What do they do in asthma:
IL4
IL5
IL10
all secreted by Th2 T cells (humoral immunity)
IL4: induce IgE
IL5: attract eosinophils
IL10: increase Th2, decrease Th1
Kartagener syndrome
- mech
- complications (4)
- defect of cilia (dynein arm), necessary for cilia movement
1. sinusitis (cilia cannot move out infection)
2. infertility (sperm)
3. situs inversus
4. bronchiectasis (infection in lung leads to inflammation)
allergic bronchopulmonary aspergillosus (ABPA)
- what is it
- classic populations
- allergic HSR to Aspergillus, leads to chronic inflammation and bronchiectasis
1. cystic fibrosis
2. asthmatics
chronic bronchitis
- mech at cell level
- histology finding
- hypertrophy of mucinous glands in the submucosa that produce mucus
- “Reed index”: normal ratio is
- chronic bronchitis: >50% of bronchial wall is mucinous glands
chronic bronchitis
-clinical presentation, complications (4)
- productive cough, tons of mucus
- “blue bloaters”–cyanosis (mucus traps CO2, so higher PACO2 and lower PAO2)
- increased risk of infection
- cor pulmonale
nonallergic causes of asthma (4)
- exercise
- viral infection
- aspirin-intolerant asthma (remember bronchospasm and nasal polyps)
- occupational exposures (eg dust)
A1AT deficiency:
-what are the genetics involved
disease severity based on alleles:
- PiMM–PiM/PiM normal. A1AT is produced
- PiMZ–PiM/PiZ: half of A1AT produced, so asymptomatic but high risk of emphysema with smoking
- PiZZ–PiZ/PiZ: high risk of panacinar emphysema and liver cirrhosis
emphysema
-cellular mech
- imbalance of proteases and antiproteases
- proteases released by neutrophils and macrophages constantly (constant inflammation)
- antiproteases (eg alpha-1 antitrypsin) neutralizes proteases to prevent damage
What do you see in mucus of asthma pts?
- MBP crystals (Charcot Leyden crystals)
- desquamated epithelium (Curschman spirals)
emphysema
- 2 categories
- how do their presentation differ?
- smoking–centriacinar (closer to smoke), upper lobes more severe (smoke rises)
- A1AT deficiency–panacinar, lower lobes more severe
chronic bronchitis
- diagnosis definition
- cause
- chronic productive cough lasting at least 3 months, over min of 2 years
- highly assoc with smoking
Emphysema caused by A1AT deficiency:
- what non-lung complication occurs?
- histology
- Liver cirrhosis may occur
- A1AT is misfolded and accumulates in hepatocytes
- pink, PAS-positive globules in ER of hepatocytes
structural difference between bronchus and bronchioles
bronchi have cartilage
bronchioles don’t
what can cause complication of secondary amyloidosis?
Bronchiectasis
-chronic inflammation leads to SAA production, SAA converts to AA, AA deposits.
Causes of bronchiectasis (5)
- cystic fibrosis (mucus leads to infection)
- Kartaganer syndrome (cannot move mucus out, infection)
- tumor/foreign body (blockage)
- Infection, necrotizing
- ABPA (Allergic bronchopulmonary aspergillus)
bronchiectasis
- clinical presentation
- complications
- cough, dyspnea, foul smelling sputum
- hypoxemia, cor pulmonale, secondary amyloidosis
Early vs late phase of asthma
early: histamine, leukotrienes
late: MBP from eosinophils (Charcot-Leyden crystals in mucus)
bronchiectasis
-mech of disorder
- chronic inflammation damages bronchi and bronchioles, leads to enlarged airways
- dilated airways lose their tone, causes air trapping.
pink, PAS-positive globules in hepatocytes
-what’s this
- A1AT accumulation inside hepatocytes b/c of misfolding.
- A1AT cannot enter blood, so results in panacinar emphysema
emphysema
-2 causes
imbalance of proteases and antiproteases
- smoking (inflammation leads to increased proteases)
- A1AT deficiency (buildup of proteases)
emphysema
-clinical presentation
- dyspnea and cough with minimal sputum
- “pink puffer” with pursed lips
- weight loss, very thin (b/c extra work of pursed lips)
- barrel chest
Asthma:
describe cellular mech, from initial exposure to allergen
In genetically susceptible individuals:
- first exposure to allergens induce Th2 T-cells
- Th2 cells secrete IL4, 5, 10.
IL4–IgE
IL5–attract eosinophils
IL10–increase Th2, decrease Th1
- Next allergen exposure leads to IgE-mediated release of histamine from mast cells. Also, mast cells produce leukotrienes. (bronchoconstriction, inflammation, edema)
- late phase: eosinophils make major basic protein, which damages cells
Histamine:
- where does vasodilation occur?
- where does fluid leakage occur?
- arterioles
- post-capillary venules
