6 - lung fibrosis mechanisms Flashcards
(40 cards)
variety of cells lining the respiratory airways
ciliated cells goblet cells basal cells alveolar T1 alveolar T2
role of alveolar T1 cells
squamous pneumocytes that make up 90% of lung surface area
forms structure of alveolar walls
flat and thin for gas exchange
role of alveolar T2 cells
secrete lipoprotein called surfactant to reduce surface tension in the alveoli
how much air do we breathe in daily
10, 000 L
factors that may expose the lungs to predispositions for disease
smoking type of workplace (carpenter) oxygen (can produce ROS) genetics viruses breathed in in air
how many viruses do we breathe in a day
500 million
what does IPF stand for
idiopathic pulmonary fibrosis
what is idiopathic pulmonary fibrosis
end stage of a heterogenous group of interstitial lung diseases
accounts for >5000 deaths a year
overall fibrosis aspect of IPF
caused by scar tissue –> collagen (ECM) depositing and building up
which prevents breathing over time
symptoms of IPF
dyspnoea (shortness of breath) coughing fever weight loss clubbing
what is clubbing
thickening of finger tips
dyspnoea
shortness of breath
what does a physical examination look for to diagnose IPF
sounds in the lungs e.g. crackling
overall/general mechanism of IPF development
fibroproliferative response to lung injury
order of steps underlying IPF development from initial injury to organ failure
- epithelial cell injury
- activation of coagulation cascade –> inflammation
- establishment of chemokine networks, leukocyte infiltrations and activation
- fibroblast recruitment, proliferation and differentiation
- loss of organ function
order of events during an active breathing cycle
- diaphragm contracts (flattens, increases thoracic volume)
- external intercostal muscles contract (rip cag moves up and out)
- -> air is sucked in - diaphragm relaxes (dome-shaped)
- internal intercostal muscles contract
what might cause bronchiolar tissue damage
trauma infection physical/chemical agents tissue necrosis foreign bodies (asbestos) immune reactions (hypersensitvity)
how is bronchiolar tissue repaired
by regeneration of damaged tissue by paranchymal cells of the same type
or by replacement by connective tissue (scar formation)
4 steps for tissue repair
- haemostasis
- inflammation
- proliferation
- remodelling
haemostasis and inflammation steps of tissue repair
- haemostasis
- -> blood vessels constrict to keep blood within damaged vessel
- -> platelets stick together, fibrin activated to reinforce plug (clotting cascade)
- -> growth factors and cytokines recruited - inflammation
- -> immune cell recruitment, 1st macrophages then neutrophils
- -> wound debridement (removal of damaged tissue by phagocytes)
which cytokines are recruited during tissue repair
TGF-a
PDGF
VEGF
PDGF
platelet derived growth factor
- regulates cell growth and division.
VEGF
vascular endothelial growth factor
- stimulates formation of blood vessels
proliferation and maturation/remodelling steps for tissue repair
step 3: proliferation
- re-epithelisation –> proliferation of epithelial cells
- angiogenesis
- fibroplasia –> myobibroblasts activated by PAMPs to make collagen
- ECM deposition to make tissue
4: maturation/remodelling
- scar formation
- collagen remodelled from TIII to TII
- collagen realigned along tension lines
- apoptosis removes unneeded cells
