L10 - interstitial lung disease Flashcards
obstructive spirometry
lower FEV1 and same FVC
Restrictive spirometry
much lower FEV1 and FVC, lower expiratory flow rate
measuring ILD
can be seen in x-rays through scarring
ILD
disease of gas exchange, increased barrier due to scarring so oxygen must travel further whilst CO2 can still escape therefore less gas exchange
lung disunion factor in ILD
reduced for carbon monoxide
Incremental shuttle walk test
walking bleep test around 2 cones
Six minute walk test
walking continuously around 2 cones for 6 minutes and recording distance walked
Resistriction of lung volumes
measured by FVC
reduction in lung gas transfer effieicny
Dlco/Tlco
Physiology testing
hypoxia in exertion/exercise
reduction in exercise capacity
IPD cause
unclear cause, therefore idiopathic
occurs through fibrosis of lung parenchyma
IPD mehcnaism
fibroblast repair damaged tissue, migrate to lungs to become myofibroblass which deposit collagen in the extracellular matrix and then proliferate to form fibroblastic foci
the thickened tissue leads to lower gas exchange efficiency int he lungs
IPD genetic susceptability
mutations in genes involved in telmere length maintenance
variations in genes responsible for cell adhesion nd integrity
single nucleotide polymorphism in MUC5B promote region
IPD Lung microbiome
increased risk of disease progression in patients due to increased overall bacterial burden, abundance of streptococcal and staphylococcal organisms
Risk of IPF is increased by genetic variation in TOLLIP
TOLLIP
gene encoding a protein that inhibits responses to microbes
Genes in maintenance of telomere length
TERT, TERC, PARN and RETEL1
IPD key featues
fibroblasts collections, thickening of alveolar interstitial, destruction of alveoli, periphery and base of lungs affected, spatial heterogeneity
Spatial heterogeneity
normal lung tissue next to abnormal lung tissue
Hypersensitivity pneumonitis
immune-mediated hypersensitivity reaction in a genetically predisposed individual
HP inducers
recurrent exposure to environmental agents
HP pathogenesis
very different to IPD
inflammation nd air trapping, may progress to fibrosis and look like UIP pattern on HRCT
type I
IgE, rapid onset
e.g. latex allergy and asthma
type II
cytotoxic, antibody e.g. acute transplant rejection
type III
immune complex deposition (antibody and antigen) e.g. hypersensitivity pneumonitis
Type IV
T cell, delayed e.g. chronic transplant rejection
HP type
type III
HP mechanism
prior sensitisation required, IgG antibodies produced by lymphocytes retain antigen immune memory
on second exposure antigen-antibody complexes are formed and deposit in lungs without being properly cleared
Repeated exposure in HP
leads to repeated symptoms and physiological decline
HP immunopathological mechanism
associated with increase of CD4+ T cells, CD4/8 ratio and Th2 activity
CD4+ Th17 cells involved in lung fibrosis development
tolerance may be mediated by regulatory T cells
CTP-ILD common
System sclerosis, rheumatoid arthritis and idiopathic inflammatory myositis
Idiopathic NSIP
up to 15% diagnosed with this are later found to have CTD
Interstitial pneumonia with autoimmune features
ILD can occur in presence of autoimmune features that do not meet specific CTD classification
CTP-ILD hypothesis
lung injury triggers local inflammation which induces auto-antigen expression causing auto-antibody generation in lung
ILD mechanism
unknown triggers cause inflammatory cells to invade interstitial and alveolar spaces
lung epithelial damage
recruitment and activation of moo/fibroblasts
which produce increased amounts of extracellular matrix proteins and populate fibrogenic cell scarring within lung
results in interstitial lung disease
Sarcoidosis
granulomatous disease characterised by presence of non-caseating granulomas involving multiple organ systems
lungs affected in over 90% of cases
Sarcoidosis cause
exact cause remains unknown but many studies suggest right combination of antigen exposure in a genetically predisposed individual under favourable environmental conditions contributes to disease devleopment
sarcoidosis exposures
insecticides, agricultural employment, work environments with mould and occupational areas with musty odours
sarcoidosis mechanism
antigen exposure and internalisation, with presentation in regional lymph nodes
CD4+ cell activation, proliferation and Th1 polarisation induced by antigen recognition and co-stimulator signals
Newly-activated circulating CD4+ cells bone, via chemokine, to tissue sites with antigen, and stimulate macrophages to organise into granulomas
chronic inflammation nd pulmonary fibrosis
