Pathology of restrictive lung disease

Question 1

what is the interstitium of the lung

Answer 1

The connective tissue space around the airways and vessels and the space between the basement membranes of the alveolar walls

Question 2

what would a patient with restrictive lung disease present with

Answer 2

abnormal CXR dyspnoea - SOB on exertion and at rest type 1 - respiratory failure (low ambient O2, low or normal CO2) heart failure

Question 3

what would you expect to happen to FEV1 and FVC values and the FEV1/FVC ratio in someone with interstitial lung disease

Answer 3

low FEV1 low FVC but FEV1/FVC normal ratio top 2^ decrease as less air can come in and equally out but the rate at which they come out remains constant

Question 4

what are some possible general causes of diffuse alveolar damage? (8)

Answer 4

idiopathic or Major trauma Chemical injury / toxic inhalation Circulatory shock - occurs due to the provision of inadequate substrates ie O2/CO2 for cellular respiration Drugs Infection Auto(immune) disease Radiation

Question 5

in restrictive lung diseases where do the disease take place

Answer 5

in the pulmonary interstitium

Question 6

how does restrictive lung disease increase the thickness of normal alveolar walls

Answer 6

because the fibroblasts and inflammatory cells are introduced into this space between the basement membranes of the alveolar walls

Question 7

what happens when lungs stiffen

Answer 7

the elastic is still in the alveolar walls but they can no longer stretch because of all the things that have been introduced eg inflammatory molecules gas exchange becomes almost impossible

Question 8

is pulmonary fibrosis reversible?

Answer 8

no, it is neither survivable when it becomes severe

Question 9

what is usual Interstitial Pneumonitis (UIP) very likely to end in what?

Answer 9

fibrosis

Question 10

what are some chronic responses of interstitial lung disease (2)

Answer 10

usual Interstitial Pneumonitis (UIP) - characterised by progressive scarring of both lungs

granulomatous responses - granuloma is a collection of macrophages formed during inflammation - immune system attempts to wall off substances it perceives as foreign but is unable to eliminate them

Question 11

what is an example of an acute response to I.L.D

Answer 11

ARDS - rapid onset of widespread inflammation in the lungs. Symptoms include SOB, hyperventilation, and cyanosis diffuse alveolar damage (DAD) can be seen in ARDS and interstitial pneumonitis - typical histological pattern due to injury in lung tissue - can lead to permanent pulmonary fibrosis

Question 12

what happens in diffuse alveolar damage

Answer 12

vast damage to the capillaries of the lung extensive leakage of alveolar capillaries (exudate) fluid fills the alveolar spaces because of damage to the alveolar walls

Question 13

when proteins leak out of pulmonary capillaries surrounding the alveoli, what forms around the alveolar sacs?

Answer 13

hyaline membrane - composed of proteins and dead cells - makes gas exchange difficult or impossible

Question 14

granulomatous responses to ILD (2)

Answer 14

• sarcoidosis - more common - idiopathic condition - multisystem granulomatous disorder
• hypersensitivity pneumonitis - pneumonia caused by hypersensitivity to inhaled organic dusts
• infections

Question 15

sarcoidosis

Answer 15

a type of granulomatous interstital lung disease

multi-system granulomatous disorder of unknown aetiology

Question 16

what is sarcoidosis characterised by

Answer 16

the formation of granulomas it doesn’t form an awful lot of fibrosis

Question 17

how would you diagnose sarcoidosis

Answer 17

it is multi-system so you would need to have the appropriate pathology in multiple parts of the body usually discovered incidentally by CXR - asymptomatic

Question 18

statistics surrounding sarcoidosis

Answer 18

commonly affects young adults and females more so than males 3-4/100,000 in uk

Question 19

what are the main organs involved in sarcoidosis

Answer 19

main ones are: - lymph nodes - lung others: - spleen - liver - skin, eyes, skeletal muscle

Question 20

how does sarcoidosis present

Answer 20

• Acute arthralgia- joint pain - Erythema nodosum- swollen fat under the skin causing red bumps and patches - Bilateral hilar- lymphadenopathy these 3 tend to resolve after 2 years^ incidental abnormal CXR - no symptoms SOB, cough and abnormal CXR these 2^ may resolve, persist or progress

Question 21

what is used to treat sarcoidosis

Answer 21

corticosteroids

Question 22

how is sarcoidosis diagnosed

Answer 22

clinical findings imaging findings testing serum for Ca2+ and ACE angiotensin converting enzyme - effects of macrophages biopsy

Question 23

importance of Ca2+ and ACE

Answer 23

Ca2+ - long story short due to the activity of macrophages ACE - the cells surrounding granulomas can produce increased amounts of ACE and the blood level of ACE may increase when sarcoidosis is present

Question 24

what type of hypersensitivity results in granuloma formation

Answer 24

type 4 but also type 3 4 = T cells - release cytokines - activate macrophages 3 = antigen-antibody complexesy deposited in tissues and not cleared - inflammation

Question 25

hypersensitivity pneumonitis: what causes the oversensitivity ie what are the antigens (4)

Answer 25

Thermophilic actinomycetes - Micropolyspora faeni Thermoactinomyces vulgaris bird/ animal proteins - faeces fungi - aspergillus chemicals many others though

Question 26

what are thermophilic actinomycetes?

