General Mechanisms of Pulmonary Pathology Flashcards
6 layers of the respiratory membrane
from air to blood:
1. surfactant
2. type I pneumocytes (simple squamous)
3. basement membrane
4. interstitial space (elastic fibers)
5. basement membrane
6. capillary endothelium (simple squamous)
pulmonary edema - overview
*excessive interstitial fluid IN THE ALVEOLI
*impairs respiratory function
*predisposes to infection
*extremely common; seen in multiple disease states
“a condition caused by excess fluid in the lungs; this fluid collects in the numerous air sacs in the lungs, making it difficult to breathe”
pulmonary edema - 2 basic mechanisms
- hemodynamic (cardiogenic)
- increased capillary permeability / microvascular injury
pulmonary edema - hemodynamic (cardiogenic) mechanism
*left-sided congestive heart failure causes increased hydrostatic pressure
*characterized by:
-engorged alveolar capillaries
-intra-alveolar transudates (finely granular pale pink material; accumulates in lower lobes)
-hemosiderin-laden macrophages (“heart failure cells”; result from long-standing pulmonary congestion)
pulmonary edema - increased capillary permeability / microvascular injury mechanism
*injury of alveolar septa; injury to vascular epithelium or to alveolar pneumocytes
*results from an inflammatory process
*findings: INFLAMMATORY CELLULAR EXUDATE (leaks into interstitial space AND alveoli)
pleural effusion - overview
*excessive accumulation of fluid in the pleural cavity
*manifestation of both primary and secondary pleural diseases
pleural effusion - pathogenic mechanisms
- increased hydrostatic pressure (ex. CHF)
- increased vascular permeability (ex. pneumonia)
- other (decreased osmotic pressure, increased intrapleural negative pressure, decreased lymphatic drainage)
examples of non-inflammatory pleural effusions
- hydrothorax
- hemothorax
- chylothorax
examples of inflammatory pleural effusions
- pleuritis
- empyema
- hemorrhagic pleuritis
pleural effusion: hydrothorax
*accumulation of serous fluid in the pleural cavity
*clear, straw colored fluid
*may be unilateral or bilateral
*commonly caused by heart failure, leading to congestion and pulmonary edema
*a non-inflammatory pleural effusion
pleural effusion: hemothorax
*accumulation of blood in the pleural cavity
*complication of trauma or, less commonly, surgery
*can also be due to an aortic aneurysm
*a non-inflammatory pleural effusion
pleural effusion: chylothorax
*accumulation of lymph in the pleural cavity
*chyle milky white because of finely emulsified fats
*usually due to thoracic duct trauma or obstruction of a major lymphatic duct
*a non-inflammatory pleural effusion
pleural effusion: pleuritis
*inflamed pleura
*associated with inflammation of the underlying lung (e.g. pneumonia, infarction, abscess, bronchiectasis)
*usually fluid exudate resorbed with resolution of lung disease
*an inflammatory pleural effusion
pleural effusion: empyema
*purulent pleural exudate
*bacterial or mycotic seeding from intrapulmonary infection
*loculated, yellow-green, creamy pus/neutrophils
*organizes into fibrosis with dense, tough fibrous adhesions obliterating the pleural space (seriously restricts pulmonary expansion)
pleural effusion: hemorrhagic pleuritis
*sanguineous exudates (looks BLACK)
*most often associated with hemorrhagic diatheses
*Rickettsial infections or NEOPLASTIC INVOLVEMENT
pulmonary embolism (PE) - risk factors
*trauma
*hypercoagulable state
*recreational drugs
*old age
*malignancy
*birth control pills/hormone replacement
*obesity, obstetrical/post-partum
*surgery
*immobilization
*serious illness
pulmonary embolism (PE) - pathogenesis
*predominantly originate from deep leg veins
*embolus breaks off and passes through the right heart into pulmonary vasculature:
-occludes the main pulmonary artery, bifurcation (saddle embolus), or pass into smaller branching arterioles
*multiple emboli may occur, causing pulmonary hypertension and right CHF
pulmonary embolism (PE) - clinical features
*presentation depends on size of embolus and location:
*most are small and clinically silent (resolve after initial event)
