Pathology Of Obstructive Lung Diseases Flashcards
Obstructive airway board definition
Characterized by an increase in resistance to air flow due to obstructions so air has issues getting out.
- TLC increased
- RV increased
- FRC increased
- FVC normal
- FEV1 significantly decreased
- FEV1/FVC decreased
COPD specific obstructive issues are irreversible obstructions
- asthma is reversible
Specific types of obstructive lung diseases
Asthma
- hyper responsiveness of bronchi
Chronic bronchitis
- large air way inflammation
Emphysema
- alveolar wall destructions
Bronchiectasis
Bronchiolitis
emphysema and chronic bronchitis often is often seen paired with each other
Emphysema
Permanent enlargement of the air spacers distal to terminal bronchioles w/ destruction of alveolar walls
- causes destruction of elastic tissue which causes bronchioles to collapse during expiration
There is no significant fibrosis
Two most common types of emphysema
- centriacinar (MOST COMMON)
- panacinar
Morphology shows loss of overalls tissues w/ NO FIBROSIS
Centriacinar emphysema
Proximal parts of the acini of the respiratory bronchioles are affected
- alveoli are spared
Lesions are more common in the upper lobes usually in apical segments
MOST common, especially in cigarette smokers
Panacinar emphysema
Distal Acini are enlarged
- alveoli are affected
Lesions are more common in the lower lung zones and more common in alpha-1 antitrypsin deficency
3 primary factors the influence the development of all types of emphysema
1) Oxidative stress and increased apoptosis/senescence
- often seen in smoking and inhaling pollutants
2) inflammatory cells and release of inflammatory mediators
- often seen in chronic infections
3) protease-antiprotease imbalance
- deficency in anti-protease levels and often seen in congenital alpha-1 antitrypsin deficiencies
Alpha-1 antitrypsin deficency quick description
Deficency in anti-trypsin production
- function is to inhibit proteases
- causes decreased protease inhibitors which causes chronic inflammation
1% of all patients w/ emphysema have this defect
- this 1% almost always develops panacinar emphysema type
Located on Pi locus on chromosome 14 w/ Z Allele being the bad allele on the gene
Severe emphysema leads to what?
Hypoxia-induced pulmonary vascular spasms and loss of pulmonary capillary surface area
- leads to pulmonary HTN and cor pulmonale
cor pulmonale or respiratory failure are the end stage emphysema causes of death
Chronic bronchitis
Clinically defined as the presence of a persistent, productive cough for at least 3 consecutive months in at least 2 consecutive years
Presence of hypersecretion of mucus is the distinctive feature in chronic bronchitis and is caused by environmental irritants (causes the consistent coughing)
- also produces hypertrophy of mucous glands, increases in mucus secreting goblet cells numbers in bronchi/bronchioles
Is common among cigarette smokers and urban dwellers in smoggy cities
How is airflow obstructed in chronic bronchitis
Two main causes (although only #1 is required)
1) mucous plugging of the bronchi and bronchiole lumen
2) coexistence emphysema
- produces severe if present
Chronic bronchitis morphology
Diagnostic feature is enlargement of mucus secreting glands.
- assessed by the ratio of thickness of the gland: bronchial wall thickness
Reid index calculates this value and any index above 0.4 is chronic bronchitis
Chronic bronchitis clinical features
Signs/symptoms
- productive severe coughing
- sometimes develops COPD w/ significant cyanosis/hypercapnia/hypoxemia
- leads to pulmonary HTN, cardiac failure and recurrent URI’s if untreated
Bronchiectasis
Permanent dilation of the bronchi/bronchioles caused by destruction of smooth muscles and support elastic tissues
- typically results from chronic necrotizing infections
- is not a primary disorder and is always secondary to persistent infections*
Produces similar coughing to chronic bronchitis except wayyy more sputum
Cystic fibrosis
Disorder of epithelial ion transport (choiride ions specifically) CFTR genes and proteins are affected.
