Pulmonary III - Restrictive Lung Disease and Diffuse Lung Syndromes

Question 1

Sarcoidosis is a disease of …

• -diagnosis is made by …
• -describe the lymphadenopathy
• -who is predisposed?

Answer 1

disease of unknown cause characterized by noncaseating granulomas in many tissues & organs

DIAGNOSIS MADE BY EXCLUSION

bilateral hilar lymphadenopathy or lung involvement is visible on radiographs in 90%

F>M; 10X greater in Blacks than Whites; highest in southeastern United States

Question 2

Pathogenesis of sarcoidosis

• -what is the cause?
• -what cells are seen?

Answer 2

cause unknown; granulomatous tissue suggests persistent, poorly degradable antigen

• -increased CD4 lymphocytes, activated macrophages; cytokine secretion
• -influx of monocytes, alveolitis, noncaseating granulomas progressing to fibrosis
• -T-cell proliferation oligoclonal, but no specific organism identified

Question 3

Morphology

Answer 3

noncaseating granulomas in all involved tissues

aggregates of tightly clustered epithelioid cells,
often w/ Langhans’ or foreign body giant cells

enclosed by fibrous rims; may be replaced by fibrous scar

laminated concretions compose of calcium and proteins known as Schaumann’s bodies

stellate inclusions known as asteroid bodies enclosed within giant cells (60%)

Question 4

What organs are involved in sarcoidosis

Answer 4

Lungs
Lymph nodes
Spleen
LIver
Bone marrow
Skin
Eye, its associated glands, and the salivary glands

Question 5

Lungs WRT to sarcoidosis

Answer 5

grossly no demonstrable alteration; coalescencing granulomas may produce small nodules

• -distributed along lymphatics around bronchi, blood vessels
• -relative frequency of submucosal lesions
• -lesions in lungs tend to heal; fibrosis and hyalinization

Question 6

Lymph nodes WRT to sarcoidosis

Answer 6

involved in almost all cases; hilar and mediastinal nodes; enlarged, discrete, and sometimes calcified

Question 7

Spleen WRT to sarcoidosis

Answer 7

75% cases, but enlarged in only 18%; barely visible nodules

Question 8

Liver WRT to sarcoidosis

Answer 8

moderately enlarged with scattered granulomas in portal triads

Question 9

Bone marrow WRT to sarcoidosis

Answer 9

phalangeal bones of hands/feet; sm. circumscribed areas of bone resorption

Question 10

Skin WRT to sarcoidosis

Answer 10

30-50% of cases; discrete subcut. nodules, erythematous plaques, or flat lesions

Question 11

Eye, its associated glands, and the salivary glands WRT to sarcoidosis

Answer 11

1/5; iritis, corneal opacities; bilateral sarcoidosis of the parotid (uveoparotid involvement - Mikulicz’s syndrome

Question 12

Clinical course of sarcoidosis

Answer 12

aried symptomology; may be found unexpectedly on chest films as bilateral hilar adenopathy

may have peripheral lymphadenopathy, cutaneous lesions, eye involvement

insidious onset of respiratory abnormalities (SOB, cough, chest pain, hemoptysis)

constitutional signs (fever, fatigue, weight loss, anorexia, night sweats)

unpredictable course; may be progressive or intermittent

may resolve spontaneously or with steroid therapy

Question 13

Sarcoidosis

• -recovery?
• -permanent damage?
• -death?

Answer 13

65-70% recover with minimal or no residual manifestations

20% have some permanent loss of lung function

10% dies of cardiac or CNS damage

Question 14

Sarcoidosis staging

Answer 14

stage I - hilar lymphadenopathy alone

stage II - adenopathy and pulmonary infiltrates

stage III - pulmonary disease and NO adenopathy - few spontaneous remissions and most likely to develop chronic pulmonary fibrosis

Question 15

Idiopathic pulmonary fibrosis

• -general features
• -advanced cases
• -progression? death?

