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
