9/14- Injury, Obstructive Lung Diseases, Infections, and Transplantation

Question 1

What is atelectasis?

Answer 1

Collapse

• Incomplete expansion (neonatal) or collapse of previously inflated lung (acquired; primarily adults)

Question 2

What are the three forms of acquired atelectasis (broadly)?

Answer 2

• Resorption (obstructive)
• Compressive
• Contraction

Question 3

What is resorption atelectasis? What can cause it?

Answer 3

Aka obstructive atelectasis

• Airway obstruction, air resorption
• Lung volume diminished and mediastinum shifts toward collapsed lung
• May be caused by mucus plugs, foreign body, tumors…

Question 4

What is compressive atelectasis? What can cause it?

Answer 4

• Pleural cavity filled with air, fluid, blood, etc.
• Mediastinum shifts away* from collapsed lung
• Pleural effusion, pneumothorax, subdiaphragmatic abscess

Question 5

What is contraction atelectasis?

Answer 5

Fibrosis or tumor involving pleura or lung prevents expansion, e.g. mesothelioma (involving lung “surface”)

Question 6

What is seen here?

Answer 6

Left: normal

Right: atelectatic lung- compressed; can see how improper drainage might predispose to infection

Question 7

What is pulmonary edema?

What are the 2 etiologies (broadly)?

Answer 7

Fluid in lungs; heavy, wet lungs (like saturated sponges)

2 etiologies:

1. Hemodynamic

2. Microvascular injury

Question 8

What are hemodynamic causes of pulmonary edema?

Answer 8

Increased hydrostatic pressure

• Left-sided failure
• Volume overload
• Pulmonary vein obstruction

Decreased oncotic pressure

• Hypoalbuminemia
• Nephrotic syndrome

Question 9

What are the microvascular injury causes of pulmonary edema?

Answer 9

(Alveolar/capillary junction)

Increase in capillary permeability

• Infections
• Shock
• Aspiration

Question 10

What is seen here?

Answer 10

Pulmonary edema

Question 11

What is DAD?

Onset?

Symptoms?

Histologically?

Outcome?

Answer 11

Diffuse Alveolar Damage (Acute Respiratory Distress Syndrome)

• Aka shock lung, Da Nang Lung, Hamman-Rich syndrome
• Acute onset (24-48 hrs)
• Sx: dyspnea, tachypnea, hypoxia, respiratory failure
• Ground glass changes with consolidation on HRCT (hazy appearance on HRCT)
• 30% mortality (most due to sepsis, multi-organ failure)

Question 12

What are the etiologies of DAD/ARDS? (covered quickly)

Answer 12

Question 13

Pathogenesis of DAD?

Answer 13

• Damage centers on capillary/alveolar junction
• Loss of integrity of microvascular endothelium and alveolar epithelium
• Inflammatory cascade initiates events*
• Leakage of fluid & inflammatory cells
• Sloughing of epithelial cells

*Imbalance of pro-inflammatory vs anti-inflammatory mediators

Question 14

What are the 2 phases of DAD? Time frame?

Other processes?

Answer 14

1. Exudative (acute) phase (under 1 wk)
2. Proliferative (organizing) phase (after 1st wk)
   - Can distinguish by macroscopic view of the lungs

Histologically:

• Edema peaks ~ day 1
• Hyaline membranes peak ~ day 3-4
• Interstitial inflammation/fibrosis characterizes proliferative stage; days 11+

Question 15

What is seen here?

Answer 15

Left: exudative phase of DAD

• Red appearance

Right: proliferative phase of DAD

• Edema/fluid is gone
• Left with granulation tissue/fibrosis of lung repairing damage in alveolar spaces

Question 16

What are the microscopic findings in the exudative phase?

Answer 16

(First week following onset injury)

Vascular congestion, interstitial/alveolar edema, intra-alveolar hemorrhage

Hyaline membranes (hist. hallmark)** key**

• Begin day 2; peak 4-5 days after injury
• Precipitated plasma proteins, cytoplasmic/nuclear debris from sloughed epithelial cells

Microvascular thrombi and mild chronic interstitial inflammation

Question 17

What is seen here?

Answer 17

Exudative phase of DAD

(This pt died of aspiration; central feature there = vegetable matter)

• Hemorrhage
• Inflammatory cells

Question 18

What is seen here?