Answer 15

idiopathic diffuse interstitial inflammation and fibrosis

general features - similar in presentation to other interstitial fibrotic processes; about 50% idiopathic

advanced cases - respiratory difficulty, hypoxemia and cyanosis with 2° pulmonary hypertension

some very rapid (weeks), most cases death occurs in about 2 years

Question 16

Pathogenesis of idiopathic pulmonary fibrosis

–inflammation response and how it effects the lung

Answer 16

stereotyped inflammatory response of the alveolar wall to injuries

alveolar wall injury –> interstitial edema and accumulation of inflammatory cells –> fibroblasts proliferate –> progressive fibrosis of interalveolar septa and intra-alveolar exudate

progressive fibrosis of interalveolar septa and intra- alveolar exudate

?immune mechanisms; high levels of circulating immune complexes or cryoimmunoglobulins; granular deposits of IgG

Question 17

Morphology of idiopathic pulmonary fibrosis

• -early
• -late

Answer 17

• -early: pulmonaryedema,intra-alveolar exudation, hyaline membranes, septal infiltrates
• -hyperplasia of type II pneumocytes; cuboidal or even columnar cells lining alveolar spaces
• -fibrous organization of the intra-alveolar exudate/ thickening of interstitial septa
• -honeycomb-lung with small cysts and intimal thickening

late: lungs become solid with alternating areas of fibrosis and normal lung

Question 18

Rheumatoid arthritis

Answer 18

• -chronic pleuritis
• -diffuse interstitial pneumonitis with fibrosis
• -intrapulmonary rheumatoid nodules
• -rheumatoid nodules with pneumoconiosis (Caplan’s syndrome)
• -pulmonary hypertension

Question 19

What are some diffuse pulmonary hemorrhage syndromes?

Answer 19

Goodpasture’s Syndrome
Wegener’s granulomatosus
Idiopathic Pulmonary Hemosiderosis

Question 20

Goodpasture’s Syndrome

• -what is this?
• -when does is present? who in?
• -what is the pathology like?
• -triggering event?

Answer 20

rare; rapidly progressive glomerulonephritis, and a necrotizing hemorrhagic interstitial pneumonitis

2nd-3rd decade; M>F

• -antibodies against antigens in glomerular and pulmonary basement membranes
• -linear deposits of immunoglobulin by immunoflourescence
• -plasma exchange to remove anti-basement membrane antibodies and mediators of inflammation

triggering event unknown: ?toxic pulmonary injury, viral infection, exposure to solvents, smoking

Question 21

Goodpasture’s

• -what is the presentation like?
• -what does the lung look like pathologically?
• -which symptoms come first?

Answer 21

hemoptysis and focal pulmonary consolidations

intra-alveolar hemorrhages, fibrous thickening of septa, hypertrophy of septal cells

areas of red-brown consolidation

respiratory symptoms precede renal glomerulonephritis; uremia cause of death

Question 22

Wegener’s granulomatosis

• -when does it present?
• -what are the pathologic presentation?

Answer 22

5th decade; progressive, fatal disease

vascular necrotizing granulomas of upper and lower respiratory tract

• -focal necrotizing vasculitis affecting small to medium-sized vessels
• -persistent pneumonitis with bilateral nodular and cavitary infiltrates
• -chronic sinusitis, ulcerations of the nasopharynx, epistaxis

Question 23

Wegener’s granulomatosis

• -inflammatory cells?
• -associated with what AB?
• -what other kind of disease is there?

Answer 23

granulomatous vasculitis with extensive fibrosis, atelectasis
–perivascular granulomatous inflammation with giant cells

associated with c-ANCA (anti-neutrophil cytoplasmic antibodies)

some have renal disease with focal or diffuse necrotizing glomerulitis

Question 24

Idiopathic pulmonary hemosiderosis

Answer 24

–hemorrhage into alveolar spaces with resulting
interstitial fibrosis and hemosiderosis
–occurs in children and younger adults
–similar to Goodpasture’s in presentation, but NO anti-basement membrane antibodies
–productive cough, hemoptysis, anemia, weight loss and diffuse pulmonary infiltrations