Pathology of Environmental / Occupational Lung Diseases

Question 1

What is a pneumonconiosis?

Answer 1

A non-neoplastic lung disorder caused by inhalation of dust, especially chronic occupational exposure

Question 2

What is the most dangerous size of a particle to be to cause damage? And how does low vs high solubility affect the pathogenesis?

Answer 2

1-5 micron particles which fit into alveoli are most dangerous

Low solubility - chronic lung injury and pulmonary fibrosis

High solubility - acute lung injury and potentially systemic disease

Question 3

What is the common pathogenesis of dust-related lung disease?

Answer 3

Chronic inhalation of particles -> phagocytosis by alveolar macs with eventual oversaturation -> longstanding activation of macrophages with induction of the inflammosome

• > production of IL-1 and IL-18
• > release of ROS, eicosanoids, cytokines, and fibroblast growth factors (i.e. TGF-beta)

-> cellular injury and pulmonary fibrosis

Question 4

What factor of the coal makes disease worse in coal workers’ pneumoconiosis / black lung?

Answer 4

Amount of silica in coal dust

-> increases risk for fibrosis and mycobacterial disease

Question 5

What is the least severe version of coal-mediated disease?

Answer 5

Anthracosis -> excessive numbers of carbon-laden macrophages in lung interstitium and regional lymph nodes

Question 6

What is the pathologic difference between simple and complicated coal workers’ pneumoconiosis?

Answer 6

Simple - has “macules” with carbon-laden macrophages and “nodules” with these macules + fibrous connective tissue

Complicated - WAY more fibrosis than simple, which leads to pulmonary dysfunction and hypertension

Question 7

How does complicated coal workers’ pneumoconiosis appear pathologically? Where in the lung is this worst?

Answer 7

Coalescence of coal nodules into large accumulations of carbon pigment associated with dense scar tissue

• > worse in upper regions of lung (progressive massive fibrosis)
• > ischemic necrosis in center of nodules w/ cavitation is common

Question 8

What is the most common type of pneumoconiosis and what jobs is it associated with?

Answer 8

Silicosis

Associated with construction, sandblasting, mining, masonry, stone-cutting, concrete demolition

Question 9

What is the most pathogenic form of silica?

Answer 9

Quartz - crystalline silica (silicon dioxide)

Way worse than noncrystalline or coated (by clay)

Question 10

What lung condition does acute silicosis cause? Is this more common or more rare than chronic silicosis?

Answer 10

Secondary pulmonary alveolar proteinosis

• > impaired ability of macrophages to clear anything, including surfactant
• > protein builds up in alveoli

Much rarer, since occupational protections are in place to prevent this much exposure at once

Question 11

What is seen in the pulmonary pathologic of chronic / classic silicosis (15-20 years of low grade exposure)?

Answer 11

Small, round nodules of dense, fibrotic dense collagen which tend to coalesce in the upper lobes of the lungs

-> form progressive massive fibrosis often involving pleural and hilar lymph nodes, with eggshell calcification sometimes seen

Question 12

What happens overtime to lung function as a result of silicosis and what are the additional complications are associated?

Answer 12

Slowly worsening pulmonary function and pulmonary hypertension

1. Inhibition of macrophages -> increased susceptibility to mycobacterial infections (both TB and non TB) -> especially upper lobes
2. Increased risk of autoimmune disorders from chronic macrophage overactivity

Question 13

What occupations tend to see asbestos exposure and which particle types are most pathogenic?

Answer 13

Asbestos mining, transporting, insulating, construction, or shipbuilding. Destroying old buildings w/ asbestos in walls (worked as a good flame retardant and insulator)

Amphibole asbestos fibers -> straight and rigid -> fit down lung passage airways easily, more pathogenic than serpentine fibers which cannot get down the passageway.

Question 14

What is asbestosis? Where is it worse? What lung condition does this cause?

Answer 14

Pulmonary interstitial fibrosis due to chronic asbestos exposure

Worse in lower lobes (near diaphragm, gravity) and subPLEURAL regions first

Causes honeycomb lung - enlarged airspaces with thick, fibrous walls, and dyspnea w/ pulmonary HTN

Question 15

Why is asbestos associated with malignancies?

Answer 15

It is a carcinogen -> functions as a tumor initiator AND promoter, and generates ROS itself

Also adsorbs carcinogens from cigarette smoke
-> massively increased risk of cancer if you also smoke when working w/ asbestos

Question 16

What are asbestos bodies?

Answer 16

Asbestos fibers coated in beaded, gold-brown, iron-protein complex

Question 17

Other than malignancies and asbestosis, what other lung pathologies does asbestos cause?

Answer 17

1. Pleural plaques - benign, collagenous plaques which are often calcified and on the PARIETAL pleura (inside ribcage) + diaphragm
2. Recurrent pleural effusions

Question 18

What three cancers are closely associated with asbestos?

Answer 18

1. Lung carcinoma - most common
2. Malignant mesothelioma
3. Laryngeal carcinoma

Question 19

Where does mesothelioma typically appear, and is it always malignant?

Answer 19

Typically pleural, encasing entire outside of the lung. Can also be on peritoneal mesothelium

Sometimes it is benign, but always grows rather aggressively in its local spread.

Question 20

What complications are associated with mesothelioma of lung?

Answer 20

Large pleural effusions - due to angiogenesis of malignancy

Spread to other body cavities, regional lymph nodes, adjacent organs, and hematogenous dissemination

Often causes dyspnea and severe chest pain, poor prognosis

Question 21

What two types of cells are microscopically identified in mesothelioma?

