pathology of restrictive lung disease Flashcards
what are restrictive lung diseases also known as
diffuse or interstitial lung disease
what area of the lung is most commonly involved in restricitve lung disease
the interstitium
what is the interstitium of the lung
he connective tissue space around the airways and vessels and the space between the basement membranes of the alveolar walls
describe the interstitium in healthy lungs
the normal alveolar wall, most of the alveolar epithelial and interstitial capillary endothelial cell beasement membranes are in direct contact
describe the changes to the alveolar wall in interstitial lung disease
alveolar wall thickened by interstitial infiltrate
inflammatory change –> fibrosis (production of tissue between the layers of the basement membrance, interferes with gas exchange)
introduction of collagen and fibrous tissue means the lungs become stiff and cannot stretch as easily
what is meant by reduced compliance
lungs are stiff and don’t expand as easliy
features of FEV1, FVC, gas transfer and V/Q ration in restrictive lung disease
low FEV1, low FVC
normal FEV1/FVC ratio
reduced gas transfer (diffusion abnormality)
V/Q imbalance when small airways are affected by pathology (not all conditions)
presentation of diffuse lung disease
discovery of abnormal CXR/CT
DYSPNOEA - on evertion or at rest
type 1 resp failure
heart failure - as a result of hypoxaemia and pulmonary vasoconstriction
what is the most common presentation of diffuse lung disease
dyspnoea
what is the difference between emphysema and interstitial lung disease on a CXR
emphysema - hyperinflated lungs
interstitial lung disease - reduced lung volumes, increased lung markings
pattern of development for interstitial lung disease
parenchymal (interstitial injury) acute response --> chronic response chronic response leads to one of 3 options: usual interstitial pnuemonitis granulomatous response other patterns
end result for all is fibrosis or end-stage honeycomb lung
what type of sensitivity is a granulomatous response
mix of type III and IV sensitivity
inflammatory conditions
inflammation is mostly chronic in the interstitium of the lung
can be acute which converts into chronic
there is relatively limited way in which the lung can respond to injury
what is diffuse alveolar damage
an altered form of acute inflammation
do all conditions lead to pulmonary fibrosis
NO
not all conditions result in scarring and fibrosis
pulmonary fibrosis is irreversible and may be fatal
some conditions are very rarely at risk of progressing this way
what is the mortality rate for DADS
> 50%
what does DADS stand for
diffuse alveolar damage syndrome
what changes occur in DADS
changes are related to alveolar epithelium and capillary endothelium
results in leaky vessels
what is DADS associated with
major trauma e.g. cardiac arrest chemical injury/toxic inhalation circulatory shock drugs infection - DADS can complicate the effects of an infection autoimmune disease radiation
can also be idiopathic
what are the 2 stages of DADS
exudative stage - oedema (0-2 days following injury) due to leaky capillaries, plasma proteins precipitate in the lungs and form a layer (1-14 days)
proliferative stage (7 days) - interstitial inflammation and fibrosis
histological features of DADS
protein rich oedema
fibrin
hyaline membranes
denuded basement membranes
(lung is trying to repair itself after the damage but isn’t good at it)
epithelial proliferation
fibroblast proliferation
scarring - interstitium and airspaces
sarcoidosis
a multisystem granulomatous disorder of unknown aeitology
most likely affects lymph nodes and lungs
most likley one to encounter in clinical practice
histopathology of sarcoidosis
epithelioid and giant cell granulomas - accumulation of macrophages
necrosis/caseation (cheese like appearance) is very unusual
little lymphoid infiltrate
variable associated fibrosis
incidence of sarcoidosis
commonly affects young adults f>m 3-4/100 000 in UK 20/100 000 in african-americans in USA low in equatorial regions it is a disease of temperate climates
organ involvement in sarcoidosis (% cases)
lymph nodes - almost 100 lung - >90 spleen - 75 liver - 70 skin, eyes, skeletal muscle - 50 bone marrow - 20 salivary glands - up to 50
sarcoidosis presentation
- young adult, acute arthralgia, erythema nodosum, bilateral hilar lymphadenopathy
- incidental abnormal CXR/CT, asymptomatic
- SOB, cough, abnormal CXR
most (esp 1) resolve after 2yrs
2 and 3 may resolve, persist or progress
what is arthralgia
joint pain
what is erythema nodosum
nodular eruptions over the skin
what is the treatment for sarcoidosis
corticosteroids
sarcoidosis diagnosis
clinical findings
imaging findings
serum Ca++ and ACE
biopsy (only needed in relatively few patients)
what is hypersensitivity pneumonitis
granulomatous response
caused by inhalation of organic antigens
what antigens cause hypersensitivity pneumonitis
thermophilic actinomycetes (fungus): micropolyspora faeni, thermoactinomyces vulgaris bird/animal proteins - faeces, bloom fungi: aspergillus spp chemicals others e.g. drugs
