Restrictive Lung Disease  - Pathoma

  • Restrict lung filling!


  • ↓ TLC
    • Get less in in total
  • ↓↓ FVC
    • Less air in there!
    • normal about 5 L
  • ↓ FEV1
    • normal about 4 L
  • ↑ FEV1:FEVC 
    • As FVC ↓ more
    • >80% 
    • as have less in in total, so the amount you get out early is proportionally higher
    • e.g. 3.5 L / 4 L  > 80%
  • Most due to interstitial disease
    • Interstitial fibrosis
      • Thickens interstitium="barrier" between air in alveolus and alveoli
      • Also makes alveoli contracted, tight and unable to expand
    • Also chest wall abnormalities - e.g. obesity
      • Difficult to overcome force to fully open up and fill lungs
Idiopathic Pulmonary Fibrosis
  • Fibrosis of lung interstitium
  • Trichrome stain - collagen:
  • Due to
    • Cyclical lung injury
    • Thus cyclical healing
    • TGF-β1 from injured pneumocytes induces fibrotic healing
      • TGF-β1 down regs telomerase so epithelial cells die     
      • TGF-β1 decs caveolin-1 (an anti firbotic protein)     
      • NB TGF-β1 imp for repair though so lack of may inc risk of damage from smoking etc!
    • Also get FGF
    • 2° causes (non-idiopathic) [some are discussed in detail later]
      • Pneuomconioses
        • Silicosis
        • Asbestosis
        • Berylliosis
        • Coal worker's pneumoconiosis
      • Drugs
        • Bleomycin
        • Amioderone
        • Methotrexate
        • Nitrofurantoin
        • Busulfan
        • Gold
        • Penicillamine
        • Crack
        • Heroin
      • Radiation therapy
      • Damage - infarct, TB, pneumonia
      • Extrinsic Allergic Aleveolitis
        • Farmer's lung - dust/mold - type III hypersens - IgG complex deposition
        • Bird fancier's lung
        • Mushroom worker's lung
        • Cheese worker's lung
      • CTDs
        • Scleroderma (= systemic sclerosis) - multisys autoimmune, inc fibroblasts activity; vascular, GI, lungs, skin
        • SLE
        • RhA
        • Mixed CTD
      • Systemic illnesses
        • Hep C
        • IBD
        • AIDS
      • Inheritied
        • Familial IPF
        • Tuberous sclerosis
        • NF
        • Niemann-Pick disease - lysosomal storage disorder, spingolipid buildup in monocytes etc - jauendice + CNS signs in vertical gaze palsy, ataxia, seizures
        • Gaucher's disease - most common lysosomal storage disorder,  deposition of glucocerebroside in cells of the macrophage-monocyte system; beta-glucocerebrosidase deficiency (can replace IV!); fatigue, hepatomegaly, splenomegaly, bone probs, bruise, dev delay
        • Hermansky-Pudlak syndrome  - albinism, visual probs
  • Presents
    • Rapid
    • SoB - progressive
    • Wheeze
    • Cough
    • Fibrosis on CXR, CT
      • Starts sub-pleural
      • Then works way into lung
        • Honeycomb lung
  • Mx
    • Stop causes if known
    • Lung transplant
    • ? ACEi
Pneumoconioses
  • Interstitial fibrosis due to occupation exposure
  • Chronic exposure
    • Need lots to cover a significant amount of lung leading to Sx
  • to Small particles
    • if were bigger, would get trapped by mucous and swept away by cilliary esclator
  • that are Fibrogenic
    • must activate macrophages
  • So get all the way to alveolus
    • Get consumed by macrophages
    • Macrophages can't deal with it, freaks out!
    • Tries to "wall off" itself and, thus, the foreign body to save the rest of the lung
    • Does this by inducing fibrosis
    • Macrophages recruit and activate T cells via IFNgamma

ExposureFindingsComment
Coal Worker'sCarbon dust
Most coal miners!
Massive exposure so diffuse fibrosis
= Black Lung
This + RhA = Caplan syndrome
Mild exposure to C just causes anthracosis - lots of "dust cells" - macrophage filled with C
No clinically significant
All of us! Pollution!
Lungs fibrosed and "shrunk"
SilicosisSilica
Silica miners, sandblasters
Fibrotic nodules in upper lung lobes 

Inc TB risk! only one that does so
Silica impairs macrophage phagolysosome formation
BerrylliosisBerryllium - miners, aerospace engineersNon-caseating granulomas in lung, hilar lymph nodes + organs
(sounds a lot like sarcoidosis! careful!)
Inc lung Ca risk
Asbestosis
Asbestos fibres
builders, plumbers, shipyard workers

Small blue fibres worse
Lung and plura (plaques) fibrosis
Inc risk of
  • Lung carcinoma
  • Mesothelioma (rarer; pleura)
Lesions may have long, gold-brown fibres stuck to iron proteins = Ferruginous (Absestos) Bodies


This is confirmatory for exposure

Causes fibrosis of lung + plura
&            Ca          of lung + plura [latter rarer] 


Sarcoidosis

  • Systemic disease 
  • Non-caseating granulomas in lungs
    • "epitheliod histiocytes"
    • non-caseating = all cells alive, no necrosis
    • esp:
    • Lungs
      • in interstitium so restrict lung filling
      • Makes lung less compliant
    • Hilar lymph nodes
    • Non caseating granuloma example:
    • Asteroid Bodies - funny bits in giant cells
    • Eye - uveitis
    • Skin - cutaneous nodules or erythema nodosum
    • Salivary and lacrimal glands - inc dental caries, "grit in eyes", xerostoma - mimics Sjogren's
    • Almost any tissues
  • Most in African females
  • Unknown cause
    • Likely unknown Ag setting of a CD4+ T helper cell response
  • Presents
    • Cough
    • Dyspnoea
    • Elevated serum ACE
    • Hypercalcaemia
      • Granulomas have 1-α-hydroxylase
      • So activate Vitamin D
      • (Same in all non-caseating granulomas - so also beryliosis etc)
  • Rx
    • Steroids
    • May resolve
    • Methotrexate
Hypersensitivity Pneuomonitis
  • Granulomatous reaction to inhaled organic Ags
  • this is the "pigeon fancier's lung" etc
  • Presents - for hours after:
    • Fever
    • Cough
    • Dyspnoea
    • Will resolve when end exposure
    • BUT chronic exposure will cause interstitial fibrosis
    • Granulomas with eosinophiles (as hypersens)
Robbins Basic Pathology, Robbins Pathologic Basis of Disease, Robbins Review of Pathology (MCQs - very path-y), Robbins Flash Cards, Baby Robbins, Robbins Atlas - some exact same images come up in the exam, 100 Cases in ClinicalPathology - possibly the best Qbank for the practical