8.3 Flashcards
(33 cards)
What is fibrosis?
Excessive deposition of extracellular matrix (ECM) that disrupts normal tissue structure and function.
What is the clinical impact of fibrosis?
It compromises tissue function and is associated with chronic diseases like cirrhosis, IPF, scleroderma, etc.
What are examples of fibrotic diseases?
Pulmonary fibrosis, liver fibrosis, myocardial infarction, scleroderma, keloids.
What are the three outcomes of injury?
Regeneration, scar formation, and fibrosis.
What distinguishes regeneration from fibrosis?
Regeneration restores normal structure; fibrosis leads to scar tissue formation due to ECM overproduction.
What is the key difference in inflammatory response between repair and fibrosis?
Repair involves resolved acute inflammation; fibrosis is driven by chronic, ongoing inflammation.
What is a myofibroblast?
A contractile cell derived from fibroblasts that produces ECM proteins during fibrosis.
What is the role of epithelial-mesenchymal transition (EMT)?
It converts epithelial cells into mesenchymal (fibroblast-like) cells contributing to fibrosis.
What protein imbalance contributes to fibrosis?
Imbalance between MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs).
What is the pattern of cell differentiation in tissue repair?
Fibroblast → myofibroblast with eventual apoptosis.
What happens to myofibroblasts in fibrosis?
They avoid apoptosis and become senescent, continuing to produce ECM.
How is ECM deposition regulated in repair vs fibrosis?
Repair: tightly regulated. Fibrosis: excessive and unregulated.
What is TGF-β?
A key profibrotic cytokine that drives ECM production and myofibroblast activation.
What pathways does TGF-β use for signalling?
Canonical (SMAD2/3 → SMAD4 → nucleus) and non-canonical (MAPK, PI3K/AKT).
What does TGF-β inhibit in fibrosis?
ECM degradation and apoptosis of myofibroblasts.
How is TGF-β activated?
From a latent form by activators like plasmin, thrombospondin, and integrins.
What is IPF?
Idiopathic Pulmonary Fibrosis: a progressive disease involving fibrotic scarring of lung interstitium.
What are key features of IPF lungs?
Collagen deposition, fibroblast foci, and lung architecture disruption.
What is the survival rate of IPF?
Around 50% at 3 years.
What challenges exist with steroid use in IPF?
Limited benefit and significant side effects.
What is nintedanib?
A TKI targeting VEGFR, FGFR, and PDGFR; slows FVC decline in IPF.
What is pirfenidone?
An anti-fibrotic agent that inhibits TGF-β and collagen production.
What are common side effects of nintedanib?
Nausea, diarrhoea, liver dysfunction.
What are common side effects of pirfenidone?
GI symptoms, weight loss, URTIs, fatigue.
