by mtoom


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What tissue (specifically) is affected by interstitial lung diseases?
Parenchyma distal to the small airways
What happens to the interstitial space in interstitial lung disease?
There is too much of something in the interstitial space.
What can accumulate in the interstitial space causing disease (3)?
  • Increased collagen and other matrix proteins
  • Increased chronic inflammatory cells
  • Granulomas
Name 4 important Interstitial Lung Diseases
  • Usual Interstitial Pneumonia (UIP)
  • Sarcoidosis
  • Hypersensitivity Pneumonitis (HP)
  • Pneumoconioses (eg. Asbestosis)
Why do UIP and HP have stupid names?
Because "pneumonia" and "pneumonitis" are not infectious processes in this context.
In Sarcoidosis, what accumulates in the interstitial space?
Interstitial granulomas
In Hypersensitivity Pneumonitis, what accumulates in the interstitial space?
Cells (inflammatory response)
What are the the important non-specific symptoms with Interstitial Lung Disease (3)?
  • SOB (most common presenting complaint)
  • Dry cough
  • Systemic symptoms (fever, weight loss)
What can be seen on the hands (1) in Interstitial Lung Disease?
Clubbing
What is heard on inspiration in Interstitial Lung Disease (1)?
Velcro rales
What is the pulmonary function abnormality in Interstitial Lung Disease (ILD)?
Restrictive
What do you see on X-Ray in Interstitial Lung Disease?
So-called "interstitial markings"
Give 2 synonyms for UIP
Usual Interstitial Pneumonia (UIP)
  • Idiopathic Pulmonary Fibrosis (IPF)
  • Cryptogenic fibrosing alveolitis (CFA)
Compare incidence of UIP to lung cancer. Any differences between genders?
UIP is about as common as long cancer

More common in men
Most causes of Usual Interstitial Pneumonia (UIP) are idiopathic. Name 4 non-idiopathic types.
  • UIP associated with Collagen Vascular Disease
  • Drug-induced UIP
  • Familial UIP
  • Pneumoconioses, mainly asbestosis
Name 3 diseases that have a high degree of association with UIP.
  • Scleroderma (high-frequency)
  • Rheumatoid arthritis (common)
  • Lupus erythematosus (uncommon)
Name 1 drug class and 2 specific drugs that are associated with UIP.
  • Most chemotherapeutic agents
     
  • Nitrofurantoin
  • Amiodarone
Regarding clinical aspects:
  • What age group is UIP most common?
  • What is the most common complaint and how abruptly does it worsen?
  • What is heard during inspiration?
  • What is seen on the hands?
  • What blood markers may be elevated
  • UIP is most common in middle-aged or elderly people
  • The most common complaint is SOB, which comes on slowly over years (ie. insidious onset)
  • Velcro rales heard during inspiration
  • Clubbing seen in 50% of patients
  • Serum inflammatory markers (ANA, RF, Cryoglobulins) may be elevated
What is seen on chest X-Ray for UIP (3)?
  • Honeycombing in advanced cases
  • Cor pulmonale (enlargement of right heart due to pulmonary hypertension)
  • Reticulonodular markers (ie. "interstitial markers"), most severe in lower zones
Where on X-ray is the fibrosis and honeycombing most prominent?
Predominantly lower-zone fibrosis and honeycombing
Where on the lung and lobule is the process worst, in UIP?
Worse in periphery of lung, lobule
In UIP, what is found in the interstitial space that causes disease (2)?
  • 1. Inflammation
  • 2. Fibrosis

Patchy inflammation and fibrosis, mixed right in with normal parenchyma. Tends to be worse in the peripheral lobule.
Microscopically, what foci are seen scattered throughout the lung, in UIP?
Scattered fibroblast foci (small tufts of granulation tissue applied to alveolar walls) are seen
Is the inflammation homogenous throughout the lung?
No, the inflammation is heterogenous.

Interstitial inflammation and airspace macrophages are only seen in honeycomb foci.

That is, the honeycomb parts of the lung are more inflammed than other parts.
What happens to granulation tissue in a normal person?
A reparative pattern of proliferating fibroblasts, accompanied by capillary channels and chronic inflammatory cells, serves to organize granulation tissue, making it into dense collagen.
What is the pathogenic mechanism that results in fibrosis in UIP? Complex answer.
Focal epithelial injury results in fibrin deposition and the outgrowth of fibroblasts (from the interstitium).

Epithelium grows over to incorporate new granulation tissue into the interstitium.

The fibroblast foci are connected to an elaborate, contiuous network of granulation tissue.
What can be said about Fibrinolytic mechanisms in UIP?
Fibrinolytic mechanisms are impaired.
What eventually happens to the Fibroblast foci? What eventually happens to the alveoli?
  • Fibroblast foci become interstitial fibrous tissue
     
  • Alveoli collapse
What is unusual about the granulation tissue in UIP, with regard to steroid treatment?
Normally, granulation tissue is sensitive to steroids, which cause apoptosis of fibroblasts.

However, in UIP, the granulation tissue is not sensitive to steroids.
Interstitial lung diseases fall under what major category of lung disease?
Restrictive Lung Disease
What are 3 findings on spirometry for restrictive lung disease?
Spirometry
  • ↓FVC, FEV1
  • ↓Total lung capacity
  • ↑FEV1/FVC ratio
What happens to compliance and diffusing capacity in restrictive lung disease?
  • ↓Compliance
  • ↓Diffusing capacity
What are 2 possible triggering injuries in UIP?
  • Exposure to environmental agents (smoke, dust)
     
  • Viral infection (Hepatitis C, Epstein-Barr)
Do immunologic factors play a major role in UIP pathogenesis?
Yes, likely so.
  • Progressive nature of UIP is consistent with an immunologic reaction
     
  • Patients often have auto-antibodies against alveolar epithelium
     
  • Th2 lymphocytes predominate in UIP, which secrete pro-fibroblast cytokines

  • IFN-gamma, inhibitor of collagen synthesis, is absent in UIP 
Explain briefly the relationship between Th1/Th2 cells and UIP.
There are more Th2 than Th1 cells in UIPTh2 are pro-fibrosis, and Th1 are anti-fibrosis.
What can be said about the cytokines seen in UIP? (1)
There are higher levels of pro-fibrotic cytokines (this relates to the high Th2/Th1 cell ratio)
What can be said about the fibroblasts in UIP? (5)

What can be said about the epithelium in UIP? (1)
Fibroblasts are highly abnormal
  • ↑motility
  • ↑proliferation
  • Apoptosis resistant
  • Anti-proliferation genes are hyper-methylated
  • Anchor-independent growth

The epithelium is also abnormal
What are the complications of UIP (4)?
  • Acute exacerbation (eg. ARDS)
  • Carcinoma of lung (10x ↑risk)
  • Pulmonary hypertension
  • Respiratory failure
What is the prognosis of UIP?
  • Median survival = 3 years
  • No response to steroids
  • No response to cyclophosphamide
Compare prognosis in NSIP (non-specific interstitial pneumonia) to UIP
In NSIP, the prognosis is much better

NSIP is just another type of idiopathic interstitial fibrosis 
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