L22- Restrictive Lung Disease Flashcards
What 2 defects in restrictivr lead yo hypoxia in the end
Restriction of lung compliance ie elasticity and chest wall movement
Or
Impaired gas rxchnage tossue eg oedema filling or fiborsis to thicken it
Altered lung parenchyma is 1 cause of restticitvie disease. What is the parenchyma
Functional lung tissue eg for diffsuion, perfusion and ventilatiom
Eg alveoli, ducts and resp bronchioles
Give examples of sltered parenchyma
Fibrotic scarring increasing thickeneds
Honeycomb destroyed tissues reducing amount of cells for excusnhe
Fibrotic deposits clotting the blood capillaries
Oedema causing collapse and also reduced diffusion of gases
Disease of what fluid filled cavity can cuase restricififr disease and givr rxamples
Pleura
Eg pneumothorax when it fills with air
Haemothorax filling with blood
Empysema pus filled
How does pleura in heslthy krep lungs inflated allowing incressed capacity
Holds a nefstivr pressure below atmospheric
If it gets dilled what happens
Causes restrircuon in lung,collapsing, dysponea, cyanosis when hypxoia occurs
Which article dusccuses the pleura
Choi 2014
What did choi 2014 aay happens in pneumothroax
Air from slveoli floods into the pleura causinf incrrased pressure and tehrefore less inflated lungs
By what % does fvc decrease in pneumothorax meaning it’s restrictive
33%
Whats the difference between fluid filled pleura and air filled on xray
Fluid causes increased consolidation
Give 2 examples of chest wall abnormalities causing restrictive disease
Rib fracture, reduces lung ability to expand
Scoliosis too
What does nueormuscular disease causing restriction mean
Either the muscles are weajnfor resp or the nerves whcih control them cussing restriction
What is an exampke of this and give the article
Duchenne muscular dystrophy
Stehling et al 2015
Which muscles are weakened in this (stehling£
Expiratort
What does this lead to redcued
Reduced pef and cough peak flow. This means refuced fvc, fev1, increased infrctions due to lack of coughing and impaired resp failure
What 3 things lead to restricted gas exchnahe in these fiseases
Ability to expand lost eg neuormusc disease
Gas exchnage surfece loss ie crll loss
Reduced gas exchnage efficiency eg oedema ot fibrotic depoditd
What can cause abnormal v/q in restrictive diseases
If there is damage to both epithelium and vasculature eg fibrosis reduces capillaries
What is stiff lung due to causing lsck of compliance
Loss of parenchyma= damage elasticity, fiborsis increase, increased interstitail fluid
Where is interstitium gas exchange surfsce
Between capillaru endothelium and the alveolar basemment membrane
What is reduced in rds in infants
Surfsctant causing alveolar collapse
Which zone do type 1 have squahsed organelles
Perinuclear zone
Where do the organelles products diffuse into
The cytoplasmic flap of type 1
If macrophages dont exit vis mucocilatort. How
Exit cis the blood/lymph shen crossing interstitium
How many people in uk affected by interstitial lung diseases
1 in 2000 (v rare)
What % caused by environemtn eg dusts
35
What are the causes of chronic ild like idiopathic pf
Idiopsthic ie unknown trigger
Hypersensitivity to dust
Immune response to infections
Autoimmune eg ra
Who usually more likely to get ipf
Men and okder acove 70
What are rhe desth toll each year in uk by ipf
2000
Cystic airspaces in endstage honeycombinf (3-10mm) is filled with what
Mucus and inflam cells where notmal tossue used to be
What is spatial and temporal heterogeneity of ipf
Occurs over a long time and some places cna be heslthy vs diseased = spatial. Temporal means at diff stages eg some areas are actively depositing whereas others are already scar tissue
Lung tissue damage cia injury eg dust is the trigger. This causes inflammation and in what sites
Bronchioles = bronchiolitis
Alveoli= alveolitis
Capillaries = vasculitis
What soes inflammation allow
Finrosis to occur or oedema if ards
What sort of profibrotic cytokines are released by damaged epi crlls during trigger in ild
Tgfb, pdgf, tnfa
What does tgfb reduce which increases levels of collagen
Mmps
Where does te fibrotic deosits go
In interstitium disrupting it
What do myofibroblasts do when fibroblasts diff into them
Excess secretion of fibrous proteins like collagen = progressive lining stiffening/density
Which 2 released were found to increasde angiogenesis even though ipf refuces capillaries
Fgf2 and vegf
Which article discusses pathogensis of ipf
King jr et al 2011
Which comorbidities adsoicated with fibrosis
Obedity, siabetes, bronchiolitis, emphysema
What aort of effects do microinjuires like smoke or dust have on the epi cells provokinf the ipf response
Cell dearh
How does myofibroblasts stimulate more of the ipf response
They induce more apoptosis of aec
What usually in nfomal wound healing happens to myofibroblasts
Get apoptosed. Doesnt happen in ipf
What stops mf apoptosing so more fibrosis occurs
Tgfb. Forms resistant myofibroblasts
Whixh wnzymes are increased wgich allow viild up of thingns like collagen
Timps which block mmps
Why is there loss of thpe 1 cells in ipf permanently
The transition from type 2 to 1 is inhibited by bm damage and ecm
What does tfb1 promote in terms of cells in ipf
Myofibroblasts transition and emt too
What mmps acticate tgf B makinf thrm profibrotic
Mmp 2 and 9
Which cells produce these
Neutrophils, macrophages and fibroblasts themselves. (All recruited in inflammation /by damaged cells)
Which Moniclonal ab treatment showrd to worsen ipf
Simtuzimab
And which drug
Pirfenidine
What tewo category drugs given for ipf
Anti fibrotic and anti inflam
Why are antacids given
Because acid can cause epithelial damage causing ipf
