Pahtology 2nd Slide Set Flashcards
young children with aeroallergen sensitization who develop lower respiratory tract viral infections (rhinovirus type C, RSV) have a 10 - 30 fold increased risk of developing what?
persistent and/or severe astham
this result from hypoplasia of bronchial cartilage in infants and is sometimes associated with other congenital cardiac and lung abnormalities
congenital lobar overinflation
What locus and chromosome encodes alpha1-antitrypsin?
Pi locus on chromosome 14
Death in most patients with emphysema is due to what?
- CAD
- respiratory failure
- right-sided heart failure
- pneumothorax
What inflammatory mediators and leukocytes have been shown to be increased in affected parts of emphysema?
- leukotriene B4
- IL-8
- TNF
WHEEZING, breathlessness, chest tightness, and cough particularly at night and/or in early morning
Asthma
What genetic variant other than alpha1-antitrypsin deficiency have been linked to risk of emphysema?
Nicotinic acetylcholine receptor - influence addictiveness
What people are at most risk for getting interstitial emphysema?
Premature children on positive pressure ventilation and adults who are being artificially ventilated
Curschmann spirals in sputum or BAL
severe asthma
persistent cough with sputum production for at least 3 months in at least 2 consecutive years in the absence of any other identifiable cause
chronic bronchitis
clinical features of chronic bronchitis after persistent productive cough
dyspnea on exertion then with passage of time
- hypercapnia
- hypoxia
- mild cyanosis (blue bloater)
Describe the small airway inflammation in emphysema?
- Goblet cell hyperplasia with mucus plugging of lumen
- inflammatory infiltrates in bronchial wall consisting of neutrophils, macrophages, B and T cells
- Thickening of bronchiolar wall due to smooth muscle hypertrophy and peribronchial fibrosis
What are the 4 major types of emphysema?
- centriacinar
- panacinar
- paraseptal
- irregular
What are the 4 main processes involved in the pathogenesis of emphysema?
- inflammatory mediators and leukocytes
- Protease-antiprotease imbalance (elastase)
- Oxidative stress
- infection
What factors relaeased from eosinophils in the late reaction of Atoplic asthma caused damage to the epithelium?
- major basic protein
- eosinophil cationic protein
What abnormality is associated with panacinar emphysema
Alpha1-antitrypsin deficiency
what people are more susceptible to COPD?
Women and African Americans
Irreversible enlargement of the airspaces distal to the terminal bronchiole accompanied by destruction of their walls without obvious fibrosis
Emphysema
Cardinal symptom of chronic bronchitis
-persistent productive cough
what is the morphology for chronic bronchitis
- edema and swelling often with squamous metaplasia
- hyperplasia of mucous gands of trachea and larger bronchi
- increased reid index (normally .4)
- in most severe, bronchiolitis obliterans
- severe persistent cough
- foul smelling sometimes bloody sputum
- sometimes hemoptysis
- in severe cases dyspnea and orthopnea
- EPISODIC
bronchiectasis
The idea that microbial exposure during early development reduces the later incidence of allergic diseases
hygiene hypothesis
What gene is linked to increased proliferation of bronchial smooth muscle cells and fibroblasts, thus contributing to bronchial hyperreactivity and subepithelial fibrosis in asthma?
ADAM33
if long standing asthma becomes fatal
Acute severe asthma (status asthmaticus)
If death occurs in chronic bronchitis from further impairment of respiratory function, what was it probably due to
superimposed acute infection
in Atopic asthma, what mediators from TH2 and mast cells activates/recuits eosinophils
IL-5
in the pathogenesis of chronic bronchitis, describe the inflammatory component
cellular DAMAGE, eliciting both acute and chronic inflammatory responses involving neutrophils, lymphocytes, and macrophages. long-standing inflammation and accompanying FIBROSIS of SMALL AIRWAYS
destruction of smooth muscle and elastic tissue by chronic necrotizing infections leads to permanent dilation of bronchi and bronchioles
bronchiectasis
What gene is associated with differetial in vivo airway hyper responsiveness in vitro response to beta-agonist stimulation?
Beta2-adrenergic receptor gene variants
What precipitate the symptoms of bronchiectasis
upper respiratory infection
Test and history or NON atopic asthma
skin tests negative
Family history less common
What drug induced asthma occurs in those with recurrent rhinitis and nasal polyps
aspirin-sensitive asthma
What proinflammatory mediators are thought to be involved in aspirin sensitive asthma
leukotrienes B4, C4, D4, and E4
What are the causes of interstitial emphysema?
- mostly alveolar tears in pulmonary emphysema
- rarely chest wounds or fractured ribs
early onset allergic asthma that responds well to corticosteroids is associated with inflammation by what cells
TH2 helper T cells
What lobes are affected in panacinar emphysema?
Lower and anterior margins
eosinophils and charcot-leyden crystals in sputum and BAL
severe asthma
What symptom of asthma overlaps with chronic bronchitis
increased mucus secretion
Patients with atopic asthma often have a history of what
allergic rhinitis or eczema
What is the earliest feature of chronic bronchitis?
hypersecretion of mucus
lung expands because air is trapped within it. common cause is subtotal obstruction of the airways by a tumor or foreign object
obstructive overinflation
COPD includes what 2 obstructive diseases
Emphysema and chronic bronchitis
When is the cough of bronchiectasis more frequent
when they rise in morning
inheritance pattern of primary ciliary dyskinesia
autosomal recessive
in Atopic Asthma, what mediators from TH2 cells stimulate production of IgE from B cells
IL-4 and IL-5
What congenital or hereditary conditions can cause bronchiectasis
- CYSTIC FIBROSIS
- intralobar sequestration
- immunodeficiency states
- primary ciliary dyskinesia
- kartagener syndroms
What are the ways that obstructive overinflation can occur?
