis?
Increase wall thickness and decreased surface area
>> Decrease diffusion capacity and gas exchange
>> Lower ventilation = V/Q mismatch
What are some clinical examination features of end-stage diffuse ILD?
Shortness of Breathe without wheezing
Cyanosis *due to V/Q mismatch)
What is observed in CXR for end-stage diffuse ILD?
Corase lines and cystic nodules observed
End-stage diffuse ILD increases the risk of ___?
How does chronic hypoxia caused by end-stage diffuse ILD manifest? (think early and late progressions)
Chronic hypoxia > Pulmonary vasoconstriction > Obliterate vessel lumen
Early = reversible vasoconstriction
Late = irreversible structural changes
What are some irreversible structural changes in End-stage diffuse ILD?
Increase in fibroblast proliferation and SM cells
Thickening of tunica intima and media
How to diagnose ILD?
*clin- radi- patho*
Based on a combination of features:
Identify etiology from history, relevant tests
What drug has no effects on honeycomb lungs?
Why is tissue examination important in diagnosing ILD?
Assess disease activity (active inflammation vs. fibrosis)
Find the cause (e.g. exposure to asbestos bodies > asbestosis)
lung fibrosis resulting from inhalation of inorganic dusts
What are some determinants of chronic inflammation in pneumoconiosis?
Chemical nature, physical state, particle size of dust
Duration, concentration of exposure
What is the agent and exposure period causing Silicosis?
exposure to silica = silicon dioxide (SiO2)
Prolonged, chronic exposure (>10-20 years)
What are some high risk occupations for silicosis?
quartz-mining, rock-cutting, glassmaking, pottery, sand-blasting
Describe the pathogenesis of silicosis.
Silica deposit in alveolar wall > macrophage release FIBROGENIC FACTORS
> Fibroblast proliferation and collagen deposition
> SILICOTIC NODULES FORM
Compare the extent of silicotic nodules in simple and advanced silicosis?
Simple: sporadic, white nodules spread throughout lung
Advanced: Massive areas of fibrosis with concentrically deposited collagen
Advanced silicosis can lead to what conditions?
What is the agent and duration of exposure of Asbestos?
Fibrous magnesium silicate
(Long/thin, curved or straight)
prolonged / heavy exposure
Sources of asbestos?
acoustic / thermal insulator,
industries, old buildings
What is the hallmark of Asbestosis?
asbestos fibers covered by a film of protein impregnated
with haemosiderin*** (RBC breakdown products)
Appearance and location of asbestos bodies?
Long, beaded, brown
In bronchial fluids, sputum
Describe the pathology of asbestosis?
asbestos deposit in airspace
Macrophage fails to ingest asbestos, fibroblast proliferation > Interstitial fibrosis
Puncture of endothelium, bleeding >> RBC broken down by asbestos and deposits haemosiderin >> Asbestos bodies
What are some asbestos related conditions?
Lung cancer > Malignant mesothelioma
cancer derived from lining (mesothelium) of pleura, pericardium, peritonium