Chronic Diffuse (Interstitial) Lung Disease

Question 1

clinical presentation of restrictive lung dz?

Answer 1

• dyspnea
• tachypnea
• end-repsiratory crackles
• NO WHEEZING - b/c there is no airway obstruction

Question 2

draw volume-pressure curves of obstructive vs restrictive disease. how does each dz effect the lung capacities (RV, FRV, VC, TLC)

Answer 2

• both decrease VC
• obstuctive: can’t get air out –> inc RV–> inc FRV –> inc TLC
• restrictive: can’t get air in –> dec RV –> dec FRV –> dec

obstructive: total air lung volume = being normal. RV makes up a higher portion of that TLC than in normal.

restrictive (interstitial) : total lung volume is significantly less than normal.

Question 3

discuss the general findings seen on images of restrictive (interstitial) lung dz

Answer 3

• bilateral
  
  • nodules
  • irregular lines
  • ground glass shadows

Question 4

what are the major potential sequale of restricive (interstitial) lung dz?

Answer 4

• pulmonary HTN –> right HF (cor pulmonale)
• severe lung scaring
  
  • “honeycomb” lung

Question 5

usual interstitial pneumonia (UIP)

• restrictive or obstructive?
• demographics?
• clinical presentation?

Answer 5

• interstitial = restrictive
• demographics = 50-70, M > F
• clinical:
  
  • subacute onset
  • non-productive cough (vs typical pneumo)
  • LOW/NO fever (vs typical pneumo)
  • later in dz –> inspiratory crackles
  • +/- finger clubbing

Question 6

usual interstitial pneumonia - gross appearance

Answer 6

*gross appearance not very telling)

• outside (pleural surface): cobblestone
• inside (cut surface): rubbert/white/firm fibrosis in LOWER LOBES

Question 7

usual interstitial pneumonia (UIP) - microscopic appearance

Answer 7

• alveolar wall lesions that
  
  • fibrotic
  • contain lymphocytes + some plasma cells
  • are patchy - adjacent to mormal lung tissue
  • are temporarily heterogenous: become less cellular over tme
    
    • early on: fibroblastic cells > collagen - bluer
    • later on: collagen >>>> cells - pinker

again, mostly in the lower lung.

Question 8

what can morphology can develop in late stage UIP?

Answer 8

• “honeycombing” of lung:
  
  • the fibrosis can lead to massive, multicystic changes:
    
    • dilated air spaces at lung periphery
• squamous metaplasia

Question 9

how to dx UIP?

Answer 9

• first, microscopic & radiographc findings: patchy interstitial fibrosis + lymphocytes / ground glass, honeycombing in lower lungs
• if not diagnostic, must do:
  
  • multiple open lung biopsies from multiple lobes
    
    • ​transbronchial biopdsies not useful

Question 10

non-specific interstitial pneumonia (NSIP_

• restrictive vs obstructive
• demographic
• clinical presentation

Answer 10

• interstitial = restrictive
• demographics: 25-60, F > M
• clinical presentation
  
  • similar to UIP (dyspnea, cough, +/- clubbing)

Question 11

NSIP gross appearance

Answer 11

not telling

Question 12

clinical differences between UIP (IPF) vs NSIP

Answer 12

• Unspecific Interstitial Pneumonia / Idiopathic Pulmonary Fibrosis
  
  • no known etiology
  • demographics: 50-70 (older), M > F
  • prognosis: poor
  • NO response to corticosteroids
• Non-Specific Interstitial Pneumonia
  
  • linked to collagen-vascular dz
  • demographics: 25-60 (younger), F > M
  • prognosis: better than UIP
  • DRAMATIC response toto corticostreroids

Question 13

NSIP microscopic apperance

Answer 13

• wall lesions that
  
  • are fibrotic
  • contain lymphocytic infiltates
  • uniform throughout age - NO temporal heterogeneity

Question 14

compare/contrast morphology of UIP and NSIP

Answer 14

both: dz in lower lung, ground class on radiograph, interstitial fibrosis

UIP:

• temporal heterogeneity: fibroblastics –> collagenous
• can form cysts (honeycomb fibrosis)

NSIP:

• < fibrosis than UIP, architecture more retained
• no temporal heterogeneity

Question 15

cryptogenic organizing pneumonia (COP)

• demographics
• clinical presentation

Answer 15

• no demographic predilection
• clinical
  
  • cough/dyspnea + flu like symptoms

Question 16

cryptogenic organizing pneumonia (COP) - morphology

Answer 16

no gross

• microscopic - can effect ANY PART of the lung!.
  
