Lung Path 1 - Embryo Histo Malformation Atelactasis Edema ARDS (Singh) Flashcards
Requirements for normal fetal lung development?
Space in the thoracic cavity for growth (lungs are soft and cannot compete for additiona room, if it is not provided)
Enough room for the chest wall to be able to move (again, due to paranchymal softness)
Sufficient amount of amniotic fluid for inhalation to occur
What are the rigidly open structures of the airway and what is these sections primarily role?
Trachea
Main bronchus (primary)
Lobar bronchus (secondary)
Segmental bronchus (tertiary)
Their fxn is to conduct air to the terminal acinar units
What structures have thin walls and high vascularity?
What is their function?
Bronchioles
Terminal Bronchioles
Respiratory Bronchioles
Fxn of resp bronchioes: Gas Exchange
Except for the vocal cords, the entire respiratory tree is lined by what type of epithelium?
Pseudostratified, tall, columnar, ciliated epithelium
How will respiratory tissue appear histologically?
Mucosal epithalium is inner most layer (cillia, goblet cells, submucosal glands)
Muscularis mucose - smooth muscles, provide peristalsis
Bronchial ring - provides rigidity
Numerous mucus-secreting goblet cells and submucosal glands are dispersed throughout the walls of which parts of the respiratory tree?
- Trachea
- Bronchi
- NOT the bronchioles
Bronchial mucosa contains population of neuroendocrine cells with neurosecretory granules containing which factors?
- Serotonin
- Calcitonin
- Gastrin-releasing peptide (bombesin)
What are 2 functions of the Type 2 pneumocytes of the alveolar epithelium?
Type 2 pneumocytes are puliprotent
- Produce surfactant
- Repair of alveolar epithelium by giving rise to type 1 pneumocytes
What are the components of the Interstitium?
Alveolar epithelium
Fused basal laminae of the alveolar epithelium and the capillary endothelium
Capillary endothelium
What is the significance of alveolar pores?
What are they called?
Alveolar pores may also be referred to as “Pores of Kohn”
They conduct air (somehwat redundant) between alveoli –> good
Also allow the spread of bacteria and cancer cells to be exchanged between alveolar cells –> not so great
What plays a particularly important role in the synthesis of surfactant?
Glucocorticoids
Analysis of what in the amniotic fluid provides a good estimate of the level of surfactant in the alveolar lining?
Phospholipids
Pulmonary hypoplasia occurs in utero and what are 2 major causes?
- Congenital diaphragmatic hernia
- Inability to inhale
- Oligohydramnios (d/2 renal agenesis) Must know Potter Sequence!
- Airway malformation (stenosis)
- Chest wall motion disorders
–> high mortality rate
Foregut cysts are most often located where in the lungs and which classification/type is most common?
Complications?
Treatment?
Hilum or middle mediastinum
Bronchogenic cysts of the respiratory lining are most common
but can be esophageal or gastroenteric
Complications: rupture, infection, or pushing/compressing airway
Treatment: Excision curative!
What are some histologic findings on an excised bronchogenic cyst?
Typical respiratory lining filled with humorous substance
Congenital pulmonary adenomatoid malformations (CPAM/CCAM) are caused by what?
“Arrested development” of pulmonary tissue –> formation of intrapulmonary cystic masses WITH connection to tracheobronchial airways and pulmonary vasculature
No differentiation! Cell division is stuck in one development stage, and keeps reproducing the same cell line.
Congenital pulmonary adenomatoid malformations can be deadly due to what complications?
What is unique about this developmental disorder if discovered early in-utero?
- Hydrops or pulmonary hypoplasia
- Can get infected later in life
Can be removed in-utero –> corrects course of development by removing the “irregular, lumpy tumor” and making space in the thoracic cavity
Pulmonary sequestration refers to a discrete area of lung with what 2 features?