- affects respiratory, GI and reproductive tracts
- also produces super salty sweat glands
Multiple different mutations can lead to CF
- the most common and lethal genetic disease that affects white people though (1:20 carrier frequency)
- is autosomal recessive though (1:2500 incidence)
Leads to dehydrated thick mucus that cannot be transported properly and blocks airways and pancreatic ducts
- leads to the following tow most important clinical manifestations found in CF:
1) recurrent URIs
2) pancreatic insufficiency
Cystic fibrosis pathogenesis
In sweat glands
- chloride ions do not leave the sweat they cant enter the sweat glands
- produces super salty sweat
In all other epithelium
- chloride ions cant get out of the epithelial cells
- results in water entering cells and dehydrating mucus making it hard/impossible for cillia to move it.
What is the most common mutation in CF?
Deletion of three nucleotides that code for phenylalanine (Phe) @ amino acid position 508
- causes misfolding and complete loss of CFTR
- 70% of all CF cases
- is autosomal recessive
What is the most serious complications of CF?
Pulmonary changes are the most severe
- result in development of lung abscesses and super imposed infections into the lungs
- hypertrophy and hyperplasia of the goblet cells, also leads to bronchiectasis
What are the 3 most common organisms to cause infections in CF?
Staph aureus
Haemophilus influenza
Pseudomonas aeruginosa
- most deadly of the three and hardest to cure
- NOTE: while not common, rates of Burkholderia cepacia are increasing slowly every year*
Pancreatic insufficiency in CF
Found in 85-90% of all cases
Milder cases
- accumulations of mucus in small ducts causes dilation in exocrine glands
Advanced cases
- ducts are completely plugged and causes atrophy of exocrine glands as well as impaired fat absorption and Vit. A deficiency
- more common, especially in the F508 mutant change
Liver involvement in CF
Similar patterns to the pancreas
- blocks ducts leadings to fatty liver and cirrhosis of the liver (similar to drinking)
Cardiorespiratory complications of CF
Chronic coughing
Persistent URIs
Develops COPD
Devolpment cor pulmonale
- most common cause of death in CF patients
80% of patients with classic CF harbor P. Aeruginosa in their lung mucus
Primary ciliary dyskinesia (kartagener syndrome)
Autosomal recessive syndrome that is super rare
- results in ciliary motor protein (dysin) defects preventing mucocillary movement
- causes similar affects to CF
Half of patients develop kartagener syndrome which is the following four issues combined:
1) situs inversus
2) bronchiectasis
3) sinusitis
4) infertility for males
Bronchiectasis clincal features
Caused by blockage from lower bronchi/bronchioles (dilates them 4x as large as normal)
Mild Signs/symptoms:
- severe persistent cough w/ Sputum
- dyspnea
- rhinposinustis
- hemoptysis
Severe signs/symptoms:
- hypoxemia
- hypercapnia
- pulmonary HTN
- cor pulmonale
Asthma
Chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness and chest tightness and coughing
Incidence is slowly increasing every year
- is a type 1 hypersensitivity
- also acute and chronic airway inflammation from outside sources can lead to de novo asthma
Hallmarks include:
- intermittent reversible airway obstructions
- chronic bronchial inflammation w/ high eosinophils
- bronchial SMC hypertrophy and hyperreactivity w/ increased mucus secretions
Classic atopic asthma
Associated with excessive type 2 Helper T cell activations
- results in IL-4 production: increases IgE production
- results in IL-5 production: activates eosinophils
- results in IL-13 production: stimulates mucus production
MOST COMMON type
Very genetic based and is often preceded by allergic rhinitis or eczema
Is a type 1 hypersensativity reaction
Early phase vs late phase activations in asthma
Early phase:
- bronchoconstriction
- increased mucus production
- vasodilation
- caused by release of histamine, prostaglandin D2 and leukotrienes and reflex pathways
Late phase:
- inflammation
- eosinophil and leukocyte recruitment
- caused by TH2 cells and resident immune cells in the airways
Non-atopic asthma
No allergen sensitization and very little evidence suggesting genetic base
Usually develops secondary to respiratory infections from virus
- is hypothesized that virus-induced inflammation lowers threshold of subepithelial vagal receptors to irritants (making them hyper reactive)
Drug-induced aspirin
Often caused by aspirin
Presents with recurrent rhinitis, nasal polyps urticaria and bronchospasms
Idiopathic epidemiology but is hypothesized to be an issue in prostaglandin metabolism from inhibition of COX-1/2 from aspirin