*obstructed small-medium sized arteries cause respiratory and hemodynamic compromises (dyspnea, chest pain referred to pleura, hemoptysis)
*recurrent “showers” lead to pulmonary hypertension & Cor pulmonale
*saddle embolus [obstruction at the bifurcation of the pulmonary arteries] often associated with sudden death
pulmonary infarction
*results from occlusion of the distal pulmonary arteries, leading to ischemia, hemorrhage, and ultimately necrosis of lung parenchyma
*results in a wedge-shaped, hemorrhagic infarction at the lung periphery
*most commonly caused by acute pulmonary embolism
*it is challenging to infarct the lung though, because the lungs are oxygenated by bronchial arteries and directly from air in the alveoli
mechanisms for pulmonary embolisms
- thromboembolism (blood clot causes the blockage; most common)
- fat embolism (follows fractures of long bones with fatty marrows)
- amniotic fluid embolism (fetal membrane tear and rupture of uterine veins)
pulmonary hypertension - overview
*increased pulmonary artery blood pressure (>25 mmHg)
*decrease in the cross-sectional area of the pulmonary vascular bed
*increased pulmonary vascular blood flow
pulmonary hypertension - pathogenesis
- primary (familial) - proliferation of endothelial and vascular smooth muscle cells
- heart disease - right side volume overload
- intrinsic lung diseases - obliterate alveolar capillaries
- chronic thromboembolic disease - increase in pulmonary vascular resistance
pulmonary hypertension - morphology
*hypertrophy of pulmonary muscular and elastic arteries
*ARTERIOSCLEROSIS (arterioles/small arteries) - medial hypertrophy and intimal fibrosis [narrowing the lumens of pinpoint channels]
*PLEXIFORM LESIONS - glomeruloid capillary formation within dilated thin-walled, small arteries; may extend outside the vessel
*COR PULMONALE - right ventricular hypertrophy
note - these pathologic findings are consistent with pulmonary hypertension regardless of the underlying pathogenesis of the disease
pulmonary hypertension - clinical features
*s/s become evident only in advanced disease:
-dyspnea and fatigue
-over time, severe respiratory distress
-cyanosis
-right ventricular hypertrophy occurs late
acute respiratory distress syndrome (ARDS) - overview
*diffuse damage to alveoli throughout the lungs causes edema and leads to respiratory failure
*acute lung injury:
-rapid onset: life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia
-bilateral non-cardiogenic pulmonary edema
acute respiratory distress syndrome (ARDS) - causes
*primary pulmonary diseases OR systemic inflammatory disorders:
-infection (pneumonia and sepsis)
-aspiration
-toxic inhalation
-physical injury (severe trauma, burns, radiation)
-pancreatitis
-DIC
-fat embolism
-TRALI transfusion reaction
acute respiratory distress syndrome (ARDS) - pathogenesis
- widespread injury to alveolar endothelial and type I pneumocyte epithelial cells
- pulmonary macrophages produce proinflammatory mediators (TNF, IL-1, IL-8)
- neutrophils in pulmonary microvasculature enter alveoli
a) produce leukotrienes, ROS, proteases, PAF
b) increased tissue damage/surfactant inactivation
c) accumulation of EDEMA FLUID
d) HYALINE MEMBRANE FORMATION - subsequent release of macrophage-derived fibrogenic cytokines
-stimulate fibroblasts and COLLAGEN DEPOSITION associated with healing phase of injury
acute respiratory distress syndrome (ARDS) - pathology: early stage
*early stage = acute exudative stage:
-DIFFUSE ALVEOLAR DAMAGE
-waxy HYALINE MEMBRANES (line alveolar walls; fibrin-rich edema mixed with necrotic epithelial cells)
-interstitial & intra-alveolar edema
acute respiratory distress syndrome (ARDS) - pathology: proliferative stage
*type II pneumocytes PROLIFERATE
*granulation in alveolar walls
-usually resolves, leaving minimal functional impairment
acute respiratory distress syndrome (ARDS) - pathology: late stage
*late stage = FIBROTIC STAGE
*fibrotic thickening (scarring) of alveolar septa
*interstitial fibrosis seen on pathology
*clinically, leads to decreased diffusion capacity (can lead to restrictive lung disease)
