Resp Path 2 - OBSTRUCTIVE DZ, Emphysema, Chronic Bronchitis, Asthma, Bronchiectasis, CF - Galbraith Flashcards
What is obstructive lung disease?
Resistance to airflow from trachea to alveoli.
Forced expiration: FEV/FVC
Together, emphysema and chronic bronchitis form….
COPD
What demographic is most susceptible to COPD?
What environmental factor has a strong association?
- Females and African Americans
- SMOKING
How is asthma distinguishable from emphysema and chronic bronchitis?
Presence of reversible bronchospasms.
Emphysema is characterized by __1__ of airspaces __2__ to terminal bronchioles.
- irreversible enlargement
- distal
Location and demographic of centriacinar emphysema.
- Destruction/enlargement of central or proximal parts of respiratory unit - SPARES DISTAL ALVEOLI.
- UPPER LOBE/APEX involvement.
- Occurs in HEAVY SMOKERS (with chronic bronchitis)
Location and associated deficiency in Panacinar Emphysema.
- Destruction/enlargement of acinus (ALVEOLI).
- Lower basal (BASE of LUNGS) zones involvement.
- Associated with alpha1-antitrypsin deficiency.
Location of distal acinar (paraseptal) emphysema.
What does this often subsequently cause?
- Involves DISTAL ACINUS.
- Near pleura and adjacent to fibrosis or scars.
- Causes spontaneous pneumothorax
What is the pathogenesis of alveolar destruction in emphysema?
Smoking/pollutant and congential a1-antitrypisin deficiency results in 3 imbalances:
1) Imbalances between pulmonary proteases and antiproteases (elastase release).
2) Inflammatory cells
3) Oxidative stress
Define a1-antitrypsin’s role in emphysema.
- An antiprotease
- Chromosome 14
- 80% of homozygotes for Z allele (PiZZ) will develop SYMPTOMATIC PANACINAR EMPHYSEMA
PiZZ
alpha1-antitrypsin deficiency, leading to panacinar emphysema
What accelerates and intensifies severity of a person with PiZZ?
SMOKER.
Why is emphysema considered an obstructive lung disease?
Destruction of elastic alveolar walls surrounding respiratory bronchioles leads to COLLAPSE of those bronchioles during EXPIRATION - normally held open by elastic recoil of lung parenchyma.
how much lung parenchyma must be loss for symptoms of emphysema to show?
1/3
What is this?
A patent presents with weight loss, dyspnea, wheezing, cough, barrel chested/overdistension, prolonged expiration due to OVER VENTILATION.
Emphysema
“Pink puffer”
What may emphysema progress to?
What 4 things are death usually due to?
Pulmonary HTN and right sided HF.
Death: respiratory acidosis/failure, RHF, pneumothorax»_space; lung collapse.
What is this?
A chronic, persistent productive cough without other identifiable cause. Common in smokers/polluted environments.
Chronic bronchitis.
What is the pathogenesis of chronic bronchitis?
- Initiating factor»_space; exposure of bronchi to inhaled irritants.
- Mucus hypersecretion
- Chronic inflammation»_space; damage and fibrosis of small airways
- Diminished ciliary action of respiratory epithelium, leading to STASIS OF MUCUS.
What are three other form of emphysema?
1) Compensatory hyperinflation
2) Obstructive overinflation
3) Insterstitial emphysema
What is compensatory hyperinflation
Form of emphysema - LOSS OF ALVEOLI but WITHOUT SEPTAL WALL DESTRUCTION
(dt surgical removal of diseased lung with recoil, allowing alveolar expansion)
What is obstructive overinflation?
Form of emphysema - expansion of lung because of TRAPPED AIR, but WITHOUT SEPTAL WALL DESTRUCTION
subtotal obstruction of an airway, thereby creating a ball-valve that admits air on inspiration but TRAPS it on expiration.
(dt tumor, FBAO, Asthma)
What is interstitial emphysema?
Form of emphysema - alveolar tears, resulting of ENTRY OF AIR INTO CONNECTIVE TISSUE of lung/mediastinum/subQ tissues.
Morphology in chronic bronchitis (5)
1) Edema of lung mucous membranes
2) Mucinous secretions plugging small bronchi and bronchioles (goblet cells)
3) Bronchilar inflammation and fibrosis
4) Mucous gland HYPERPLASIA (*Reid index)
5) bronchial epith SQUAMOUS METAPLASIA and dysplasia.
What is the Reid index
Ratio of mucous glad layer thickness to distance from epithleium to cartilage.
- Normally 0.4
- > 0.4 = increased thickness = hyperplasia of mucous glads
What is this?
Persistent, productive cough. Dyspnea on exertion. Classically: Hypercapnic, hypoxia, mild cyanosis.