Answer 21

1. Atypical epithelioid - plump, rounded to columnar

2. Sarcomatoid - spindle-shaped

Question 22

In what professions are you likely to get berylliosis?

Answer 22

Machining, mining, and metal alloy manufacturing, especially nuclear power, airspace, and electronics (relatively new problem)

Question 23

How is berylliosis pathogenesis unique versus the other pneuomoconioses?

Answer 23

Genetic predisposition plays a large role -> due to a Type IV, delayed-type hypersensitivity

-> beryllium + protein is presented on MHC Class II of APCs, activating CD4+ Th1 cells and ultimately macrophages

Question 24

What characterizes the overall pathology of berylliosis (chronic beryllium disease)?

Answer 24

Formation of non-necrotizing granulomas, followed by fibrosis

• > occurs most frequently in lung, impairing pulmonary function
• > beryllium is also absorbed through skin, so granulomas can appear systemically, looks like sarcoidosis

Question 25

What is Caplan syndrome and when was it first described?

Answer 25

Pneumoconiosis + positive rheumatoid factor / rheumatoid arthritis -> first described in relation to coal workers’ pneumoconiosis but can happen in any

Question 26

What is the pulmonary pathology of Caplan syndrome?

Answer 26

Multiple well-defined round, peripheral lung nodules (rheumatoid nodules) comprised of mineral dust and degenerating collaged which is completely surrounded by fibrobalsts and macrophages

• > nodules can cavitate or calcify
• > if your nodules (i.e. in silicosis) are very large but you have this, your prognosis is much better than if you’re not RF+

Question 27

What is hypersensitivity pneumonitis and how does it differ from asthma?

Answer 27

Extrinsic allergic alveolitis

• > this is hypersensitivity of the small airways and alveoli
• > asthma affects the large airways

Question 28

What types of things can trigger a hypersensitivity pneumonitis?

Answer 28

Organic dusts. For example:

1. Microbial antigens
   - > i.e. spores of fungi / moldy hay
2. Animal protein antigens
   - > bird feathers or droppings
3. Low molecular weight chemicals -> can adduct to host proteins and be antigenic
   - > plastics or rubbers

Question 29

What two types of hypersensitivity cause hypersensitivity pneumonitis?

Answer 29

Type III - causes acute

Type IV - causes subacute and chronic. More insidious onset.

Question 30

What is the pathogenesis of acute the acute phase of hypersensitivty pneumonitis? Give symptoms.

Answer 30

Flu-like symptoms within hours of antigen exposure. Resolves in hours to days

Type III hypersensitivity -Immune complex formation and tissue deposition, with complement activation and Ig deposition in vessel walls

Question 31

What is the pathogenesis of subacute or chronic phase of hypersensitivity pneumonitis? Give symptoms.

Answer 31

Insidious, progress dyspnea, cough, and fatigue

Type IV hypersensitivity

• > delayed-type = CD4 cell activation and macrophage coactivation, creating poorly-formed granulomas
• > cytotoxic = sensitization of certain antigen-specific CD8 T cells -> apoptosis of target cells

Question 32

How does the pulmonary pathology of hypersensitivity pneumonitis appear? How do we treat?

Answer 32

Mononuclear inflammatory infiltrate (lymphocytic / macrophage) within lung, creating loose, poorly-formed, nonnecrotizing granulomas adjacent to bronchioles
-> fibrosis can occur with continued exposure

Treat my removing from the area which is providing the hypersensitivity stimulus (offending antigen)

Question 33

Why do highly soluble gases like ammonia and sulfur dioxide rarely progress to diffuse alveolar damage and Acute Respiratory Distress Syndrome (ARDS)?

Answer 33

Highly soluble -> irritating to eyes and upper airways

-> you will leave the area before they have time to cause lower lung damage

Question 34

What are the symptoms of ARDS and what things generally cause it?

Answer 34

Acute onset profound respiratory insufficiency with dyspnea, tachypnea, tachycardia, cyanosis, hypoxemia

Caused by many things. Anything which can injure the respiratory endothelium, especially toxins (from outside, i.e. nitrogen oxides, mustard gas) or sepsis (from inside)

Question 35

What is the pathogenesis of ARDS?

Answer 35

Endothelial injury -> release of proinflammatory cytokines (by alveolar macrophages) and endothelial activation

• > infiltration by macrophages and neutrophils
• > endothelial damage, increased vascular permeability
• > vasconstriction and thrombosis
• > hyaline membrane formation due to leakage of plasma proteins in and dead pneumocytes

Question 36

What characterizes the early pathology of the lung in ARDS (1-2 weeks)?

Answer 36

Hyperemia, edema, intra-alveolar hemorrhage, thrombi formation

*intra-alveolar hyaline membranes due to necrotic debris and fibrin-rich edema fluid

Diffuse damage throughout the lung

Question 37

What happens in later stage of ARDS?

Answer 37

Assuming you survive, Type II pneumocytes can repopulate on the basement membrane and fibroblasts can help organize the lung tissue
-> can lead to a full recovery

Question 38

What are some occupational-induced asthma causes? What is the pathogenesis?

Answer 38

1. Inhaled particles / dusts
   - > wood, vegetable, metal dusts
2. Inhaled fumes and vapors
   - > industrial chemicals, i.e. formaldehyde - Dr. Bosch!

Causes a hypersensitivity reaction in the large airways!