(14.1) Pulmonary Pathology (Singh) Flashcards
Describe the progression of normal fetal lung development
Embryonic (lung bud) –> Pseudoglandular –> Canalicular –> Saccular –> Alveolar
What are the clinical uses for knowing the stage of fetal lung development?
Knowing the stage can help the clinician determine the age of the fetus
What are the requirements for normal fetal lung development?
- Space in the thoracic cavity
- Ability to inhale (chest call must be able to move, and there must be enough material (amniotic fluid) present to inhale
What are the main structures you will see histologically of the trachea and main bronchi?
Cartilage
Glandular tissue
Respiratory epithelium
Smooth muscle layer
Lamina propria
Describe what you would encounter with a low-power image of lung parenchyma
Alveoli
Blood vessels
Bronchioles
Describe what you would encounter with a high-power image of lung parenchyma
Erythrocytes
Macrophages
Type 1/2 pneumocytes
What is CRUCIAL to the sucessful oxygen exchange occuring in the lungs?
A very THIN layer between the circulating erythrocytes and alveolar lumen so that there is easy exchange
Describe the function of Type I pneumocytes
Facilitate gas exchange
*Support and line the alveoli
Describe the function of Type II pneumocytes
Product surfactant
Replace type 1 pneumocytes (they are pluripotent)
What is the function of alveolar pores (of Kohn)?
“holes” that allow aeration but also bacteria/cells/exudate to travel between alveoli
What is this pathology?
Pulmonary hypoplasia
What causes pulmonary hypoplasia?
Reduced space in the thoracic cavity (eg. diaphragmatic hernia taking up the space by the lungs)
Impaired ability to inhale (eg. oligohydraminos from renal agenesis, airway malformation, chest wall motion disorders)
What is the mortality rate of pulmonary hypoplasia?
HIGH! (up to 95%)
If lung weight is <40%, immediate death occurs in neonatal period
What are foregut cysts?
Detached outpouchings of foregut
Seen along hilum and mediastinum
Can be respiratory, esophageal or gastroenteric
Often asymptomatic and seen incidentally; complications include rupture, infection, or airway compression
Tx: Excision is curative
What is congenital pulmonary adenomatoid malformation (CPAM)?
What are the complications?
“Arrested development” (stuck at a stage) of pulmonary tissue branching from the tracheobronchial tree with formation of intrapulmonary cystic masses that repeats itself; can be detected via US
can lead to hydrops fetalis, pulmonary hypoplasia (since the CPAM is taking up the space for the lung to grow) or get infected later in life
What are pulmonary sequestrations?
Nonfunctioning lung tissue that forms as an aberrant accessory“lung bud”, not connected to the tracheobronchial tree unlike CPAM
*Typically found in the region of the left lower lobe
How are pulmonary sequestrations characterized?
Lack of connection to the tracheobronchial tree
Independent (systemic) arterial supply, but they are non functional so they do not tend to get blood flow
What is this image an example of?
Intralobar pulmonary sequestration (ILS)
What are intralobar pulmonary sequestration (ILS)s susceptible to?
Lack of airway perfusion makes ILS’s susceptible to infection and absess formation
What is this an example of?
Extralobar pulmonary sequestrations (ELS)
How are extralobar pulmonary sequestrations (ELS) different from ILS?
ELS have their own PLEURA, appears as a mass in the chest or abdomen
What comes to attention sooner…
ILS or ELS?
ELS
Describe the differences between these congenital anomalies:
CPAM/CCAM
vs
Pulmonary sequestraion
CPAM/CCAM = INTRApulmonary cystic malformation w/ CONNECTION to tracheobronchial airways and pulmonary vasculature
Pulmonary sequestration = INTRA or EXTRA pulmonary lung tissue with NO CONNECTION to pulmonary vasculature or tracheobronchial tree
What is atelectasis?
Partial or complete collapse of the lung
What are the three major types of atelectasis?
- Resorption
- Compression
- Contraction
What causes resorption atelectasis?
Airway obstruction - parenchyma does not get air = gradual resorption of air reduces lung expansion
What causes compression atelectasis?
Accumulated material in pleural cavity compresses the lung parenchyma and prevents it from expanding
What causes contraction atelectasis?
