Pathology - Lecture 3 ( Restrictive Diseases )

Question 1

General features of parenchymal disease

Answer 1

• Diffuse parenchymal lung disease (DPLD) - most accurate
• Characterized by normal FEV1:FVC, reduced DLCO & increased A-a gradient

Question 2

Extra-parenchymal

Answer 2

Chest wall disorders
o Kyphoscoliosis
o Neuromuscular diseases (e.g. Myasthenia gravis)
o Obesity
- Pleural disorders (effusions/pneumothorax)
- Characterized by normal FEV1:FVC, normal DLCO & normal A-a gradient

Question 3

Interstitial lung disease

Answer 3

—involves the interstitium
-inflammation and fibrosis of the alveolar septa

• “Alveolitis” – Damage to pneumocytes and endothelial cells
• Leads to leukocytes releasing cytokines which mediate and stimulate
interstitial fibrosis Decreased lung compliance (stiff)

Question 4

Complications of ILD

Answer 4

-Hypoxia
-pulmonary vasoconstriction
-pulmonary htn and cor pulmonale

Question 5

Idiopathic pulmonary fibrosis (usual interstitial pneumonia)

Answer 5

Clinicopathologic syndrome marked by progressive interstitial pulmonary fibrosis and respiratory
• Males > Females
• Older age group (55-75 yrs)
-presents as dry cough and dyspnea on exertion ,cyanosis ,cor pulmonale and clubbing

Question 6

Gross appearance of IPF

Answer 6

-Cobble stone appearance of pleural surface-Retraction of scars along interlobular septa
• Firm, fibrotic parenchyma markedly in lower lobe and subpleural regions
• Honeycomb cysts
-patchy interstitial fibrosis

Question 7

Nonspecific Interstitial Pneumonia(NSIP)

Answer 7

-Younger demographic; female non-smokers
-histology: uniform fibrosing process
-cellular variant /fibrosing variant
-lung architecture is preserved
-some respond to steroids

Question 8

Cryptogenic Organizing Pneumonia
Also called: Bronchiolitis obliterans organizing pneumonia (BOOP)

Answer 8

-Patchy sub-pleural or peri-bronchial areas of airspace consolidation.
-histology: Polypoid plugs of loose organizing connective tissue(called Masson bodies) in alveoli, alveolar ducts and often bronchioles
• All lesions are of the same age, and the underlying lung architecture is normal
• There is no interstitial fibrosis or honeycomb lung

Question 9

Pneumoconiosis etiology

Answer 9

common- coal dust, silica (most common) and asbestos

Question 10

ASBESTOS RELATED DISEASES

Answer 10

• Inhalation of asbestos fibers (fibrous silicates)- pro inflammatory
• Serpentine (more common) and amphibole (more pathogenic) forms
-worsening dyspnea which appears 10- 20 years after exposure

Question 11

Pathogenesis of asbestos related diseases

Answer 11

-asbestos fiber deposition in lungs
-asbestos body formation
-asbestos body leads to iron catalyzed reactions forming free radicals (on histo : golden brown roots with translucent center )
-DNA damage
-carcinogens

Question 12

Asbestos gross appearance

Answer 12

-thickened visceral pleura
-interstitial fibrosis affecting the lower lobe
-pleural plaques

Question 13

Pleural plaques

Answer 13

• Contain dense collagen and calcification
• No asbestos bodies seen
• Most frequently on the anterior and posterolateral
aspects of the parietal pleura and over the domes of the diaphragm

Question 14

SILICOSIS

Answer 14

-Caused by inhalation of proinflammatory crystalline silicon dioxide (silica)
-they interact with the epithelial cells and macrophages
-leads to fibrosis
- Increased risk of Pulmonary Tuberculosis - Crystalline silica inhibits the ability of pulmonary macrophages to kill phagocytosed mycobacteria.