- something acting as a ball valve
- collaterals (pores of Kohn and canals of Lambert) bring air in behind the block
What IL gene has strongest and most consistent associations with asthma?
IL13 (but don’t forget about 3, 4, 5, 9 and receptor IL4)
What are the major conditions associated with bronchiectasis
obstruction and infection
What are the 4 obstructive pulmonary diseases?
- emphysema
- chronic bronchitis
- asthma
- bronchiectasis
Where does distal acinar (paraseptal) emphysema occur
- more striking adjacent to pleura
- along lobular connective tissue septa
- at margins of lobules
- adjacent to areas of fibrosis, scarring, or atelectasis
- upper half of lungs
what inflammatory mediators are involved in the hypersecretion of chronic bronchitis
histamine and IL-13
Tell me about tests and history for Atopic asthma
- may have high serum IgE
- postive family history of asthma
- skin test: WHEAL and FLARE reaction
- RAST
what happens to smaller bronchiles in bronchiectasis
progressively obliterated as a result of fibrosis (bronchiolitis obliterans
Atopic asthma is what type of hypersensitivity
type 1 (IgE mediated)
What cells and what mediator is responsible for recruitment of neutrophils in Atopic ashtma
TH17 and IL-17
What type of emphysema?
- Heavy smoker often with chronic bronchitis (COPD)
- central or proximal part of acini (distal spared)
- More severe and common in upper lobes
Centriacinar
in Atopic asthma, the allergens most frequently act in synergy with other proinflammatory environmental cofactors, most notably what?
respiratory viral infections
There are no symptoms in emphysema until how much of the lung is affected/
1/3
when does atopic asthma usually begin
childhood
What leads to stasis and increased risk for infection in chronic bronchitis
smoke interferes with ciliary actions of respiratory epithelium
What gene associated with asthma responsible for cleaving chitin, a polysaccharide in many human parasites and cell walls of fungi?
-correlated with disease severity, airway remodeling, and decreased pulmonary function
YKL-40
Severe emphysema symptoms
- weight loss
- barrel chest
- prolonged expiration
- “pink puffer”
- sits forward in hunched-over position and breathes through pursed lips
in Atoplic asthma, what mediator stimulates mucus secretion from bronchial submucosal glands and promotes IgE production
IL-13
Entrance of air into connective tissue stroma of the lung, mediastinum, or subcutaneous tissue
interstitial emphysema
What cells release the chemotactic factors in the pathogenesis of emphysema?
Lung epithelial cells and macrophages
What gene variants are associated with atopy, elevation total serum IgE, and asthma
IL-4 receptor gene
What is airspace enlargement with fibrosis (irregular emphysema) almost invariably associated with?
Scarring
Dilation of alveoli in response to loss of lung substance elsewhere. hyperexpansion of residual lung parenchyma following surgical removal of a diseased lung or lobe
Compensetory hyperinflation
What type of emphysema probably underlies many cases of spontaneous pneumothorax?
Distal acinar (paraseptal) emphysema
Long standing severe chronic bronchitis commonly leads to what
cor pulmonale and cardiac failure
The early reaction of atopic asthma is dominated by what features?
- bronchoconstriction
- increased mucus production
- variable degrees of vasodilation
- increased vascular permeability
the 3 things involved in pathogenesis of chronic bronchitis?
- mucus hypersecretion
- inflammation
- infection
What gene is associated with protection of oxidative stress from tobacco smoke and emphysema
NFR2
Who commonly gets chronic bronchitis
smokers and inhabitants of smog-laden cities
What is the late phase reaction in Atopic asthma dominated by?
recruitment of leukocytes, notably eosinophils, neurtrophils, and more T cells
What area of lungs does bronchiectasis usually affect?
lower lobes bilaterally
occurs in patients with asthma and cystic fibrosis who develop periods of exacerbation and remission that may lead to proximal bronchiectasis and fibrotic lung disease
Allergic bronchopulmonary aspergillosis
Homozygous for what allele have markedly decreased serum levels of alpha1-antitrypsin?
PiZZ
Bacterial species that cause infection in CF patients
- S. aureus
- H. influenzae
- Berkholderia cepacia
- Pseudomonas aeruginosa
describe the airway remodeling that occurs after repeated allergen exposure and reaction
- bronchial wall smooth muscle hypertrophy and hyperplasia
- subepithelial fibrosis (collagen 1 and 3)
- submucosal gland hyperplasia; increased goblet cells
- increased thickness of the airway wall
asthmatic attack with urticaria
aspirin sensitive asthma
What are charcot-leyden crystals composed of
an eosinophil protein called galectin-10
The bronchoconstriction in the early phase of an atopic asthmatic reaction is triggered by what?
- direct stimulation of sub epithelial vagal (parasympathetic) receptors
- Luekotrienes C4, D4, and E4
- acetylcholine
What causes an obstructive overinflation to become life threatening?
affected portion distends sufficiently to compress remaining lung
What is the major trigger of COPD?
Cigarette smoke
What gene is linked to production of IgE antibodies against some antigens such as ragweed pollen?
class II HLA
Common triggers for Non-atopic asthma
- Respiratory infections due to viruses (rhinovirus, parainfluenza, RSV)
- inhalation of irritants
- cold
- exercise
Initial symptoms of emphysema
Dyspnea, cough, and wheezing
- ciliary dyskinesia
- sinusitis
- bronchiectasis
- situs inversus
Kartagener syndrome