Chronic Bronchitis, “Blue Bloater”
hypoxia=trouble moving air in/out
What does long standing chronic bronchitis often progress to?
Cor pulmonale with HF.
Death can be secondary to infection.
What are two defining characteristics of:
1) Emphysema
2) Chronic bronchitis
3) Asthma
Emph/CB due to chornic injury/small airway dz:
1) Alveolar wall destruction, overinflation.
2) Productive cough, airway inflammation
Asthma due to bronchial hyperresponiveness (triggered by allergen, infection)
3) Reversible obstruction
What is this?
Recurrent wheezing, SOB/chest tightness, cough. More frequent in early AM/late PM.
Asthma
What are three characteristics of asthma?
1) **RECURRENT BRONCHOCONSTRICTION (unique)
2) Inflammation of bronchial walls
3) Increased mucucs secretion
What is atopic asthma?
- Most common
- Caused by IgE hypersensitivity reaction to environmental allergen (or NSAIDS)
- Family Hx
Pathogenesis of atopic asthma
Th2 stimulated production of IgE recruits eosinophils and stimulates mucus production.
- Reexposure links IgE on mast cells»_space;> degranulation and IMMEDIATE hypersens reaction.
What characterizes the two phases of atopic asthma?
1) Immediate phase - minutes (Ag bind to IgE mast cells = LT and cytokine release)
- Bronchoconstriction, mucus secretion, increased vascular permeability
2) Late phase - hours (recruited leukocytes)
- Persistent bronchospasm and edema, Inflam cell recruitment»_space; DAMAGE TO MUCOSAL TISSUE
What triggers nonatopic asthma (4 things)?
1) Respiratory viruses
2) Inhalation of irritants
3) Cold air
4) Exercise
In asthma, what does repeated allergen exposure induce?
AIRWAY REMODELING
- Bronchial wall smooth m hypertrophy and hyperplasia (and inc goblet/subepith cells).
- Subepithelial fibrosis
- Submucosal gland hyperplasia, increased goblet cells
- Increased airway vascularity
- Increased thickness of airway wall.
Genetics of asthma
- HLA alleles
- polymorphisms in IL-13
- CD14
- ADAM-33
- B2-R
- IL-4-R
Curschmann spirals, think what?
ASTHMA - expelled in sputum/BAL as bronchi and bronchioles occluded by thick mucus plugs
Chorcot-Leyden crystals, think what?
ATPOIC ATHMA
-Contained (with eosino) in sputum/BAL
What is this?
Chronic, RECURRENT NECROTIZING INFECTIONS eventually destroying smooth muscle and elastic tissue.
What does this lead to?
Bronchiectasis
- Leads to permanent dilation of bronchi and bronchioles.
What does the recurrent necrotizing infection in bronchiectasis result in?
Inflammation and destruction and plugging up of small airways. Can obliterate nearby bronchioles»_space; obstructive.
- Lower lobes
Predisposing conditions for bronchiectasis
Anything that affects mucus clearing - primary ciliary dyskinesia (kartageners), CF, Allergic Bronchopulmonary Aspergillosis
- Immunodeficiency
What is this caused by? PERIOBRONCHIAL FIBROSIS»_space; bronchiolitis obliterans
Repeated attempts to resolve inflammatory process that causes bronchiectasis
Describe the genetics and dysfunction in CF.
CFTR, ch7»_space; abnormal function of, or lack of epithelial chloride channel.
CTFR function in sweat glands v. other epithelia
Sweat glands: Cl from surface INTO CELL
Other: from cell TO THE LUMEN
What is CTFR’s normal function?
Dysfunction?
Normally inhibits ENaC, found on all non-sweat glad epithelial cell apical surfaces.
Dysfunction results in overactive ENaC, resulting in epithelia taking up Na ions»_space; WATER FOLLOWS
What is the result of airway CTFR dysfunction in CF?
DEHYDRATED MUCUS because Cl is not transported out of the cel, so lots of Na comes into cell, followed by lots of water.
Deficient hydration of airway mucus leads to what in CF?
defective ciliary activity»_space; inability to clear mucus»_space; CHRONIC INFECTION»_space; BRONCHIECTASIS
What are the 4 primary infectious species in CF?
Bacteria - S. aureus, H flu, Burkholderia cepacia.
- Pseudomonas aeruginosa
What does Pseudomonas aeruginosa do that makes it more resistant to antibiotics and inflammatory cells in a CF patient?
Produces a mucoid capsule that allows it to form a protective biofilm.
Classis s/s for:
“persistent cough with productive sputum”
Bronchitis
Obstructive disease means what change in FEV1/FVC??
Decreased
Describe the pathogenesis of bronchitis.
Smoking = increase proteinase, normal antiproteinase
alpha1-antitrypsin deficiency = normal proteinase, decreased antiproteinase