Non-functioning lung tissue forming abberant “lung bud” that
- Lacks any connection to the airway system
- Has abnormal blood supply arising from aorta or its branches
When do intralobal pulmonary sequestrations typically present and are often due to what?
Older children/adults
Due to recurrent localized infection or bronchiectasis due to “stasis” caused lack of airway
Extralobar pulmonary sequestrations most commonly come to attention in infants how?
As mass lesions in the chest or abdomen
Usually associated w/ other congenital anomalies
May have independent airways
Via which imaging modality can congenital pulmonary adenomatoid malformations be detected?
Fetal ultrasound
What are the differences between CPAM and Pulmonary sequesteration?
CPAM
always inrapulmonary
connection to airways and pum vasculature
Sequesteration
intra- or extrapulmonary
NO connection to bronchial tree of pulm vasculature
What are the 3 main types of acquired atelectasis and what is each caused by?
- Resorption due to obstruction of airway (mucus plugs) which gradually reduces lung expansion
- Compression due to accumulation of material or air/material within pleural cavity (i.e., transudate/exudate/blood or pneumothorax) that compresses the parenchyma
- Contraction due to fibrosis or restrictive processes in pleura preventing the lungs from filling completely
Atelectasis is a reversible disorder, except in cases caused by what?
Contraction atelectasis
Which type of acquired atelectasis causes the mediastinum/trachea to shift toward the affected lung; which type causes a shift away?
- Resorption —> mediastinum shifts toward affected lung
- Compression –> mediastinum shifts away from affected lung
Which type of acquired atelectasia occurs in the setting of asbestosis?
Contraction atelectasis
Where does fluid accumulate initially in pulmonary edema due to hydrostatic pressure being greatest in these sites (dependent edema)?
Basal regions of the lower lobes
Hemodynamic pulmonary edema is due to an increase in what; most commonly occuring in what setting?
Pushing out: ↑ hydrostatic pressure secondary to
1) volume overload or 2) pulm vein obstruction
–> left-sided CHF
OR
Leaking out: reduced colloid pressure due to
hypoalbuminemia
nephrotic syndrome
liver disease with reduced protein production
List 4 causes of decreased oncotic pressure, which cause “leaking out” and pulmonary edema?
- Hypoalbuminemia
- Nephrotic syndrome
- Liver disease
- Protein-losing enteropathies
List some of the etiologies which can cause direct injury to the alveolar wall leading to pulmonary edema?
- Infections: bacterial pneumonia
- Sepsis
- Inhaled gases: high [O2] and smoke
- Liquid aspiration: gastric contents; near drowing; or foreing objects
- Radiation
What are 2 causes of pulmonary edema of undetermined origin?
- High altitude
- Neurogenic (CNS trauma)
What are the histological findings of pulmonary edema due to HF?
dilated capillaries full of blood.
“Microhemorrhage” in alveolar spaces
scattered hemosiderin- laden macrophages accumulate within alveoli –> “heart failure cells”
What is the histological appearance of of the alveolar capillaries in hemodynamic pulmonary edema?
Engorged, and an intra-alveolar transudate appears as finely granular pale PINK material
In long-standing pulmonary congestion (i.e., mitral stenosis), hemosiderin-laded macrophages are abundant, and what is the gross morphology of the lungs?
Soggy lungs become firm and brown (brown induration)
When the edema associated with pneumonia fails to stay localized and instead becomes diffuse alveolar edema what fatal condition may this lead to?
ARDS
The radiographic and pathologic features of acute interstitial pneumonia are identical to what?
Organizing stage of ALI
Define ARDS terminology
Acute Lung Injury (ALI) –> Acute onset, hypoxemia, bilateral infiltrates without HF
Acute Respiratory Distress Syndrome (ARDS) –> Worsening hypoxemia that is not cardiac in nature
Diffuse Alveolar Damage (DAD) –> Histologic manifestation of ARDS
ARDS is a diagnosis of exclusion using the criteria which can be remembered with mnemonic A.R.D.S.