Fibrotic or other innate restrictive process in the pleura or peripheral lung restricts lung expansion
What is the LEAST common form of atelectasis?
Contraction atelectasis
What pathologic process is occuring here?
Pulmonary edema
What are the major causes of pulmonary edema?
“Pushing out” –> as in left sided heart failure (backing to pulm circ. = too much blood in pulm .circuit = leak out = pulm edema)
“Leaking out” –> pulmonary vessels cannot keep blood in and it leaks out in the lungs (e.g. low albumin/oncotic pressure)
Injury to alveolar wall
Unsure mechanisms (neurologic, high altitude pulmonary edema)
What are the clinical criteria for acute lung injury (ALI)?
Acute onset
Hypoxemia (PaO2/FiO2 <300)
Bilateral infiltrates
No evidence of cardiac failure
What is the clinical criteria for acute respiratory distress syndrome (ARDS)?
Abrupt onset of symptoms
Hypoxemia (PaO2/FiO2 <200)
Bilateral infiltration
Non cardiac in nature
What is diffuse alveolar damage (DAD)?
Histologic manifestation of ARDS
What is the pathology?
Acute respiratory distress syndrome (ARDS)
What is the pathophysiology of ARDS?
Fluid leaks into the endothelium from the capillary into the alveoli > damage to the Type 1 and 2 pneumocytes > debris forms hyaline deposits on the alveoli
What is the pathology?
Diffuse alveolar damage (DAD)
Edema + Fibrin + Cell debris = HYALINE MEMBRANES
What are the three stages of ARDS?
- Exudate
- Proliferative
- Fibrotic
What occurs during the exudative stage of ARDS?
Edema
Hyaline membranes
Neutrophils
What occurs during the proliferative stage of ARDS?
Fibroblast proliferation
Organizing pneumonia
Can lead to resolution or Early fibrosis
What occurs during the fibrotic stage of ARDS?
Extensive fibrosis
Loss of normal alveolar architecture
ARDS : resolution
After the fibroproliferative phase, 2 pathways may ensue… what are they?
Resolution OR Fibrosis (irreversible)
Describe the histologic differences b/w a normal lung and a lung w/ hyaline membranes
Lung w/ hyaline membranes has THICKENED walls that make oxygen exchange nearly impossible
This is what accounts for the decreased PaO2/FiO2 values observed
What is acute interstitial pneumonia (AIP)?
Same clinical presentation as ARDS
Same histology as ARDS/DAD
***CANNOT BE ATTRIBUTED TO A SPECIFIC ETIOLOGY
What is restrictive lung disease?
aka interstitial lung dz, characterized by volume restriction (stiff lungs) = cannot fill the lung
FEV1/FVC ratio is normal or increased (both are reduced BUT the ratio is not necessarily reduced)
(FEV=force expiratory volume, FVC=forced vital capacity)
What is obstructive lung disease?
Decreased flow
LOW FEV1/FVC ratio
***(FEV=force expiratory volume, FVC=forced vital capacity)
What are examples of obstructive pulmonary diseases?
Emphysema
Chronic bronchitis
Asthma
What is the most common cause of COPD/Chronic bronchitis?
Smoking
Describe what is occuring during a chronic bronchitis state
Smoke chemicals cause inflammation and mucus production
- Mucus hypersecretion (mucinous layer with goblet cell hyperplasia/hypertrophy) > cillia is “drowning” and cannot get rid of the debris/chemicals
- predisposes to more inflammation and infection
What is the criteria for diagnosing chronic bronchitis?
Persistent cough w/ sputum production for 3 months out of 2 consecutive years
What is the predominant pathophysiologic mechanism of chronic bronchitis?
Mucous gland hyperplasia
What are the complications of chronic bronchitis?
Squamous cell metaplasia of the bronchi > dysplasia > carcinoma
Bronchiectasis
Death for respiratory infection
What is the pathology?
Emphysema
*Notice the extremly dilated spaces within the lung parynchema
Why is emphysema considered an obstructive process?
There is a compressed duct proximal to the alveolar sac > causes the destruction of the alveolar sacs that define emphysema
Smoking induced emphysema: centriacinar emphysema (upper lobes)
What is the clinical presentation of emphysema?
Clear but enlarged lungs on CXR
“Barrel chest”
FEV1/FVC ratio is reduced
What does “blue bloaters” refer to?