Answer 18

Acute form of DAD (exudative phase)?

• Pink material against alveolar walls = hyaline membranes

Question 19

What is seen here?

Answer 19

Hyaline membranes (pink) are hallmark of acute/exudative phase of DAD

• Mixed inflammatory infiltrate: lymphocytes and neutrophils

Question 20

What is seen here?

Answer 20

Again, acute form of DAD

• Plasma proteins and nuclear/cytoplasmic debris

Question 21

What are the microscopic findings of the organizing (proliferative) phase of DAD?

Answer 21

(End of first week)

- Type 2 pneumocyte hyperplasia (alveolar repair cells)

- Organization of exudate with proliferation of myofibroblasts and fibroblasts (intra-alveolar granulation tissue)

• Alveolar septal thickening (loose granulation tissue)
• Resolution of organization (macrophages remove cell debris; granulation tissue matures into dense fibrous tissue)

Question 22

What is seen here?

Answer 22

Alveolar septal tissue expanded due to proliferating, organizing tissue

Right: granulation tissue in alveolar space

• Over time, incorporated into adjacent septal tissue

Question 23

What is seen here?

Answer 23

Type 2 pneumocyte lining alveoli (A) and within granulation tissue (B)

Question 24

What is seen here?

Answer 24

Fibrosis (in proliferative phase of DAD)

• May cause extensive narrowing of the lung and loss of lung function

Question 25

What are key pulmonary function value differences that distinguish obstructive vs. restrictive pulmonary disease?

Answer 25

- **Obstructive**: decreased flow rate (FEV1) - **Restrictive**: decreased TLC (ex ILDs)

Question 26

What are common obstructive pulmonary diseases? Key characteristics/pulmonary function findings?

Answer 26

- Asthma - Chronic bronchitis - Bronchiectasis - Emphysema _Typically involves:_ - Increased resistance to air flow due to obstruction (asthma) or loss of elastic recoil (emphysema) - Decreased FEV1 (max amt of air exhaled in 1s)

Question 27

What is asthma? What is seen microscopically?

Answer 27

Chronic inflammatory disorder of airways; bronchconstriction due to bronchospasm and inflammation - **Hyperinflated** lungs (CXR) - **Globet cell metaplasia**; **submucosal gland hypertrophy** - **Mucus plugs** (**Curschmann** spirals)- mucus casts of the involved bronchioles - **Thickened basement membrane** and **muscle** wall **hypertrophy** (in response to constant bronchoconstriction)

Question 28

What population is commonly afflicted by chronic bronchitis?

Answer 28

Long time smokers

Question 29

What is chronic bronchitis? What is seen microscopically?

Answer 29

Persistent cough with sputum production for **at least 3 mo** in at least **2 consecutive yrs** - Chronic irritation leads to submucosal gland hypertrophy/hyperplasia; increase Reid index - Mucus plugs obstructs airways - Goblet cell metaplasia; chronic inflammation

Question 30

What is bronchiectasis? Commonly seen in what population?

Answer 30

- Destruction of muscle/elastic tissue with inflammation and fibrosis due to repeated bouts of infection and obstruction - Permanent dilation of bronchi/bronchioles (lower lobe disease) - Commonly seen with **cystic fibrosis**

Question 31

What is emphysema? What are the two most common types?

Answer 31

Permanent enlargement airspaces, distal to the terminal bronchiole _Types:_ - **Centriacinar** (**centrilobular**): only central acinus involved - **Panacinar** (**panlobular**): entire pulmonary acinus involved in permanent enlargement of airspaces

Question 32

Which form of emphysema do smokers typically get?

Answer 32

Centriacinar (centrilobular)

Question 33

Which form of emphysema is most common?

Answer 33

Centriacinar (centrilobular)- 95% of cases

Question 34

Characteristics of centriacinar (centrilobular) emphysema?

Answer 34

- **Upper** lobe dominant - Both emphysematous **and normal** airspaces present in lobule

Question 35

Characteristics of panacinar (panlobular) emphysema?

Answer 35

- **Alpha-1-antitrypsin** deficiency - **Lower** lobe dominant - **No** normal airspaces in lobule

Question 36

What are the defense mechanisms of the lung?