- Abnormal CXR (bilateral lung opacities)
- Respiratory failure within 1 week of alveolar insult (ABRUPT)
- Decreased PaO2/FiO2 ≤200 = hypoxia
- Symptoms of respiratory failure are NOT due to HF/fluid overload
The causes of ARDS may be remembered with “SPARTAS.”
- Sepsis
- Pancreatitis/Pneumonia
- Aspiration
- uRemia
- Trauma
- Amniotic fluid embolism
- Shock
Acute lung injury (aka noncardiogenic pulmonary edema) is characterized by the abrupt onset of significant _________ and __________ in the absence of __________.
Acute lung injury (aka noncardiogenic pulmonary edema) is characterized by the abrupt onset of significant hypoxemia and bilateral pulmonary infiltrates in the absence of cardiac failure.
What is the typical presentation of someone with Acute Interstitial Pneumonia?
Pt presents w/ ARF following an illness of <3 weeks duration that resembles a URI
What is the term used to describe widespread ALI of unknown etiology associated with a rapidly progressive clinical course?
Acute interstitial pneumonia (aka idiopathic ALI-DAD)
What is an important early event in the pathogenesis of ALI/ARDS?
Endothelial activation
Following endothelial activation in ALI/ARDS there is adhesion and extravastion of which immune cells and what is the result?
- Neutrophils
- Degranulate and release proteases, ROS, and cytokines
Which factor is released inside of alveoli during ALI/ARDS that acts to sustain the ongoing pro-inflammatory response leading to more endothelial injury and local thrombosis?
Macrophage migration inhibitory factor (MIF)
ALI/ARDS is more common and associated with a worse prognosis in whom?
Chronic smokers and alcoholics
Pt’s with ALI will have what sx’s?
- Profound dyspnea and tachypnea
- Followed by ↑ cyanosis and hypoxemia
During the acute stage of ALI/ARDS what is seen morphologically in the lungs?
- Lungs are heavy, firm, red, and boggy
- Exhibit congestion, interstitial and intra-alveolar edema, inflammation, fibrin deposition, and DAD
- Alveolar walls become lined with waxy hyaline membranes
The thickened protein-rich edema fluid + debris from dead alveolar cells accumulate in ALI/ARDS, and lead to the formation of what?
HYALINE membranes
The histologic manifestation of both ALI and ARDS is what?
Diffuse alveolar damage (DAD)
In the proliferating (organizing pneumonia) stage of ALI/ARDS what are the type 2 pneumocytes doing and what begins to form?
- Type 2 pneumocytes are proliferating –> fibroblasts
- Granulation tissue forms in the alveolar walls and spaces
Following the fibroproliferative phase in ARDS, what 2 pathways may ensue and the result of each?
- Resolution –> restoration of normal cellular structure and function
- Fibrosis –> destruction and distortion of normal cellular structure –> IRREVERSIBLE
If there is resolution of the injury in ARDS/ALI, what factors are released from macrophages which stimulate fibroblast growth and collagen deposition leading to fibrosis of alveolar walls?
- TGF-β
- PDGF
Why may the hypoxemia associated with ALI/ARDS be refractory to O2 therapy; what acid-base disturbance may develop?
Due to ventilation perfusion mismatching and respiratory acidosis may develop
What is the cause of the ventilation perfusion mismatch and hypoxemia in ALI/ARDS?
- Poorly aerated regions continue to be perfused
- Perfusion = normal; but ventilation = decreased
What is seen on radiographic imaging of patient with ALI?
Diffuse bilateral infiltrates
When do most deaths associated with Acute Interstitial Pneumonia occur?
Within 1-2 months
What are the various stages of ARDS?
EXUDATIVE
Edema, hyaline membranes, neutrophils
PROLIFERATIVE
Fibroblast proliferation, organizing pneumonia, early fibrosis
FIBROTIC
Extensive fibrosis, loss of normal alveolar architecture
