Introduction to Pathology of Interstitial Lung disease

Question 1

Definition of interstitial lung disease

Answer 1

Disease that affects the parenchyma distal to the small airways (bronchioles)

Question 2

Characterization of interstitial lung disease

Answer 2

Characterized by too much of something in the interstitial space:

a) increased collagen and other matrix proteins
b) increased chronic inflammatory cells
c) Granulomas
d) water

Question 3

Normal interstitial space in normal lung

Answer 3

Extremely small (almost invisible)

Question 4

Common interstitial lung diseases

Answer 4

1) Usual interstitial pneumonia
2) Sarcoidosis
3) Hypersensitivity pneumonitis (HP)
4) Pneumoconioses such as asbestosis
* *many interstitial lung diseases have pneumonia in the name –> but are not infectious processes!!

Question 5

Clinical features of interstitial lung disease -presenting complaints

Answer 5

-Shortness of breath
-Dry cough frequently present
-Systemic symptoms (fever, weight loss) in some
-clubbing with severe disease
(especially UIP)
-Velcro rales - classic on auscultation on inspiration at lung bases
-most forms have interstitial markings on chest x-ray (coarse lines = reticular markings)

Question 6

Synonyms usual interstial pneumonia (UIP)

Answer 6

• idiopathic pulmonary fibrosis (PIF)

- cryptogenic fibrosing alveolitis (CFA)

Question 7

Risk factors UIP

Answer 7

-increases with age

Question 8

Causes of morphologic UIP (i.e. things that look like UIP)

Answer 8

1) Idiopathic (most cases)
2) Collagen vascular diseases

Less common

1) Drug induced UIP
2) Familial UIP
3) Pneumoconioses –> mainly asbestosis –> sometimes look like UIP

Question 9

Collagen vascular disease frequency of association with UIP

Answer 9

1) Scleroderma (very high frequency- almost 70% of patients)
2) Rheumatoid arthritis (common)
3) Lupus erythematosus (uncommon)

Question 10

Drugs that are associated with UIP picture

Answer 10

1) Most chemotherapeutic agents
2) Nitrofurantion*
3) Amiodarone *
* also associated with other types of interstitial lung diseases

Question 11

Clinical features of UIP

Answer 11

1. Disease of middle aged/elderly (increased frequency with age)
2. History of shortness of breath - increasing over a period of many years
3. Velcro rales on inspiration
4. Clubbing (in as many as 50%)
5. ANA, RF, cryoglubulins may be elevated even in those without collagen vascular disease
6. Restrictive functional abnormality

Question 12

CT scan of UIP

Answer 12

• reticulation (showing fibrosis)

- stacked cysts = honeycoming (

Question 13

Distribution of UIP

Answer 13

• predominantly lower zone fibrosis and honeycombing
• process is worse in periphery of lung
• process is worse in peripheyr of lobule

Question 14

Honeycoming

Answer 14

Holes with thick fibrous walls

* not specific to UIP

Question 15

Microscopic features of UIP

Answer 15

1)
Mixture of inflammation and fibrosis mixed in with normal lung parenchyma
-PATCHY FIBROSIS (normal to fibrosis to normal again within a small area i.e. a lobule - as disease get more severe get more and more fibrosis mixed in with normal parenchyma)
2) Fibroblast foci
3) Abnormal artery (tiny diameter)

Question 16

Granulation tissue

Answer 16

• a reparative pattern of proliferating fibroblasts

- often accompanied by capillary channels and chronic inflammatory cells

Question 17

Organization of granulation tissue

Answer 17

• happens in most organs

- granulation tissue is gradually transformed into dense collagen (i.e. the process of scar formation)

Question 18

Granulation tissue and steroids

Answer 18

• extremely sensitive to steroids

- causes granulation tissue to apoptose and does not organize into scar tissue

Question 19

Morphogenesis of UIP

Answer 19

1. Focal alveolar epithelial injury
2. Local fibrin deposition
3. outgrowth of fibroblasts from insterstitium to organize the fibrin into granulation tissue (i.e. the fibroblast foci)
4. Mechanism that normally make fibrin go away (fibrinolytic) are impaired in UIP + overproduction of plasminogen activator inhibitors= inhibits liberation of plasminogen which normally degrades fibrin

NET EFFECT: Persisting fibrin
So granulation tissue (fibroblast foci) grows

4. Granulation tissue eventually becomes collagen
5. Epithelium grows over to incorporate (organize) the new granulation tissue into the intersititum (as interstial fibrous tissue = collagen!)

Little bits of fibrosis added at a time into a lung –> instead of being removed granulation tissue organizes an is incorporated progressively into the lung as intersitial fibrosis

6. alveolar collapse with organization (fibrosis leads to loss of alveoli)
7. Both these process end as old dense scar tissue with reorgnization of the parenchyma

Question 20

Granulation tissue of UIP + steroids

Answer 20

While normal granulation tissue is very sensitive to steroids (fibroblasts undergo apoptosis with steroids and scar does not form)
-granulation tissue of uIP are not sensitive to steroids at all (very abnormal fibroblasts!)
Therefore in UIP steroids have no affect

Question 21

Causes of restrictive lung diseases

Answer 21

1) Interstitial lung disease
2) Densely fibrotic pleura (fibrothorax)
3) Chest wall muscle weakness
4) Chest wall deformity or massive obesity

• anything that prevents lung from expanding during inspiration

Question 22

Findings in restrictive lung diseases

-i.e. measures/tests

Answer 22

• small volumes on spirometry (FVC, FEV1 small)
• small volumes in body box (TLC small)
• flows preserved or increased (FEV1/FVC )
• compliance decreased
• typically diffusing capacity decreased

Question 23

Why diffusion capacity decreased in restrictive lung disease

Answer 23

-Because get ventilation perfusion mismatch

In restrictive disease the volumes are small
but the flows are fast
(while in obstructive the volumes are high and the flows are much slower in comparison)

Question 24

% predicted TLC with interstitial fibrosis + why

Answer 24

-put anything into the interstitial space and get a lung that has less distensibility than normal so % of predicted TLC with pressure is quite low

Question 25

Potential triggering injuries that lead to UIP

Answer 25

-all suggested by epidemiologic studies
a) cigarette smoke
b) metal dust
c) wood dust
or suggested in expiremental models
-viral infection (Hep C, Epstein-Barr)

Question 26

Disturbance of immunologic system in UIP

Answer 26

-get TH2 predominace vs. TH1
Important because TH1 mediated stystems tend to restore tissue
while TH2 mediated systems tend to result in fibrosis
-also increased proinflammatory cytokines

Question 27

Complications of UIP

Answer 27

• acute exacerbation (UIP superimposed with ARDS)
• carcinoma of the lung (10x risk)
• pulmonary hypertension
• respiratory failure

Question 28

Prognosis UIP *survival

Answer 28

-median survival 3 years

Question 29

Treatment UIP

Answer 29

None except for lung transplantation for young patients

especially because don’t have mechanism can target -all are just theories