Pathology of restrictive lung disease Flashcards
what is the interstitium of the lung
The connective tissue space around the airways and vessels and the space between the basement membranes of the alveolar walls
what would a patient with restrictive lung disease present with
abnormal CXR dyspnoea - SOB on exertion and at rest type 1 - respiratory failure (low ambient O2, low or normal CO2) heart failure
what would you expect to happen to FEV1 and FVC values and the FEV1/FVC ratio in someone with interstitial lung disease
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
what are some possible general causes of diffuse alveolar damage? (8)
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
in restrictive lung diseases where do the disease take place
in the pulmonary interstitium
how does restrictive lung disease increase the thickness of normal alveolar walls
because the fibroblasts and inflammatory cells are introduced into this space between the basement membranes of the alveolar walls
what happens when lungs stiffen
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
is pulmonary fibrosis reversible?
no, it is neither survivable when it becomes severe
what is usual Interstitial Pneumonitis (UIP) very likely to end in what?
fibrosis
what are some chronic responses of interstitial lung disease (2)
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
what is an example of an acute response to I.L.D
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
what happens in diffuse alveolar damage
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
when proteins leak out of pulmonary capillaries surrounding the alveoli, what forms around the alveolar sacs?
hyaline membrane - composed of proteins and dead cells - makes gas exchange difficult or impossible
granulomatous responses to ILD (2)
- sarcoidosis - more common - idiopathic condition - multisystem granulomatous disorder
- hypersensitivity pneumonitis - pneumonia caused by hypersensitivity to inhaled organic dusts
- infections
sarcoidosis
a type of granulomatous interstital lung disease
multi-system granulomatous disorder of unknown aetiology
what is sarcoidosis characterised by
the formation of granulomas it doesn’t form an awful lot of fibrosis
how would you diagnose sarcoidosis
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
statistics surrounding sarcoidosis
commonly affects young adults and females more so than males 3-4/100,000 in uk
what are the main organs involved in sarcoidosis
main ones are: - lymph nodes - lung others: - spleen - liver - skin, eyes, skeletal muscle
how does sarcoidosis present
- 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
what is used to treat sarcoidosis
corticosteroids
how is sarcoidosis diagnosed
clinical findings imaging findings testing serum for Ca2+ and ACE angiotensin converting enzyme - effects of macrophages biopsy
importance of Ca2+ and ACE
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
what type of hypersensitivity results in granuloma formation
type 4 but also type 3 4 = T cells - release cytokines - activate macrophages 3 = antigen-antibody complexesy deposited in tissues and not cleared - inflammation
hypersensitivity pneumonitis: what causes the oversensitivity ie what are the antigens (4)
Thermophilic actinomycetes - Micropolyspora faeni Thermoactinomyces vulgaris bird/ animal proteins - faeces fungi - aspergillus chemicals many others though
what are thermophilic actinomycetes?
a group of bacteria that can cause ‘farmer’s lung’ they grow in wet straw, spores are released and breathed in by farmers
acute presentation of hypersensitivity pneumonitis
Fever, dry cough, myalgia, Chills 4-9 hours after Ag exposure Crackles, tachyopnoea, wheeze Precipitating antibody
chronic presentation of hypersensitivity pneumonitis
Insidious - develops gradually as to be well established before becoming apparent Malaise, SOB, cough Low grade illness Crackles and some wheeze
what can hypersensitivity pneumonitis lead on to if it continues to develop and isn’t recognised
can lead to respiratory failure
where does hypersensitivity pneumonitis take place around
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
what is more likely to cause fibrosis:- hypersensitivity or sarcoidosis
hypersensitivity
what is usual interstitial pneumonitis UIP
chronic response to intersitial lung disease
what is the commonest cause of interstitial lung disease?
idiopathic pulmonary fibrosis IPF - type of interstitial pneumonia. Inflammatory cell infiltrate and pulmonary fibrosis of unknown cause
TRUE or FALSE UIP is virtually impossible to treat
TRUE
In what other circumstances may UIP be seen
Connective tissue diseases; esp scleroderma and rheumatoid disease Drug reaction Post infection Industrial exposure - asbestos
what is a ‘honeycomb lung’?
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
other patterns causing chronic interstitital lung disease
Non specific NSIP asbestos silicosis - inhalation of dust containing silica smoking related fibrosis
do you tend to get patients presenting with type 2 respiratory failure if they have interstitial diseases?
no because the diseases impair gas diffusion but do not usually affect the CO2 equilibrium
what happens to equilibration in interstitial disease
can increase from 0.25s to close to 0.75 gets longer and longer and this may affect diffusion at rest
acute sarcoidosis:- presentation/ symptoms diagnosis/investigation management
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
causes of bilateral lymphadenopathy (6)
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
idiopathic pulmonary fibrosis clinical info
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
what is interstitial lung disease?
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
Describe summary of interstitial lung diseases
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
