9/14- Injury, Obstructive Lung Diseases, Infections, and Transplantation Flashcards
What is atelectasis?
Collapse
- Incomplete expansion (neonatal) or collapse of previously inflated lung (acquired; primarily adults)
What are the three forms of acquired atelectasis (broadly)?
- Resorption (obstructive)
- Compressive
- Contraction
What is resorption atelectasis? What can cause it?
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…
What is compressive atelectasis? What can cause it?
- Pleural cavity filled with air, fluid, blood, etc.
- Mediastinum shifts away* from collapsed lung
- Pleural effusion, pneumothorax, subdiaphragmatic abscess
What is contraction atelectasis?
Fibrosis or tumor involving pleura or lung prevents expansion, e.g. mesothelioma (involving lung “surface”)
What is seen here?
Left: normal
Right: atelectatic lung- compressed; can see how improper drainage might predispose to infection
What is pulmonary edema?
What are the 2 etiologies (broadly)?
Fluid in lungs; heavy, wet lungs (like saturated sponges)
2 etiologies:
1. Hemodynamic
2. Microvascular injury
What are hemodynamic causes of pulmonary edema?
Increased hydrostatic pressure
- Left-sided failure
- Volume overload
- Pulmonary vein obstruction
Decreased oncotic pressure
- Hypoalbuminemia
- Nephrotic syndrome
What are the microvascular injury causes of pulmonary edema?
(Alveolar/capillary junction)
Increase in capillary permeability
- Infections
- Shock
- Aspiration
What is seen here?
Pulmonary edema
What is DAD?
Onset?
Symptoms?
Histologically?
Outcome?
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)
What are the etiologies of DAD/ARDS? (covered quickly)
Pathogenesis of DAD?
- 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
What are the 2 phases of DAD? Time frame?
Other processes?
- Exudative (acute) phase (under 1 wk)
-
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+
What is seen here?
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
What are the microscopic findings in the exudative phase?
(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
What is seen here?
Exudative phase of DAD
(This pt died of aspiration; central feature there = vegetable matter)
- Hemorrhage
- Inflammatory cells
What is seen here?
Acute form of DAD (exudative phase)?
- Pink material against alveolar walls = hyaline membranes
What is seen here?
Hyaline membranes (pink) are hallmark of acute/exudative phase of DAD
- Mixed inflammatory infiltrate: lymphocytes and neutrophils
What is seen here?
Again, acute form of DAD
- Plasma proteins and nuclear/cytoplasmic debris
What are the microscopic findings of the organizing (proliferative) phase of DAD?
(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)
What is seen here?
Alveolar septal tissue expanded due to proliferating, organizing tissue
Right: granulation tissue in alveolar space
- Over time, incorporated into adjacent septal tissue
What is seen here?
Type 2 pneumocyte lining alveoli (A) and within granulation tissue (B)
What is seen here?
Fibrosis (in proliferative phase of DAD)
- May cause extensive narrowing of the lung and loss of lung function
What are key pulmonary function value differences that distinguish obstructive vs. restrictive pulmonary disease?
- Obstructive: decreased flow rate (FEV1)
- Restrictive: decreased TLC (ex ILDs)
What are common obstructive pulmonary diseases?
Key characteristics/pulmonary function findings?
- 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)
What is asthma? What is seen microscopically?
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)
What population is commonly afflicted by chronic bronchitis?
Long time smokers
What is chronic bronchitis?
What is seen microscopically?
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
What is bronchiectasis?
Commonly seen in what population?
- 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
What is emphysema?
What are the two most common types?
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
Which form of emphysema do smokers typically get?
Centriacinar (centrilobular)
Which form of emphysema is most common?
Centriacinar (centrilobular)- 95% of cases
Characteristics of centriacinar (centrilobular) emphysema?
- Upper lobe dominant
- Both emphysematous and normal airspaces present in lobule
Characteristics of panacinar (panlobular) emphysema?
- Alpha-1-antitrypsin deficiency
- Lower lobe dominant
- No normal airspaces in lobule
What are the defense mechanisms of the lung?
- Cough reflex
- Mucociliary escalator
- Alveolar macrophage
- Host resistance
(We inhale ~10,000 microorganisms/day)
What is the mucociliary escalator?
Movement of mucus containing foreign material by beating of cilia in tracheobronchial tree
What is seen here?
- Ciliated endobronchial cells
- Some macrophages
- Pigment seen is carbon pigment; present in ambient air
What is the definition of pneumonia?
Any infection of lung parenchyma?
What are the subtypes of pneumonia?
- Community acquired
- Nosocomial
- Aspiration
- Immunocompromised host
What are the infectious agents associated with community acquired pneumonia?
Variety of bacteria and viruses
What are the infectious agents associated with nosocomial pneumonia?
- Gram (-) rods (Pseudomonas)
- Staph aureus
What are the infectious agents associated with aspiration pneumonia?
Variety of aerobes/anaerobes from oral flora
What are the infectious agents associated with immunocompromised host pneumonia?
- CMV
- Aspergillosis
- Pneumocystis
What are the anatomic patterns of pneumonia?
- Bronchopneumonia
- Lobar pneumonia
May overlap; etiology most important, clinically
What is seen here?
Bronchopneumonia
- Inflammation begins with airway
What is seen here?
Lobar pneumonia
- Inflammation begins with alveolar tissue
- Inflammatory process extending into adjacent alveolar tissue
What are the 4 histological patterns of lobar peumonia?
- Congestion/edema
- Red hepatization
- Gray hepatization
- Resolution
What is seen in the congestion/edema histologic pattern of lobar pneumonia?
- Vascular congestion
- Intra-alveolar fluid
What is seen in the red hepatization histologic pattern of lobar pneumonia?
- Massive exudate of RBCs, WBCs, fibrin
- Airless, firm consistency (like liver)
What is seen in the gray hepatization histologic pattern of lobar pneumonia?
- Breakdown of RBCs, persistence of fibrin and neutrophils
- Airless, firm consistency (like liver)
What is seen in the resolution histologic pattern of lobar pneumonia?
- Granulation tissue: exudate becomes organized; removed by macrophages
- Reformation of lung architecture
What are some complications of pneumonia?
- Abscess
- Empyema
- Septicemia resulting in multiorgan abscesses (ex, pt with osteomyelitis)
What are the most common indications for lung transplantation?
- Idiopathic pulmonary fibrosis
- Cystic fibrosis
- Primary pulmonary hypertension
What are complications of lung transplantations?
- Postoperative (Rare)
- Infections (immunosuppressed to prevent organ rejection)
- Rejection (acute and chronic)
Recall: more extensive list of infectious agents of an immunocompromised host (age, chemo, transplant)?
- Aspergillus: Y-shaped branching of septated hyphae
- Cryptococcus
- Hisotplasma
- Penumocystis
- Herpes
- CMV
- Bacterial pneumonias as well
Acute rejection
- Timeline
- Grading
Weeks to months after surgery
- Graded by International Working Formulation
What is seen here?
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
Chronic rejection
- Timeline
- Characteristics
3-5 yrs after surgery
- Significant problem in ~ 50% of transplants
- Bronchiolitis obliterans (histologic hallmark**)- luminal fibrosis +/- inflammation
Summary slide of obstructive lung diseases