Answer 36

- Cough reflex - Mucociliary escalator - Alveolar macrophage - Host resistance (We inhale ~10,000 microorganisms/day)

Question 37

What is the mucociliary escalator?

Answer 37

Movement of mucus containing foreign material by beating of cilia in tracheobronchial tree

Question 38

What is seen here?

Answer 38

- Ciliated endobronchial cells - Some macrophages - Pigment seen is carbon pigment; present in ambient air

Question 39

What is the definition of pneumonia?

Answer 39

Any infection of lung parenchyma?

Question 40

What are the subtypes of pneumonia?

Answer 40

- Community acquired - Nosocomial - Aspiration - Immunocompromised host

Question 41

What are the infectious agents associated with community acquired pneumonia?

Answer 41

Variety of bacteria and viruses

Question 42

What are the infectious agents associated with nosocomial pneumonia?

Answer 42

- Gram (-) rods (Pseudomonas) - Staph aureus

Question 43

What are the infectious agents associated with aspiration pneumonia?

Answer 43

Variety of aerobes/anaerobes from oral flora

Question 44

What are the infectious agents associated with immunocompromised host pneumonia?

Answer 44

- CMV - Aspergillosis - Pneumocystis

Question 45

What are the anatomic patterns of pneumonia?

Answer 45

**- Bronchopneumonia** **- Lobar pneumonia** May overlap; etiology most important, clinically

Question 46

What is seen here?

Answer 46

Bronchopneumonia - Inflammation begins with airway

Question 47

What is seen here?

Answer 47

**Lobar pneumonia** - Inflammation begins with **alveolar tissue** - Inflammatory process extending into adjacent alveolar tissue

Question 48

What are the 4 histological patterns of lobar peumonia?

Answer 48

1. Congestion/edema 2. Red hepatization 3. Gray hepatization 4. Resolution

Question 49

What is seen in the congestion/edema histologic pattern of lobar pneumonia?

Answer 49

- Vascular congestion - Intra-alveolar fluid

Question 50

What is seen in the red hepatization histologic pattern of lobar pneumonia?

Answer 50

- Massive exudate of RBCs, WBCs, fibrin - Airless, firm consistency (like liver)

Question 51

What is seen in the gray hepatization histologic pattern of lobar pneumonia?

Answer 51

- Breakdown of RBCs, persistence of fibrin and neutrophils - Airless, firm consistency (like liver)

Question 52

What is seen in the resolution histologic pattern of lobar pneumonia?

Answer 52

- Granulation tissue: exudate becomes organized; removed by macrophages - Reformation of lung architecture

Question 53

What are some complications of pneumonia?

Answer 53

- Abscess - Empyema - Septicemia resulting in multiorgan abscesses (ex, pt with osteomyelitis)

Question 54

What are the most common indications for lung transplantation?

Answer 54

- Idiopathic pulmonary fibrosis - Cystic fibrosis - Primary pulmonary hypertension

Question 55

What are complications of lung transplantations?

Answer 55

- Postoperative (Rare) - Infections (immunosuppressed to prevent organ rejection) - Rejection (acute and chronic)

Question 56

Recall: more extensive list of infectious agents of an immunocompromised host (age, chemo, transplant)?

Answer 56

- Aspergillus: Y-shaped branching of septated hyphae - Cryptococcus - Hisotplasma - Penumocystis - Herpes - CMV - Bacterial pneumonias as well

Question 57

Acute rejection - Timeline - Grading

Answer 57

Weeks to months after surgery - Graded by International Working Formulation

Question 58

What is seen here?

Answer 58

_Different grades of acute rejection_ **A1**- Minimal; Small perivascular lymphocyte infiltrates **A2**- Mild; Large perivascular lymphocyte infiltrates **A3**- Moderate; Perivascular infiltrates into interstitium **A4**- Severe; Neutrophils with fibrin and hemorrhage Switch from lymphocytes -\> neutrophils as grade gets more severe

Question 59

Chronic rejection - Timeline - Characteristics

Answer 59

3-5 yrs after surgery - Significant problem in ~ 50% of transplants - Bronchiolitis obliterans (histologic hallmark\*\*)- luminal fibrosis +/- inflammation

Question 60

Summary slide of obstructive lung diseases

Answer 60