W4 - Pathology of Restrictive Lung Diseases

Question 1

The interstitium of the lung is comprised of connective tissue space around what 3 things?

Answer 1

Airways
Vessels
Basement membranes of alveolar walls

Question 2

In normal alveolar walls, what 2 things are in direct contact with each other?

Answer 2

Alveolar epithelial (pneumocyte)

Interstitial capillary endothelial cell basement membranes

Question 3

Histologically, how do healthy alveoli vs alveoli in restrictive lung disease appear? What’s the physiological relevance of this difference?

Answer 3

In healthy tissue, alveolar walls are 2 cells thick.

In restrictive lung disease, they are thickened by interstitial infiltrate

The thickening means gas exchange is much more difficult

Question 4

What does FEV1, FVC and the ratio look like in restrictive lung disease?

Answer 4

FEV1 reduced
FVC reduced
FEV1/FVC ratio normal

Question 5

How does restrictive lung disease affect compliance and why?

Answer 5

Reduced lung compliance as fibrous material prevents lungs stretching

Question 6

Reduced gas transfer from restrictive lung disease is an abnormality of what?

Answer 6

Diffusion

Question 7

Describe ventilation/perfusion balance in restrictive lung disease

Answer 7

Imbalance when small airways are affected by pathology

Question 8

There’s more than 100 restrictive lung diseases, so it’s tricky to generalise. But what 4 symptoms are typical of restrictive lung disease?

Answer 8

Incidentally discovered on CXR or CT (asymptomatic)

Dyspnoea, initially SOB on exertion, then at rest as disease progresses

Type 1 Resp Failure

Heart failure, caused by cor pulmonale

Question 9

An acute response to interstitial lung injury is called what?

Answer 9

Diffuse Alveolar Damage (DAD)

Question 10

Name 3 types of chronic responses to interstitial lung disease

Answer 10

Usual Interstitial Pneumonitis (UIP)

Granulomatous Responses

Other Patterns

Question 11

Chronic responses to interstitial lung disease lead to what?

Answer 11

Fibrosis or end-stage honeycomb lung

Question 12

Define the natural history of restrictive lung disease generally, IPF and sarcoidosis

Answer 12

Generally variable

IPF - 3-6 year survival

Sarcoidosis - relatively benign self-limiting course. 20% develop pulmonary fibrosis

Question 13

Name 3 examples of occupational lung diseases

Answer 13

Coal Worker’s pneumoconiosis
Silicosis
Asbestosis

Question 14

Name 2 granulomatous diseases of restrictive lung disease

Answer 14

Sarcoidosis

Hypersensitivity pnemonitis

Question 15

Give 3 examples of types of hypersensitivity pneumonitis

Answer 15

Farmer’s Lung
Bird Fancier’s Lung
Bark Stripper’s Lung

Question 16

Give an example of idiopathic pulmonary fibrosis

Answer 16

Usual Interstitial pneumonia

Question 17

Name 8 causes of DADS

Answer 17

Major trauma
Chemical injury/toxic inhalation
Circulatory shock, cardiac failure, blood loss
Drugs
Infection inc viruses
Autoimmune disease
Radiation
Idiopathic

Question 18

What is DADS?

Answer 18

Diffuse Alveolar Damage Syndrome - acute inflammatory response in lung interstitium

Question 19

Name 6 histological features of DADS

Answer 19

Protein rich oedema
Fibrin
Hyaline membranes
Denuded basement membranes
Epithelial or fibroblast proliferation
Scarring in interstitium and airspaces (fatal)

Question 20

What 2 things peak in the exudative stage of DADS, then which 2 things rise in the proliferative stage?

Answer 20

Exudative - oedema then hyaline membranes

Proliferative - interstitial inflammation and interstitial fibrosis

Question 21

What is sarcoidosis in 3 words? Where is it more common? Who does it mainly affect in terms of age and gender?

Answer 21

Multisystem granulomatous disorder
More common in temporate climates
Mainly young adults, F>M

Question 22

Name 4 histopathological features of sarcoidosis

Answer 22

Epithelioid and giant cell granulomas
Unlikely to have necrosis
Little lymphoid infiltrate
Variable associated fibrosis

Question 23

In what 3 ways does sarcoidosis present?

Answer 23

Young adult with acute arthralgia, erythema nodosum or bilateral hilar lymphadenopathy

Asymptomatic with incidental abnormal CXR/CT

SOB, cough, abnormal CXR

Question 24

In what 4 ways is sarcoidosis diagnosed?

Answer 24

Clinical findings
Imaging findings
Serum Ca++ and ACE
Biopsy or EBUS cytology

Question 25

How is sarcoidosis treated?

Answer 25

Corticosteroids

Question 26

How do you distinguish between sarcoidosis and hypersensitivity pneumonitis in histology?

Answer 26

Sarcoidosis - distinct granulomas HP - thickening of alveolar walls and softer, more diffuse granulomas

Question 27

Define hypersensitivity pneumonitis

Answer 27

Granulomatous condition from hypersensitivity reaction to exogenous inhaled materials

Question 28

Name 5 antigens that can lead to HP

Answer 28

Thermophilic actinomycetes (micropolyspora faeni, thermoactinomyces vulgaris) Bird/animal proteins Fungi (aspergillus) Chemicals Other

Question 29

In what 8 ways does HP present if acute?

Answer 29

Fever, dry cough, myalgia, chills 4-9 hrs after Ag exposure, crackles, tachyopnoea, wheeze, precipitating antibody

Question 30

In what 6 ways does HP present if chronic?

Answer 30

Insidious Malaise SOB Cough Low grade illness Crackles and some wheeze

Question 31

Name 6 histopathology features of HP

Answer 31

* Immune complex mediated combined Type III and IV Hypersensitivity reaction * Soft centriacinar epithelioid granulomata * Interstitaial pneumonitis * Foamy histiocytes * Bronchiolitis obliterans Upper zone disease

Question 32

Name 3 types of HP

Answer 32

Farmer's Lung Bird Fancier's Lung Bark Stripper's Lung

Question 33

What 2 other diseases may UIP present in?

Answer 33

Scleroderma Rheumatoid disease

Question 34

What 5 things may cause UIP?

Answer 34

Connective tissue disease Drug reaction Post infection Industrial exposure (asbestos) Other

Question 35

What age and sex is UIP more prevalent in?

Answer 35

>50, M>F

Question 36

In what 5 ways does UIP present?

Answer 36

Dyspnoea Cough Basal crackles Cyanosis Clubbing

Question 37

What 4 things does CXR of UIP show?

Answer 37

Basal/posterior Diffuse infiltrates Cysts "ground glass"

Question 38

Name 5 histopathology features of UIP

Answer 38

* Patchy interstitial chronic inflammation * Type II pneumocyte hyperplasia * Smooth muscle and vascular proliferation * Evidence of old and recent injury (temporal heterogeneity or spatial heterogeneity) * Proliferating fibroblastic foci

Question 39

What does UIP stand for?

Answer 39

Usual Interstitial Pneumonitis

Question 40

What 4 treatments can be used for UIP and what is their effectiveness? What is the prognosis for UIP?

Answer 40

Steroids or anti-inflammatories (don't work very well) Anti-angiogenic agents (minor improvement) Transpulmonary transplantation 5 year survival

Question 41

What is the endstage of restrictive lung diseases? What causes it and what do the lungs look like?

Answer 41

Endstage lung fibrosis/honeycomb lung Here, progressive fibrosis damages more and more of the lungs. The lungs try to repair themselves but fail, leading to shrunken lung with non-smooth surface.