Chronic bronchitis (actually the initial stage of emphysema)
cyanotic and edematous (rhonchi - mucus)
compensation still going on so Hgb is elevated
What does “pink puffers” refer to?
Emphysema
Older and thin, severe dyspnea, pursed lips trying to prolong expiratory wheezing
What is alpha1-antitrypsin?
Alpha1-antitrypsin coats the lungs protecting them from neutrophil elastase
Neutrophil elastase is produced by white blood cells to break down harmful bacteria
What is an alpha1-antitrypsin deficiency?
Lungs LACK alpha1-antitrypsin coating coded by Pi gene on Cr.14 (Homozygous mutatnt is PIZZ)
This leaves lungs vulnerable to damage by neutrophil elastase > panacinar emphysema (lower lobes since it contacts more elastase from the capillaries in the setting of decreased a1-antitrypsin)
presents as dyspnea + cirrhosis in genetically susceptible individuals
Describe the type of emphysema associated with each image
Alpha1 antitrypsin deficiency demonstrates a ___________ emphysema pattern
BASILAR panacinar
What are the complications of emphysema?
Respiratory failure
Pneumothorax with lung collapse
CAD
Right heart failure (cor pulmonale)
What are the basic mechanisms of asthma?
Inflammation > airway hyperresponsiveness + airway obstruction (reversible)
What are the classifications of asthma?
Atopic (extrinsic)
Non-atopic (intrinsic)
Describe atopic asthma
2/3 of all patients
May be any age, usually children
FH of asthma
triggered by allergies, Elevated IgE levels (type I hypersensitivity)
Triggers may include a variety of allergens
Describe the pathogenesis of atopic asthma
TH2 > interleukins > recruit inflammatory cells
TH2 > leukotrienes C4, D4, E4 > bronchoconstriction, increased vascular perm, mucus secretion
Mast cell cross linked to IgE > histamine
Describe non-atopic asthma
1/3 of all patients
Often older pts
NORMAL IgE levels
Triggers include cold, exercise, infection
Why is it SO important to make sure your asthmatic patients’ have “controlled” asthma?
High potential for irreversible airway remodeling with each subsequent asthma attack
What are some of the results of airway remodeling?
Fibrosis
Smooth muscle hyperplasia
Increased goblet cells and submucosal glands
*now irreversible
Pharmacologically, what is a huge problem in patients that have undergone airway remodeling?
DECREASED response to therapeutic agents:
Bronchodilators
Corticosteroids
What is status asthmaticus?
Unremitting, potentially fatal asthma attack
Characterized by bronchial occlusion by thick mucus
*Hallmark = curschmann spirals (coiled mucus plugs) and Charcot Leyden crystals (eosinophlic crystals) found in mucus
What is aspirin-sensitive asthma?
Unique sensitivity to aspirin that induces asthma
Highly associated with: nasal polyps and recurring rhinitis (Samter’s triad)
What is the pathogenesis of aspirin sensitive asthma?
Aspirin inhibits COX-1 > AA accumulates > becomes Leukotriene C4, D4, E4
What is bronchiectasis?
What conditions predispose to bronchiectasis?
Necrotizing inflammatory response that is an end stage process of multiple processes that can include infection or obstruction
ABPA, Cystic Fibrosis, Chronic Infection (TB), Primary ciliary dyskinesia
Describe the path of cystic fibrosis
CFTR gene is affected
Chloride transport is impaired > cells absorb extra Na+,Cl and H20 instead of lubricating the mucus –> Leads to dehydrated mucus that forms plugs > predispose to infection > bronchiectasis
What is kartagener’s syndrome?
Aka Primary ciliary dyskinesia –> Dysfunction of dynein arm of microtubules –> impaired ciliary function
Triad of : Sinusitis, bronchiectasis, situs inversus
dextrocardia (cillia helps rotate the organs in utero)
***Often male infertility (sperm cannot swim)
What is this pathology?
Allergic Bronchopulmonary Aspergillosis (ABPA)
What is allergic bronchopulmonary aspergillosis (ABPA)?
Exaggerated hypersensitivity response to Aspergillus infection overlying chronic lung disease
–> Background of asthma or CF
-Increased IgE on serum testing, positive skin test
***Thick mucus in bronchi