  • loose granulation tissue in terminal airways + alveoli
  • INTRALUMINAL fibroblast plugs - i.e. within - bronchioles/alveoli/alveolar ducts
    
    • NO interstitial fibrosis
      
      • so, NO honeycomb lung
    • no temporal changes

Question 17

tx for COP (cryptogenic organization pneumonia)

Answer 17

corticosteroids

Question 18

contrast COP to UID & NSIP

Answer 18

• found in ANY part of the lung - unlike UID/NSIP (ower lobes only)
  
  • NO interstitial fibrosis - unlike UID/NSIP
  • INTRAluminal fibrosis (unlike UID/NSIP)
  • no temporal heterogeneity (unlike UID, like NSIP)
• presents with flu-like symptoms (unlike UID & NSIP)
• improves w/ corticosteroids (unlike UID, like NSIP)

Question 19

what is coal workers pneumoconiosis (CWP)?

describe its pathogenesis:

Answer 19

• chronic lung disease caused by inhalation of coal particles + dust
• pathogenesis:
  
  • inhaled irritatants induce macrophages to –> produce ROS & fibrogenic cytokines
  • development of disease depends ondepends on:
    
    • [] of particles
    • duration of exposure
    • efficacy of lung clearance mechanisms
      
      • cigarrette smoking lowers
    • size/shape of particles
    • particle solubility
• variations of coal workers pneumoconiosis:
  
  • anthracocis
  • simle CWP
  • complicated CWP

Question 20

anthracosis

• defintion
• morphology
• sequelae

Answer 20

• type of CWP
• characterized by accumulation of carbon pigment-filled macrophages in the connective tissue of the lymphatics/lymph nodes/lung him amongst otherwise intact parynchyma
• sequelae: innocuous

Question 21

simple CWP

• pathogenesis
• morphology
• sequelae

Answer 21

• pathogenesis: like all CWP
• mophology: characterized by
  
  • coal macules + coal nodules scattered throughout the lungs but especially in the ubber lobes (adj to resp. bronchioles)
    
    • coal macules: 1-2mm carbon laden macrophages
    • coal nodes: larger carbon filled macrophages + c_ollagen fibers_
• seqelae –> poss emphysema

Question 22

complicated CWP

• pathogenesis
• morphology
• sequelae

Answer 22

• pathognesis: due to progressive massive fibrosis (PMF) that typically follows years of simpe CWP that destroys lung parynchma
• mophology: intensely blackened scars (1-10 cm) that consist of haphazardly distributed dense collagen bunds + carbon pigment
  
  • +/- necrotic cefnter

Question 23

who is at higher risk of CWP?

Answer 23

pt who inhale a lot of silica

Question 24

silicosis

• demographics
• pathogenesis
• clinical presentaiton

Answer 24

• demographics:
  
  • AA> caucasion
  • workers exposed to silicon
• pathogenesis:
  
  • crystalline silica inhaled –> phagocytzed by macrophages –> _activates inflammasom_e – IL-1 release –> fibrosis
    
    • amorphous crysals less severe, still = fiboriss
• • progression depends on exposure:
    * mos/yrs (acute)–> lipoprotein accumulation
    * decades (chronic) –> fibrosis

Question 25

silicosis - gross morphology

Answer 25

* early: **discrete nodules** in _hilar lymph nodes_ + _upper lung zones_ * then, **hard, colllagenous scars** (formed by discrete nodules) * then, **eggshell calcification** * **​**shees of calficiation around non-calcified zone * late: progressive massive fibrosis (**PMF**)

Question 26

silicosis - microscopic morphology

Answer 26

l_ight microscope_: **coalescent** collagenous nodules _polarized light microscopy_: **bright white needle like crystals ("befringmenet" silica)**

Question 27

what is the most chronic occupational disease in the world?

Answer 27

silicosis

Question 28

silicosis sequelae

Answer 28

* slow to kill but can cause serious diability * _increases_ risk of contracting _tuberuosis_ * _doubles_ the risk for _lung cancer_

Question 29

what is asbestos and asbestos related diseases?