Question 15

Morphological changes in silicosis

Answer 15

• Collagenous nodule/ scar
(usually in the hilar lymph nodes
and upper lung field).
• Eggshell calcification – sheets
of calcification in the lymph
nodes- Radiographic finding.
• Progressive massive fibrosis

Question 16

Microscopy of silicosis

Answer 16

• Central area of whorled collagen
fibers with dust-laden
macrophages
• Weakly birefringent silica in the
centre under polarized microscopy

Question 17

Coal workers pneumoconiosis

Answer 17

-Inhalation of coal particles and other admixed forms of dust
- coal contains mainly carbon , metallic , silica and organic compounds

Question 18

CWP morphology- anthracosis

Answer 18

Accumulation of carbon pigment mostly in peri lymphatic regions and lymph nodes
Asymptomatic, no appreciable pathologic changes

Question 19

CWP morphology- simple CWP

Answer 19

Macules ( 1-2 mm) and nodules Aggregates of dust-laden macrophages Fibrosis minimal or absent
Little or no pulmonary dysfunction

Question 20

CWP morphology- complicated

Answer 20

Coalescence of nodules into fibrous scars (Blackened scars 1 cm&>)
• Impaired pulmonary function
• Probably < 10% of simple CWP progress to complicated

Question 21

Sarcoidosis

Answer 21

-characterized by noncaseating granulomatous inflammation in many tissues and organs
-less than 40 years of age

Question 22

Pathogenesis of sarcoidosis

Answer 22

-genetic involvement
-Cell mediated (Type IV) hypersensitivity reaction to unidentified antigen

Question 23

Morphology of Sarcoidosis

Answer 23

-non necrotizing epitheloid granulomatoma
-hyalinized scar
-some progress and diffuse interstitial fibrosis and honeycomb king
-Schumann bodies
-asteroid bodies

Question 24

Schumann bodies

Answer 24

laminated concretions of calcium and protein

Question 25

Asteroid bodies

Answer 25

stellate inclusion in giant cells

Question 26

Clinical features sarcoidosis

Answer 26

-fever -asymptotic for a long time - other organ systems involved

Question 27

Diagnosis of sarcoidosis

Answer 27

-hypercalcemia -elevated ACE -CD4:CD8 increased -Typical bilateral hilar lymphadenopath

Question 28

Hypersensitivity Pneumonitis

Answer 28

Immunologically mediated, predominantly interstitial lung disorders caused by intense, often prolonged exposure to inhaled organic antigens -primarily involving alveolar walls -acute : signs and symptoms show up 4-8 hours after exposure -chronic : onset of cough, dyspnea, malaise, and weight loss

Question 29

Etiology of hypersensitivity pneomonotis

Answer 29

• Farmers’ lung: moldy hay, thermophilic actinomycetes bacteria, Saccharopolyspora rectivirgula • Silo fillers’ disease: Inhalation of gases from plant material (oxides of nitrogen) • Byssinosis: Cotton, linen, hemp; Textile factory workers- “Monday morning blues”

Question 30

Pathogenesis of hypersensitivity pneomonitis

Answer 30

Both type III and type IV hypersensitivity reaction patterns 1st exposure : IgG 2nd exposure : inflammatory response Chronic exposure - granuloma formation

Question 31

Morphology of hypersensitivity pneomonitis

Answer 31

-Airway centered process • Chronic inflammatory infiltrate • Organizing pneumonia • Poorly formed non- necrotizing granulomata with giant cells

Question 32

Pulmonary Alveolar Proteinosis

Answer 32

-Rare disease caused by defects in pulmonary macrophage function due to deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling, which results in the accumulation of surfactant in the intra-alveolar and bronchiolar spaces -Autoimmune

Question 33

Pulmonary alveolar proteinosis presentation

Answer 33

-accumulation of intra-alveolar precipitates containing surfactant proteins, causing focal-to confluent consolidation of large areas of the lungs with minimal inflammatory reaction -bilateral patchy asymmetric pulmonary opacifications -gelatinous sputum

Question 34

Acute Interstitial Pneumonia-Hamman Rich syndrome

Answer 34

-Very aggressive form of interstitial lung disease -May also occur as an acute phase of acceleration of IPF -Presents with diffuse alveolar damage and hyaline membranes