Answer 26

a group of bacteria that can cause ‘farmer’s lung’ they grow in wet straw, spores are released and breathed in by farmers

Question 27

acute presentation of hypersensitivity pneumonitis

Answer 27

Fever, dry cough, myalgia, Chills 4-9 hours after Ag exposure Crackles, tachyopnoea, wheeze Precipitating antibody

Question 28

chronic presentation of hypersensitivity pneumonitis

Answer 28

Insidious - develops gradually as to be well established before becoming apparent Malaise, SOB, cough Low grade illness Crackles and some wheeze

Question 29

what can hypersensitivity pneumonitis lead on to if it continues to develop and isn’t recognised

Answer 29

can lead to respiratory failure

Question 30

where does hypersensitivity pneumonitis take place around

Answer 30

the terminal bronchioles but also tends to affect the upper part of the lung and this can make the upper part become completely non-functional

Question 31

what is more likely to cause fibrosis:- hypersensitivity or sarcoidosis

Answer 31

hypersensitivity

Question 32

what is usual interstitial pneumonitis UIP

Answer 32

chronic response to intersitial lung disease

Question 33

what is the commonest cause of interstitial lung disease?

Answer 33

idiopathic pulmonary fibrosis IPF - type of interstitial pneumonia. Inflammatory cell infiltrate and pulmonary fibrosis of unknown cause

Question 34

TRUE or FALSE UIP is virtually impossible to treat

Answer 34

TRUE

Question 35

In what other circumstances may UIP be seen

Answer 35

Connective tissue diseases; esp scleroderma and rheumatoid disease Drug reaction Post infection Industrial exposure - asbestos

Question 36

what is a ‘honeycomb lung’?

Answer 36

widespread fibrosis and is defined by the presence of small cystic spaces with irregularly thickened walls composed of fibrous tissue usually end stage- a lot of damage - UIP granulomatous responses and other patterns can all lead to this

Question 37

other patterns causing chronic interstitital lung disease

Answer 37

Non specific NSIP asbestos silicosis - inhalation of dust containing silica smoking related fibrosis

Question 38

do you tend to get patients presenting with type 2 respiratory failure if they have interstitial diseases?

Answer 38

no because the diseases impair gas diffusion but do not usually affect the CO2 equilibrium

Question 39

what happens to equilibration in interstitial disease

Answer 39

can increase from 0.25s to close to 0.75 gets longer and longer and this may affect diffusion at rest

Question 40

acute sarcoidosis:- presentation/ symptoms diagnosis/investigation management

Answer 40

presents with:- Fever bilateral hilar lymphodenopathy - enlargement of lymph nodes at hilum Erythema nodosum - swollen fat under skin if pulmonary cause 90% have abnormal CXR with BHL and maybe pulmonary infiltrates or fibrosis symptoms:- due to pulmonary disease - dry cough, progressive SOB, decreased exercise tolerance, chest pain skin lesions eye lesions weight loss diagnosis/investigation:- CXR then CT if abnormal CXR FBC transbronchial biopsy - +ve result in 90% serum ACE - cells around granulomas produce increased ACE (Serum Angiotensin Converting Enzyme) PFTs - restrictive effect urine test - increase in Ca2+ management NSAIDs non steroidal anti-inflammatory drugs systemic and topical steroids bed rest 60% with thoracic sarcoidosis resolve in 2 yrs

Question 41

causes of bilateral lymphadenopathy (6)

Answer 41

sarcoidosis infection e.g TB, mycoplasma malignancy e.g lymphoma, carcinoma, mediastinal tumours organic dust disease e.g silicosis hypersensitivity pneumonitis histocytosis x - langerhan’s cell histocytosis

Question 42

idiopathic pulmonary fibrosis clinical info

Answer 42

Elderly >50 M>F Generally involves the basal and posterial parts of the lung Dyspnoea, Cough, Basal Crackles, Cyanosis, Clubbing Progressive Disease : Most dead within 5 years CXR : Basal/Posterior, Diffuse infiltrates, Cysts, ‘ Ground Glass’ Restrictive PFT & Reduced Gas Transfer Poor Prognosis : Some fulminant, some steroid responsive

Question 43

what is interstitial lung disease?

Answer 43

Umbrella term for a number of conditions that affect the lung parenchyma in a diffuse manner (DAD) characterised by chronic inflammation and/or progressive interstitial fibrosis

Question 44

Question 45

Describe summary of interstitial lung diseases

Answer 45

ILDs = umbrella term for number of conditions that affect the lung parenchyma in a diffuse manner (DAD) characterised by chronic inflammation and/or progressive interstitial fibrosis

Known causes:-

• connective tissue diseases
• occupational causes
• drug side-effects

Granulomatous type of ILD:-

• Sarcoidosis
• hypersensitivity pneumonitis
• infections

Branch of ILDs called idiopathic interstitial pneumonias:-

can be major, unclassifiable or rare

Major ones:-

• chronic fibrosing - idiopathic pulmonary fibrosis and non-specific interstitial pneumonia
• acute and subacute - acute interstitial pneumonia