Answer 29

* asbestos: a family of **pro-inflammatory crystalline hydrated silicates (silica + iron + magnesium)** * asbestos related diseases: come from inhalation of asbestos * fibrous plaques, interstitial fibrosis * pleural effusions * tumors: * lung carcinoma * mesothelioma * neopasma of larnx/ovary/colon

Question 30

what are the two main geometric forms of asbestos?

Answer 30

1. serptentine (chrystotile) 2. amphibole (amosite and crocidolite)

Question 31

serptentine asbestos * also called? * shape * pathological effects * prevalence?

Answer 31

* chrysotile * **flexible, curved** * due to shape, it easily gets lodged lodged in upper respiratory passages then _removed_ by _mucociliary action_ * thus, **l**_**ess pathogeni**c_ than amphibole * more prevalent than amphibole

Question 32

amphibole asbestos * is also called? * shape * pathogenic effects * prevalence

Answer 32

* amosite and crocidolite * **straight, stiff** * **​**less likely to get "caught" in airstream, and may _carried deeper_ in to the lungs to penetrate epithelial cells * thus, more pathogenic than serpentine * prevalence: less prevalent then serpentine

Question 33

Answer 33

serptentin (crysotile) asbestos - flexible, curved less pathogenic asbestos

Question 34

Answer 34

**amphibole asbestos** (amosite and crocidolite) more pathogenic asbestos

Question 35

asbestos morphology (gross, histologic)

Answer 35

gross - unimportant * histologic: * characterized by **diffuse interstitial fibrosis** that _begins in the lower lobes subpleurally_ and spreads to middle, superior lobes, as well as: * **asbestos & ferruginous bodies**: * abestos bodies = _brown, fusiform beaded rods_ * **pleural plaque:** well circumscribed plaqutes of DENSE CT that dont contain asbestos bodies

Question 36

Answer 36

abestos bodies

Question 37

Answer 37

dense CT comprising **pleural plaques** seen in asbestos

Question 38

sarcoidosis * demographics * clinical presentation

Answer 38

* AA, 20-40, F \> M * clinical presentation * triad: * erythema nodosum * bilateral hilar lymphadenopahty * polyarthralgia

Question 39

sarcoidosis morphology

Answer 39

* characterized by small, **non-necrotizing, epitheliod interstitial granulomas** made of * _histiocytes_ * _mutinucleated giant cells,_ which can contain * asteroid bodies * schumann bodies

Question 40

hypersensitivity pneumonitis * pathognesis * morphology * treatment

Answer 40

* pathogenesis: _immune mediated_ reaction to various antigens * animal protein from *bird feathers/feces* * thermophillic actinomycetes in *moldy hay* * thermophilic bacteria in heated *water reserroirs* * morphology * small, ill defined non-caseating granulomas * tx * stop exposure to allergn

Question 41

desquamative interstitial pneumonia * pathogenesis * demographics * clinical presentation * morphology

Answer 41

* pathogenesis: **directly related to cigaratte smoking** * demographics: _middle aged smokers_ * clinical: cough, dyspnea * morphology * microscopic * **intra-alveolar collections of macrophages** * NO fibroblast foci * minimal fibrosis / wall thickening * (in contrast to other interitial dz - UIP, NSIP)

Question 42

pulmonary langerhans cell histiocytosis * pathogenesis * clinical presentation * morphology

Answer 42

* pathogenesis - highly linked to **_cigarette smoking_** * clinical presentation - cough/dyspnea * morphology: collections of **langerhans cells** * **​**langerhans cells: * have _round/oval nuclei_ w/ **frequent nuclear grooves** * can contain **Birbeck granules** (zipper like structures) * are associated with **eisonophils** * form innto --\> **stellate nodules** * **​(**_around bronchioles_**)**

Question 43

pulmonary alveolar proteinosis * pathogenesis * clinical presentation * morphology

Answer 43

* pathogenesis: defects in GM-CSF --\> alveoli filled with surfactant proteinaceous material * clinical presentation: cough w/ _abundant gelatinous sputum_ * morphology: * gross: * marked increase in _lung size/weight_ * congested lung parenchyma * microscopic: * alveoli filled with **granular, proteinatious material t**hat stains **_PAS positive_**