what is hypersensitivity pneumonitis also known as
extrinsic allergic alveolitis
acute presentation of hypersensitivity pneumonitis
fever, dry cough, myalgia
chills 4-9hrs after antigen exposure
crackles, tachyopnoea, wheeze
precipitating antibody
high dose of the antigen can lead to infection-like presentation
chronic presentation of hypersensitivity pneumonitis
insidious
malaise, SOB, cough
low grade illness
crackles and some wheeze
can lead to resp failure, low gas transfer
histopathology of hypersensitivity pneumonitis
immune complex mediated combined type III and IV hypersensitivity reaction
soft centriacinar epithelioid granulomata
interstitial pneumonitis
foamy histiocytes
bronchiolitis obliterans
why is hypersensitivity pneumonitis an upper zone disease
the parts of the lung most affected are the areas where the inhaled material first lands
laminar flow –> diffusion point, inhaled material is no longer carried and is deposited
centriacinar regions of the lung are where most pathology occurs
which condition is most likely to progress to severe pulmonary firbosis
usual interstitial pneumonitis
can be fatal and lead to resp failure
poor prognosis
where may usual interstitial pneumonitis (UIP) be seen
connective tissue disease - esp scleroderma and rheumatoid disease drug reaction post-infection - viruses indusrtial exposure - asbestos others
what generally causes UIP
most are cryptogenic or idiopathic (generally cannot determine a possible cause)
Idiopathic pulmonary fibrosis (IPF) or cryptogenic fibrosing alveolitis (CFA)
don’t say the patient has UIP, say they have IPF/CFA
histopathology of UIP
patchy interstitial chronic inflammation
type II pneumocyte hyperplasia
smooth muscular and vascular proliferation
evidence of old and recent injury (temporal and spatial heterogeneity)
proliferating fibroblastic foci
what is the importance of proliferating fibroblastic foci in UIP
they aren’t unique to UIP
manifestation of the repair and fibrosis process
they are both a very important part of the pathological process
clinical example of idiopathic UIP
> 50, m>f
clinically show: dyspnoea, cough, basal crackles, cyanosis, clubbing
progressive disease - most dead in 5yrs
restrictive PFT and reduced gas transfer
what would a CXR oF UIP show
basal/posterior
diffuse infiltrates
cysts
‘ground glass’
what is the prognosis for UIP
some fulminant
some steroid responsive
overall poor prognosis
pulmonary fibrosis confers an increased risk of developing lung cancer
appearance of the lung in UIP
basal and posterior fibrosis and scarring with honeycombing
creation of cystic spaces in the lung - byproduct of the attempt of the lung tissue to repair itself which has failed
normal pulmonary gas exchange
air flow in airways is laminar or turbulent, depends on pressure difference
beyond terminal bronchiole - diffusion
how saturated is the blood leaving the capillary bed and why
98% saturated for FIO2 of 0.21
Hb affinity for oxygen
normal PaO2
10.5-13.5 kPa
normal PaCO2
4.8-6 kPa
type I respiratory failure
PaO2 <8 kPa
PaCO2 normal or low
type II respiratory failure
PaCO2 >6.5kPa
PaO2 usually low
what are the 4 abnormal states associated with hypoxaemia
alveolar hypoventilation
shunt
ventilation/perfusion imbalance
diffusion impairment - generally doesn’t lead to CO2 retention
alveolar hypoventilation
amount of air moved in and out of lungs
hypoventilation increases PACO2 and thus increases PaCO2
PACO2 rise decreases PAO2 which causes PaO2 to fall
fall in PaO2 due to hypoventilation is corrected by raising FIO2
V/Q mismatch
normal V/Q is 0.8
low V/Q is COMMONEST cause of hypoxaemia encountered clinically
low V/Q in some alveoli arises due to local alveolar hypoventilation due to some focal disease
hypoxaemia due to low V/Q responds well to small increases in FIO2
what does gas flow through a membrane depend on
thickness and SA of the membrane and gas pressure across it
how much faster does CO2 diffuse than O2 and why
20x
greater solubility
does diffusion impairment change CO2 levels
diseases impairing gas diffusion usually do no change CO2 levels
it means it takes longer for blood and alveolar air to equilibrate, particularly for oxygen
how long does equilibration normally take
normally 0.25s
in disease equilibration may take close to 0.75s
how long does capillary transit time take
0.75s at rest
the time RBC spend in the alveolar capillary network
when may PaO2 falls occur in diffusion impairment disease
on exercise as capillary transit time falls
exercise can precipitate hypoxaemia in interstitial lung disease
how can hypoxaemia by diffusion impairment be corrected
increasing FIO2
increases PAO2 therefore increasing rate of diffusion
rarely clinically the sole cause of hypoxaemia
define shunt and normal values
blood passing from R to L side of heart w/o contacting ventilated alveoli
normally 2-4% shunt
when can pathological shunt occur
AV malformations
congenital heart disease
pulmonary disease
do large shunts respond to increases in FIO2
they respond poorly
blood leaving the normal lung is already 98% saturated
