Pulmonary fibrosis Flashcards

1
Q

What is interstitial lung disease?

A

Wide range of diseases

At the most extreme end culminate in pulmonary fibrosis

7% of lung diseases culminate in ILD

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2
Q

Where does gas exchange take place in the lung?

A

Across fused basement membrane of the endothelial and epithelial cells

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3
Q

What is the space between the endothelial and epithelial basement membrane called?

A

Interstitial space

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4
Q

What is the histology of a normal intestitial space?

A

Narrow bridge of lung tissue

Populated by occasional fibroblast

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5
Q

What happens to the structure of the lung during ILD?

A

Increase in size of the interstitial space

Gas exchange is compromised

Fibroblastic foci around the alveolar capillary approach alveolar space

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6
Q

What does the lung look like in late stages of ILD?

A

Lung becomes scarred, fibrotic and difficult to see original structure

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7
Q

What is the lung’s response to injury?

A

Limited response

Hard to predict - depends on genetic background

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8
Q

Why is the lung easily injured?

A

Very exposed to toxins in the blood and allergens

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9
Q

What can be used to observe the response of lungs to injury?

A

CT scan

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10
Q

What are the 3 ways in which the lung can respond to injury?

A

Response can be:

Inflammatory - immune systen

Fibrotic scarring - fibroblast proliferation and ECM production

Or both

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11
Q

What is the role of T cells and macrophages in ILD?

A

Th2 produce IL 13 which works with TGF b to differentiate and proliferate the fibroblasts -> myofibroblasts

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12
Q

What induces the differentiation of fibroblasts -> myofibroblasts?

A

TGF b

IL 13

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13
Q

How do you diagnose pulmonary fibrosis?

A

Blood test and in-depth history to conclude source

Full history - jobs done and houses lived in

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14
Q

What are the 3 types of ILD?

A

Organising pneumonia

Interstitial pneumonia

Non-specific interstitial pneumonia

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15
Q

Characteristics of organising pneumonia

A

Whirls of not well organised fibroblasts

Not much ECM has been laid down

Patient will be left with some fibrosis

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16
Q

Characteristics of interstitial pneumonia

A

Most fibrotic form of lung response to injury

Whirls of fibroblasts produce ECM - highly proliferative

Honeycombing

17
Q

Characteristics of non-specific interstitial pneumonia

A

Mixture of inflammatory cells

Airways pulled apart due to fibrosis

Underlying fibrosis when inflammation treated

18
Q

What are the causes of pulmonary fibrosis?

A

Rheumatoid arthritis

Systemic sclerosis

Drugs and dust - asbestosis

Granulomatous disease

Idiopathic

19
Q

What is Granulomatous disease?

A

Presense of granulomas in histopathology

Caused by

Sarcoidosis

Hypersensitivity pneumonitis - allergic response to inhaled exogenous substances

20
Q

Characteristics of idiopathic pulmonary fibrosis

A

CT loss of lung capacity and interstitial shadowing at bases

Honeycombed appearance

Shortness of breath, clubbing, crackles, debilitating cough

Majority of patients die within 2 to 5 years after diagnosis

No cure - halt the decline via transplant

21
Q

What are the 3 cells important in the development of pulmonary fibrosis?

A

Type I alveolar epithelial cells

Fibroblasrs

Neutrophils - unkown

22
Q

How are Type I alveolar epithelial cells important in the development of pulmonary fibrosis?

A

Death and apoptosis of these cells during fibrosis

Replaces with type II epithelial cells

23
Q

How are fibroblasts important in the development of pulmonary fibrosis?

A

Produce excessive amounts of EC collagen

Undergo proliferation

Resistant to apoptosis

24
Q

What are common molecular targets in pulmonary fibrosis?

A

Fibroblasts -> myofibroblasts

Th2/ Th1 imbalance

MMP imbalance

25
Q

Why is it difficult to develop drugs for ILD?

A

Initiating events are not known

26
Q

Describe targetting fibroblast -> myofibroblast transition in developing drugs for ILD

A

Epithelial mesenchymal transition

Driven by TGFb

Activation of TGF b is dependent on integrin expressed

Can’t target TGF b - essential for other processes

27
Q

Describe targetting Th1/Th2 imbalance

A

Inhibiting Th2 is beneficial to treating ILD

28
Q

What is a biomarker for pulmonary fibrosis?

A

MMP

29
Q

How do we taget MMPs to treat ILD?

A

Inhibition of MMPs is beneficial

30
Q

Role of neutrophuls in development of pulmonary fibrosis

A

Patients with idiopathic pulmonary fibrosis = increased neutrophil count in bronchoalveolar lavage

The more neutrophils = the worse the outcome

31
Q

Pathogenesis of pulmonary fibrosis

A

Epithelial cells undergo inkury

Chemokines are released from local cells and macrophages

This recruits neutropjils

Form ROS - more damage to cells

More TGF b produced

More EMT transition and epithelial cells transform into myofibroblasts

Increased deposition of ECM