General Mechanisms of Pulmonary Pathology

Question 1

6 layers of the respiratory membrane

Answer 1

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)

Question 2

pulmonary edema - overview

Answer 2

*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”

Question 3

pulmonary edema - 2 basic mechanisms

Answer 3

1. hemodynamic (cardiogenic)
2. increased capillary permeability / microvascular injury

Question 4

pulmonary edema - hemodynamic (cardiogenic) mechanism

Answer 4

*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)

Question 5

pulmonary edema - increased capillary permeability / microvascular injury mechanism

Answer 5

*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)

Question 6

pleural effusion - overview

Answer 6

*excessive accumulation of fluid in the pleural cavity
*manifestation of both primary and secondary pleural diseases

Question 7

pleural effusion - pathogenic mechanisms

Answer 7

1. increased hydrostatic pressure (ex. CHF)
2. increased vascular permeability (ex. pneumonia)
3. other (decreased osmotic pressure, increased intrapleural negative pressure, decreased lymphatic drainage)

Question 8

examples of non-inflammatory pleural effusions

Answer 8

1. hydrothorax
2. hemothorax
3. chylothorax

Question 9

examples of inflammatory pleural effusions

Answer 9

1. pleuritis
2. empyema
3. hemorrhagic pleuritis

Question 10

pleural effusion: hydrothorax

Answer 10

*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

Question 11

pleural effusion: hemothorax

Answer 11

*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

Question 12

pleural effusion: chylothorax

Answer 12

*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

Question 13

pleural effusion: pleuritis

Answer 13

*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

Question 14

pleural effusion: empyema

Answer 14

*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)

Question 15

pleural effusion: hemorrhagic pleuritis

Answer 15

*sanguineous exudates (looks BLACK)
*most often associated with hemorrhagic diatheses
*Rickettsial infections or NEOPLASTIC INVOLVEMENT

Question 16

pulmonary embolism (PE) - risk factors

Answer 16

*trauma
*hypercoagulable state
*recreational drugs
*old age
*malignancy
*birth control pills/hormone replacement
*obesity, obstetrical/post-partum
*surgery
*immobilization
*serious illness

Question 17

pulmonary embolism (PE) - pathogenesis

Answer 17

*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

Question 18

pulmonary embolism (PE) - clinical features

Answer 18

*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

Question 19

pulmonary infarction

Answer 19

*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

Question 20

mechanisms for pulmonary embolisms

Answer 20

1. thromboembolism (blood clot causes the blockage; most common)
2. fat embolism (follows fractures of long bones with fatty marrows)
3. amniotic fluid embolism (fetal membrane tear and rupture of uterine veins)

Question 21

pulmonary hypertension - overview

Answer 21

*increased pulmonary artery blood pressure (>25 mmHg)
*decrease in the cross-sectional area of the pulmonary vascular bed
*increased pulmonary vascular blood flow

Question 22

pulmonary hypertension - pathogenesis

Answer 22

1. primary (familial) - proliferation of endothelial and vascular smooth muscle cells
2. heart disease - right side volume overload
3. intrinsic lung diseases - obliterate alveolar capillaries
4. chronic thromboembolic disease - increase in pulmonary vascular resistance

Question 23

pulmonary hypertension - morphology

Answer 23

*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

Question 24

pulmonary hypertension - clinical features

Answer 24

*s/s become evident only in advanced disease:
-dyspnea and fatigue
-over time, severe respiratory distress
-cyanosis
-right ventricular hypertrophy occurs late

Question 25

acute respiratory distress syndrome (ARDS) - overview

Answer 25

*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

Question 26

acute respiratory distress syndrome (ARDS) - causes

Answer 26

*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

Question 27

acute respiratory distress syndrome (ARDS) - pathogenesis

Answer 27

1. widespread injury to alveolar endothelial and type I pneumocyte epithelial cells 2. pulmonary macrophages produce proinflammatory mediators (TNF, IL-1, IL-8) 3. 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 4. subsequent release of macrophage-derived fibrogenic cytokines -stimulate fibroblasts and COLLAGEN DEPOSITION associated with healing phase of injury

Question 28

acute respiratory distress syndrome (ARDS) - pathology: early stage

Answer 28

*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

Question 29

acute respiratory distress syndrome (ARDS) - pathology: proliferative stage

Answer 29

*type II pneumocytes PROLIFERATE *granulation in alveolar walls -usually resolves, leaving minimal functional impairment

Question 30

acute respiratory distress syndrome (ARDS) - pathology: late stage

Answer 30

*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)